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Anaesthesia Feb 2018Loop diuretics remain a fundamental pharmacological therapy to remove excess fluid and improve symptom control in acute decompensated heart failure. Several recent... (Comparative Study)
Comparative Study Meta-Analysis
Continuous infusion vs. intermittent bolus injection of furosemide in acute decompensated heart failure: systematic review and meta-analysis of randomised controlled trials.
Loop diuretics remain a fundamental pharmacological therapy to remove excess fluid and improve symptom control in acute decompensated heart failure. Several recent randomised controlled trials have examined the clinical benefit of continuous vs. bolus furosemide in acute decompensated heart failure, but have reported conflicting findings. The aim of this review was to compare the effects of continuous and bolus furosemide with regard to mortality, length of hospital stay and its efficacy profile in acute decompensated heart failure. All parallel-arm randomised controlled trials from MEDLINE, EMBASE, PubMed and the Cochrane Database of Systematic Reviews from inception until May 2017 were included. Cross-over randomised controlled trials, observational studies, case reports, case series and non-systematic reviews that involved children were excluded. Eight trials (n = 669) were eligible for inclusion. There was no difference between furosemide continuous infusion and bolus administration for all-cause mortality (four studies; n = 491; I = 0%; OR 1.65; 95%CI 0.93-2.91; p = 0.08) or duration of hospitalisation (six studies; n = 576; I = 71%; mean difference 0.27; 95%CI -1.35 to 1.89 days; p = 0.74). Continuous infusion of intravenous furosemide was associated with increased weight reduction (five studies; n = 516; I = 0%; mean difference 0.70; 95%CI 0.12-1.28 kg; p = 0.02); increased total urine output in 24 h (four studies; n = 390; I = 33%; mean difference 461.5; 95%CI 133.7-789.4 ml; p < 0.01); and reduced brain natriuretic peptide (two studies; n = 390; I = 0%; mean difference 399.5; 95%CI 152.7-646.3 ng.l ; p < 0.01), compared with the bolus group. There was no difference in the incidence of raised creatinine and hypokalaemia between the two groups. In summary, there was no difference between continuous infusion and bolus of furosemide for all-cause mortality, length of hospital stay and electrolyte disturbance, but continuous infusion was superior to bolus administration with regard to diuretic effect and reduction in brain natriuretic peptide.
Topics: Acute Disease; Diuretics; Furosemide; Heart Failure; Humans; Infusions, Intravenous; Injections, Intravenous; Length of Stay
PubMed: 28940440
DOI: 10.1111/anae.14038 -
JAMA Internal Medicine Nov 2014Current guidelines recommend an intravenous bolus dose of a proton pump inhibitor (PPI) followed by continuous PPI infusion after endoscopic therapy in patients with... (Comparative Study)
Comparative Study Meta-Analysis Review
IMPORTANCE
Current guidelines recommend an intravenous bolus dose of a proton pump inhibitor (PPI) followed by continuous PPI infusion after endoscopic therapy in patients with high-risk bleeding ulcers. Substitution of intermittent PPI therapy, if similarly effective as bolus plus continuous-infusion PPI therapy, would decrease the PPI dose, costs, and resource use.
OBJECTIVE
To compare intermittent PPI therapy with the currently recommended bolus plus continuous-infusion PPI regimen for reduction of ulcer rebleeding.
DATA SOURCES
Searches included MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials databases through December 2013; US and European gastroenterology meeting abstracts from 2009 to 2013; and bibliographies of systematic reviews.
STUDY SELECTION
Randomized trials of patients with endoscopically treated high-risk bleeding ulcers (active bleeding, nonbleeding visible vessels, and adherent clots) comparing intermittent doses of PPIs and the currently recommended regimen (80-mg intravenous bolus dose of a PPI followed by an infusion of 8 mg/h for 72 hours).
DATA EXTRACTION AND SYNTHESIS
Duplicate independent data extraction and risk-of-bias assessment were performed. Data were pooled using a fixed-effects model or a random effects model if statistical heterogeneity was present.
MAIN OUTCOMES AND MEASURES
The primary outcome was rebleeding within 7 days; additional predefined outcomes included rebleeding within 3 and 30 days, need for urgent intervention, mortality, red blood cell transfusion, and length of hospital stay. The primary hypothesis, defined before initiation of the literature review, was that intermittent use of PPIs was noninferior to bolus plus continuous infusion of PPIs, with the noninferiority margin predefined as an absolute risk difference of 3%.
