Clinical benefits of dexmedetomidine versus propofol in adult intensive care unit patients: a meta-analysis of randomized clinical trials

Background

This meta-analysis was performed to assess the influence of dexmedetomidine and propofol for adult intensive care unit (ICU) sedation, with respect to patient outcomes and adverse events.

Materials and methods

A systematic review was conducted of all randomized controlled trials exploring the clinical benefits of dexmedetomidine versus propofol for sedation in adult intensive care patients. The primary outcomes of this study were length of ICU stay, duration of mechanical ventilation, and risk of ICU mortality. Secondary outcomes included risk of delirium, hypotension, bradycardia and hypertension.

Results

Ten randomized controlled trials, involving 1202 patients, were included. Dexmedetomidine significantly reduced the length of ICU stay by <1 d (five studies, 655 patients; mean difference, −0.81 d; 95% confidence interval [CI], −1.48 to −0.15) and the incidence of delirium (three studies, 658 patients; relative risk [RR], 0.40; 95% CI, 0.22–0.74) in comparison with propofol, whereas there was no difference in the duration of mechanical ventilation (five studies, 895 patients; mean difference, 0.53 h; 95% CI −2.66 to 3.72) or ICU mortality (five studies, 267 patients; RR, 0.83; 95% CI, 0.32–2.12) between these two drugs. Dexmedetomidine was associated with an increased risk of hypertension (three studies, 846 patients; RR, 1.56; 95% CI, 1.11–2.20) compared with propofol. Other adverse event rates were similar between dexmedetomidine and propofol groups.

Conclusions

For ICU patient sedation, dexmedetomidine may offer advantages over propofol in terms of decrease in the length of ICU stay and the risk of delirium. However, transient hypertension may occur when dexmedetomidine is administered with a loading dose or at high infusion rates.     

Quetiapine for delirium prophylaxis in high-risk critically ill patients

BackgroundDelirium is common in patients admitted to the surgical trauma intensive care unit (ICU), and the risk factors for these patients differ from medical patients. Given the morbidity and mortality associated with delirium, efforts to prevent it may improve patient outcomes, but previous efforts pharmacologically have been limited by side effects and insignificant results. We hypothesized that scheduled quetiapine could reduce the incidence of delirium in this population.MethodsThe study included 71 adult patients who were at high-risk for the development of delirium (PRE-DELIRIC Score ≥50%, history of dementia, alcohol misuse, or drug abuse). Patients were randomized to receive quetiapine 12.5 mg every 12 h for delirium or no pharmacologic prophylaxis within 48 h of admission to the ICU. The primary end point was the incidence of delirium during admission to the ICU. Secondary end points included time to onset of delirium, ICU and hospital length of stay (LOS), ICU and hospital mortality, duration of mechanical ventilation, and adverse events.ResultsThe incidence of delirium during admission to the ICU was 45.5% (10/22) in the quetiapine group and 77.6% (38/49) in the group that did not receive pharmacological prophylaxis. The mean time to onset of delirium was 1.4 days for those who did not receive prophylaxis versus 2.5 days for those who did (p = 0.06). The quetiapine group significantly reduced ventilator duration from 8.2 days to 1.5 days (p = 0.002).ConclusionsThe findings suggested that scheduled, low-dose quetiapine is effective in preventing delirium in high-risk, surgical trauma ICU patients.     

Effect of dexmedetomidine on delirium during sedation in adult patients in intensive care units: A systematic review and meta-analysis

Study objectiveTo compare the effect of sedation protocols with and without dexmedetomidine on delirium risk and duration in adult patients in intensive care units (ICUs).DesignA meta-analysis of randomized controlled trials.Review methodsWe searched the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, and ISI Web of Science from inception to September 3, 2020. We included studies comparing the effect of dexmedetomidine-based sedation on delirium risk with non-dexmedetomidine-based sedation in adult patients in ICUs. We pooled the data using a random-effects model using Review Manager 5.2, and assessed publication bias using Stata 11.0. The quality of evidence was rated using the Grading of Recommendations, Assessment, Development and Evaluation system.Main resultsWe included 36 studies involving 9623 participants. The use of dexmedetomidine was associated with reduced risk of delirium (risk ratio [RR], 0.63; 95% confidence interval [CI], 0.54–0.75; very low-quality evidence), but higher incidences of hypotension and bradycardia during hospital stay. Dexmedetomidine was also associated with shorter durations of ICU stay, hospital stay and mechanical ventilation. Dexmedetomidine did not affect ICU mortality (RR, 1.01; 95% CI, 0.89–1.14; low-quality evidence), hospital mortality (RR, 1.01; 95% CI, 0.91–1.12; very low-quality evidence), or 30-day mortality (RR, 0.77; 95% CI, 0.58–1.01; moderate-quality evidence), or duration of delirium (mean difference, −0.74 days; 95% CI, −1.83 to 0.36 days; very low-quality evidence). We identified publication bias for risk and duration of delirium, length of ICU stay, and hospital stay.ConclusionsLow- or very low-quality evidence suggests that dexmedetomidine was associated with a clinically-small reduction of delirium risk, ICU/hospital stay and mechanical ventilation duration, but were not associated with improved mortality or shorter delirium duration in ICU patients. These findings were inconclusive because of publication bias, heterogeneity, and limited sample size. Significant adverse effects of dexmedetomidine include hypotension and bradycardia.PROSPERO registration number: CRD42018095358.     

