Clinical Practice Guidelines

Decompensated

cirrhosis

These slides give a comprehensive overview of the EASL clinical practice guidelines on the management of decompensated cirrhosis

• The guidelines were first presented at the International Liver Congress 2018 and are published in the Journal of Hepatology
  • A full copy of the publication can be downloaded from the Clinical Practice Guidelines section of the EASL website

Please feel free to use, adapt, and share these slides for your own personal use; however, please acknowledge EASL as the source

• Definitions of all abbreviations shown in these slides are provided within the slide notes

When you see a home symbol like this one: , you can click on this to return to the outline or topics pages, depending on which section you are in

These slides are intended for use as an educational resource and should not be used in isolation to make patient management decisions. All information included should be verified before treating patients or using any therapies described in these materials

• Please send any feedback to: [email protected]
• Chair

• • Paolo Angeli
• Panel
  • Càndid Villanueva, Claire Francoz, Rajeshwar P Mookerjee, Jonel Trebicka, Aleksander Krag,

Wim Laleman,

Pere Gines,

Mauro Bernardi (EASL Governing Board Representative)

• Reviewers
  • Alexander Gerbes, Thierry Gustot, Guadalupe Garcia-Tsao

Methods

• Grading evidence and recommendations

Background

• Definition and pathophysiology of decompensated cirrhosis

Guidelines

• Key recommendations

Methods

Grading evidence and recommendations

Grading evidence and recommendations

Grading is adapted from the GRADE system1

Grade of evidence
I	Randomized, controlled trials
II-1	Controlled trials without randomization
II-2	Cohort or case-control analytical studies
II-3	Multiple time series, dramatic uncontrolled experiments
III	Opinions of respected authorities, descriptive epidemiology
Grade of recommendation
1	Strong recommendation: Factors influencing the strength of the recommendation included the quality of the evidence, presumed patient-important outcomes, and cost
2	Weaker recommendation: Variability in preferences and values, or more uncertainty: more likely a weak recommendation is warranted Recommendation is made with less certainty: higher cost or resource consumption

1. Guyatt GH, et al. BMJ. 2008:336:924–6;

EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Background

Definition and pathophysiology of decompensated cirrhosis

ACLF

Stage 6: late decompensation:

Refractory ascites, persistent PSE or jaundice,

infections, renal and other organ dysfunction

End stage

Death

• Transition from compensated cirrhosis to DC occurs at a rate of ~5–7% per year
• DC is a systemic disease, with multi-organ/system dysfunction

Compensated

Stage 0: no varices, mild PH LSM >15 and <20 or HVPG >5 and <10 mmHg

Stage 1: no varices, CSPH LSM ≥20 or HVPG ≥10 mmHg

Stage 2: varices (=CSPH)

Decompensated

Stage 3: Bleeding

Stage 4: First non-bleeding decompensation

Stage 5: Second decompensating event

• Transition from compensated cirrhosis to DC occurs at a rate of ~5–7% per year
• DC is a systemic disease, with multi-organ/system dysfunction

Stage 0: no varices, mild PH

LSM >15 and <20 or HVPG >5 and <10 mmHg

Stage 1: no varices, CSPH

LSM ≥20 or HVPG ≥10 mmHg

Stage 2: varices (=CSPH)

Stage 3: Bleeding

Stage 4:

First non-bleeding decompensation

Stage 5:

Second decompensating event

ACLF

Stage 6: late decompensation:

Refractory ascites, persistent PSE or jaundice,

infections, renal and other organ dysfunction

End stage

Median survival: 2 years

Symptomatic

Decompensated

Median survival: 12 years

Asymptomatic

Compensated

Death

Liver injury

Cirrhosis

Damaged cells/DAMPs

	Portal hypertension
Bacterial translocation/PAMPs

Other potential mechanisms

Release of pro-inflammatory molecules (ROS/RNS)

Activation of innate pattern recognition receptors

++

Splanchnic arteriolar vasodilation and

cardiovascular dysfunction

Adrenal dysfunction

HE Kidney

dysfunction

HPS

Bernardi M, et al. J. Hepatol 2015;63:1272–84;

• Management of DC aims to improve outcomes of complications

Refractory

Ascites

Uncomplicated

Hepatic hydrothorax

CKD

AKI

Renal impairment

Hyponatremia

Complications of DC

Bacterial infections

ACLF

RAI

GI bleeding

PPHT

HPS

CCM

Cardiopulmonary

Increased understanding of DC pathophysiology permits the development of more comprehensive therapeutic and prophylactic approaches

to prevent or delay disease progression

Key recommendations

Overall management of DC

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• • Suppression of aetiological factor(s)
  • Treatment of key pathogenic factors

1. Management of specific complications of DC
   • Ascites
   • Refractory ascites
   • Hepatic hydrothorax
   • Hyponatremia
   • Gastrointestinal bleeding
   • Bacterial infections
   • Renal impairment
   • Acute-on-chronic liver failure
   • Relative adrenal insufficiency
   • Cardiopulmonary complications

• Management should aim to prevent progression, not treat complications

No treatment exists that can act on cirrhosis progression directly

• Two alternative approaches can be taken:
  • Suppress aetiological factor(s) that cause liver inflammation and cirrhosis development
  • Target key factors in the pathogenesis of cirrhosis decompensation and progression

Impact is variable

• Probably depends on the status of liver disease at the time

Recommendation Grade of evidence Grade of recommendation
In patients with DC the aetiological factor should be removed, particularly alcohol consumption and hepatitis B or C virus infection, as this strategy is associated with decreased risk of decompensation and increased survival	II-2	1

Several strategies have been evaluated to prevent disease progression in patients with DC

• • Targeting microbiome abnormalities and bacterial translocation to improve the gut–liver axis (i.e. rifaximin)
  • Improving the disturbed circulatory function (i.e. long-term albumin)
  • Treating the inflammatory state (i.e. statins)
  • Targeting portal hypertension (i.e. β-blockers)

Further clinical research is needed to confirm the safety and potential benefits of these therapeutic approaches to

prevent cirrhosis progression in patients with DC

Most common complication of decompensation in cirrhosis

• • Develops in 5–10% of patients with compensated cirrhosis per year

Significant impact on patients

• • Impairs patient working and social life
  • Frequently leads to hospitalization
  • Requires chronic treatment
  • Direct cause of further complications
  • Poor prognosis (5-year survival, ~30%)

Ascites can be uncomplicated or refractory

• • Ascites is uncomplicated when not infected, refractory or associated with impairment of renal function

Cirrhosis is responsible for 80% of cases of ascites

• Initial patient evaluation:
  • History
  • Physical examination
  • Abdominal ultrasound
  • Laboratory assessment
    • Liver and renal function, serum and urine electrolytes, analysis of ascitic fluid

Ascites is graded based on amount of fluid in the abdominal cavity

Grading of ascites*
Grade 1	Mild ascites: only detectable by ultrasound examination
Grade 2	Moderate ascites: manifest by moderate symmetrical distension of abdomen
Grade 3	Large or gross ascites: provokes marked abdominal distension

*Ascites recurring on ≥3 occasions within a 12-month period despite dietary sodium restriction and adequate diuretic dosage are considered recurrent

Diagnostic paracentesis is indicated in:*

• • All patients with new-onset grade 2 or 3 ascites
  • Patients hospitalized for worsening ascites or any complication of cirrhosis

Recommendation Grade of evidence Grade of recommendation
Neutrophil count and culture of ascitic fluid culture† should be performed to exclude bacterial peritonitis Neutrophil count >250 cells/µl denotes SBP	II-2	1
Ascitic total protein concentration should be performed to identify patients at higher risk of developing SBP‡	II-2	1
The SAAG should be calculated when the cause of ascites is not immediately evident, and/or when conditions other than cirrhosis are suspected§	II-2	1
Cytology should be performed to differentiate malignancy-related from non-malignant ascites	II-2	1

*Grade of evidence II-2, grade of recommendation 1; †Bedside inoculation blood culture bottles with 10 ml fluid each;

‡A total protein concentration <1.5 g/dl is generally considered a risk factor for SBP;

§SAAG ≥1.1 g/dl indicates that portal hypertension is involved in ascites formation with an accuracy of about 97%

Development of ascites in patients with cirrhosis is associated with a poor prognosis

• • 1-year mortality: 40%
  • 2-year mortality: 50%

Patients with ascites should be considered for referral for LT

Recommendation Grade of evidence Grade of recommendation
Since the development of grade 2 or 3 ascites in patients with cirrhosis is associated with reduced survival, LT should be considered as a potential treatment option	II-2	1

• Patients may not receive adequate priority in transplant lists

– Most commonly used prognostic scores can underestimate mortality risk

Improved methods to assess prognosis in these patients are needed

• Grade 1 or mild ascites
  • No data on evolution and not known if treatment modifies natural history
• Grade 2 or moderate ascites
  • Hospitalization not required
  • Correct sodium imbalance:
    • Dietary restriction and increased renal excretion with diuretics

Recommendation Grade of evidence Grade of recommendation
Moderate restriction of sodium intake (80–120 mmol/day, corresponding to 4.6–6.9 g of salt) is recommended	I	1
Generally equivalent to a no added salt diet with avoidance of pre-prepared meals. Adequate nutritional education of patients on how to manage dietary sodium is also recommended	II-2	1
Very low sodium diets (<40 mmol/day) should be avoided	II-2	1
Prolonged bed rest cannot be recommended	III	1

Mainstay of medical treatment are anti-mineralocorticoid drugs*

• Loop diuretics may be added in patients with long-standing ascites

Recommendation Grade of evidence Grade of recommendation
First episode of grade 2 ascites Anti-mineralocorticoid drug alone (from 100 mg/day with 100 mg stepwise increased every 72 hours to a maximum of 400 mg/day if no response to lower doses)	I	1
In patients who do not respond to anti-mineralocorticoids† or who develop hyperkalaemia, furosemide should be added (from 40 mg/day with 40 mg stepwise increases to a maximum of 160 mg/day)	I	1
Long-standing or recurrent ascites Combination of an anti-mineralocorticoid drug and furosemide (dose increased sequentially according to response)	I	1
Torasemide can be given in patients exhibiting a weak response to furosemide	I	2

*Spironolactone, canrenone or K-canrenoate; †Body weight reduction <2 kg/week

Patients with cirrhosis and ascites are highly susceptible to rapid reductions in extracellular fluid volume

• • Can lead to renal failure and hepatic encephalopathy

Recommendation Grade of evidence Grade of recommendation
GI haemorrhage, renal impairment, hepatic encephalopathy, hyponatraemia, or alterations in serum potassium concentration, should be corrected before starting diuretic therapy In these patients, cautious initiation of diuretic therapy and frequent clinical and biochemical assessments should be performed	III	1
Diuretic therapy is generally not recommended in patients with persistent overt hepatic encephalopathy	III	1

Loop diuretics can lead to potassium and magnesium depletion and hyponatraemia

• Muscle cramps can impair quality of life in patients receiving diuretics

Recommendation Grade of evidence Grade of recommendation
Frequent clinical and biochemical monitoring during the first weeks of treatment (particularly on first presentation)	I	1
Recommended maximum weight loss: 0.5 kg/day in patients without oedema, 1 kg/day in patients with oedema	II-2	1
Once ascites have largely resolved, the dose of diuretics should be reduced to the lowest effective dose	III	1
Discontinue diuretics in case of severe hyponatraemia,* AKI, worsening hepatic encephalopathy, or incapacitating muscle cramps	III	1
Discontinue furosemide for severe hypokalaemia (<3 mmol/L ) Discontinue anti-mineralocorticoids for hyperkalaemia (>6 mmol/L)	III	1
Albumin infusion or baclofen administration† are recommended in patients with muscle cramps	I	1

*Serum sodium <125 mmol/L; †10 mg/day, with a weekly increase of 10 mg/day up to 30 mg/day

• Grade 3 or large ascites
  • LVP, under strict sterile conditions, is the treatment of choice
    • Ascites should be completely removed in a single session*
  • Contraindications to LVP include:
    • Uncooperative patient, abdominal skin infection at puncture sites, pregnancy, severe coagulopathy, severe bowel distention

Recommendation Grade of evidence Grade of recommendation
LVP should be followed with plasma volume expansion	I	1
Plasma volume expansion should be performed by albumin infusion (8 g/L ascites) For >5 L of ascites: more effective than other plasma expanders For <5 L of ascites (low risk of PPCD): treat with albumin due to concerns about use of alternative plasma expanders	I III	1 1
After LVP, patients should receive the minimum dose of diuretics necessary to prevent re-accumulation of ascites	I	1
When needed, LVP should be performed in patients with AKI or SBP	III	1

*Grade of evidence I, grade of recommendation 1

• Patients with DC and ascites are at increased risk of renal impairment from several types of drug

Recommendation Grade of evidence Grade of recommendation
NSAIDs should not be used (high risk of developing further sodium retention, hyponatraemia, and AKI)	II-2	1
Angiotensin-converting enyzme inhibitors, angiotensin II antagonists, or 1-adrenergic receptor blockers should not generally be used (increased risk of renal impairment)	II-2	1
Aminoglycosides are discouraged (increased risk of AKI) Reserved for patients with severe bacterial infections that cannot be treated with other antibiotics	II-2	1
Contrast media In patients with preserved renal function: does not appear to be associated with increased risk of renal impairment In patients with renal failure: insufficient data, cautious use and preventative measures recommended	II III	2 1

• International Ascites Club:

“Ascites that cannot be mobilized or the early recurrence of which

(after LVP) cannot be satisfactorily prevented by medical therapy”

Diuretic intractable

Diuretic resistant

Refractory ascites

Ascites that cannot be mobilized or the early recurrence of which cannot be prevented because of a lack of response to sodium

restriction and diuretic treatment

Ascites that cannot be mobilized or the early recurrence of which

cannot be prevented because of the development of diuretic-induced complications that preclude the use of an effective diuretic dosage

Diagnostic criteria
Treatment duration	Patients must be on intensive diuretic therapy* for at least 1 week and on a salt-restricted diet of less than 90 mmol/day
Lack of response	Mean weight loss of <0.8 kg over 4 days and urinary sodium output less than the sodium intake
Early ascites recurrence	Reappearance of grade 2 or 3 ascites within 4 weeks of initial mobilization
Diuretic- induced complications	HE: development of encephalopathy in the absence of any other precipitating factor Renal impairment: increase of serum creatinine by >100% to a value >2 mg/dl (177 µmol/L) in patients with ascites responding to treatment Hyponatraemia: a decrease of serum sodium by >10 mmol/L to a serum sodium of <125 mmol/L Hypo- or hyperkalaemia: a change in serum potassium to <3 mmol/L or >6 mmol/L despite appropriate measures Incapacitating muscle cramps

*Spironolactone 400 mg/day and furosemide 160 mg/day

Refractory ascites is associated with a poor prognosis

• • Median survival around 6 months

Recommendation Grade of evidence Grade of recommendation
The diagnosis of refractory ascites relies on the assessment of the response of ascites to diuretic therapy and salt restriction Evaluation should be done in stable patients without associated complications, such as bleeding or infection, after ascertaining patient compliance to treatment	III	1
Patients with refractory ascites should be evaluated for LT	III	1

LVP is a safe and effective treatment

• • Should be associated with albumin administration to prevent PPCD

Drug treatments are controversial or inadequately studied

Recommendation Grade of evidence Grade of recommendation
Repeated LVP plus albumin (8 g/L of ascites removed) are recommended as first-line treatment for refractory ascites	I	1
Diuretics should be discontinued in patients with refractory ascites who do not excrete >30 mmol/day of sodium under diuretic treatment	III	1
Although controversial data exist on the use of NSBBs in refractory ascites, caution should be exercised in severe cases* High doses of NSBB should be avoided (i.e. propranolol >80 mg/day) Carvedilol can not be recommended at present	II-2 I	1 2

*See also section on gastrointestinal bleeding

TIPS decompresses the portal system*

• • Short term: accentuates peripheral arterial vasodilation
  • Within 4–6 weeks: improves effective volaemia and renal function to increase renal sodium excretion

Recommendation Grade of evidence Grade of recommendation
Patients should be evaluated for TIPS insertion when: There is refractory or recurrent ascites Paracentesis is ineffective	I III	1 1
TIPS insertion is recommended in patients: With recurrent ascites as it improves survival With refractory ascites as it improves the control of ascites	I I	1 1
The use of small-diameter PTFE-covered stents is recommended to reduce the risk of TIPS dysfunction and hepatic encephalopathy	I	1
After TIPS insertion, continue the following until ascites resolution: Diuretics and salt restriction Close clinical follow-up	II-2 III	1 1

*By shunting an intrahepatic portal branch into a hepatic vein

Definition

• • Accumulation of transudate in the pleural space
    • In the absence of cardiac, pulmonary or pleural disease
  • Ascites moves through small diaphragmatic defects
    • Negative intrathoracic pressure induced by inspiration
  • Can lead to respiratory failure
  • Can be complicated by spontaneous bacterial infections (empyema)
  • Associated with poor prognosis
    • Median survival: 812 months

Diagnosis

• • Once pleural effusion has been ascertained, cardiopulmonary and

primary pleural diseases should be excluded*

• • Diagnostic thoracentesis is required to rule out bacterial infection*

*Grade of evidence III, grade of recommendation 1

• First-line management relies on treatment of ascites with diuretics and/or LVP
  • Not rare for pleural effusion to persist (refractory hepatic hydrothorax)

Therapeutic thoracentesis is required to relieve dyspnoea

Recommendation Grade of evidence Grade of recommendation
Patients with hydrothorax should be evaluated for LT	III	1
Diuretics and thoracentesis are recommended as the first-line management of hepatic hydrothorax	III	1
Therapeutic thoracentesis is indicated in patients with dyspnoea	III	1
Chronic pleural drainage should not be performed because of the
frequent occurrence of complications	II-2	1

Hepatic hydrothorax:

beyond diuretics and thoracentesis

• Other treatments are appropriate in selected patients

Recommendation Grade of evidence Grade of recommendation
In selected patients, TIPS insertion for recurrent symptomatic hepatic hydrothorax is recommended	II-2	1
Pleurodesis can be suggested to patients with refractory hepatic hydrothorax not amenable to LT or TIPS insertion The frequent occurrence of side effects restricts its use to selected patients	I	2
Mesh repair of diaphragmatic defects is suggested for the management of hepatic hydrothorax in very selected patients The best results are achieved in patients with non-advanced cirrhosis without renal dysfunction	II-2	2

Hyponatraemia

Common in patients with advanced cirrhosis

• • Arbitrarily defined as serum sodium concentration <130 mmol/L

Hypo- and hypervolaemic hyponatraemia can occur

• Associated with:
  • Increased mortality and morbidity, particularly neurological complications
  • Reduced survival after LT

Recommendation Grade of evidence Grade of recommendation
Patients with cirrhosis who develop hyponatraemia should be evaluated for LT	II-2	1
Removal of the cause and administration of normal saline are recommended in the management of hypovolaemic hyponatraemia	III	1
Fluid restriction* to 1,000 ml/day is recommended in the management of hypervolaemic hyponatraemia since it may prevent a further reduction in serum sodium levels	III	1

*Beyond fluid restriction, hypertonic saline should be limited to rare patients with life-threatening complications. It can be considered in patients with severe hyponatraemia who are expected to undergo LT within days. Correction of serum sodium concentration after attenuation of symptoms should be slow (≤8 mmol/L per day) to avoid irreversible neurological sequelae (II-3;1). Albumin can be administered but data are very limited (II-3;2). Use of vaptans should be limited to clinical trials (III;1)

Occurs when variceal wall ruptures due to excessive wall tension

• • Portal pressure is a key factor in both rupture and severity of bleeding

70% of GI bleeding events result from VH in patients with portal

hypertension

• • Second most common decompensating event
  • Most severe and immediate life threatening complication

Recommendation Grade of evidence Grade of recommendation
Patients with DC are at high risk and should have an OGD to screen for varices, unless previously diagnosed and treated	II-2	1
If OGD is performed, the presence, size and presence of red wale marks should be reported	II-2	1
In patients without varices in whom aetiological factor persists and/or remain decompensated, screening OGD should be repeated yearly In other patients the screening interval could be prolonged, but the exact interval is unclear and more data are required	III	2

High risk of death when VH occurs in patients with DC

• • Strategies to adequately treat VH and prevent (re)bleeding and death should be actively pursued

Recommendation Grade of evidence Grade of recommendation
Primary prophylaxis must be initiated upon detection of high-risk varices* because of increased risk of VH	I	1
Patients with small varices with red wale marks or Child–Pugh C should be treated with NSBBs	III	1
Patients with medium–large varices should be treated with either NSBBs or EBL Choice of treatment can be based on local resources and expertise, patient preference, contraindications and AEs NSBBs could be preferred because in addition to lowering portal pressure, they also exert other potential beneficial effects	I III II-2	1 2 2

*High-risk = small varices with red signs, medium or large varices irrespective of Child–Pugh classification or small varices in Child–Pugh C patients

NSBBs and EBL are equally effective in preventing first bleeding in patients with high-risk varices

• • Choice between options depends on factors such as patient preference, contraindications or adverse events

Recommendation Grade of evidence Grade of recommendation
Ascites is not a contraindication for NSBBs. However, caution should be exercised in cases of severe or refractory ascites High doses of NSBBs should be avoided The use of carvedilol can not be recommended at present	I II-2 I	1 1 2
NSBBs should be discontinued in patients with progressive hypotension or those who develop an acute intercurrent condition* After recovery, reinstatement of NSBBs can be attempted When NSBB intolerance or contraindications persist, patient’s bleeding risk should be managed by expeditious EBL	III III III	1 2 1

NSBBs and EBL in combination reduces the risk of re-bleeding compared with monotherapy

Recommendation
Combination therapy of NSBBs + EBL is recommended	I	1
Covered TIPS placement is recommended in patients who continue to be intolerant to NSBBs*	III	1

*Provided that there are no absolute contraindications

• Medical emergency: high rate of complications and mortality in DC
  • Requires immediate treatment and close monitoring

Acute GI bleed + portal hypertension Initial assessment* and resuscitation

Early diagnostic endoscopy (<12 hours)

Confirm variceal bleeding

Endoscopic band ligation

Immediate start of vasoactive drug therapy† Antibiotic prophylaxis (I;1)‡

Airway Breathing Circulation

• Volume replacement with colloids and/or crystalloids should be initiated promptly (III;1)

Starch should not be used (I;1)

• Restrictive transfusion is recommended in most patients (Hb threshold, 7 g/dl; target range 7–9 g/dl) (I;1)

ENDOSCOPY

Balloon tamponade or oesophageal stenting

(if massive bleeding)

ENDOSCOPY

+

Maintain drug therapy for 3–5 days and antibiotics‡

Control

(~85% of cases)

Further bleeding

(~15% of cases)

 

Consider early TIPS in high risk patients Rescue with TIPS

*History, physical and blood exam, cultures; †Somatostatin/terlipressin; ‡Ceftriaxone (1 g/24 hours) is the first choice in patients with DC, those already on quinolone prophylaxis, and in hospital settings with high prevalence of quinolone-resistant bacterial infections. Oral quinolones (norfloxacin 400 mg BID) should be used in the remaining patients (I;1)

Figure adapted from de Franchis R, et al. J Hepatol 2015;63:74352;

Vasoactive drugs and ligation are the primary options for acute VH

• • There may be a role for TIPS in selected high-risk patients

Recommendation Grade of evidence Grade of recommendation
The combination of vasoactive drugs and ligation is recommended as the first therapeutic option in acute variceal bleeding	I	1
Early pre-emptive covered TIPS (placed within 24–72 hours) can be suggested in selected high-risk patients, such as those with Child–Pugh class C with score <14 However, the criteria for high-risk patients, particularly Child–Pugh B with active bleeding, remains debatable and needs further study	I	2

• Up to 10–15% of patients have persistent bleeding or early re-bleeding
  • Despite treatment with vasoactive drugs and EBL, and prophylactic antibiotics

