The sequential organ failure assessment (SOFA) score is prognostically superior to the model for end-stage liver disease (MELD) and MELD variants following paracetamol (acetaminophen) overdose.

BACKGROUND: The prognostic value of the model for end-stage liver disease (MELD) and sodium-based MELD variants in predicting survival following paracetamol overdose remains unclear. AIM: To examine the prognostic accuracy of sodium-based MELD variants in paracetamol-induced acute liver injury compared with the sequential organ failure assessment (SOFA) score. METHODS: Retrospective analysis of 138 single time point paracetamol overdoses admitted to a tertiary liver centre. Individual laboratory samples were correlated with the corresponding clinical parameters in relation to time post-overdose, and the daily MELD, MELD-Na, MELDNa, MESO, iMELD, UKELD, updated MELD and SOFA scores were calculated. RESULTS: Sixty-six (47.8%) patients developed hepatic encephalopathy, of whom 7 were transplanted and 21 died without liver transplantation. SOFA had a significantly greater area under the receiver operator characteristic for the prediction of spontaneous survival compared with MELD at both 72 (P = 0.024) and 96 (P = 0.017) h post-overdose. None of the sodium-based MELD variants improved the prognostic accuracy of MELD. A SOFA score >6 by 72 h or >7 by 96 h, post-overdose predicted death/transplantation with a negative predictive value of 96.9 (95% CI 90.2-99.4) and 98.8 (95% CI 93.6-99.9) respectively. SOFA and MELD had similar accuracy for predicting the development of hepatic encephalopathy (P = 0.493). CONCLUSIONS: The SOFA score is superior to MELD in predicting spontaneous survival following paracetamol-induced acute liver injury. Modification of the MELD score to include serum sodium does not improve prognostic accuracy in this setting. SOFA may have potential as a quantitative triage marker following paracetamol overdose.

Acute liver failure in Scotland between 1992 and 2009; incidence, aetiology and outcome.

AIM: To describe incidence, aetiology and outcome data for Scotland since the inception of the Scottish Liver Transplant Unit (SLTU) in 1992. BACKGROUND: Acute liver failure (ALF) is a rare but frequently fatal condition. Few studies have adequate patient numbers to draw convincing conclusions over demographic features, aetiology and outcome. DESIGN: Statistical analysis of prospectively collected data on aetiology, demographic, clinical and outcome of all admissions, including those with ALF, to the SLTU. METHODS: Incidence data presented for admissions and ALF. Descriptive frequencies for aetiology, clinical, demographic and outcome data presented; including split analysis for paracetamol and non-paracetamol aetiologies. Univariate and multivariate analysis of admission factors predictive of outcome is described. RESULTS: Nine hundred and forty-nine patients were admitted to the SLTU between 1992 and 2009. Five hundred and twenty-four patients had ALF. The annual incidence of ALF in the Scottish population is 0.62 per 100,000 and paracetamol overdose (POD) was the largest causative factor; responsible for 0.43 cases of ALF per 100,000 population per year. The odds ratio (OR) of transplantation or death was 0.47 in the POD group compared to other aetiologies; yet of not being a transplant candidate having met the Kings College Hospital poor prognostic criteria OR was 4.9. Of admissions listed for transplant 76.0% were transplanted. Of those listed and not transplanted mortality was approaching 100% and 76.1% of those transplanted survived to discharge. CONCLUSION: This large, prospective, single centre study with a defined geographical area and well-recorded population provides accurate data regarding ALF between 1992 and 2009.

The systemic inflammatory response syndrome and sequential organ failure assessment scores are effective triage markers following paracetamol (acetaminophen) overdose.

BACKGROUND: The systemic inflammatory response syndrome (SIRS) and sequential organ failure assessment (SOFA) scores are widely used as prognostic markers in critical care settings and could improve triage of high-risk paracetamol (acetaminophen) overdose patients. AIM: To evaluate the prognostic accuracy of the SIRS and SOFA scores following single time point paracetamol overdose. METHODS: Analysis of 100 single time point paracetamol overdoses admitted to a tertiary liver centre, with subsequent prospective validation of identified thresholds. Individual laboratory samples were correlated with the corresponding clinical parameters in relation to time post-overdose, and the daily SOFA and SIRS scores calculated. RESULTS: A total of 74 (74%) patients developed the SIRS, which occurred significantly earlier in patients who died (n=21) compared with spontaneous survivors (n=53, P=0.05). The SIRS occurred in 70 (70%) patients by 96h post-overdose, with a 30% mortality rate; compared with 0% mortality in the 30 non-SIRS patients (P=0.001). Median SOFA scores were significantly higher in nonsurvivors at 48 (P=0.009), 72 (P<0.001), and 96h (P<0.001). A SOFA score >7 during the first 96h post-overdose predicted death/transplantation with a sensitivity of 95.0 (95% CI 78.5-99.1) and specificity of 70.5 (95% CI 66.3-71.6). A validation cohort of 38 single time point paracetamol overdoses confirmed the extremely high negative predictive value of both the SIRS and SOFA thresholds. CONCLUSIONS: The absence of either a SOFA score >7 or a SIRS response during the first 96 h following paracetamol overdose could improve triage and reduce transfers of lower risk patients to tertiary liver centres.