Dexmedetomidine use and mortality in mechanically ventilated patients with severe burns: A cohort study using a national inpatient database in Japan

BackgroundDexmedetomidine is an alpha 2-adrenergic receptor agonist. Apart from its sedative effects, dexmedetomidine can potentially reduce mortality through its anti-inflammatory effect. However, the impact of dexmedetomidine on in-hospital outcomes of patients with severe burns remains unclear. Therefore, we aimed to elucidate the association between dexmedetomidine use and mortality in mechanically ventilated patients with severe burns, using a Japanese nationwide database of in-hospital patients.MethodsWe included adults with severe burns (burn index ≥ 10) who were registered in the Japanese Diagnosis Procedure Combination national inpatient database from 2010 to 2018, started mechanical ventilation within 3 days of admission, and received any sedative drug (dexmedetomidine, midazolam, or propofol). One-to-one propensity score matching was performed between patients who received dexmedetomidine on the day of mechanical ventilation initiation (dexmedetomidine group) and those who did not receive dexmedetomidine (control group). The primary outcome was all-cause 30-day in-hospital mortality. Secondary outcomes were length of hospital stay and duration of mechanical ventilation in patients and survivors.ResultsEligible patients (n = 1888) were classified into the dexmedetomidine group (n = 371) or the control group (n = 1517). After one-to-one propensity score matching, we compared 329 patients from both groups. No significant difference was observed in the 30-day mortality between patients in the dexmedetomidine and control groups (22.8% vs. 22.5%, respectively; odds ratio, 1.02; 95% confidence interval, 0.71–1.46). Moreover, there were no significant differences between patients in the dexmedetomidine and control groups in terms of the length of hospital stay or the duration of mechanical ventilation.ConclusionsWe found no significant association between dexmedetomidine use and in-hospital outcomes (mortality, length of hospital stay, and length of mechanical ventilation) in mechanically ventilated patients with severe burns. Dexmedetomidine use may not improve the aforementioned outcomes; therefore, its selection should be based on the patient’s general condition and the target level of sedation.     

A randomized control trial comparing prophylactic dexmedetomidine versus clonidine on rates and duration of delirium in older adult patients undergoing coronary artery bypass grafting

Study objectivePostoperative delirium occurs in 20–50% of elderly patients undergoing cardiac surgery and increases morbidity and mortality. We investigated whether prophylactic dexmedetomidine could reduce delirium incidence in elderly patients after coronary artery bypass grafting (CABG), compared with clonidine.DesignProspective observational trial.SettingAcademic university hospital.ParticipantsPatients (60–70 years old) who underwent CABG and received either dexmedetomidine or clonidine infusion postoperatively.InterventionsPatients were randomly allocated to dexmedetomidine or clonidine groups. In the dexmedetomidine group, patients received an initial infusion of 0.7–1.2 μg/kg/h; sedation and analgesia were evaluated after 45–60 min. If the Richmond assessment sedation score (RASS) increased from +1 to +4, the infusion rate was increased by 0.1–0.2 μg/kg/h every 30 min, up to 1–1.4 μg/kg body-weight/h. Dexmedetomidine infusion was not discontinued pre-extubation; thereafter, infusion was reduced by 0.1 μg/kg/h until 0.2 μg/kg/h. The maximum infusion duration was 72 h. In the clonidine group, patients received an initial infusion of 0.5 μg/kg, followed by 1–2 μg/kg/h, if the RASS changed from +1 to +4. This was continued throughout mechanical ventilation.MeasurementsPatients were followed up to 5 days post-surgery. Delirium incidence, extubation time, lengths of intensive care unit (ICU) and hospital stay, need for inotropic support or vasopressors, mean arterial blood pressure and heart rate, hospital mortality rate, total postoperative morphine dose, number of patients receiving haloperidol, and adverse events were recorded.Main resultsTwo-hundred-and-eighty-six patients (dexmedetomidine, 144; clonidine, 142) were studied. Dexmedetomidine was associated with lower risk and duration of delirium, shorter mechanical ventilation duration and ICU stay, lower mortality rate, and lower morphine consumption than the clonidine group. Dexmedetomidine significantly decreased heart rates after ICU admission.ConclusionsPostoperative infusion of dexmedetomidine provides a feasible option for postoperative control of delirium after CABG in adult patients.     

