A systematic review and trial sequential analysis of intravenous vs. oral peri-operative paracetamol.

Postoperative pain might be different after intravenous vs. oral paracetamol. We systematically reviewed randomised controlled trials in patients >15 years that compared intravenous with oral paracetamol for postoperative pain. We identified 14 trials with 1695 participants. There was inconclusive evidence for an effect of route of paracetamol administration on postoperative pain at 0-2 h (734 participants), 2-6 h (766 participants), 6-24 h (1115 participants) and >24 h (248 participants), with differences in standardised mean (95%CI) pain scores for intravenous vs. oral of -0.17 (-0.45 to 0.10), -0.09 (-0.24 to 0.06), 0.06 (-0.12 to 0.23) and 0.03 (-0.22 to 0.28), respectively. Trial sequential analyses suggested that a total of 3948 participants would be needed to demonstrate a meaningful difference in pain or its absence at 0-2 h. There were no differences in secondary outcomes. Intravenous paracetamol is more expensive than oral paracetamol. Substitution of oral paracetamol in half the patients given intravenous paracetamol in our hospital would save around £ 38,711 (€ 43,960 or US$ 47,498) per annum.

The effect of therapeutic drug monitoring of beta-lactam and fluoroquinolones on clinical outcome in critically ill patients: the DOLPHIN trial protocol of a multi-centre randomised controlled trial.

BACKGROUND: Critically ill patients undergo extensive physiological alterations that will have impact on antibiotic pharmacokinetics. Up to 60% of intensive care unit (ICU) patients meet the pharmacodynamic targets of beta-lactam antibiotics, with only 30% in fluoroquinolones. Not reaching these targets might increase the chance of therapeutic failure, resulting in increased mortality and morbidity, and antibiotic resistance. The DOLPHIN trial was designed to demonstrate the added value of therapeutic drug monitoring (TDM) of beta-lactam and fluoroquinolones in critically ill patients in the ICU. METHODS: A multi-centre, randomised controlled trial (RCT) was designed to assess the efficacy and cost-effectiveness of model-based TDM of beta-lactam and fluoroquinolones. Four hundred fifty patients will be included within 24 months after start of inclusion. Eligible patients will be randomly allocated to either study group: the intervention group (active TDM) or the control group (non-TDM). In the intervention group dose adjustment of the study antibiotics (cefotaxime, ceftazidime, ceftriaxone, cefuroxime, amoxicillin, amoxicillin with clavulanic acid, flucloxacillin, piperacillin with tazobactam, meropenem, and ciprofloxacin) on day 1, 3, and 5 is performed based upon TDM with a Bayesian model. The primary outcome will be ICU length of stay. Other outcomes amongst all survival, disease severity, safety, quality of life after ICU discharge, and cost effectiveness will be included. DISCUSSION: No trial has investigated the effect of early TDM of beta-lactam and fluoroquinolones on clinical outcome in critically ill patients. The findings from the DOLPHIN trial will possibly lead to new insights in clinical management of critically ill patients receiving antibiotics. In short, to TDM or not to TDM? TRIAL REGISTRATION: EudraCT number: 2017-004677-14. Sponsor protocol name: DOLPHIN. Registered 6 March 2018 . Protocol Version 6, Protocol date: 27 November 2019.

In-hospital cardiovascular events after liver transplantation: predictors and long-term outcome.

INTRODUCTION: Liver transplantation has emerged as a successful therapy for end-stage liver disease. However, cardiovascular mortality is the leading cause of fatality in the postoperative period. The aim of this study was to reveal the prevalence and identify risk factors of early cardiovascular events (CVEs). METHODS: We performed a retrospective study of all consecutive patients who underwent a primary liver transplantation from 1986 to 2017 (n = 916). We investigated the occurrence of in-hospital CVEs, their predictors, and short- and long-term outcome. RESULTS: The prevalence of CVEs was 11%. The adjusted analysis showed that higher age (OR 1.06, 95% CI 1.03-1.09), higher MELD score (OR 1.04, 95% CI 1.01-1.07 CI) and sinus tachycardia at time of screening (OR 3.12, 95% CI 1.45-6.72) were positive predictors for a CVE. Preoperative propranolol use showed a trend towards a higher risk of CVE (OR 1.66, 95% CI 1.00-2.77, p = 0.051). In a sub-analysis of patients where echocardiography data were available (n = 597), a larger left atrial diameter and a higher E/E' ratio were related to early CVEs. Ten-year survival in 30-day survivors was favourable (68.6%; 56.0% vs. 69.8% in the CVE+ vs. the CVE-group, respectively, p = 0.056). DISCUSSION: In conclusion, besides known risk factors (age and MELD score), sinus tachycardia (related to the presence of acute liver failure and cirrhosis) was an independent predictor for CVE after liver transplantation.