Safety Of Continuous Infusion Research Articles

Extended Infusion of Beta-Lactams and Glycopeptides: A New Era in Pediatric Care? A Systematic Review and Meta-Analysis.

Optimizing antibiotic therapy is imperative with rising bacterial resistance and high infection mortality. Extended infusion defined as a continuous infusion (COI) or prolonged infusion (PI) of beta-lactams and glycopeptides might improve efficacy and safety compared to their intermittent administration (IA). This study aimed to evaluate the efficacy and safety of extended infusion in pediatric patients. Adhering to Cochrane standards, we conducted a systematic review with meta-analysis investigating the efficacy and safety of COI (24 h/d) and PI (>1 h/dose) compared to IA (≤1 h/dose) of beta-lactams and glycopeptides in pediatrics. Primary outcomes included mortality, clinical success, and microbiological eradication. Five studies could be included for the outcome mortality, investigating meropenem, piperacillin/tazobactam, cefepime, or combinations of these. The pooled relative risk estimate was 0.48 (95% CI 0.26-0.89, p = 0.02). No significant differences between the administration modes were found for the outcomes of clinical success, microbiological eradication (beta-lactams; glycopeptides), and mortality (glycopeptides). No study reported additional safety issues, e.g., adverse drug reactions when using COI/PI vs. IA. Our findings suggest that the administration of beta-lactams by extended infusion leads to a reduction in mortality for pediatric patients.

Comparative effectiveness and safety of bolus vs. continuous infusion of loop diuretics: Results from the MIMIC-III Database

BackgroundIt is unclear whether fluid management goals are best achieved by bolus injection or continuous infusion of loop diuretics. In this study, we compared the effectiveness and safety of a continuous infusion with that of a bolus injection when an increased loop diuretic dosage is required in intensive care unit (ICU) patients. MethodsWe obtained data from the MIMIC-III database for patients who were first-time ICU admissions and required an increased diuretic dosage. Patients were excluded if they had an estimated glomerular filtration rate <15 ml/min/1.73 m2, were receiving renal replacement therapy, had a baseline systolic blood pressure <80 mmHg, or required a furosemide dose <120 mg. The patients were divided into a continuous group and a bolus group. Propensity score matching was used to balance patients’ background characteristics. ResultsThe final dataset included 807 patients (continuous group, n = 409; bolus group, n = 398). After propensity score matching, there were 253 patients in the bolus group and 231 in the continuous group. The 24 h urine output per 40 mg of furosemide was significantly greater in the continuous group than in the bolus group (234.66 ml [95% confidence interval (CI) 152.13–317.18, p < 0.01]). There was no significant between-group difference in the incidence of acute kidney injury (odds ratio 0.96, 95% CI 0.66–1.41, p = 0.85). ConclusionsOur results indicate that a continuous infusion of loop diuretics may be more effective than a bolus injection and does not increase the risk of acute kidney injury in patients who need an increased diuretic dosage in the ICU.

Continuous infusion versus intermittent bolus injection of propofol during endoscopic retrograde cholangiopancreatography.

Background/AimsIt is unclear whether continuous infusion or intermittent bolus injection of propofol is better for achieving adequate sedation in endoscopic retrograde cholangiopancreatography (ERCP). We aimed to compare the efficacy and safety of continuous infusion and intermittent bolus injection of propofol during therapeutic ERCP.MethodsIn this prospective study, we randomly assigned 232 patients undergoing therapeutic ERCP to either continuous infusion (CI group, n = 113) or intermittent bolus injection (BI group, n = 119) of propofol. The primary outcome was the quality of sedation as assessed by the endoscopist. Other sedation-related parameters included sedation induction time, total dose of propofol, recovery time, involuntary patient movement, and adverse events.ResultsOverall satisfaction with sedation by the endoscopist and monitoring nurse were significantly higher in the CI group than the BI group (mean satisfaction score, 9.66 vs. 8.0 and 9.47 vs. 7.96, respectively, p < 0.01 for both). However, patients in the CI group had a significantly longer sedation induction time (5.28 minutes vs. 4.34 minutes, p < 0.01) and received a higher dose of propofol than patients in the BI group (4.22 mg/kg vs. 2.08 mg/kg, p < 0.01). There was no significant difference in adverse events between the two groups.ConclusionsContinuous infusion of propofol during therapeutic ERCP had the advantage over intermittent bolus injection of maintaining a constant level of sedation without increasing adverse events. However, it was associated with an increased total dose of propofol and prolonged sedation induction time.