RESULTS
The risk ratio of rebleeding within 7 days for intermittent vs bolus plus continuous infusion of PPIs was 0.72 (upper boundary of 1-sided 95% CI, 0.97) and the absolute risk difference was -2.64% (upper boundary of 1-sided 95% CI, -0.28%, which is well below the predefined noninferiority margin of 3%). Risk ratios for rebleeding within 30 days and 3 days, mortality, and urgent interventions were less than 1 and mean differences for blood transfusion and hospital length of stay were less than 0, indicating that no summary estimate showed an increased risk with intermittent therapy. The upper boundaries of 95% CIs for absolute risk differences were less than 1.50% for all predefined rebleeding outcomes.
CONCLUSIONS AND RELEVANCE
Intermittent PPI therapy is comparable to the current guideline-recommended regimen of intravenous bolus plus a continuous infusion of PPIs in patients with endoscopically treated high-risk bleeding ulcers. Guidelines should be revised to recommend intermittent PPI therapy.
Topics: Humans; Infusions, Intravenous; Peptic Ulcer; Peptic Ulcer Hemorrhage; Proton Pump Inhibitors
PubMed: 25201154
DOI: 10.1001/jamainternmed.2014.4056 -
BMC Pregnancy and Childbirth Jan 2019Oxytocin for postpartum hemorrhage (PPH) prophylaxis is commonly administered by either intramuscular (IM) injection or intravenous (IV) infusion with both routes... (Randomized Controlled Trial)
Randomized Controlled Trial
Intramuscular injection, intravenous infusion, and intravenous bolus of oxytocin in the third stage of labor for prevention of postpartum hemorrhage: a three-arm randomized control trial.
BACKGROUND
Oxytocin for postpartum hemorrhage (PPH) prophylaxis is commonly administered by either intramuscular (IM) injection or intravenous (IV) infusion with both routes recommended equally and little discussion of potential differences between the two. This trial assesses the effectiveness and safety of 10 IU oxytocin administered as IM injection versus IV infusion and IV bolus during the third stage of labor for PPH prophylaxis.
METHODS
In two tertiary level Egyptian maternity hospitals, women delivering vaginally without exposure to pre-delivery uterotonics were randomized to one of three prophylactic oxytocin administration groups after delivery of the baby. Blood loss was measured 1 h after delivery, and side effects were recorded. Primary outcomes were mean postpartum blood loss and proportion of women with postpartum blood loss ≥500 ml in this open-label, three-arm, parallel, randomized controlled trial.
RESULTS
Four thousand nine hundred thirteen eligible, consenting women were randomized. Compared to IM injection, mean blood loss was 5.9% less in the IV infusion arm (95% CI: -8.5, - 3.3) and 11.1% less in the IV bolus arm (95% CI: -14.7, - 7.8). Risk of postpartum blood loss ≥500 ml in the IV infusion arm was significantly less compared to IM injection (0.8% vs. 1.5%, RR = 0.50, 95% CI: 0.27, 0.91). No side effects were reported in any arm.
CONCLUSIONS
Intravenous oxytocin is more effective than intramuscular injection for the prevention of PPH in the third stage of labor. Oxytocin delivered by IV bolus presents no safety concerns after vaginal delivery and should be considered a safe option for PPH prophylaxis.
TRIAL REGISTRATION
clinicaltrials.gov # NCT01914419 , posted August 2, 2013.
Topics: Administration, Intravenous; Adult; Delivery, Obstetric; Egypt; Female; Humans; Infusions, Intravenous; Injections, Intramuscular; Labor Stage, Third; Oxytocics; Oxytocin; Postpartum Hemorrhage; Pregnancy; Treatment Outcome
PubMed: 30658605
DOI: 10.1186/s12884-019-2181-2 -
PloS One 2018Meropenem exhibits time-dependent antimicrobial activity and prolonged infusion (PI) (extended infusion or continuous infusion, EI or CI) of meropenem can better achieve... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Meropenem exhibits time-dependent antimicrobial activity and prolonged infusion (PI) (extended infusion or continuous infusion, EI or CI) of meropenem can better achieve pharmacodynamics target when comparing with intermittent bolus (IB). However, the clinical outcomes between two groups remain inconclusive.
OBJECTIVE
To evaluate current published literatures by meta-analysis to ascertain whether PI of meropenem can improve clinical outcomes.
METHODS
Medline, Cochrane database and EMBASE were searched. Randomized control trails (RCT) and observational studies which compared the clinical outcomes of PI and IB groups were included and evaluated for quality. The data of studies were extracted and meta-analysis was performed using Revman 5.3 software.
