METHODS: Seventy-five patients were given propofol for induction of anaesthesia. Twenty-five patients received a single bolus, 25 patients received an infusion, and 25 patients received a bolus followed by an infusion. Computer simulation was used to derive the central compartment concentration. The keo that brought about the same value for Ce at loss of the eyelash reflex using the three methods of injection was derived.
RESULTS: Keo was found to be 0.80 min(-1). Mean (SD) Ce at loss of the eyelash reflex was 2.27 (0.69) microg ml(-1).
CONCLUSIONS: The effect compartment equilibrium rate constant and concentration at loss of the eyelash reflex can be derived without the use of electronic central nervous system monitors.
DESIGN: Double-blind, placebo-controlled, multicenter randomized trial.
SETTING: Tertiary care hospitals.
INTERVENTIONS: Cardiac surgery patients (n = 1,000) with postoperative myocardial dysfunction (defined as patients with intraaortic balloon pump and/or high-dose standard inotropic support) will be randomized to receive a continuous infusion of either levosimendan (0.05-0.2 μg/[kg min]) or placebo for 24-48 hours.
MEASUREMENTS AND MAIN RESULTS: The primary end point will be 30-day mortality. Secondary end points will be mortality at 1 year, time on mechanical ventilation, acute kidney injury, decision to stop the study drug due to adverse events or to start open-label levosimendan, and length of intensive care unit and hospital stay. We will test the hypothesis that levosimendan reduces 30-day mortality in cardiac surgery patients with postoperative myocardial dysfunction.
CONCLUSIONS: This trial is planned to determine whether levosimendan could improve survival in patients with postoperative low cardiac output syndrome. The results of this double-blind, placebo-controlled randomized trial may provide important insights into the management of low cardiac output in cardiac surgery.
METHODS: This was a two-centre randomised controlled trial of CI versus IB dosing of beta-lactam antibiotics, which enrolled critically ill participants with severe sepsis who were not on renal replacement therapy (RRT). The primary outcome was clinical cure at 14 days after antibiotic cessation. Secondary outcomes were PK/PD target attainment, ICU-free days and ventilator-free days at day 28 post-randomisation, 14- and 30-day survival, and time to white cell count normalisation.
RESULTS: A total of 140 participants were enrolled with 70 participants each allocated to CI and IB dosing. CI participants had higher clinical cure rates (56 versus 34 %, p = 0.011) and higher median ventilator-free days (22 versus 14 days, p MIC than the IB arm on day 1 (97 versus 70 %, p
METHODS: : Nulliparas with uncomplicated PROM at term, a Bishop score less than or equal to 6, and who required labor induction were recruited for a double-blind randomized trial. Participants were randomly assigned to 3-mg dinoprostone pessary and oxytocin infusion or placebo and oxytocin infusion. A cardiotocogram was performed before induction and maintained to delivery. Dinoprostone pessary or placebo was placed in the posterior vaginal fornix. Oxytocin intravenous infusion was commenced at 2 milliunits/min and doubled every 30 minutes to a maximum of 32 milliunits/min. Oxytocin infusion rate was titrated to achieve four contractions every 10 minutes. Primary outcomes were vaginal delivery within 12 hours and maternal satisfaction with the birth process using a visual analog scale (VAS) from 0 to 10 (higher score, greater satisfaction).
RESULTS: : One hundred fourteen women were available for analysis. Vaginal delivery rates within 12 hours were 25 of 57 (43.9%) for concurrent treatment compared with 27/57 (47.4%) (relative risk 0.9, 95% confidence interval 0.6-1.4, P=.85) for oxytocin only; median VAS was 8 (interquartile range [IQR] 2) compared with 8 (IQR 2), P=.38. Uterine hyperstimulation was 14% compared with 5.3%, P=.20; overall vaginal delivery rates were 59.6% compared with 64.9%, P=.70; and induction to vaginal delivery interval 9.7 hours compared with 9.4 hours P=.75 for concurrent treatment compared with oxytocin, respectively. There was no significant difference for any other outcome.
CONCLUSION: : Concurrent vaginal dinoprostone and intravenous oxytocin for labor induction of term PROM did not expedite delivery or improve patient satisfaction.
CLINICAL TRIAL REGISTRATION: : Current Controlled Trials, www.controlled-trials.com, ISRCTN74376345
LEVEL OF EVIDENCE: : I.
