Obese (body mass index, BMI>30) and morbidly obese (BMI>40) parturients are increasingly common. Obesity is associated with an increased risk of preeclampsia, left or right heart failure, airway difficulties, aspiration risk, thromboembolism, and technical challenges to regional anesthetic techniques. Obesity contributes to increased maternal mortality. Early anesthetic involvement in labor may permit time for epidural or combined spinal/epidural techniques that may be too time-consuming in the emergency situation. General anesthesia is potentially hazardous and should only be undertaken by senior, experienced personnel. Specialized equipment needs to be available. Bariatric operating tables, extralarge beds, hover mattresses, and hoists are essential for the supermorbidly obese (BMI>50). Management in the immediate postoperative period following cesarean section should be considered in advance. There is a risk of inadequate ventilation or airway compromise postoperatively leading to hypoxemia. There should be a low threshold for admitting these women to a critical care area capable of managing obese patients. Maintenance of epidural analgesia into the postoperative period may limit respiratory depression from opioid use and permits rapid reestablishment of anesthesia.

Obese (body mass index, BMI>30) and morbidly obese (BMI>40) parturients are increasingly common. Obesity is associated with an increased risk of pre-eclampsia, left or right heart failure, airway difficulties, aspiration risk, thromboembolism and technical challenges to regional anaesthetic techniques. Obesity contributes to increased maternal mortality. Early anaesthetic involvement in labour may permit time for epidural or combined spinal/epidural techniques which may be too time consuming in the emergency situation. General anaesthesia is potentially hazardous and should only be undertaken by senior, experienced personnel. Specialised equipment needs to be available. Bariatric operating tables, extra large beds, hover mattresses and hoists are essential for the super morbidly obese (BMI>50). Management in the immediate post-operative period following Caesarean section should be considered in advance. There is a risk of inadequate ventilation or airway compromise post-operatively leading to hypoxaemia. There should be a low threshold for admitting these women to a high-dependency area capable of managing obese patients. Maintenance of epidural analgesia into the post-operative period may limit respiratory depression from opioid use and permits rapid re-establishment of anaesthesia.

Nurofen Plus is a common analgesic containing ibuprofen and codeine. We present a case of a 38-year-old lady who developed renal tubular acidosis with severe hypokalaemia, after chronic abuse of Nurofen Plus tablets. She presented with confusion and profound biochemical abnormalities requiring critical care admission for electrolyte replacement. Ibuprofen causes renal tubular acidosis due to its effects on carbonic anhydrase activity.

