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Biomedical subjects

Julia Wendon

Publications and source records attributed to Julia Wendon.

9 recordsLinked to original sources

The effects of supraphysiological doses of corticosteroids in hypotensive liver failure.

BACKGROUND: In septic shock, supraphysiological doses of corticosteroids reduce norepinephrine requirements. We reviewed our experience of this treatment in hypotensive liver failure. METHODS: We retrospectively analysed 20 patients with liver failure who were treated with supraphysiological doses of hydrocortisone because of norepinephrine dependence. We compared their norepinephrine requirements, outcome, microbiology and incidence of gastrointestinal bleeding to an historical control group treated with norepinephrine but not corticosteroids. RESULTS: After 48 h of steroid treatment, the median norepinephrine dose was reduced (0.14 microg/kg/min to 0.08 microg/kg/min; P < 0.05) while the blood pressure over the same period of time did not change significantly (67.3 mm Hg to 70 mm Hg). Duration of ITU stay was longer in the steroid treated group (13.5 days vs 3 days; P < 0.05) but survival was similar in both groups. There were 23 episodes of positive bacterial cultures after norepinephrine was started in the steroid treated group, compared with 18 episodes in the control group. More of the positive cultures were due to resistant organisms in the steroid treated group (65% vs 17% in the control group; P < 0.002). There was no significant bleeding due to gastrointestinal inflammation in either group. CONCLUSIONS: Supraphysiological doses of corticosteroids reduce norepinephrine requirements in hypotensive liver failure. They do not improve survival but may extend time to find a suitable donor in those awaiting urgent liver transplantation.

Adrenal Cortex Hormones↗

Acute sickle cell hepatopathy represents a potential contraindication for percutaneous liver biopsy.

After several complications following percutaneous liver biopsy in patients with sickle cell disease, we reviewed our experience. We examined 14 patients with sickle cell disease who underwent a percutaneous liver biopsy. Clinicopathologic findings were correlated with outcome. Of 14 patients, 5 (36%) suffered serious hemorrhage; 4 died (80%; 28% of all patients). None of the 9 patients without biopsy complications was in an acute sickling crisis at the time of biopsy; 4 of 5 patients with complications were in acute sickling crisis. Of the 5 patients with complications, 4 underwent biopsy for an emergency indication. Chronic venous outflow obstruction, marked hepatic sequestration of erythrocytes, and sinusoidal dilatation were strongly associated with complications. Data obtained by biopsy in group 1 were not of substantial value in clinical management, in contrast to group 2 (8/9; 89%). Acute hepatic disease complicating sickle cell anemia represents a newly identified contraindication to percutaneous liver biopsy.

Acute Disease↗

Blood lactate as an early predictor of outcome in paracetamol-induced acute liver failure: a cohort study.

BACKGROUND: Although the King's College Hospital (KCH) selection criteria for emergency liver transplantation in paracetamol-induced acute liver failure are widely used, strategies to improve sensitivity and facilitate earlier transplantation are required. We investigated the use of arterial blood lactate measurement for the identification of transplantation candidates. METHODS: In a single-centre study, we measured arterial blood lactate early (median 4 h) and after fluid resuscitation (median 12 h) in patients admitted to a tertiary-referral intensive-care unit. Threshold values that best identified individuals likely to die without transplantation were derived in a retrospective initial sample of 103 patients with paracetamol-induced acute liver failure and applied to a prospective validation sample of 107 patients. Predictive value and speed of identification were compared with those of KCH criteria. FINDINGS: In the initial sample, median lactate was significantly higher in non-surviving patients than in survivors both in the early samples (8.5 [range 1.7--21.0] vs 1.4 [0.53--7.9] mmol/L, p<0.0001) and after fluid resuscitation (5.5 [1.3--18.6] vs 1.3 [0.26--3.2], p<0.0001). Applied to the validation sample, a threshold value of 3.5 mmol/L early after admission had sensitivity 67%, specificity 95%, positive likelihood ratio 13, and negative likelihood ratio 0.35; the corresponding values for a threshold of 3.0 mmol/L after fluid resuscitation were 76%, 97%, 30, and 0.24. Combined early and postresuscitation lactate concentrations had similar predictive ability to KCH criteria but identified non-surviving patients earlier (4 [3--13] vs 10 [3.5--19.5] h, p=0.01). Addition of postresuscitation lactate concentration to KCH criteria increased sensitivity from 76% to 91% and lowered negative likelihood ratio from 0.25 to 0.10. INTERPRETATION: Arterial blood lactate measurement rapidly and accurately identifies patients who will die from paracetamol-induced acute liver failure. Its use could improve the speed and accuracy of selection of appropriate candidates for transplantation.

Acetaminophen↗

The clinical importance of adrenal insufficiency in acute hepatic dysfunction.

