Target Sedation Research Articles

Efficacy and Safety of Ciprofol Sedation in ICU Patients Undergoing Mechanical Ventilation: A Multicenter, Single-Blind, Randomized, Noninferiority Trial.

To determine the effectiveness and safety of ciprofol for sedating patients in ICUs who required mechanical ventilation (MV). A multicenter, single-blind, randomized, noninferiority trial. Twenty-one centers across China from December 2020 to June 2021. A total of 135 ICU patients 18 to 80 years old with endotracheal intubation and undergoing MV, who were expected to require sedation for 6-24 hours. One hundred thirty-five ICU patients were randomly allocated into ciprofol (n = 90) and propofol (n = 45) groups in a 2:1 ratio. Ciprofol or propofol were IV infused at loading doses of 0.1 mg/kg or 0.5 mg/kg, respectively, over 4 minutes ± 30 seconds depending on the physical condition of each patient. Ciprofol or propofol were then immediately administered at an initial maintenance dose of 0.3 mg/kg/hr or 1.5 mg/kg/hr, to achieve the target sedation range of Richmond Agitation-Sedation Scale (+1 to -2). Besides, continuous IV remifentanil analgesia was administered (loading dose: 0.5-1 μg/kg, maintenance dose: 0.02-0.15 μg/kg/min). Of the 135 patients enrolled, 129 completed the study. The primary endpoint-sedation success rates of ciprofol and propofol groups were 97.7% versus 97.8% in the full analysis set (FAS) and were both 100% in per-protocol set (PPS). The noninferiority margin was set as 8% and confirmed with a lower limit of two-sided 95% CI for the inter-group difference of -5.98% and -4.32% in the FAS and PPS groups. Patients who received ciprofol had a longer recovery time (p = 0.003), but there were no differences in the remaining secondary endpoints (all p > 0.05). The occurrence rates of treatment-emergent adverse events (TEAEs) or drug-related TEAEs were not significantly different between the groups (all p > 0.05). Ciprofol was well tolerated, with a noninferior sedation profile to propofol in Chinese ICU patients undergoing MV for a period of 6-24 hours.

548 Volatile Sedation in the Burn Intensive Care Unit: A Quality Improvement Initiative

Abstract Introduction Achieving optimal sedation and analgesia in patients with major burn injuries can be challenging. Reliance on benzodiazepines results in longer durations of mechanical ventilation, delirium and withdrawal. Recent evidence and local experience in our critical care unit has supported the application of volatile agents such as isoflurane for sedation. A local audit determined that 70% of mechanically ventilated patients in our burn center are managed on 3 or more continuous sedative infusions. The aim of this initiative was to reduce the number of continuous sedative infusions to maintain target sedation range (SAS 2-4) by 25% in the 48 hour period following initiation of isoflurane. Methods A multifaceted education approach was applied to engage all bedside staff, including burn surgeons, respiratory therapists and nurses. Training occurred though self-directed modules, in-person learning and just-in-time training upon new patient initiation. Data from the 18 month period since implementation were collected retrospectively via manual chart review. Results Since implementation in March 2021, 18 patients were sedated using isoflurane in our burn intensive care unit (ICU). Within 48 hours of isoflurane initiation, 50% (9/18) of patients had a decrease in the number of sedative infusions and 56% (10/18) obtained an optimal level of sedation using isoflurane and hydromorphone alone. Conclusions Volatile agents provide a safe and reliable method of sedation in mechanically ventilated patients with major burn injuries. Despite limitations related to specialized equipment and training, the introduction of this strategy has been well received, with positive feedback relating to both ease of implementation and titration. Applicability of Research to Practice Patients with major burn injuries require multiple painful surgeries and dressing changes. Volatile sedation has been shown to reduce the number of sedative infusions, specifically, our reliance on benzodiazepines.

