Early Sedation Research Articles

Early Sedation with Dexmedetomidine in Patients with Acute Myocardial Infarction Requiring Mechanical Ventilation.

Patients with acute myocardial infarction (AMI) who require invasive mechanical ventilation (IMV) represent a critically ill population with limited data on optimal sedative and analgesic use. Clinical trials assessing dexmedetomidine use exclude or poorly represent patients with AMI. This study aimed to compare the use of early sedation with dexmedetomidine to usual-care sedation in patients with AMI requiring IMV. We utilized the Vizient® Clinical Data Base to identify patients aged ≥18 years admitted between 2015 and 2019 with a primary diagnosis of AMI who required IMV. Patients receiving dexmedetomidine on the first day of IMV were included in the early dexmedetomidine group while the remaining patients were assigned to the usual care group. Inverse probability of treatment weighting (IPTW) was used to estimate adjusted risk differences between groups. We identified 15,928 patients, of which 1,620 (10.2%) received early dexmedetomidine. Patients who received early dexmedetomidine were more likely to present with cardiogenic shock (52.0% vs. 47.7%, P=0.001). In unadjusted analyses, patients receiving early dexmedetomidine had lower in-hospital mortality (33.0% vs 42.1%) and more ventilator-free days (13.6 vs 12.1) compared to usual care (both, P<0.05). After IPTW, patients receiving early dexmedetomidine had a 11.0% (95% confidence interval [CI]: 8.6% to 13.5%) lower mortality and more ventilator-free days (mean difference: +2.2 days, 95% CI: 1.6-2.8 days). Early sedation with dexmedetomidine was associated with lower mortality compared to usual care in patients with AMI requiring IMV. A randomized controlled trial of sedative agents in this population is warranted.

A randomized controlled trial investigating the impact of early goal-directed sedation dominated by dexmedetomidine on cerebral oxygen metabolism and inflammatory mediators in patients with severe brain injury.

The aim of this study is to assess the neuroprotective efficacy of early goal-directed sedation (EGDS) primarily governed by dexmedetomidine in patients experiencing severe traumatic brain injury, and to elucidate its potential underlying mechanisms. All participants were randomly allocated into two groups: the experimental group-dexmedetomidine-dominated EGDS group (group D, n = 30) and the control group-the standard propofol sedation group (group P, n = 30). Patients in the experimental group received sedation primarily with dexmedetomidine, while those in the control group received propofol sedation. Subsequently, retrograde catheterization of the internal jugular vein on the affected side was performed, blood gas analysis samples were collected, cerebral oxygen extraction rates were computed, and levels of interleukin 6 (IL-6) and interleukin 1β (IL-1β) were assessed. One-way ANOVA and Chi-square tests were used for statistical analysis. In group D, significant reductions were observed in the duration of ventilator dependency (p < 0.05).Compared to those documented in group P, tracheostomy incidence, and pulmonary infection rates were no different (p > 0.05). On the second, third and the seventh day, the SjvO2 levels in group D exhibited a statistically significant elevation compared to group P, while the CERO2 levels were notably lower in group D than in group P (p < 0.05). The GCS scores of patients in group D was significantly higher than that of the patients in group P and the baseline value on the seventh day and the time of discharge (p < 0.05). Additionally, the IL-6 levels in group D were significantly lower than those in group P and their corresponding baseline levels on the third and seventh days (p < 0.05). The IL-1β levels were no significant difference between the two groups. A predominance of dexmedetomidine in EGDS demonstrates efficacy in reducing the duration of ICU stay and ventilator dependency, enhancing cerebral oxygen metabolism, and attenuating the infiltration of inflammatory factors.

Early sedation using ciprofol for intensive care unit patients requiring mechanical ventilation: a pooled post-hoc analysis of data from phase 2 and phase 3 trials

