Effect of Remifentanil vs Neuromuscular Blockers During Rapid Sequence Intubation on Successful Intubation Without Major Complications Among Patients at Risk of Aspiration: A Randomized Clinical Trial.

Importance: It is uncertain whether a rapid-onset opioid is noninferior to a rapid-onset neuromuscular blocker during rapid sequence intubation when used in conjunction with a hypnotic agent. Objective: To determine whether remifentanil is noninferior to rapid-onset neuromuscular blockers for rapid sequence intubation. Design, Setting, and Participants: Multicenter, randomized, open-label, noninferiority trial among 1150 adults at risk of aspiration (fasting for <6 hours, bowel occlusion, recent trauma, or severe gastroesophageal reflux) who underwent tracheal intubation in the operating room at 15 hospitals in France from October 2019 to April 2021. Follow-up was completed on May 15, 2021. Interventions: Patients were randomized to receive neuromuscular blockers (1 mg/kg of succinylcholine or rocuronium; n = 575) or remifentanil (3 to 4 µg/kg; n = 575) immediately after injection of a hypnotic. Main Outcomes and Measures: The primary outcome was assessed in all randomized patients (as-randomized population) and in all eligible patients who received assigned treatment (per-protocol population). The primary outcome was successful tracheal intubation on the first attempt without major complications, defined as lung aspiration of digestive content, oxygen desaturation, major hemodynamic instability, sustained arrhythmia, cardiac arrest, and severe anaphylactic reaction. The prespecified noninferiority margin was 7.0%. Results: Among 1150 randomized patients (mean age, 50.7 [SD, 17.4] years; 573 [50%] women), 1130 (98.3%) completed the trial. In the as-randomized population, tracheal intubation on the first attempt without major complications occurred in 374 of 575 patients (66.1%) in the remifentanil group and 408 of 575 (71.6%) in the neuromuscular blocker group (between-group difference adjusted for randomization strata and center, -6.1%; 95% CI, -11.6% to -0.5%; P = .37 for noninferiority), demonstrating inferiority. In the per-protocol population, 374 of 565 patients (66.2%) in the remifentanil group and 403 of 565 (71.3%) in the neuromuscular blocker group had successful intubation without major complications (adjusted difference, -5.7%; 2-sided 95% CI, -11.3% to -0.1%; P = .32 for noninferiority). An adverse event of hemodynamic instability was recorded in 19 of 575 patients (3.3%) with remifentanil and 3 of 575 (0.5%) with neuromuscular blockers (adjusted difference, 2.8%; 95% CI, 1.2%-4.4%). Conclusions and Relevance: Among adults at risk of aspiration during rapid sequence intubation in the operating room, remifentanil, compared with neuromuscular blockers, did not meet the criterion for noninferiority with regard to successful intubation on first attempt without major complications. Although remifentanil was statistically inferior to neuromuscular blockers, the wide confidence interval around the effect estimate remains compatible with noninferiority and limits conclusions about the clinical relevance of the difference. Trial Registration: ClinicalTrials.gov Identifier: NCT03960801.

BET 2: Is the use of long-acting neuromuscular blocking agents for intubation associated with reduced provision of postintubation sedation?

A short cut review was conducted to assess if the use of rocuronium in the ED was associated with a decrease in the provision of postintubation sedation. Four papers were identified that presented the best evidence to answer the question. Again the studies, relevant outcomes, results and weaknesses are tabulated. All the identified studies were retrospective and there was a plethora of outcome measures used. When compared with suxamethonium, rocuronium was associated with a delayed initiation and reduced dose of postintubation sedation.

A multicenter investigation of the hemodynamic effects of induction agents for trauma rapid sequence intubation.

