Background:

It is estimated that between 2.6% and 3.4% of patients undergoing rapid sequence intubation (RSI) experience awareness with paralysis, with the highest risk observed in patients receiving rocuronium. Several studies have now demonstrated prolonged time to sedation following RSI with long-acting paralytics, including a 2024 single-centered retrospective chart review by Dukes et al., which found that fewer than half of patients in the ICU receiving rocuronium for RSI were administered sedation within 15 minutes of intubation. The following study by Cappuccilli et al. sought to compare differences in sedation practices between the ED and ICUs at the same institution, hypothesizing that patients undergoing RSI in the ED would experience similar delays in sedation to those in the ICU. 

Study Design:

• Retrospective chart review of patients aged 18-89 who were intubated with rocuronium in the ED or ICU at a single academic tertiary care center in the United States
• Excluded patients receiving a sedative bolus or infusion in the 30 minutes prior to induction, those with timing discrepancies in induction or paralytic administration, and patients undergoing RSI during cardiac arrest
• Primary outcome was the proportion of patients who received a sedative agent within 15 minutes of induction
• Secondary outcomes:
  • Time to sedation (minutes) after intubation
  • Total amount of sedative an analgesic administered in the first 60 minutes vs. 61-120 minutes post-RSI
  • Sedation Intensity Score (SIS): Non-validated tool designed to compare relative amounts of sedatives administered across a population during a specific timeframe

Baseline Characteristics:

• Total of 370 intubations included in the final analysis, with 178 taking place in the ED and 192 in the ICU
• ICU patients were more frequently hypotensive at baseline compared to ED patients (31% vs 21%)
• ED patients had a lower GCS compared to ICU patients (7 vs. 11)
• Primary induction agent used among all areas was ketamine (62% in ED and 72% in ICU)
• Etomidate was more frequently used for induction in the ED than ICU (38% vs 26%)
• Most common choice for post-intubation sedation was a propofol infusion (56% in ED and 57% in ICU)

Key Results:

• Primary outcome
  • Proportion of patients receiving sedation within 15 minutes of induction was similar between the ED and ICUs (39 vs. 40%; difference 0.8%, 95% CI – 10.6% to 9.1%). This finding was consistent regardless of pre-intubation GCS.
  • A quarter of patients in the study received no sedation within 2 hours of induction agent administration.
• Secondary outcomes
  • Median time from intubation to sedation administration was 15 min (IQR 8-35) in the ED and 13 min (IQR 5-36) in the ICU.
  • Propofol infusion rates were lower in the ED compared to the ICU during the first hour (5 mcg/kg/min vs. 10 mcg/kg/min) and the second hour (10 mcg/kg/min vs. 17.5 mcg/kg/min).
  • SIS was higher in the second hour compared to the first for both groups.

Conclusions:

• Although no significant difference was observed between groups, rates of sedation within 15 minutes were low overall. 
• The median time to sedation of 13-15 minutes suggests that appropriate sedation was likely only achieved in patients receiving ketamine for induction, as its duration of action is 15-20 minutes compared to etomidate's 3-12 minutes. 
• The increase in sedative administration during the second hour post-intubation likely corresponds with resolution of neuromuscular blockade.

Bottom line:

• Awareness with paralysis is considered a never event, as it has been associated with serious long-term psychological consequences. This study highlights the crucial need for improvement of timely sedation administration after RSI in all settings.

References

1. Pappal RD, Roberts BW, Mohr NM et al. The ED-AWARENESS study: a prospective observational cohort study of awareness with paralysis in mechanically ventilated patients admitted from the emergency department. Ann Emerg Med. 2021; 77(5): 532-44.
2. Fuller BM, Pappal RD, Mohr NM et al. Awareness with paralysis in among critically ill emergency department patients: a prospective cohort study. Crit Care Med. 2022; 50(10): 1449-560.
3. Lembersky O, Golz D, Kramer C et al. Factors associated with post-intubation sedation after emergency department intubation: a report from the National Emergency Airway Registry. Am J Emerg Med; 2020; 38(3): 466-70.
4. Berg K, Gregg V, Cosgrove P, Wilkinson M. The administration of postintubation sedation in the pediatric emergency department. Pediatr Emerg Care. 2021; 37(11): e732.
5. Dukes J, Sarangarm P, Murtagh N, Kaucher KA. Proportion of intensive care unit patients receiving sedation after rapid sequence intubation with rocuronium. JAPhA Pharmacother. 2024; 1(3): 100007.
6. Cappuccilli AC, Sarangarm P, Dukes J, Kaucher KA. Comparison of time to sedation after rapid sequence intubation using long-acting neuromuscular blockers between the ED and ICU. Am J Emerg Med. 2025; 96: 128-133.