RESULTS
Six RCTs and 4 observation studies with relatively high quality were included in this analysis. Compared to IB group, PI group had a higher clinical success rate (odd ratio 2.10, 95% confidence interval 1.31-3.38) and a lower mortality (risk ratio 0.66, 95% confidence interval 0.50-0.88). The sensitivity analysis showed the results were stable.
CONCLUSION
PI of meropenem was associated with a higher clinical improvement rate and a lower mortality. It is recommended for patients with severe infection or infected by less sensitive microbial.
Topics: Anti-Bacterial Agents; Drug Administration Schedule; Humans; Infections; Infusions, Intravenous; Meropenem; Observational Studies as Topic; Randomized Controlled Trials as Topic; Severity of Illness Index; Time Factors; Treatment Outcome
PubMed: 30059536
DOI: 10.1371/journal.pone.0201667 -
Critical Care (London, England) Jun 2022Fluid challenges are widely adopted in critically ill patients to reverse haemodynamic instability. We reviewed the literature to appraise fluid challenge... (Review)
Review
INTRODUCTION
Fluid challenges are widely adopted in critically ill patients to reverse haemodynamic instability. We reviewed the literature to appraise fluid challenge characteristics in intensive care unit (ICU) patients receiving haemodynamic monitoring and considered two decades: 2000-2010 and 2011-2021.
METHODS
We assessed research studies and collected data regarding study setting, patient population, fluid challenge characteristics, and monitoring. MEDLINE, Embase, and Cochrane search engines were used. A fluid challenge was defined as an infusion of a definite quantity of fluid (expressed as a volume in mL or ml/kg) in a fixed time (expressed in minutes), whose outcome was defined as a change in predefined haemodynamic variables above a predetermined threshold.
RESULTS
We included 124 studies, 32 (25.8%) published in 2000-2010 and 92 (74.2%) in 2011-2021, overall enrolling 6,086 patients, who presented sepsis/septic shock in 50.6% of cases. The fluid challenge usually consisted of 500 mL (76.6%) of crystalloids (56.6%) infused with a rate of 25 mL/min. Fluid responsiveness was usually defined by a cardiac output/index (CO/CI) increase ≥ 15% (70.9%). The infusion time was quicker (15 min vs 30 min), and crystalloids were more frequent in the 2011-2021 compared to the 2000-2010 period.
CONCLUSIONS
In the literature, fluid challenges are usually performed by infusing 500 mL of crystalloids bolus in less than 20 min. A positive fluid challenge response, reported in 52% of ICU patients, is generally defined by a CO/CI increase ≥ 15%. Compared to the 2000-2010 decade, in 2011-2021 the infusion time of the fluid challenge was shorter, and crystalloids were more frequently used.
Topics: Critical Illness; Crystalloid Solutions; Fluid Therapy; Hemodynamic Monitoring; Hemodynamics; Humans; Shock, Septic
PubMed: 35729632
DOI: 10.1186/s13054-022-04056-3 -
Translational Psychiatry May 2023N,N-dimethyltryptamine (DMT) is distinct among classic serotonergic psychedelics because of its short-lasting effects when administered intravenously. Despite growing... (Randomized Controlled Trial)
Randomized Controlled Trial
N,N-dimethyltryptamine (DMT) is distinct among classic serotonergic psychedelics because of its short-lasting effects when administered intravenously. Despite growing interest in the experimental and therapeutic use of intravenous DMT, data are lacking on its clinical pharmacology. We conducted a double-blind, randomized, placebo-controlled crossover trial in 27 healthy participants to test different intravenous DMT administration regimens: placebo, low infusion (0.6 mg/min), high infusion (1 mg/min), low bolus + low infusion (15 mg + 0.6 mg/min), and high bolus + high infusion (25 mg + 1 mg/min). Study sessions lasted for 5 h and were separated by at least 1 week. Participant's lifetime use of psychedelics was ≤20 times. Outcome measures included subjective, autonomic, and adverse effects, pharmacokinetics of DMT, and plasma levels of brain-derived neurotropic factor (BDNF) and oxytocin. Low (15 mg) and high (25 mg) DMT bolus doses rapidly induced very intense psychedelic effects that peaked within 2 min. DMT infusions (0.6 or 1 mg/min) without a bolus induced slowly increasing and dose-dependent psychedelic effects that reached plateaus after 30 min. Both bolus doses produced more negative subjective effects and anxiety than infusions. After stopping the infusion, all drug effects rapidly decreased and completely subsided within 15 min, consistent with a short early plasma elimination half-life (t) of 5.0-5.8 min, followed by longer late elimination (t = 14-16 min) after 15-20 min. Subjective effects of DMT were stable from 30 to 90 min, despite further increasing plasma concentrations, thus indicating acute tolerance to continuous DMT administration. Intravenous DMT, particularly when administered as an infusion, is a promising tool for the controlled induction of a psychedelic state that can be tailored to the specific needs of patients and therapeutic sessions.Trial registration: ClinicalTrials.gov identifier: NCT04353024.
