Target Richmond Agitation Sedation Scale Research Articles

Prehospital Use of Ketamine Versus Midazolam for Sedation in Acute Severe Agitation

Objective: Acute severe agitation often requires pharmacologic sedation. While benzodiazepines and antipsychotics are traditional first-line medications for this purpose, recent evidence has shown that prehospital intramuscular (IM) administration of ketamine results in rapid, effective sedation. However, ketamine may be associated with adverse clinical events including a higher intubation rate. The purpose of this study is to compare the efficacy and safety of IM ketamine versus IM midazolam as medications to achieve sedation in the prehospital setting. Methods: This is a retrospective cohort study of agitated patients with an initial Richmond Agitation-Sedation Scale (RASS) score of at least 3, who were sedated and transported by ambulance to Hartford Hospital. The primary endpoint was incidence of endotracheal intubation occurring during transportation and within one hour after arrival to the emergency department (ED). Secondary endpoints included the percentage of patients who achieved an improved RASS score post drug administration, the use of additional sedating agents and the need for airway and breathing support, and differences in adverse events. Results: 66 patients in the ketamine group and 68 patients in the midazolam group met inclusion criteria. While more patients in the midazolam group achieved target RASS score of -1, 0, or 1 post drug administration, patients in the ketamine group had a lower mean RASS score post drug administration. There was no difference in endotracheal intubation rates between the two groups (6.1% versus 2.9%, respectively; p = 0.383). However, upon arrival to the ED, more patients in the ketamine group required additional sedating agents as well as airway or respiratory support Conclusion: Both ketamine and midazolam are relatively safe and efficacious in the prehospital environment. IM ketamine resulted in deeper sedation without increasing intubation rate. However, ED providers receiving patients treated with IM ketamine should prepare for additional sedating agents and airway interventions.

Prehospital Use of Ketamine Versus Midazolam for Sedation in Acute Severe Agitation

Objective: Acute severe agitation often requires pharmacologic sedation. While benzodiazepines and antipsychotics are traditional first-line medications for this purpose, recent evidence has shown that prehospital intramuscular (IM) administration of ketamine results in rapid, effective sedation. However, ketamine may be associated with adverse clinical events including a higher intubation rate. The purpose of this study is to compare the efficacy and safety of IM ketamine versus IM midazolam as medications to achieve sedation in the prehospital setting. Methods: This is a retrospective cohort study of agitated patients with an initial Richmond Agitation-Sedation Scale (RASS) score of at least 3, who were sedated and transported by ambulance to Hartford Hospital. The primary endpoint was incidence of endotracheal intubation occurring during transportation and within one hour after arrival to the emergency department (ED). Secondary endpoints included the percentage of patients who achieved an improved RASS score post drug administration, the use of additional sedating agents and the need for airway and breathing support, and differences in adverse events. Results: 66 patients in the ketamine group and 68 patients in the midazolam group met inclusion criteria. While more patients in the midazolam group achieved target RASS score of -1, 0, or 1 post drug administration, patients in the ketamine group had a lower mean RASS score post drug administration. There was no difference in endotracheal intubation rates between the two groups (6.1% versus 2.9%, respectively; p = 0.383). However, upon arrival to the ED, more patients in the ketamine group required additional sedating agents as well as airway or respiratory support Conclusion: Both ketamine and midazolam are relatively safe and efficacious in the prehospital environment. IM ketamine resulted in deeper sedation without increasing intubation rate. However, ED providers receiving patients treated with IM ketamine should prepare for additional sedating agents and airway interventions.

Prospective Observational Study of Volatile Sedation with Sevoflurane After Aneurysmal Subarachnoid Hemorrhage Using the Sedaconda Anesthetic Conserving Device.