Acute liver failure and septic shock share many clinical features, including hyperdynamic cardiovascular collapse. Adrenal insufficiency may result in a similar cardiovascular syndrome. In septic shock, adrenal insufficiency, defined using the short synacthen test (SST), is associated with hemodynamic instability and poor outcome. We examined the SST, a dynamic test of adrenal function, in 45 patients with acute hepatic dysfunction (AHD) and determined the association of these results with hemodynamic profile, severity of illness, and outcomes. Abnormal SSTs were common, occurring in 62% of patients. Those who required noradrenaline (NA) for blood pressure support had a significantly lower increment (median, 161 vs. 540 nmol/L; P <.001) following synacthen compared with patients who did not. Increment and peak were lower in patients who required ventilation for the management of encephalopathy (increment, 254 vs. 616 nmol/L, P <.01; peak, 533 vs. 1,002 nmol/L, P <.01). Increment was significantly lower in those who fulfilled liver transplant criteria compared with those who did not (121 vs. 356 nmol/L; P <.01). Patients who died or underwent liver transplantation had a lower increment (148 vs. 419 nmol/L) and peak (438 vs. 764 nmol/L) than those who survived (P <.01). There was an inverse correlation between increment and severity of illness (Sequential Organ Failure Assessment, r = -0.63; P <.01). In conclusion, adrenal dysfunction assessed by the SST is common in AHD and may contribute to hemodynamic instability and mortality. It is more frequent in those with severe liver disease and correlates with severity of illness.

Adolescent↗

Predicting the decrease of conjugated bilirubin with extracorporeal albumin dialysis MARS using the predialysis molar ratio of conjugated bilirubin to albumin.

Extracorporeal albumin dialysis with the molecular adsorbent recirculating system (MARS) machine is a new supportive intervention for patients with liver failure. It removes bilirubin and other albumin-bound toxins from the patient and has been shown by preliminary studies of liver failure patients to be beneficial. Our study examines the ability of predialysis molar ratio of bilirubin to albumin to predict the decrease of bilirubin by MARS. We had 5 patients and results from 29 treatments. The results showed a significant correlation between the predialysis molar ratio of bilirubin (total and conjugated) to albumin to the reduction in bilirubin (total and conjugated): R(2) = 0.27 and 0.62 respectively, P <.005 for both. There was no significant correlation with the predialysis molar ratio of unconjugated bilirubin to albumin to the reduction in unconjugated bilirubin. The ratio of change in total bilirubin (micromol/L) to the predialysis molar ratio of total bilirubin to albumin and the ratio of change in conjugated bilirubin (micromol/L) to the predialysis molar ratio of conjugated bilirubin to albumin were 6.2 (+/- 4.2) and 10.8 (+/- 4.3), respectively (mean (+/- SD)). The results enable us to predict the likely reduction in bilirubin (especially conjugated) after each MARS treatment and also suggest to us that albumin infusion before MARS treatment may reduce the efficacy of bilirubin removal. Whether this ratio applies to other albumin-bound toxins remains open for investigation.

Bilirubin↗

Brain edema in liver failure: basic physiologic principles and management.

In patients with severe liver failure, brain edema is a frequent and serious complication that may result in high intracranial pressure and brain damage. This short article focuses on basic physiologic principles that determine water flux across the blood-brain barrier. Using the Starling equation, it is evident that both the osmotic and hydrostatic pressure gradients are imbalanced across the blood-brain barrier in patients with acute liver failure. This combination will tend to favor cerebral capillary water influx to the brain. In contrast, the disequilibration of the Starling forces seems to be less pronounced in patients with cirrhosis because the regulation of cerebral blood flow is preserved and the arterial ammonia concentration is lower compared with that of patients with acute liver failure. Treatments that are known to reverse high intracranial pressure tend to decrease the osmotic pressure gradients across the blood-brain barrier. Recent studies indicate that interventions that restrict cerebral blood flow, such as hyperventilation, hypothermia, and indomethacin, are also efficient in preventing edema and high intracranial pressure, probably by decreasing the transcapillary hydrostatic pressure gradient. In our opinion, it is important to recall that rational fluid therapy, adequate ventilation, and temperature control are of direct importance to controlling cerebral capillary water flux in patients with acute liver failure. These simple interventions should be secured before more advanced experimental technologies are instituted to treat these patients.

Acute Disease↗

Management of variceal bleeding.

Variceal hemorrhage complicates cirrhosis in as many as 50% of patients and results in considerable morbidity and mortality. This review covers all areas of importance in the prevention and treatment of this area, highlighting recent developments. Primary prophylaxis prevents first bleed, and pharmacotherapy with beta-blockade is the most widely accepted option. In an acute variceal hemorrhage, initial resuscitation and multiple organ support are paramount and are recommended along with antibiotic prophylaxis and specific medical therapies that may be given empirically before emergency endoscopy to reduce bleeding. Endoscopic techniques usually arrest bleeding, but when they fail, salvage therapy in the form of balloon tamponade, then transjugular intrahepatic portosystemic shunts or surgery, may be appropriate. Secondary prophylaxis to prevent rebleeding is often instituted in the ICU and is vital to prevent recurrence of this life-threatening complication.

Endoscopy, Gastrointestinal↗