The Effect of Dexmedetomidine as a Sedative Agent for Mechanically Ventilated Patients With Sepsis: A Systematic Review and Meta-Analysis.
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SUBMITTER: Wang C
PROVIDER: S-EPMC8711777 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundGuidelines currently recommend targeting light sedation with dexmedetomidine or propofol for adults receiving mechanical ventilation. Differences exist between these sedatives in arousability, immunity, and inflammation. Whether they affect outcomes differentially in mechanically ventilated adults with sepsis undergoing light sedation is unknown.MethodsIn a multicenter, double-blind trial, we randomly assigned mechanically ventilated adults with sepsis to receive dexmedetomidine (0.2 to 1.5 μg per kilogram of body weight per hour) or propofol (5 to 50 μg per kilogram per minute), with doses adjusted by bedside nurses to achieve target sedation goals set by clinicians according to the Richmond Agitation-Sedation Scale (RASS, on which scores range from -5 [unresponsive] to +4 [combative]). The primary end point was days alive without delirium or coma during the 14-day intervention period. Secondary end points were ventilator-free days at 28 days, death at 90 days, and age-adjusted total score on the Telephone Interview for Cognitive Status questionnaire (TICS-T; scores range from 0 to 100, with a mean of 50±10 and lower scores indicating worse cognition) at 6 months.ResultsOf 432 patients who underwent randomization, 422 were assigned to receive a trial drug and were included in the analyses - 214 patients received dexmedetomidine at a median dose of 0.27 μg per kilogram per hour, and 208 received propofol at a median dose of 10.21 μg per kilogram per minute. The median duration of receipt of the trial drugs was 3.0 days (interquartile range, 2.0 to 6.0), and the median RASS score was -2.0 (interquartile range, -3.0 to -1.0). We found no difference between dexmedetomidine and propofol in the number of days alive without delirium or coma (adjusted median, 10.7 vs. 10.8 days; odds ratio, 0.96; 95% confidence interval [CI], 0.74 to 1.26), ventilator-free days (adjusted median, 23.7 vs. 24.0 days; odds ratio, 0.98; 95% CI, 0.63 to 1.51), death at 90 days (38% vs. 39%; hazard ratio, 1.06; 95% CI, 0.74 to 1.52), or TICS-T score at 6 months (adjusted median score, 40.9 vs. 41.4; odds ratio, 0.94; 95% CI, 0.66 to 1.33). Safety end points were similar in the two groups.ConclusionsAmong mechanically ventilated adults with sepsis who were being treated with recommended light-sedation approaches, outcomes in patients who received dexmedetomidine did not differ from outcomes in those who received propofol. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01739933.).
| S-EPMC8162695 | biostudies-literature
Project description:OBJECTIVE: To evaluate the effect of oral decontamination on the incidence of ventilator associated pneumonia and mortality in mechanically ventilated adults. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline, Embase, CINAHL, the Cochrane Library, trials registers, reference lists, conference proceedings, and investigators in the specialty. REVIEW METHODS: Two independent reviewers screened studies for inclusion, assessed trial quality, and extracted data. Eligible trials were randomised controlled trials enrolling mechanically ventilated adults that compared the effects of daily oral application of antibiotics or antiseptics with no prophylaxis. RESULTS: 11 trials totalling 3242 patients met the inclusion criteria. Among four trials with 1098 patients, oral application of antibiotics did not significantly reduce the incidence of ventilator associated pneumonia (relative risk 0.69, 95% confidence interval 0.41 to 1.18). In seven trials with 2144 patients, however, oral application of antiseptics significantly reduced the incidence of ventilator associated pneumonia (0.56, 0.39 to 0.81). When the results of the 11 trials were pooled, rates of ventilator associated pneumonia were lower among patients receiving either method of oral decontamination (0.61, 0.45 to 0.82). Mortality was not influenced by prophylaxis with either antibiotics (0.94, 0.73 to 1.21) or antiseptics (0.96, 0.69 to 1.33) nor was duration of mechanical ventilation or stay in the intensive care unit. CONCLUSIONS: Oral decontamination of mechanically ventilated adults using antiseptics is associated with a lower risk of ventilator associated pneumonia. Neither antiseptic nor antibiotic oral decontamination reduced mortality or duration of mechanical ventilation or stay in the intensive care unit.