Volatile sedation is still used with caution in patients with acute brain injury because of safety concerns. We analyzed the effects of sevoflurane sedation on systemic and cerebral parameters measured by multimodal neuromonitoring in patients after aneurysmal subarachnoid hemorrhage (aSAH) with normal baseline intracranial pressure (ICP). In this prospective observational study, we analyzed a 12-h period before and after the switch from intravenous to volatile sedation with sevoflurane using the Sedaconda Anesthetic Conserving Device with a target Richmond Agitation Sedation Scale score of - 5 to - 4. ICP, cerebral perfusion pressure (CPP), brain tissue oxygenation (PBrO2), metabolic values of cerebral microdialysis, systemic cardiopulmonary parameters, and the administered drugs before and after the sedation switch were analyzed. We included 19 patients with a median age of 61years (range 46-78years), 74% of whom presented with World Federation of Neurosurgical Societies grade 4 or 5 aSAH. We observed no significant changes in the mean ICP (9.3 ± 4.2 vs. 9.7 ± 4.2mm Hg), PBrO2 (31.0 ± 13.2 vs. 32.2 ± 12.4mm Hg), cerebral lactate (5.0 ± 2.2 vs. 5.0 ± 1.9mmol/L), pyruvate (136.6 ± 55.9 vs. 134.1 ± 53.6µmol/L), and lactate/pyruvate ratio (37.4 ± 8.7 vs. 39.8 ± 9.2) after the sedation switch to sevoflurane. We found a significant decrease in mean arterial pressure (MAP) (88.6 ± 7.6 vs. 86.3 ± 5.8mm Hg) and CPP (78.8 ± 8.5 vs. 76.6 ± 6.6mm Hg) after the initiation of sevoflurane, but the decrease was still within the physiological range requiring no additional hemodynamic support. Sevoflurane appears to be a feasible alternative to intravenous sedation in patients with aSAH without intracranial hypertension, as our study did not show negative effects on ICP, cerebral oxygenation, or brain metabolism. Nevertheless, the risk of a decrease of MAP leading to a consecutive CPP decrease should be considered.

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.

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.

Reactive Oxygen Species Scavenger in Acute Intracerebral Hemorrhage Patients: A Multicenter, Randomized Controlled Trial.

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Predictors of a response to dexmedetomidine in intubated, critically ill adult patients.

Dexmedetomidine is a centrally acting α-2 receptor agonist used to maintain light analgosedation in mechanically ventilated adults. This study was conducted to determine factors predictive of successful maintenance of light sedation (Richmond Agitation-Sedation Scale (RASS) 0 to -2) for ≥60% of the first 48h of mechanical ventilation with dexmedetomidine. This was a single-center, retrospective, cohort study of critically ill adult patients receiving dexmedetomidine and admitted to an intensive care unit (ICU) between January 1, 2013, and August 31, 2019. A multivariable logistic regression analysis was performed in patients receiving dexmedetomidine for sedation to assess patient and clinical characteristics associated with a positive clinical response to dexmedetomidine. Of 1065 patients reviewed for study inclusion, 158 patients were included. Sixty-two percent of patients initiated on dexmedetomidine to maintain light sedation were able to remain within this sedation target ≥60% of the time during the first 48 hours of therapy. Patients maintained within the target RASS score ≥60% of the time had a higher percentage of ventilator-free days at 14days (p=0.044). The odds of having a mean time within goal RASS score ≥60% in the first 48 hours of mechanical ventilation after intubation were decreased by 9% for every point increase in sequential organ failure assessment score (odds ratio: 0.91, 95% confidence interval: 0.82-0.99). Patients were less likely to maintain light sedation with dexmedetomidine as their degree of critical illness increased. The duration of time maintained within goal sedation after dexmedetomidine initiation and the impact on patient outcomes remain a research priority.

Impact of Multiple Daily Clinical Pharmacist-Enforced Assessments on Time in Target Sedation Range

Objectives: Incorporation of a single daily assessment by a clinical pharmacist to improve adherence with a sedation protocol is associated with reduced duration of mechanical ventilation and intensive care unit (ICU) length of stay (LOS). We test the feasibility of incorporating a clinical pharmacist into more frequent sedation assessments and observed whether there are any potential differences in the sedatives administered. Methods: Prospective, quasi-experimental, pilot study of patients admitted to the medical ICU. Patients were included in the analysis if ≥18 years of age within the first 24 hours of initiation of mechanical ventilation. Our primary intent was to test the clinical feasibility surrounding more frequent sedation assessments by a clinical pharmacist by evaluating potential differences in time in target sedation range and sedative administration. Exploratory efficacy end points included time in target sedation range (0 to −2) using the Richmond Agitation Sedation Scale (RASS) and sedative exposure. Patients were assigned to receive either 3 assessments with a clinical pharmacist per day (intervention) or a single assessment by a clinical pharmacist per day (standard of care). During the assessments, clinical pharmacists participated in the RASS administration and made dosing adjustments according to an established sedation protocol. Main Results: Seventeen patients were enrolled (n = 6 intervention group, n = 11 standard of care). Duration of mechanical ventilation was similar in the 2 groups (intervention 100.0 hours [52.5-197.5] vs control 76.0 hours [46.0-201.0], P = .95), but patients in the intervention group exhibited a greater percentage time in the target RASS range (intervention 76.0% [53.7-81.5%] vs control 45.2% [35.3-67.0], P = .11) that was not statistically significant. Patients in the intervention group received less fentanyl per day (820.9 µg [227.3-1579.4] vs 1997 µg [1648.2-2477.2], P = .02) than in the control group. Conclusion: Incorporating a clinical pharmacist into more frequent daily sedation assessments was associated with a reduction in fentanyl administration. There were no observed differences in time in target sedation range or reduction in duration of mechanical ventilation.