Efficacy and safety of remimazolam for procedural sedation during ultrasound-guided transversus abdominis plane block and rectus sheath block in patients undergoing abdominal tumor surgery: a single-center randomized controlled trial

BackgroundTo explore the efficacy and safety of remimazolam for procedural sedation during ultrasound-guided nerve block administration in patients undergoing abdominal tumor surgery, in order to improve and optimize remimazolam use in procedural sedation and clinical anesthesia.MethodsThe enrolled patients were randomly divided into three groups: 50 patients in the remimazolam group (R group), 50 patients in the dexmedetomidine group (D group), and 50 patients in the midazolam group (M group). Before administering an ultrasound-guided nerve block, all patients received sufentanil AND remimazolam or midazolam or dexmedetomidine. Remimazolam 5 mg was administered intravenously in group R, dexmedetomidine 0.6 µg/kg was administered intravenously in group D, and midazolam 0.025 mg/kg was administered intravenously in group M. Sedation was evaluated by the Modified Observer’s Assessment of Alertness and Sedation scale.When the Modified Observer’s Alertness/Sedation (MOAA/S) score was ≤ 2, block operation was started. If the target sedation level was not reached, rescue sedatives of remimazolam 2.5 mg may be intravenously given in group R, dexmedetomidine 0.4 µg/kg be intravenously given in group D, 0.01 mg/kg midazolam may be intravenously given in Group M. Hemodynamic indicators (systolic and diastolic blood pressure, heart rate), pulse oxygen saturation, depth of anesthesia (Narcotrend), MOAA/S,and the incidences of hypoxemia, injection pain, bradycardia and requirement for rescue sedatives were monitored and recorded.ResultsCompared with the control groups (midazolam and dexmedetomidine groups), the Narcotrend index and MOAA/S decreased more in the remimazolam group (P < 0.01). Compared with the control groups, the incidence of hypoxemia and injection pain was slightly higher in the remimazolam group, but the difference was not statistically significant (P > 0.05). Compared with the dexmedetomidine group, the incidence of bradycardia was significantly lower in the remimazolam group.ConclusionRemimazolam can be used safely for procedural sedation during ultrasound-guided nerve block administration in patients undergoing abdominal tumor surgery. The sedation effect is better than that with either midazolam or dexmedetomidine, and sedation can be achieved quickly without obvious hemodynamic fluctuations. Remimazolam is associated with better heart rate stability, and slightly higher incidences of hypoxemia and injection pain than are midazolam and dexmedetomidine (no statistically significant difference). The higher incidence of hypoxemia with remimazolam may be related to enhanced sufentanil opioid analgesia, and the mechanism of injection pain with remimazolam must be studied further and clarified.Trial registrationThis study was approved by the Ethics Committee of Anhui Provincial Cancer Hospital (Ethical Review 2021, No. 23) and registered at https://www.chictr.org.cn (ChiCTR2000035388). The pre-registration time of this experiment is 09/08/2020, due to ethical committee of the hospital met irregularly,the ethical approval time is 21/06/2021. The recruitment of patients began after the ethical approval (21/06/2021) and registration update (06/07/2021).The study protocol followed the CONSORT guidelines. The study protocol was performed in the relevant guidelines.

Nonconvulsive status epilepticus following cardiac arrest—are we missing the beginning?

Abstract Background Status epilepticus (SE) is a common complication in patients surviving a cardiac arrest, but little is known about the frequency of nonconvulsive status epilepticus (NCSE). Objectives To compile the first the evidence from the literature of the overall frequency of NCSE in adults with persistent coma following cardiac arrest. Secondarily, to assess the emergence of NCSE in comatose resuscitated patients within the first hours of the return of spontaneous circulation (ROSC) and before inducing target temperature management. Material and methods The medical search engine PubMed was screened to identify prospective and retrospective studies in English reporting on the frequency of NCSE in comatose post-resuscitated patients. Study design, time of EEG performance, detection of SE and NCSE, outcomes, and targeted temperature management were assessed. Results Only three cohort studies (one prospective and two retrospective) reported on the EEG evaluation describing NCSE during ongoing sedation and target temperature management. Overall, we identified 213 patients with SE in 18–38% and NCSE in 5–12%. Our review found no study reporting NCSE in resuscitated adult patients remaining in coma within the first hours of ROSC and prior to targeted temperature management and sedation. Conclusion Studies of NCSE after ROSC in adults are rare and mostly nonsystematic. This and the low proportion of patients reported having NCSE following ROSC suggest that NCSE before target temperature management and sedation is often overlooked. The limited quality of the data does not allow firm conclusions to be drawn regarding the effects of NCSE on outcome calling for further investigations. Clinicians should suspect NCSE in patients with persistent coma before starting sedation and targeted temperature management.

A Narrative Review of the Impact of Extracorporeal Membrane Oxygenation on the Pharmacokinetics and Pharmacodynamics of Critical Care Therapies.