BackgroundCiprofol was approved for use in intensive care unit (ICU) patients requiring sedation during mechanical ventilation in July 2022. A pooled post-hoc analysis of phase 2 and phase 3 trials was conducted primarily to explore hypotension-free outcome in ICU patients who required mechanical ventilation and achieved the target light sedation goal at an early stage after being sedated with ciprofol or propofol.MethodsAll eligible ICU patients who were expected to require sedation for 6–24 h were randomly assigned in a 2:1 ratio to either a ciprofol or propofol group. Ciprofol or propofol was initially infused at loading doses of 0.5 or 1.0 mg/kg followed by maintenance doses of 0.3 or 1.5 mg/kg/h. Ciprofol or propofol dosages were adjusted up or down at rates of 0.05–0.10 mg/kg/h or 0.25–0.50 mg/kg/h, respectively, to achieve the target light sedation (a Richmond Agitation-Sedation Scale of -2 to + 1). The primary post-hoc outcome was the hypotension-free rate in patients who had achieved the target sedation goal after 30-min administration of ciprofol or propofol.ResultsIn total, 174 patients were enrolled for pooled post-hoc analysis, of whom 116 and 58 were assigned to the ciprofol and propofol groups, respectively. The hypotension-free rate was significantly higher in patients who achieved the target sedation goal after 30-min administration of ciprofol (93.0% vs. 81.0%, P = 0.018), and especially in the subgroups of males and patients aged < 65 years. Multivariable analysis revealed that ciprofol treatment, a younger age and lower baseline body mass index were independent favorable predictors for a higher hypotension-free rate in patients who achieved the target sedation goal after 30-min of drug administration. Moreover, hypotension-free patients who reached the target sedation level after 30 min had a more favorable short-term prognosis including a lower incidence of drug-related treatment-emergent adverse events, shorter time to extubation and fewer dose adjustments of ciprofol or propofol (all P < 0.05).ConclusionICU patients undergoing mechanical ventilation and sedated with ciprofol had significantly lower rate of hypotension during the early phase of achieving light sedation during a 6–24 h period, leading to a more favorable short-term prognosis (within 24 h).Trial registrationPhase 2 trial (clinicaltrials.gov, NCT04147416. Registered November 1, 2019, https://classic.clinicaltrials.gov/ct2/show/NCT04147416) and phase 3 trial (clinicaltrials.gov, NCT04620031. Registered November 6, 2020, https://classic.clinicaltrials.gov/ct2/show/NCT04620031).

Association of Early Dexmedetomidine Utilization With Clinical Outcomes After Moderate-Severe Traumatic Brain Injury: A Retrospective Cohort Study.

Traumatic brain injury (TBI) is an expensive and common public health problem. Management of TBI oftentimes includes sedation to facilitate mechanical ventilation (MV) for airway protection. Dexmedetomidine has emerged as a potential candidate for improved patient outcomes when used for early sedation after TBI due to its potential modulation of autonomic dysfunction. We examined early sedation patterns, as well as the association of dexmedetomidine exposure with clinical and functional outcomes among mechanically ventilated patients with moderate-severe TBI (msTBI) in the United States. We conducted a retrospective cohort study using data from the Premier dataset and identified a cohort of critically ill adult patients with msTBI who required MV from January 2016 to June 2020. msTBI was defined by head-neck abbreviated injury scale (AIS) values of 3 (serious), 4 (severe), and 5 (critical). We described early continuous sedative utilization patterns. Using propensity-matched models, we examined the association of early dexmedetomidine exposure (within 2 days of intensive care unit [ICU] admission) with the primary outcome of hospital mortality and the following secondary outcomes: hospital length of stay (LOS), days on MV, vasopressor use after the first 2 days of admission, hemodialysis (HD) after the first 2 days of admission, hospital costs, and discharge disposition. All medications, treatments, and procedures were identified using date-stamped hospital charge codes. The study population included 19,751 subjects who required MV within 2 days of ICU admission. The patients were majority male and white. From 2016 to 2020, the annual percent utilization of dexmedetomidine increased from 4.05% to 8.60%. After propensity score matching, early dexmedetomidine exposure was associated with reduced odds of hospital mortality (odds ratio [OR], 0.59; 95% confidence interval [CI], 0.47-0.74; P < .0001), increased risk for liberation from MV (hazard ratio [HR], 1.20; 95% CI, 1.09-1.33; P = .0003), and reduced LOS (HR, 1.11; 95% CI, 1.01-1.22; P = .033). Exposure to early dexmedetomidine was not associated with odds of HD (OR, 1.14; 95% CI, 0.73-1.78; P = .56), vasopressor utilization (OR, 1.10; 95% CI, 0.78-1.55; P = .60), or increased hospital costs (relative cost ratio, 1.98; 95% CI, 0.93-1.03; P = .66). Dexmedetomidine is being utilized increasingly as a sedative for mechanically ventilated patients with msTBI. Early dexmedetomidine exposure may lead to improved patient outcomes in this population.

Use of Early Ketamine Sedation and Association With Clinical and Cost Outcomes Among Mechanically Ventilated Patients With COVID-19: A Retrospective Cohort Study.