Recommendation Grade of evidence Grade of recommendation
TIPS should be used as the rescue therapy of choice in cases of persistent bleeding or early re-bleeding	I	1
With the pre-requisite of expertise, balloon tamponade should be used in case of uncontrolled bleeding as a temporary ‘‘bridge” (max 24 hours) until definitive treatment can be instituted Removable, covered and self-expanding oesophageal stents can be used as an alternative to balloon tamponade	III I	1 2
In the context of bleeding, where encephalopathy is commonly encountered, prophylactic lactulose may be used to prevent encephalopathy, but further studies are needed	I	2
β-blockers and vasodilators should be avoided during the acute bleeding episode	III	1

• Risk of bacterial infection in patients with cirrhosis is caused by multiple factors
  • Liver dysfunction
  • Portosystemic shunting
  • Gut dysbiosis
  • Increased BT
  • Cirrhosis-associated immune dysfunction
  • Genetic factors

Spontaneous bacterial peritonitis

• • Definition: bacterial infection of ascitic fluid without any intra-abdominal surgically treatable source of infection
  • Prevalence: all patients with cirrhosis and ascites are at risk
    • 1.5–3.5% in outpatients; 10% in hospitalized patients
  • Prognosis: mortality exceeded 90% when first described
    • Reduced to ~20% with early diagnosis and treatment

Diagnosis is based on diagnostic paracentesis

• 50% of SBP episodes are present at hospital admission
  • Signs/symptoms of peritonitis: abdominal pain, tenderness, vomiting or

diarrhoea, ileus

• • Signs of systemic inflammation: hyper- or hypothermia, chills, altered WBC count
  • Worsening liver function, HE, shock, renal impairment, GI bleeding

However: SPB may be asymptomatic, particularly in outpatients

Diagnosis is based on diagnostic paracentesis

• 50% of SBP episodes are present at hospital admission
  • Signs/symptoms of peritonitis: abdominal pain, tenderness, vomiting or

diarrhoea, ileus

• • Signs of systemic inflammation: hyper- or hypothermia, chills, altered WBC count
  • Worsening liver function, HE, shock, renal failure, GI bleeding

Recommendation Grade of evidence Grade of recommendation
Diagnostic paracentesis should be carried out in: Patients with cirrhosis and ascites, at admission, to rule out SBP Patients with GI bleeding, shock, fever or other signs of systemic inflammation, worsening liver and/or renal function, and HE	II-2	1
SBP diagnosed by a neutrophil count in ascitic fluid >250/mm3 Neutrophil count is determined by microscopy or flow cytometry No clear evidence to support routine use of reagent strips	II-2	1
Ascitic fluid culture positivity is not a prerequisite for SBP diagnosis*	II-2	1

*Culture should be performed to guide antibiotic therapy (Grade of evidence II-2, grade of recommendation 1)

• Empirical IV antibiotics should be started immediately following diagnosis*
• Several factors should guide empirical antibiotic use†
  • Environment (community acquired vs. nosocomial)
  • Local bacterial resistance profiles
  • Severity of infection

Recommendation Grade of evidence Grade of recommendation
Third-generation cephalosporins are recommended as first-line antibiotic treatment for community-acquired SBP in countries with low rates of antibiotic resistance In countries with high rates of antibiotic resistance piperacillin/tazobactam or carbapenem should be considered	I II-2	1 1
Antibiotic resistance is more likely in healthcare-associated and nosocomial SBP Piperacillin/tazobactam: in areas with low prevalence of MDR bacteria Carbapenem: in areas with high prevalence of ESBL-producing Enterobacteriaceae Carbapenem + glycopeptides, daptomycin linezolid in areas with high prevalence of gram-positive MDR bacteria	I	1

*Grade of evidence II-2, grade of recommendation 1; †Grade of evidence I, grade of recommendation 1

Antibiotic therapy should be carefully controlled and monitored

Recommendation Grade of evidence Grade of recommendation
Severe infections by XDR bacteria may require antibiotics known to be highly nephrotoxic in patients with cirrhosis (e.g. vancomycin or aminoglycosides) In these cases, patients’ plasma levels should be monitored in accordance with local policy thresholds	III	1
De-escalation according to bacterial susceptibility based on positive cultures is recommended to minimize resistance selection pressure	II-2	1
Antibiotic efficacy should be checked with a second paracentesis at 48 hours from starting treatment Suspect failure of first-line antibiotic if worsening clinical signs and symptoms and/or increase, or no marked reduction in leucocyte count (at least 25%) in 48 hours	II-2	1
The duration of treatment should be at least 5–7 days	III	1
Spontaneous bacterial empyema should be managed similarly to SBP	II-2	2

• In patients with SBP treated with a third generation intravenous cephalosporin antibiotic, albumin significantly decreased the incidence of type-1 hepatorenal syndrome and reduced mortality1

Recommendation Grade of evidence Grade of recommendation
The administration of albumin is recommended in patients with SBP 1.5 g/kg at diagnosis and 1 g/kg on Day 3	I	1

1. Sort P, et al. N Engl J Med 1999;341:403–9;

Patients with cirrhosis and low ascitic fluid protein concentration (<10 g/L) and/or high serum bilirubin levels are at high risk of developing a first episode of SBP1

Recommendation Grade of evidence Grade of recommendation
Primary prophylaxsis with norfloxacin (400 mg/day) is recommended in patients with: Child–Pugh score ≥9 and serum bilirubin level ≥3 mg/dl, and Either impaired renal function or hyponatraemia, and Ascitic fluid protein lower than 15 g/L	I	1
Norfloxacin prophylaxis should be stopped in patients with long-lasting improvement of their clinical condition and disappearance of ascites	III	1

• • In patients who survive an episode of SBP, the cumulative recurrence rate at 1 year is approximately 70%1

Recommendation Grade of evidence Grade of recommendation
Prophylactic norfloxacin (400 mg/day, orally) is recommended in patients who recover from an episode of SBP	I	1
At present, rifaximin cannot be recommended as an alternative to norfloxacin for secondary prophylaxis of SBP At present, no recommendation can be given to guide prophylaxis of SBP among patients already on rifaximin for the prevention of recurrent HE	I	2
Patients who recover from SBP have a poor long-term survival and should be considered for LT	II-2	1
PPIs may increase the risk for the development of SBP, their use should be restricted to those with a clear indication	II-2	1

Non-SBP infections are frequent in patients with cirrhosis

• • • Associated with increased mortality

Recommendation Grade of evidence Grade of recommendation
Hospitalized patients with cirrhosis should be monitored closely for the presence of infections to enable early diagnosis and treatment	II-1	1
Empirical antibiotic therapy should be commenced promptly	II-1	1
Empirical antibiotic therapy should be based on: environment, local resistance profiles, severity and type of infection	I	1
In the context of high bacterial resistance to antibiotics, carbapenem alone or in combination with other antibiotics should be preferred*	I	1
Severe infections by XDR bacteria may require antibiotics known to be highly nephrotoxic in patients with cirrhosis (e.g. vancomycin or aminoglycosides) In these cases, patients’ plasma level should be monitored in accordance with local policy thresholds	III	1
Routine use of albumin not recommended in infections other than SBP	I	1

*Carbapenem alone or in combination with other antibiotics proved to be superior to third-generation

Good outcome

qSOFA and Sepsis-3 criteria have been validated in patients with cirrhosis1

• • • Can be used to assess severity of infection

Is baseline SOFA score available?

No

Yes

Apply sepsis-3 criteria and qSOFA

Poor outcome

Patient with need for transfer to ICU

Sepsis-3 positive and qSOFA negative

Good outcome

Sepsis-3 and qSOFA positive

Sepsis-3 and qSOFA negative

Negative

Positive

Apply sepsis-3 criteria

Grey zone Monitoring SOFA score is required

1. Singer M, et al. JAMA 2016;315:801–10; Figure adapted from Piano S, et al. Gut 2017; doi: 10.1136/gutjnl-2017-314324.

Nosocomial

Healthcare- associated

Community- acquired

Other infections:

recommended empirical antibiotic treatment

Cellulitis

Piperacillin- tazobactam or 3rd-gen

cephalosporin + oxacillin

AREA DEPENDENT:

Like nosocomial infections if high prevalence of MDROs

or if sepsis

3rd-gen cephalosporin or meropemen + oxacillin or glycopeptides or daptomycin or linezolid

Pneumonia UTI

Nosocomial

Healthcare- associated

Community- acquired

Nosocomial

Healthcare- associated

Community- acquired

Piperacillin- tazobactam

or ceftriaxone + macrolide or levofloxacin or moxifloxacin

AREA DEPENDENT:

Like nosocomial infections if high prevalence of MDROs

or if sepsis

Ceftazidime or meropemen + levofloxacin ± glycopeptides or linezolid

UNCOMPLICATED:

ciprofloxacin or cotrimoxazole

IF SEPSIS: 3rd-gen cephalosporin

or piperacillin-

tazobactam

AREA DEPENDENT:

Like nosocomial infections if high prevalence of MDROs

or if sepsis

UNCOMPLICATED:

fosfomycin or nitrofurantoin IF SEPSIS:

meropemen + teicoplanin or vancomycin

Other infections:

recommended empirical antibiotic treatment

Cellulitis

Most clinically relevant

3rd-gen cephalosporin or meropemen + oxacillin or glycopeptides or daptomycin or linezolid

AREA DEPENDENT:

Like nosocomial infections if high prevalence of MDROs

or if sepsis

Piperacillin- tazobactam or 3rd-gen

cephalosporin + oxacillin

Nosocomial

Healthcare- associated

Community- acquired

UTI

Pneumonia

Ceftazidime or meropemen + levofloxacin ± glycopeptides or linezolid

AREA DEPENDENT:

Like nosocomial infections if high prevalence of MDROs

or if sepsis

Piperacillin- tazobactam

or ceftriaxone + macrolide or levofloxacin or moxifloxacin

Nosocomial

Healthcare- associated

Community- acquired

Nosocomial

Healthcare- associated

Community- acquired

UNCOMPLICATED:

ciprofloxacin or cotrimoxazole

IF SEPSIS: 3rd-gen cephalosporin

or piperacillin-

tazobactam

AREA DEPENDENT:

Like nosocomial infections if high prevalence of MDROs

or if sepsis

UNCOMPLICATED:

fosfomycin or nitrofurantoin IF SEPSIS:

meropemen + teicoplanin or vancomycin

Definitions of renal impairment and staging of AKI have been updated

Recommendation Grade of evidence Grade of recommendation
In patients with liver diseases, even a mild increase in SCr should be considered since it may underlie a marked decrease of GFR	II-2	1
First step is to establish CKD, AKD, AKI or overlap	II-2	1
Diagnosis of CKD should be based on a GFR <60 ml/min/1.73 m2 estimated by SCr-based formulas, with or without signs of renal parenchymal damage* for at least 3 months	II-2	1
The diagnostic process should be completed by staging CKD, which relies on GFR levels, and by investigating its cause Note that SCr-based formulae overestimate GFR in cirrhosis	II-2	1
Diagnosis of AKI should be based on adapted KDIGO criteria Either an increase in SCr of >0.3 mg/dl from baseline within 48 hours, or an increase of ≥50% from baseline within 3 months	II-2	1
Staging of AKI should be based on an adapted KDIGO system†	II-2	1

• • Definitions of renal impairment and staging of AKI have been updated

Recommendation Grade of evidence Grade of recommendation
In patients with liver diseases, even a mild increase in SCr should be considered since it may underlie a marked decrease of GFR	II-2	1
First step is to establish CKD, AKD, AKI or overlap	II-2	1
Diagnosis of CKD should be based on a GFR <60 ml/min/1.73 m2 estimated by SCr-based formulas, with or without signs of renal parenchymal damage* for at least 3 months	II-2	1
The diagnostic process should be completed by staging CKD, which relies on GFR levels, and by investigating its cause Note that SCr-based formulae overestimate GFR in cirrhosis	II-2	1
Diagnosis of AKI should be based on adapted KDIGO criteria Either an increase in SCr of >0.3 mg/dl from baseline within 48 hours, or an increase of ≥50% from baseline within 3 months	II-2	1
Staging of AKI should be based on an adapted KDIGO system†	II-2	1

KDIGO group definitions

Definition	Functional criteria	Structural criteria
AKI	Increase in sCr ≥50% within 7 days, OR increase in sCr ≥0.3 mg/dl within 2 days	No criteria
AKD	GFR <60 ml/min per 1.73m2 for <3 months, OR decrease in GFR ≥35% for <3 months, OR increase in sCr ≥50 % for <3 months	Kidney damage for <3 months
CKD	GFR <60 ml/min per 1.73 m2 for ≥3 months	Kidney damage for ≥3 months

• • KDIGO group definitions

Increase in sCr ≥50% within 7 days,

OR

increase in sCr ≥0.3 mg/dl within 2 days

Definition	Functional criteria	Structural criteria
AKI	Increase in sCr ≥50% within 3 months*	No criteria
AKD	GFR <60 ml/min per 1.73m2 for <3 months, OR decrease in GFR ≥35% for <3 months, OR increase in sCr ≥50 % for <3 months	Kidney damage for <3 months
CKD	GFR <60 ml/min per 1.73 m2 for ≥3 months	Kidney damage for ≥3 months

*International Club of Ascites-recommended adaptation of KDIGO group criteria

Subject	Definition
Baseline sCr	sCr obtained within 3 months prior to admission If >1 value within the previous 3 months, the value closest to the admission If no previous sCr, the sCr on admission should be used
Definition of AKI	Increase in sCr ≥0.3 mg/dl (≥26.5 µmol/L) within 48 hours or Increase sCr ≥50% within the prior 7 days
Staging of AKI	Stage 1: increase in sCr ≥0.3 mg/dl (≥26.5 µmol/L) or an increase in sCr ≥1.5-fold to 2-fold from baseline Stage 2: increase in sCr >2-fold to 3-fold from baseline Stage 3: increase of sCr >3-fold from baseline or sCr ≥4.0 mg/dl (353.6 µmol/L) with acute increase ≥0.3 mg/dl (≥26.5 µmol/L) or initiation of renal replacement therapy
Progression of AKI	Progression Progression of AKI to a higher stage and/or need for RRT		Regression Regression of AKI to a lower stage
Response to treatment	No response No regression of AKI	Partial response Regression of AKI stage with a reduction of sCr to ≥0.3 mg/dl (≥26.5 µmol/L) above baseline		Full response Return of sCr to a value within 0.3 mg/dl (≥26.5 µmol/L) of baseline

Subject	Definition
Baseline sCr	sCr obtained within 3 months prior to admission If >1 value within the previous 3 months, the value closest to the admission If no previous sCr, the sCr on admission should be used
Definition of AKI	Increase in sCr ≥0.3 mg/dl (≥26.5 µmol/L) within 48 hours or Increase sCr ≥50% within the prior 7 days
Staging of AKI	Stage 1A (sCr <1.5mg/dl)* Stage 1B (sCr ≥1.5mg/dl)*
	Stage 2: increase in sCr >2-fold to 3-fold from baseline Stage 3: increase of sCr >3-fold from baseline or sCr ≥4.0 mg/dl (353.6 µmol/L) with acute increase ≥0.3 mg/dl (≥26.5 µmol/L) or initiation of renal replacement therapy
Progression of AKI	Progression Progression of AKI to a higher stage and/or need for RRT		Regression Regression of AKI to a lower stage
Response to treatment	No response No regression of AKI	Partial response Regression of AKI stage with a reduction of sCr to ≥0.3 mg/dl (≥26.5 µmol/L) above baseline		Full response Return of sCr to a value within 0.3 mg/dl (≥26.5 µmol/L) of baseline

• Stage 1: increase in sCr ≥0.3 mg/dl (≥26.5 µmol/L) or an increase in sCr ≥1.5-fold to 2- fold from baseline

*ICA recommended adaptations of KDIGO group criteria

Investigation and management should begin immediately

Initial AKI* stage 1A

Initial AKI* stage >1A

NO

YES

Response

Does AKI meet criteria of HRS?

NO

YES

Specific treatment for

other AKI phenotypes

Vasoconstrictors and albumin

*Initial AKI stage is defined as AKI stage at the time of first fulfilment of the AKI criteria;

Persistance

Further treatment of AKI decided on a case-by-case basics

Close follow-up

Progression

Resolution

Withdrawal of diuretics (if not yet applied) and volume expansion with albumin (1 g/kg) for 2 days

Close monitoring

Remove risk factors (withdrawal of nephrotoxic drugs, vasodilators and NSAIDs, taper/withdraw diuretics and β-blockers, expand plasma volume, treat infections† when diagnosed)

†Treatment of spontaneous bacterial peritonitis should include albumin infusion according to current guidelines

• • All types of AKI can occur in patients with cirrhosis
    • Pre-renal, HRS, intrinsic, particularly ATN, and post-renal
  • Key point is to differentiate HRS-AKI from ATN
  • Classification of HRS was recently revised by the ICA1
    • Type 1 HRS now corresponds to HRS-AKI
    • Type 2 HRS includes renal impairment that fulfills the criteria of HRS but not of AKI (non-AKI-HRS or NAKI)

Recommendation Grade of evidence Grade of recommendation
It is important to differentiate among types of AKI in patients with cirrhosis	II-2	1
The diagnosis of HRS-AKI is based on revised ICA criteria (see next slide) As kidney biopsy is rarely performed in the setting of AKI, biomarkers should be implemented In clinical practice among the different biomarkers to date, urinary NGAL can be used to distinguish between ATN and HRS	II-2	2

1. Angeli et al. J. Hepatol 2015;62:968–74;
   • Cirrhosis and ascites
   • Diagnosis of AKI according to ICA-AKI criteria
   • No response after 2 consecutive days of diuretic withdrawal and plasma volume expansion with albumin 1 g per kg of body weight
   • Absence of shock
   • No current or recent use of nephrotoxic drugs (NSAIDs, aminoglycosides, iodinated contrast media, etc.)
   • No macroscopic signs of structural kidney injury,* defined as:
     • Absence of proteinuria (>500 mg/day)
     • Absence of microhaematuria (>50 RBCs per high power field)
     • Normal findings on renal ultrasonography

*Patients who fulfil these criteria may still have structural damage such as tubular damage Angeli et al. J. Hepatol 2015;62:96874;

First-line therapy is terlipressin plus albumin*

Recommendation Grade of evidence Grade of recommendation
All patients meeting the current definition of HRS-AKI stage >1A should be expeditiously treated with vasoconstrictors and albumin	III	1
Terlipressin can be administered by IV boluses (1 mg every 4–6 hours) or by continuous IV infusion (2 mg/day)† In case of non-response (decrease in SCr <25% from the peak value) after 2 days, the dose of terlipressin should be increased in a stepwise manner to a maximum of 12 mg/day	I	1
Albumin solution (20%) should be used at 20–40 g/day Serial measures assessing central blood volume can help to titrate the dose of albumin to prevent circulatory overload	II-2	1
Noradrenaline can be an alternative to terlipressin‡ Requires a central venous line often in an ICU Midodrine + octreotide can be an option when terlipressin or noradrenaline are unavailable (but efficacy is much lower)	I I I	2 1 1

*Grade of evidence I, grade of recommendation 1;

†Continuous IV infusion allows for dose reduction to reduced adverse effects; ‡ Limited data are available

Management of HRS-AKI: screening and monitoring

Patients receiving treatment for HRS-AKI should be monitored for AEs and treatment response

• • • AEs related to terlipressin or noradrenaline include ischaemic and cardiovascular events

Recommendation Grade of evidence Grade of recommendation
Careful clinical screening including ECG before starting the treatment is recommended The decision to treat on a regular ward or transfer to higher dependency care should be case based Close monitoring of patients for the duration of treatment is important Treatment should be modified or discontinued according to the type and severity of side effects	I	1
Response to treatment: CR: final SCr within 0.3 mg/dl (26.5 µmol/L) from baseline PR: regression of AKI stage to a final SCr ≥0.3 mg/dl (26.5 µmol/L) from baseline	III	1
In case of recurrence a repeat course of therapy should be given	I	1

*Continuous IV infusion allows for dose reduction to reduced adverse effects

In most patients with HRS-AKI TIPS is contraindicated because of severe degree of liver failure

Recommendation Grade of evidence Grade of recommendation
There is insufficient data to advocate TIPS in HRS-AKI It could be suggested in selected patients with HRS-NAKI	II-2	2
LT is the best therapeutic option for patients with HRS regardless of the response to drug therapy	I	1
The decision to initiate RRT should be based on the individual severity of illness	I	2
The indication for liver-kidney transplantation remains controversial Should be considered in patients with significant CKD or sustained AKI including HRS-AKI with no response to drug therapy	II-2	1

• • Based on the use of albumin in patients who develop SBP and the prevention of SBP using norfloxacin

Recommendation Grade of evidence Grade of recommendation
Albumin (1.5 g/kg at diagnosis and 1 g/kg on Day 3) should be given in patients with SBP to prevent AKI	I	1
Norfloxacin (400 mg/day) should be given as prophylaxis of SBP to prevent HRS-AKI	I	1

Frequent occurrence in cirrhotic patients

• • • 30% of admitted patients and 25% of outpatients

Major cause of death in patients with cirrhosis (50% mortality rate)

• • Develops on a background of acute decompensation

Characterized by hepatic and extrahepatic organ failure, highly activated systemic inflammation and a high 28-day mortality

• • Precipitating events vary between populations and may include:
    • Bacterial infections (3057% of cases)
    • Active alcohol intake or alcohol binge
    • Reactivation of HBV
    • Superimposed HAV and HEV infection

EASL-CLIF prognostic and diagnostic scores for ACLF

10 x [0.033 x Clif OFs + 0.04 x Age + 0.63 x Ln(WBC) – 2]

CLIF-C ACLF score for mortality prediction1*

Chronic liver failure – organ failure score system1
Organ/system†		1 point	2 points	3 points
Liver (bilirubin, mg/dl)		<6	≥6–<12	≥12.0
Kidney (creatinine, mg/dl)		<2.0	≥2.0–<3.5	≥3.5 or renal replacement
Brain/HE (West Haven Criteria)		Grade 0	Grades 1–2	Grades 3–4‡
Coagulation (INR, PLT count)		<2.0	≥2.0–<2.5	≥2.5
Circulation (MAP, mmHg and vasopressors)		≥70	<70	Use of vasopressors
Lungs	PaO2/FiO2, or	>300	≤300–>200	≤200§
	SpO2/FiO2	>357	>214–≤357	≤214§

*Age in years, creatinine in mg/dL, WBC in 106 cells/L, sodium in mmol/L;

†Bold text indicates the diagnostic criteria for organ failures; ‡Patients submitted to mechanical ventilation due to HE and not to a respiratory failure were considered as presenting a cerebral failure (cerebral score = 3); §Other patients enrolled in the study with mechanical ventilation were considered as presenting a respiratory failure (respiratory score = 3)

1. Jalan R, et al. J Hepatol 2014;61:1038–47;

Even mild renal or brain dysfunction in the presence of another organ failure, is associated with a significant short-term mortality and therefore defines the presence of ACLF

Grades of ACLF	Clinical characteristics
NO ACLF	No organ failure, or single non-kidney organ failure, creatinine <1.5 mg/dl, no HE
ACLF 1a	Single renal failure
ACLF 1b	Single non-kidney organ failure, creatinine 1.5–1.9 mg/dl and/or HE grade 1–2
ACLF II	Two organ failures
ACLF III	Three or more organ failures

Moreau R, et al. Gastroenterology 2013;144:1426–37;

Diagnosis of ACLF is based on organ failure in the presence of AD in patients with cirrhosis

Recommendation Grade of evidence Grade of recommendation
ACLF diagnosis: cirrhosis and AD* plus organ failure(s) involving high short-term mortality	II-2	1
Diagnosis and grading should be based using the CLIF-C Organ Failure score	II-2	1
Potential precipitating factor(s) should be investigated† Hepatic: heavy alcohol intake, viral hepatitis, DILI, autoimmune hepatitis Extrahepatic: infections haemodynamic derangements following haemorrhage, surgery	II-2	1