BACKGROUND: Several options exist for induction agents during rapid sequence intubation (RSI) in trauma patients, including etomidate, ketamine, and propofol. These drugs have reported variable hemodynamic effects (hypotension with propofol and sympathomimetic effects with ketamine) that could affect trauma resuscitations. The purpose of this study was to compare the hemodynamic effects of these three induction agents during emergency department RSI in adult trauma. We hypothesized that these drugs would display a differing hemodynamic profile during RSI. METHODS: We performed a retrospective (2014-2019), multicenter trial of adult (≥18 years) trauma patients admitted to eight ACS-verified Level I trauma centers who underwent emergency department RSI. Variables collected included systolic blood pressure (SBP) and pulse before and after RSI. The primary outcomes were change in heart rate and SBP before and after RSI. RESULTS: There were 2,092 patients who met criteria, 85% received etomidate (E), 8% ketamine (K), and 7% propofol (P). Before RSI, the ketamine group had a lower SBP (E, 135 vs. K, 125 vs. P, 135 mm Hg, p = 0.04) but there was no difference in pulse (E, 104 vs. K, 107 vs. P, 105 bpm, p = 0.45). After RSI, there were no differences in SBP (E, 135 vs. K, 130 vs. P, 133 mm Hg, p = 0.34) or pulse (E, 106 vs. K, 110 vs. P, 104 bpm, p = 0.08). There was no difference in the average change of SBP (E, 0.2 vs. K, 5.2 vs. P, -1.8 mm Hg, p = 0.4) or pulse (E, 1.7 vs. K, 3.5 bpm vs. P, -0.96, p = 0.24) during RSI. CONCLUSION: Contrary to our hypothesis, there was no difference in the hemodynamic effect for etomidate versus ketamine versus propofol during RSI in trauma patients. LEVEL OF EVIDENCE: Therapeutic, Level IV.

Pre-oxygenation using high-flow nasal oxygen vs. tight facemask during rapid sequence induction.

Pre-oxygenation using high-flow nasal oxygen can decrease the risk of desaturation during rapid sequence induction in patients undergoing emergency surgery. Previous studies were single-centre and often in limited settings. This randomised, international, multicentre trial compared high-flow nasal oxygen with standard facemask pre-oxygenation for rapid sequence induction in emergency surgery at all hours of the day and night. A total of 350 adult patients from six centres in Sweden and one in Switzerland undergoing emergency surgery where rapid sequence induction was required were included and randomly allocated to pre-oxygenation with 100% oxygen using high-flow nasal oxygen or a standard tight-fitting facemask. The primary outcome was the number of patients developing oxygen saturations <93% from the start of pre-oxygenation until 1 min after tracheal intubation. Data from 349 of 350 patients who entered the study were analysed (174 in the high-flow nasal oxygen group and 175 in the facemask group). No difference was detected in the number of patients desaturating <93%, five (2.9%) vs. six (3.4%) patients in the high-flow nasal oxygen and facemask group, respectively (p = 0.77). The risk of desaturation was not increased during on-call hours. No difference was seen in end-tidal carbon dioxide levels in the first breath after tracheal intubation or in the number of patients with signs of regurgitation between groups. These results confirm that high-flow nasal oxygen maintains adequate oxygen levels during pre-oxygenation for rapid sequence induction.

Rapid Sequence Induction With a Standard Intubation Dose of Rocuronium After Magnesium Pretreatment Compared With Succinylcholine: A Randomized Clinical Trial.

BACKGROUND: Succinylcholine remains the muscle relaxant of choice for rapid sequence induction (RSI) but has many adverse effects. High-dose rocuronium bromide may be an alternative to succinylcholine for RSI but recovery times are nearly doubled compared with a standard intubating dose of rocuronium. Magnesium sulfate significantly shortens the onset time of a standard intubating dose of rocuronium. We set out to investigate whether intravenous (IV) pretreatment with MgSO4 followed by a standard intubating dose of rocuronium achieved superior intubation conditions compared with succinylcholine. METHODS: Adults were randomized to receive a 15-minute IV infusion of MgSO4 (60 mg·kg-1) immediately before RSI with propofol 2 mg·kg-1, sufentanil 0.2 µg·kg-1 and rocuronium 0.6 mg·kg-1, or a matching 15-minute IV infusion of saline immediately before an identical RSI, but with succinylcholine 1 mg·kg-1. Primary end point was the rate of excellent intubating conditions 60 seconds after administration of the neuromuscular blocking agent and compared between groups using multivariable log-binomial regression model. Secondary end points were blood pressure and heart rate before induction, before and after intubation, and adverse events up to 24 hours postoperatively. RESULTS: Among 280 randomized patients, intubating conditions could be analyzed in 259 (133 MgSO4-rocuronium and 126 saline-succinylcholine). The rate of excellent intubating conditions was 46% with MgSO4-rocuronium and 45% with saline-succinylcholine. The analysis adjusted for gender and center showed no superiority of MgSO4-rocuronium compared with saline-succinylcholine (relative risk [RR] 1.06, 95% confidence interval [CI], 0.81-1.39, P = .659). The rate of excellent intubating conditions was higher in women (54% [70 of 130]) compared with men (37% [48 of 129]; adjusted RR 1.42, 95% CI, 1.07-1.91, P = .017). No significant difference between groups was observed for systolic and diastolic blood pressures. Mean heart rate was significantly higher in the MgSO4-rocuronium group. The percentage of patients with at least 1 adverse event was lower with MgSO4-rocuronium (11%) compared with saline-succinylcholine (28%) (RR 0.38, 95% CI, 0.22-0.66, P < .001). With saline-succinylcholine, adverse events consisted mainly of postoperative muscle pain (n = 26 [19%]) and signs of histamine release (n = 13 [9%]). With MgSO4-rocuronium, few patients had pain on injection, nausea and vomiting, or skin rash during the MgSO4-infusion (n = 5 [4%]). CONCLUSIONS: IV pretreatment with MgSO4 followed by a standard intubating dose of rocuronium did not provide superior intubation conditions to succinylcholine but had fewer adverse effects.

