Methods: Four ampoules of intravenous co-trimoxazole were injected into an infusion bag containing either 480 (1:25 v/v), 380 (1:20 v/v), 280 (1:15 v/v) or 180 (1:10 v/v) mL of glucose 5% solution. Three bags for each dilution (total 12 bags) were prepared and stored at room temperature. An aliquot was withdrawn immediately (at 0 hour) and after 0.5, 1, 2 and 4 hours of storage for high-performance liquid-chromatography (HPLC) analysis, and additional samples were withdrawn every half an hour for microscopic examination. Each sample was analysed for the concentration of trimethoprim and sulfamethoxazole using a stability indicating HPLC method. Samples were assessed for pH, change in colour (visually) and for particle content (microscopically) immediately after preparation and on each time of analysis.
Results: Intravenous co-trimoxazole at 1:25, 1:20, 1:15 and 1:10 v/v retained more than 98% of the initial concentration of trimethoprim and sulfamethoxazole for 4 hours. There was no major change in pH at time zero and at various time points. Microscopically, no particles were detected for at least 4 hours and 2 hours when intravenous co-trimoxazole was diluted at 1:25 or 1:20 and 1:15 v/v, respectively. More than 1200 particles/mL were detected after 2.5 hours of storage when intravenous co-trimoxazole was diluted at 1:15 v/v.
Conclusions: Intravenous co-trimoxazole is stable over a period of 4 hours when diluted with 380 mL of glucose 5% solution (1:20 v/v) and for 2 hours when diluted with 280 mL glucose 5% solution (1:15 v/v).
METHODS: Subjects were 200 consecutive patients admitted to Kuala Tereng-ganu General Hospital, Malaysia with severe hypertension in pregnancy between August 1989 and June 1990. Admission criteria were an ongoing viable pregnancy more than 28 weeks and diastolic blood pressure (DBP) more than 120 mmHg. The patients were randomly divided into 2 groups. In group I, sublingual nifedipine 5 mg was administered and repeated after 15 minutes if DBP > 120 mmHg; and in group II hydrallazine 5 mg was intravenously injected and repeated after 15 minutes if DBP > 120 mmHg. Both groups were put on hydrallazine infusion if DBP > 120 mmHg after 30 minutes. The Chi-square test was used for analysis with significance at p < 0.05.
RESULTS: There was no statistical difference in the efficacy of therapy for decreasing blood pressure between the 2 groups. The groups were comparable by age, parity, gestational age at presentation, birth weight of infants, incidence of postpartum haemorrhage and fetal distress. Caesarian section rates were similar. In the observational studies on nurses administering the drugs, no significant difficulties were observed.
CONCLUSION: Sublingual nifedipine was comparable to IV hydrallazine in the treatment of acute hypertension of pregnancy. Nurses were able to administer lingual nifedipine without difficulty.
METHODS: Parous women with favorable cervixes after amniotomy for labor induction were randomized to immediate titrated oxytocin or placebo intravenous infusion in a double-blind noninferiority trial. After 4 hours, study infusions were stopped, the women were assessed, and open-label oxytocin was started if required. Maternal satisfaction with the birth process was assessed with a 10-point visual numerical rating scale (lower score, greater satisfaction).
RESULTS: Vaginal delivery rates at 12 hours were 91 of 96 (94.8%) compared with 91 of 94 (96.8%) (relative risk 0.98, 95% confidence interval [CI] 0.92-1.04, P=.72), and maternal satisfaction on a visual numerical rating scale (median [interquartile range]) was 3 [3-4] compared with 3 [3-5], P=.36 for immediate compared with delayed arm, respectively). Cesarean delivery, maternal fever, postpartum hemorrhage, uterine hyperactivity, and adverse neonatal outcome rates were similar between arms. The immediate oxytocin arm had a shorter amniotomy-to-delivery interval of 5.3±3.1 compared with 6.9±2.9 hours (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.
METHODS: This single-blinded, randomized controlled trial was conducted in a single emergency department. Patients with acute long bone fractures and numerical rating scale (NRS) pain scores ≥ 6 following an initial dose of intravenous morphine were assigned to receive either a LDK (0.3 mg/kg) over 15 min or intravenous MOR at a dose of 0.1 mg/kg administered over 5 min. Throughout a 120-min observation period, patients were regularly evaluated for pain level (0-10), side effects, and the need for additional rescue analgesia.