Extracorporeal membrane oxygenation (ECMO) utilization is increasing on a global scale, and despite technological advances, minimal standardized approaches to pharmacotherapeutic management exist. This objective was to create a comprehensive review for medication dosing in ECMO based on the most current evidence. A literature search of PubMed was performed for all pertinent articles prior to 2022. The following search terms were utilized: ECMO, pharmacokinetics, pharmacodynamics, sedation, analgesia, antiepileptic, anticoagulation, antimicrobial, antifungal, nutrition. Retrospective cohort studies, case-control studies, case series, case reports, and ex vivo investigations were reviewed. PubMed (1975 through July 2022) was the database used in the literature search. Non-English studies were excluded. Search terms included both drug class categories, specific drug names, ECMO, and pharmacokinetics. Medications with high protein binding (>70%) and high lipophilicity (logP > 2) are associated with circuit sequestration and the potential need for dose adjustment. Volume of distribution changes with ECMO may also impact dosing requirements of common critical care medications. Lighter sedation targets and analgosedation may help reduce sedative and analgesia requirements, whereas higher antiepileptic dosing is recommended. Vancomycin is minimally affected by the ECMO circuit and recommendations for dosing in critically ill adults are reasonable. Anticoagulation remains challenging as optimal aPTT goals have not been established. This review describes the anticipated impacts of ECMO circuitry on sedatives, analgesics, anticoagulation, antiepileptics, antimicrobials, antifungals, and nutrition support and provides recommendations for drug therapy management. Medication pharmacokinetic/pharmacodynamic parameters should be considered when determining the potential impact of the ECMO circuit on attainment of therapeutic effect and target serum drug concentrations, and should guide therapy choices and/or dose adjustments when data are not available.

Remimazolam besylate versus propofol for long-term sedation during invasive mechanical ventilation: a pilot study

ObjectiveThe aim of this study was to evaluate the efficacy and safety of remimazolam besylate compared with propofol in maintaining mild-to-moderate sedation in patients receiving long-term mechanical ventilation.MethodsIn this single-centered randomized pilot study, adult patients mechanically ventilated longer than 24 h were randomized to receive remimazolam besylate or propofol. The target sedation range was − 3 to 0 on the Richmond Agitation and Sedation Scale (RASS). The primary outcome was the percentage of time in the target sedation range without rescue sedation. The secondary outcomes were ventilator-free days at day 7, the length of ICU stay and 28-day mortality.ResultsThirty patients were assigned to each group. No difference was identified between the remimazolam group and propofol group in median age [60.0 (IQR, 51.5–66.3) years vs. 64.0 (IQR, 55.0–69.3) years, respectively, p = 0.437] or the median duration of study drug infusion [55.0 (IQR, 28.3–102.0) hours vs. 41.0 (IQR, 24.8–74.3) hours, respectively, p = 0.255]. The median percentage of time in the target RASS range without rescue sedation was similar in remimazolam and propofol groups [73.2% (IQR, 41.5–97.3%) vs. 82.8% (IQR, 65.6–100%), p = 0.269]. No differences were identified between the two groups in terms of ventilator-free days at day 7, length of ICU stay, 28-day mortality or adverse events.ConclusionsThis pilot study suggested that remimazolam besylate was effective and safe for long-term sedation in mechanically ventilated patients compared with propofol.

Efficacy and Safety of Remimazolam Besylate versus Dexmedetomidine for Sedation in Non-Intubated Older Patients with Agitated Delirium After Orthopedic Surgery: A Randomized Controlled Trial

PurposeThe purpose of the present study was to investigate the efficacy and safety of remimazolam besylate compared with dexmedetomidine for the relief of agitated delirium in non-intubated older patients after orthopedic surgery.Patients and methodsSeventy-five patients were randomly divided into two groups. Patients assigned to the remimazolam group received a loading dose of 0.075 mg/kg remimazolam besylate over 1 minute, followed by a continuous infusion of 0.1 to 0.3 mg/kg/h. Subjects randomized to the dexmedetomidine group received a loading infusion of 0.5 μg/kg dexmedetomidine over 10 minutes, followed by a maintenance dose of 0.2 to 0.7 μg/kg/h. Meanwhile, RASS score-guided dose titration was followed. To assess the efficacy of the study drugs in terms of time to resolution of agitation, time to first achievement of target sedation, percentage of time within the target sedation range, and time to delirium resolution. Safety of the sedatives was evaluated by adverse events during hospitalization.ResultsTime to resolution of agitation did not differ between the two groups. The time to first achievement of target sedation was 19.0 (9.5 to 31.0) minutes for remimazolam besylate vs 43.5 (15.0 to 142.5) minutes for dexmedetomidine (P < 0.001). Percentage of time within the target sedation range was 77.8% for remimazolam besylate-treated patients and 67.4% for dexmedetomidine-treated patients (P = 0.001). Patients in the remimazolam group had longer time to delirium resolution (29.5 [21.3 to 32.5] hours) than those in the dexmedetomidine group (22.8 [18.9 to 28.5] hours) (P = 0.042). Patients sedated with remimazolam besylate had more oversedation (P = 0.036) but less hypotension (P = 0.007).ConclusionCompared with dexmedetomidine, remimazolam besylate was equally effective in relieving agitation, and resulted in earlier achievement of sedation goal and more controllable sedation. Remimazolam may be an ideal agent for obtaining rapid tranquillisation.