Inappropriate utilization of intravenous proton pump inhibitors in hospital practice--a prospective study of the extent of the problem and predictive factors.

BACKGROUND: Intravenous (IV) proton pump inhibitors (PPI) reduce rebleeding from high-risk peptic ulcers following endoscopic therapy. The majority of IV PPI prescriptions in US hospital practice are inappropriate, leading to unnecessary drug costs, drug shortages and potential adverse events. To date, little is known about UK hospital IV PPI prescribing practice. AIMS: To examine IV PPI use in a large university teaching hospital to determine factors predicting inappropriate prescribing practices. METHODS: Prospective study of 276 recently hospitalized patients initiated on IV PPI over a 6-month period. IV PPI use was deemed appropriate for the following indications: endoscopic evidence of recent upper gastrointestinal (UGI) haemorrhage, patient nil by mouth with a valid indication for oral PPI therapy and stress ulcer prophylaxis in a critical care setting. RESULTS: The majority (208/276, 75.4%) of IV PPI prescriptions were deemed inappropriate in terms of either indication for use, dose or duration of therapy. The majority (168/276, 60.9%) of prescriptions were initiated on non-medical wards. Inappropriate prescribing was more common amongst female patients, surgical admissions, non-UGI haemorrhage cases and when initiated by junior hospital doctors. Surgical admission [odds ratio (OR) 2.88, 95% confidence interval (CI) 1.12-7.42] and female gender [OR 3.92 (95% CI 1.84-8.34)] were independently predictive of inappropriate use. CONCLUSION: This study suggests that the majority of IV PPI prescriptions in hospital are inappropriate, particularly when initiated for non-UGI bleeding indications. Improving prescribing awareness through education of junior medical staff on non-medical wards could reduce inappropriate IV PPI use.

Systematic review: prognostic tests of paracetamol-induced acute liver failure.

BACKGROUND: Paracetamol (acetaminophen) toxicity remains the leading cause of acute liver failure (ALF) in the developed world. In the UK, the recently modified King's College Criteria are used to list patients for emergency liver transplantation, but these criteria have been criticized for their low sensitivity and for spectrum bias in their application. AIM: To evaluate existing prognostic criteria critically for predicting death without transplantation in paracetamol-induced ALF. METHODS: MEDLINE, EMBASE and CINAHL were searched to identify studies containing adult patients with paracetamol-induced ALF. Selected studies were evaluated and data were pooled if appropriate, to calculate sensitivity, specificity and diagnostic odds ratios (DORs) of applied prognostic tests. RESULTS: Of 6507 studies identified, 14 were eligible for inclusion, evaluating 1960 patients. The original King's College Criteria had a pooled sensitivity of 58.2% and specificity of 94.6%, with a DOR of 27.7. Addition of arterial lactate to the King's College Criteria reduced the DOR to 26.1. Several other clinical and laboratory variables had higher DORs than the King's College Criteria, but were only evaluated in single studies of limited quality. CONCLUSIONS: The original King's College Criteria remain well-validated criteria with high prognostic accuracy. Other potential prognostic variables should be prospectively assessed in multicentre studies to refine the criteria further.

Review article: the current management of acute liver failure.

BACKGROUND: Acute liver failure is a devastating clinical syndrome with a persistently high mortality rate despite critical care advances. Orthotopic liver transplantation (OLT) is a life-saving treatment in selected cases, but effective use of this limited resource requires accurate prognostication because of surgical risks and the requirement for subsequent life-long immunosuppression. AIM: To review the aetiology of acute liver failure, discuss the evidence behind critical care management strategies and examine potential treatment alternatives to OLT. METHODS: Literature review using Ovid, PubMed and recent conference abstracts. RESULTS: Paracetamol remains the most common aetiology of acute liver failure in developed countries, whereas acute viral aetiologies predominate elsewhere. Cerebral oedema is a major cause of death, and its prevention and prompt recognition are vital components of critical care support, which strives to provide multiorgan support and 'buy time' to permit either organ regeneration or psychological and physical assessment prior to acquisition of a donor organ. Artificial liver support systems do not improve mortality in acute liver failure, whilst most other interventions have limited evidence bases to support their use. CONCLUSION: Acute liver failure remains a truly challenging condition to manage, and requires early recognition and transfer of patients to specialist centres providing intensive, multidisciplinary input and, in some cases, OLT.