To describe the utilization of early ketamine use among patients mechanically ventilated for COVID-19, and examine associations with in-hospital mortality and other clinical outcomes. Retrospective cohort study. Six hundred ten hospitals contributing data to the Premier Healthcare Database between April 2020 and June 2021. Adults with COVID-19 and greater than or equal to 2 consecutive days of mechanical ventilation within 5 days of hospitalization. The exposures were early ketamine use initiated within 2 days of intubation and continued for greater than 1 day. Primary was hospital mortality. Secondary outcomes included length of stay (LOS) in the hospital and ICUs, ventilator days, vasopressor days, renal replacement therapy (RRT), and total hospital cost. The propensity score matching analysis was used to adjust for confounders. Among 42,954 patients, 1,423 (3.3%) were exposed to early ketamine use. After propensity score matching including 1,390 patients in each group, recipients of ketamine infusions were associated with higher hospital mortality (52.5% vs. 45.9%, risk ratio: 1.14, [1.06-1.23]), longer median ICU stay (13 vs. 12 d, mean ratio [MR]: 1.15 [1.08-1.23]), and longer ventilator days (12 vs. 11 d, MR: 1.19 [1.12-1.27]). There were no associations for hospital LOS (17 [10-27] vs. 17 [9-28], MR: 1.05 [0.99-1.12]), vasopressor days (4 vs. 4, MR: 1.04 [0.95-1.14]), and RRT (22.9% vs. 21.7%, RR: 1.05 [0.92-1.21]). Total hospital cost was higher (median $72,481 vs. $65,584, MR: 1.11 [1.05-1.19]). In a diverse sample of U.S. hospitals, about one in 30 patients mechanically ventilated with COVID-19 received ketamine infusions. Early ketamine may have an association with higher hospital mortality, increased total cost, ICU stay, and ventilator days, but no associations for hospital LOS, vasopressor days, and RRT. However, confounding by the severity of illness might occur due to higher extracorporeal membrane oxygenation and RRT use in the ketamine group. Further randomized trials are needed to better understand the role of ketamine infusions in the management of critically ill patients.

Early sevoflurane sedation in severe COVID-19-related lung injury patients. A pilot randomized controlled trial

BackgroundThis study aimed to assess a potential organ protective effect of volatile sedation in a scenario of severe inflammation with an early cytokine storm (in particular IL-6 elevation) in patients suffering from COVID-19-related lung injury with invasive mechanical ventilation and sedation.MethodsThis is a small-scale pilot multicenter randomized controlled trial from four tertiary hospitals in Switzerland, conducted between April 2020 and May 2021. 60 patients requiring mechanical ventilation due to severe COVID-19-related lung injury were included and randomized to 48-hour sedation with sevoflurane vs. continuous intravenous sedation (= control) within 24 h after intubation. The primary composite outcome was determined as mortality or persistent organ dysfunction (POD), defined as the need for mechanical ventilation, vasopressors, or renal replacement therapy at day 28. Secondary outcomes were the length of ICU and hospital stay, adverse events, routine laboratory parameters (creatinine, urea), and plasma inflammatory mediators.Results28 patients were randomized to sevoflurane, 32 to the control arm. The intention-to-treat analysis revealed no difference in the primary endpoint with 11 (39%) sevoflurane and 13 (41%) control patients (p = 0.916) reaching the primary outcome. Five patients died within 28 days in each group (16% vs. 18%, p = 0.817). Of the 28-day survivors, 6 (26%) and 8 (30%) presented with POD (p = 0.781). There was a significant difference regarding the need for vasopressors (1 (4%) patient in the sevoflurane arm, 7 (26%) in the control one (p = 0.028)). Length of ICU stay, hospital stay, and registered adverse events within 28 days were comparable, except for acute kidney injury (AKI), with 11 (39%) sevoflurane vs. 2 (6%) control patients (p = 0.001). The blood levels of IL-6 in the first few days after the onset of the lung injury were less distinctly elevated than expected.ConclusionsNo evident benefits were observed with short sevoflurane sedation on mortality and POD. Unexpectedly low blood levels of IL-6 might indicate a moderate injury with therefore limited improvement options of sevoflurane. Acute renal issues suggest caution in using sevoflurane for sedation in COVID-19.Trial registrationThe trial was registered on ClinicalTrials.gov (NCT04355962) on 2020/04/21.

Sedation and Delirium Management in the Intensive Care Unit: A Comprehensive Review

In Intensive Care Units (ICUs), managing pain, sedation, and delirium is critical for patient comfort and outcomes. Historically, deep sedation was common, but advances in ventilator technology and shorteracting sedatives have led to a shift towards lighter sedation strategies. Delirium, often linked to oversedation, is associated with increased mortality and negative long-term outcomes, emphasizing the need for balanced approaches. Current guidelines recommend an "analgesia-first" approach, promoting lighter sedation to minimize ventilation duration and facilitate early mobilization. Preferred sedatives include propofol and dexmedetomidine, with benzodiazepines generally avoided due to their association with delirium. Research suggests that early light sedation in the ICU improves clinical outcomes, including reduced mortality, shorter ventilation, and ICU stays. However, the timing of initiating light sedation, sedation assessment tools, and the combination of sedative agents present challenges in practical implementation. Multimodal sedation approaches involving various agents at lower doses aim to enhance patient comfort while minimizing side effects. Delirium-prevention strategies, including nonpharmacological interventions, are also crucial. Frameworks like the ICU Liberation Bundle and the eCASH approach emphasize patient-centered care, early assessment and intervention, and family involvement to optimize outcomes. In conclusion, achieving optimal sedation outcomes in ICU patients requires a comprehensive strategy that combines analgesia-first principles, light sedation, multimodal approaches, and delirium prevention measures.