| S-EPMC1857782 | biostudies-literature
Project description:INTRODUCTION:The effect of dexmedetomidine on length of intensive care unit (ICU) stay and time to extubation is still unclear. MATERIALS AND METHODS:Pertinent studies were independently searched in BioMedCentral, PubMed, Embase, and the Cochrane Central Register of clinical trials (updated February first 2013). Randomized studies (dexmedetomidine versus any comparator) were included if including patients mechanically ventilated in an intensive care unit (ICU). Co-primary endpoints were the length of ICU stay (days) and time to extubation (hours). Secondary endpoint was mortality rate at the longest follow-up available. RESULTS:The 27 included manuscripts (28 trials) randomized 3,648 patients (1,870 to dexmedetomidine and 1,778 to control). Overall analysis showed that the use of dexmedetomidine was associated with a significant reduction in length of ICU stay (weighted mean difference (WMD)?=?-0.79 [-1.17 to -0.40] days, p for effect <0.001) and of time to extubation (WMD?=?-2.74 [-3.80 to -1.65] hours, p for effect <0.001). Mortality was not different between dexmedetomidine and controls (risk ratio?=?1.00 [0.84 to 1.21], p for effect?=?0.9). High heterogeneity between included studies was found. CONCLUSIONS:This meta-analysis of randomized controlled studies suggests that dexmedetomidine could help to reduce ICU stay and time to extubation, in critically ill patients even if high heterogeneity between studies might confound the interpretation of these results.
| S-EPMC3877008 | biostudies-literature
Project description:IntroductionThe aim of this study was to explore the use of dexmedetomidine as a safe and efficacious sedative agent in post-cardiac surgery patients.MethodsA systematic literature search of MEDLINE, EMBASE, the Cochrane Library and Science Citation Index until January 2012 and review of studies was conducted. Eligible studies were of randomized controlled trials or cohort studies, comparing dexmedetomidine with a placebo or an alternative sedative agent in elective cardiac surgery, using dexmedetomidine for postoperative sedation and available in full text. Two reviewers independently performed study selection, quality assessment, and data extraction.ResultsThe search identified 530 potentially relevant publications; 11 met selection criteria in this meta-analysis. Our results revealed that dexmedetomidine was associated with a shorter length of mechanical ventilation (mean difference -2.70 [-5.05, -0.35]), a lower risk of delirium (risk ratio 0.36 [0.21, 0.64]), ventricular tachycardia (risk ratio 0.27 [0.08, 0.97]) and hyperglycemia (risk ratio 0.78 [0.61, 0.99]), but may increase the risk of bradycardia (risk ratio 2.08 [1.16, 3.74]). But there was no significant difference in ICU stay, hospital stay, and morphine equivalents between the included studies. Dexmedetomidine may not increase the risk of hypotension, atrial fibrillation, postoperative nausea and vomiting, reintubation within 5 days, cardiovascular complications, postoperative infection or hospital mortality.ConclusionsDexmedetomidine was associated with shorter length of mechanical ventilation and lower risk of delirium following cardiac surgery. Although the risk of bradycardia was significantly higher compared with traditional sedatives, it may not increase length of hospital stay and hospital mortality. Moreover, dexmedetomidine may decrease the risk of ventricular tachycardia and hyperglycemia. Thus, dexmedetomidine could be a safe and efficacious sedative agent in cardiac surgical patients.
