‘He remembered waking up with someone pulling very hard on his injured leg, which caused severe pain. He thinks he was in the ED. The patient said this was the worst pain he had every had and it was unbearable, and said he felt “scarred” by going through such intense pain. Reported that he tried to move but could not. He remembers hearing alarms, hearing and seeing 3-4 people standing around his bed and 1 person pulling hard on his injured leg.
Records noted that patient’s open fracture / dislocation was reduced in the ED after intubation and before transfer; reported “spike in blood pressure” during this event.’
-Patient reported memory / awareness experience-
Awareness with recall of paralysis is the recollection of sensory perceptions while under the influence of a neuromuscular blocking agent. When caring for critically ill intubated patients we tread a thin line of adequately managing analgesia and sedation without overdoing it and contributing to hypotension, or ICU delirium; all the while trying not to underdo it and leave our patients aware of paralysis, resulting in increased rates of PTSD, clinical depression, and complex phobias. (Up to 70% incidence in some studies).
What is Known:
- Previous operating room-based studies show IV anesthetic agents, and the use of long-acting neuromuscular blocking agents are associated with higher rates of awareness.
- ED studies have shown that in patients receiving longer acting neuromuscular blocking agents, there is a longer delay in the initiation of post intubation analgesia and sedation, (27 vs 15 min, ) and that once initiated, it is given in lower doses. (30 vs 42 mcg/kg/min )
- Anesthesia studies on a healthier population than is typically seen in the ED can help to provide baseline data and can help to potentially identify factors associated with awareness during anesthesia.
- The British NAP5 audit on Accidental Awareness during General Anesthesia  was an audit of all anesthetics provided over a 1-year timespan, with all patients surveyed after anesthesia. The NAP5 authors found an overall incidence of awareness of 1:19,600. Awareness during anesthesia when a neuromuscular blocking agent was used was 1:8200. Factors contributing to awareness during the induction phase of anesthesia were: Thiopental use, Rapid Sequence Intubation, Obesity, difficult airway management, and the use of a neuromuscular blocking agent.
- One EM relevant recommendation from NAP5: ‘These results suggest that more careful attention to dosing of induction agent is needed, along with a proper assessment that it has worked sufficiently well before neuromuscular blocking drugs are administered’. This is essentially a DSI strategy to ensure anesthesia before paralysis.
Pappal RD 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. PMID: 33485698 [Access on Read by QxMD]
Clinical Question: What is the prevalence of awareness with paralysis among ED patients receiving mechanical ventilation?
What They Did:
- Study objective: Assess the prevalence of awareness with paralysis in ED patients receiving mechanical ventilation.
- Single center prospective cohort study from June 2019 – May 2020 at a large academic emergency department (census 90,000 patients per year)
- Separately published study protocol in BMJ open 
- All medication data including sedative dosing and NMB dosing was collected
- Sedation depth was recorded using the Richmond Agitation-Sedation Scale
- Interviewers sought to purposely separate memories of ICU care while lightly sedated from memories with awareness of paralysis
- Memories were categorized as either factual / memories of feelings / delusional
- Awareness was considered to be present when a patient reported a memory of the period between losing consciousness and waking up. (Question 3 on the modified Brice questionnaire).
- Brice-Modified Questionnaire
- What was the last thing you remember before going to sleep?
- What is the first thing you remember after waking up?
- Do you remember anything between going to sleep and waking up?
- Did you dream during your procedure?
- Were your dreams disturbing to you?
- Awareness with paralysis was considered present when patients reported a memory of paralysis with concurrent documentation of a NMB having been administered.
- All patients reporting awareness of paralysis had a qualitative report of their experience.
- All reports of awareness were adjudicated by 3 experts. Awareness was confirmed when 2 out of 3 experts agreed
- Enrollment Timing: A full calendar year was selected to avoid any seasonal bias of reason for intubation (summer has increased trauma intubations, winter has increased respiratory illness related intubations)
- Sample size: Large enough to capture approximately 10 events, with likely 15% rate of death before extubation, and 30% rate of neurological impairment that prevents participation in survey
- Primary: Prevalence of awareness (Awareness with Paralysis – AWS)
- Secondary: Perceived threat (mediator for development of PTSD)
- ≥18 years of age
- Mechanical ventilation in ED (including transferred patients intubated at outside facilities)
- Death before extubation
- Neuro injury with deficit that precluded patient from participating in awareness survey (TBI, hypoxic brain injury, CVA)
- Transfer to another facility
- Refusal to answer questionnaire
- 833 mechanically ventilated patients assessed for eligibility
- 450 excluded
- 252 acute neuro injury with residual deficit
- 131 death before extubation
- 26 transferred to another facility
- 41 attrition
- 450 excluded
- 383 mechanically ventilated patients included in final analysis
- 27 patients were assessed for reports of awareness with paralysis
- Awareness with Paralysis (AWP): 10 pts (2.6%)
- 373 patients with no awareness with paralysis
- 9.9% of the 383 patients had no definite NMB documented
- Prevalence of AWP for patients definitely receiving a NMB was 2.9% (10/345)
- Exposure to rocuronium (during intubation, or after intubation):
- AWP: 70%
- No AWP: 31.4%
- Odds ratio: 5.1 (95% CI: 1.30 – 20.1)
- Of the 7 definite AWP patients, 4 received Etomidate, and 3 received Ketamine as their induction agent.
