Systematic review and meta-analysis of surgical outcomes comparing mechanical valve replacement and bioprosthetic valve replacement in infective endocarditis.

BACKGROUND: Infective endocarditis (IE) is an infection involving either native or prosthetic heart valves, the endocardial surface of the heart or any implanted intracardiac devices. IE is a rare condition affecting 3-15 patients per 100,000 population. In-hospital mortality rates in patients with IE remain high at around 20% despite treatment advances. There is no consensus recommendation favoring either bioprosthetic valve or mechanical valve implantation in the setting of IE; patient age, co-morbidities and preferences should be considered selecting the replacement prosthesis. METHODS: A systematic review and meta-analysis of studies reporting the outcomes of patients undergoing bioprosthetic or mechanical valve replacement for infective endocarditis with data extracted for overall survival, valve reinfection rates and valve reoperation. RESULTS: Eleven relevant studies were identified, with 2,336 patients receiving a mechanical valve replacement and 2,057 patients receiving a bioprosthetic valve replacement. There was no significant difference for overall survival between patients treated with mechanical valves and those treated with bioprosthetic valves [hazard ratio (HR) 0.94, 95% confidence interval (CI): 0.73-1.21, P=0.62]. There was no significant difference in reoperation rates between patients treated with a bioprosthetic valve and those treated with a mechanical valve (HR 0.82, 95% CI: 0.34-1.98, P=0.66) and there was no significant difference in the rate of valve reinfection rates (HR 0.95, 95% CI: 0.48-1.89, P=0.89). CONCLUSIONS: The presence of infective endocarditis alone should not influence the decision of which type of valve prosthesis that should be implanted. This decision should be based on patient age, co-morbidities and preferences.

Population pharmacokinetics of intravenous acetaminophen and its metabolites in major surgical patients.

Intravenous acetaminophen is a commonly used analgesic following surgery. The aims of this study were to determine the population pharmacokinetic profile of intravenous acetaminophen and its metabolites in adult surgical patients and to identify patient characteristics associated with acetaminophen metabolism in the postoperative period. 53 patients were included in the dataset; 28 were men, median age (range) 60 years (33-87), median weight (range) 74 kg (54-129). Patients received 1, 1.5 or 2 g of intravenous acetaminophen every 4-6 h. Plasma and urine samples were collected at various intervals for up to 6 days after surgery. Simultaneous modelling of parent acetaminophen and its metabolites was conducted in Phoenix(®) NLME™ to estimate pharmacokinetic parameters. The population mean estimate (CV%) for central (plasma) volume of distribution of parent acetaminophen (VC) was 13.9 (4.41) L, peripheral (tissue) volume of distribution (VT) was 50.9 (2.96) L, and intercompartmental clearance (Q) was 77.5 (9.29) L/h. The population mean (CV%) metabolic clearances for glucuronidation (CLPG) was 8.92 (3.25) L/h, sulfation (CLPS) was 0.903 (3.47) L/h, and oxidation (CLPO) was 0.533 (7.90) L/h. The population mean (CV%) urinary clearances of parent acetaminophen (CLRP) was 0.137 (5.46) L/h, acetaminophen glucuronide (CLRG) was 3.81 (6.71) L/h, acetaminophen sulfate (CLRS) was 3.13 (4.32) L/h, and acetaminophen cysteine + mercapturate (CLRO) was 3.51 (9.98) L/h. Age was found to be a significant covariate on the formation of acetaminophen glucuronide, and renal function (estimated as creatinine clearance) on the urinary excretion of acetaminophen glucuronide.

The pharmacokinetic profile of intravenous paracetamol in adult patients undergoing major abdominal surgery.

BACKGROUND: Intravenous (IV) paracetamol is commonly used in the postoperative period for the treatment of mild to moderate pain. The main pathways for paracetamol metabolism are glucuronidation, sulfation, and oxidation, accounting for approximately 55%, 30%, and 10% of urinary metabolites, respectively. The aim of this study was to describe the pharmacokinetics of IV paracetamol and its metabolites in adult patients after major abdominal surgery. METHODS: Twenty patients were given 1 g of paracetamol by IV infusion at induction of anesthesia (Interval 1) and every 6 hours thereafter, with the final dose given at 48-72 hours (Interval 2). Plasma and urine samples were collected for up to 8 hours after infusion for both intervals. The samples were analyzed by high-performance liquid chromatography to determine the amount of paracetamol and its metabolites. The data were modeled in Phoenix WinNonlin using a user-defined ASCII parent-metabolite model with linear disposition, to obtain the estimates for volume of distribution, metabolic and urinary clearance. RESULTS: Mean (95% confidence interval) metabolic clearance to paracetamol glucuronide increased from 0.06 (0.05-0.08) to 0.14 (0.11-0.18) L · h⁻¹ · kg⁻¹, P value <0.001 and urinary clearance increased from 0.08 (0.07-0.09) to 0.14 (0.10-0.17) L · h⁻¹ · kg⁻¹, P value 0.002. The mean (95% confidence interval) volume of distribution of paracetamol increased from 0.17 (0.12-0.21) to 0.43 (0.27-0.59) L · kg⁻¹, P value 0.032. CONCLUSIONS: After major abdominal surgery, there were apparent increases in the metabolic conversion to paracetamol glucuronide and its urinary clearance suggesting potential induction of paracetamol glucuronidation.