Sedation for Rapid Sequence Induction and Intubation of Neurologically Injured Patients.

There are subtle physiologic and pharmacologic principles that should be understood for patients with neurologic injuries. These principles are especially true for managing patients with traumatic brain injuries. Prevention of hypotension and hypoxemia are major goals in the management of these patients. This article discusses the physiology, pitfalls, and pharmacology necessary to skillfully care for this subset of patients with trauma. The principles endorsed in this article are applicable both for patients with traumatic brain injury and those with spinal cord injuries.

Anaesthetic management for hiatal hernia repair in a child with Bartter's syndrome: A case report.

Bartter syndrome is a rare disorder characterized by reduced sodium chloride transport in the distal nephrons of the kidney. Its clinical features are renal salt wasting, hypokalemic metabolic alkalosis, elevated renin and aldosterone levels with normal or low blood pressure, polyuria, hypercalciuria and malnutrition. The pathophysiologic and biochemical changes in these patients should be kept in mind when considering anaesthetic management. This case report describes our management in a nineteen months old, 3.6 kg weight male child with Bartter's syndrome who underwent elective repair of hiatal hernia and gastrostomy.

The Use of Ketamine for Air Medical Rapid Sequence Intubation Was Not Associated With a Decrease in Hypotension or Cardiopulmonary Arrest.

OBJECTIVE: Rapid sequence intubation (RSI) is associated with a number of complications that can increase morbidity and mortality. Among RSI agents used to blunt awareness of the procedure and produce amnesia, ketamine is unique in its classification as a dissociative agent rather than a central nervous system depressant. Thus, ketamine should have a lower risk of peri-RSI hypotension because of the minimal sympatholysis compared with other agents. Recent recommendations include the use of ketamine for RSI in hemodynamically unstable patients. The main goal of this analysis was to explore the incidence of hypotension and/or cardiopulmonary arrest in patients receiving ketamine, etomidate, midazolam, and fentanyl during air medical RSI. We hypothesized that ketamine would be associated with a lower risk of hemodynamic complications, particularly after adjusting for covariables reflecting patient acuity. In addition, we anticipated that an increased prevalence of ketamine use would be associated with a decreased incidence of peri-RSI hypotension and/or arrest. METHODS: This was a retrospective, observational study using a large air medical airway database. A waiver of informed consent was granted by our institutional review board. Descriptive statistics were used to present demographic and clinical data. The incidence rates of hypotension and cardiopulmonary arrest were calculated for each sedative/dissociative agent. Multivariable logistic regression was used to calculate the odds ratios of both hypotension and arrest for each of the sedative/dissociative agents. The prevalence of use for each agent and the incidence of hemodynamic complications (hypotension and arrest) were determined over time. RESULTS: A total of 7,466 RSI patients were included in this analysis. The use of ketamine increased over the duration of the study. Ketamine was associated with a higher incidence of both hypotension and arrest compared with other agents, even after adjustment for multiple covariables. The overall incidence of hypotension, desaturation, and cardiopulmonary arrest did not change over the study period. CONCLUSIONS: Although the incidence of hemodynamic complications was higher in patients receiving ketamine, this may reflect a selection bias toward more hemodynamically unstable patients in the ketamine cohort. The incidence of hypotension and arrest did not change over time despite an increase in the prevalence of ketamine use for air medical RSI. These data do not support a safer hemodynamic profile for ketamine.