Prospective comparison of acupuncture with sham acupuncture to determine impact on sedation and analgesia in mechanically ventilated critically ill patients (PASSION study): protocol for a randomised controlled trial

IntroductionSedation and analgesia are recommended to be employed in the intensive care unit (ICU) to enhance patient comfort and safety, facilitate mechanical ventilation and reduce oxygen demands. However, the increasing...

Safety and Feasibility of AnaConDa™ to Deliver Inhaled Isoflurane for Sedation in Patients Undergoing Elective Postoperative Mechanical Ventilation: A Prospective, Open-label, Interventional Trial (INSTINCT I Study).

AimSedation is essential during invasive mechanical ventilation, and conventionally intravenous analgesic and sedative drugs are used. Sedation with inhaled anesthetics using anesthesia conserving device (ACD) is an alternative. There is no data on the safety and ease of use of AnaConDa™ from India.Materials and methodsAfter IEC approval and informed consent, we used AnaConDa™-S for Isoflurane sedation in 50 hemodynamically stable (need for <0.5 µg/kg/min of Noradrenaline infusion), ASA I and II patients aged 18–80 years, undergoing elective mechanical ventilation for up to 24 hours after elective oncosurgeries. Patients with mental obtundation (GCS <14), or if pregnant, were excluded. The primary outcome was time spent between RASS scores of -3 and -4, while secondary outcomes were incidence of delirium, technical problems with AnaConDa™, and adverse systemic effects of isoflurane. Bolus doses of isoflurane 0.2–0.5 mL were given if the Richmond agitation sedation scale (RASS) score was not achieved.ResultsFifty patients received isoflurane infusion for a median of 720 (IQR 630–900) minutes, and all remained in the target sedation range. Median time to awakening [19 (IQR, 5–85) minutes], to follow simple verbal commands [20 (IQR 5–180) minutes], and extubation after stopping the infusion of isoflurane was quick [100 (10–470) minutes]. All patients remained hemodynamically stable. None of the patients had delirium.ConclusionTarget sedation levels were achieved with initial boluses of isoflurane using AnaConDa™-S. Isoflurane sedation delivery using AnaConDa™-S is safe and feasible.How to cite this articleKulkarni AP, Bhosale SJ, Kalvit KR, Sahu TK, Mohanty R, Dhas MM, et al. Safety and Feasibility of AnaConDa™ to Deliver Inhaled Isoflurane for Sedation in Patients Undergoing Elective Postoperative Mechanical Ventilation: A Prospective, Open-label, Interventional Trial (INSTINCT I Study). Indian J Crit Care Med 2022;26(8):906–912.

High initial target blood concentration in target-controlled infusion: A randomized controlled trial.

ObjectiveOur previously modified propofol intravenous sedation (IVS) method using a target‐controlled infusion (TCI) pump with initial target blood concentration (TBC) set at 2.2 μg/ml enables the prediction of the personal optimal intraoperative TBC during induction with a minimal gap. This study aimed to verify whether this method can be useful in case of higher initial TBCs to reduce induction time.MethodsForty‐five patients scheduled to undergo oral surgery under IVS with propofol were randomly divided into three groups (group 1, TCI started with TBC set at 2.2 μg/ml; group 2, TBC was set at 2.6 μg/ml; group 3, TBC was set at 3.0 μg/ml). Immediately after reading the calculated brain concentration when the target sedation was achieved (value A), the initial TBC was manually reset to value A. We manually controlled the intraoperative TBC to maintain moderate sedation, according to the clinical signs and bispectral index values. Of the regulated TBC values, the value farthest from value A was defined as value B. The maximum discrepancy between values B and A and the induction time were compared among the three groups.ResultsThe maximum discrepancy (mean ± standard deviation [SD]) was significantly larger in group 3 (1.0 ± 1.3 μg/ml, p = .005) and group 2 (0.8 ± 0.2 μg/ml p = .008) than in group 1 (0.5 ± 0.3 μg/ml). The induction time (mean ± SD) was significantly shorter in group 3 (124 ± 126 min, p = .004) and group 2 (135 ± 33 min, p = .006) than in group 1 (245 ± 1913 min). With the initial TBC set at 2.6 μg/ml, the maximum discrepancy was large at 0.8 μg/ml, but with a small SD (0.2 μg/ml).ConclusionConsidering this discrepancy, this method with an initial TBC set at 2.6 μg/ml may be acceptable for clinical use for moderate sedation (UMIN 000017197).