A comparison of single‐dose dexmedetomidine or propofol on the incidence of emergence delirium in children undergoing general anaesthesia for magnetic resonance imaging

Emergence delirium is a significant problem in children regaining consciousness following general anaesthesia. We compared the emergence characteristics of 120 patients randomly assigned to receive a single intravenous dose of dexmedetomidine 0.3 μg.kg^?1, propofol 1 mg.kg^?1, or 10 ml saline 0.9% before emerging from general anaesthesia following a magnetic resonance imaging scan. Emergence delirium was diagnosed as a score of 10 or more on the Paediatric Anaesthesia Emergence Delirium scale. The incidence of emergence delirium was 42.5% in the dexmedetomidine group, 33.3% in the propofol group and 41.5% in the saline group (p = 0.671). Three patients in the dexmedetomidine group, none in the propofol group and two in the saline group required pharmacological intervention for emergence delirium (p = 0.202). Administration of neither dexmedetomidine nor propofol significantly reduced the incidence, or severity, of emergence delirium. The only significant predictor for emergence delirium was the time taken to awaken from general anaesthesia, with every minute increase in wake‐up time reducing the odds of emergence delirium by 7%.     

重症患者右美托咪啶和咪达唑仑镇静效果的比较:Meta分析

目的 采用Meta分析比较右美托咪啶和咪达唑仑用于重症患者镇静的效果.方法 检索PubMed、EMbase、Cochrane图书馆、万方数据库、CNKI、VIP等数据库,收集右美托咪啶和咪达唑仑用于重症患者镇静的临床随机对照研究.采用Cochrane协作网系统评价纳入文献的质量,采用Rev-Man 5.0软件对收集的患者资料进行Meta分析.结果 共纳入6项研究,包括613例患者,其中右美托咪啶组385例,咪达唑仑组228例.与咪达唑仑组比较,右美托咪啶组ICU住院时间缩短,机械通气时间、心动过缓、低血压和谵妄的发生率、病死率差异无统计学意义(P＞0.05).结论 与咪达唑仑相比,右美托咪啶可缩短ICU住院时间,提示右美托咪啶有利于重症患者的转归.     

Early mobilization of trauma patients admitted to intensive care units: A systematic review and meta-analyses

ObjectiveTo determine the effect of early mobilization (EM) in trauma patients admitted to the ICU. Outcomes of interest included mortality, hospital and ICU length of stay (LOS), and duration of mechanical ventilation.MethodsWe performed a systematic review of 4 electronic databases (Ovid MEDLINE, Embase, CINAHL, Cochrane Library) and the grey literature. Eligible study designs included randomized control trials, prospective cohorts, or retrospective cohorts. Studies must have compared EM to usual care (i.e., delayed or no mobilization) in trauma patients admitted to ICU. Overall, there were 2982 articles screened and 9 were included in the analysis. Two authors independently performed data extraction using a standardized form. Pertinent study design and population characteristics were recorded, as were prespecified outcome measures. Meta-analyses were performed using random effects models. Study quality was assessed using the Newcastle-Ottawa Scale.ResultsStudy cohorts ranged from 15 to 1132 patients (median 63) and varied in their inclusion criteria. Most studies utilized a progressive mobility protocol as their intervention. Mortality was reported in 5 studies, of which 3 observed a lower rate with EM; however, meta-analysis showed no difference in mortality between patients mobilized early and those receiving usual care. Eight studies reported on LOS (in-hospital and ICU); although all 8 studies found EM reduced LOS, the difference in LOS was not significant on meta-analysis. Finally, 3 studies reported on ventilator days, all of which observed a reduction in the EM group. On meta-analysis, duration of mechanical ventilation was significantly lower with EM (mean difference −1.18 days, 95% CI, −2.17 – −0.19).ConclusionsFew studies have investigated the effects of EM in trauma ICU patients. The available evidence suggests that patients who receive EM require fewer days of mechanical ventilation, but have similar mortality and LOS compared to those receiving usual care.     