DATA SOURCES: MEDLINE, EMBASE, PubMed, and the Cochrane Database of Systematic reviews were searched from their inception until June 2017.
REVIEW METHODS: All randomized controlled trials, observational studies, and case-control studies were included. Case reports, case series, nonsystematic reviews, and studies that involved children were excluded.
RESULTS: Nine studies (n = 464) were eligible in the data synthesis. Both continuous and bolus furosemide resulted in no difference in all-cause mortality (7 studies; n = 396; I2 = 0%; fixed-effect model [FEM]: odds ratio [OR] 1.15 [95% confidence interval (CI) 0.67-1.96]; p = 0.64). Continuous furosemide was associated with significant greater total urine output (n = 132; I2 = 70%; random-effect model: OR 811.19 [95% CI 99.84-1,522.53]; p = 0.03), but longer length of hospital stay (n = 290; I2 = 40%; FEM: OR 2.84 [95% CI 1.74-3.94]; p < 0.01) in comparison to the bolus group. No statistical significance was found in the changes of creatinine and estimated glomerular filtration rate between both groups.
CONCLUSIONS: In this meta-analysis, continuous furosemide was associated with greater diuretic effect in total urine output as compared with bolus. Neither had any differences in mortality and changes of renal function tests. However, a large adequately powered randomized clinical trial is required to fill this knowledge gap.
OBJECTIVES: In this individual patient data meta-analysis of critically ill patients with severe sepsis, we aimed to compare clinical outcomes of those treated with continuous versus intermittent infusion of β-lactam antibiotics.
METHODS: We identified relevant randomized controlled trials comparing continuous versus intermittent infusion of β-lactam antibiotics in critically ill patients with severe sepsis. We assessed the quality of the studies according to four criteria. We combined individual patient data from studies and assessed data integrity for common baseline demographics and study endpoints, including hospital mortality censored at 30 days and clinical cure. We then determined the pooled estimates of effect and investigated factors associated with hospital mortality in multivariable analysis.
MEASUREMENTS AND MAIN RESULTS: We identified three randomized controlled trials in which researchers recruited a total of 632 patients with severe sepsis. The two groups were well balanced in terms of age, sex, and illness severity. The rates of hospital mortality and clinical cure for the continuous versus intermittent infusion groups were 19.6% versus 26.3% (relative risk, 0.74; 95% confidence interval, 0.56-1.00; P = 0.045) and 55.4% versus 46.3% (relative risk, 1.20; 95% confidence interval, 1.03-1.40; P = 0.021), respectively. In a multivariable model, intermittent β-lactam administration, higher Acute Physiology and Chronic Health Evaluation II score, use of renal replacement therapy, and infection by nonfermenting gram-negative bacilli were significantly associated with hospital mortality. Continuous β-lactam administration was not independently associated with clinical cure.
CONCLUSIONS: Compared with intermittent dosing, administration of β-lactam antibiotics by continuous infusion in critically ill patients with severe sepsis is associated with decreased hospital mortality.
METHODS: Patients (n = 94) scheduled for gynaecological laparotomy received i.v. fentanyl infusion (3 μg/kg/h) after induction of general anaesthesia. Post-operative fentanyl requirements were quantified by using a patient-controlled analgesia and the number of i.v. fentanyl rescue analgesia required were recorded. Pain control was assessed using visual analogue scores (VAS) and fentanyl's adverse effects were documented. CYP3A4*4, CYP3A4*5 and CYP3A4*18 alleles of cytochrome P450 3A4 were identified by polymerase chain reaction-restriction fragment length polymorphism. Differences in fentanyl requirements, VAS scores and adverse effects among the various genotypes were compared.
RESULTS AND DISCUSSION: No CYP3A4*4 and CYP3A4*5 alleles were detected. Eighty-nine patients (94·7%) were wild-type, five (5·3%) were heterozygous and none was homozygous. No significant difference was demonstrated between the genotype groups in terms of fentanyl consumption, pain control and adverse effects.
WHAT IS NEW AND CONCLUSION: CYP3A4*4 and CYP3A4*5 are rare in the Malaysian Malay population. Genetic polymorphism of CYP3A4*18 may not play an important role in influencing postoperative fentanyl requirements.