Adherence to Sedation Targets With Weight-Based Propofol and Dexmedetomidine in Patients With Morbid Obesity.

Propofol and dexmedetomidine are routinely used in intensive care units (ICUs). Both are lipophilic, potentially leading to accumulation in adipose tissue. Limited evidence exists on what body weight to utilize in patients with morbid obesity. The purpose of this research was to evaluate the safety and efficacy of weight-based sedation with propofol and dexmedetomidine in ICU patients with morbid obesity. Retrospective review of ICU patients admitted from January 2018 to January 2020 who were sedated for ≥48 hours was performed. The primary outcome was the percentage of time within target sedation during the first 48 hours, stratified by body mass index (BMI) <40 or ≥40 kg/m2. Additional outcomes included adverse events and the infusion rate to achieve target sedation. Data were evaluated using descriptive statistics. A total of 80 patients were analyzed. Patients on propofol with a BMI <40 kg/m2 were in their target Richmond Agitation-Sedation Scale (RASS) 11.7% versus 16.1% with a BMI ≥40 kg/m2 (P = .580). Patients with a BMI <40 kg/m2 on dexmedetomidine were in their target RASS 27.6% versus 10.7% with a BMI ≥40 kg/m2 (P = .053). Body mass index did not significantly alter propofol target sedation attainment. However, patients with morbid obesity on dexmedetomidine demonstrated significantly less time in target sedation. An actual body weight dosing strategy of these drugs did not achieve desired target sedation for those with a BMI ≥40 versus BMI <40 kg/m2. These findings support future research on the optimal sedation dosing strategy in this patient population.

Sequential use of midazolam and dexmedetomidine for long-term sedation may reduce weaning time in selected critically ill, mechanically ventilated patients: a randomized controlled study

BackgroundCurrent sedatives have different side effects in long-term sedation. The sequential use of midazolam and dexmedetomidine for prolonged sedation may have distinct advantages. We aimed to evaluate the efficacy and safety of the sequential use of midazolam and either dexmedetomidine or propofol, and the use of midazolam alone in selected critically ill, mechanically ventilated patients.MethodsThis single-center, randomized controlled study was conducted in medical and surgical ICUs in a tertiary, academic medical center. Patients enrolled in this study were critically ill, mechanically ventilated adult patients receiving midazolam, with anticipated mechanical ventilation for ≥ 72 h. They passed the spontaneous breathing trial (SBT) safety screen, underwent a 30-min-SBT without indication for extubation and continued to require sedation. Patients were randomized into group M-D (midazolam was switched to dexmedetomidine), group M-P (midazolam was switched to propofol), and group M (sedation with midazolam alone), and sedatives were titrated to achieve the targeted sedation range (RASS − 2 to 0).ResultsTotal 252 patients were enrolled. Patients in group M-D had an earlier recovery, faster extubation, and more percentage of time at the target sedation level than those in group M-P and group M (all P < 0.001). They also experienced less weaning time (25.0 h vs. 49.0 h; HR1.47, 95% CI 1.05 to 2.06; P = 0.025), and a lower incidence of delirium (19.5% vs. 43.8%, P = 0.002) than patients in group M. Recovery (P < 0.001), extubation (P < 0.001), and weaning time (P = 0.048) in group M-P were shorter than in group M, while the acquisition cost of sedative drug was more expensive than other groups (both P < 0.001). There was no significant difference in adverse events among these groups (all P > 0.05).ConclusionsThe sequential use of midazolam and dexmedetomidine was an effective and safe sedation strategy for long-term sedation and could provide clinically relevant benefits for selected critically ill, mechanically ventilated patients.Trial registrationNCT02528513. Registered August 19, 2015.