Dexmedetomidine as an adjunct for sedation in patients with traumatic brain injury

In patients with traumatic brain injury (TBI), optimizing sedation is challenging because maintaining a clinical examination is important in being able to detect neurological deterioration. Propofol (PROP) is frequently used as a sedative in TBI since it has been shown to reduce the cerebral metabolic rate, but it may lead to PROP-related infusion syndrome and hemodynamic compromise. Dexmedetomidine (DEX) is a sedative that produces minimal respiratory depression with opioid-sparing effects. The purpose of this study was to determine whether sedation with DEX would be safe in patients with severe TBI. This prospective observational single-center study was conducted from 2011 to 2013. Patients with severe TBI were treated according to standard of care per the Brain Trauma Foundation guidelines. Sedative agents were titrated using the Richmond Agitation Sedation Scale (RASS) while maintaining intracranial pressure of less than 20 mm Hg and cerebral perfusion pressure of greater than 60 mm Hg. The primary outcome measure was the mean time in target RASS (0 = alert and calm to -2 = light sedation). A total of 198 patients were enrolled in the study. Patient-days (1,028 in total) were stratified into four groups: DEX only (n = 222), DEX + PROP (n = 148), PROP only (n = 599), and NEITHER (n = 59). Regression analyses indicated a significant difference in target RASS between sedative agents (p = 0.001). The DEX-only group had the highest adjusted mean daily estimate of 16.0 hours in target RASS. Hypotension was significantly higher in both the DEX only (p = 0.01) and DEX + PROP (p = 0.01) groups than in the PROP-only group. Dexmedetomidine was found to be associated with significantly more hypotension. Therefore, larger studies are needed to identify the role of DEX in TBI. Therapeutic study, level III.

Changes in arterial blood pressure induced by passive leg raising predict hypotension during the induction of sedation in critically ill patients without severe cardiac dysfunction

Background Hypotension due to the induction of sedation with dexmedetomidine infusion may be harmful in critically ill patients. Changes in pulse pressure induced by the passive leg raising test (PLR-ΔPP) as marker of fluid responsiveness, assessed prior to sedation, may predict hemodynamic changes. The present study was to investigate the power of the PLR test in critically ill patients in predicting hypotension induced by the induction of dexmedetomidine sedation. Methods Fluid responsiveness was estimated by a passive leg raising (PLR) test before dexmedetomidine sedation. Patients were assigned to either the “Nonresponders” or “Responders” group according to their hemodynamic responses to the PLR test (“Nonresponders”, PLR-ΔPP &lt;10.3%; “Responders”, PLR-ΔPP ≥10.3%). Sedation was performed with a dexmedetomidine infusion (0.5 μg/kg over a 10-minute loading period, then 0.2-0.7 μg·kg-1·h-1) and titrated to maintain the target Richmond agitation sedation scale (RASS) score in the range of −2 to −1 and the bispectral index value in the range of 60 to 75. Radial artery pulse pressure, heart rate (HR), and central venous pressure (CVP) were measured at each phase of the study procedure. Hemodynamic fluctuations during the use of dexmedetomidine sedation were recorded and compared between the two groups. Results Fifty patients had a median (25%-75% interquartile range) of 71 (61-78) years old were studied. At baseline, 39 of the 50 patients were “Nonresponders” and 11 were “Responders”. Following dexmedetomidine sedation, patients classified as “Responders” had a significantly greater systolic blood pressure decrease during the induction of dexmedetomidine sedation than the “Nonresponders” ((−26.3 ± 6.8)% vs. (−11.8 ± 8.5)%, P &lt;0.001). In addition, the “Responders” group required significantly more fluid boluses (8 vs. 3; P &lt;0.001) and vasopressors (2 vs. 0; P &lt;0.05) than the “Nonresponders” group to restore blood pressure. Finally, PLR-ΔPP was positively correlated with changes in systolic blood pressure (PLR-ΔSBP) (r 2 = 0.576; P &lt;0.001) and significantly correlated with dexmedetomidine infusion-induced changes in SBP (r 2=0.202; P &lt;0.05). AUC for PLR-ΔPP was 0.84 (95%CI 0.71-0.93). PLR-ΔPP predicted hypotension with a sensitivity of 73% and a specificity of 92%. Conclusions The fluid responsiveness assessment pre-sedation was found to predict blood pressure fluctuation during the induction of dexmedetomidine sedation. The PLR test conducted prior to sedation may be a useful tool to identify patients with a high risk of hemodynamic events and may be used to indicate the need for prophylactic treatment.