Background & Aims: Transjugular intrahepatic stent-shunt (TIPSS) insertion, in patients with uncontrolled gastro-intestinal bleeding, often results in worsening of the systemic hemodynamics which can be associated with intracranial hypertension but the underlying mechanisms are unclear. This study explored the hypothesis that TIPSS insertion results in acute endotoxemia which is associated with increased nitric oxide production resulting in systemic and cerebral vasodilatation.Methods: Twelve patients with cirrhosis who were undergoing TIPSS for uncontrolled variceal bleeding were studied prior to and 1-h after TIPSS insertion. Changes in cardiac output (CO) and cerebral blood flow (CBF) were measured. NO production was measured using stable isotopes using L[guanidino-(15)N(2)] arginine and L-[ureido-(13)C;5,5-(2)H(2)] citrulline infusion. The effect of pre- and post-TIPSS plasma on nitric oxide synthase (NOS) activity on human endothelial cell-line (HUVEC) was measured.Results: TIPSS insertion resulted in a significant increase in CO and CBF. Endotoxin and induced neutrophil oxidative burst increased significantly without any significant changes in cytokines. Whole body NO production increased significantly and this was associated with increased iNOS activity in the HUVEC lines. The change in NO production correlated with the changes in CO and CBF. Brain flux of ammonia increased without significant changes in arterial ammonia.Conclusions: In conclusion, the insertion of TIPSS results in acute endotoxemia which is associated with increased nitric oxide production possibly through an iNOS dependent mechanism which may have important pathophysiological and therapeutic relevance to understanding the basis of circulatory failure in the critically ill cirrhotic patient. (C) 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Background: The development of effective therapies for acute liver failure (ALF) is limited by our knowledge of the pathophysiology of this condition, and the lack of suitable large animal models of acetaminophen toxicity. Our aim was to develop a reproducible invasively-monitored porcine model of acetaminophen-induced ALF.Method: 35kg pigs were maintained under general anaesthesia and invasively monitored. Control pigs received a saline infusion, whereas ALF pigs received acetaminophen intravenously for 12 hours to maintain blood concentrations between 200-300 mg/l. Animals surviving 28 hours were euthanased.Results: Cytochrome p450 levels in phenobarbital pre-treated animals were significantly higher than non pre-treated animals (300 vs 100 pmol/mg protein). Control pigs (n = 4) survived 28-hour anaesthesia without incident. Of nine pigs that received acetaminophen, four survived 20 hours and two survived 28 hours. Injured animals developed hypotension (mean arterial pressure; 40.8 +/- 5.9 vs 59 +/- 2.0 mmHg), increased cardiac output (7.26 +/- 1.86 vs 3.30 +/- 0.40 l/min) and decreased systemic vascular resistance (8.48 +/- 2.75 vs 16.2 +/- 1.76 mPa/s/m3). Dyspnoea developed as liver injury progressed and the increased pulmonary vascular resistance (636 +/- 95 vs 301 +/- 26.9 mPa/s/m3) observed may reflect the development of respiratory distress syndrome. Liver damage was confirmed by deterioration in pH (7.23 +/- 0.05 vs 7.45 +/- 0.02) and prothrombin time (36 +/- 2 vs 8.9 +/- 0.3 seconds) compared with controls. Factor V and VII levels were reduced to 9.3 and 15.5% of starting values in injured animals. A marked increase in serum AST (471.5 +/- 210 vs 42 +/- 8.14) coincided with a marked reduction in serum albumin (11.5 +/- 1.71 vs 25 +/- 1 g/dL) in injured animals. Animals displayed evidence of renal impairment; mean creatinine levels 280.2 +/- 36.5 vs 131.6 +/- 9.33 mu mol/l. Liver histology revealed evidence of severe centrilobular necrosis with coagulative necrosis. Marked renal tubular necrosis was also seen. Methaemoglobin levels did not rise >5%. Intracranial hypertension was not seen (ICP monitoring), but there was biochemical evidence of encephalopathy by the reduction of Fischer's ratio from 5.6 +/- 1.1 to 0.45 +/- 0.06.Conclusion: We have developed a reproducible large animal model of acetaminophen-induced liver failure, which allows in-depth investigation of the pathophysiological basis of this condition. Furthermore, this represents an important large animal model for testing artificial liver support systems.

CLINICAL S179medical therapy during 2001-2007.Demographic, clinical and laboratory parameters were recorded at the beginning and end of each treatment.Six months survival and the need for LTx were recorded.Logistic regression analysis was performed to determine factors predicting survival.Variables analyzed included demographic, clinical and treatment-related data, and laboratory parameters at baseline. Results:The study population included 113 acute (ALF), 62 acute-onchronic (AOCLF), 11 graft failure (GF), and 6 miscellaneous liver failure patients.Contraindication to Ltx existed in 35% of patients and 18 patients became untransplantable during treatment.Transplantation-free survival was 68% in ALF, 18% in AOCLF and 60% in GF.The poorest six month survival (6%) was noted in a subgroup of patients with alcohol-related AOCLF and cirrhosis.AOCLF patients with merely steatotic liver had a 55% survival.Percentage of transplanted patients was 29% in ALF, 18% in AOCLF and 55% in GF.The six month survival of transplanted patients was 94% in ALF, 73% in AOCLF and 83% in re-transplanted GF patients.The prognostic factors for survival included encephalopathy grade (P = 0.001) in paracetamol-related ALF, coagulation factor levels (P = 0.049) and encephalopathy grade (P = 0.064) in nonparacetamolrelated ALF, and alanine aminotransferase (P = 0.013) and coagulation factor V levels (P = 0.022) in unknown etiology ALF.In other subgroups prognostic factors could not be identified. Conclusion:The etiology of liver failure was the most important predictor of survival in MARS treated patients (P < 0.0001).MARS treatment seems to be futile in chronic alcohol-related AOCLF patients with cirrhosis, but some patients with merely steatotic liver may benefit even without transplantation.