*Defined as the acute development or worsening of ascites, overt encephalopathy, GI haemorrhage, non-obstructive jaundice and/or bacterial infections; †Note that in a significant proportion of patients, a precipitant factor may not be identified

There is no specific therapy for ACLF

• • Treatment is based on organ support and management of

complications

Recommendation Grade of evidence Grade of recommendation
Treatment of ACLF should be based on organ support, management of precipitants and associated complications	III	1
Patients should be treated in intermediate care or intensive care settings	III	1
ACLF is a dynamic condition and organ function should be monitored frequently and carefully throughout hospitalization Particularly, liver, kidney, brain, lung, coagulation, and circulation Monitoring and management should be individualized, mainly according to patients’ age and comorbidities	III	1

• • The cause of liver injury can be treated in certain situations, e.g. HBV
  • Early action is crucial to patient survival
    • Treatment of precipitating factors
    • Referral for LT before evolution of ACLF makes LT impossible

Recommendation Grade of evidence Grade of recommendation
Early identification and treatment of precipitating factors of ACLF, particularly bacterial infections, is recommended. However, in some patients ACLF progresses despite treatment of precipitating factors	III	1
Nucleoside analogues (tenofovir, entecavir) should be instituted as early as possible in patients with HBV-related ACLF	I	1
Early referral of patients with ACLF to LT centres for immediate evaluation is recommended	II-3	1
Withdrawal of intensive care support after 1 week can be suggested in patients who are not LT candidates and have ≥4 organ failures	II-2	2
Administration of G-CSF cannot be recommended at present	I	2

Relative adrenal insufficiency

• Inadequate cortisol response to stress in the setting of critical illness*

– Pathophysiology in cirrhosis is not well defined

• Diagnosis is influenced by the method used to measure cortisol
• It is not known whether cortisol supplementation in clinically stable cirrhosis with RAI is of any value

Recommendation Grade of evidence Grade of recommendation
Diagnosis of RAI <248 nmol/L (9 lg/dl) change in total serum cortisol after 250 lg corticotropin injection, or Random total cortisol of <276 nmol/L (<10 lg/dl)	II-2	1
Salivary cortisol determination can be preferred Serum free cortisol concentration can be influenced by reduced serum levels of CBG and albumin, frequently seen in patients with cirrhosis	II-2	2
Hydrocortisone treatment (at a dose of 50 mg/6 hours) of RAI cannot be recommended	I	2

*Also known as critical illness-related corticosteroid insufficiency (CIRCI)

CCM occurs in patients with established cirrhosis characterized by:

• • • Blunted contractile response to stress (pharmacological/surgery or inflammatory)
    • Altered diastolic left ventricular relaxation or/and increased left atrial volume
    • Electrophysiological abnormalities e.g. prolonged QTc
    • Cardiac output tending to decrease with decompensation
    • Systolic dysfunction: LVEF <55%

CCM is largely subclinical but its presence influences prognosis in advanced disease

• • Numerous electrocardiographic criteria, along with transmitral Doppler assessment, are used for the evaluation and diagnosis of diastolic dysfunction
    • However, there is the need for more controlled studies and correlation with clinical endpoints

Recommendation Grade of evidence Grade of recommendation
ECG in patients with cirrhosis should be performed with dynamic stress testing* (systolic dysfunction may be masked by hyperdynamic circulation and reduced afterload) Lack of increased CO after physiological/pharmacological stress† indicates systolic dysfunction	II-1	1
Myocardial strain imaging and assessment of GLS may be useful in the assessment of left ventricular systolic function in patients with DC	II-2	2
Cardiac MRI may identify structural changes	III	2
Diastolic dysfunction may occur as an early sign of CCM in the setting of normal systolic function, and should be diagnosed using ASE criteria: Average E/e’>14 Tricuspid velocity >2.8 m/s LAVI >34 ml/m2	II-1	1

*Either pharmacologically, or through exercise; †And in the absence of influence of β-blockade

• • Cardiac evaluation in patients with cirrhosis is important since CCM can influence prognosis

Recommendation Grade of evidence Grade of recommendation
In patients with AD, reduced CO (as a manifestation of CCM) is associated with the development of AKI (specifically hepatorenal dysfunction) after infections such as SBP	II-1	1
QTc interval prolongation is common in cirrhosis and may indicate a poor outcome Agents that can prolong the QT interval should be used cautiously	II-2	2
Detailed functional cardiac characterization should be part of the assessment for TIPS insertion LT	II-2 II-1	2 1
Standardized criteria and protocols for the assessment of systolic and diastolic function in cirrhosis are needed	II-2	2

• • Four main pulmonary complications may occur in patients with chronic liver disease
    • Pneumonia
    • Hepatic hydrotorax
    • HPS
    • Portopulmonary hypertension
  • HPS is defined as a disorder in pulmonary oxygenation, caused by intrapulmonary vasodilatation and, less commonly, by pleural and pulmonary arteriovenous communications occurring in the clinical setting of portal hypertension
  • Clinical manifestations of HPS in patients with chronic liver disease primarily involve dyspnoea and platypnoea

 

• Hepatic injury/failure
• Portal hypertension
• Portosystemic shunt
• Hyperdynamic circulation
• Bacterial translocation

Increased ET-1 release

ETB

Endothelial activation

receptor

Pulmonary capillary

CX3CL1

Systemic inflammation

Macrophage

Endothelial cell

of CX3CL1

Genetic

Increased eNOS

expression and activity

factors

Endothelial cell

Endothelial cell

Increased adherence

endothelial cells

monocytes to

of macrophages/

VFG-A release

recruitment

in the lungs

Endothelial cell

proliferation

Increased iNOS and HO

expression and activity

VASODILATION

ANGIOGENESIS

HEPATOPULMONARY SYNDROME

Increased NO

and CO release VASODILATION

• • Hypoxia with partial pressure of oxygen <80 mmHg or alveolar–arterial oxygen gradient ≥15 mmHg in ambient air (≥20 mmHg in patients older than 65 years)
  • Pulmonary vascular defect with positive findings on contrast-enhanced echocardiography or abnormal uptake in the brain (>6%) with radioactive lung-perfusion scanning
  • Commonly in presence of portal hypertension, and in particular:
    • Hepatic portal hypertension with underlying cirrhosis
    • Pre-hepatic or hepatic portal hypertension in patients without underlying cirrhosis
  • Less commonly in presence of:
    • Acute liver failure, chronic hepatitis
  • In patients with portal hypertension and the clinical suspicion of HPS partial pressure of oxygen (PaO₂) in ABG should be assessed

Recommendation Grade of evidence Grade of recommendation
In patients with chronic liver disease, HPS should be suspected and investigated in presence of tachypnoea and polypnoea, digital clubbing and/or cyanosis	II-2	1
Screening in adults: If pulse oximetry SpO2 <96% – ABG analysis should be performed If ABG PaO2 <80mmHg and/or P[A-a]O2 ≥15 mmHg* (in ambient air) – further investigations should be performed	II-2	1
The use of contrast (microbubble) echocardiography to characterize HPS is recommended	II-2	1

*For adults ≥65 years a P[A-a]O2 ≥20 mmHg cut-off should be used

• • When PaO₂ suggests HPS, further investigations are needed to determine the underlying mechanism

Recommendation Grade of evidence Grade of recommendation
MAA scan should be performed to quantify the degree of shunting in patients with severe hypoxaemia and coexistent intrinsic lung disease, or to assess the prognosis in patients with HPS and very severe hypoxaemia (PaO2 <50 mmHg)	II-2	1
Neither contrast echocardiography nor MAA scan can definitively differentiate discrete arteriovenous communications from diffuse precapillary and capillary dilatations or cardiac shunts Pulmonary angiography should be performed only in patients with the severe hypoxaemia (PaO2 <60 mmHg), poorly responsive to administration of 100% oxygen, and in whom there is a strong suspicion of arteriovenous communications that are amenable to embolization	II-2	1
Trans-oesophageal contrast-enhanced echocardiography (although associated with risks) can definitively exclude intra-cardiac shunts	II-2	2

• • There is no established medical therapy currently available for HPS, the only successful treatment for HPS is LT

Recommendations for medical treatment Grade of evidence Grade of recommendation
Long-term oxygen therapy is recommended in patients with HPS and severe hypoxaemia despite the lack of available data concerning effectiveness, tolerance, cost effectiveness, compliance and effects on survival rates of this therapy	II-2	1
No recommendation can be proposed regarding the use of drugs or the placement of TIPS for the treatment of HPS	I	1
Recommendations for liver transplantation
Patients with HPS and PaO2 <60 mmHg should be evaluated for LT since it is the only treatment for HPS that has been proven to be effective to date	II-2	1
Severe hypoxaemia (PaO2 <45–50 mmHg) is associated with increased post-LT mortality ABG analysis should be carried out every 6 months to facilitate prioritization to LT	II-2	1

• • PPHT occurs in patients with portal hypertension in the absence of other causes of arterial or venous hypertension
  • Classification is based on mean pulmonary arterial pressure (mPAP), and assumes high pulmonary vascular resistance (PVR) and normal pulmonary occlusion pressures
    • Mild: mPAP ≥25 and <35 mmHg
    • Moderate: mPAP ≥35 and <45 mmHg
    • Severe: mPAP ≥45 mmHg
  • Incidence between 3–10% cirrhosis patients based on haemodynamic criteria; women are at 3x greater risk and it is more common in autoimmune liver disease
  • There is no clear association between the severity of liver disease or portal hypertension and the development of severe PPHT

The evidence base for pharmacological therapies in PPHT is limited

Recommendation Grade of evidence Grade of recommendation
Screening for PPHT should be via TDE in patients deemed potential recipients for TIPS or LT In those with a positive screening test, right heart catheterization should be performed	II-1	1
In patients with PPHT who are listed for LT, echocardiography should be repeated on the waitlist (the specific interval is unclear)	III	1
β-blockers should be stopped and varices managed by endoscopic therapy in cases of proven PPHT	II-3	1
Therapies approved for primary pulmonary arterial hypertension may improve exercise tolerance and haemodynamics in PPHT However, endothelin antagonists should be used with caution because of concerns over hepatic impairment	II-2	1
TIPS should not be used in patients with PPHT	II-3	1

• • Although severe PPHT has, historically, been a contraindication for LT, the advent of improved haemodynamic control (with agents such as IV prostacyclin) allows LT to be considered

Recommendation Grade of evidence Grade of recommendation
If mPAP <35 mmHg and right ventricular function is preserved, LT should be considered mPAP of ≥45 mmHg should be considered an absolute contraindication to LT irrespective of therapy applied	II-2 III	1 1
Therapy to lower mPAP and improve right ventricular function should be commenced in patients with mPAP ≥35 mmHg Right ventricular function should be periodically evaluated	II-2	1
MELD exception can be considered in patients with proven PPHT in whom targeted therapy fails to decrease mPAP <35 mmHg but does facilitate normalization of PVR to <240 dyn.s/cm-5 and right ventricular function	II-3	2
MELD exception should be advocated in patients with proven PPHT of moderate severity (mPAP ≥35 mmHg) in whom targeted treatment lowers mPAP <35 mmHg and PVR <400 dyn.s/cm-5	II-2	1

Additional recommendations

Portal hypertension gastropathy

• • Often presents in patients with DC
    • Natural history significantly influenced by the severity of liver disease and portal hypertension

Recommendation Grade of evidence Grade of recommendation
NSBB and iron supplementation and/or blood transfusion, when indicated, are recommended as first-line therapy for chronic haemorrhage from PHG	I	1
In patients with transfusion-dependent PHG in whom NSBBs fail or are not tolerated, covered TIPS placement may be used in the absence of contraindications	II-3	2
Acute PHG bleeding may be treated with somatostatin analogues or terlipressin but substantiating data are limited	I	2

Gastric varices: classification, prevalence and risk

• • The Sarin classification is most commonly used for risk stratification and management of gastric varices

Type Definition		Relative frequency	Overall bleeding risk without treatment
Gastro-oesophageal varices (GOV)
GOV type 1	OV extending below cardia into lesser curvature	70%	28%
GOV type 2	OV extending below cardia into fundus	21%	55%
Isolated gastric varices (IGV)
IGV type 1	Isolated varices in the fundus	7%	78%
IGV type 2	Isolated varices else in the stomach	2%	9%

• • Gastric varices are present in about 20% of patients with cirrhosis

Recommendation Grade of evidence Grade of recommendation
NSBBs are suggested for primary prevention of VH from GOV type 2 or IGV type 1	III	2
Primary prevention for GOV type 1 follows the recommendations of oesophageal varices	III	2
Acute gastric VH should be treated medically, like oesophageal VH Cyanoacrylate is the recommended endoscopic haemostatic treatment for cardiofundal varices (GOV type 2 or IGV type 1)	I I	1 2
TIPS with potential embolization efficiently controls bleeding and prevents re-bleeding in fundal VH (GOV type 2 or IGV type 1) and should be considered in appropriate candidates	II-2	1
Selective embolization (BRTO/BATO) may also be used to treat bleeding from fundal varices associated with large gastro/splenorenal collaterals, although more data is required	III	2

Both neutrophil count and culture results should be taken into account

Recommendation Grade of evidence Grade of recommendation
Patients with bacterascites (neutrophil count <250/mm3 but positive bacterial culture) exhibiting signs of systemic inflammation or infection should be treated with antibiotics Otherwise, the patient should undergo a second paracentesis If the culture results come back positive again, regardless of the neutrophil count, the patient should be treated	II-2 III	1 1
Spontaneous bacterial pleural empyema diagnosed by: Positive pleural fluid culture and neutrophil count >250/mm3 or Negative pleural fluid culture and neutrophil count >500/mm3 in the absence of pneumonia	II-2	1
Secondary bacterial peritonitis should be suspected in case of multiple organisms on ascitic culture, very high ascitic neutrophil count and/or high ascitic protein concentration, or in those patients with an inadequate response to therapy Patients with suspected secondary bacterial peritonitis should undergo prompt CT scanning and early considerations for surgery	III	1

SBP or SBE

Nosocomial SBP or SBE

Healthcare-associated SBP or SBE

Community-acquired SBP or SBE

3rd-gen cephalosporin or

piperacillin-tazobactam

AREA DEPENDENT:

Like nosocomial infections if high prevalence of MDROs or if sepsis

Carbapenem alone or + daptomycin, vancomycin (or linezolid*) if high prevalence of MDR Gram+ bacteria or sepsis

*In areas with a high prevalence of vancomycin-resistant enterococci Adapted from Jalan R, et al. J Hepatol 2014;60:1310–24;

Investigation and management should begin immediately

Recommendation Grade of evidence Grade of recommendation
Investigate AKI cause as soon as possible to prevent AKI progression Management should begin immediately (even absent obvious cause) Screening and treatment of infection are most important	II-2	1
Diuretics and/or β-blockers as well as other drugs that could be associated with the occurrence of AKI such as vasodilators, NSAIDs and nephrotoxic drugs should be immediately stopped	II-2	1
Volume replacement should be used in accordance with the cause and severity of fluid losses	II-2	1
In case of no obvious cause of AKI, AKI stage >1A or infection-induced AKI: 20% albumin solution should be used at a dose of 1 g /kg of body weight (maximum of 100 g of albumin) for 2 consecutive days	III	1
In patients with AKI and tense ascites, therapeutic paracentesis should be associated with albumin infusion even when a low volume of ascitic fluid is removed	III	1

• • HRS-NAKI has an impaired response to vasorestrictors

Recommendation Grade of evidence Grade of recommendation
Vasoconstrictors and albumin are not recommended the treatment of HRS outside the criteria of AKI (HRS-NAKI)* Terlipressin plus albumin is effective in the treatment of HRS-NAKI, but recurrence after withdrawal of treatment is the norm, and controversial data exist on the impact of the treatment on long-term clinical outcome, particularly from the perspective of LT	I	1

*Formerly known as HRS type II

Previous CLIF prognostic and diagnostic scores

10 x [0.03 x Age + 0.66 x Ln(Creatinine) + 1.71 x Ln(INR) + 0.88 x

Ln(WBC) 0.05 x Sodium + 8]

CLIF-C Acute decompensation score1*

Sequential Organ Failure Assessment (SOFA) score
Organ/system*	0	1	2	3	4
Liver (bilirubin mg/dl)	<1.2	≥1.2–<2.0	≥2.0–<6.0	≥6.0–<12.0	≥12.0
Kidney (creatinine mg/dl)	<1.2	≥1.2–<2.0	≥2.0–<3.5	≥3.5–<5.0	≥5.0
Cerebral (HE grade)	NO HE	Grade I	Grade II	Grade III	Grade IV
Coagulation (INR and PLT count)	<1.1	≥1.1–<1.25	≥1.25–<1.5	≥1.5–<2.5	≥2.5 or PLT ≤20,000/mm3
Circulation (MAP mmHg and vasopressors†)	≥70	<70	Dopamine ≤5 or dobutamine or terlipressin	Dopamine >5 or A ≤0.1 or NA ≤0.1	Dopamine >15 or A >0.1 or NA >0.1
Lungs
PaO2/FiO2, or	>400	>300–≤400	>200–≤300	>100–≤200	≤100
SpO2/FiO2	>512	>357–≤512	>214–≤357	>89- ≤214	≤89

*Bold text indicates the diagnostic criteria for organ failures; †μg/kg/min

 

Dàn bài

• 1. Đại cương
  2. Bệnh sinh
  3. Nguyên nhân
  4. Biểu hiện lâm sàng
  5. Cận lâm sàng
  6. Biến chứng
  7. Phòng ngừa

ĐẠI CƯƠNG

Loét dạ dày hoặc/và loét tá tràng là những vết loét ở niêm mạc dạ dày hoặc tá tràng, sâu xuống lớp cơ niêm. Cả hai bệnh loét dạ dày và loét tá tràng đều có liên quan đến tác động phá hủy niêm mạc của pepsin và a-xít hydrochloric ở đường tiêu hóa trên. Các ổ loét thường có đường kính từ 3 mm đến vài xen-ti-mét.

Trong trường hợp bệnh Loét dạ dày-tá tràng không có biến chứng, có rất ít dấu hiệu lâm sàng và không đặc hiệu. Đau thượng vị là triệu chứng thường gặp nhất trong loét dạ dày và trong loét tá tràng.

Các thử nghiệm cận lâm sàng thường qui thường không có ích đối với phần lớn bệnh nhân bị Loét dạ dày-tá tràng không có biến chứng. Nội soi đường tiêu hóa trên là thử nghiệm chẩn đoán được chọn.

Dịch tễ học

Ở Mỹ, hàng năm, Loét dạ dày-tá tràng ảnh hưởng đến khoảng 4,5 triệu người. Khoảng 10% dân số Mỹ có bằng chứng loét tá tràng tại một thời điểm bất kỳ. Nhìn chung, tỉ lệ mới bị loét tá tràng giảm trong 3-4 thập niên qua. Mặc dù, tỉ lệ loét dạ dày không có biến chứng giảm, nhưng tỉ lệ loét dạ dày có biến chứng và nhập viện vẫn không thay đổi. Tỉ lệ nhập viện vì Loét dạ dày-tá tràng khoảng 30 bệnh nhân trong 100.000 ca bệnh. Tỉ lệ bệnh Loét dạ dày-tá tràng thay đổi từ chiếm ưu thế ở nam thành tỉ lệ tương tự giữa nam và nữ. Tỉ lệ mắc bệnh trong suốt cuộc đời khoảng 11-14% ở nam và 8-11% ở nữ. Các xu thế tuổi bị loét giảm ở nữ trẻ, nhất là đối với loét tá tràng và tăng ở nữ lớn tuổi. Xu thế này phản ánh những thay đổi phức tạp về yếu tố nguy cơ của Loét dạ dày-tá tràng, gồm đoàn hệ tuổi với nhiễm H.pylori và sử dụng NSAIDs trong dân số người lớn tuổi. Ở những người nhiễm H.pylori, tỉ lệ bị bệnh Loét dạ dày-tá tràng trong suốt cuộc đời khoảng 20%. Chỉ khoảng 10% người trẻ bị nhiễm H.pylori; tỉ lệ nhiễm trùng ngày càng tăng theo tuổi.

Tần suất Loét dạ dày-tá tràng ở các nước khác thay đổi.

Giải phẫu

Xem lại trong sách giải phẫu học

BỆNH SINH

Trước đây người ta cho rằng “No gastric acid, no peptic ulcer”. Tuy nhiên, tiết a- xít dạ dày quá nhiều chỉ là một yếu tố trong bệnh sinh của bệnh Loét dạ dày-tá tràng. Khả năng bảo vệ niêm mạc chống lại tác động phá hủy của a-xít dạ dày bị giảm cũng là căn nguyên gây loét. Tính toàn vẹn của đường tiêu hóa trên phụ thuộc vào tình trạng cân bằng giữa các yếu tố “phá hủy” như a-xít của dạ dày, H.pylori, NSAIDs và pepsin và các yếu tố “bảo vệ” như prostaglandins, chất nhầy, bicarbonate và lưu lượng máu đến niêm mạc ảnh hưởng đến niêm mạc dạ dày ruột.

Bình thường, tế bào biểu mô của dạ dày hoặc tá tràng tiết chất nhầy chống lại những kích thích ở lớp biểu mô và kích thích cholinergic. Bề mặt niêm mạc dạ dày và tá tràng được phủ một lớp gel, lớp này không thấm a-xít và pepsin. Những tế bào nhầy của dạ dày và tá tràng tiết bicarbonate, bicarbonate giúp đệm lớp a-xít nằm kề cận niêm mạc. Prostaglandins E (PGE) có vai trò quan trọng trong bảo vệ niêm mạc dạ dày, vì PGE làm tăng sản xuất bicarbonate và chất nhầy.

Trong trường hợp a-xít và pepsin đi vào tế bào biểu mô, có những cơ chế hỗ trợ để giảm bớt tổn thương. Bơm ion trong màng của các tế bào biểu mô giúp điều hòa pH trong tế bào bằng cách loại bỏ các ion hydrogen. Do tiến trình phục hồi, những tế bào lành sẽ di chuyển đến vị trí tổn thương. Dòng máu ở niêm mạc loại bỏ a-xít khuếch tán vào niêm mạc bị tổn thương và cung cấp bicarbonate cho tế bào biểu mô bề mặt. Trong điều kiện bình thường, cân bằng sinh lý giữa tiết a- xít dạ dày và bảo vệ niêm mạc dạ dày tá tràng.

Tổn thương niêm mạc dạ dày và tá tràng xảy ra khi tác động có hại của a-xít dạ dày lấn át tính chất bảo vệ niêm mạc. Ức chế tổng hợp prostaglandin nội sinh làm giảm tiết bicarbonate, nhầy của tế bào biểu mô, giảm lưu lượng máu đến niêm mạc, giảm tăng sinh tế bào biểu mô và sức đề kháng của niêm mạc với chấn thương. Sức đề kháng của niêm mạc giảm khiến niêm mạc dễ bị tổn thương bởi những yếu tố nội sinh như a-xít, pepsin và a-xít mật và những yếu tố ngoại sinh như NSAIDs, rượu và các chất độc hại khác.

Như vậy, tổn thương niêm mạc và Loét dạ dày-tá tràng xảy ra khi tình trạng cân bằng giữa các yếu tố phá hủy và cơ chế bảo vệ bị phá vỡ. Những yếu tố phá hủy như NSAIDs, nhiễm H.pylori, rượu bia, muối mật, a-xít và pepsin có thể làm thay đổi khả năng bảo vệ niêm mạc cho phép các ion hydrogen khuếch tán ngược và làm tổn thương tế bào biểu mô. Những cơ chế bảo vệ gồm tình trạng liên kết chặt chẽ giữa các bào, chất nhầy, dòng máu của niêm mạc, quá trình phục hồi tế bào và tình trạng tái sinh biểu mô.