Low-Dose Esketamine as an Adjuvant to Propofol Sedation for Same-Visit Bidirectional Endoscopy: Protocol for a Multicenter Randomized Controlled Trial.

BackgroundSame-visit bidirectional endoscopy (esophagogastroduodenoscopy and colonoscopy) is widely performed under sedation. At present, the optimal sedation regimen remains unclear. This study aims to test the hypothesis that a low-dose esketamine added to propofol sedation reduces hemodynamic and respiratory adverse events in these procedures.MethodsIn this multicenter, randomized, double-blind, placebo-controlled trial, 660 adult patients scheduled for same-visit bidirectional endoscopy under sedation from 3 teaching hospitals in China will be recruited. Patients will be randomly allocated, in a 1:1 ratio, to an esketamine group or a normal saline group (n = 330 in each group), stratified by study center. All patients will receive intravenous propofol 0.5 mg/kg and sufentanil 0.1 μg/mL for induction of sedation, followed by intravenous esketamine 0.15 mg/kg or the same volume of normal saline. Propofol will be titrated to the target sedation levels during the procedures. The primary endpoint is a composite of desaturation (peripheral oxygen saturation < 90%) and hypotension (systolic blood pressure <80 mmHg or decrease >30% of baseline). Secondary endpoints include desaturation, hypotension, total dose of propofol, pain scores and fatigue scores on the 0–10 numerical rating scale, dizziness or headache, hallucination or nightmare, nausea or vomiting, endoscopist satisfaction, and patient satisfaction. All analyses will be intention-to-treat.DiscussionWe expect that a low-dose esketamine adjunct to propofol-based sedation will improve cardiorespiratory stability in patients undergoing same-visit bidirectional endoscopy, providing reference for clinical sedation practice during these procedures.Trial RegistrationChinese Clinical Trial Registry (Identifier: ChiCTR-ChiCTR2200055938).

Gabapentin as Add-On to Fentanyl and Midazolam in Patients Receiving Mechanical Ventilation: A Randomized, Blinded Study.

Objective:Fentanyl and midazolam are popular drugs for sedation and analgesia in intensive care unit. Gabapentin has sedative and analgesic effects, as well. Our purpose was to study gabapentin addition to fentanyl and midazolam to reach the target sedation level in patients requiring mechanical ventilation.Methods:This was a randomized and double-blinded trial. Fifty patients receiving mechanical ventilation and aged from 18 to 70 years were randomized 1 : 1 to 300 mg gabapentin q8hr or placebo. The initial infusion rates of fentanyl and midazolam were 1-2 µg kg-1 h-1 and 0.06-0.2 mg kg-1 h-1, respectively, in both groups. Treatments continued prior to weaning. Ramsay sedation scale score (2-3) and behavioral pain scale score (≤4) were used for the evaluation of sedation and analgesia levels, respectively.Results:A total of 43 patients were studied. Both treatment modalities reached the target sedation and analgesia levels. In the intervention group, there were significant reductions in daily consumption of fentanyl and midazolam (P < .01). Duration of ventilation was shorter in the intervention group (4.1 ± 1.7 days vs 5.1 ± 1.3 days, P > .05). There was no significant difference in intensive care hospitalization, although it was shorter in the intervention group (201 ± 24 hours vs 224 ± 19 hours, P > .05).Conclusions:This trail showed that both treatment modalities could reach target sedation and analgesia levels without significant differences. Add-on therapy with gabapentin could reduce the total dose of fentanyl and midazolam.

The efficacy and safety of nurse-initiated sedation management in an intensive care unit: A two-phase prospective study in Japan.