Sa1489 CONTINUOUS INFUSION VERSUS INTERMITTENT BOLUS INJECTION OF PROPOFOL DURING ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY

It is unclear whether continuous infusion or intermittent bolus injection of propofol is better for achieving adequate sedation in endoscopic retrograde cholangiopancreatography (ERCP). We aimed to compare the efficacy and safety of continuous infusion and intermittent bolus injection of propofol during therapeutic ERCP.

Continuous intravenous infusion Rh-endostatin in combination with dacarbazine and cisplatin as the first-line therapy for metastatic melanoma.

e21007 Background: Immunotherapy and targeted therapy have dramatically improved the survival of advanced melanoma patients (pts), but they show relative lower efficacy in Asian pts especially in acral and mucosal subtypes. Rh-Endostatin (endostar) is a potent endogenous inhibitor of angiogenesis. Previous studies have indicated that endostar combined with dacarbazine (DTIC) was effective in the treatment of metastatic melanoma. To further improve the effectiveness, this study was designed to observe the efficacy and safety of continuous infusion (CIV) of endostar combined with DTIC and cisplatin as the first line therapy for advanced melanoma pts. Methods: Pts with treatment naive, ECOG 0/1, and unresectable stage IIIC or IV melanoma were enrolled. DTIC (250 mg/m2, intravenous infusion, day 1-5), cisplatin (75 mg/m2, intravenous infusion, separated in 3 days) and endostar (15 mg/m2, CIV, day 1-14) were administered in a 28-day cycle until disease progression or intolerable toxicity. The primary endpoint was progression free survival (PFS). Secondary endpoints included disease control rate (DCR) and safety. Results: From January 2016 to May 2018, 64 pts were enrolled and 50 pts were evaluable. 26 pts were female. The median age was 50 years (range 28-71 years) old. 10/64 (15.6%) were primary mucosal and 21/64 (32.8%) were primary acral, 40 pts were at stage IV and 32% pts got BRAF mutation. At the last follow up of Dec 2018, 5 pts achieved partial response and 27 pts got stable disease. The objective response rate was 10%. The DCR was 64%. The median PFS was 6.0 months (95% CI 1.7-10.3 months). The median overall survival was not reached. The most common adverse events were nausea (56.25%), vomiting (31.25%) and leucopenia (29.7%). Grade 3-4 toxicity was few, one got intermittent palpitation and one got atrial fibrillation, which caused drug discontinuation and recovered to normal. Conclusions: Continuous infusion of endostar plus DTIC and cisplatin improved median PFS as the first line therapy for advanced melanoma. This combination therapy was well tolerated and might be recommended as the first line therapy for advanced melanoma. Clinical trial information: NCT03095079.

Continuous infusion of recombinant factor VIII formulated with sucrose in surgery: non-interventional, observational study in patients with severe haemophilia A.

In haemophilia A, continuous infusion (CI) of FVIII perioperatively provides a more constant FVIII level than conventional bolus injections, avoiding low trough levels that could increase bleeding risk. Due to the low number of surgical cases in clinical trials, especially in haemophilia, more information on the clinical practice of CI from observational studies is helpful. We aimed to evaluate the effectiveness and safety of CI with recombinant factor VIII formulated with sucrose (rFVIII-FS) in a typical surgery practice setting. This was a non-interventional study in 12 centres. Patients with severe haemophilia A who received rFVIII-FS by CI during and after surgery were included in this study if they had more than 150 exposure days (EDs) to any FVIII product and had no history of inhibitors before CI. Patients were observed during the entire course of CI, with monitoring up to 3 months thereafter. Twenty-five patients with 28 surgeries were included in the analysis. Median age was 51.7 (range 10-75). Most (75%; 21/25) patients underwent orthopaedic surgeries. The median dose of rFVIII-FS consumed during CI was 376 IU kg(-1) (range 157.9-3605.6 IU kg(-1)) with a greater median dose for orthopaedic surgeries (424.0 IU kg(-1)) compared to non-orthopaedic surgeries (278.5 IU kg(-1)). 95% of all FVIII measurements (214/224) were on target. Efficacy and tolerability were rated as good/excellent in 89.3% (25/28) of surgeries. No inhibitors were observed during or after surgery. This study demonstrates the effectiveness of CI with rFVIII-FS during surgery in patients with severe haemophilia A in a clinical practice setting.

