The influence of analgesic-based sedation protocols on delirium and outcomes in critically ill patients: A randomized controlled trial.
ABSTRACT: To investigate the influence of analgesic-based midazolam sedation on delirium and outcomes in critically ill patients and to analyze the risk factors of delirium.Single center, prospective randomized controlled trial.A surgical intensive care unit (ICU) in a tertiary care hospital in China.Mechanically ventilated patients requiring sedation.Patients admitted to the surgical intensive care unit who required sedation and were undergoing mechanical ventilation for longer than 24 hours were randomly divided into three groups: 1) the remifentanil group received remifentanil and midazolam, 2) the fentanyl group received fentanyl and midazolam, and 3) the control group received only midazolam. The analgesic effect, sedation depth, and presence of delirium were evaluated. To compare the effect of different therapies on the occurrence of delirium, days of mechanical ventilation, length of the ICU stay, and 28-day mortality were measured along with the risk factors for delirium. A total of 105 patients were enrolled, and 35 patients were included in each group. Compared to the control group, patients who received remifentanil and fentanyl required less midazolam each day (P = 0.038 and <0.001, respectively). Remifentanil has a significant effect on reducing the occurrence of delirium (P = 0.007). The logistic regression analysis of delirium demonstrated that remifentanil (OR 0.230, 95%Cl 0.074-0.711, P = 0.011) is independent protective factors for delirium, and high APACHE II score (OR 1.103, 95%Cl 1.007-1.208, P = 0.036) is the independent risk factor for delirium.Remifentanil and fentanyl can reduce the amount of midazolam required, and remifentanil could further reduce the occurrence of delirium.
Project description:Background:The aim of this clinical study was to evaluate the efficacy of neurobehavioral, hemodynamics and sedative characteristics of dexmedetomidine compared with morphine and midazolam-based regimen after cardiac surgery at equivalent levels of sedation and analgesia in improving clinically relevant outcomes such as delirium. Methods:Sixty patients were randomly allocated into one of two equal groups: group A = 30 patients received dexmedetomidine infusion (0.4-0.7 ?g/kg/h) and Group B = 30 patients received morphine in a dose of 10-50 ?g/kg/h as an analgesic with midazolam in a dose of 0.05 mg/kg up to 0.2 mg/kg as a sedative repeated as needed. Titration of the study medication infusions was conducted to maintain light sedation (Richmond agitation-sedation scale) (-2 to +1). Primary outcome was the prevalence of delirium measured daily through confusion assessment method for intensive care. Results:Group A was associated with shorter length of mechanical ventilation, significant shorter duration of intensive care unit (ICU) stay (P = 0.038), and lower risk of delirium following cardiac surgery compared to Group B. Group A showed statistically significant decrease in heart rate values 4 h after ICU admission (P = 0.015) without significant bradycardia. Group A had lower fentanyl consumption following cardiac surgery compared to Group B. Conclusion:Dexmedetomidine significantly reduced the length of stay in ICU in adult cardiac surgery with no significant reduction in the incidence of postoperative delirium compared to morphine and midazolam.
Project description:<h4>Objectives</h4>We examined the relationship between dominant sedation strategy, risk of delirium and patient-centred outcomes in adults admitted to intensive care units (ICUs).<h4>Design</h4>Retrospective propensity-matched cohort study.<h4>Setting</h4>Mechanically ventilated adults (≥ 18 years) admitted to four Canadian hospital medical/surgical ICUs from 2014 to 2016 in Calgary, Alberta, Canada.<h4>Participants</h4>2837 mechanically ventilated adults (≥ 18 years) requiring admission to a medical/surgical ICU were evaluated for the relationship between sedation strategy and delirium.<h4>Interventions</h4>None.<h4>Primary and secondary outcome measures</h4>The primary exposure was dominant sedation strategy, defined as the sedative infusion, including midazolam, propofol or fentanyl, with the longest duration before the first delirium assessment. The primary outcome was 'ever delirium' identified using the Intensive Care Delirium Screening Checklist. Secondary outcomes included mortality, length of stay (LOS), ventilation duration and days with delirium. The cohort was analysed in two propensity score (patient characteristics and therapies received) matched cohorts (propofol vs fentanyl and propofol vs midazolam).<h4>Results</h4>2837 patients (60.7% male; median age 57 years (IQR 43-68)) were considered for propensity matching. In propensity score-matched cohorts(propofol vs midazolam, n=712; propofol vs fentanyl, n=1732), the odds of delirium were significantly higher with midazolam (OR 1.46 (95% CI 1.06 to 2.00)) and fentanyl (OR 1.22 (95% CI 1.00 to 1.48)) compared with propofol dominant sedation strategies. Dominant sedation strategy with midazolam and fentanyl were associated with a longer duration of ventilation compared with propofol. Fentanyl was also associated with increased ICU mortality (OR 1.50, 95% CI 1.07 to 2.12)) ICU and hospital LOS compared with a propofol dominant sedation strategy.<h4>Conclusions</h4>We identified a novel association between fentanyl dominant sedation strategies and an increased risk of delirium, a composite outcome of delirium or death, duration of mechanical ventilation, ICU LOS and hospital LOS. Midazolam dominant sedation strategies were associated with increased delirium risk and mechanical ventilation duration.