This study aimed to evaluate whether nurse-initiated sedation management could provide more appropriate sedation compared to usual care in a Japanese intensive care unit (ICU). We conducted a single-center, prospective observational study before and after implementing nurse-initiated sedation using instruction sheets. Patients who had been admitted to a general adult ICU were enrolled. Before our ICU started nurse-initiated sedation (pre-implementation care), adjustment of sedatives and analgesics was performed only by a physician's written or verbal order; however, after implementing nurse-initiated sedation, nurses titrated drugs using instruction sheets. The primary outcome was the efficacy of nurse-initiated sedation, evaluated by the proportion achieving the target Richmond Agitation-Sedation Scale (RASS) score. The analgesic status evaluated by Critical-Care Pain Observation Tool (CPOT), days of delirium, ventilator days, ICU mortality and hospital mortality were also evaluated. The study examined 30 patients in the pre-implementation care phase and 30 patients in the nurse-initiated sedation phase. The proportions achieving the target RASS were 68% in the nurse-initiated sedation group and 42% in the pre-implementation care group (mean difference, 25%; 95% confidence interval, 13.4%-37.5%; P <.001). Almost all measured CPOT were within the range of 0-3 during both phases. Days of delirium, ventilator days, ICU survival, and hospital survival did not differ significantly between the two groups. Nurse-initiated sedation management achieved a significantly higher degree of target sedation status and was incorporated as part of the care in our ICU. It is a safe approach in countries, such as Japan, where sedation protocols are not widely used.

Efficacy and Safety of Remimazolam Tosilate Combined With Esketamine for Analgesic Sedation in Mechanically Ventilated ICU Patients: A Single-Arm Clinical Study Protocol.

IntroductionPatients in the intensive care unit (ICU) frequently experience increased heart rate, blood pressure, and respiration rate as a product of anxiety and restlessness about their condition and treatments. Analgesia and sedation commonly involve benzodiazepines or opioids that lead to respiratory suppression and other adverse reactions. Remimazolam tosilate is a short-acting GABAA receptor agonist with reduced cardiovascular and respiratory inhibition compared to other commonly used benzodiazepines. Esketamine is a non-competitive N-methyl-D-aspartic acid (NMDA) receptor inhibitor that inhibits hyperalgesia and prolongs postoperative analgesia. It also reduces postoperative pain, delirium, and the use and acute tolerance of opioids. This study aims to assess the efficacy and safety of remimazolam tosilate combined with esketamine and sufentanil for sedation and analgesia in mechanically ventilated ICU patients.Methods and AnalysisThis prospective, single-arm, single-center, open-label clinical trial will be conducted from January 2022 to December 2023. The study will include 200 adult patients (≥ 18 years) from Shandong Provincial Hospital (affiliated with Shandong First Medical University) who are mechanically ventilated and admitted to the ICU between 24 and 72 h from the time of ventilation and who are administered analgesia and sedatives. Patients will undergo arterial blood gas analysis before administration. Remimazolam tosilate (0.2 mg/kg) will be injected intravenously within 30 s, followed by continuous infusion at a rate of 0.1 to 0.3 mg/kg/h via micropump. Esketamine (0.25 mg/kg) will be injected intravenously and maintained at 0.15 mg/kg/h, while sufentanil will be maintained at the rate of 0.1 to 0.2 μg/kg/h. The primary study outcome is the overall time required to maintain sedation. Secondary outcomes will include the total dosage used to reach the target sedation level, total mechanical ventilation time, awakening time, length of hospital stay, and incidence of cardiorespiratory-related adverse events and delirium. Adverse events (AEs) will be reported regardless of their relationship to the experimental drugs. AEs associated with adverse drug reactions will be classified as “affirmative correlation,” “possible relevance,” and “unable to determine.” A paired t-test or Wilcoxon signed-rank test will be used to compare the changes of observed indexes before and after treatment. A P < 0.05 will be considered statistically significant.Ethics and DisseminationThis study was approved by the local ethics committee at Shandong Provincial Hospital affiliatied to Shandong First Medical University. The results of this trial will be disseminated in peer-reviewed journals and at scientific conferences.Trial RegistrationThe trial is registered at the Chinese Clinical Trial Registry: ChiCTR2100053106; date of registration: 2021-11-10.

Continuous Determination of the Optimal Bispectral Index Value Based on Cerebrovascular Reactivity in Moderate/Severe Traumatic Brain Injury: A Retrospective Observational Cohort Study of a Novel Individualized Sedation Target.

