Dataset Information

Remi-fent 1-A pragmatic randomised controlled study to evaluate the feasibility of using remifentanil or fentanyl as sedation adjuncts in mechanically ventilated patients.

ABSTRACT:

Objective

To evaluate the feasibility of conducting a prospective randomised controlled trial (pRCT) comparing remifentanil and fentanyl as adjuncts to sedate mechanically ventilated patients.

Design

Single-center, open-labelled, pRCT with blinded analysis.

Setting

Australian tertiary intensive care unit (ICU).

Participants

Consecutive adults between June 2020 and August 2021 expected to receive invasive ventilation beyond the next day and requiring opioid infusion were included. Exclusion criteria were pregnant/lactating women, intubation >12 h, or study-drug hypersensitivity.

Interventions

Open-label fentanyl and remifentanil infusions per existing ICU protocols.

Outcomes

Primary outcomes were feasibility of recruiting ≥1 patient/week and >90 % compliance, namely no other opioid infusion used during the study period. Secondary outcomes included complications, ICU-, ventilator- and hospital-free days, and mortality (ICU, hospital). Blinded intention-to-treat analysis was performed concealing the allocation group.

Results

208 patients were enrolled (mean 3.7 patients/week). Compliance was 80.6 %. More patients developed complications with fentanyl than remifentanil: bradycardia (n = 44 versus n = 21; p < 0.001); hypotension (n = 78 versus n = 53; p < 0.01); delirium (n = 28 versus n = 15; p = 0.001). No differences were seen in ICU (24.3 % versus 27.6 %,p = 0.60) and hospital mortalities (26.2 % versus 30.5 %; p = 0.50). Ventilator-free days were higher with remifentanil (p = 0.01).

Conclusions

We demonstrated the feasibility of enrolling patients for a pRCT comparing remifentanil and fentanyl as sedation adjuncts in mechanically ventilated patients. We failed to attain the study-opioid compliance target, likely because of patients with complex sedative/analgesic requirements. Secondary outcomes suggest that remifentanil may reduce mechanical ventilation duration and decrease the incidence of complications. An adequately powered multicentric phase 2 study is required to evaluate these results.

SUBMITTER: Rajamani A

PROVIDER: S-EPMC10790007 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Publications

Remi-fent 1-A pragmatic randomised controlled study to evaluate the feasibility of using remifentanil or fentanyl as sedation adjuncts in mechanically ventilated patients.

Rajamani Arvind A Subramaniam Ashwin A Lung Brian B Masters Kristy K Gresham Rebecca R Whitehead Christina C Lowrey Julie J Seppelt Ian I Kumar Hemant H Kumar Jayashree J Hassan Anwar A Orde Sam S Bharadwaj Pranav Arun PA Arvind Hemamalini H Huang Stephen S

Critical care and resuscitation : journal of the Australasian Academy of Critical Care Medicine 20231213 4

<h4>Objective</h4>To evaluate the feasibility of conducting a prospective randomised controlled trial (pRCT) comparing remifentanil and fentanyl as adjuncts to sedate mechanically ventilated patients.<h4>Design</h4>Single-center, open-labelled, pRCT with blinded analysis.<h4>Setting</h4>Australian tertiary intensive care unit (ICU).<h4>Participants</h4>Consecutive adults between June 2020 and August 2021 expected to receive invasive ventilation beyond the next day and requiring opioid infusion w ...[more]