NGUYÊN NHÂN

A-xít dạ dày

1/3 bệnh nhân bị loét tá tràng tăng cung lượng a-xít cơ bản (BAO) và cung lượng a-xít tối đa (MAO). Trong một nghiên cứu, BAO tăng đi kèm với tỉ số chênh 3,5 và MAO tăng đi kèm với tỉ số chênh 7 đối với sự phát triển loét tá tràng. Những người đặc biệt có nguy cơ cao là những người có BAO lớn hơn 15 mEq/giờ.

H.pylori

Mối liên hệ giữa xoắn khuẩn H.pylori gram âm với viêm dạ dày được đề cập lần đầu tiên vào năm 1983. Từ đó, các nghiên cứu phát hiện H.pylori là một phần quan trọng trong bộ ba bao gồm a-xít và pepsin, góp phần khởi đầu gây bệnh Loét dạ dày-tá tràng. Vi khuẩn gây viêm niêm mạc và ở một số người, vi khuẩn làm bệnh loét dạ dày trầm trọng hơn. H.pylori có những đặc điểm vi sinh độc đáo, như sản xuất urease làm kiềm hóa môi trường xung quanh vi khuẩn và tồn tại trong nhiều năm trong môi trường a-xít không thân thiện của dạ dày và sản xuất những yếu tố độc lực khác như catalase, cytotoxin tạo không bào và lipopolysaccharide.

H.pylori định cư ở niêm mạc dạ dày, thường gây viêm niêm mạc. Mối liên hệ nhân quả giữa viêm dạ dày do H.pylori và loét tá tràng hiện nay đã được chứng minh rõ trong y văn trên người. Ở những bệnh nhân bị nhiễm H.pylori, nồng độ gastrin và pepsinogen cao, nồng độ somatostatin bị giảm và tá tràng tăng tiếp xúc với a-xít. Ngoài ra, ở bệnh nhân bị loét tá tràng, thường làm trống dạ dày nhanh; một lượng lớn a-xít tống thoát vào đoạn đầu tá tràng, do đó loét hành tá tràng chiếm 95% loét tá tràng. Hầu hết ở bệnh nhân loét tá tràng, bài tiết bicarbonate của tá tràng bị hư hỏng, điều này đã được chứng minh là do H.pylori vì tiệt trừ H.pylori làm thay đổi hoàn toàn khiếm khuyết này. Tăng tiết a-xít dạ dày và giảm tiết bicarbonate tá tràng càng làm giảm thấp pH ở tá tràng. Toan hóa tá tràng khiến chuyển sản dạ dày – thay thế các tế bào có lông của tá tràng bằng những tế bào có đặc điểm về hình dạng và bài tiết của biểu mô dạ dày – tạo môi trường thích hợp cho H.pylori định cư. Nhiễm H.pylori trong những vùng chuyển sản dạ dày gây viêm tá tràng và khiến niêm mạc dễ nhạy cảm với tổn thương do a-xít, tạo điều kiện thuận lợi gây loét tá tràng.

Nhiễm trùng H.pylori ở dạ dày giải thích cho đa số các trường hợp Loét dạ dày- tá tràng. Vi khuẩn này cũng có vai trò trong sự hình thành lymphoma dạng MALT và ung thư biểu mô tuyến dạ dày. Nhiễm trùng H.pylori thực sự có liên quan với viêm dạ dày hoạt động, nhưng chỉ khoảng 10-15% người bị nhiễm trùng phát triển thành Loét dạ dày-tá tràng thực sự. Tác động của H.pylori trên đường tiêu hóa (Viêm dạ dày, Loét dạ dày-tá tràng, Lymphoma dạng MALT, Ung thư dạ dày) là hậu quả của tác động tương hỗ phức tạp giữa kí chủ và vi khuẩn.

Yếu tố vi khuẩn

H.pylori có thể tự tạo điều kiện thuận lợi để cư trú ở dạ dày, gây tổn thương niêm mạc dạ dày và thoát khỏi hệ thống bảo vệ của ký chủ. Các chủng H.pylori khác nhau sản xuất yếu tố độc tính khác nhau. Vùng đặc hiệu của bộ gen của vi khuẩn, còn được gọi là đảo gây bệnh, mã hóa các yếu tố độc tính Cag A và pic

B. Mặc dù không được mã hóa trong đảo gây bệnh, nhưng Vac A cũng góp phần sinh bệnh. Những yếu tố độc lực này, cùng với những yếu tố cấu thành của vi khuẩn, có thể gây tổn thương niêm mạc. Urease cho phép vi khuẩn cư trú trong dạ dày có tính a-xít. Urease sinh ra NH₃ có thể làm tổn thương tế bào biểu mô. Vi khuẩn sản xuất những yếu tố bề mặt có tác động như các hóa chất góp phần gây tổn thương tế bào biểu mô. H.pylori sản xuất protease và phospholipases, phân hủy phức hợp glycoprotein lipid của chất nhầy ở niêm mạc, do vậy làm giảm hiệu quả của lớp bảo vệ niêm mạc đầu tiên này. Adhesins của H.pylori tạo điều kiện thuận lợi cho sự kết dính của vi khuẩn vào tế bào biểu mô của dạ dày. Lipopolysaccharide của H.pylori có hoạt tính miễn dịch thấp so với lipopolysaccharide của các vi khuẩn khác, có thể thúc đẩy tiến trình viêm mạn diễn tiến âm ỉ.

Yếu tố kí chủ

Đáp ứng viêm với H.pylori gồm huy động bạch cầu đa nhân trung tính, lympho bào (T và B), đại thực bào và tương bào. Tác nhân gây bệnh khiến tổn thương tại chỗ do gắn kết với các phân tử MHC lớp II được biểu hiện trên các tế bào biểu mô của dạ dày, gây chết tế bào. Ngoài ra, chủng vi khuẩn mã hóa cag-PAI có thể đưa Cag A vào tế bào ký chủ, gây tổn thương tế bào thêm và hoạt hóa con đường tế bào, tham gia vào tiến trình sản xuất cytokine. Trong biểu mô dạ dày của người bị nhiễm H.pylori, nồng độ nhiều loại cytokine tăng cao gồm interleukin(IL) 1/, IL-2, IL-6, IL-8, yếu tố hoại tử bướu- và interferon (IFN-

). Nhiễm H.pylori cũng gây đáp ứng niêm mạc và đáp ứng thể dịch toàn thân; tuy nhiên, đáp ứng này không tiệt trừ vi khuẩn mà còn làm tế bào biểu mô bị tổn thương nặng thêm. Ngoài ra, H.pylori có thể gây tổn thương tế bào biểu mô theo các cơ chế bổ sung khác như (1) sản xuất các gốc nitơ hoặc oxygen phản ứng qua trung gian bạch cầu đa nhân trung tính đã được hoạt hóa và tốc độ hoạt động của tế bào biểu mô tăng nhanh và (2) tế bào chết theo lập trình do tương tác với tế bào T (tế bào giúp đỡ T 1 hoặc T_H1) và IFN-.

Kháng viêm nonsteroids

Sử dụng NSAID là nguyên nhân thường gặp gây Loét dạ dày-tá tràng. Những thuốc này phá vỡ hàng rào thấm của niêm mạc, làm niêm mạc dễ tổn thương. Khoảng 30% người lớn sử dụng NSAIDs có tác dụng phụ trên dạ dày ruột. Những yếu tố đi kèm làm tăng nguy cơ loét dạ dày-tá tràng trong bệnh cảnh sử dụng NSAID gồm tiền sử bị Loét dạ dày-tá tràng, tuổi cao ( 5 tuổi), nữ, liều cao hoặc phối hợp nhiều NSAIDs, sử dụng NSAID lâu dài, sử dụng đồng thời với corticosteroid và các thuốc kháng đông, bệnh nặng xảy ra đồng thời.

Đầu tiên NSAIDs làm tổn thương tại chỗ do bản chất a-xít của thuốc. NSAIDs làm giảm tính kỵ nước của dịch nhầy và giảm sản xuất chất nhầy trong dạ dày, nên pepsin và a-xít nội sinh của dạ dày dễ làm tổn thương biểu mô bề mặt. Tác động toàn thân của NSAIDs chủ yếu do tổng hợp prostaglandins ở niêm mạc bị giảm. A-xít arachidonic, tiền thân của prostaglandins, được xúc tác bởi hai isoenzyme cyclo-oxygenase, cyclo-oxygenase-1 và cyclo-oxygenase-2. Gen cyclo-oxygenase-1, enzyme nội dịch, duy trì cân bằng nội môi của các cơ quan. Cyclo-oxygenase-2, enzyme gây viêm, dễ cảm ứng. Mặc dù NSAIDs ức chế cả

hai isoenzyme cyclo-oxygenase, nhưng chỉ gen cyclo-oxygenase-2 chứa thành phần kìm hãm đáp ứng với corticosteroid. Đặc tính kháng viêm của NSAIDs qua trung gian ức chế cyclo-oxgenase-2; còn những tác dụng phụ, như loét dạ dày và tá tràng, xảy ra là hậu quả chủ yếu của những tác động trên cyclo-oxygenase-1. NSAIDs gây loét dạ dày nhiều hơn loét tá tràng.

Hiện nay hầu hết bằng chứng ủng hộ xác nhận rằng H.pylori và NSAIDs có tác động hiệp lực gây bệnh Loét dạ dày-tá tràng. Nhiễm H.pylori thường gặp ở bệnh nhân dùng NSAIDs chiếm tỉ lệ 22-63%.

Bướu tiết gastrin (hội chứng Zollinger-Ellison)

Hội chứng Zollinger-Ellison gồm Loét dạ dày-tá tràng (thường nhiều ổ loét), tăng tiết a-xít dạ dày lượng lớn và bướu tế bào sản xuất gastrin. Bướu tiết gastrin ở tụy chiếm tỉ lệ khoảng 50% bệnh nhân bị bướu tiết gastrin. 20% bệnh nhân có bướu gastrin ở tá tràng hoặc ở những nơi khác như dạ dày, hạch bạch huyết quanh tụy, gan, buồng trứng hoặc mạc treo ruột non.

Hội chứng Zollinger-Ellison chỉ chiếm 0,1% trong Loét dạ dày-tá tràng. ¼ bệnh nhân có hội chứng này là hội chứng đa tân sinh typ I (MEN I).

Lâm sàng nghĩ đến hội chứng này khi bệnh nhân bị loét nặng, khó chữa; nội soi hoặc chụp X quang thấy phì đại các nếp dạ dày; bệnh nhân bị tiêu chảy (tiêu chảy nước hoặc tiêu chảy mỡ do a-xít bất hoạt lipase) và trào ngược dạ dày thực quản. Khoảng 75% bệnh nhân có các triệu chứng xảy ra từng đợt. Bệnh nhân thường có nồng độ gastrin huyết thanh lúc đói lớn hơn 200 pg/mL (Nên ngừng điều trị với các thuốc ức chế bơm proton ít nhất 2 tuần trước khi đo nồng độ gastrin) và cung lượng a-xít cơ bản lớn hơn 15 mEq/giờ.

Tăng calci máu

Tăng calci máu có liên quan trực tiếp đến tăng tiết a-xít dạ dày ở bệnh nhân bị hội chứng Zollinger-Ellison và MEN I. Ở những người tình nguyện không bị bệnh, truyền calci tĩnh mạch làm tăng tiết acid dạ dày. Ngoài ra, in vivo và in vitro đã chứng minh calci kích thích trực tiếp phóng thích gastrin từ bướu gastrin. Giải quyết tình trạng tăng calci máu (bằng cách cắt tuyến cận giáp) làm giảm cung lượng a-xít cơ bản và nồng độ gastrin huyết thanh ở bệnh nhân bị bướu gastrin lúc đói và những bệnh nhân bị MEN I.

Gen

Các yếu tố gen đóng vai trò quan trọng trong bệnh sinh Loét dạ dày-tá tràng. Tỉ lệ mắc bệnh trong suốt cuộc đời đối với Loét dạ dày-tá tràng trong những người thân hàng thứ nhất khoảng ba lần nhiều hơn so với dân số chung. Hơn 20% bệnh nhân loét tá tràng có tiền sử gia đình bị bệnh; loét dạ dày cũng có những nhóm thành viên trong gia đình bị ảnh hưởng như vậy.

Ngoài ra, có mối liên hệ không chắc chắn giữa loét tá tràng và nhóm máu O. Những bệnh nhân không tiết kháng nguyên ABO trong nước bọt và dịch vị có nguy cơ cao hơn. Lý do của những mối liên hệ về gen này chưa rõ.

Mối liên hệ về gen hiếm giữa tăng pepsinogen máu gia đình type I (kiểu hình về gen gây tăng tiết pepsin) và loét tá tràng. Tuy nhiên, H.pylori có thể làm tăng tiết pepsin và một phân tích hồi cứu huyết thanh của một gia đình được nghiên cứu trước khi khám phá H.pylori phát hiện nồng độ pepsin của họ cao chắc chắn có liên quan với nhiễm H.pylori.

Hút thuốc

Y văn cho thấy mối tương quan mạnh giữa hút thuốc lá và tỉ lệ mới bị Loét dạ dày-tá tràng, tử vong, biến chứng, tái phát và chậm lành bệnh. Những người hút thuốc có khả năng bị Loét dạ dày-tá tràng nhiều hơn người không hút thuốc 2 lần. Hút thuốc làm niêm mạc tăng nhạy cảm, giảm những yếu tố bảo vệ niêm mạc hoặc tạo môi trường thuận lợi hơn đối với nhiễm H.pylori, sự xâm nhập ở niêm mạc hang vị của H.pylori dày đặc hơn. Hút thuốc và H.pylori là những đồng yếu tố hình thành Loét dạ dày-tá tràng. Hút thuốc trong bệnh cảnh nhiễm H.pylori làm tăng nguy cơ tái phát Loét dạ dày-tá tràng.

Chấn động tâm lí

Nhiều nghiên cứu phát hiện những kết luận trái ngược nhau về vai trò của các yếu tố tâm lí trong bệnh sinh và diễn tiến tự nhiên của bệnh Loét dạ dày-tá tràng. Những chấn động cấp làm tăng nhịp tim, huyết áp, lo lắng, nhưng chỉ ở những bệnh nhân bị loét tá tràng chấn động cấp thực sự gây tăng tiết a-xít cơ bản đáng kể. Không có chứng minh rõ ràng về nhân cách ‘loét’. Những bệnh nhân bị loét điển hình có biểu hiện tâm lí tương tự dân số chung, nhưng hình như họ cảm nhận mức độ chấn động nhiều hơn. Ngoài ra, không có bằng chứng rằng các yếu tố nghề nghiệp khác biệt ảnh hưởng tỉ lệ mới bị bệnh loét.

Những tình huống gây chấn động nặng có thể gây Loét dạ dày-tá tràng như phỏng, chấn thương thần kinh trung ương, phẫu thuật và bệnh nội khoa trầm trọng. Bệnh toàn thân nặng, nhiễm trùng, hạ huyết áp, suy hô hấp và đa chấn thương làm tăng nguy cơ loét (do chấn thương) thứ phát.

Loét Cushing là loét dạ dày cấp đi kèm với chấn thương não hoặc bướu não gây tăng áp lực nội sọ, kích thích nhân thần kinh phế vị  kích thích acetylcholine

 kích thích thụ thể M3 ở tế bào thành của dạ dày  tăng tiết a-xít dạ dày. Điển hình là ổ loét sâu, đơn độc dễ thủng. Ngoài dạ dày, có thể loét ở thực quản đoạn thấp, hoặc phần đầu tá tràng.

Loét Curling là loét tá tràng cấp thường gặp ở bệnh nhân bị phỏng nặng gây giảm thể tích huyết tương, chiếm tỉ lệ 10%, nhất là ở trẻ em.

Rượu và chế độ ăn

Mặc dù rượu gây tổn thương niêm mạc dạ dày trên súc vật thử nghiệm, nhưng có vẻ như do sử dụng ethenol tuyệt đối. Rượu tinh khiết là lipid hòa tan và gây tổn thương niêm mạc cấp. Vì hầu hết mọi người không uống rượu tuyệt đối, nên chắc chắn không tổn thương niêm mạc ở nồng độ rượu dưới 10%. Rượu nồng độ thấp (5%) có thể kích thích tiết a-xít dạ dày vừa phải; nồng độ cao làm giảm tiết a-xít.

Một số loại thức ăn và đồ uống gây chứng khó tiêu. Không có bằng chứng cho thấy chế độ ăn đặc biệt nào gây bệnh Loét dạ dày-tá tràng. Các nghiên cứu dịch tễ không phát hiện mối liên quan giữa các thức uống có cà-phê, không có cà-phê hoặc cola, bia hoặc sữa với nguy cơ bệnh loét tăng. Thay đổi chế độ ăn không cần thiết ở bệnh nhân bị loét, trừ trường hợp cần tránh những thức ăn gây đau.

Những yếu tố căn nguyên bổ sung

Những tình trạng sau đây có thể đi kèm với Loét dạ dày-tá tràng:

• Xơ gan
• Bệnh phổi tắc nghẽn mạn tính
• Viêm dạ dày dị ứng và viêm dạ dày tăng bạch cầu ái toan
• Nhiễm Cytomegalovirus
• Bệnh mảnh ghép tấn công ký chủ
• Bệnh dạ dày do tăng ure máu
• Viêm dạ dày Henoch-Schönlein
• Bệnh dạ dày do chất ăn mòn
• Bệnh Celiac
• Bệnh dạ dày do mật
• Bệnh tự miễn
• Bệnh Crohn
• Các bệnh viêm dạ dày dạng hạt khác (sarcoidosis, histiocytosis X, lao)
• Các bệnh nhiễm khác, nhiễm Epstein-Barr virus, HIV, Helicobacter heilmannii, herpes simplex, cúm, giang mai, Candida albicans, histoplasmosis, mucormycosis và nhiễm giun tròn
• Hóa trị, như 5-fluorouracil, methotrexate và cyclophosphamide
• Tia xạ tại chỗ gây tổn thương niêm mạc, có thể gây loét tá tràng
• Sử dụng cocaine cứng, gây co mạch cục bộ, làm giảm lưu lượng máu và có thể gây tổn thương niêm mạc

BIỂU HIỆN LÂM SÀNG

Tiền sử

Điều tra tiền sử Loét dạ dày-tá tràng, nhiễm H.pylori, uống NSAIDs hoặc hút thuốc là cần thiết để có chẩn đoán đúng.

Bệnh sử

Loét dạ dày thường không thể phân biệt với loét tá tràng nếu chỉ đơn thuần dựa vào bệnh sử, mặc dù một số triệu chứng có thể gợi ý.

Đau thượng vị là triệu chứng thường gặp nhất trong loét dạ dày và trong loét tá tràng. Đau thượng vị có đặc trưng là cảm giác cồn cào khi đói hoặc nóng rát xảy ra sau bữa ăn – kinh điển, cảm giác này xảy ra ngay sau khi ăn trong loét dạ dày và 2-3 giờ sau bữa ăn trong loét tá tràng. Thức ăn hoặc antacide làm giảm đau do loét tá tràng, đối với loét dạ dày thuốc chỉ làm giảm đau rất ít.

Loét tá tràng thường khiến bệnh nhân thức giấc vào ban đêm. Khoảng 30-80% bệnh nhân loét tá tràng bị đau ban đêm, ngược lại chỉ 30-40% bệnh nhân loét dạ dày và 20-40% bệnh nhân bị chứng khó tiêu không loét bị đau ban đêm. Điển hình đau xuất hiện theo kiểu đau liên tục suốt ngày, tăng sau khi ăn no trong loét dạ dày hoặc tăng khi đói trong loét tá tràng. Đau lan ra sau lưng gợi ý loét dạ dày thủng vào tụy gây viêm tụy cấp.

Đau bụng ở bệnh nhân loét được giải thích bằng nhiều giả thuyết gồm tác động của a-xít trên thụ thể hóa học trong tá tràng, tăng độ nhạy của tá tràng với a-xít mật và pepsin hoặc vận động dạ dày tá tràng bị thay đổi.

Những biểu hiện khác có thể gặp gồm:

• Khó tiêu, gồm ợ hơi, chướng hơi, căng bụng và khó dung nạp thức ăn béo
• Tiết nước bọt nhiều
• Ợ nóng
• Khó chịu vùng ngực
• Buồn nôn, nôn thường sau khi nôn bệnh nhân thấy dễ chịu hơn
• Ói ra máu hoặc tiêu phân đen gặp do chảy máu ổ loét. Tiêu phân đen có thể từng đợt trong nhiều ngày hoặc nhiều lần trong một ngày duy nhất
• Hiếm gặp, loét chảy máu lượng nhiều gây tiêu máu đỏ
• Những triệu chứng đi kèm với thiếu máu (mệt mỏi, khó thở)
• Đợt triệu chứng xảy ra đột ngột báo hiệu thủng

Loét dạ dày do NSAID có thể không triệu chứng, nhất là ở những người lớn tuổi. Những ‘dấu hiệu báo động’ khiến bệnh nhân phải đến khám tiêu hóa gồm:

• thiếu máu
• tiêu phân đen do chảy máu đường tiêu hóa
• mau no
• sụt cân
• nuốt đau hoặc khó nuốt tăng dần
• nôn tái đi tái lại
• tiền sử gia đình bị ung thư đường tiêu hóa

Khám thực thể

Loét dạ dày-tá tràng không biến chứng, ít dấu hiệu lâm sàng và không đặc hiệu, gồm những dấu hiệu sau:

• Đau thượng vị (thường nhẹ)
• Đau ¼ trên phải gợi ý căn nguyên đường mật hoặc hiếm hơn là Loét dạ dày-tá tràng
• Tiếng óc ách do biến chứng hẹp môn vị một phần hoặc hoàn toàn

CHẨN ĐOÁN PHÂN BIỆT

Nghi ngờ Loét dạ dày-tá tràng ở bệnh nhân có khó chịu và đau thượng vị; tuy nhiên, những triệu chứng này không đặc hiệu. Không đáp ứng với điều trị Loét dạ dày-tá tràng thông thường nên nghĩ đến những chẩn đoán khác chứ không phải là Loét dạ dày-tá tràng lành tính và phải nội soi hoặc chụp X quang bụng.

Chứng khó tiêu không loét hoặc khó tiêu chức năng

Chứng khó tiêu chức năng là chẩn đoán loại trừ ở bệnh nhân bị đau thượng vị mạn và không có bệnh thực thể. Bệnh nhân chủ yếu đau thượng vị được qui cho là chứng khó tiêu kiểu loét hoặc có triệu chứng đầy bụng sau bữa ăn được qui cho chứng khó tiêu vận động.

Bệnh Crohn

Bệnh Crohn có thể ảnh hưởng bất cứ nơi nào của đường tiêu hóa từ niêm mạc miệng đến trực tràng. Mặc dù Crohn có thể khu trú ở tá tràng và hồi tràng, nhưng hiếm gặp Crohn khu trú ở dạ dày.

Hội chứng vành cấp

• Phình động mạch chủ bụng

Viêm đường mật

• Viêm túi mật

Sỏi mật

• Viêm thực quản

Viêm dạ dày cấp

• Viêm dạ dày mạn

Viêm dạ dày ruột

• Bệnh trào ngược dạ dày thực quản
• Viêm gan virus

CẬN LÂM SÀNG

Hầu hết ở bệnh nhân Loét dạ dày-tá tràng không biến chứng, những thử nghiệm thường qui thường không có ích trong chẩn đoán bệnh. Nếu nghi ngờ chẩn đoán, các thử nghiệm công thức máu, chức năng gan, amylase và lipase có thể hữu ích để phân biệt chẩn đoán. Công thức máu và sắt huyết thanh giúp phát hiện thiếu máu, thiếu máu là dấu hiệu báo động chỉ định nội soi sớm để loại bỏ những căn nguyên khác gây mất máu đường tiêu hóa mạn.