右美托咪定联合地佐辛在ICU机械通气患者中镇痛镇静的效果

目的观察右美托咪定联合地佐辛或芬太尼在ICU机械通气患者术后镇痛镇静的效果。方法选择2016年6~12月我院ICU机械通气患者57例,男35例,女22例,年龄18~75岁,将患者按随机数字表法分为三组:右美托咪定组(A组,n=17例)、右美托咪定联合芬太尼组(B组,n=20例)和右美托咪定联合地佐辛组(C组,n=20例)。比较三组患者一般状况、疼痛评分、用药前后MAP和HR、达理想镇痛镇静的时间、机械通气总时间等指标。结果三组一般资料、重症疼痛观察(CPOT)评分、治疗前后不同时点MAP和HR、机械通气时间差异无统计学意义,达到理想镇静镇痛的时间C组明显快于A组和B组(P0.05)。结论右美托咪定联合地佐辛较单用右美托咪定及右美托咪定联合芬太尼能更快达到理想镇静镇痛效果。     

Age-adjusted shock index: From injury to arrival

BackgroundStudies have demonstrated the superiority of the shock index, pediatric age-adjusted (SIPA) in predicting outcomes in pediatric blunt trauma patients. However, all have utilized SIPA calculated on emergency department (ED) arrival. We sought to evaluate the utility of SIPA at the trauma scene and describe changes in SIPA from the trauma scene to the ED.MethodsWe used 2014–2016 Trauma Quality Improvement Program Data to identify blunt trauma patients 1–15 years old with an injury severity score (ISS) > 15. We calculated SIPA using vitals obtained at the trauma scene and on ED arrival. Outcome measures included ISS, transfusion within 24 h, intensive care unit (ICU), hospital length of stay (LOS), ventilator days, and mortality.ResultsWe identified 2917 patients, and 34.2% had a persistently elevated SI from the injury scene to ED arrival, whereas 17.9% had a persistently elevated SIPA. An elevated SIPA at the trauma scene was more predictive of greater ISS, LOS, and ventilator requirements. Furthermore, a SIPA that remained abnormal was associated with greater ISS, LOS, ICU admission, mechanical ventilation, and mortality.ConclusionsPrehospital SIPA values predict worse outcomes in pediatric trauma patients, and their change over time may have greater predictive utility than a single value alone.Level of EvidenceIIType of StudyPrognosis Study.     

Dexmedetomidin

Dexmedetomidine is a highly selective α₂-receptor agonist with sedative, analgetic and anxiolytic effects. It is chemically related to clonidine and has been an authorized drug in Europe since September 2011. Dexmedetomidine enables a level of sedation in which mechanically ventilated patients may be woken by verbal stimulation (Richmond agitation sedation scale RASS 0–?3). In this respect dexmedetomidine achieves the same desired effect as propofol and midazolam; however, in direct comparison to a sedation regime with benzodiazepines, dexmedetomidine reduces the prevalence, duration and severity of delirium in intensive care. Patients sedated by dexmedetomidine can statistically be extubated earlier and an influence on duration of stay in the intensive care unit (ICU) has not been shown. Daily therapy costs are approximately 5 times higher than those of propofol but an objective standpoint in relation to clinical cost efficiency is unattainable.     

Acute post-traumatic muscle atrophy on CT scan predicts prolonged mechanical ventilation and a worse outcome in severe trauma patients

