Serum phosphate is an early predictor of outcome in severe acetaminophen-induced hepatotoxicity

Abstract

Hypophosphatemia is frequently observed in acetaminophen-induced hepatotoxicity and may be involved in the pathogenesis of hepatic failure. The aim of the study was to evaluate the prognostic value of serial measurements of serum phosphate in patients with severe acetaminophen poisoning. Prospectively, serial measurements of serum phosphate were performed in 125 patients with severe acetaminophen poisoning. The optimum threshold value of serum phosphate to discriminate nonsurvivors was identified. Prognostic value and speed of identification were compared with those of the King's College Hospital (KCH) criteria. Phosphate concentrations were significantly higher in nonsurvivors than in survivors at 48 to 72 hours after overdose (mean 2.65 ؎ 1.18 mmol/L vs. 0.68 ؎ 0.22 mmol/L, P < .001) as well as 72 to 96 hours after overdose (2.12 ؎ 0.22 mmol/L vs. 0.59 ؎ 0.23 mmol/L, P < .001). A threshold phosphate concentration of 1.2 mmol/L at 48 to 96 hours after overdose had sensitivity 89%, specificity 100%, accuracy 98%, positive predictive value 100%, and negative predictive value 98%. The phosphate criteria had higher sensitivity, accuracy, and positive and negative predictive values than the KCH criteria, and it identified patients significantly earlier after transferal [median 1 hour (range 1-38 hours) vs. 12 hours (2-192 hours), P < .05, respectively]. In nonsurvivors, the degree of hyperphosphatemia correlated with renal dysfunction (R ‫؍‬ .55; P ‫؍‬ .02). In conclusion, hyperphosphatemia after acetaminophen overdose is seen exclusively in nonsurvivors, which makes it a highly specific as well as sensitive predictor of nonsurvival. We propose that hyperphosphatemia is caused by renal dysfunction in the absence of hepatic regeneration, as the latter appears to be associated with lowering of serum phosphate. (HEPATOLOGY 2002;36:659-665.)

MELD score as a predictor of liver failure and death in patients with acetaminophen-induced liver injury

“…11 Attempts have been made to amend these drawbacks by proposing the addition of sensitive and early prognostic markers such as lactate and phosphate. 10,12,[33][34][35] However, none of these markers have been generally accepted, and there is still a need for better prognostic indicators in acetaminophen poisoning.…”

“…Among several selection criteria for urgent liver transplantation, the King's College Hospital (KCH) criteria have gained considerable acceptance. [3][4][5][6][7][8][9][10] However, shortcomings of the KCH criteria have been a limited sensitivity and a late identification of the patients who require transplantation. 11 It has therefore been of interest to discover prognostic indicators with the capability of identifying transplant candidates at an earlier stage of liver failure, perhaps even prior to the onset of hepatic encephalopathy (HE).…”

“…11 It has therefore been of interest to discover prognostic indicators with the capability of identifying transplant candidates at an earlier stage of liver failure, perhaps even prior to the onset of hepatic encephalopathy (HE). 10,12 The Model for End-Stage Liver Disease (MELD) scoring system was originally designed for the assessment of short-term prognosis in patients with liver cirrhosis undergoing a transjugular intrahepatic portosystemic shunt (TIPS) to alleviate portal hypertension. 13 Subsequently, its use has been expanded to predict survival in end-stage chronic liver disease in general, and the MELD score has been applied as a disease severity index in organ allocation decisions for liver transplantation in patients with chronic liver disease.…”

ACMT Position Statement: Duration of Intravenous Acetylcysteine Therapy Following Acetaminophen Overdose

“…In APAP poisoning, many predictors of poor prognosis have been described. In practice, decreased pH, increases in phosphate, increased lactate, increases in prothrombin time/INR, and increases in serum creatinine are the most readily available predictors of poor prognosis [8,10,11]. Treatment with 21 h of IV NAC is highly effective at preventing hepatotoxicity in most patients following acute APAP overdose and in reducing mortality in those with established hepatotoxicity [12].…”

Broadening the view of acetaminophen hepatotoxicity

“…It is remarkable how little progress has been made in almost two decades given the shortcomings of the King's College Hospital criteria in acetaminophen-induced acute liver failure, although the full impact of more recent observations relating to serum lactate and phosphate have yet to be determined. [12][13][14] The relevance of effective prognostic criteria mainly is due to the application of liver transplantation in the management of the most severe cases of acetaminophen-induced liver failure. The need for accuracy is self-evident, given the desired objectives of avoiding unnecessary transplantation and offering all those in need the opportunity to benefit from a liver graft.…”