The optimal dose of succinylcholine for rapid sequence induction: a systematic review and meta-analysis of randomized trials.

BACKGROUND: The evidence base for the widely accepted standard regimen of succinylcholine for rapid sequence induction (1.0 mg kg- 1) remains unclear. METHODS: We performed a systematic review and meta-analysis of randomized trials comparing any succinylcholine regimen with the standard regimen (1.0 mg kg- 1) and reporting on intubating conditions and/or apnoea times. Results were expressed as absolute risk differences (ARD) for dichotomous data and mean differences (MD) for continuous data. RESULTS: We retrieved six trials with relevant data of 864 patients (ASA 1 or 2, aged 18-65 years, body mass index < 30 kg m- 2). Four regimens (0.3, 0.4, 0.5, 0.6 mg kg- 1) were compared with 1.0 mg kg- 1 in at least three trials each, and three (0.8, 1.5, 2 mg kg- 1) in one each. With 0.3 to 0.5 mg kg- 1, the likelihood of excellent intubating conditions was significantly decreased (ARD - 22% to - 67%). With 0.3 and 0.4 mg kg- 1, but not with 0.5, 0.6, 0.8, 1.5 and 2.0 mg kg- 1, the likelihood of unacceptable intubating conditions was significantly increased (ARD + 22% and + 32%, respectively). With 2.0 mg kg- 1, but not with 0.8 or 1.5 mg kg- 1, the likelihood of excellent intubating conditions was significantly increased (ARD + 23%). Apnoea times were significantly shorter with regimens ≤0.8 mg kg- 1 (MD - 1.0 to - 3.4 min) but were not reported with 1.5 or 2.0 mg kg- 1. CONCLUSIONS: With succinylcholine regimens ≤0.5 mg kg- 1, excellent intubating conditions are less likely and apnoea times are shorter, compared with 1 mg kg- 1. With 0.3 and 0.4 mg kg- 1, unacceptable intubating conditions are more common. Succinylcholine 1.5 mg kg- 1 does not produce more often excellent conditions compared with 1 mg kg- 1, while 2.0 mg kg- 1 does, but the database with these regimens is weak and apnoea times remain unknown. Limited information size and strong statistical heterogeneity decrease the certainty of the evidence.

Neuromuscular monitoring during modified rapid sequence induction: A comparison of TOF-Cuff® and TOF-Scan®.

BACKGROUND: Acceleromyometry is the clinical standard for quantitative neuromuscular monitoring, mostly using the stimulation pattern train-of-four (TOF). TOF-Cuff®, a recently introduced neuromuscular monitor with stimulating electrodes integrated within a blood pressure cuff, assesses the muscular response in the upper arm. METHODS: The time from administration of a neuromuscular blocking agent to TOF-ratio 0% during modified rapid sequence induction was compared between TOF-Cuff® and acceleromyometry (TOF-Scan®). Included were 26 adults with body mass index <35 kg/m2. TOF-Scan® and TOF-Cuff® were simultaneously fitted on patients' opposite arms. The mean difference to TOF-ratio 0% was compared using the one sample t-test (p < 0.05) and Bland-Altman plots. RESULTS: After anesthesia induction, atracurium 0.9 mg/kg (±0.08) i.v. was administered. The mean time to TOF ratio 0% for TOF-Scan® was 140.4 s (±34.3), and 132.7 s (±32.5) for TOF-Cuff®, with a mean difference of 5.4 (95% CI: -9.9 to 20.7, p = 0.472). The maximum difference between the two modalities was 135 s when the TOF-Cuff® was faster and 60 s when the TOF-Scan® was faster. CONCLUSIONS: No statistically significant systematic difference was found between TOF-Scan® and TOF-Cuff®. However, there was high variability and wide limits of agreement. The two devices cannot be used interchangeably.

Comparison of drugs used for intubation of pediatric trauma patients.