BackgroundThe aim of present study was to assess the association between acute post-traumatic atrophy (APTMA) determined on psoas computed tomography [CT] scan and the duration of mechanical ventilation and outcomes in severe trauma patients.MethodsA retrospective analysis of severe trauma patients (Injury Severity Score [ISS], >15) hospitalized in the intensive care unit (ICU) for more than 7 days between January 2010 and December 2015 was performed. The psoas muscle index (PMI) was measured on admission and at delayed CT scan. ΔPMI was calculated as the percentage PMI loss between these two scans. Three groups were defined and compared a posteriori using the quartiles of the ΔPMI values: low (lower quartile), moderate, and severe (higher quartile) APTMA groups. Linear regression analysis was performed to predict the duration of mechanical ventilation, of catecholamines, length of stay (LOS) in the ICU and hospital, and complications were assessed.ResultsA total of 114 trauma patients were included (median age, 40 years; [IQR, 25–54 years]; ISS, 33 [IQR, 25–41]). Based on the ΔPMI determination, 29 patients were allocated in the low APTMA group (range ?PMI, 0%–6%), 56 in the moderate APTMA group (range ?PMI, 6%–18%), and 29 in the APTMA group (range ?PMI, ≥19%). Severity of APTMA was significantly associated with the duration of mechanical ventilation and catecholamines, ICU and hospital LOS (P<0.001). Delayed pneumonia (P=0.006) and other delayed infections (P=0.014), as well as thromboembolic events (P=0.04) were statistically associated with the severity of APTMA, whereas mortality did not differ between the three groups (P=0.20). Using linear regression analysis, each ?PMI increase of 1% was significantly associated with 0.90 supplementary days of mechanical ventilation (P<0.001), 0.29 supplementary days of catecholamines (P<0.001) and 0.82 supplementary days of hospitalization (P<0.001). All these statistical associations were confirmed in multivariate analysis (P<0.001).ConclusionAcute muscle atrophy diagnosed on CT scan by psoas area measurement (ΔPMI) was strongly associated with poor outcomes in severe trauma patients.     

The survival benefit of low molecular weight heparin over unfractionated heparin in pediatric trauma patients

IntroductionVenous thromboembolism (VTE) prophylaxis in pediatric patients is controversial and is mainly dependent on protocols derived from adult practices. Our study aimed to compare outcomes among pediatric trauma patients who received low molecular weight heparin (LMWH) compared to those who received unfractionated heparin (UFH).MethodsWe performed 2 years (2015–2016) retrospective analysis of the Pediatrics ACS-TQIP database. Pediatric trauma patients (age ≤ 17) who received thromboprophylaxis with either LMWH or UFH were included. Patients were stratified into three age groups. Analysis of each subgroup and the entire cohort was performed. Outcome measures included VTE events (deep vein thrombosis [DVT] and pulmonary embolism [PE]), hospital and ICU length of stay (LOS) among survivors, and mortality. Propensity score matching was used to match the two cohorts LMWH vs UFH.ResultsA matched cohort of 1,678 pediatric trauma patients was analyzed. A significant difference in survival, DVT events, and in-hospital LOS was seen in the age groups above 9 years. Overall, the patients who received LMWH had lower mortality (1.4% vs 3.6%, p < 0.01), DVT (1.7% vs 3.7%, p < 0.01), and hospital LOS among survivors (7 days vs 9 days, p < 0.01) compared to those who received UFH. There was no significant difference in the ICU LOS among survivors and the incidence of PE between the two groups.ConclusionLMWH is associated with increased survival, lower rates of DVT, and decreased hospital LOS compared to UFH among pediatric trauma patients age 10–17 years.Level of EvidenceLevel III Prophylactic.Study TypeProphylactic.     

ICU sedation after coronary artery bypass graft surgery: dexmedetomidine-based versus propofol-based sedation regimens

OBJECTIVE: To compare dexmedetomidine-based to propofol-based sedation after coronary artery bypass graft (CABG) surgery in the intensive care unit (ICU). DESIGN: Randomized, open label. SETTING: Twenty-five centers in the United States and Canada. PARTICIPANTS: Two hundred ninety-five adults undergoing CABG surgery. INTERVENTIONS: At sternal closure, patients in group A received 1.0 microg/kg of dexmedetomidine over 20 minutes and then 0.2 to 0.7 microg/kg/h to maintain a Ramsay sedation score > or =3 during assisted ventilation and > or =2 after extubation. Patients could be given propofol for additional sedation if necessary; group B patients received propofol-based care according to each investigator's standard practice. MEASUREMENTS AND MAIN RESULTS: Mean sedation levels were within target ranges in both groups. Mean times to weaning and extubation were similar, although fewer dexmedetomidine patients remained on the ventilator beyond 8 hours. Morphine use was significantly reduced in the dexmedetomidine group. Only 28% of the dexmedetomidine patients required morphine for pain relief while ventilated versus 69% of propofol-based patients (p < 0.001). Propofol patients required 4 times the mean dose of morphine while in the ICU. Mean blood pressure increased initially in both groups, then decreased to 3 mmHg below baseline in dexmedetomidine patients; mean arterial pressure remained at 9 mmHg above baseline in propofol patients. No ventricular tachycardia occurred in the dexmedetomidine-sedated patients compared with 5% of the propofol patients (p = 0.007). Respiratory rates and blood gases were similar. Fewer dexmedetomidine patients received beta-blockers (p = 0.014), antiemetics (p = 0.015), nonsteroidal anti-inflammatory drugs (p < 0.001), epinephrine (p = 0.030), or high-dose diuretics (p < 0.001). CONCLUSION: Dexmedetomidine provided safe and effective sedation for post-CABG surgical patients and significantly reduced the use of analgesics, beta-blockers, antiemetics, epinephrine, and diuretics.     