Stability, efficacy, and safety of continuously infused sucrose‐formulated recombinant factor VIII (rFVIII‐FS) during surgery in patients with severe haemophilia

Bolus injection (BI) of sucrose-formulated recombinant factor VIII (rFVIII-FS) is an approved treatment for haemophilia patients undergoing major surgery. Continuous infusion (CI) during surgery has potential benefits by providing steady administration of replacement factor to the patient, avoiding high peaks and low troughs. We tested the stability of rFVIII-FS under CI conditions and conducted a single-centre, open-label, phase III study to evaluate the efficacy and safety of CI using rFVIII-FS in haemophilia A patients undergoing surgery. Patients received bolus rFVIII-FS to achieve >or=80% FVIII levels 30-60 min presurgery, followed by CI of rFVIII-FS at a rate calculated to maintain haemostatic factor levels until days 8-10 post surgery. The rate of infusion was adjusted according to daily calculations derived from the actual clearance. The stability of rFVIII-FS was found to be appropriate for CI for 7 days under the same conditions as clinical settings. Fourteen patients (mean age 37.8 years) receiving on-demand FVIII treatment without a history of inhibitors underwent 15 surgical procedures including joint replacements, synovectomies, multiple tooth extractions, and cholecystectomy. Bleeding was similar to that observed in non-haemophilia patients undergoing similar operations in the same department. Haemostasis during surgery was considered by the attending surgeons as 'excellent' or 'good' in all cases; study investigators rated all 15 cases as 'excellent' overall. There were no adverse events, including inhibitor formation, related to rFVIII-FS. rFVIII-FS was found to be suitable for use in CI in haemophilia A patients undergoing major surgery.

Continuous terlipressin versus vasopressin infusion in septic shock: the TERLIVAP study

The results of the Vasopressin in Septic Shock Trial suggest that early administration of vasopressin may be superior to a last resort treatment. However, it is still unknown whether vasopressin is superior to terlipressin. We therefore performed a randomized study to compare the efficacy and safety of continuous infusions of either vasopressin or terlipressin as first-line therapy in patients with septic shock.

Administration of enoxaparin by continuous infusion in a naturalistic setting: analysis of renal function and safety1

To describe the clinical use and safety of continuous infusion (CI) enoxaparin in a naturalistic setting and to evaluate the influence of renal function on enoxaparin elimination. Retrospective medical record review. 1000-bed tertiary care teaching centre. Hospitalized patients that received enoxaparin by CI during a 2-year period. None. Specific details of dosage and monitoring were collected. Adverse drug reactions (ADR) were recorded. Creatinine clearance (CrCl) was calculated using Cockroft and Gault and Brater equations. A population pharmacokinetic analysis was performed using the non-linear mixed effect model (NONMEM). For patients located in the intensive care unit (ICU) and ward, POSTHOC pharmacokinetic parameter estimates were evaluated using the Wilcoxon rank-sum. Pearson correlation coefficient was calculated to determine the association between renal function and anti-Xa clearance. Sixty-seven patients received enoxaparin by CI of which 61.2% were in the ward and 38.8% in the ICU. The average initial rate and duration of infusion were 5.2 mg/h and 5.6 days, respectively. The number of anti-Xa concentration measurements averaged five per patient. Nine patients experienced an ADR. The most frequent ADR was gastrointestinal bleeding (n = 4). Among the 67 patients, 48 had available anti-Xa concentrations and were included in the NONMEM model. The anti-Xa CL and volume of distribution for ICU and ward patients averaged 0.64 +/- 0.34 L/h, 10.6 +/- 1.55 L and 1.01 +/- 0.39 L/h, 9.08 +/- 1.17 L, respectively. CrCl was not a significant covariate when included in the NONMEM model, and the association between CrCl and anti-Xa clearance was not significant (R2 = 0.0005; P = 0.8916). This study is the first to report the use and safety of prolonged CI enoxaparin. Pharmacokinetic parameters of enoxaparin differ in ICU vs. ward patients. Overall, we found the safety of CI to be comparable to subcutaneous administration. Also, we found no effect of renal function on enoxaparin elimination.

Efficacy and safety of continuous infusion of Mononine® during five surgical procedures in three hemophilic patients

We report here five surgeries successfully performed with a continuous infusion of Mononine (Armour Pharmaceutical Company, Kankakee, IL) in three hemophilic B patients. Before surgery the patients received a bolus dose of 40 to 100 U/kg according to the type of surgery. This injection was followed by a continuous infusion of Mononine, with an infusion rate of 3.5-7 U/kg/hr in order to maintain a factor IX level between 50 and 100% during the whole surgery and the following 6 days. The infusion rate was further adjusted according to the type of surgery until hospital discharge. This method appears to be safe and efficient, since no abnormal bleeding occurred during surgery and none of the patients presented any thrombotic complication. However, this alternative to intermittent administration of factor IX should be standardized and precisely evaluated, regarding the level and the amount of factor IX required, and the cost of the infused material. In our hands, this cost was decreased by 30-40% compared to previous therapeutic schedules at our institution.