| S-EPMC3682268 | biostudies-literature
Project description:IntroductionNosocomial pneumonia is the most important infectious complication in patients admitted to intensive care units. Kinetic bed therapy may reduce the incidence of nosocomial pneumonia in mechanically ventilated patients. The objective of this study was to investigate whether kinetic bed therapy reduces the incidence of nosocomial pneumonia and improves outcomes in critically ill mechanically ventilated patients.MethodsWe searched Medline, EMBASE, CINAHL, CENTRAL, and AMED for studies, as well as reviewed abstracts of conference proceedings, bibliographies of included studies and review articles and contacted the manufacturers of medical beds. Studies included were randomized or pseudo-randomized clinical trials of kinetic bed therapy compared to standard manual turning in critically ill mechanically ventilated adult patients. Two reviewers independently applied the study selection criteria and extracted data regarding study validity, type of bed used, intensity of kinetic therapy, and population under investigation. Outcomes assessed included the incidence of nosocomial pneumonia, mortality, duration of ventilation, and intensive care unit and hospital length of stay.ResultsFifteen prospective clinical trials were identified, which included a total of 1,169 participants. No trial met all the validity criteria. There was a significant reduction in the incidence of nosocomial pneumonia (pooled odds ratio (OR) 0.38, 95% confidence interval (CI) 0.28 to 0.53), but no reduction in mortality (pooled OR 0.96, 95%CI 0.66 to 1.14), duration of mechanical ventilation (pooled standardized mean difference (SMD) -0.14 days, 95%CI, -0.29 to 0.02), duration of intensive care unit stay (pooled SMD -0.064 days, 95% CI, -0.21 to 0.086) or duration of hospital stay (pooled SMD 0.05 days, 95% CI -0.18 to 0.27).ConclusionWhile kinetic bed therapy has been purported to reduce the incidence of nosocomial pneumonia in mechanically ventilated patients, the overall body of evidence is insufficient to support this conclusion. There appears to be a reduction in the incidence of nosocomial pneumonia, but no effect on mortality, duration of mechanical ventilation, or intensive care or hospital length of stay. Given the lack of consistent benefit and the poor methodological quality of the trials included in this analysis, definitive recommendations regarding the use of this therapy cannot be made at this time.
| S-EPMC1550950 | biostudies-literature
Project description:IntroductionPleural effusions are frequently drained in mechanically ventilated patients but the benefits and risks of this procedure are not well established.MethodsWe performed a literature search of multiple databases (MEDLINE, EMBASE, HEALTHSTAR, CINAHL) up to April 2010 to identify studies reporting clinical or physiological outcomes of mechanically ventilated critically ill patients who underwent drainage of pleural effusions. Studies were adjudicated for inclusion independently and in duplicate. Data on duration of ventilation and other clinical outcomes, oxygenation and lung mechanics, and adverse events were abstracted in duplicate independently.ResultsNineteen observational studies (N = 1,124) met selection criteria. The mean PaO2:FiO2 ratio improved by 18% (95% confidence interval (CI) 5% to 33%, I2 = 53.7%, five studies including 118 patients) after effusion drainage. Reported complication rates were low for pneumothorax (20 events in 14 studies including 965 patients; pooled mean 3.4%, 95% CI 1.7 to 6.5%, I2 = 52.5%) and hemothorax (4 events in 10 studies including 721 patients; pooled mean 1.6%, 95% CI 0.8 to 3.3%, I2 = 0%). The use of ultrasound guidance (either real-time or for site marking) was not associated with a statistically significant reduction in the risk of pneumothorax (OR = 0.32; 95% CI 0.08 to 1.19). Studies did not report duration of ventilation, length of stay in the intensive care unit or hospital, or mortality.ConclusionsDrainage of pleural effusions in mechanically ventilated patients appears to improve oxygenation and is safe. We found no data to either support or refute claims of beneficial effects on clinically important outcomes such as duration of ventilation or length of stay.