Những bệnh nhân đáp ứng với điều trị Loét dạ dày-tá tràng tối ưu không cần thử nghiệm đặc biệt. Tuy nhiên, những bệnh nhân khó chữa (không lành sau 8 tuần điều trị) hoặc tái phát nên định lượng nồng độ gastrin máu và calci máu để tầm soát bướu gastrin và đa tân sinh nội tiết (MEN). Nên khảo sát a-xít dạ dày của những bệnh nhân này để xác định xem có phải loét là do tăng tiết a-xít dạ dày (cung lượng a-xít cơ bản vượt quá 10 mEq/giờ) hoặc do giảm khả năng bảo vệ. Những bệnh nhân bị Loét dạ dày-tá tràng khó chữa hoặc tái phát cần thử nghiệm H.pylori.

X quang dạ dày tá tràng cản quang

X quang dạ dày tá tràng cản quang là phương pháp chẩn đoán loét dạ dày và loét tá tràng phổ biến và được chấp nhận.

Mặc dù là thử nghiệm ít xâm lấn so với nội soi, nhưng chụp X quang dạ dày tá tràng cản quang bị hạn chế vì độ chính xác và độ nhạy kém để xác định tổ thương ở niêm mạc hoặc phân biệt loét lành tính với ác tính. Ở những bệnh nhân có biến dạng giải phẫu do phẫu thuật dạ dày trước đó hoặc sẹo do viêm mạn, có thể khó đọc phim chụp dạ dày tá tràng cản quang. X quang dạ dày tá tràng có tỉ lệ âm giả 30% và dương giả 10%.

Nội soi chẩn đoán Loét dạ dày-tá tràng

Nội soi thực quản dạ dày tá tràng là phương pháp trực tiếp và chính xác nhất để chẩn đoán Loét dạ dày-tá tràng. Ngoài việc nhận biết ổ loét, vị trí và kích thước ổ loét, chuyên gia nội soi còn có cơ hội phát hiện những sang thương khó thấy ở niêm mạc và sinh thiết tổn thương để khảo sát mô học. Sinh thiết qua nội soi được chỉ định đối với tất cả các trường hợp loét dạ dày được phát hiện tại thời điểm chẩn đoán. Hầu hết loét tá tràng lành tính, nên không cần phải sinh thiết để chẩn đoán trong những trường hợp thông thường.

Nội soi chẩn đoán H.pylori

Thử nghiệm H.pylori qua nội soi là những thử nghiệm xâm lấn gồm thử nghiệm urease nhanh, mô học và nuôi cấy thường sử dụng để chẩn đoán nhiễm H.pylori, nhưng thử nghiệm này có thể âm giả ở những bệnh nhân điều trị thuốc ức chế bơm proton.

Thử nghiệm urease nhanh

Thử nghiệm urease nhanh được xem là thử nghiệm chẩn đoán qua nội soi được chọn. Sự hiện diện của H.pylori trong mẫu niêm mạc dạ dày được phát hiện dựa vào urease của vi khuẩn. Mẫu sinh thiết được đặt vào dung dịch hoặc gel có chứa urea và đỏ phenol. Nếu trong mẫu sinh thiết có urease của H.pylori, urea bị thủy phân phóng thích ammonia, pH môi trường tăng và đổi sang màu hồng. Tại thời điểm 3 giờ, độ nhạy của thử nghiệm là 90%. Độ đặc hiệu 95%. Sử dụng kỹ thuật này, cho chẩn đoán nhanh hơn khảo sát mô học.

Khảo sát mô học mẫu sinh thiết nhuộm eosin và hematoxylin chuẩn

Khảo sát mô học các mảnh sinh thiết ở hang vị trong khi nội soi là tiêu chuẩn vàng để chẩn đoán H.pylori.

Nuôi cấy

Nội soi lấy mẫu để nuôi cấy H.pylori. Tuy nhiên, nuôi cấy thường qui H.pylori

thường không thực hiện vì vi khuẩn khó mọc.

Định type H.pylori

Việc phát hiện và phân týp H.pylori có thể được thực hiện bằng nhiều phương pháp như giải trình tự, PCR và lai phân tử với mẫu dò đặc hiệu. Phương pháp PCR đã được sử dụng thành công để phát hiện và phân týp cagA và vacA trực tiếp từ mẫu sinh thiết dạ dày. Thử nghiệm có độ nhạy 64% và độ đặc hiệu 80%.

Các thử nghiệm H.pylori khác

Thử nghiệm H.pylori chủ yếu cho tất cả bệnh nhân bị Loét dạ dày-tá tràng.

Huyết thanh chẩn đoán H.pylori

Thử nghiệm máu tìm kháng thể kháng H.pylori là thử nghiệm dễ thực hiện, nhanh và rẻ. Có độ nhạy 85% và độ đặc hiệu 79% để chẩn đoán nhiễm trùng H.pylori. Tuy nhiên, thử nghiệm này không phân biệt được nhiễm H.pylori đã xảy ra trong quá khứ và đang nhiễm H.pylori. Kháng thể vẫn còn có thể được phát hiện trong huyết thanh nhiều tháng sau điều trị tiệt trừ thành công. Do đó, không sử dụng thử nghiệm này để chứng minh hiệu quả của việc tiệt trừ vi khuẩn.

Tìm kháng nguyên trong phân

Thử nghiệm kháng nguyên trong phân là thử nghiệm không xâm lấn, xác định nhiễm trùng H.pylori hoạt động nhờ phát hiện kháng nguyên H.pylori trong phân. Thử nghiệm này chính xác hơn thử nghiệm kháng thể và ít tốn kém hơn so với thử nghiệm thở urea. Thử nghiệm tìm kháng nguyên H.pylori trong phân có độ nhạy 91% và độ đặc hiệu 93% để chẩn đoán nhiễm trùng H.pylori. Thử nghiệm này được sử dụng để chẩn đoán nhiễm H.pylori và để xác nhận hiệu quả của việc tiệt trừ H.pylori nếu được thực hiện ít nhất 4 tuần sau khi điều trị.

Thở Urea

Thử nghiệm thở urea phát hiện nhiễm H.pylori đang hoạt động dựa vào hoạt tính enzym urease của vi khuẩn. Nhờ sự hiện diện của urease (do H.pylori sản xuất) carbon đồng vị được đánh dấu (C¹³ hoặc C¹⁴) được sản sinh ra trong dạ dày, được hấp thu vào máu, khuếch tán vào phổi và thở ra. Thử nghiệm này không xâm lấn, cho kết quả nhanh trong vòng 20 phút, chính xác nhất để chẩn đoán nhiễm H.pylori, có độ nhạy và độ đặc hiệu 95%; thường được sử dụng để chứng minh hiệu quả của việc tiệt trừ vi khuẩn. Tuy nhiên, thử nghiệm này khá đắt tiền.

Thử nghiệm kích thích Secretin

Thử nghiệm kích thích tiết secretin có thể cần thiết nếu không thể chẩn đoán hội chứng Zollinger-Ellison dựa vào nồng độ gastrin máu đơn thuần. Thử nghiệm này có thể giúp chẩn đoán phân biệt hội chứng Zollinger-Ellison với các tình trạng bệnh khác đi kèm với nồng độ gastrin máu cao, như điều trị kháng tiết bằng các thuốc ức chế bơm proton, suy thận hoặc hẹp môn vị.

BIẾN CHỨNG

Xuất huyết, thủng/xuyên thấu và hẹp môn vị vẫn còn là những biến chứng chính đi kèm với Loét dạ dày-tá tràng mặc dù khả năng có được của thuốc trị loét có hiệu quả. Ở Mỹ, tỉ lệ biến chứng mỗi năm từ 2-5%.

Ung thư dạ dày

Bệnh nhân bị loét dạ dày có nguy cơ phát triển thành ung thư dạ dày. Nguy cơ này khoảng 2% trong 3 năm đầu. Một trong những yếu tố nguy cơ quan trọng là nhiễm H.pylori. H.pylori đi kèm với viêm teo dạ dày, viêm teo dạ dày tạo điều kiện thúc đẩy thành ung thư dạ dày. Nhiễm H.pylori đi kèm với lymphoma dạ dày hoặc lymphoma dạng MALT. Niêm mạc dạ dày bình thường không có mô dạng lympho. Nhiễm H.pylori khiến tiếp nhận thâm nhập tế bào dạng lympho và hình thành các đám hoặc nang dạng lympho từ đó bướu lymphoma dạng MALT phát triển. Tiệt trừ H.pylori rất quan trọng trong nhóm bệnh nhân này vì tiệt trừ H.pylori cho thấy giảm lymphoma dạng MALT. Cần nghi ngờ bệnh ác tính nếu loét dạ dày kéo dài không lành.

Xuất huyết tiêu hóa

(Bài đọc thêm ‘Chẩn đoán Xuất huyết tiêu hóa’, sách Bệnh học Nội)

Xuất huyết tiêu hóa ảnh hưởng đến 5-20% (thường là loét tá tràng) và là biến chứng thường gặp nhất trong Loét dạ dày-tá tràng. Xuất huyết thường xảy ra ở nam nhiều hơn nữ. khoảng 75-80% trường hợp xuất huyết tự ngừng.

Biểu hiện lâm sàng thường gặp là tiêu phân đen đơn thuần hoặc tiêu phân đen kèm nôn ra máu; hiếm khi tiêu máu đỏ.

Chẩn đoán mức độ xuất huyết có thể dựa vào các dấu hiệu lâm sàng sau:

	nhẹ	trung bình	nặng
Lượng máu mất	<1 L	1–2 L	2 L
Huyết áp tâm thu	bình thường > 90 mmHg	giới hạn dưới bình thường 80 – < 90 mmHg	hạ áp < 80 mmHg
Hạ áp tư thế	Không	có thể	chắc chắn
Mạch nhanh	Không 90 – < 100 lần/ ph	vừa phải  100 – 120 l / ph	nhiều (>120 lần/phút)
Da	ấm, tưới máu tốt	đổ mồ hôi	mát – lạnh, ẩm ướt
Nhịp thở	bình thường	bình thường – giảm nhẹ	bất thường
Nước tiểu	bình thường	giảm	vô niệu
Tri giác	tỉnh/lo âu	lo âu	lẫn lộn/ngủ gà

Nguồn: Initial Management of Acute Upper Gastrointestinal Bleeding: From Initial Evaluation up to Gastrointestinal Endoscopy – Cappell MS Friedel D – Med Clin N Am 92 (2008) 491–509.

Cần lưu ý:

• tốc độ mất máu và lượng máu mất là quan trọng
• ở người trẻ khỏe
  • mất 500ml máu trong 15 phút: có thể không có triệu chứng
  • mất 1000ml máu / 15 phút: nhịp tim nhanh, hạ huyết áp, mệt mỏi
  • mất 2000ml máu trong 15 phút: sốc nặng, tử vong

Tiên lượng Xuất huyết tiêu hóa trên do Loét dạ dày-tá tràng theo tiêu chuẩn Rochall để đánh giá nguy cơ tử vong:

Yếu tố đánh giá	Điểm 0	Điểm 1	Điểm 2	Điểm 3	Điểm tối đa cho yếu tố này
Tuổi (năm)	< 60	≥ 0 & ≤ 79	≥ 80		Tối đa 2
Tình trạng choáng	Không (Mạch <100 HATT ≥ 100)	Nhịp tim nhanh (Mạch ≥ 100 HATT ≥ 100)	Hạ huyết áp HATT < 100 mmHg		Tối đa 2
Bệnh kèm theo	Không		Suy tim Thiếu máu cơ tim Bệnh ác tính chưa di căn	Suy thận Suy gan Bệnh ác tính di căn	Tối đa 3
Chẩn đoán bệnh dựa nội soi	Hội chứng Mallory Weiss Không tổn thương	Loét dạ dày-tá tràng Viêm trợt Viêm thực quản	Bệnh ác tính của đường tiêu hóa		Tối đa 2
Dấu hiệu mới xuất huyết khi nội soi	Không cục máu đông Chấm đen phẳng		Máu trong đường tiêu hóa Đang chảy máu Cục máu đông Lộ mạch		Tối đa 2

Thủng

Thủng thường gặp ở người lớn tuổi điều trị NSAID kinh niên và thường gặp trong loét dạ dày nhiều hơn so với loét tá tràng. Tỉ lệ thủng ở nam cao hơn nữ. Khoảng 15% bệnh nhân tử vong do thủng ổ loét. Bệnh cảnh lâm sàng nặng và cấp. Bệnh sử và khám thực thể gợi ý chẩn đoán thủng. Dấu hiệu hơi tự do trong bụng chiếm tỉ lệ khoảng 70% trường hợp.

Khoảng 5-10% bệnh nhân Loét dạ dày-tá tràng bị thủng vào xoang bụng. Thủng tự do xảy ra khi các chất chứa trong lòng dạ dày hoặc tá tràng đổ vào xoang bụng. Đây là một tình trạng bụng cấp, dễ chẩn đoán.

5-10% ổ loét xói mòn toàn bộ thành dạ dày hoặc tá tràng vào cơ quan kề cận như tụy (thường gặp nhất), ống mật, gan, ruột non hoặc ruột già. Đợt khởi phát của

các biến chứng đi kèm như viêm tụy cấp, viêm đường mật hoặc tiêu ra thức ăn chưa tiêu hóa gợi ý chẩn đoán bệnh. Chẩn đoán thủng vào các cơ quan khó hơn thủng tự do.

Hẹp môn vị

Ít hơn 5% bệnh nhân bị hẹp môn vị. Loét tá tràng thường gây hẹp môn vị nhiều hơn loét dạ dày. Loét dạ dày-tá tràng có thể gây hẹp môn vị với nhiều mức độ hẹp khác nhau do viêm sưng phồng ống môn vị hoặc do sẹo xơ hóa mạn tính. Bệnh nhân bị hẹp môn vị thường có bệnh sử buồn nôn, nôn và đau thượng vị hoặc đầy bụng. Cận lâm sàng có thể thấy thiếu máu, albumin huyết thanh thấp và kiềm hóa tăng kali máu. Khảo sát quang tuyến thường giúp chẩn đoán, bóng dạ dày to kèm mức nước hơi. Nội soi là phương pháp tốt nhất để đánh giá hẹp môn vị sau khi giải áp dạ dày 12-24 giờ.

TIÊN LƯỢNG

Khi giải quyết được nguyên nhân cơ bản, tiên lượng tốt. Hầu hết bệnh nhân được điều trị tiệt trừ nhiễm H.pylori thành công, tránh sử dụng NSAIDs và điều trị kháng tiết thích hợp. Tiệt trừ nhiễm H.pylori làm thay đổi diễn tiến tự nhiên của bệnh, giảm tỉ lệ loét tái phát từ 60-90% còn khoảng 10-20%. Tuy nhiên, hiện nay tỉ lệ loét tại phát cao hơn báo cáo trước đây, gợi ý số ca bệnh loét không do nhiễm H.pylori gia tăng.

Đối với loét do NSAID, tỉ lệ mới bị thủng khoảng 0,3% mỗi bệnh nhân mỗi năm và tỉ lệ mới bị hẹp môn vị khoảng 0,1% mỗi bệnh nhân mỗi năm. Vừa loét dạ dày vừa loét tá tràng, tỉ lệ bị biến chứng trong tất cả các nhóm tuổi là khoảng 1- 2% mỗi vết loét mỗi năm.

Tỉ lệ tử vong do Loét dạ dày-tá tràng khoảng 1/100.000 ca. Nếu xem xét tất cả những bệnh nhân loét tá tràng, tỉ lệ tử vong do xuất huyết do loét tá tràng khoảng 5%. Trong 20 năm qua, tỉ lệ tử vong do xuất huyết tiêu hóa do loét không thay đổi đáng kể mặc dù sự xuất hiện của các thuốc kháng thụ thể histamine-2 và các thuốc ức chế bơm proton. Tuy nhiên, chứng cứ từ các phân tích gộp và những nghiên cứu khác cho thấy tỉ lệ tử vong do Loét dạ dày-tá tràng xuất huyết giảm khi sử dụng thuốc ức chế bơm proton sau khi điều trị cầm máu qua nội soi thành công.

PHÒNG NGỪA

Béo phì có liên quan với bệnh Loét dạ dày-tá tràng, nên tư vấn về hiệu quả của việc giảm cân. Tư vấn giảm chấn động tâm lí có thể có lợi trong những trường hợp riêng lẻ nhưng không cần thiết thường qui.

Phòng ngừa cấp một loét do NSAID gồm:

• Tránh sự dụng NSAIDs khi không cần thiết
• Sử dụng acetaminophen hoặc salicylates nonacetylated nếu được
• Sử dụng liều hiệu quả thấp nhất NSAID và chuyển sang NSAIDs ít độc hơn, như NSAIDs thế hệ mới hơn hoặc các thuốc ức chế cyclooxygenase- 2 (COX-2), ở bệnh nhân có nguy cơ cao mà không có bệnh tim mạch

Cân nhắc điều trị phòng ngừa đối với những bệnh nhân:

• Bệnh nhân bị loét do NSAID, cần điều trị NSAID kinh niên mỗi ngày
• Bệnh nhân trên 0 tuổi
• Bệnh nhân có tiền sử Loét dạ dày-tá tràng hoặc biến chứng như xuất huyết tiêu hóa
• Bệnh nhân sử dụng steroids hoặc kháng đông đồng thời hoặc bệnh nhân có bệnh nội khoa nặng đồng thời

Phác đồ làm giảm đáng kể nguy cơ Loét dạ dày-tá tràng do NSAID gồm sử dụng thuốc đồng phân prostaglandin hoặc thuốc ức chế bơm prtoton.

TÀI LIỆU THAM KHẢO

1. Greenwald AD, Brandt JL (2010). The Upper Gastrointestinal Tract. In: Fillit MH, Rockwood K, Woodhouse K. Brocklehurst’s Textbook of Geriatric medicine and Gerontology, 7^th ed., 614-615. Saunders, Philadelphia.
2. Gyawali CP, Manasra A (2010). Gastrointestinal Diseases. In: Foster C, Mistry FN, Peddi FP, Sharma S. The Washington Manual of Medical Therapeutics, 33^rd ed., 596-599. Wolters Kluwer  Lippincott Williams & Wilkins, United States.
3. Gyawali CP (2012). Upper Gastrointestinal Bleeding. In: Kollef M, Isakow

W. The Washington Mannual of Critical Care. 2^nd 397-407. Wolters Kluwer 

Lippincott Williams & Wilkins, USA.

1. Malfertheiner P, Chan LKF, McColl LEK (2009). Peptic ulcer disease. Lancet, 374: 1449-1461.
2. Valle DJ (2010). Peptic Ulcer Diseases and Related Disorders. In: Longo LD, Fauci SA. Harrison’s Gastroenterology and Hepatology, 125-144. The McGraw-Hill Companies, China.

Author:

Leonard I Ganz, MD, FHRS, FACC

Section Editors:

Peter J Zimetbaum, MD

Ary L Goldberger, MD

James Hoekstra, MD

Deputy Editor:

Brian C Downey, MD, FACC

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Oct 2017. | This topic last updated: Jul 20, 2017.

INTRODUCTION — Tachycardias are broadly categorized based upon the width of the QRS complex on the electrocardiogram (ECG).

●A narrow QRS complex (<120 msec) reflects rapid activation of the ventricles via the normal His-Purkinje system, which in turn suggests that the arrhythmia originates above or within the atrioventricular (AV) node (ie, a supraventricular tachycardia [SVT]).

●A widened QRS (≥120 msec) occurs when ventricular activation is abnormally slow for one of the following reasons (see “Approach to the diagnosis of wide QRS complex tachycardias”, section on ‘Causes of WCT’):

•The arrhythmia originates outside of the normal conduction system (ie, ventricular tachycardia [VT])

•Abnormalities within the His-Purkinje system (ie, SVT with aberrancy)

•Pre-excitation with an SVT conducting antegrade over an accessory pathway, resulting in direct activation of the ventricular myocardium

A wide complex tachycardia (WCT) represents a unique clinical challenge for two reasons:

●Diagnosing the arrhythmia is difficult – Although most WCTs are due to VT, the differential diagnosis includes a variety of SVTs. Diagnostic algorithms to differentiate these two etiologies are complex and imperfect.

●Urgent therapy is often required – Patients may be unstable at the onset of the arrhythmia or deteriorate rapidly at any time, particularly if the WCT is VT [1-4].

The management of patients with a wide QRS complex tachycardia will be discussed here. The clinical manifestations, diagnosis, and initial evaluation of patients with a wide QRS complex tachycardia, as well as discussion of narrow QRS complex tachycardias, is presented separately. (See “Approach to the diagnosis of wide QRS complex tachycardias” and “Overview of the acute management of tachyarrhythmias” and “Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy” and “Clinical manifestations, diagnosis, and evaluation of narrow QRS complex tachycardias”.)

MANAGEMENT — The acute management of a patient with wide complex tachycardia (WCT) depends on the hemodynamic stability of the patient. Urgent or emergency management is required in unstable patients, with management taking precedence over further diagnostic workup until the patient has been stabilized. Following initial management and stabilization of the patient, chronic management of the patient with WCT will be directed by the etiology of the WCT (supraventricular versus ventricular).

Initial management — All patients with a WCT should have a brief immediate assessment of the symptoms, vital signs, and level of consciousness to determine if they are hemodynamic stable or unstable. While the assessment of hemodynamic status is being performed by a clinician, other members of the health care team should:

●Administer supplemental oxygen

●Establish intravenous access

●Send blood for appropriate initial studies (see “Approach to the diagnosis of wide QRS complex tachycardias”, section on ‘Ancillary testing’)

●Attach the patient to a continuous cardiac monitor

●Obtain a 12-lead electrocardiogram (ECG)

Differentiation between a hemodynamically stable versus unstable patient is as follows (see “Approach to the diagnosis of wide QRS complex tachycardias”, section on ‘Assessment of stability’):

●An unstable patient will have evidence of hemodynamic compromise, such as hypotension, altered mental status, chest pain, or heart failure, but generally remains awake with a discernible pulse. Patients who become unresponsive or pulseless are considered to have a cardiac arrest and are treated according to standard resuscitation algorithms.

●A stable patient shows no evidence of hemodynamic compromise despite a sustained rapid heart rate, but should have continuous monitoring and frequent reevaluations due to the potential for rapid deterioration as long as the WCT persists.

Patients who are initially stable may rapidly become unstable, particularly in the setting of extremely rapid heart rates (greater than 200 beats per minute) or significant underlying cardiac comorbidities.

Unstable patients — Hemodynamic compromise may occur with any WCT, regardless of the etiology, but is more likely in patients with ventricular tachycardia (VT). Patients who are felt to be hemodynamically unstable require prompt treatment with electrical cardioversion/defibrillation to prevent further clinical deterioration or sudden cardiac arrest (SCA).

●Patients with WCT who are hemodynamically unstable and pulseless, or who become pulseless during the course of evaluation and treatment, should be managed according to standard advance cardiac life support (ACLS) resuscitation algorithms, with immediate high-energy countershock and cardiopulmonary resuscitation (CPR) (algorithm 1). Patients should initially be treated with a synchronized (if possible) 120 to 200 joule shock from a biphasic defibrillator or a 360 joule shock from a monophasic defibrillator; if synchronization is not possible, then an unsynchronized countershock should be delivered, typically at higher energy doses [5]. (See “Advanced cardiac life support (ACLS) in adults” and “Basic life support (BLS) in adults” and “Supportive data for advanced cardiac life support in adults with sudden cardiac arrest”.)

●For patients with WCT who are hemodynamically unstable, but still responsive with a discernible blood pressure and pulse, we recommend urgent cardioversion (with procedural sedation when feasible). The selection of energy level and the choice between synchronized and unsynchronized shocks depends on the clinical situation (algorithm 2):

•If the QRS complex and T wave can be distinguished, an attempt at emergent synchronized cardioversion can be performed. Initial cardioversion is performed with a synchronized shock of 100 joules using either a biphasic or monophasic defibrillator, with upward titration of the energy if additional shocks are needed [5].

•If the QRS complex and T wave cannot be distinguished accurately, a synchronized shock is not possible. Patients should initially be treated with an unsynchronized 120 to 200 joule shock from a biphasic defibrillator or a 360 joule shock from a monophasic defibrillator [5].