Project description:INTRODUCTION: This randomised, open-label, multicentre study compared the safety and efficacy of an analgesia-based sedation regime using remifentanil with a conventional hypnotic-based sedation regime in critically ill patients requiring prolonged mechanical ventilation for up to 10 days. METHODS: One hundred and five randomised patients received either a remifentanil-based sedation regime (initial dose 6 to 9 microg kg(-1) h(-1) (0.1 to 0.15 microg kg(-1) min(-1)) titrated to response before the addition of midazolam for further sedation (n = 57), or a midazolam-based sedation regime with fentanyl or morphine added for analgesia (n = 48). Patients were sedated to an optimal Sedation-Agitation Scale (SAS) score of 3 or 4 and a pain intensity (PI) score of 1 or 2. RESULTS: The remifentanil-based sedation regime significantly reduced the duration of mechanical ventilation by more than 2 days (53.5 hours, P = 0.033), and significantly reduced the time from the start of the weaning process to extubation by more than 1 day (26.6 hours, P < 0.001). There was a trend towards shortening the stay in the intensive care unit (ICU) by 1 day. The median time of optimal SAS and PI was the same in both groups. There was a significant difference in the median time to offset of pharmacodynamic effects when discontinuing study medication in patients not extubated at 10 days (remifentanil 0.250 hour, comparator 1.167 hours; P < 0.001). Of the patients treated with remifentanil, 26% did not receive any midazolam during the study. In those patients that did receive midazolam, the use of remifentanil considerably reduced the total dose of midazolam required. Between days 3 and 10 the weighted mean infusion rate of remifentanil remained constant with no evidence of accumulation or of a development of tolerance to remifentanil. There was no difference between the groups in SAS or PI score in the 24 hours after stopping the study medication. Remifentanil was well tolerated. CONCLUSION: Analgesia-based sedation with remifentanil was well tolerated; it reduces the duration of mechanical ventilation and improves the weaning process compared with standard hypnotic-based sedation regimes in ICU patients requiring long-term ventilation for up to 10 days.
Project description:Delirium is a primary adverse event in ventilated patients who receive long-term monosedative treatment. Sequential sedation may reduce these adverse effects. This study evaluated risk factors for delirium in sequential sedation patients.A total of 141 patients who underwent sequential sedation were enrolled. Delirium was diagnosed using Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) scale. Univariate and multivariate Cox proportional hazards regressions were used to predict risk factors.Older age (?51) (RR = 2.432, 95% CL 1.316-4.494, p = 0.005), higher SOFA score (?14) (RR = 2.022, 95% CL 1.076-3.798, p = 0.029), regular smoking (RR = 2.366, 95% CL 1.277-4.382, p = 0.006), and higher maintenance dose of midazolam (RR = 1.052, 95% CL 1.000-1.107, p = 0.049) and fentanyl (RR = 1.045, 95% CL 1.019-1.072, p = 0.001) when patients met sequential criteria, were independent risk factors of delirium. Sequential sedation with dexmedetomidine (RR = 0.448, 95% CL 0.209-0.963, p = 0.040) was associated with a lower risk of delirium.Older age, higher SOFA score, regular smoking, and higher maintenance dose of midazolam and fentanyl when patients met sequential criteria were independent risk factors of delirium in sequential sedation patients. Sequential sedation with dexmedetomidine reduced risk of delirium.