Topics: Humans; N,N-Dimethyltryptamine; Hallucinogens; Healthy Volunteers; Administration, Intravenous; Anxiety
PubMed: 37221177
DOI: 10.1038/s41398-023-02477-4 -
Frontiers in Endocrinology 2021Adrenocorticotropic hormone (ACTH) is widely used in adrenal vein sampling (AVS) and can be administered as a bolus injection or continuous infusion. The optimal... (Clinical Trial)
Clinical Trial Comparative Study
BACKGROUND
Adrenocorticotropic hormone (ACTH) is widely used in adrenal vein sampling (AVS) and can be administered as a bolus injection or continuous infusion. The optimal administration method has not been determined. We aimed to compare the effects of ACTH bolus with infusion on cannulation success, lateralization assessment and adverse events (AEs).
METHODS
Retrospectively collected data from patients with primary aldosteronism who underwent AVS with ACTH at a tertiary hospital in China. Rate of successful cannulation, lateralization index (LI), complete biochemical remission and AEs related to AVS were analyzed.
RESULTS
The study included 80 patients receiving ACTH bolus and 94 receiving infusions. The rate of successful cannulation was comparable between bolus and infusion groups (75/80, 93.4% vs 88/94, 93.6%). In those with successful cannulation, the bolus group had a higher selectivity index than the infusion group, while LI [6.4(1.8-17.5) vs. 7.6(2.0-27.8), P=0.48] and rate of complete biochemical remission (43/44, 97.7% vs 53/53, 100%, P=0.45) did not significantly differ between the two groups. One in the bolus and one patient in the infusion group had adrenal vein rupture but they recovered with conservative treatment. The bolus group reported more transient AEs such as palpitation (52.9% vs 2.2%) and abdominal discomfort (40.0% vs 2.2%) than the infusion group.
CONCLUSIONS
Due to their similar effects on cannulation success and lateralization, but a lower rate of transient AEs in the infusion group, the continuous infusion method should be recommended for ACTH stimulation in AVS.
Topics: Adrenal Glands; Adrenocorticotropic Hormone; Adult; Blood Specimen Collection; Catheterization; Female; Humans; Hyperaldosteronism; Infusions, Intravenous; Injections, Intravenous; Male; Middle Aged; Retrospective Studies
PubMed: 34899614
DOI: 10.3389/fendo.2021.784706 -
Journal of Aerosol Medicine and... Aug 2023In the critically ill, pulmonary vasodilators are often provided off label to intubated patients using continuous nebulization. If additional aerosol therapies such as...
In the critically ill, pulmonary vasodilators are often provided off label to intubated patients using continuous nebulization. If additional aerosol therapies such as bronchodilators or antibiotics are needed, vasodilator therapy may be interrupted. This study assesses aerosol systems designed for simultaneous delivery of two aerosols using continuous nebulization and bolus injection without interruption or circuit disconnection. One i dual-port breath-enhanced jet nebulizer (BEJN) or two Aerogen Solo vibrating mesh nebulizers (VMNs) were installed on the dry side of the humidifier. VMN were stacked; one for infusion and the second for bolus drug delivery. The BEJN was powered by air at 3.5 L/min, 50 psig. Radiolabeled saline was infused at 5 and 10 mL/h with radiolabeled 3 and 6 mL bolus injections at 30 and 120 minutes, respectively. Two adult breathing patterns (duty cycle 0.13 and 0.34) were tested with an infusion time of 4 hours. Inhaled mass (IM) expressed as % of initial syringe activity (IM%/min) was monitored in real time with a ratemeter. All delivered radioaerosol was collected on a filter at the airway opening. Transients in aerosol delivery were measured by calibrated ratemeter. IM%/h during continuous infusion was linear and predictable, mean ± standard deviation (SD): 2.12 ± 1.45%/h, 2.47 ± 0.863%/h for BEJN and VMN, respectively. BEJN functioned without incident. VMN continuous aerosol delivery stopped spontaneously in 3 of 8 runs (38%); bolus delivery stopped spontaneously in 3 of 16 runs (19%). Tapping restarted VMN function during continuous and bolus delivery runs. Bolus delivery IM% (mean ± SD): 20.90% ± 7.01%, 30.40% ± 11.10% for BEJN and VMN, respectively. Simultaneous continuous and bolus nebulization without circuit disconnection is possible for both jet and mesh technology. Monitoring of VMN devices may be necessary in case of spontaneous interruption of nebulization.