•Intravenous analgesics or sedatives should be cautiously administered if the blood pressure will tolerate their use. However, the use of such agents must be balanced against the risks of further hemodynamic deterioration, and therapy should not be unnecessarily delayed if the ability to administer conscious sedation is not readily available.

Stable patients with uncertain WCT etiology — In a patient with WCT who is hemodynamically stable, additional time may be spent attempting to determine the diagnosis. If the initial diagnosis of WCT was made from a single-lead rhythm strip, a full 12-lead ECG should be obtained during the WCT and methodically reviewed as this may provide additional clues to the etiology. In addition, a trial of vagal maneuvers and/orpharmacologic intervention can provide both diagnostic information and, on occasion, prove therapeutic if there is resolution of the WCT. (See “Approach to the diagnosis of wide QRS complex tachycardias”, section on ‘Evaluation of the electrocardiogram’.)

For hemodynamically stable patients with WCT which is regular and monomorphic in whom the etiology of the WCT remains uncertain, we suggest the following approach (algorithm 2):

●Perform vagal maneuvers (Valsalva, carotid sinus massage, etc) – Introducing transient block at the atrioventricular (AV) node can serve as a diagnostic/therapeutic challenge. Most supraventricular tachycardias (SVTs) are AV node dependent (eg, atrioventricular nodal reentrant tachycardia, atrioventricular reentrant tachycardia [AVRT]), so transient AV nodal block will terminate most SVTs. Atrial flutter and atrial tachycardia may be “unmasked” by transient AVN block. Vagal maneuvers should have no significant effect on VT. (See “Vagal maneuvers”.)

●Administer adenosine – Intravenous adenosine has essentially the same effect as vagal maneuvers on SVT and atrial flutter/tachycardia. Some idiopathic VTs (eg, right ventricular outflow tract [RVOT] VT) may terminate with adenosine. Resuscitation equipment should be immediately available as rarely adenosine will precipitate hemodynamic collapse. The initial dose of adenosine is 6 mg; if this has no effect, 12 mg can be administered.

●Avoidance of other pharmacologic agents – Intravenous beta blockers, calcium channel blockers, and digoxin are not typically used, due to the potential for hemodynamic deterioration (often the result of hypotension) in patients with a previously stable WCT.

●Further treatment is directed by the response to vagal maneuvers and/or adenosine, specifically targeting VT or the relevant SVT. If the WCT persists and the etiology remains uncertain, we proceed as though the WCT is VT and treat accordingly. (See ‘Stable patients with known WCT etiology’ below.)

While any ECG analysis and diagnostic/therapeuticmaneuvers are being performed, close observation and continuous ECG monitoring are paramount, as patients with WCT who appear stable initially may experience a rapid deterioration of their clinical status with little or no warning.

Vagal maneuvers — In patients with WCT of uncertain etiology, the response to vagal maneuvers may provide insight to the mechanism responsible for the arrhythmia. We perform one or more vagal maneuvers in all patients with WCT who are hemodynamically stable, often while preparing for pharmaceutical therapy or cardioversion. However, these interventions are associated with some risk, primarily the potential for hemodynamic deterioration in a borderline unstable patient, and as such should only be performed by experienced individuals in an environment capable of dealing with potential sequelae.

Vagal maneuvers increase parasympathetic input to the heart, which slows the rate of sinus node impulse formation and slows AV node conduction velocity while simultaneously lengthening the refractory period. The Valsalva maneuver and carotid sinus massage, two of the most commonly performed vagal maneuvers which enhance vagal tone and therefore depresses sinus and AV nodal activity, can be easily and quickly done at the bedside. (See “Vagal maneuvers”.)

Examples of how various arrhythmias respond to vagal stimulation include (see “Clinical manifestations, diagnosis, and evaluation of narrow QRS complex tachycardias”, section on ‘Possible outcomes following vagal maneuvers or adenosine administration’):

●Sinus tachycardia will gradually slow during the maneuver and then accelerate upon completion of the maneuver.

●During atrial tachycardia or atrial flutter, the ventricular response will transiently slow (due to increased AV nodal blockade). The arrhythmia itself, which occurs within the atria, is usually unaffected.

●A paroxysmal SVT (either atrioventricular nodal reentrant tachycardia [AVNRT] or AVRT) will frequently terminate because of the dependence on the AV node.

●VT is generally unaffected by vagal maneuvers, although these maneuvers may slow or block retrograde conduction. In some cases, this response exposes AV dissociation by altering the sinus rate (or PP intervals). Rarely, VT terminates in response to carotid sinus pressure.

Pharmacologic interventions — In patients with WCT of uncertain etiology, the response to the administration of certain drugs can provide diagnostic information, which in certain circumstances may also provide a therapeutic benefit (eg, adenosine which may terminate some SVTs). However, some drugs used for the diagnosis or treatment of SVT (eg, verapamil, adenosine, or beta blockers) can cause severe hemodynamic deterioration (often the result of hypotension) in patients with a previously stable VT, potentially resulting in ventricular fibrillation (VF) and cardiac arrest [1-3]. Thus, other than adenosine, these medications are generally reserved for the treatment of patients in whom the diagnosis of SVT is already known; they are rarely used for diagnostic purposes for a WCT. (See ‘Supraventricular tachycardia’below.)

Adenosine slows conduction time through the AV node. Arrhythmias that are dependent upon the AV node (eg, AVNRT, AVRT) will frequently be terminated following adenosine administration. Adenosine will usually not terminate other non-AV node dependent arrhythmias; a subgroup of atrial tachycardias may be adenosine sensitive. In addition, some idiopathic VTs (specifically RV outflow tract VT) may terminate with adenosine. If the tachycardia does not terminate, the ventricular response following adenosine administration is often helpful in distinguishing the etiology of the WCT. Not infrequently, adenosine will promote the conversion of SVT to atrial fibrillation (AF). If the patient has underlying Wolff-Parkinson-White (WPW) syndrome, this may lead to extremely rapid ventricular rates, and potentially deterioration to VF. Thus, an external defibrillator should always be available. (See “Clinical manifestations, diagnosis, and evaluation of narrow QRS complex tachycardias”, section on ‘Possible outcomes following vagal maneuvers or adenosine administration’.)

●If there is no change in the ventricular rate and rhythm, the WCT is likely VT. One exception would be if the adenosine was not properly administered (ie, rapid intravenous push followed by saline flush) and, because of its short half-life and metabolism by red blood cells, did not reach the heart.

●If the ventricular activity temporarily slows or ceases (for 5 to 10 seconds), the remaining atrial activity is typically easily seen on the ECG and can be analyzed to determine the etiology of WCT. A second dose of 12 mg of adenosine, although appropriate for the treatment of known SVT, is probably not appropriate for WCT that is not known to be SVT.

Adenosine is administered via rapid intravenous push, followed immediately by 10 mL saline flush. Common side effects include facial flushing, shortness of breath, palpitations, chest pain, and lightheadedness. (See “Clinical manifestations, diagnosis, and evaluation of narrow QRS complex tachycardias”, section on ‘Administration and side effects’.)

Stable patients with known WCT etiology — In a patient with WCT who is hemodynamically stable, therapy may be targeted to the specific arrhythmia (VT or SVT) when identifiable from the available data. (See “Approach to the diagnosis of wide QRS complex tachycardias”, section on ‘Our approach’.)

●VT should be suspected in patients with clearly identified AV dissociation, patients with QRS concordance and a right superior axis (or axis shift of greater than 40 degrees from baseline), and in patients with known structural heart disease. VT is typically regular, though slight variation of the RR interval may be seen.

●SVT should be suspected in young patients with structurally normal hearts in whom none of the historical (eg, family history of sudden cardiac death), physical, or ECG criteria supporting VT are present, or in patients with a history of SVT with a similar presentation. The RR interval in SVT is generally very regular.

●Significant irregularity in a WCT is most often seen in patients with AF and aberrant conduction, though polymorphic VT is also irregular. Patients with AF should have similar QRS morphologies for every beat, while the QRS morphology varies in polymorphic VT. An important exception is pre-excited AF in patients with WPW syndrome, in which the QRS morphology is variable in width and morphology. (See “Epidemiology, clinical manifestations, and diagnosis of the Wolff-Parkinson-White syndrome”, section on ‘Atrial fibrillation’.)

Ventricular tachycardia — Once the WCT has been established as VT, therapy should be promptly provided. Patients with VT who are hemodynamically stable may remain stable or may become unstable rapidly and without warning. The choice of initial treatments for hemodynamically stable VT includes electrical or pharmacologic cardioversion. Some of our experts proceed directly to electrical cardioversion, while others prefer to begin with an intravenous antiarrhythmic agent and reserve cardioversion for refractory patients or for those who become unstable.

●If electrical cardioversion with appropriate procedural sedation is the chosen approach, intravenous analgesics or sedatives should be cautiously administered if the blood pressure will tolerate their use. If the QRS complex and T wave can be distinguished, an attempt at emergent synchronized cardioversion can be performed with a synchronized shock of 100 joules using either a biphasic or monophasic defibrillator. If the QRS complex and T wave cannot be distinguished accurately, and a synchronized shock is not possible, we administer an unsynchronized 120 to 200 joule shock from a biphasic defibrillator or a 360 joule shock from a monophasic defibrillator.

●If pharmacologic cardioversion is the chosen approach, we administer intravenous amiodarone (150 mg IV over 10 minutes, followed by 1 mg/minute for the next six hours) or procainamide (20 to 50 mg per minute until arrhythmia terminates or a maximum dose of 17 mg/kg is administered). Often administration of these drugs may result in hypotension, which may hasten the need for electrical cardioversion. (See ‘Recurrent or refractory WCT’ below.)

●Any associated conditions should be treated, including cardiac ischemia, heart failure, electrolyte abnormalities, or drug toxicities.

●For patients with one of the known syndromes of VT in structurally normal hearts, calcium channel blockers or beta blockers may be used, particularly if the patient has been successfully treated in the past with such medications. These drugs can be used either to terminate the arrhythmia, or after cardioversion to suppress recurrences. (See “Monomorphic ventricular tachycardia in the absence of apparent structural heart disease”.)

Given the risk for hemodynamic deterioration at any time, an external defibrillator should be immediately available at all times prior to and during the administration of any antiarrhythmic drugs.

Supraventricular tachycardia — Once the WCT has been definitively established as SVT, therapy directed at the SVT may be given. In such cases, management is similar to an SVT with a normal QRS duration. The ECG recording when the tachycardia slows or terminates can provide valuable information for diagnosing the specific type of SVT. Thus, in a stable patient, a continuous rhythm strip, preferably a 12-lead rhythm strip, should be recorded during any intervention intended to terminate the arrhythmia or slow the ventricular response.

For patients with known SVT, we suggest the following approach:

●If the SVT is likely to be AVNRT or AVRT, or if the specific SVT diagnosis is uncertain, the following treatments are recommended:

•Vagal maneuvers – We recommend Valsalva maneuver or carotid sinus pressure (if no carotid bruits are present) as the initial intervention, given the ease with which this can be rapidly performed at the bedside.

•Adenosine – For patients with persistent SVT following vagal maneuvers, adenosine is highly effective in terminating many SVTs (eg, AVNRT, AVRT), and for others (eg, AF, atrial flutter), adenosine may facilitate the diagnosis by slowing the ventricular response to allow clearer assessment of atrial activity [6]. The usual initial dose is 6 mg, which can be followed by a maximal single dose of 12 mg if not successful. The drug is administered by rapid intravenous injection over one to two seconds at a peripheral site, followed by a normal saline flush, most easily accomplished through a three-way stopcock. Repeated dosing beyond the 12 mg bolus is not usually effective. If a central intravenous access site is used, the initial dose should not exceed 3 mg and may be as little as 1 mg. Not infrequently, adenosine will promote the conversion of SVT to AF. If the patient has underlying WPW syndrome, this may lead to extremely rapid ventricular rates, and potentially deterioration to VF. Thus, an external defibrillator should always be available. (See “Clinical manifestations, diagnosis, and evaluation of narrow QRS complex tachycardias”, section on ‘Administration and side effects’.)

•Calcium channel blockers or beta blockers – If SVT persists after vagal maneuvers and adenosine administration, the choice of initial pharmacologic therapies includes non-dihydropyridine calcium channel blockers and beta blockers. We generally start with intravenous verapamil (2.5 to 5 mg IV) or diltiazem (5 to 20 mg IV), although a beta blocker (eg, metoprolol 5 to 10 mg IV) may be given. These medications can terminate AVNRT or AVRT, as well as some atrial tachycardias. If the specific SVT diagnosis remains unknown, these drugs may slow the ventricular response and facilitate diagnosis.

•Cardioversion – Electrical cardioversion is rarely necessary in patients with a stable SVT. However, if WCT persist after the above interventions, synchronized cardioversion is usually effective in restoring sinus rhythm. Following appropriate procedural sedation, an initial synchronized shock of 100 to 200 joules (monophasic) or 50 to 100 joules (biphasic) is administered.

●If the arrhythmia is known to be atrial fibrillation, atrial flutter, or an atrial tachycardia, management options include rate control and cardioversion (ie, rhythm control). Decisions regarding which strategy is appropriate in a given patient are addressed separately. (See “Overview of atrial flutter” and “Overview of atrial fibrillation”.)

After the WCT is terminated or controlled, the further management of an SVT depends upon which SVT is present. (See “Atrioventricular nodal reentrant tachycardia” and “Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway”.)

Patients with a pacemaker — Patients with a permanent pacemaker are subject to the same array of WCTs as patients without a pacemaker. Rarely, however, WCT can result from a pacemaker tracking an underlying atrial arrhythmia or be due to pacemaker-mediated tachycardia. Most patients with WCT involving a pacemaker will be hemodynamically stable, unless the resulting tachycardia exacerbated underlying comorbidities (eg, angina, heart failure, etc).

If the WCT is thought to be directly related to the function of the pacemaker, the appropriate therapy is the placement of a magnet over the pacemaker. The magnet will disable all pacemaker sensing, thereby terminating the ability of the pacemaker to track atrial impulses. With the magnet, the pacemaker will function in an asynchronous, fixed-rate mode (ie, VOO or DOO). In this situation, there will be pacemaker stimuli that do not sense the P wave or QRS complex and will occur with a fixed rate (ie, the lower rate limit of the pacemaker). If WCT is due to pacemaker-mediated tachycardia (PMT) or “pseudo PMT” (non-reentrant repetitive VA synchrony), transient magnet application will terminate the WCT, and sinus rhythm will ensue when the magnet is removed. If the WCT is due to inappropriate tracking of atrial fibrillation or atrial flutter, the WCT will likely resume once the magnet is removed.

Patients with pacemakers may also be subject to WCTs that do not involve the pacemaker, like other patients. In stable patients, the pacemaker programmer can be used to telemeter the intracardiac electrograms from the pacemaker leads. Examination of these electrograms may yield the diagnosis, as in the electrophysiology laboratory.

Patients with an ICD — Patients with an implantable cardioverter-defibrillator (ICD) represent a specific high-risk population in whom WCT is far more likely to represent VT. Patients who underwent ICD implantation for secondary prevention have previously experienced a sustained ventricular tachyarrhythmia or sudden cardiac death, while those who received an ICD for primary prevention were felt to be at increased risk of sustained ventricular tachyarrhythmia. In either case, WCT in patients with an ICD should be treated as VT until proven otherwise. When no ICD therapy has been delivered, and the device cannot be immediately interrogated (due either to lack of equipment or personnel, or patient instability), the initial management should proceed as if no ICD were present.

The presence of an ICD has a number of unique implications for patients with a WCT. Although the ICD should be programmed to delivery therapies (either antitachycardia pacing or shocks) for a WCT, such therapies are usually delivered within the first minutes of the arrhythmia.

●In a patient with a persistent or recurrent WCT, the ICD may not always provide definitive management if the device has reached the limit of programmed therapies. Patients with a WCT which persists following multiple ICD therapies most likely have either VT storm with an underlying trigger (eg, ischemia, hypokalemia) or an SVT with aberrant conduction which recurs or persists in spite of the ICD therapies. (See “Electrical storm and incessant ventricular tachycardia”.)

●Patients with and ICD and WCT will not receive therapy from the ICD if the WCT rate is lower than the programmed rate for ICD therapy.

●Patients with an ICD who receive multiple shocks but do not have a tachycardia most likely have device malfunction, usually related to lead malfunction. In these patients, magnet application can temporarily suspend tachycardia therapy and prevent further inappropriate shocks. Magnet application is also appropriate in patients receiving shocks for narrow complex tachyarrhythmias (SVT, AF, atrial flutter, sinus tachycardia). (See “Cardiac implantable electronic devices: Long-term complications”.)

All modern ICDs also have the capacity to function as a pacemaker. Patients with a single lead ICD (typically an endovascular lead in the right ventricle) cannot sense and track atrial arrhythmias and, as such, are not subject to WCT associated with the device. Conversely, patients with both an atrial and a ventricular lead have the capacity to sense and track atrial arrhythmias and therefore can potentially develop WCT associated with the pacemaker. However, given the risk of WCT representing VT in a patient with an ICD, pacemaker-associated WCT should be considered only after exclusion of other WCT etiologies and following ICD interrogation. Magnet application does not force asynchronous pacing in ICDs and will therefore not terminate PMT in patients with ICDs. As in pacemaker patients, telemetered intracardiac recordings may be helpful diagnostically. (See ‘Patients with a pacemaker’above.)

Recurrent or refractory WCT — If the WCT recurs or persists following initial attempts at vagal maneuvers, diagnostic pharmacologic interventions, and electrical cardioversion, suppression of the arrhythmia by pharmacologic means should be attempted and further evaluation should focus upon the presence of arrhythmia triggers (eg, ischemia, electrolyte abnormalities, and drug toxicity). Amiodarone is generally the most effective agent for treatment of recurrent or refractory WCT, particularly VT [5]. Cardioversion or defibrillation should be repeated as necessary in patients who are hemodynamically unstable. (See “Sustained monomorphic ventricular tachycardia in patients with a prior myocardial infarction: Treatment and prognosis”.)

●For patients with recurrent VT or WCT of uncertain etiology, we suggest the following:

•Amiodarone is administered in most settings, due to its efficacy in the suppression of both atrial and ventricular arrhythmias. The initial dose is 150 mg IV over 10 minutes followed by an infusion of 1 mg/minute for six hours, then 0.5 mg/minute for an additional 18 hours or longer. Repeat amiodarone boluses can be administered if necessary.

•Procainamide is an alternative to amiodarone that also suppresses both SVTs and VT. The initial dose is 15 to 18 mg/kg administered as slow infusion over 25 to 30 minutes, followed by 1 to 4 mg/minute by continuous infusion. In addition, because of its ability to suppress conduction over a bypass tract, procainamide is recommended if antidromic AVRT or an SVT conducting over a bypass tract is suspected. For pre-excited atrial fibrillation or atrial flutter, intravenous procainamide or ibutilide is recommended; amiodarone and AV nodal blocking agents are not recommended. (See “Treatment of symptomatic arrhythmias associated with the Wolff-Parkinson-White syndrome”.)

●For patients with a known SVT that recurs or persists, intravenous verapamil, diltiazem, or beta blockers may be used.

Multiple recurrences of WCT should raise concern about cardiac ischemia, hypokalemia, digitalis toxicity, and polymorphic VT with or without QT prolongation, all of which have specific appropriate therapy. (See “Overview of the acute management of ST-elevation myocardial infarction” and “Overview of the acute management of non-ST elevation acute coronary syndromes” and “Cardiac arrhythmias due to digoxin toxicity” and “Clinical manifestations and treatment of hypokalemia in adults”, section on ‘Treatment’ and “Acquired long QT syndrome”, section on ‘Acute therapy of TdP’.)

Chronic therapy — Chronic therapy for patients with WCT will be driven by the underlying etiology of the WCT.

●Patients with VT should generally undergo implantation of an ICD. Following ICD implantation, those patients with recurrent symptomatic VT, or those who have received multiple ICD therapies, may require adjunctive antiarrhythmic therapy in an effort to suppress recurrent VT. In some cases, radiofrequency catheter ablation may be an option to reduce the frequency of VT. An important exception is idiopathic VT, which is treated with ablation or pharmacologic therapy, not with ICD. (See “Sustained monomorphic ventricular tachycardia in patients with a prior myocardial infarction: Treatment and prognosis”, section on ‘Chronic therapy’ and “Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy”, section on ‘Other treatment options’.)

●The approach to patients with WCT due to an SVT will vary significantly depending upon the etiology of the SVT.

•Patients with AVNRT or AVRT associated with a concealed accessory pathway may require no therapy, may be able to self-terminate arrhythmias using vagal maneuvers, may be candidates for pharmacologic suppressive therapy, or may be effectively cured with catheter ablation. (See “Atrioventricular nodal reentrant tachycardia”, section on ‘Preventive therapy’ and “Treatment of symptomatic arrhythmias associated with the Wolff-Parkinson-White syndrome”, section on ‘Treatment to prevent recurrent arrhythmias’.)

•Patients with AVRT associated with a manifest accessory pathway or pre-excited atrial fibrillation or atrial flutter (ie, patients with arrhythmias related to WPW) should undergo electrophysiology testing and catheter ablation of accessory pathway due to the small risk of sudden cardiac death in patients with symptomatic WPW syndrome. (See “Treatment of symptomatic arrhythmias associated with the Wolff-Parkinson-White syndrome”, section on ‘Treatment to prevent recurrent arrhythmias’.)

•The approach to a patient with atrial fibrillation may include ventricular rate control, restoration of sinus rhythm, or catheter ablation. (See “Overview of atrial fibrillation”, section on ‘Treatment issues’.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See “Society guideline links: Arrhythmias in adults”.)

SUMMARY AND RECOMMENDATIONS

●The acute management of a patient with wide QRS complex tachycardia (WCT) depends on the hemodynamic stability of the patient. Urgent or emergency management is required in unstable patients, with management taking precedence over further diagnostic workup until the patient has been stabilized. Following initial management and stabilization of the patient, chronic management of the patient with WCT will be directed by the etiology of the WCT (supraventricular versus ventricular). (See ‘Management’ above.)

●All patients with a WCT should have a brief immediate assessment of the symptoms, vital signs, and level of consciousness to determine if they are hemodynamic stable or unstable. An unstable patient will have evidence of hemodynamic compromise, such as hypotension, altered mental status, chest pain, or heart failure, whereas a stable patient shows none of these despite a sustained rapid heart rate. (See ‘Initial management’ above.)

●While the assessment of hemodynamic status is being performed by a clinician, other members of the health care team should administer supplemental oxygen, establish intravenous access, send blood for appropriate initial studies, attach the patient to a continuous cardiac monitor, and obtain a 12-lead electrocardiogram (ECG). (See ‘Initial management’ above and “Approach to the diagnosis of wide QRS complex tachycardias”, section on ‘Ancillary testing’.)

●Patients with WCT who are hemodynamically unstable and pulseless, or who become pulseless during the course of evaluation and treatment, should be managed according to standard advance cardiac life support (ACLS) resuscitation algorithms, with immediate high-energy defibrillation and cardiopulmonary resuscitation (CPR) (algorithm 1). Patients should initially be treated with a synchronized (if possible) 120 to 200 joule shock from a biphasic defibrillator or a 360 joule shock from a monophasic defibrillator. An unsynchronized shock should be delivered if synchronization is not possible [5]. (See ‘Unstable patients’ above and “Advanced cardiac life support (ACLS) in adults” and “Basic life support (BLS) in adults”.)

●For patients with WCT who are hemodynamically unstable, but still responsive with a discernible blood pressure and pulse, we recommend urgent cardioversion (with procedural sedation when feasible) (Grade 1A). (See ‘Unstable patients’ above.)

•If the QRS complex and T wave can be distinguished, an attempt at emergency synchronized cardioversion can be performed with a synchronized shock of 100 joules using either a biphasic or monophasic defibrillator.

•If the QRS complex and T wave cannot be distinguished accurately, and a synchronized shock is not possible, we administer an unsynchronized 120 to 200 joule shock from a biphasic defibrillator or a 360 joule shock from a monophasic defibrillator.