Association of Early Dexmedetomidine Utilization With Clinical and Functional Outcomes Following Moderate-Severe Traumatic Brain Injury: A Transforming Clinical Research and Knowledge in Traumatic Brain Injury Study.

To examine early sedation patterns, as well as the association of dexmedetomidine exposure, with clinical and functional outcomes among mechanically ventilated patients with moderate-severe traumatic brain injury (msTBI). Retrospective cohort study with prospectively collected data. Eighteen Level-1 Trauma Centers, United States. Adult (age > 17) patients with msTBI (as defined by Glasgow Coma Scale < 13) who required mechanical ventilation from the Transforming Clinical Research and Knowledge in TBI (TRACK-TBI) study. None. Using propensity-weighted models, we examined the association of early dexmedetomidine exposure (within the first 5 d of ICU admission) with the primary outcome of 6-month Glasgow Outcomes Scale Extended (GOS-E) and the following secondary outcomes: length of hospital stay, hospital mortality, 6-month Disability Rating Scale (DRS), and 6-month mortality. The study population included 352 subjects who required mechanical ventilation within 24 hours of admission. The initial sedative medication was propofol for 240 patients (68%), midazolam for 59 patients (17%), ketamine for 6 patients (2%), dexmedetomidine for 3 patients (1%), and 43 patients (12%) never received continuous sedation. Early dexmedetomidine was administered in 77 of the patients (22%), usually as a second-line agent. Compared with unexposed patients, early dexmedetomidine exposure was not associated with better 6-month GOS-E (weighted odds ratio [OR] = 1.48; 95% CI, 0.98-2.25). Early dexmedetomidine exposure was associated with lower DRS (weighted OR = -3.04; 95% CI, -5.88 to -0.21). In patients requiring ICP monitoring within the first 24 hours of admission, early dexmedetomidine exposure was associated with higher 6-month GOS-E score (OR 2.17; 95% CI, 1.24-3.80), lower DRS score (adjusted mean difference, -5.81; 95% CI, -9.38 to 2.25), and reduced length of hospital stay (hazard ratio = 1.50; 95% CI, 1.02-2.20). Variation exists in early sedation choice among mechanically ventilated patients with msTBI. Early dexmedetomidine exposure was not associated with improved 6-month functional outcomes in the entire population, although may have clinical benefit in patients with indications for ICP monitoring.

Abstract 16861: Early Sedation With Dexmedetomidine in Patients With Acute Myocardial Infarction Who Require Mechanical Ventilation

Background: Patients with acute myocardial infarction (AMI) who require mechanical ventilation (MV) are a critically ill population which require sedatives and analgesia for comfort. However, clinical trials, including those for dexmedetomidine, exclude or poorly represent patients with AMI. Research Question: Is early sedation with dexmedetomidine associated with lower hospital mortality compared to usual-care sedation in patients with AMI who require MV? Methods: We utilized the Vizient® Clinical Data Base to identify patients aged ≥18 years who were admitted between 2015 and 2019 with a primary diagnosis of AMI and required MV within 7 days of admission. Patients were assigned to the early dexmedetomidine group if they received dexmedetomidine on the first day of MV; the remaining patients were assigned to the usual care group. Inverse probability of treatment weighting (IPTW) was used to estimate adjusted risk differences between groups. Results: Of the 21,303 patients included in the study, 1,620 (7.6%) received early dexmedetomidine ( Table ). Patients who received early dexmedetomidine were younger (66 vs 67 years) and less likely to be female (29.3% vs 33.8%) (both, P &lt;0.05). Median ventilator days for early dexmedetomidine vs usual care was 4 and 3 days, respectively ( P &lt;0.001). Patients who received early dexmedetomidine had lower hospital mortality compared to usual care (33.0% vs 46.0%, P &lt;0.001) despite higher prevalence of cardiogenic shock. After IPTW, the early dexmedetomidine group had a 16.2% (95% confidence interval [CI]: 13.6%-18.7%) lower mortality. The early dexmedetomidine group had more ventilator-free days (13.6 vs 9.7, P &lt;0.001), which persisted after IPTW (mean difference: +4.9 days, 95% CI: 4.2-5.5 days). Conclusion: Early sedation with dexmedetomidine may be associated with lower mortality compared to usual care in patients with AMI who require MV. A randomized controlled trial of sedative agents in this population is warranted.