Project description:The purpose of this study was to determine if the Entonox gas could cause adequate analgesic and sedative effects in patients who need cardioversion. In this randomized not blinded clinical trial, the sedative and analgesic effects of midazolam and fentanyl were compared with Entonox. Eligible patients who need synchronized cardioversion because of dysrhythmia were randomly divided into two groups. The first group received intravenous midazolam and fentanyl; the second group received Entonox through a blower-dependent mask. Onset and end of sedation, sedation level, and pain score were recorded. There were nonsignificant differences between the two groups (22 patients in each group) regarding age, gender, weight, sedation level, and frequency and level of shock. The pain score recorded in the first group was 5.05 ± 1.32, and 3.9 ± 0.7 in the second group (P = 0.002). Furthermore, sedation duration and time to full recovery consciousness were shorter in the second group (P < 0.001). In the first group, seven patients needed additional doses to induce and maintain sedation. In addition, as a result of apnoea, four patients required airway support. None of them occurred in the second group. Entonox is a suitable medication in rapid cardioversion, as it has minimal side effects and adequate analgesic and sedative effects.
Project description:Hospitals are increasingly forced to consider the economics of technology use. We estimated the incremental cost-consequences of remifentanil-based analgo-sedation (RS) vs. conventional analgesia and sedation (CS) in patients requiring mechanical ventilation (MV) in the intensive care unit (ICU), using a modelling approach.A Markov model was developed to describe patient flow in the ICU. The hourly probabilities to move from one state to another were derived from UltiSAFE, a Dutch clinical study involving ICU patients with an expected MV-time of two to three days requiring analgesia and sedation. Study medication was either: CS (morphine or fentanyl combined with propofol, midazolam or lorazepam) or: RS (remifentanil, combined with propofol when required). Study drug costs were derived from the trial, whereas all other ICU costs were estimated separately in a Dutch micro-costing study. All costs were measured from the hospital perspective (price level of 2006). Patients were followed in the model for 28 days. We also studied the sub-population where weaning had started within 72 hours.The average total 28-day costs were €15,626 with RS versus €17,100 with CS, meaning a difference in costs of €1474 (95% CI -2163, 5110). The average length-of-stay (LOS) in the ICU was 7.6 days in the RS group versus 8.5 days in the CS group (difference 1.0, 95% CI -0.7, 2.6), while the average MV time was 5.0 days for RS versus 6.0 days for CS. Similar differences were found in the subgroup analysis.Compared to CS, RS significantly decreases the overall costs in the ICU.Clinicaltrials.gov NCT00158873.
Project description:<h4>Background</h4>According to current guidelines flexible bronchoscopy is usually performed under sedation. Previously it has been demonstrated that combined sedation with e. g. the combination of midazolam and propofol or an opioid might have several advantages over sedation with just one sedative drug. However, little is known about the efficacy and safety of combined sedation with midazolam, fentanyl and propofol (MFP) compared to sedation with midazolam and fentanyl (MF) or midazolam and propofol (MP).<h4>Methods</h4>We carried out a retrospective analysis of bronchoscopies performed under triple (MFP) or double sedation (MF and MP) in an academic hospital. 1392 procedures were analyzed (MFP: n = 824; MF: n = 272; MP: n = 296). In particular, we compared the occurrence of complications and the dosage of administered sedative drugs between the groups.<h4>Results</h4>The occurrence of adverse events (MFP vs. MF: odds ratio (OR) 1.116 [95% CI 0.7741 to 1.604]; MFP vs. MP: OR 0.8296 [95% CI 0.5939 to 1.16] and severe adverse events (MFP vs. MF: OR 1.581 [95% CI 0.5594 to 4.336]; MFP vs. MP: OR 3.47 [95% CI 0.908 to 15.15]; all p>0.05) was similar in all groups. The dosage of midazolam was lower in the MFP compared to the MF or MP group (MFP vs. MF: Cohen's d 0.075; MFP vs. MP: Cohen's d 0.225; all p<0.001). In addition patients in the MFP group received significantly less propofol compared to the MP group (Cohen's d 1.22; p<0.001).<h4>Conclusions</h4>In summary we were able to demonstrate that triple sedation can safely be administered during flexible bronchoscopy and is associated with a reduced dosage of midazolam and propofol.