Reducing Deep Sedation and Delirium in Acute Lung Injury Patients

Deep sedation and delirium are common in the ICU. Mechanically ventilated patients with acute lung injury are at especially high risk for deep sedation, delirium, and associated long-term physical and neuropsychiatric impairments. We undertook an ICU-wide structured quality improvement project to decrease sedation and delirium. Prospective quality improvement project in comparison with a retrospective acute lung injury control group. Sixteen-bed medical ICU in an academic teaching hospital with pre-existing use of goal-directed sedation with daily interruption of sedative infusions. Consecutive acute lung injury patients. A "4Es" framework (engage, educate, execute, evaluate) was used as part of the quality improvement process. A new sedation protocol was created and implemented, which recommends a target Richmond Agitation Sedation Scale score of 0 (alert and calm) and requires failure of intermittent sedative dosing prior to starting continuous infusions. In addition, twice-daily delirium screening using the Confusion Assessment Method for the ICU was introduced into routine practice. Sedative use and delirium status in acute lung injury patients after implementation of the quality improvement project (n = 82) were compared with a historical control group (n = 120). During the quality improvement vs. control periods, use of narcotic and benzodiazepine infusions were substantially lower (median proportion of medical ICU days per patient: 33% vs. 74%, and 22% vs. 70%, respectively, both p < 0.001). Further, wakefulness increased (median Richmond Agitation Sedation Scale score per patient: -1.5 vs. -4.0, p < 0.001), and days awake and not delirious increased (median proportion of medical ICU days per patient: 19% vs. 0%, p < 0.001). Through a structured quality improvement process, use of sedative infusions can be substantially decreased and days awake without delirium significantly increased, even in severely ill, mechanically ventilated patients with acute lung injury.

Dexmedetomidine vs Midazolam for Sedation of Critically Ill Patients&lt;subtitle&gt;A Randomized Trial&lt;/subtitle&gt;

Gamma-aminobutyric acid receptor agonist medications are the most commonly used sedatives for intensive care unit (ICU) patients, yet preliminary evidence indicates that the alpha(2) agonist dexmedetomidine may have distinct advantages. To compare the efficacy and safety of prolonged sedation with dexmedetomidine vs midazolam for mechanically ventilated patients. Prospective, double-blind, randomized trial conducted in 68 centers in 5 countries between March 2005 and August 2007 among 375 medical/surgical ICU patients with expected mechanical ventilation for more than 24 hours. Sedation level and delirium were assessed using the Richmond Agitation-Sedation Scale (RASS) and the Confusion Assessment Method for the ICU. Dexmedetomidine (0.2-1.4 microg/kg per hour [n = 244]) or midazolam (0.02-0.1 mg/kg per hour [n = 122]) titrated to achieve light sedation (RASS scores between -2 and +1) from enrollment until extubation or 30 days. Percentage of time within target RASS range. Secondary end points included prevalence and duration of delirium, use of fentanyl and open-label midazolam, and nursing assessments. Additional outcomes included duration of mechanical ventilation, ICU length of stay, and adverse events. There was no difference in percentage of time within the target RASS range (77.3% for dexmedetomidine group vs 75.1% for midazolam group; difference, 2.2% [95% confidence interval {CI}, -3.2% to 7.5%]; P = .18). The prevalence of delirium during treatment was 54% (n = 132/244) in dexmedetomidine-treated patients vs 76.6% (n = 93/122) in midazolam-treated patients (difference, 22.6% [95% CI, 14% to 33%]; P < .001). Median time to extubation was 1.9 days shorter in dexmedetomidine-treated patients (3.7 days [95% CI, 3.1 to 4.0] vs 5.6 days [95% CI, 4.6 to 5.9]; P = .01), and ICU length of stay was similar (5.9 days [95% CI, 5.7 to 7.0] vs 7.6 days [95% CI, 6.7 to 8.6]; P = .24). Dexmedetomidine-treated patients were more likely to develop bradycardia (42.2% [103/244] vs 18.9% [23/122]; P < .001), with a nonsignificant increase in the proportion requiring treatment (4.9% [12/244] vs 0.8% [1/122]; P = .07), but had a lower likelihood of tachycardia (25.4% [62/244] vs 44.3% [54/122]; P < .001) or hypertension requiring treatment (18.9% [46/244] vs 29.5% [36/122]; P = .02). There was no difference between dexmedetomidine and midazolam in time at targeted sedation level in mechanically ventilated ICU patients. At comparable sedation levels, dexmedetomidine-treated patients spent less time on the ventilator, experienced less delirium, and developed less tachycardia and hypertension. The most notable adverse effect of dexmedetomidine was bradycardia. clinicaltrials.gov Identifier: NCT00216190 Published online February 2, 2009 (doi:10.1001/jama.2009.56).