Abstract 145: Deploying Early Cooling at ICECAP Sites: A Barrier Assessment

Introduction: Best practices for implementing early temperature control in comatose survivors of cardiac arrest have yet to be defined. We surveyed sites enrolling in the Influence of Cooling Duration on Efficacy in Cardiac Arrest Patients (ICECAP) trial to understand variability in temperature control practices and identify barriers to rapid induction of cooling. Methods: A 23 question electronic survey was sent to principal investigators at 68 active ICECAP sites. Participants were queried on temperature control practices and asked to upload institutional protocols. Results: Fifty-two sites (76.5%) responded to the survey. While 45 sites (86.5%) had an institutional temperature control protocol, only 33 (63.5%) had an emergency department (ED)-specific protocol. Intravascular cooling was available at 21 sites (40.4%). The most frequent barriers to early initiation of temperature control were clinical skepticism regarding the importance of early cooling (n=32, 35.9%), insufficient nursing availability (n=18, 20.2%), lack of access to a cooling device in the ED (n=17, 19.1%), inability to achieve target temperature despite rapid connection to a cooling device (n=17, 19.1%), and delay due to procedures or intensive care unit transfer (n=5 5.6%). ED average boarding time exceeded two hours in 23 sites (44.2%). Fourteen (28%) sites did not have institutional protocols for early sedation or paralysis to help rapidly lower core body temperature during induction of temperature control. Paralytics were infrequently used during the induction phase; at the majority of sites (n=30, 61.2%) paralytics were used less than 20% of the time. Activation in the ICECAP trial resulted in quality improvements to institutional cooling protocols (n=14, 26.9%), such as purchase of cooling devices for the ED, development of sedation or paralytic protocols, and educational initiatives to shorten the time to target temperature. Conclusion: Many of the identified barriers for rapid initiation of temperature control are modifiable. Nursing and provider education regarding the importance of early cooling and development of standardized sedation and paralytic protocols may be effective strategies to improve early cooling practices.

Early sedation with dexmedetomidine in post‐operative adult intensive care unit patients

AbstractBackgroundDelirium is a leading healthcare concern in adult Intensive Care Units (ICU) and has a reported prevalence of up to 80%. Although individual studies report that early sedation with dexmedetomidine in post‐operative patients including its nocturnal administration can improve sleep quality and reduction in ICU delirium, these have not been synthesized in a systematic review.AimThe aim of this systematic review was to evaluate the effectiveness of early administration of dexmedetomidine infusion in the prevention of delirium, reduction in agitation, and improved sleep quality among post‐operative adults in ICU.Study DesignA systematic search was conducted across PubMed, CINAHL, MEDLINE, and EMBASE, together with a search for grey literature. Two authors independently screened the search results, extracted data, and assessed risk of bias (ROB). Data were meta‐analysed using RevMan 5.4 software. A simplified Cochrane approach was used in this review.ResultsFive randomized controlled trials with 2173 participants were included. ROB was assessed with the five studies included in this review. Of the five included studies, two were identified as having components with a high ROB; one study reporting high ROB in the domain of other biases, and the other study in the domains of allocation concealment as well as in the domains of blinding of participants and personnel. All other studies and domains were either low or unclear ROB. The result indicated that the incidence of delirium was reduced among the dexmedetomidine group (RR: 0.08, 95% CI −0.15 to −0.01, 3 studies, 1045 patients) when compared with those who received other medications. There was no difference in agitation (RR: 0.85, 95% CI 0.51 to 1.44, 2 studies, 779 patients), and although better sleep was associated with the dexmedetomidine group, no data focusing on the sleep quality was reported.ConclusionThe pooled result of this systematic review indicated a reduction in the incidence of delirium among ventilated patients who received early administration of dexmedetomidine post‐operatively. Although pooled sample sizes are relatively high, each outcome is based on one or two studies of primarily low or unclear ROB. Further research is warranted to determine the potential benefit of dexmedetomidine on agitation and sleep quality.Relevance to clinical practiceThe findings from this study support the use of light sedation, such as dexmedetomidine as recommended in the Society of Critical Care Medicine's guidelines.

Fentanyl-Propofol Versus Ketamine-Propofol Combination for Sedation and Recovery in ERCP: A Double-Blinded Randomized Clinical Trial

Objective: The main goal of this study was to investigate the groups receiving fentanyl-propofol (fentP) against ketamine-propofol (ketP) in ERCP in terms of sedation, rescue sedation requirement, and recovery scores. Additionally, evaluated were the procedure's hemodynamic changes, postoperative pain score, complications, and endoscopist satisfaction. Methodology: A double-blinded randomized clinical trial was undertaken at the Dr. Ruth K.M. Pfau Civil Hospital Karachi's endoscopic room (DUHS) for six months. By using OPEN EPI sample size calculator, sample size was calculated. A total of 124 patients for elective ERCP were randomized into two groups by SNOSE protocol. Groups A and B, fentanyl-propofol (fentP) and ketamine-propofol (ketP), respectively, each contain 62 patients. All patients were given a loading dose of propofol 0.5 mg/kg, followed by a 75 ug/kg/minute infusion. The group fentP received fentanyl 1ml/kg (1 ug/kg) and the group ketP received ketamine 1ml/kg (0.5mg/kg). Ramsay sedation scores, the necessity for rescue sedation, and the Aldrete score post-operatively were noted. Hemodynamics during surgery and complications were also noted. Results: Sedation began noticeably earlier than usual in the group B at 0, 2 and 4 minutes (p-value &lt;0.05), whereas sedation scores were higher in the group A at 8,10, and 15 minutes (p-value &lt;0.05). Early sedation in the group B led to less consumption of rescue sedation doses (p-value &lt;0.01). However, recovery scores were comparable in each groups (p-value &gt;0.05). Conclusion: We were able to conclude that during ERCP, ketP had a significantly faster sedative onset than fentP, with less complication and a quicker recovery. Keywords: Propofol, KetP, FentP, ketamine, fentanyl, Sedation, Analgesia, ERCP, Monitored Anesthesia care.