BACKGROUND:We have sought to develop methodology for deriving optimal bispectral index (BIS) values (BISopt) for patients with moderate/severe traumatic brain injury, using continuous monitoring of cerebrovascular reactivity and bispectral electroencephalography.METHODS:Arterial blood pressure, intracranial pressure, and BIS (a bilateral measure that is associated with sedation state) were continuously recorded. The pressure reactivity index, optimal cerebral perfusion pressure (CPPopt), and BISopt were calculated. Using BIS values and the pressure reactivity index, a curve fitting method was applied to determine the minimum value for the pressure reactivity index thus giving the BISopt.RESULTS AND CONCLUSIONS:Identification of BISopt was possible in all of the patients, with both visual inspection of data and using our method of BISopt determination, demonstrating a similarity of median values of 44.62 (35.03–59.98) versus 48 (39.75–57.50) (p = 0.1949). Furthermore, our method outperformed common CPPopt curve fitting methods applied to BISopt with improved percent (%) yields on both the left side 52.1% (36.3–72.4%) versus 31.2% (23.0–48.9%) (p < 0.0001) and the right side 54.1% (35.95–75.9%) versus 33.5% (12.5–47.9%) (p < 0.0001). The BIS values and BISopt were compared with cerebral perfusion pressure, mean arterial pressure, and CPPopt. The results indicated that BISopt’s impact on pressure reactivity was distinct from CPPopt, cerebral perfusion pressure, or mean arterial pressure. Real-time BISopt can be derived from continuous physiologic monitoring of patients with moderate/severe traumatic brain injury. This BISopt value appears to be unassociated with arterial blood pressure or CPPopt, supporting its role as a novel physiologic metric for evaluating cerebral autoregulation. BISopt management to optimize cerebrovascular pressure reactivity should be the subject of future studies in moderate/severe traumatic brain injury.

A comparative study of sedo-analgesic effect of dexmedetomidine and dexmedetomidine with ketamine in postoperative mechanically ventilated patients.

Background and Aims:To compare the sedoanalgesic effects of dexmedetomidine alone or with combination of ketamine.Material and Methods:After getting ethical approval and informed patient consent, 60 adult surgical patients, were randomly divided into two groups. Group KD (n = 30); received dexmedotomidine 0.5 μg/kg/h mixed with ketamine 0.5 μg/kg/h and Group DEX (n = 30); received dexmedotomidine at 0.5 mg/kg/h infusion only. In both the groups, study drugs were titrated (dexmedetomidine- 0.2-0.7 μg/kg/h and ketamine 0.2-0.7 mg/kg/h) to achieve target sedation. Hemodynamic variables, pain scores, sedation scores, and patient satisfaction were recorded. Qualitative and Quantitative data were analyzed with Pearson Chi-squared test and analysis of variance test, respectively. All analyses were done by using statistical package for social sciences (SPSS) version 16.0.Results:Pain scores were higher in group DEX than in group KD at 2 h and 4 h which was statistically significant (P < 0.05). At the end of 2 h, sedation scores were higher in group KD than in group DEX and was statistically significant (P < 0.05). Length of intensive care unit stay was almost comparable in both groups, and the time to tracheal extubation was lesser in ketamine-dexmedetomidine group as compared to the dexmedetomidine alone group. However the difference was statistically non-significant.Conclusions:By combining dexmedetomidine with ketamine we observed lower incidence of hypotension and bradycardia. Dexmedetomidine with ketamine combination therapy could be used safely and effectively as sedo-analgesic agent.

Implementation of a sedation protocol: a quality improvement project to enhance sedation management in the paediatric intensive care unit

BackgroundProper sedation is integral to ensuring the safety and comfort of children on mechanical ventilation (MV). Sedation protocols help to achieve this goal and reduce the duration of MV. We...

Experience of Dexmedetomidine using for intraoperative analgosedation during ophthalmic operations

Background. The aim of the study is to evaluate the quality and safety of the sedative effect of anesthesia in ambulant ophthalmic surgery by using continuous intravenous infu­sion of Dexmedetomidine. Materials and Methods. Patients were randomized into groups by age (people from 65 to 75 years old, old age 76 years, middle age, young people, children), by gender (men, women). The physical status of patients was assessed using the ASA scale and the dynamics of vegetatic activity by the Kerdo index. Sedation was assessed using the Richmond Sedation Scale RASS.Results. It was found that the difference in the frequency of adverse effects of the appointment of Dexmedetomidine clearly confirms the need to adjust the dose of Dexmede­tomidine, depending on the state of the autonomic nervous system. The use of Dexmedetomidine according to the rec­ommendations made it possible to achieve a safe level of sedation and eliminate side effects in ambulant ophthalmic surgery.Conclusions:&#x0D; &#x0D; Parenteral continuous infusion of Dexmedetomidine pro­vides an effective level of sedation for ambulant ophthalmic surgery and maintaining patient­surgeon contact.&#x0D; Safety is confirmed by a low level of critical incidents, no respiratory depression at the target sedation level.&#x0D; The patency of the upper airways was better compared to previous experience with propofol.&#x0D;