Association between dexmedetomidine administration and outcomes in critically ill patients with sepsis-associated acute kidney injury

Study objectiveTo investigate the association between dexmedetomidine administration and outcomes in critically ill patients with sepsis-associated acute kidney injury (SA-AKI).DesignA single-center, retrospective, cohort study.SettingIntensive care unit (ICU).PatientsA total of 2192 critically ill patients with SA-AKI were included in the analysis, which identified from the Medical Information Mart for Intensive Care (MIMIC-IV) database between 2008 and 2019.InterventionsIntravenous infusion of dexmedetomidine.MeasurementsThe primary outcome was recovery of renal function. In-hospital mortality, vasopressor requirements, length of ICU and hospital stay were considered secondary outcomes. The Cox proportional hazards, logistic regression, and linear regression models were used to assess the association between dexmedetomidine and outcomes. Propensity score matching (PSM) analysis was used to match patients receiving dexmedetomidine to those without treatment.Main resultsAfter PSM, 719 matched patient pairs were derived from patients who received dexmedetomidine and those who did not. The administration of dexmedetomidine was associated with a higher rate of renal recovery [61.8% vs. 55.8%, hazard ratio (HR) 1.35; P = 0.01], reduced in-hospital mortality [28.3% vs. 41.3%, HR 0.56; P < 0.001], and prolonged intensive care unit (ICU) stay [15.8d vs 12.6d, HR 2.34; P < 0.001] and hospital stay [23.7d vs 19.7d, HR 4.47; P < 0.001]. No significant difference was found in vasopressor requirements in patients with SA-AKI. Nevertheless, results illustrated that dose receiving between 0.30 and 1.00 μg/kg/h and duration using under 48 h of dexmedetomidine was associated with improvements in renal function recovery in SA-AKI patients.ConclusionDexmedetomidine administration was associated with improvements in renal function recovery and in-hospital survival in critically ill patients with SA-AKI. The results need to be verified in further randomized controlled trials.     

Methohexital zur Analgosedierung bei beatmeten Intensivpatienten

Background

Delirium is defined by the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision (DSM-IV-TR) as a potentially reversible disturbance of consciousness and a change of cognition caused by a medical condition, drug intoxication, or medication side effect. Delirium affects up to 80?% of intensive care unit (ICU) patients and is associated with increased morbidity and mortality. One risk factor for development of delirium in ventilated intensive care unit patients is sedation. The German S3 guidelines on “Analgesie, Sedierung und Delirmanagement in der Intensivmedizin” (analgesia, sedation and delirium management in intensive care medicine) of the DGAI (German Society for Anesthesiology and Intensive Care Medicine) and the DIVI (German Interdisciplinary Association for Intensive Care and Emergency Medicine) recommend midazolam and propofol for sedation, although both drugs are associated with a high incidence of delirium.

Aim

Within the framework of this study the question arose whether the barbiturate methohexital could be associated with a lower incidence of delirium in comparison to midazolam or propofol in analgosedated and ventilated ICU patients.

Material and methods

This was a prospective nonrandomized observational cohort study in a mixed medical surgical intensive care unit. Patients ventilated within 72 h after admittance were consecutively allocated to either propofol/remifentanil versus methohexital/remifentanil (expected ventilation duration ≤?7 days) or midazolam/fentanyl versus methohexital/fentanyl (expected ventilation duration >?7 days) by the attending senior consultant anesthetist at the time of admission and/or intubation. Primary endpoint was delirium at any time during the ICU stay. Delirium was checked every 8 h by ICU nurses using the intensive care delirium screening checklist (ICDSC), with delirium defined as ICDSC ≥?4 points. Before evaluation of the ICDSC the Richmond agitation sedation scale (RASS) score and the visual analogue scale for pain (VAS target ≤?4) were measured. To assure reliable evaluation of the ICDSC, the RASS score of the patient at the time of evaluation had to be ≥???2. Assuming an incidence of delirium in the midazolam group of 70?% and in the methohexital group of 35?%, 16 patients were needed each in the midazolam/fentanyl and the methohexital/fentanyl cohorts (p?=?0.05, β =?0.1). Assuming an incidence of delirium in the propofol group of 50?% and in the methohexital group again of 35?%, 94 patients were needed in the propofol/remifentanil and methohexital/remifentanil groups, respectively (p?=?0.05, β =?0.1).