Health Status Perception and Psychological Sequelae in Buried Victims: An Observational Study on Survivors of the Earthquake in Amatrice (Italy), Three Years Later.

The extrication from rubble is particularly critical for the survival of the victims of an earthquake. Early repeated infusion of sedative agents (SAs) in the acute trauma phase may interfere with neural processes leading to posttraumatic stress disorder (PTSD). This study aimed to analyze the psychological status reported by the buried victims of the earthquake in Amatrice (August 24, 2016; Italy) by considering type of the SAs administered during the extrication maneuvers. This was an observational study on data from 51 patients directly rescued under the rubble during the earthquake in Amatrice. During extrication maneuvers, a moderate sedation was administered by titrating ketamine (0.3-0.5mg/kg) or morphine (0.1-0.15mg/kg) with respect to the Richmond Agitation and Sedation Scale (RASS; between -2 and -3) in buried victims.Three years following the rescue, the survivors were interviewed on their perceived health status and stress using a questionnaire which consisted of 17 items: the standard four-item set of healthy days core questions (CDC HRQOL-4); the 12-item General Health Questionnaire (GHQ-12); and in addition, survivors were asked if they had a diagnosis for anxiety, depression, or for PTSD. The study analyzed data from the complete clinical documentation of 51 survivors; 30 were males and 21 females, with an average age of 52 years. Twenty-six (26) subjects were treated with ketamine, while 25 were treated with morphine, during the extrication procedures. Concerning the quality-of-life analysis, only 10 survivors out of 51 perceived their health status as good; the others reported psychological disorders. The GHQ-12 scores showed that all survivors had psychological distress with a mean total score of 22.2 (SD = 3.5). Eighteen (18) victims declared to have had a diagnosis of generalized anxiety (35%), while 29 were treated for depression (57%) and PTSD (57%) by a specialist. With regards to the perceived distress level and the anxiety disorder, this analysis showed significant associations with SAs used during extrication, with a better performance for ketamine than for morphine. These findings suggest investigating whether early sedation with ketamine directly in the disaster setting may promote the prophylaxis and reduce the risk of developing trauma-related disorders (TRDs) on the buried victims of major natural disasters in future studies.

Early Light Sedation Increased the Duration of Mechanical Ventilation in Patients With Severe Lung Injury.

The international guidelines recommend light sedation management for patients receiving mechanical ventilation. One of the benefits of light sedation management during mechanical ventilation is the preservation of spontaneous breathing, which leads to improved gas-exchange and patient outcomes. Conversely, recent experimental animal studies have suggested that strong spontaneous breathing effort may cause worsening of lung injury, especially in severe lung injury cases. The association between depth of sedation and patient outcomes may depend on the severity of lung injury. This study aimed to describe the patients' clinical outcomes under deep or light sedation during the first 48 h of mechanical ventilation and investigate the association of light sedation on patient outcomes for each severity of lung injury. The researchers performed a retrospective observational study at a university hospital in Japan. Patients aged ≥20 years, who received mechanical ventilation for at least 48 h were enrolled. A total of 413 patient cases were analyzed. Light sedation was associated with significantly shorter 28-day ventilator-free days compared with deep sedation in patients with severe lung injury (0 [IQR 0-5] days vs. 16 [0-19] days, P = .038). In the groups of patients with moderate and mild lung injury, the sedation depth was not associated with ventilator-free days. After adjusting for the positive end-expiratory pressure and APACHE II score, it was found that light sedation decreased the number of ventilator-free days in patients with severe lung injury (-10.8 days, 95% CI -19.2 to -2.5, P = .012). Early light sedation for severe lung injury may be associated with fewer ventilator-free days.

The Profile of Early Sedation Depth and Clinical Outcomes of Mechanically Ventilated Patients in Korea.