Project description:Introduction The ?2 agonist dexmedetomidine is a new sedative and analgesic agent which is licensed in the USA for post-operative intensive care sedation. We compared dexmedetomidine with the mixture of midazolam and morphine for post-operative patient who required mechanical ventilation in intensive care unit (ICU). Objective : To compare the effect of dexmedetomidine and midazolam-morphine mixture among post-operative patients in ICU; in term of the amount of analgesic (PCA morphine) requirement, sedation score, haemodynamic profiles and time of extubation. Methodology : Prospective, double-blinded randomized controlled trial study design involved post-operative patients admitted to the Intensive Care Unit (ICU) of Hospital Universiti Sains Malaysia (HUSM) conducted from June 2003 to June 2004. Thirty-four mechanically ventilated post-operative patients were randomly assigned to receive short-term (minimum 4 hours) sedation with either continuous intravenous infusion of dexmedetomidine (group Dex. n=17) or midazolam-morphine mixture (group MM, n=17). Both groups received similar intraoperative anaesthetic regime. Patient controlled analgesia (PCA Morphine) was given to patient as rescue analgesic. Analgesic (PCA morphine) used (mg/hour), Ramsay sedation scoring, extubation time (minute), systolic blood pressure, diastolic blood pressure, mean arterial pressure and heart rate were Medical Sciences, Universiti Sains Malaysia had approved this study on 9th April 2003. Result : Mean extubation time of dexmedetomidine group was significantly lower than midazolam and morphine mixture group [mean (s.d.): 40.3 ± 16.5 minutes versus 57.9 ± 17.7 minutes. p=0.05]. Within the first 4 hours drug infusion, mean systolic blood pressure [mean (s.d.): 105 ±14 mmHg vs 127 ± 24 mmHg, (p=0.000)], mean diastolic blood pressure [mean (s.d.): 59 ± 8mmHg vs 66 ± 13 mmHg (p=0.000)], mean arterial pressure [mean (s.d.): 76 ± 9 mmHg vs 86 ± 15mmHg (p=0.000)] and mean heart rate [mean (s.d.): 88 ± 13 beats per minute vs 102 ± 24 beats per minute (p=0.000)] were significantly lower in dexmedetomidine group than those in midazolam and morphine mixture. There was significant difference of mean Ramsay sedation score between dexmedetomidine and midazolam morphine mixture (p=0.000). However, there was no significant difference of mean dose of morphine per hour between dexmedetomidine groups and midazolam morphine mixture [(mean (s.d.); 1.4 ± 0.7 mg/hour) versus mean (s.d.); 1.1 ± 0.8 mg/hour). p= 0.157 ]. Conclusion : Dexmedetomidine provides safe, effective sedation and analgesia for postoperative long surgical patient in intensive care unit. Haemodynamic variables of dexmedetomidine group was more stable than midazolam and morphine mixtures group. Thus dexmedetomidine provides better perioperative haemodynamic control or a long sugery. The use of dexmedetomidine also allowed for more rapid tracheal extubation. Dr. Saedah Ali : Supervisor Dr. Nik Abdullah Nik Mohamed : Co-Supervisor
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.
Project description:The aim of the investigation is to clarify the beneficial sedative effects for patients with postoperative intubation in the intensive care unit (ICU) after oral and maxillofacial surgery. Forty patients with postoperative intubation were divided into two groups in method of random number table: midazolam group and dexmedetomidine group. The Ramsay score, the behavioral pain scale (BPS) score, SpO2, HR, MAP, and RR were recorded before sedation (T0), 30 minutes (T1), 1 hour (T2), 2 hours (T3), 6 hours (T4), and 12 hours (T5) after dexmedetomidine or midazolam initiation in intensive care unit, and 10 minutes after extubation (T6). The rate of incidences of side effects was calculated. Sedation with midazolam was as good as standard sedation with dexmedetomidine in maintaining target sedation level. The BPS score in the midazolam group was higher than that in the dexmedetomidine group. The time of tracheal catheter extraction in the dexmedetomidine group was shorter than that in the midazolam group (p ? 0.001). The incidence of bradycardia in the dexmedetomidine group was higher than that in the midazolam group (p = 0.028). There was no statistically significant difference in the incidence of hypotension between the two groups (p = 0.732). The incidence of respiratory depression of group midazolam was higher than that of group dexmedetomidine (p = 0.018). The incidence of delirium in the dexmedetomidine group was significantly lower than that in the midazolam group, and the difference was statistically significant (p = 0.003). Dexmedetomidine and midazolam can meet the needs for sedation in ICU patients. And dexmedetomidine can improve patients' ability to communicate pain compared with midazolam.