| S-EPMC3221976 | biostudies-literature
Project description:BackgroundThis systematic review and meta-analysis aimed to determine the effectiveness of systematic early mobilization in improving muscle strength and physical function in mechanically ventilated intensive care unit (ICU) patients.MethodsWe conducted a two-stage systematic literature search in MEDLINE, EMBASE and the Cochrane Library until January 2019 for randomized controlled trials (RCTs) examining the effects of early mobilization initiated within 7 days after ICU admission compared with late mobilization, standard early mobilization or no mobilization. Priority outcomes were Medical Research Council Sum Score (MRC-SS), incidence of ICU-acquired weakness (ICUAW), 6-min walk test (6MWT), proportion of patients reaching independence, time needed until walking, SF-36 Physical Function Domain Score (PFS) and SF-36 Physical Health Component Score (PCS). Meta-analysis was conducted where sufficient comparable evidence was available. We evaluated the certainty of evidence according to the GRADE approach.ResultsWe identified 12 eligible RCTs contributing data from 1304 participants. Two RCTs were categorized as comparing systematic early with late mobilization, nine with standard early mobilization and one with no mobilization. We found evidence for a benefit of systematic early mobilization compared to late mobilization for SF-36 PFS (MD 12.3; 95% CI 3.9-20.8) and PCS (MD 3.4; 95% CI 0.01-6.8), as well as on the proportion of patients reaching independence and the time needed to walking, but not for incidence of ICUAW (RR 0.62; 95% CI 0.38-1.03) or MRC-SS. For systematic early compared to standard early mobilization, we found no statistically significant benefit on MRC-SS (MD 5.8; 95% CI - 1.4 to 13.0), incidence of ICUAW (RR 0.90; 95% CI 0.63-1.27), SF-36 PFS (MD 8.1; 95% CI - 15.3 to 31.4) or PCS (MD - 2.4; 95% CI - 6.1 to 1.3) or other priority outcomes except for change in 6MWT from baseline. Generally, effects appeared stronger for systematic early compared to late mobilization than to standard early mobilization. We judged the certainty of evidence for all outcomes as very low to low.ConclusionThe evidence regarding a benefit of systematic early mobilization remained inconclusive. However, our findings indicate that the larger the difference in the timing between the intervention and the comparator, the more likely an RCT is to find a benefit for early mobilization.Study registrationPROSPERO (CRD42019122555).
| S-EPMC7789482 | biostudies-literature
Project description:Dexmedetomidine is a selective alpha-2 adrenergic agonist with concurrent sedative and analgesic effects, and it is being increasingly used in pediatric anesthesia and intensive care. This study aimed to investigate the pharmacokinetics of intravenous dexmedetomidine in mechanically ventilated children in the intensive care unit (ICU) after neurosurgery. Pediatric patients aged 2-12 years, who were mechanically ventilated in ICU after neurosurgery, were allocated into a low-dose (n = 15) or high-dose (n = 14) group. The low-dose group received dexmedetomidine at a loading dose of 0.25 µg/kg for 10 min, followed by a maintenance dose of 0.25 µg/kg/h for 50 min, whereas the high-dose group received dexmedetomidine at a loading dose of 0.5 µg/kg for 10 min, followed by a maintenance dose of 0.5 µg/kg/h for 50 min. Serial blood samples were collected for a pharmacokinetic analysis up to 480 min after the end of the infusion. The sedative effect of dexmedetomidine was assessed using the Bispectral Index and University of Michigan Sedation Scale. Adverse reactions, electrocardiography findings, and vital signs were monitored for a safety assessment. A population pharmacokinetic analysis was performed using non-linear mixed effects modeling. Dexmedetomidine induced a moderate-to-deep degree of sedation during infusion in both groups. The pharmacokinetics of dexmedetomidine were best described by a two-compartment disposition model with first-order elimination kinetics. The parameters were standardized for a body weight of 70 kg using an allometric power model. The population estimates (95% confidence interval) per 70 kg body weight were as follows: clearance of 81.0 (72.9-90.9) L/h, central volume of distribution of 64.2 (50.6-81.0) L, intercompartment clearance of 116.4 (90.6-156.0) L/h, and peripheral volume of distribution of 167 (132-217) L. No serious adverse reactions or hemodynamic changes requiring the discontinuation of dexmedetomidine were observed. Dexmedetomidine had increased clearance and volume of distribution in mechanically ventilated children in ICU after neurosurgery, thereby indicating the need to adjust the dosage to obtain a target plasma concentration.