Liver transplantation (LT) may be life-saving in severe acute liver failure (ALF). The aim of this study was to compare the utilization of LT in acetaminophen and non-acetaminophen ALF. Between 1992 and 2006, 469 patients with ALF were admitted, and 104 underwent LT. Acetaminophen was the most common etiology, but LT proceeded more frequently in the non-acetaminophen cohort (acetaminophen: 45/326 patients received LT, 13.8%; non-acetaminophen: 59/143 patients received LT, 41.3%; P < 0.01). A retrospective analysis of the individual steps in the management of patients revealed more ALF patients in the non-acetaminophen cohort fulfilled the King's College Hospital poor prognostic criteria (non-acetaminophen: 91/143, 63.6%; acetaminophen: 165/326, 50.6%; P < 0.01), more patients had contraindications to LT in the acetaminophen cohort (acetaminophen: 99/165, 60%; non-acetaminophen: 21/91, 23.1%; P < 0.01), and survival on the LT waiting list was reduced in the acetaminophen cohort (acetaminophen: 45/66, 68.2%; non-acetaminophen: 59/70, 84.3%; P < 0.05). Post-LT survival was similar in the 2 groups. An analysis of cohorts admitted in 1993-1996 and 2002-2005 revealed that LT proceeded less commonly in acetaminophen ALF in the later cohort (1993-1996: 16/99 LT, 16.2%; 2002-2005: 4/81 LT, 5%; P < 0.01) in comparison with the non-acetaminophen cohort, in which transplantation proceeded more commonly in the later cohort (1993-1996: 11/34 LT, 32.4%; 2002-2005: 24/49 patients, 49.0%; P < 0.01). This was due to an increase in the number of patients with psychiatric contraindications to transplantation (predominantly resistant and severe alcohol dependence). In conclusion, at all decision steps between admission and emergency LT, LT is favored in non-acetaminophen patients, and nonoperative management is favored in acetaminophen ALF patients.

Background: Although renal dysfunction is a common complication of acute liver failure (ALF) with significant prognostic implications, the pathophysiological mechanisms remain unclear. The current hypothesis suggests that the renal dysfunction may mirror the hepatorenal syndrome of cirrhosis. However, ALF has distinct clinical characteristics and the circulatory derangement may be more comparable with sepsis.Objectives: To examine the relationship between the systemic inflammatory response syndrome (SIRS) and renal dysfunction in ALF, and to identify additional risk factors for renal dysfunction.Methods: A single-centre retrospective study of 308 patients with ALF was carried out. Renal dysfunction was defined according to the RIFLE criteria for acute kidney injury.Results: 67% of patients developed renal dysfunction. On univariate analysis, renal dysfunction patients were more likely to be hypothermic (p = 0.010), had a faster heart rate (p < 0.001), a higher white cell count (p = 0.001) and a lower PaCO2 (p = 0.033). 78% of renal dysfunction patients and 53% of non-renal dysfunction patients had SIRS (p < 0.001). On multivariate analysis, the risk factors for renal dysfunction were age (p = 0.024), fulfilled Kings College Hospital prognostic criteria (p < 0.001), hypotension (p, 0.001), paracetamol-induced ALF (p < 0.001), infection (p = 0.077) and SIRS (p = 0.017). SIRS remained an independent predictor of renal dysfunction in the subgroup of patients with non-paracetamol-induced ALF (n = 91, p = 0.001). In contrast, in patients with paracetamol-induced ALF (n = 217), no relationship between SIRS and renal dysfunction was demonstrated (p = 0.373).Conclusion: SIRS is strongly associated with the development of renal dysfunction in patients with non-paracetamol-induced ALF. It is proposed that the systemic inflammatory cascade plays a key role in its pathogenesis.