Current international guidelines recommend against deep sedation as it is associated with worse outcomes in the intensive care unit (ICU). However, in Korea the prevalence of deep sedation and its impact on patients in the ICU are not well known. From April 2020 to July 2021, a multicenter, prospective, longitudinal, noninterventional cohort study was performed in 20 Korean ICUs. Sedation depth extent was divided into light and deep using a mean Richmond Agitation-Sedation Scale value within the first 48 hours. Propensity score matching was used to balance covariables; the outcomes were compared between the two groups. Overall, 631 patients (418 [66.2%] and 213 [33.8%] in the deep and light sedation groups, respectively) were included. Mortality rates were 14.1% and 8.4% in the deep and light sedation groups (P = 0.039), respectively. Kaplan-Meier estimates showed that time to extubation (P < 0.001), ICU length of stay (P = 0.005), and death (P = 0.041) differed between the groups. After adjusting for confounders, early deep sedation was only associated with delayed time to extubation (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.55-0.80; P < 0.001). In the matched cohort, deep sedation remained significantly associated with delayed time to extubation (HR, 0.68; 95% CI, 0.56-0.83; P < 0.001) but was not associated with ICU length of stay (HR, 0.94; 95% CI, 0.79-1.13; P = 0.500) and in-hospital mortality (HR, 1.19; 95% CI, 0.65-2.17; P = 0.582). In many Korean ICUs, early deep sedation was highly prevalent in mechanically ventilated patients and was associated with delayed extubation, but not prolonged ICU stay or in-hospital death.

Early Sedation Depth and Clinical Outcomes in Mechanically Ventilated Patients in a Hospital: Retrospective Cohort Study

This study aimed to identify the early sedation depth in the first 48hours of mechanical ventilation and its relationship to clinical outcomes to promote the transition to light sedation. This retrospective single-center cohort study was conducted in two medical intensive care units (MICUs) at a general tertiary hospital, using a standardized sedation protocol. To investigate the early sedation depth, the Sedation Index was used, which can indicate changes over the first 48hours. Patients were divided into three groups based on tertiles of Sedation Index. The primary outcome was mortality at 30, 90, and 180 days. The secondary outcomes included length of stay in the ICU and ventilator-free days. Kaplan-Meier analysis and multivariable Cox regression were conducted to compare factors influencing mortality. This study included 394 patients. The deepest sedation group showed more severe illness, delirium, and deeper sedation at admission (p<.001). The survival curve decreased as sedation increased, even within the light sedation levels. In the deepest sedation group, 30-day mortality (hazard ratio [HR] 2.11, 95% confidence interval [CI] 1.33-3.34), 90-day mortality (HR 2.00, 95% CI 1.31-3.06), and 180-day mortality (HR 1.77, 95% CI 1.17-2.67) increased. The length of stay in the ICU and ventilator-free days did not show statistical differences. These results indicate that early deep sedation is a modifiable factor that can potentially affect mortality. The protocol for inducing the transition into light sedation must comply with recommendations to improve clinical outcomes.

Isoflurane vs. propofol for sedation in invasively ventilated patients with acute hypoxemic respiratory failure: an a priori hypothesis substudy of a randomized controlled trial

BackgroundAcute hypoxemic respiratory failure (AHRF) is a leading concern in critically ill patients. Experimental and clinical data suggest that early sedation with volatile anesthestics may improve arterial oxygenation and reduce the plasma and alveolar levels of markers of alveolar epithelial injury and of proinflammatory cytokines.MethodsAn a priori hypothesis substudy of a multicenter randomized controlled trial (The Sedaconda trial, EUDRA CT Number 2016-004551-67). In the Sedaconda trial, 301 patients on invasive mechanical ventilation were randomized to 48 h of sedation with isoflurane or propofol in a 1:1 ratio. For the present substudy, patients with a ratio of arterial pressure of oxygen (PaO2) to inspired fraction of oxygen (FiO2), PaO2/FiO2, of ≤ 300 mmHg at baseline were included (n = 162). The primary endpoint was the change in PaO2/FiO2 between baseline and the end of study sedation. A subgroup analysis in patients with PaO2/FiO2 ≤ 200 mmHg was performed (n = 82).ResultsBetween baseline and the end of study sedation (48 h), oxygenation improved to a similar extent in the isoflurane vs. the propofol group (isoflurane: 199 ± 58 to 219 ± 76 mmHg (n = 70), propofol: 202 ± 62 to 236 ± 77 mmHg (n = 89); p = 0.185). On day seven after randomization, PaO2/FiO2 was 210 ± 79 mmHg in the isoflurane group (n = 41) and 185 ± 87 mmHg in the propofol group (n = 44; p = 0.411). In the subgroup of patients with PaO2/FiO2 ≤ 200 mmHg, PaO2/FiO2 increase between baseline and end of study sedation was 152 ± 33 to 186 ± 54 mmHg for isoflurane (n = 37), and 150 ± 38 to 214 ± 85 mmHg for propofol (n = 45; p = 0.029). On day seven, PaO2/FiO2 was 198 ± 69 mmHg in patients randomized to isoflurane (n = 20) and 174 ± 106 mmHg in patients randomized to propofol (n = 20; p = 0.933). Both for the whole study population and for the subgroup with PaO2/FiO2 ≤ 200 mmHg, no significant between-group differences were observed for PaCO2, pH and tidal volume as well as 30-day mortality and ventilator-free days alive.ConclusionsIn patients with AHRF, inhaled sedation with isoflurane for a duration of up to 48 h did not lead to improved oxygenation in comparison to intravenous sedation with propofol.Trial registration The main study was registered in the European Medicines Agency’s EU Clinical Trial register (EudraCT), 2016-004551-67, before including the first patient. The present substudy was registered at German Clinical Trials Register (DRKS, ID: DRKS00018959) on January 7th, 2020, before opening the main study data base and obtaining access to study results.