| S-EPMC6832515 | biostudies-literature
Project description:BACKGROUND:Daily sedative interruption and intermittent sedation are effective in abbreviating the time on mechanical ventilation. Whether one is superior to the other has not yet been determined. Our aim was to compare daily interruption and intermittent sedation during the mechanical ventilation period in a low nurse staffing ICU. METHODS:Adult patients expected to need mechanical ventilation for more than 24 hours were randomly assigned, in a single center, either to daily interruption of continuous sedative and opioid infusion or to intermittent sedation. In both cases, our goal was to maintain a Sedation Agitation Scale (SAS) level of 3 or 4; that is patients should be calm, easily arousable or awakened with verbal stimuli or gentle shaking. Primary outcome was ventilator-free days in 28 days. Secondary outcomes were ICU and hospital mortality, incidence of delirium, nurse workload, self-extubation and psychological distress six months after ICU discharge. RESULTS:A total of 60 patients were included. There were no differences in the ventilator-free days in 28 days between daily interruption and intermittent sedation (median: 24 versus 25 days, P?=?0.160). There were also no differences in ICU mortality (40 versus 23.3%, P?=?0.165), hospital mortality (43.3 versus 30%, P?=?0.284), incidence of delirium (30 versus 40%, P?=?0.472), self-extubation (3.3 versus 6.7%, P?=?0.514), and psychological stress six months after ICU discharge. Also, the nurse workload was not different between groups, but it was reduced on day 5 compared to day 1 in both groups (Nurse Activity Score (NAS) in the intermittent sedation group was 54 on day 1 versus 39 on day 5, P?<?0.001; NAS in daily interruption group was 53 on day 1 versus 38 on day 5, P?<?0.001). Fentanyl and midazolam total dosages per patient were higher in the daily interruption group. The tidal volume was higher in the intermittent sedation group during the first five days of ICU stay. CONCLUSIONS:There was no difference in the number of ventilator-free days in 28 days between both groups. Intermittent sedation was associated with lower sedative and opioid doses. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT00824239.
| S-EPMC4026117 | biostudies-literature
Project description:Purpose: This meta-analysis was performed to access the influence of dexmedetomidine versus propofol for adult patients with sepsis undergoing mechanical ventilation. Materials and Methods: NCBI PUBMED, Cochrane Library, Embase, China National Knowledge Internet (CNKI), and China Biological Medicine (CBM) were searched. Revman 5.3 and Stata software (version 12.0, Stata Corp LP, College Station, TX, United States) were used for meta-analysis. Results: Fifteen studies were included, and the data from the included studies were incorporated into the meta-analysis. Also, the result shows that compared with propofol, dexmedetomidine does not reduce 28-day mortality [risk ratios (RR) =0.97, 95% confidence interval (CI) =0.83-1.13, p = 0.70]. However, our analysis found that dexmedetomidine could reduce intensive care unit (ICU) stays {standard mean difference (SMD): -0.15; 95% CI: [-0.30-(-0.01)], p = 0.03}, duration of mechanical ventilation {SMD: -0.22; 95% CI: [-0.44-(-0.01)], p = 0.043}, sequential organ failure assessment (SOFA) {SMD: -0.41; 95% CI: [-0.73-(-0.09)], p = 0.013}, levels of interleukin-6 (IL-6) at 24 h (SMD: -2.53; 95% CI: -5.30-0.24, p = 0.074), and levels of CK-MB at 72 h {SMD: -0.45; 95% CI: [-0.83-(-0.08)], p = 0.017}. Conclusions: This meta-analysis (MA) suggests that in terms of 28-day mortality, sepsis patients with the treatment of dexmedetomidine did not differ from those who received propofol. In addition, more high-quality trials are needed to confirm these findings. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/#recordDetails, identifier CRD42021249780.
| S-EPMC8551708 | biostudies-literature