PURPOSE: Rapid sequence intubation (RSI) drugs, such as propofol, affect clinical outcomes, but this has not been examined in the pediatric population. This descriptive study compares the outcomes associated with intubation drugs used in pediatric traumatic brain injury (TBI) patients. METHODS: A retrospective chart review and descriptive analysis of intubated TBI patients, ages 0-17, admitted to Children's Hospital London Health Sciences Centre (LHSC) from January 2006-December 2016 was performed. RESULTS: Out of 259 patients intubated, complete data was available for 107 cases. Average injury severity score was 28; 46 were intubated at LHSC, 55 at primary care site, and 6 on scene. Intubation attempts were recorded in 87 of 107 paper charts. First-pass intubation success rate was 88.5%. Propofol (n = 21), midazolam (n = 31), etomidate (n = 13), and ketamine (n = 7) were the most commonly used intubation drugs. Paralytics were used in 50% of patients. Following use of propofol, Pediatric Adjusted Shock Index was increased as a result of worsening hypotension. Mean total hospital length of stay was 21 days with 7.5 days in ICU. Survival was 87%. CONCLUSION: Great variability exists in the use of induction agents and paralytics for RSI. Propofol was commonly used and is potentially associated with poorer clinical outcomes. TYPE OF STUDY: Retrospective. LEVEL OF EVIDENCE: IV.

Video Laryngoscopy Compared to Augmented Direct Laryngoscopy in Adult Emergency Department Tracheal Intubations: A National Emergency Airway Registry (NEAR) Study.

OBJECTIVE: The objective was to compare first-attempt intubation success using direct laryngoscopy augmented by laryngeal manipulation, ramped patient positioning, and use of a bougie (A-DL) with unaided video laryngoscopy (VL) in adult emergency department (ED) intubations. METHODS: This study was a secondary analysis of a multicenter prospective observational database of ED intubations from the National Emergency Airway Registry (NEAR). We compared all VL procedures to seven exploratory permutations of A-DL using multivariable regression models. We further stratified by blade shape into hyperangulated VL (HA-VL) and standard-geometry VL (SG-VL). We report differences in first-attempt intubation success and peri-intubation adverse events with cluster-adjusted odds ratios (ORs) with 95% confidence intervals (CIs). We report univariate comparisons in patient characteristics, difficult airway attributes, and intubation methods using descriptive statistics and OR with 95% CI. RESULTS: We analyzed 11,714 intubations performed from January 1, 2016, through December 31, 2017. Of these encounters, 6,938 underwent orotracheal intubation with either A-DL or unaided VL on first attempt. A-DL was used first in 3,936 (56.7%, 95% CI = 46.9 to 66.5) versus unaided VL in 3,002 (43.3%, 95% CI = 33.5 to 53.1). Of the A-DL first intubations 1,787 (45.4%) employed ramped positioning alone, 1,472 (37.4%) had external laryngeal manipulation (ELM), and 365 (9.3%) used a bougie. Rapid sequence intubation (RSI) was the most common method used in 5,602 (80.8%, 95% CI = 77.0 to 84.5) cases. First-attempt success was significantly higher with all VL (90.9%, 95% CI = 88.7 to 93.1) versus all A-DL (81.1%, 95% CI = 78.7 to 83.5) despite the VL group having more patients with reduced mouth opening, neck immobility, and an initial impression of airway difficult. Multivariable regression analyses controlling for indication, method, operator specialty and year of training, center clustering, and all registry-recorded difficult airway predictors revealed first-attempt success was higher with all unaided VL compared with any A-DL (adjusted OR [AOR] = 2.8, 95% CI = 2.4 to 3.3), DL with bougie (AOR = 2.7, 95% CI = 2.1 to 3.5), DL with ELM (AOR = 1.8, 95% CI = 1.5 to 2.2), DL with ramped positioning (AOR = 2.8, 95% CI = 2.3 to 3.3), or DL with ELM plus bougie (AOR = 2.8, 95% CI = 2.3 to 3.3). Subgroup analyses of HA-VL and SG-VL compared with any A-DL yielded similar results (AOR = 3.2, 95% CI = 2.6 to 3.0; and AOR = 2.4, 95% CI = 1.9 to 3.0, respectively). The propensity score-adjusted odds for first-attempt success with VL was also 2.8 (95% CI = 2.4 to 3.3). Fewer esophageal intubations were observed in the VL cohort (0.4% vs. 1.3%, AOR = 0.2, 95% CI = 0.1 to 0.5). CONCLUSIONS: Video laryngoscopy used without any augmenting maneuver, device, or technique results in higher first-attempt success than does DL that is augmented by use of a bougie, ELM, ramping, or combinations thereof.