In this Issue of CCR

Point of View: A four-step model to aid teaching, clinical assessment and communication of circulatory disorders amongst junior clinicians Editorial: Midodrine – why don't you just work better? Review: Midodrine Use in Critically Ill Patients – A Narrative Review Original Articles: Study protocol and statistical analysis plan for the 20% Human Albumin Solution Fluid Bolus Administration Therapy in Patients after Cardiac Surgery-II (HAS FLAIR-II) trial Early sedation in traumatic brain injury: a multicentre international observational study The association between vital signs abnormalities during post-anaesthesia care unit stay and deterioration in the general ward following major abdominal cancer surgery assessed by continuous wireless monitoring Mortality associated with Acute Respiratory Distress Syndrome 2009-2019: A systematic review and meta-analysis The prevalence of post extubation dysphagia in critically ill adults: An Australian data linkage study ANTIPORT: adaptation of a transfusion prediction score to an Australian cardiac surgery population

Stress response during early sedation with dexmedetomidine compared with usual-care in ventilated critically ill patients

BackgroundSedative agents may variably impact the stress response. Dexmedetomidine is a sympatholytic alpha2-adrenergic agonist mainly used as a second-line sedative agent in mechanically ventilated patients. We hypothesised that early sedation with dexmedetomidine as the primary agent would result in a reduced stress response compared to usual sedatives in critically ill ventilated adults.MethodsThis was a prospective sub-study nested within a multi-centre randomised controlled trial of early sedation with dexmedetomidine versus usual care. The primary outcome was the mean group differences in plasma levels of stress response biomarkers measured over 5 days following randomisation. Other hormonal, biological and physiological parameters were collected. Subgroup analyses were planned for patients with proven or suspected sepsis.ResultsOne hundred and three patients were included in the final analysis. Baseline illness severity (APACHE II score), the proportion of patients receiving propofol and the median dose of propofol received were comparable between groups. More of the usual-care patients received midazolam (57.7% vs 33.3%; p = 0.01) and at higher dose (median (95% interquartile range) 0.46 [0.20–0.93] vs 0.14 [0.08–0.38] mg/kg/day; p < 0.01). The geometric mean (95% CI) plasma level of the stress hormones, adrenaline (0.32 [0.26–0.4] vs 0.38 [0.31–0.48]), noradrenaline (4.27 [3.12–5.85] vs 6.2 [4.6–8.5]), adrenocorticotropic hormone (17.1 [15.1–19.5] vs 18.1 [15.9–20.5]) and cortisol (515 [409–648] vs 618 [491–776)] did not differ between dexmedetomidine and usual-care groups, respectively. There were no significant differences in any other assayed biomarkers or physiological parameters Sensitivity analyses showed no effect of age or sepsis.ConclusionsEarly sedation with dexmedetomidine as the primary sedative agent in mechanically ventilated critically ill adults resulted in comparable changes in physiological and blood-borne parameters associated with the stress-response as with usual-care sedation.

Association of early sedation level with patient outcomes in moderate-to-severe acute respiratory distress syndrome: Propensity-score matched analysis.

PurposeStudies of early depth of sedation in mixed critically ill populations have suggested benefit to light sedation; however, the relationship of early depth of sedation with outcomes in patients with acute respiratory distress syndrome (ARDS) is unknown.Materials and methodsWe performed a propensity-score matched analysis of early light sedation (Richmond Agitation Sedation Scale Score, RASS 0 to −1 or equivalent) versus deep sedation (RASS −2 or lower) in patients enrolled in the non-intervention group of The Reevaluation of Systemic Early Neuromuscular Blockade trial. Primary outcome was 90 day mortality. Secondary outcomes included days free of mechanical ventilation, days not in ICU, days not in hospital at day 28.Results137 of 486 participants (28.2%) received early light sedation. Vasopressor usage and Apache III scores significantly differed between groups. Prior to matching, 90-day mortality was higher in the early deep sedation (45.3%) compared to light sedation (34.2%) group. In the propensity score matched cohort, there was no difference in 90-day mortality (Odds Ratio (OR) 0.72, 95% CI 0.41, 1.27, p = 0.26) or secondary outcomes between the groups.ConclusionsWe did not find an association between early depth of sedation and clinical outcomes in this cohort of patients with moderate-to-severe ARDS.