King's College Criteria for Acetaminophen Toxicity

Arterial pH <7.30 (after fluid resuscitation)

INR >6.5 (PT >100 sec)

Creatinine >3.4 mg/dL

Grade III-IV Hepatic Encephalopathy

Result: –

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Recommends who should be immediately referred for liver transplant.

Why Use

Acetaminophen poisoning is the most common cause of acute liver failure in the US, the UK and many other countries. The only treatment option that radically improves the outcome of acute liver failure is emergency liver transplantation. Therefore proper identification of which to refer/transfer is critically important. In addition, appropriate transplant candidates must be identified as early as possible to provide a realistic window for a graft to become available.

When to Use

The KCC are a well-accepted criteria that show the degree of multiorgan dysfunction from acetaminophen-induced liver failure. Used alone or with serum lactate and phosphate, the KCC can predict patients with poor prognosis.

Formula

Series of Yes/No Questions.

Pearls / Pitfalls

The King’s College Criteria (KCC) were developed to determine which patients with fulminant hepatic failure (FHF) should be referred for liver transplant. Apply to all (acute or chronic) acetaminophen ingestions with signs of severe acute liver injury. There are no worldwide standard criteria for transplantation, but the KCC are the most widely applied. The KCC indicators predict a poor prognosis, and select patients most likely to benefit from immediate liver transplant referral. The etiology of the acute liver failure is important in determining indicators of poor prognosis (acetaminophen vs. other causes). Metabolic acidosis alone OR combined grade III or IV hepatic encephalopathy AND a PT time > 100s AND creatinine > 3.4 mg/dL predicted 77% of total deaths. Points to keep in mind: KCC is criticized for predicting mortality often when patients are too sick for transplant. The use of prolonged N-acetylcysteine therapy - not standard when the KCC was created - has significantly lowered the complication rate and need for transplant. PT values are often not comparable across laboratories (due to use of different reagents). Serum lactate (marker of liver injury), and phosphate (marker of liver regeneration), have been used as alternative early prognostic indicators or adjuncts to the KCC. Specific but not sensitive: that is, while fulfillment of the criteria carries a poor prognosis, lack of fulfillment can still carry an unfavorable outlook.

Management

All patients with acetaminophen-induced hepatotoxicity should receive N-acetylcysteine (see NAC calculator ). Frequent monitoring should be performed for coagulation parameters, complete blood counts, metabolic panels, blood gases, and blood glucose. Serum aminotransferases and bilirubin should be monitored daily. Patients should be monitored and treated for hypoglycemia, hypokalemia, and hypophosphatemia. Fresh frozen plasma (FFP) is indicated only in the setting of active hemorrhage or prior to invasive procedures in coagulopathic patients. Prophylactic administration of FFP is not recommended since it does not improve mortality and can interfere with assessments of liver function.

Critical Actions

Patients with acute liver failure should be managed in centers with expertise in caring for these patients. This includes patients who do not yet appear to be gravely ill, since it can be hazardous to transfer patients later in the disease course.

Advice

The presence of one of the following should prompt a referral/transfer to a liver transplantation center: Acidosis (admission arterial pH <7.30) OR Hepatic encephalopathy (grade III or IV), AND coagulopathy (PT >100 s), AND acute kidney injury (creatinine >3.4 mg/dL), OR Hyperlactatemia (4-hour lactate >3.5 mmol/L, or 12-hour lactate >3.0 mmol/L), OR Hyperphosphatemia (48-96 hour phosphate >3.7 mg/dL) in patients with acetaminophen-induced fulminant hepatic failure.

More Information

Criteria PPV Sensitivity Specificity Predictive Accuracy Arterial pH <7.30 0.95 0.49 0.99 0.81 HE + PT + Cr 0.67 0.45 0.94 0.83 Lactate* 0.81 0.95 0.92 Phosphate** 1 0.89 1 0.98 PPV = Positive predictive value; HE = Hepatic encephalopathy stage III/IV; PT = prothrombin time >100 s; Cr = creatinine >3.4 mg/dL * Either lactate >3.5 mmol/L after early resuscitation, or >3.0 mmol/L after full resuscitation. ** Phosphate >3.7 mg/dL between 48 – 96 hours. For more information on Hepatic Encephelopathy Stages, click here .