●For hemodynamically stable patients with WCT which is regular and monomorphic in whom the etiology of the WCT remains uncertain, we suggest vagal maneuvers (ie, Valsalva, carotid sinus massage) followed by intravenous adenosine if no response to the vagal maneuvers (Grade 2C). Further treatment is directed by the response to vagal maneuvers and/or adenosine, specifically targeting ventricular tachycardia (VT) or the relevant supraventricular tachycardia (SVT). If the WCT persists and the etiology remains uncertain, we proceed as though the WCT is VT and treat accordingly. (See ‘Stable patients with uncertain WCT etiology’ above.)

●For patients who are hemodynamically stable and known to have VT, some of our experts proceed directly to electrical cardioversion, while others prefer to begin with an intravenous antiarrhythmic agent and reserve cardioversion for refractory patients or for those who become unstable. (See ‘Ventricular tachycardia’ above.)

●For patients who are hemodynamically stable and known to have SVT, we suggest the following approach (Grade 2C) (see ‘Supraventricular tachycardia’ above):

•If the SVT is likely to be atrioventricular nodal reentrant tachycardia (AVNRT) or atrioventricular reciprocating tachycardia (AVRT), we perform vagal maneuvers, followed by adenosine, followed by intravenous verapamil or diltiazem, and, in refractory cases, electrical cardioversion. If the SVT terminates after any of the interventions, the subsequent interventions are not performed acutely.

•If the arrhythmia is known to be atrial fibrillation (AF), atrial flutter, or an atrial tachycardia, management options include rate control and cardioversion (ie, rhythm control). (See “Overview of atrial flutter”and “Overview of atrial fibrillation”.)

●If the WCT is thought to be directly related to the function of pacemaker, the appropriate therapy is the placement of a magnet over the pacemaker. (See ‘Patients with a pacemaker’above.)

●Chronic therapy for patients with WCT will be driven by the underlying etiology of the WCT, with patients having VT generally considered for implantable cardioverter-defibrillator (ICD) implantation, while therapy for patients with SVT will need to be tailored to the underlying arrhythmia. (See ‘Chronic therapy’ above.)

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REFERENCES

1. Buxton AE, Marchlinski FE, Doherty JU, et al. Hazards of intravenous verapamil for sustained ventricular tachycardia. Am J Cardiol 1987; 59:1107.
2. Stewart RB, Bardy GH, Greene HL. Wide complex tachycardia: misdiagnosis and outcome after emergent therapy. Ann Intern Med 1986; 104:766.
3. Dancy M, Camm AJ, Ward D. Misdiagnosis of chronic recurrent ventricular tachycardia. Lancet 1985; 2:320.
4. Akhtar M, Shenasa M, Jazayeri M, et al. Wide QRS complex tachycardia. Reappraisal of a common clinical problem. Ann Intern Med 1988; 109:905.
5. Link MS, Atkins DL, Passman RS, et al. Part 6: electrical therapies: automated external defibrillators, defibrillation, cardioversion, and pacing: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010; 122:S706.
6. Gupta AK, Thakur RK. Wide QRS complex tachycardias. Med Clin North Am 2001; 85:245.

Topic 101641 Version 6.0

Approach to the diagnosis of wide QRS complex tachycardias

Author:

Leonard I Ganz, MD, FHRS, FACC

Section Editors:

Peter J Zimetbaum, MD

Ary L Goldberger, MD

James Hoekstra, MD

Deputy Editor:

Brian C Downey, MD, FACC

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Oct 2017. | This topic last updated: Oct 22, 2015.

INTRODUCTION — Tachycardias are broadly categorized based upon the width of the QRS complex on the electrocardiogram (ECG).

●A narrow QRS complex (<120 msec) reflects rapid activation of the ventricles via the normal His-Purkinje system, which in turn suggests that the arrhythmia originates above or within the atrioventricular (AV) node (ie, a supraventricular tachycardia [SVT]).

●A widened QRS (≥120 msec) occurs when ventricular activation is abnormally slow for one of the following reasons (see ‘Causes of WCT’below):

•The arrhythmia originates outside of the normal conduction system (ie, ventricular tachycardia [VT])

•Abnormalities within the His-Purkinje system (ie, SVT with aberrancy)

•Pre-excitation with a SVT conducting antegrade over an accessory pathway, resulting in direct activation of the ventricular myocardium

A wide complex tachycardia (WCT) represents a unique clinical challenge for two reasons:

●Diagnosing the arrhythmia is difficult – Although most WCTs are due to ventricular tachycardia (VT), the differential diagnosis includes a variety of SVTs. Diagnostic algorithms to differentiate these two etiologies are complex and imperfect.

●Urgent therapy is often required – Patients may be unstable at the onset of the arrhythmia or deteriorate rapidly at any time, particularly if the WCT is VT [1-4].

The clinical manifestations, diagnosis, and initial evaluation of patients with a wide QRS complex tachycardia will be discussed here. The management of wide QRS complex tachycardias, as well as discussion of narrow QRS complex tachycardias, is presented separately. (See “Approach to the management of wide QRS complex tachycardias” and “Overview of the acute management of tachyarrhythmias” and “Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy” and “Clinical manifestations, diagnosis, and evaluation of narrow QRS complex tachycardias”.)

INITIAL APPROACH — The first priority when evaluating a patient with a wide complex tachycardia (WCT) is an assessment of patient stability. Unstable patients should be treated immediately, before an extensive diagnostic evaluation. (See ‘Assessment of stability’ below and “Approach to the management of wide QRS complex tachycardias”, section on ‘Unstable patients’.)

Stable patients will most often have already had an electrocardiogram (ECG) showing the presence of a WCT. In a stable patient, the ECG should be thoroughly and systematically reviewed in an effort to determine the etiology of the WCT. (See ‘Evaluation of the electrocardiogram’ below.)

In a stable patient, a focused clinical evaluation should include the following:

●History

●Physical examination

●Laboratory testing

●Diagnostic maneuvers in selected patients

The primary goals of the initial evaluation of a stable patient with WCT are to determine the etiology of the WCT (through evaluation of the ECG) and to elucidate any underlying conditions related to the event (eg, heart failure, myocardial ischemia, drug reaction, or electrolyte abnormalities). (See ‘Evaluation of the electrocardiogram’ below.)

Assessment of stability — Immediate assessments of the patient’s symptoms, vital signs, and the level of consciousness are of primary importance [5]. In the discussions that follow, patients are categorized as follows:

●Unstable – An unstable patient with WCT will have evidence of hemodynamic compromise, such as hypotension, altered mental status, chest pain, or heart failure, but generally remains awake with a discernible pulse. In this setting, emergency synchronized cardioversion is the treatment of choice regardless of the mechanism of the arrhythmia. (See “Approach to the management of wide QRS complex tachycardias”, section on ‘Unstable patients’.)

Patients who become unresponsive or pulseless are considered to have a cardiac arrest and are treated according to standard resuscitation algorithms. (See “Advanced cardiac life support (ACLS) in adults” and “Basic life support (BLS) in adults”.)

●Stable – A stable patient with WCT shows no evidence of hemodynamic compromise despite a sustained rapid heart rate. Such patients should have continuous monitoring and frequent reevaluations due to the potential for rapid deterioration as long as the WCT persists.

The presence of hemodynamic stability should not be regarded as diagnostic of supraventricular tachycardia (SVT) [4,6]. Misdiagnosis of ventricular tachycardia (VT) as SVT based upon hemodynamic stability is a common error that can lead to inappropriate and potentially dangerous therapy [3,4]. (See “Approach to the management of wide QRS complex tachycardias”, section on ‘Pharmacologic interventions’.)

History — When evaluating the stable patient with a WCT, the following historical features may help determine the likely etiology and/or guide therapy:

●History of heart disease – The presence of structural heart disease, especially coronary heart disease and/or a previous myocardial infarction, strongly suggests VT as an etiology [4,7]. It is also important to establish whether a cardiac arrhythmia has occurred in the past and, if so, whether the patient is aware of the etiology. (See ‘Epidemiology’ below.)

●Presence of an implantable cardioverter defibrillator (ICD) – The presence of an ICD implies a known increased risk of VTs and suggests strongly (but does not prove) that the WCT is VT. (See “Implantable cardioverter-defibrillators: Overview of indications, components, and functions”.)

●Presence of a pacemaker – The patient should be asked about the presence of pacemaker, which raises the possibility of a device-associated WCT. (See ‘Supraventricular tachycardia’ below.)

●Atrial arrhythmias – In a patient known to have persistent atrial fibrillation (AF), a regular WCT is likely VT as aberrant conduction during AF would create an irregular rhythm. An exception is when AF “organizes” into atrial flutter; this can occur spontaneously but occurs much more commonly in the setting of antiarrhythmic drugs (especially class IC agents, amiodarone, or dronedarone).

●Age – In a patient over the age of 35 years, a WCT is likely to be VT (positive predictive value 85 percent in one series) [8]. SVT is more likely in younger patients (positive predictive value 70 percent). However, VT must be considered in younger patients, particularly those with a family history of ventricular arrhythmias or premature sudden cardiac death.

●Duration of the tachycardia – SVT is more likely if the tachycardia has recurred over a period of more than three years [5]. The first occurrence of the tachycardia after a myocardial infarction strongly implies VT [7].

●Symptoms – Symptoms are not useful in determining the diagnosis, but they are important as an indicator of the severity of hemodynamic compromise. Symptoms are primarily due to the elevated heart rate, associated heart disease, and the presence of left ventricular dysfunction [4,5,7]. Some patients with a WCT have few or no symptoms (palpitations, lightheadedness, diaphoresis), while others have severe manifestations including chest pain or angina, syncope, shock, seizures, and cardiac arrest [5].

Medications — Many medications have proarrhythmic effects, either directly by prolonging the QT interval or indirectly via alterations in electrolyte levels, and obtaining a medication history is among the first priorities in the evaluation of a patient with a WCT. The most common drug-induced WCT is a form of polymorphic VT called torsades de pointes (TdP). This arrhythmia is associated with QT interval prolongation when the patient is in sinus rhythm. Many medications (eg, antiarrhythmic drugs, anti-infective drugs, psychotropic drugs, etc) are known to prolong the QT interval (table 1) and are associated with a risk of polymorphic VT. An internet resource with updated lists of specific drugs that cause TdP is available at www.crediblemeds.org/. (See “Acquired long QT syndrome”, section on ‘Drug-induced TdP’.)

The class I antiarrhythmic drugs (table 2) can cause both aberrancy during an SVT and also VT. These drugs, especially class IC agents, slow conduction and have a property of “use-dependency” (a progressive decrease in impulse conduction velocity and wider QRS complex duration at faster heart rates). As a result, these drugs can cause rate-related aberration and a wide QRS complex during any SVT. However, they can also cause VT with a very wide, bizarre QRS, which may be incessant [9,10]. (See ‘Supraventricular tachycardia’ below and “Myocardial action potential and action of antiarrhythmic drugs”.)

Physical examination — As with the history, the initial physical examination should focus upon evidence of underlying cardiovascular disease which can impact the likelihood that the WCT is VT.

Findings suggestive of cardiovascular disease include:

●Signs of acute or chronic heart failure. (See “Treatment of acute decompensated heart failure: General considerations” and “Evaluation of the patient with suspected heart failure”.)

●A healed sternal incision as evidence of previous cardiothoracic surgery.

●The sequelae of peripheral artery disease or stroke.

●A pacemaker or ICD. These devices are usually palpable and are in the left or, less commonly, right pectoral area below the clavicle; some earlier ICDs are found in the anterior abdominal wall.

Ancillary testing — A number of additional tests may provide further insight to the mechanism of the tachycardia and the presence of associated conditions.

●Laboratory testing – Initial laboratory testing in all patients with a WCT should include electrolytes and cardiac troponin, with additional testing for elevated serum drug levels in patients taking certain medications.

•The plasma potassium and magnesium concentrations should be measured as part of the initial evaluation, since hypokalemia and hypomagnesemia both predispose to the development of VTs. Hyperkalemia can cause a wide QRS complex rhythm with the loss of a detectable P wave, although this usually is a supraventricular rhythm with a slow rate (so-called “sinoventricular rhythm”). (See “Causes and evaluation of hyperkalemia in adults” and “ECG tutorial: Miscellaneous diagnoses”, section on ‘Hyperkalemia’.)

•Cardiac troponin testing should be performed in patients with WCT, especially if the patient is having ongoing chest pain or hemodynamic instability. Cardiac troponin can be elevated in the setting of myocardial ischemia (as the result of myocardial oxygen supply and demand mismatch) or myocardial infarction (as a possible cause of the arrhythmia). Elevated cardiac troponin is associated with an increased risk of adverse outcomes and may guide hospital admission decisions, cardiac testing, and/or anti-ischemic therapy.

•In patients taking digoxin, quinidine, or procainamide, plasma concentrations of these drugs should be measured to assist in evaluating possible toxicity.

●Chest radiograph – A chest radiograph can provide evidence suggestive of structural heart disease, such as cardiomegaly. Evidence of previous cardiothoracic surgery and the presence of a pacemaker or ICD can also be detected.

Early diagnostic/therapeutic interventions — In patients with a WCT who are hemodynamically stable, certain vagal maneuvers (ie, carotid sinus massage) or the administration of certain intravenous medications (eg, adenosine, beta blockers, verapamil) may be both helpful for establishing the diagnosis and potentially therapeutic, although they do carry a risk of hemodynamic deterioration and should only be performed in closely monitored settings by experienced clinicians. These potential interventions are discussed in detail separately. (See “Approach to the management of wide QRS complex tachycardias”, section on ‘Vagal maneuvers’.)

EPIDEMIOLOGY — Ventricular tachycardia (VT) is the most common cause of wide complex tachycardia (WCT), particularly in patients with a history of cardiac disease. In series of unselected patients, VT accounted for up to 80 percent of cases of WCT [2,4,5,11]. VT frequency can exceed 90 percent in patients with structural heart disease (eg, those with a prior myocardial infarction) [7].

Supraventricular tachycardia (SVT) results in WCT much less frequently than VT. Among patients with WCT due to SVT, aberrant conduction is the most common reason for a widened QRS (21 percent of cases in one series) [11]. However, an aberrantly conducted SVT is still much less common than VT as the cause of WCT.

Antidromic atrioventricular reentrant tachycardia (AVRT) is a relatively uncommon cause of WCT (6 percent of cases in one series) [11].

CLINICAL MANIFESTATIONS — Patients with wide complex tachycardia (WCT) are rarely asymptomatic, although the type and intensity of symptoms will vary depending upon the rate of the WCT, the presence or absence of significant comorbid conditions, and whether the WCT is ventricular tachycardia (VT) or supraventricular tachycardia (SVT). Patients with WCT typically present with one or more of the following symptoms:

●Palpitations

●Chest pain

●Shortness of breath

●Syncope or presyncope

●Sudden cardiac arrest

Few physical examination findings in patients with a WCT are unique to WCT. By definition, patients will have a pulse exceeding 100 beats per minute related to the tachycardia. Patients may be hypotensive, which may result in alterations in consciousness. Patients with underlying heart disease in whom heart failure results from the WCT may have crackles on lung examination.

In addition, the physical examination in patients with WCT can reveal evidence of atrioventricular (AV) dissociation, which is present in up to 75 percent of patients with VT, although it is not always easy to detect [5,7,12]. During AV dissociation, the normal coordination of atrial and ventricular contraction is lost, which may produce characteristic physical findings. The presence of AV dissociation strongly suggests VT, although its absence is less helpful.

Although AV dissociation is typically diagnosed on the electrocardiogram (ECG), characteristic physical examination findings include (see ‘AV dissociation’below):

●Marked fluctuations in the blood pressure because of the variability in the degree of left atrial contribution to left ventricular filling, stroke volume, and cardiac output.

●Variability in the occurrence and intensity of heart sounds (especially S1) (“cacophony of heart sounds”), which is heard more frequently when the rate of the tachycardia is slower.

●Cannon “A” waves – Cannon A waves are intermittent and irregular jugular venous pulsations of greater amplitude than normal waves. They reflect simultaneous atrial and ventricular activation, resulting in contraction of the right atrium against a closed tricuspid valve. Prominent A waves can also be seen during some SVTs. Such prominent waves result from simultaneous atrial and ventricular contraction occurring with every beat. (See “Examination of the jugular venous pulse”.)

CAUSES OF WCT — Wide complex tachycardias (WCTs) most often result from ventricular tachycardia (VT), with other less common causes which include supraventricular tachycardia (SVT) with aberrant conduction, SVT with preexcitation, SVT with ventricular pacing, and some types of artifact mimicking WCT (table 3).

Ventricular tachycardia — VT usually originates within the ventricular myocardium, outside of the normal conduction system, resulting in direct myocardial activation. Compared with a normally conducted supraventricular beat (which activates the ventricular myocardium via the normal atrioventricular [AV] node-His-Purkinje system), ventricular activation during VT is slower and proceeds in a different sequence. Thus, the QRS complex is wide and abnormal (waveform 1). As there may be slight changes of the activation sequence during the VT, reflecting the abnormal pathway of impulse conduction, there may be subtle changes in QRS complex morphology or in the ST-T waves.

VT may be either monomorphic (having a uniform and a fairly stable QRS morphology during an episode), polymorphic (having a continuously varying QRS complex morphology and/or axis during an episode), or bidirectional (in which every other beat has a different axis as it travels alternately down different conduction pathways). The features of each form of VT are discussed separately. (See “Sustained monomorphic ventricular tachycardia: Clinical manifestations, diagnosis, and evaluation”and “Catecholaminergic polymorphic ventricular tachycardia and other polymorphic ventricular tachycardias with a normal QT interval” and “Congenital long QT syndrome: Epidemiology and clinical manifestations”.)

Artifact mimicking VT — ECG artifact, particularly when observed on a single-lead rhythm strip, may be misdiagnosed as VT (waveform 2) [13]. The presence of narrow-complex beats that can be seen to “march” through the supposed WCT at a fixed rate strongly supports the diagnosis of artifact.

Supraventricular tachycardia — When an SVT conducts to the ventricles via the normal AV node and His-Purkinje system, the activation wavefront spreads quickly through the ventricles and the QRS is usually narrow. In addition, the pathway of conduction to the ventricles is fixed and the same for each impulse, accounting for the uniformity of the QRS complexes and ST-T waves. However, SVT can also produce a widened QRS by a number of mechanisms, including aberrant conduction, preexcitation, and the activation of ventricular pacing.

Aberrant conduction — The conduction of a supraventricular impulse can be delayed or blocked in the bundle branches or in the distal Purkinje system, resulting in a wide, abnormal QRS. This phenomenon is referred to as aberrancy. (See “Basic approach to delayed intraventricular conduction”.)

Aberrant conduction may either be present at baseline or under certain conditions, such as faster heart rates.

●In patients with a left bundle branch block (LBBB), right bundle branch block (RBBB), or a nonspecific intraventricular conduction delay (IVCD) on their baseline electrocardiogram (ECG), any SVT will have a widened QRS. Thus, if time allows, review of a baseline ECG can be helpful in differentiating VT from SVT with aberrancy. The presence of a conduction abnormality on the baseline ECG does not prove that the tachycardia is SVT with aberrancy, but the more similar the QRS during the WCT is to the QRS during sinus rhythm, the more likely it is that the WCT is an SVT with aberrancy.

In patients with aberrancy at baseline who manifest a WCT in which the QRS complex is narrower than the baseline QRS, the WCT is likely VT originating near the ventricular septum, with early engagement of the specialized conducting system. This scenario is extremely unusual.

●In patients with a narrow QRS complex at baseline which widens at faster heart rates, conduction is normal during sinus rhythm but aberrant during the tachycardia. The most common reason for this is rate-related aberration (functional bundle branch block), in which rapidly generated impulses reach the conducting fibers before they have fully recovered from the previous impulse. Such a delay in recovery may also be the result of underlying disease of the His-Purkinje system, hyperkalemia, or the actions of antiarrhythmic drugs, particularly the class IC agents (eg, flecainide, propafenone). (See “Myocardial action potential and action of antiarrhythmic drugs”.)

Preexcitation syndrome — In the preexcitation syndromes, AV conduction can occur over the normal conduction system and also via an accessory AV pathway (figure 1A-C). These two pathways create the anatomic substrate for a reentrant circuit (macroreentrant circuit), facilitating the development of a circus movement or reentrant tachycardia known as atrioventricular reentrant tachycardia (AVRT). (See “ECG tutorial: Preexcitation syndromes” and “Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway”, section on ‘Orthodromic AVRT’ and “Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway”, section on ‘Antidromic AVRT’.)

AVRT can present with a narrow or a wide QRS complex:

●If antegrade conduction to the ventricles occurs over the AV node and retrograde conduction is over the accessory pathway, the QRS complex will be narrow (unless there is aberrant conduction at baseline with a wide QRS complex). This narrow complex AVRT is known as an orthodromic AVRT (figure 2 and waveform 3). Orthodromic AVRT can also occur with rate-related aberrancy, creating a WCT.

●If antegrade conduction occurs over an accessory pathway and retrograde conduction occurs over the AV node or a second accessory pathway, the QRS complex will be wide with an unusual morphology. This is known as an antidromic AVRT (figure 3 and waveform 4). Antidromic AVRT is difficult to differentiate from VT, because ventricular activation starts outside the normal intraventricular conduction system in both types of tachycardia (ie there is direct myocardial activation). (See ‘VT versus AVRT’below.)

In addition, patients with an accessory pathway may develop a different SVT (eg, atrial tachycardia, atrial fibrillation [AF], or atrial flutter). In such cases, the atrial impulses may use the accessory pathway to conduct to the ventricles, and the QRS could be either narrow or wide, depending upon whether ventricular activation occurs over the normal conduction system, the accessory pathway, or both (waveform 5 and waveform 6 and waveform 7). (See “Epidemiology, clinical manifestations, and diagnosis of the Wolff-Parkinson-White syndrome”, section on ‘Arrhythmias associated with WPW’.)

Pacemakers — When the ventricles are activated by a pacing device, the QRS complex is generally wide:

●Most transvenous ventricular pacemakers pace the right ventricle, causing a wide QRS complex of the LBBB type. Typically, the surface ECG shows a broad R wave in lead I, indicating conduction from right to left. (See “Overview of cardiac pacing in heart failure”.)

●Pacemakers used in cardiac resynchronization therapy (CRT) usually pace both ventricles. Although CRT generates a QRS complex that is narrower than the patient’s baseline (a chronically widened QRS is one of the components of the indication for CRT), it is still usually longer than 120 msec. The surface ECG typically shows a Q wave or QS complex in lead I, indicating activation from left to right. (See “Cardiac resynchronization therapy in heart failure: Indications”.)

Recognizing that a QRS complex is due to ventricular pacing can be challenging, particularly during a tachycardia. In addition to characteristic QRS morphology, a pacing “spike” or stimulus artifact can often be identified. The stimulus artifact is a narrow electrical signal too rapid to represent myocardial depolarization.

Among patients with a pacemaker or an ICD, further possibilities need to be considered in addition to the usual differential diagnosis of a WCT. These include:

●In the presence of sinus tachycardia or some SVTs (eg, an atrial tachycardia, AF, or atrial fibrillation), the device may “track” the atrial impulse and pace the ventricle at the rapid rate, resulting in a WCT. (See “Modes of cardiac pacing: Nomenclature and selection”, section on ‘Mode switching’.)

●A WCT can result if ventricular paced beats are conducted retrograde (backward) through the AV node to the atrium, resulting in an atrial signal, which the pacemaker senses and tracks with another ventricular stimulus. This ventricular paced beat is also conducted retrograde, and the cycle repeats indefinitely, a process termed pacemaker-mediated tachycardia (PMT) or endless loop tachycardia. PMT usually occurs at the upper rate limit. A different mechanism of pacemaker-associated tachycardia, non-reentrant repetitive VA synchrony, also creates a wide complex rhythm, but usually at the lower rate limit or sensor mediated rate rather than at the upper rate limit.