RESULTS: A total of 58 subjects participated, with 27 in the MOR group and 31 in the LDK group. Demographic variables and baseline NRS scores were comparable between the MOR (8.3 ± 1.3) and LDK (8.9 ± 1.2) groups. At 30 min, the LDK group showed a significantly greater mean reduction in NRS scores (3.1 ± 2.03) compared to the MOR group (1.8 ± 1.59) (p = 0.009). Similarly, at 60 min, there were significant differences in mean NRS score reductions (LDK 3.5 ± 2.17; MOR mean reduction = 2.4, ± 1.84) with a p-value of 0.04. No significant differences were observed at other time intervals. The incidence of dizziness was higher in the LDK group at 19.4% (p = 0.026).
CONCLUSION: Short infusion low-dose ketamine, as an adjunct to morphine, is effective in reducing pain during the initial 30 to 60 min and demonstrated comparability to intravenous morphine alone in reducing pain over the subsequent 60 min for acute long bone fractures. However, it was associated with a higher incidence of dizziness.
TRIAL REGISTRATION: NMRR17318438970 (2 May 2018; www.nmrr.gov.my ).
AIMS: To investigate the effect of intraperitoneal administration of ondansetron for postoperative pain management as an adjuvant to intravenous acetaminophen in patients undergoing laparoscopic cholecystectomy.
METHODS: Patients scheduled for elective laparoscopic cholecystectomy were randomized into two groups (n = 25 each) to receive either intraperitoneal ondansetron or saline injected in the gall bladder bed at the end of the procedure. The primary outcome was the difference in pain from baseline to 24-h post-operative assessed by comparing the area under the curve of visual analog score between the two groups.
RESULTS: The derived area under response curve of visual analog scores in the ondansetron group (735.8 ± 418.3) was 33.97% lower than (p = 0.005) that calculated for the control group (1114.4 ± 423.9). The need for rescue analgesia was significantly lower in the ondansetron (16%) versus in the control group (54.17%) (p = 0.005), indicating better pain control. The correlation between the time for unassisted mobilization and the area under response curve of visual analog scores signified the positive analgesic influence of ondansetron (rs =0.315, p = 0.028). The frequency of nausea and vomiting was significantly lower in patients who received ondansetron than that reported in the control group (p = 0.023 (8 h), and 0.016 (24 h) respectively).
CONCLUSIONS: The added positive impact of ondansetron on postoperative pain control alongside its anti-emetic effect made it a unique novel option for patients undergoing laparoscopic cholecystectomy.
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.
MATERIALS AND METHODS: Retrospective data were obtained for 36 patients with CKD stage 4 and 5 after parathyroid surgery, correlating albumin-corrected serum calcium with the infusion rate of calcium gluconate. Calcium flux was characterised along with excursions out of the target calcium range of 2 to 3 mmol/L. With this data, an improved titration regimen was constructed.
RESULTS: Mean peak efflux rate (PER) from the extracellular calcium pool was 2.97 mmol/h occurring 26.6 hours postoperatively. Peak calcium efflux tended to occur later in cases of severe POH. Eighty-one per cent of patients had excursions outside of the target calcium range of 2 to 3 mmol/L. Mean time of onset for hypocalcaemia was 2 days postoperatively. Hypocalcaemia was transient in 25% and persistent in 11% of patients.
CONCLUSION: A simple titration regimen was constructed in which a 10% calcium gluconate infusion was started at 4.5 mL/h when serum calcium was <2 mmol/L, then increased to 6.5 mL/h and finally to 9.0 mL/h if calcium continued falling. Preoperative oral calcium and calcitriol doses were maintained. Blood testing was done 6-hourly, but when a higher infusion rate was needed, 4-hourly blood testing was preferred. Monitoring was discontinued if no hypocalcaemia developed in the fi rst 4 days after surgery. If hypocalcaemia persisted 6 days after surgery, then the infusion was stopped with further monitoring for 24 hours.
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: 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.