Objective. To study the total amount of sedative drugs administered to patients in the intensive care unit (ICU) before and after tracheostomy. Design. Prospective observational study. Setting. Twelve-bedded general ICU that was expanded to an 18-bedded general ICU. Subjects. Twenty-two patients who had a tracheostomy inserted during their ICU stay. Interventions. None. End points. The total amount of sedative drugs administered to patients three days before and three days after insertion of tracheostomy. Measurements and main results. During the study period 447 patients were admitted to ICU, 27 (5.6%) had a tracheostomy. Four patients were excluded from the study because of the presence of hypoxic brain damage or a permanent tracheostomy prior to ICU admission. Twenty-three patients were studied. The median age was 65, median initial 24 h APACHE II score was 22, median length of stay was 36 days, and median time of performing the tracheostomy was 14 days. Twelve (52%) patients died and one patient was transferred to another centre the day after tracheostomy and was therefore not included in the comparison of sedation use before and after tracheostomy. Alfentanil, morphine, propofol and midazolam were used in 17 (77.3%), 8 (36.4%), 19 (86.4%) and 9 (40.9%) patients respectively. Overall, there was a significant reduction in the total amount of alfentanil (p=0.01) and propofol (p=0.01) administered before and after tracheostomy. One patient (4.5%) did not receive sedation before or after tracheostomy. Sedative drug use was reduced after tracheostomy in 13 (59%) patients and slightly increased in one (4.5%) patient. Sedative drugs were altered in 7 (31.8%) patients. Ten patients received only propofol and/or alfentanil for sedation. For these patients, there was a significant reduction in the use of both these agents after tracheostomy, p=0.02 and p<0.01 respectively. Conclusions. Tracheostomy results in a reduction in the amount of sedative drugs administered to patients in ICU, especially when propofol and alfentanil are used.

Background/Aims: The study aims were to determine the role of inflammation in the pathogenesis of increased intracranial pressure (ICP) in patients with acute liver failure (ALF) and its interplay with cerebral blood flow (CBF) and ammonia. Methods: Twenty-one patients with ALF were studied from the time they were ventilated for grade 4 encephalopathy until receiving specific treatment for increased ICP. Depending upon the ICP, the patients were divided into two groups; those that required specific treatment (ICP > 20 mmHg, group 1: n = 8, ICP: 32 (28-54) mmHg); and those that did not (ICP less than or equal to 20 mmHg, group 2: n = 13, ICP: 15 (10 - 20) mmHg). Results: Inflammatory markers, arterial ammonia and CBF were significantly higher in the group 1 patients. TNFalpha levels correlated with CBF (r = 0.80). Four patients from group 2 developed surges of increased ICP (32 (15-112) hours from enrolment). These were associated increases in markers of inflammation and TNFalpha, and an increase in CBF. There was no change in these inflammatory markers, CBF or ICP in the other 9 group 2 patients. Conclusions: The results of this study suggest that inflammation plays an important synergistic role in the pathogenesis of increased ICP possibly through its effects on CBF. (C) 2004 Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver.

There is increasing evidence that terlipressin is useful in patients with cirrhosis and hepatorenal syndrome, but there are no data of its use in patients with acute liver failure (ALF) in whom hepatorenal syndrome is common. Although terlipressin produces systemic vasoconstriction, it produces cerebral vasodilatation and may increase cerebral blood flow (CBF). Increased CBF contributes to intracranial hypertension in patients with ALF. The aim of this study was to evaluate the safety of terlipressin in patients with ALF with respect to cerebral hemodynamics. Six successive patients with ALF were ventilated electively for grade IV hepatic encephalopathy. Patients were monitored invasively and CBF was measured (Kety-Schmidt technique). Measurements were made before and at 1, 3, and 5 hours after intravenous (single bolus) administration of terlipressin (0.005 mg/kg), median, 0.25 mg (range, 0.2-0.3 mg). There was no significant change in heart rate, mean arterial pressure, or cardiac output. CBF and jugular venous oxygen saturation both increased significantly at 1 hour (P = 0.016). Intracranial pressure increased significantly at 1 hour (P = 0.031), returning back to baseline values at 2 hours. In conclusion, administration of terlipressin, at a dose that did not alter systemic hemodynamics, resulted in worsening of cerebral hyperemia and intracranial hypertension in patients with ALF and severe hepatic encephalopathy. These data suggest the need to exercise extreme caution in the use of terlipressin in these patients in view of its potentially deleterious consequences on cerebral hemodynamics.