Results

A total of 222 patients were evaluated, 34 in the methohexital vs. midazolam group and 188 in the methohexital vs. propofol group. Out of 16 patients sedated with midazolam, 15 developed delirium (94?%) in contrast to only 5 out of 18 patients sedated with methohexital (28?%). Thus compared to midazolam the sedation with methohexital reduced the incidence of delirium by 66?% (p?<?0.001) corresponding to a number needed to treat (NNT) of 1.5. Out of 94 patients in the propofol/remifentanil group, 64 developed delirium (68?%) in contrast to only 23 out of 94 in the methohexital/remifentanil group (24?%). Thus compared to propofol the sedation with methohexital reduced the incidence of delirium by 44?% (p?<?0.001), corresponding to an NNT of 2.5.

Conclusion

Sedation with methohexital compared to midazolam or propofol reduced the incidence of delirium by more than 50?% in ventilated ICU patients.     

The effect of dexmedetomidine on delirium and agitation in patients in intensive care: systematic review and meta-analysis with trial sequential analysis

Delirium is common in intensive care patients. Dexmedetomidine is increasingly used for sedation in this setting, but its effect on delirium remains unclear. The primary aim of this review was to examine whether dexmedetomidine reduces the incidence of delirium and agitation in intensive care patients. We sought randomised clinical trials in MEDLINE, EMBASE, PubMed and CENTRAL from their inception until June 2018. Observational studies, case reports, case series and non-systematic reviews were excluded. Twenty-five trials including 3240 patients were eligible for inclusion in the data synthesis. In the patients who received dexmedetomidine (eight trials, 1425 patients), delirium was reduced, odds ratio (95%CI) 0.36 (0.26–0.51), p < 0.001 and high quality of evidence. The use of dexmedetomidine was associated with a reduced incidence of agitation, OR (95%CI) 0.34 (0.20–0.59), p < 0.001, moderate quality of evidence. Patients who were randomly assigned to dexmedetomidine had a significantly higher incidence of bradycardia, OR (95%CI) 2.18 (1.46–3.24), p < 0.001, moderate quality of evidence; and hypotension, OR (95%CI) 1.89 (1.48–2.41), p < 0.001, high quality of evidence. We found no evidence of an effect on mortality, OR (95%CI) 0.86 (0.66–1.10), p = 0.23, moderate quality of evidence. The trial sequential analyses for the incidence of delirium, bradycardia and hypotension was conclusive but not for the incidence of agitation and mortality. In summary, this meta-analysis suggests that dexmedetomidine reduces the incidence of delirium and agitation in intensive care patients. The general quality of evidence ranged from moderate to high.     

A comparison of single dose dexmedetomidine with propofol for the prevention of emergence delirium after desflurane anaesthesia in children

Emergence delirium is a common problem in children recovering from general anaesthesia. We performed a study comparing emergence characteristics in 100 patients who were randomly allocated to receive either 0.3 μg.kg^?1 dexmedetomidine, 1 mg.kg^?1 propofol or saline 0.9% and undergoing infra‐umbilical surgery. The Pediatric Anesthesia Emergence Delirium scale was used to grade emergence delirium. Emergence delirium occurred in 9.4% of children in the dexmedetomidine group compared with 13.9% in the propofol group and 40.6% in the control group (p = 0.004). In the dexmedetomidine group, sedation occurred in 62.5% of children at 10 min after transfer to the recovery area, compared with 44.4% in the propofol group and 12.5% in the control group (p = 0.010). We conclude that dexmedetomidine significantly reduced the incidence of emergence delirium but this was at the expense of a greater incidence of sedation in the recovery period.     

Factors contributing to a longer length of stay in adults admitted to a quaternary spinal care center

Background

Longer hospital length of stay (LOS) has been associated with worse outcomes and increased resource utilization. However, diagnostic and patient-level factors associated with LOS have not been well studied on a large scale. The goal was to identify patient, surgical and organizational factors associated with longer patient LOS for adult patients at a high-volume quaternary spinal care center.

Methods

We performed a retrospective analysis of 13,493 admissions from January 2006 to December 2019. Factors analyzed included age, sex, admission status (emergent vs scheduled), ASIA grade, operative vs non-operative management, mean blood loss, operative time, and adverse events. Specific adverse events included surgical site infection (SSI), other infection (systemic or UTI), neuropathic pain, delirium, dural tear, pneumonia, and dysphagia. Diagnostic categories included trauma, oncology, deformity, degenerative, and “other”. A multivariable linear regression model was fit to log-transformed LOS to determine independent factors associated with patient LOS, with effects expressed as multipliers on mean LOS.