PMID: 38234321

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Project description:Background: As the first-line treatment for mechanically ventilated patients with critical illness, fentanyl and its analogs (e.g., sufentanil and remifentanil) are commonly used in the intensive care unit (ICU). However, the pharmacokinetics, metabolism, and potency of these agents differed. Their effects on clinical outcomes have not been well-understood. Materials and Methods: Using a well-established registry, we conducted a cohort study. Patients who consistently underwent mechanical ventilation (MV) for more than 24 h were identified. We used a time-varying exposure definition, in which we coded each type of opioids as prescribed or not prescribed on each day from initiation of MV to extubation and ICU discharge. We used Fine-Gray competing risk models to compare the effects of fentanyl, sufentanil, and remifentanil on hazards for extubation, ventilator mortality, ICU discharge, and ICU mortality. All models were adjusted using a combination of fixed-time and time-varying covariates. Missing data were imputed using multiple imputation by chained equations. Results: A total of 8,165 patients were included. There were, respectively, 4,778, 4,008, and 2,233 patients receiving at least 1 day of fentanyl, sufentanil, and remifentanil dose. Compared to fentanyl, sufentanil was associated with shorter duration to extubation (hazard ratio 1.31, 95% CI, 1.20-1.41) and ICU discharge (hazard ratio 1.63, 95% CI, 1.38-1.92), and remifentanil was associated with shorter duration to extubation (hazard ratio 1.60, 95% CI, 1.40-1.84) and ICU discharge (hazard ratio 2.02, 95% CI, 1.43-2.84). No significant differences in time to extubation (Hazard ratio 1.14, 95% CI, 0.92-1.41) and ICU discharge (Hazard ratio 1.31, 95% CI, 0.81-2.14) were found between sufentanil and remifentanil. No differences were observed between any two of the agents regarding ventilator mortality or ICU mortality. The effects were similar in patients with versus without surgery. Conclusion: Sufentanil and remifentanil may be superior to fentanyl in shortening the time to extubation and ICU discharge. The effects on ventilator mortality and ICU mortality appeared similar across these agents, while further research is warranted.

Project description:ObjectivesDeep sedation in the emergency department (ED) is common, increases deep sedation in the ICU, and is negatively associated with outcome. Limiting ED deep sedation may, therefore, be a high-yield intervention to improve outcome. However, the feasibility of conducting an adequately powered ED-based clinical sedation trial is unknown. Our objectives were to assess trial feasibility in terms of: 1) recruitment, 2) protocol implementation and practice change, and 3) safety. Patient-centered clinical outcomes were assessed to better plan for a future large-scale clinical trial.DesignPragmatic, multicenter ( n = 3), prospective before-after pilot and feasibility trial.SettingThe ED and ICUs at three medical centers.PatientsConsecutive, adult mechanically ventilation ED patients.InterventionsAn educational initiative aimed at reliable ED sedation depth documentation and reducing the proportion of deeply sedated patients (primary outcome).Measurements and main resultsSedation-related data in the ED and the first 48 ICU hours were recorded. Deep sedation was defined as a Richmond Agitation-Sedation Scale of -3 to -5 or a Sedation-Agitation Scale of 1-3. One thousand three hundred fifty-six patients were screened; 415 comprised the final population. Lighter ED sedation was achieved in the intervention group, and the proportion of deeply sedated patients was reduced from 60.2% to 38.8% ( p < 0.01). There were no concerning trends in adverse events (i.e., inadvertent extubation, device removal, and awareness with paralysis). Mortality was 10.0% in the intervention group and 20.4% in the preintervention group ( p < 0.01). Compared with preintervention, the intervention group experienced more ventilator-free days [22.0 (9.0) vs 19.9 (10.6)] and ICU-free days [20.8 (8.7) vs 18.1 (10.4)], p < 0.05 for both.ConclusionsThis pilot trial confirmed the feasibility of targeting the ED in order to improve sedation practices and reduce deep sedation. These findings justify an appropriately powered clinical trial regarding ED-based sedation to improve clinical outcomes.