- Patient reported memory / awareness experience vignettes are documented in table 2 of the article and make for some sobering reading that should encourage all clinicians to confirm adequate sedation / analgesia prior to intubation / painful procedures.
- 27 patients were assessed for reports of awareness with paralysis
- Largest study of its kind in ED population
- Prospectively enrolled population
- Rigorous questionnaire
- Separates awareness of intubation from awareness during paralysis
- Enrollment of large, diverse ED population increases external validity of results
- Small sample size, single center study: Hypothesis generating study only
- Possible that an event was missed. (Unlikely given previous OR rates with iv anesthesia, and increased risk of awareness in ED population)
- Hawthorne effect amongst treating clinicians: If they know awareness is being watched for, their sedation and analgesia practices may be better than usual.
- Surveying for awareness could induce false memories. The associated higher perceived threat in patients with awareness suggests the patients’ experiences were real.
- Patients with definite, and possible awareness were included. This could inflate the event rate.
- 1.8% rate of definite awareness with paralysis is still a concerning result
- In the ED there appears to be a pattern of delayed intravenous sedation along with frequent administration of longer-acting neuromuscular blocking agents
- Solution: Order analgesia/sedation prior to intubation so that it is ready once patient is intubated
- Although a 2.6% rate of awareness with paralysis seems low, this was a small number of patients from a single institution. Extrapolated to multiple Emergency Departments across the globe this could equate to several thousand patients who are aware during paralysis
- The use of Rocuronium is a significant risk factor or awareness with paralysis. All patients with awareness with paralysis in the post-intubation phase of care had a longer-acting neuromuscular blocking agent
- Awareness with paralysis can result in psychological sequelae including PTSD, depression, and complex phobias, as stated before. In this trial patients with awareness with paralysis had a higher degree of perceived threats (i.e. perceived vulnerability during the hospital stay and after discharge)
“Awareness with paralysis occurs in a significant minority of ED patients who receive mechanical ventilation. Potential associations of awareness with paralysis with ED care and increased perceived threat warrant further evaluation.”
- When faced with the dual challenge of not adding to the risk of ICU delirium from oversedation, and not inflicting psychological trauma from patient’s awareness during paralysis, a reasonable strategy is to ensure moderate / deep sedation for the full duration of paralysis in the ED. This could be up to 90 min after a 1.5 mg/kg dose of Rocuronium.
- In patients in shock receiving a reduced dose of sedative, consider a DSI strategy to ensure sedation prior to paralysis
- Awareness with paralysis had a prevalence of 2.6% in this cohort of ED patients receiving mechanical ventilation and was associated with Rocuronium exposure
- These results should be considered exploratory and hypothesis generating
- Further studies are warranted to further quantify the risk of awareness with paralysis in the ED and should explore targeted interventions to reduce this risk
- Watt JM et al. Effect of Paralytic Type on Time to Post-Intubation Sedative Use in the Emergency Department. Emerg Med J 2013. PMID: 23139098
- Korinek JD et al. Comparison of Rocuronium and Succinylcholine on Post-intubation Sedative and Analgesic Dosing in the Emergency Department. Eur J Emerg Med 2014. PMID: 23510899
- Pandit JJ et al. 5th National Audit Project (NAP5) on Accidental Awareness During General Anaesthesia: Summary of Main Findings and Risk Factors. Br J Anaesth 2014. PMID: 25204697
- Pappal RD 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. PMID: 33485698 [Access on Read by QxMD]
- Pappal RD et al. Protocol for a Prospective, Observational Cohort Study of Awareness in Mechanically Ventilated Patients Admitted From the Emergency Department: The ED-AWARENESS Study. BMJ Open 2019. PMID: 31594905
Post Peer Reviewed By: Salim R. Rezaie, MD (Twitter: @srrezaie)