Results

Mean LOS for the population (SD) was 15.8 (34.0) days. Factors significantly (p < 0.05) associated with longer LOS were advanced patient age [multiplier on mean LOS 1.011/year (95% CI: 1.007–1.015)], emergency admission [multiplier on mean LOS 1.615 (95% CI: 1.337–1.951)], ASIA grade [multiplier on mean LOS 1.125/grade (95% CI: 1.051–1.205)], operative management [multiplier on mean LOS 1.211 (95% CI: 1.006–1.459)], and the occurrence of one or more AEs [multiplier on mean LOS 2.613 (95% CI: 2.188–3.121)]. Significant AEs included postoperative SSI [multiplier on mean LOS 1.749 (95% CI: 1.250–2.449)], other infections (systemic infections and UTI combined) [multiplier on mean LOS 1.650 (95% CI: 1.359–2.004)], delirium [multiplier on mean LOS 1.404 (95% CI: 1.103–1.787)], and pneumonia [multiplier on mean LOS 1.883 (95% CI: 1.447–2.451)]. Among the diagnostic categories explored, degenerative patients experienced significantly shorter LOS [multiplier on mean LOS 0.672 (95%CI: 0.535–0.844), p < 0.001] compared to non-degenerative categories.

Conclusion

This large-scale study taking into account diagnostic categories identified several factors associated with patient LOS. Future interventions should target modifiable factors to minimize LOS and guide hospital resource allocation thereby improving patient outcomes and quality of care and decreasing healthcare-associated costs.

     

Delirium prevention program in the surgical intensive care unit improved the outcomes of older adults

Background

Hospital-acquired delirium is a known risk factor for negative outcomes in patients admitted to the surgical intensive care unit (SICU). Outcomes worsen as the duration of delirium increases. The purpose of this study was to evaluate the efficacy of a delirium prevention program and determine whether it decreased the incidence and duration of hospital-acquired delirium in older adults (age >50 y) admitted to the SICU.

Methods

A prospective pre- or post-intervention cohort study was done at an academic level I trauma center. Older adults admitted to the SICU were enrolled in a delirium prevention program. Those with traumatic brain injury, dementia, or 0 d of obtainable delirium status were excluded from analysis. The intervention consisted of multidisciplinary education, a pharmacologic protocol to limit medications associated with delirium, and a nonpharmacologic sleep enhancement protocol. Primary outcomes were incidence of delirium and delirium-free days/30. Secondary outcomes were ventilator-free days/30, SICU length of stay (LOS), daily and cumulative doses of opioids (milligram, morphine equivalents) and benzodiazepines (milligram, lorazepam equivalents), and time spent in severe pain (greater than or equal to 6 on a scale of 1 - 10). Delirium was measured using the Confusion Assessment Method for the ICU. Data were analyzed using Chi-squared and Wilcoxon rank sum analysis.

Results

Of 624 patients admitted to the SICU, 123 met inclusion criteria: 57 preintervention (3/12–6/12) and 66 postintervention (7/12–3/13). Cohorts were similar in age, gender, ratio of trauma patients, and Injury Severity Score. Postintervention, older adults experienced delirium at the same incidence (pre 47% versus 58%, P = 0.26), but for a significantly decreased duration as indicated by an increase in delirium-free days/30 (pre 24 versus 27, P = 0.002). After intervention, older adults with delirium had more vent-free days (pre 21 versus 25, P = 0.03), shorter SICU LOS (pre 13 [median 12] versus 7 [median 6], P = 0.01) and were less likely to be treated with benzodiazepines (pre 85% versus 63%, P = 0.05) with a lower daily dose when prescribed (pre 5.7 versus 3.6 mg, P = 0.04). After intervention, all older adults spent less time in pain (pre 4.7 versus 3.1 h, P = 0.02), received less total opioids (pre 401 versus 260 mg, P = 0.01), and had shorter SICU LOS (pre 9 [median 5] versus 6 [median 4], P = 0.04).

Conclusions

Although delirium prevention continues to be a challenge, this study successfully decreased the duration of delirium for older adults admitted to the SICU. Our simple, cost-effective program led to improved pain and sedation outcomes. Older adults with delirium spent less time on the ventilator and all patients spent less time in the SICU.