Project description:ObjectiveKetamine has been shown to decrease sedative requirements in intensive care unit (ICU). Randomized trials are limited on patient-centered outcomes. We designed this pilot trial to evaluate the feasibility of a large randomized controlled trial (RCT) testing the effect of ketamine as an adjunct analgosedative compared with standard of care alone as a control group (CG) in critically ill patients with mechanical ventilation (MV). We also provided preliminary evidence on clinically relevant outcomes to plan a larger trial.Material and methodsPilot, active-controlled, open-label RCT was conducted at medical, surgical, and transplant ICUs at a large tertiary and quaternary care medical institution (King Faisal Specialist Hospital and Research Center, Saudi Arabia). The study included adult patients who were intubated within 24 h, expected to require MV for the next calendar day, and had institutional pain and sedation protocol initiated. Patients were randomized in a 1:1 ratio to adjunct ketamine infusion 1-2 μg/kg/min for 48 h or CG alone.ResultsOf 437 patients screened from September 2019 through November 2020, 83 (18.9%) patients were included (43 in CG and 40 in ketamine) and 352 (80.5%) were excluded. Average enrollment rate was 3-4 patients/month. Consent and protocol adherence rates were adequate (89.24% and 76%, respectively). Demographics were balanced between groups. Median MV duration was 7 (interquartile range [IQR] 3-9.25 days) in ketamine and 5 (IQR 2-8 days) in CG. Median VFDs was 19 (IQR 0-24.75 days) in ketamine and 19 (IQR 0-24 days) in the CG (p = 0.70). More patients attained goal Richmond Agitation-Sedation Scale at 24 and 48 h in ketamine (67.5% and 73.5%, respectively) compared with CG (52.4% and 66.7%, respectively). Sedatives and vasopressors cumulative use, and hemodynamic changes were similar. ICU length-of-stay was 12.5 (IQR 6-21.2 days) in ketamine, compared with 12 (IQR 5.5-23 days) in CG. No serious adverse events were observed in either group.ConclusionsKetamine as an adjunct analgosedative agent appeared to be feasible and safe with no negative impact on outcomes, including hemodynamics. This pilot RCT identified areas of improvement in study protocol before conducting a large, adequately powered, multicenter RCT which is likely justified to investigate ketamine association with patient-centered outcomes further. Trial registration ClinicalTrials.gov: NCT04075006. Registered on 30 August 2019. Current controlled trials: ISRCTN14730035. Registered on 3 February 2020.

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.).

Project description:Purpose: To investigate physicians' perception of patients' tolerance levels regarding sedation, which could affect sedation practice for mechanically ventilated (MV) patients. Methods: This is a questionnaire survey combined with a 24 h cross-sectional study. The physician's propensity score for light sedation (PS-LS) was estimated by his/her response to the given answers for each item of the questionnaire, which tested the levels of interviewee's desire to manage MV patient with light sedation. Thereby, the mean physicians' PS-LS of each participating ICU (ICU-meanPS-LS) was calculated. The practical measurements of all variables listed on the questionnaire were used to semi-quantitatively assess stimulus intensity of what the recruited patients suffered (i.e., semi-quantitative stimulus intensity, SSI). Sedation depth was assessed by Richmond Agitation Sedation Scale (RASS). Results: 555 of 558 (99.5%) physicians from 102 ICUs were concerned with patients' tolerance levels regarding sedation while titrating sedation depth. The physician's PS-LS was non-normally distributed with median (IQR) of 3 (0-5). ICU-meanPS-LS was calculated in 92 out of 102 ICUs participating in the cross-sectional study, which was ranged from -5 to 7 with a median (IQR) of 2.37 (0.16-4.33). A significant increasing trend in prevalence of light sedation was observed over increasing ICU-meanPS-LS quartiles (from Q1 to Q4, χ2-test for trend, p = 0.002). Moreover, odds ratio for probability of light sedation remained significant in MV patients from Q4 ICUs vs. Q1 ICUs, adjusted by APACHE II score (OR, 2.332; 95% CI: 1.463-3.717; p < 0.001) or SSI score (OR, 2.445; 95% CI: 1.468-4.074; p = 0.001). Notably, adjusted OR for mortality was significant in deeply sedated MV patients (OR, 2.034; 95% CI: 1.435-2.884; p < 0.001). Conclusions: ICU physician's individualized perception for patients' tolerance levels regarding sedation, in light sedation affected sedation practice for MV patients.

Dataset Information

Remi-fent 1-A pragmatic randomised controlled study to evaluate the feasibility of using remifentanil or fentanyl as sedation adjuncts in mechanically ventilated patients.

Objective

Design

Setting

Participants

Interventions

Outcomes

Results

Conclusions

Publications

Remi-fent 1-A pragmatic randomised controlled study to evaluate the feasibility of using remifentanil or fentanyl as sedation adjuncts in mechanically ventilated patients.

Similar Datasets

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