Topics: Adult; Humans; Respiration, Artificial; Administration, Inhalation; Albuterol; Aerosols; Nebulizers and Vaporizers; Bronchodilator Agents; Drug Delivery Systems; Equipment Design
PubMed: 37256713
DOI: 10.1089/jamp.2022.0057 -
Cancer Nov 2019In view of the recent opioid crisis, ways to promote safe and effective opioid-related practices are needed. Faster intravenous (iv) opioid infusion rates can result in...
BACKGROUND
In view of the recent opioid crisis, ways to promote safe and effective opioid-related practices are needed. Faster intravenous (iv) opioid infusion rates can result in increased adverse effects and risk for nonmedical opioid use. Data on best practices regarding safe iv opioid administration for cancer pain are limited. This study examined iv opioid bolus infusion practices and perceptions about opioids in cancer pain among 4 groups of inpatient oncology nurses.
METHODS
An anonymous cross-sectional survey was conducted among oncology nurses working in medical, surgical, intensive care unit (ICU), and emergency department (ED) settings. An iv opioid bolus infusion speed less than 120 seconds was considered too fast.
RESULTS
The participant response rate was 59% (731 of 1234). Approximately 58%, 54%, and 58% of all nurses administered morphine, hydromorphone, and fentanyl, respectively, in less than 120 seconds. The median morphine infusion speeds were 55, 60, 60, and 85 seconds for ICU, surgical, ED, and medical unit nurses, respectively (P = .0002). The odds ratios for infusing too fast were 2.04 and 2.52 for ED (P = .039) and ICU nurses (P = .003), respectively, in comparison with medical unit nurses, and they were 0.27 and 0.18 with frequent (P = .003) and very frequent use of a timing device (P = .0001), respectively, in comparison with no use.
CONCLUSIONS
More than half the nurses working in the inpatient setting reported administering iv opioids too fast. ICU nurses administered opioids the fastest. Nurses who frequently used a timing device were less likely to infuse too fast. Further research is needed to standardize and improve the safe intermittent administration of iv opioids to patients with cancer.
Topics: Adult; Analgesics, Opioid; Cancer Pain; Clinical Competence; Cross-Sectional Studies; Female; Fentanyl; Humans; Hydromorphone; Infusions, Intravenous; Male; Middle Aged; Morphine; Neoplasms; Nurses; Pain Management; Surveys and Questionnaires; Time Factors
PubMed: 31291011
DOI: 10.1002/cncr.32380 -
Experimental Physiology May 2024Endotoxin administration is commonly used to study the inflammatory response, and though traditionally given as a bolus injection, it can be administered as a continuous...
Endotoxin administration is commonly used to study the inflammatory response, and though traditionally given as a bolus injection, it can be administered as a continuous infusion over multiple hours. Several studies hypothesize that the latter better represents the prolonged and pronounced inflammation observed in conditions like sepsis. Yet very few experimental studies have administered endotoxin using both strategies, leaving significant gaps in determining the underlying mechanisms responsible for their differing immune responses. We used mathematical modelling to analyse cytokine data from two studies administering a 2 ng kg dose of endotoxin, one as a bolus and the other as a continuous infusion over 4 h. Using our model, we simulated the dynamics of mean and subject-specific cytokine responses as well as the response to long-term endotoxin administration. Cytokine measurements revealed that the bolus injection led to significantly higher peaks for interleukin (IL)-8, while IL-10 reaches higher peaks during continuous administration. Moreover, the peak timing of all measured cytokines occurred later with continuous infusion. We identified three model parameters that significantly differed between the two administration methods. Monocyte activation of IL-10 was greater during the continuous infusion, while tumour necrosis factor and IL-8 recovery rates were faster for the bolus injection. This suggests that a continuous infusion elicits a stronger, longer-lasting systemic reaction through increased stimulation of monocyte anti-inflammatory mediator production and decreased recovery of pro-inflammatory catalysts. Furthermore, the continuous infusion model exhibited prolonged inflammation with recurrent peaks resolving within 2 days during long-term (20-32 h) endotoxin administration.
Topics: Humans; Endotoxins; Cytokines; Male; Inflammation; Interleukin-10; Models, Theoretical; Infusions, Intravenous; Monocytes; Interleukin-8; Tumor Necrosis Factor-alpha; Adult; Female; Lipopolysaccharides
PubMed: 38466166
DOI: 10.1113/EP091552