These and other arrhythmias associated with pacemakers are discussed in detail separately. (See “Unexpected rhythms with normally functioning dual-chamber pacing systems”, section on ‘Pacemaker-mediated tachycardia’.)

EVALUATION OF THE ELECTROCARDIOGRAM — In most patients, a probable diagnosis (ventricular tachycardia [VT] or supraventricular tachycardia [SVT]) may be made by closely reviewing the electrocardiogram (ECG), although definitive diagnosis is not always possible and may be time-consuming, especially for clinicians unfamiliar with the criteria for distinguishing VT from SVT. To perform an adequate ECG analysis, both a 12-lead ECG and a rhythm strip should be obtained. If available, a previous ECG when the patient was in normal sinus rhythm may be helpful. However, if there are any questions regarding the patient’s stability, detailed ECG evaluation should be deferred in favor of urgent therapy, although if time allows, an ECG should be obtained for later review prior to urgent cardioversion. (See “Approach to the management of wide QRS complex tachycardias”, section on ‘Unstable patients’.)

Basic features — As with the interpretation of any ECG, the standard initial approach includes an assessment of rate, regularity, axis, QRS duration, and QRS morphology.

●Rate – The rate of the wide complex tachycardia (WCT) is of limited use in distinguishing VT from SVT. When the rate is approximately 150 beats per minute, atrial flutter with 2:1 atrioventricular (AV) block and with aberrant conduction should be considered, although this diagnosis should not be accepted without other supporting evidence.

●Regularity – VT is generally regular, although slight variation in the RR intervals is sometimes seen. Slight irregularity suggests VT as opposed to most SVTs, which are characterized by uniformity of the RR intervals. When the onset of the arrhythmia is available for analysis, a period of irregularity (“warm-up phenomenon”), suggests VT. More marked irregularity of RR intervals occurs in polymorphic VT and in atrial fibrillation (AF) with aberrant conduction.

●Morphology – When describing WCTs, the QRS morphology in lead V1 is the key. If the complex is primarily negative in lead V1, the WCT is said to be left bundle branch block (LBBB)-like. If the QRS is primarily positive in lead V1, the WCT is said to be right bundle branch block (RBBB)-like. (See ‘QRS morphology’ below.)

●Axis – The QRS axis in the frontal plane can be useful in distinguishing SVT from VT. (See “Basic principles of electrocardiographic interpretation”, section on ‘QRS axis’.)

•A right superior axis (axis from -90 to ±180 degrees), sometimes called an indeterminate or “northwest” axis, is rare in SVT and strongly suggests VT [5]. There are two exceptions to this rule. The first is an antidromic atrioventricular reentrant tachycardia (AVRT) seen with ventricular preexcitation. In this situation there is direct activation of the ventricular myocardium, bypassing the normal His-Purkinje system, and the QRS complex may have an indeterminate axis. The second is a biventricular pacemaker in which the axis is often indeterminate with an initial Q wave in lead I.

•Compared with the axis during sinus rhythm (when an old ECG is available for review), an axis shift during the WCT of more than 40 degrees suggests VT [14].

•In a patient with a RBBB-like WCT, a QRS axis to the left of -30 degrees suggests VT. (See ‘QRS morphology’ below.)

•In a patient with an LBBB-like WCT, a QRS axis to the right of +90 degrees suggests VT [15]. (See ‘QRS morphology’ below.)

●QRS duration – In general, a wider QRS favors VT. In a RBBB-like WCT, a QRS duration >140 msec suggests VT; while in a LBBB-like WCT, a QRS duration >160 msec suggests VT [5,15]. (See ‘QRS morphology’ below.)

In an analysis of several studies, a QRS duration >160 msec was a strong predictor of VT (likelihood ratio >20:1) [16]. However, a QRS duration >160 msec is not helpful in some settings, including SVT with an AV accessory pathway; the presence of drugs capable of slowing intraventricular conduction, such as class I antiarrhythmic drugs; and in association with hyperkalemia [15,17,18]. A very wide QRS complex may also be seen with a dilated cardiomyopathy in which diffuse fibrosis may produce a marked slowing of impulse conduction through the ventricular myocardium. (See ‘VT versus AVRT’ below and ‘Medications’above.)

A QRS duration <140 msec does not exclude VT, since VT originating from the septum or within the His-Purkinje system (as opposed to the myocardium) may be associated with a relatively narrow QRS complex. (See “Monomorphic ventricular tachycardia in the absence of apparent structural heart disease”, section on ‘Idiopathic left ventricular tachycardia’.)

Concordance — Concordance is present when the QRS complexes in all six precordial leads (V1 through V6) are monophasic with the same polarity. They can either all be entirely positive with tall, monophasic R waves, or all be entirely negative with deep monophasic QS complexes. If any of the six leads has a biphasic QRS (qR or RS complexes), concordance is not present.

●Negative concordance is strongly suggestive of VT but is not definitive. Rarely, SVT with LBBB aberrancy will demonstrate negative concordance, but there is almost always some evidence of an R wave in the lateral precordial leads.

●Positive concordance is most often due to VT but can also occur in the relatively rare case of antidromic AVRT with a left posterior accessory pathway [5,15]. (See “Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome”.)

While the presence of concordance strongly suggests VT (>90 percent specificity), its absence is not helpful diagnostically (approximately 20 percent sensitivity) [11].

AV dissociation — AV dissociation is characterized by atrial activity that is independent of ventricular activity (waveform 8).

In a WCT with AV dissociation, an atrial rate slower than the ventricular rate strongly suggests VT. An atrial rate that is faster than the ventricular rate is seen with some SVTs, such as atrial flutter or an atrial tachycardia with 2:1 AV conduction. In these settings, however, there is a consistent relationship between the P waves and the QRS complexes, so there is not true AV dissociation.

While the presence of AV dissociation largely establishes VT as the diagnosis, its absence is not as helpful for two reasons:

●AV dissociation may be present but not obvious on the ECG.

●In some cases of VT, the ventricular impulses conduct backwards through the AV node and capture the atrium (referred to as 1:1 retrograde conduction), so in fact there is AV association rather than AV dissociation [19]. This may be seen more commonly when the rate of VT is slower. VT with retrograde Wenckebach conduction, or with 2:1 VA conduction, technically does not exhibit AV dissociation, though the ventricular rate exceeds the atrial rate. In all cases in which there is retrograde VA conduction, the P waves will be inverted in the inferior leads.

Dissociated P waves — P waves are said to be dissociated if they are not consistently coupled to the QRS complexes, as evidenced by the following:

●PP and RR intervals are different

●PR intervals are variable

●There is no association between P and QRS complexes

●The presence of a P wave with one, but not all, QRS complexes

During a WCT, P waves are often difficult to identify. If P waves are not evident on the surface ECG, direct recordings of atrial activity (eg, via an implanted pacemaker or implantable cardioverter-defibrillator [ICD], or via an esophageal electrode or temporary pacing catheter or epicardial pacing wires after heart surgery) can reveal AV dissociation [20].

Fusion and capture beats — Fusion and/orcapture beats, when identified on the surface ECG in a patient with WCT, are diagnostic for VT.

●Fusion beats occur when one impulse originating from the ventricle and a second supraventricular impulse simultaneously activate the ventricular myocardium. The resulting QRS complex has a morphology intermediate between that of a sinus beat and a purely ventricular complex (waveform 9). Intermittent fusion beats during a WCT are diagnostic of AV dissociation and therefore of VT.

●Capture beats, or Dressler beats, are QRS complexes during a WCT that are identical to the sinus QRS complex (waveform 9). The term “capture beat” implies that the normal conduction system has momentarily “captured” control of ventricular activation from the VT focus.

Fusion beats and capture beats are more commonly seen when the tachycardia rate is slower.

QRS morphology — Frequently, the above criteria do not provide a definitive diagnosis. Further ECG evaluation involves assessment of the morphology of the QRS complex.

Analysis of QRS morphology is based upon an understanding of the relationships between the sites of tachycardia origin, ventricular activation patterns, and the resulting morphologies of the QRS complex in the 12 standard ECG leads.

Diagnostic criteria — A number of criteria have been developed to facilitate the evaluation of QRS morphology. Most of these approaches involve classifying the WCTs as having one of two patterns:

●An RBBB-like pattern – QRS polarity is positive in lead V1

●An LBBB-like pattern – QRS polarity is negative in lead V1

This distinction does not, by itself, make the diagnosis, but additional features favor VT in either RBBB-like or LBBB-like WCTs. However, the value of these morphologic criteria is subject to several limitations:

●Associations between the QRS morphology and WCT diagnosis are often based upon statistical correlations with substantial overlap.

●Morphologic criteria favoring VT can be present in patients with an intraventricular conduction delay or bundle branch block during sinus rhythm, limiting their applicability in these cases [21]. On occasion a rate-related bundle branch block may have atypical features, suggesting VT.

●Morphologic criteria tend to misclassify antidromic AVRT as VT. They may also misclassify SVT associated with a cardiomyopathy. (See ‘VT versus AVRT’ below.)

In the discussions that follow, upper- and lower-case letters are used to indicate the relative magnitude of the described electrocardiographic waves. As examples, the term “qR” implies a small Q wave followed by a large R wave.

●V1-positive (RBBB) pattern – In the patient with a WCT and positive QRS polarity in lead V1, the following associations have been made [5,11,15,22-24]:

•Findings in lead V1 – A monophasic R or biphasic qR complex in lead V1 favors VT.

A triphasic RSR’ or RsR’ complex (the so-called “rabbit-ear” sign) in lead V1 usually favors SVT. As an exception, if the left peak of the RsR’ complex is taller than the right peak, VT is more likely [16,25].

•Findings in lead V6 – An rS complex (R wave smaller than S wave) in lead V6 favors VT [16]. By contrast, an Rs complex (R wave larger than S wave) in lead V6 favors SVT.

●V1-negative (LBBB) pattern – In the patient with a WCT and negative QRS polarity in lead V1, the following associations have been made [5,11,15,22-24]:

•Findings in lead V1 or V2 – A broad initial R wave of 40 msec duration or longer in lead V1 or V2 favors VT. In contrast, the absence of an initial R wave or a small initial R wave of less than 40 msec in lead V1 or V2 favors SVT.

Two other findings that favor VT are a slurred or notched downstroke of the S wave in lead V1 or V2, and a duration from the onset of the QRS complex to the nadir of the QS or S wave of ≥60 msec in lead V1 or V2. In an analysis of several studies, the presence of any of these three criteria (broad R wave, slurred or notched downstroke of S wave, and delayed nadir of S wave) was a strong predictor of VT [16].

By contrast, a swift, smooth downstroke of the S wave in lead V1 or V2 with a duration of <60 msec favors SVT.

•Findings in lead V6 – The presence of any Q or QS wave in lead V6 favors VT [16]. By contrast, the absence of a Q wave in lead V6 favors SVT.

Variation in QRS and ST-T shape — Subtle, non-rate-related fluctuations or variations in QRS and ST-T wave configuration suggest VT and may reflect variations in the VT reentrant circuit within the myocardium as well as a subtle difference in the activation sequence of the myocardium reflecting activation that bypasses the normal conduction system. AV dissociation can cause variability in the ST segment and T wave morphology. By contrast, SVT, because it follows a fixed conduction pathway to and through the ventricular myocardium, is characterized by uniformity of QRS and ST-T shape unless the rate changes.

DIAGNOSIS — Most patients with wide complex tachycardia (WCT) will have some, but not all, of the electrocardiogram (ECG) features favoring ventricular tachycardia (VT). There is no single criterion or combination of criteria that provides complete diagnostic accuracy in evaluating a WCT. It is typically necessary, therefore, to integrate multiple ECG findings into a diagnostic strategy. Several strategies have been proposed, of which the Brugada criteria are the most widely known [16,26,27]. (See ‘Brugada criteria’ below.)

However, because the diagnosis of a WCT cannot always be made with complete certainty even when using multiple ECG criteria, an unknown or uncertain rhythm should be presumed to be VT in the absence of contrary evidence [28]. VT is far more common than supraventricular tachycardia (SVT), by a factor of four in unselected populations and by as much as 10-fold in patients with prior myocardial infarction. Additionally, presuming VT guards against inappropriate and potentially dangerous therapies directed at an SVT which can precipitate hemodynamic deterioration in patients with VT, and treatment of SVT as if it were VT is safe and frequently effective in restoring sinus rhythm. (See “Approach to the management of wide QRS complex tachycardias”, section on ‘Management’.)

An algorithmic approach to the diagnosis of a WCT will be reviewed here, with emphasis on the distinction between VT and SVT. The approach to a narrow QRS complex tachycardia is discussed separately. (See “Clinical manifestations, diagnosis, and evaluation of narrow QRS complex tachycardias”.)

Our approach — Once a WCT has been identified on the ECG, prompt diagnosis and management is important. Unstable patients should be presumed to have VT and treated as such. While the Brugada criteria are the most widely known and applied criteria for distinguishing VT from SVT, time and/ortechnical limitations may not allow for immediate review of the ECG in such detail, particularly in a symptomatic or borderline unstable patient. Our approach emphasizes immediate ECG review for key high-yield features in parallel with a brief history that can guide the management of most patients with a WCT.

●Is the rhythm regular or irregular? – VT and most SVTs are generally regular, though slight variation of the RR interval can be seen in VT. An irregular WCT usually represents atrial fibrillation (AF) with aberrant conduction, although polymorphic VT should also be considered. (See ‘Basic features’ above.)

●What is the QRS axis? – A right superior axis (axis from -90 to ±180 degrees) strongly favors VT, as does any axis shift of greater than 40 degrees when compared with baseline or concordance of the QRS complexes. (See ‘Basic features’ above and ‘Concordance’above.)

●Is there atrioventricular (AV) dissociation? – If AV dissociation can be quickly identified, an atrial rate slower than the ventricular rate, along with any fusion or capture beats, strongly suggests VT. (See ‘AV dissociation’ above.)

●Is there a history of heart disease or arrhythmias? – A quick history focusing on structural heart disease, particularly coronary heart disease and/or prior myocardial infarction, as well as any known arrhythmias or cardiac implantable electronic devices (eg, pacemaker or implantable cardioverter-defibrillator [ICD]), can aid in identifying the most likely etiology of WCT. The WCT is far more likely to be VT in patients over 35 years of age with known coronary heart disease or prior myocardial infarction, and in those with an ICD. (See ‘History’ above.)

The absence of the historical or ECG features of VT does not confirm a diagnosis of SVT. The diagnosis of SVT should be considered primarily in young patients, whose hearts are structurally normal, in whom none of the historical (eg, family history of sudden cardiac death), physical, or ECG criteria supporting VT are present, or in patients with a history of SVT with a similar presentation. When the diagnosis of a WCT remains uncertain, we recommend that the patient be treated as if the rhythm is VT until definitively proven otherwise.

Brugada criteria — The Brugada criteria are a stepwise approach in which four criteria for VT are sequentially assessed (algorithm 1) [26]. If any of the criteria is satisfied, the diagnosis of VT is made, and if none are fulfilled, an SVT is diagnosed. An exception is an antidromic atrioventricular reentrant tachycardia (AVRT) in Wolff-Parkinson-White syndrome.

The steps are as follows:

●Leads V1-V6 are inspected to detect an RS complex. If there are no RS complexes, concordance is present and the diagnosis of VT can be made. (See ‘Concordance’ above.)

●If an RS complex is present, measure the interval between the onset of the R wave and the nadir of the S wave (RS interval). If the longest RS interval in any lead is >100 msec and the R wave is wider than the S wave, the diagnosis of VT can be made. This reflects that with VT, the entire QRS complex is wide and abnormal (even the initial R wave portion), while aberration is due to a terminal delay resulting in a wider terminal portion of the QRS complex (ie, S wave).

This criterion, however, may be limited in the presence of an underlying diffuse cardiomyopathy, as in this situation even initial ventricular activation may be slow and abnormal.

●If the longest RS interval is <100 msec, the presence or absence of AV dissociation is assessed. If AV dissociation is seen, the diagnosis of VT is made. (See ‘AV dissociation’above.)

●If AV dissociation cannot clearly be demonstrated, the QRS morphology criteria for V1-positive and V1-negative wide QRS complex tachycardias are considered. QRS morphology criteria consistent with VT must be present in leads V1 or V2 and in lead V6 to diagnose VT. If either the V1-V2 or the V6 criteria are not consistent with VT, an SVT is assumed. (See ‘QRS morphology’ above.)

Alternative approaches — Several alternative approaches have been proposed in the literature, although none are as commonly used as the Brugada criteria. These approaches are generally best performed in consultation with an electrophysiologist with expertise in the diagnosis of WCT.

●An alternative algorithm (Vereckei approach) uses a stepwise approach similar to the Brugada criteria, but includes different ECG features (algorithm 2) [27]. Two unique features of this algorithm include an initial R wave in aVR (diagnostic of VT), and the Vi:Vt ratio. Vi and Vt are the magnitude of voltage change in the initial and terminal 40 msec of a QRS, respectively. Vi and Vt should be measured from the same biphasic or multiphasic QRS complex. A Vi:Vt ratio ≤1 is diagnostic of VT.

One study of 51 patients with WCT induced during electrophysiology study showed equivalent sensitivity for diagnosis between the Vereckei and Brugada approaches (89 versus 90 percent), but the Vereckei approach yielded significantly fewer incorrect diagnoses following the first step (2 versus 27 percent) and was slightly faster to perform (9.1 versus 9.9 seconds) [29].

●A Bayesian approach utilizes likelihood ratios (LR) for six ECG criteria [16]. Patients are presumed to start with a “prior odds ratio” of 4.0 (4:1) in favor of VT. As each criterion is evaluated sequentially, the associated LR is multiplied by the prior odds ratio to calculate the new probability of VT. The final odds ratio (posterior probability) is considered consistent with VT if the value is ≥1.0, and SVT if the value is <1.0.

●Intravenous adenosine may be administered as both a diagnostic and potentially therapeutic agent. (See “Approach to the management of wide QRS complex tachycardias”, section on ‘Pharmacologic interventions’.)

VT versus AVRT — Differentiation between VT and antidromic AVRT is particularly difficult. Because there is direct myocardial activation since ventricular activation begins outside of the normal conduction system in both VT and antidromic AVRT, many of the standard criteria are not able to discriminate antidromic AVRT from VT. The clinical significance of this problem is often limited, however, because preexcitation is an uncommon cause of WCT (6 percent in one series), particularly if other clinical factors (eg, age, underlying heart disease) suggest VT [11].

For cases in which preexcitation is thought to be likely (such as a young patient without structural heart disease, or a patient with a known accessory pathway), a separate algorithm was developed which consists of the following three steps (algorithm 3) [26]:

●The predominant polarity of the QRS complex in leads V4 through V6 is defined either as positive or negative. If predominantly negative, the diagnosis of VT can be made.

●If the polarity of the QRS complex is predominantly positive in V4 through V6, the ECG should be examined for the presence of a qR complex in one or more of precordial leads V2 through V6. If a qR complex can be identified, VT can be diagnosed.

●If a qR wave in leads V2 through V6 is absent, the AV relationship is then evaluated (AV dissociation). If a 1:1 AV relationship is not present and there are more QRS complexes present than P waves, VT can be diagnosed.

When any of these criteria are met, VT is likely. However, if the ECG does not display any of the three morphologic characteristics diagnostic of VT in this algorithm, the diagnosis of antidromic AVRT must be considered. Importantly, the QRS complex morphology and ST-T waves are uniform with AVRT as every impulse to the ventricle is conducted through the same accessory pathway.

Algorithm performance — Algorithms often perform well in initial reports. However, such studies include selected populations and experienced ECG analysts.

●In its initial description, the reported sensitivity and specificity of the Brugada criteria were 98.7 and 96.5 percent, respectively [26]. However, in two subsequent reports in which a total of nine clinicians (two cardiologists, two emergency department clinicians, and five internists) used these criteria in interpreting a total of 168 WCTs that had been diagnosed with electrophysiologic testing, the sensitivity ranged from 79 to 92 percent, and specificity from 43 to 70 percent [30,31].

●In a comparison of the Brugada criteria and the Bayesian approach, the two approaches performed similarly, with sensitivities of 92 and 97 and specificities of 44 and 56 percent, respectively [31].

●In the initial description of the alternative algorithm described above, it was significantly more accurate than the Brugada criteria [27]. Further study is necessary to confirm both the overall accuracy of this approach and its superiority to the Brugada criteria.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See “Society guideline links: Arrhythmias in adults”.)

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Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)

●Basics topics (see “Patient education: Ventricular tachycardia (The Basics)”)

SUMMARY AND RECOMMENDATIONS

●Ventricular tachycardia (VT) is the most common cause of wide complex tachycardia (WCT), particularly in patients with a history of cardiac disease, while supraventricular tachycardia (SVT) results in WCT (due to aberrant conduction, preexcitation, or ventricular pacing) much less frequently. WCT is identified as VT in up to 80 percent of unselected patients and more than 90 percent of patients with known structural heart disease. (See ‘Epidemiology’ above and ‘Causes of WCT’above.)

●Patients with WCT are rarely asymptomatic, although the type and intensity of symptoms will vary depending upon the rate of the WCT, the presence or absence of significant comorbid conditions, and whether the WCT is VT or SVT. Patients with WCT typically present with one or more of palpitations, chest pain, shortness of breath, syncope/presyncope, or sudden cardiac arrest. (See ‘Clinical manifestations’ above.)

●The first priority when evaluating a patient with a WCT is an immediate assessment of patient stability, including the patient’s symptoms, vital signs, and the level of consciousness. An unstable patient will have evidence of hemodynamic compromise, such as hypotension, altered mental status, chest pain, or heart failure.

•A patient who is unresponsive or pulseless should be treated according to standard advanced cardiac life support (ACLS) algorithms (algorithm 4). (See ‘Assessment of stability’ above and “Advanced cardiac life support (ACLS) in adults”.)

•For a patient who is unstable but conscious, we recommend immediate synchronized cardioversion (Grade 1B). (See ‘Assessment of stability’ above and “Approach to the management of wide QRS complex tachycardias”, section on ‘Unstable patients’.)

•In a stable patient, or following cardioversion to stabilize an unstable patient, our initial approach includes the following:

-A succinct history and physical examination, focusing on the presence of structural heart disease, especially coronary heart disease and/or a previous myocardial infarction, as well as the history of any arrhythmias and the presence of a pacemaker or implantable cardioverter defibrillator (ICD). (See ‘History’ above and ‘Physical examination’ above.)

-Review of the patient’s medications for drugs which may be proarrhythmic (by prolonging the QT interval or promoting electrolyte disturbances). (See ‘Medications’ above.)

-Ancillary testing including serum electrolyte levels, cardiac troponin, and a chest radiograph in all patients. (See ‘Ancillary testing’ above.)

●In most patients with WCT, a probable diagnosis (VT or SVT) may be made by closely reviewing the electrocardiogram (ECG), although definitive diagnosis is not always possible and may be time-consuming. The standard initial approach to ECG interpretation includes an assessment of rate, regularity, axis, QRS duration, and QRS morphology. (See ‘Evaluation of the electrocardiogram’ above.)

●Most patients with WCT will have some, but not all, of the ECG features favoring VT. There is no single criterion or combination of criteria that provides complete diagnostic accuracy in evaluating a WCT, even when employing an algorithmic approach to the diagnosis of a WCT, most commonly using the Brugada criteria. (See ‘Diagnosis’ above.)

•ECG features consistent with VT include concordance, AV dissociation, fusion/capture beats, and specific QRS morphologies.

•The absence of the historical or ECG features of VT does not confirm a diagnosis of SVT. The diagnosis of SVT should be considered primarily in young patients, whose hearts are structurally normal, in whom none of the historical (eg, family history of sudden cardiac death), physical, or ECG criteria supporting VT are present, or in patients with a history of SVT with a similar presentation.

•When the diagnosis of a WCT is uncertain, we recommend that the patient be treated as if the rhythm is VT (Grade 1B).

ACKNOWLEDGMENT — The editorial staff at UpToDate would like to acknowledge Philip Podrid, MD, who contributed to an earlier version of this topic review.

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