Critical Care Alert, Critical Care, Airway, Toxicology

Critical Care Alert: Effect of Noninvasive Airway Management of Comatose Patients with Acute Poisoning: A Randomized Clinical Trial

ARTICLE:Freund Y, Viglino D, Cachanado M, et al. Effect of noninvasive airway management of comatose patients with acute poisoning: a randomized clinical trial. JAMA. 2023;330(23):2267-2274.


To evaluate how a strategy of withholding intubation on patients with GCS ≤ 8 due to suspected acute poisonings would affect a composite of clinical outcomes


Patients with a decreased level of consciousness may be at an elevated risk of aspiration due to loss of airway protective reflexes. Aspiration can lead to complications such as pneumonitis, pneumonia, respiratory distress, and respiratory failure which could lead to increased morbidity and mortality. One patient population that is transiently at risk for severe altered mental status are those with acute poisoning due to sedating substances such as alcohol, certain medications, and/or other illicit substances. Historically, this has led to a high rate of intubation in these altered patients with depressed Glasgow Coma Scale (GCS) scores.1 Often, this patient population is relatively healthy and would be expected to make a full recovery with minimal further medical intervention.  

"GCS less than 8, intubate" is a phrase learned by all emergency medicine trainees. Although not always strictly followed, it has acted as a quick reference for generations of physicians. The GCS scale was originally developed to objectively assess the level of consciousness in patients with head injuries.2 Given the vast etiologies of altered mental status, its validity in all scenarios has been debated.3,4 Currently, there are no high-evidence studies to guide the decision to intubate comatose patients with acute poisonings. Studies specifically looking at aspiration risk with decreased GCS have been mainly observational, and have had mixed results.5,6 Further obscuring the picture, the complications we are attempting to avoid with intubation can also be complications of intubation itself. That list includes aspiration, hemodynamic instability, and hypoxia but there are also complications of the intubation/ventilation exclusively such as ventilator-associated lung injury, ventilator-associated pneumonia, difficult intubation tissue injury, and dental injuries. 

Given the lack of evidence in comatose patients with acute poisoning, the authors designed this randomized clinical trial to determine whether a strategy of withholding intubation would improve outcomes compared to routine practice in which the decision of intubation was left to the discretion of the physician.


This study was a multicenter, unblinded, randomized parallel-group trial to compare a strategy of withholding tracheal intubation in comatose patients (GCS < 9) with acute poisoning compared to that of routine practice. The study took place in France between May 2021 and May 2023. There were 21 participating sites including 20 EDs and 1 ICU. Due to the participants’ decreased level of consciousness, informed consent before enrollment was waived. When available, consent was sought out from the patient's next of kin and delayed informed consent was obtained when the patient's state allowed it

Patients were randomly assigned in a 1:1 ratio to the control or intervention group and stratified by hospital.  For the intervention group, intubation was withheld unless an emergency intubation criteria was met. In the control group, the decision to intubate was left at the discretion of the treating emergency physician. Emergency criteria for intubation included: seizure, respiratory distress (defined as peripheral oxygen saturation < 90% after nasal cannula oxygen therapy), vomiting, and shock (defined as SBP < 90 mmHg that persisted after 1L crystalloid fluid resuscitation). Patients were closely monitored by a nurse or physician for the first 4 hours, or until the patient had recovered a sufficient level of consciousness, whichever occurred first. After 4 hours, the intervention was defined as complete and the patient was managed according to routine practice at the discretion of the emergency physician. Patients were then followed until hospital discharge or until 28 days after inclusion if still hospitalized. Adverse events from intubation were recorded in addition to the primary and secondary outcomes.

Primary and secondary analyses included all randomized patients except those who were opposed to the use of their data or were under legal protection. A per-protocol analysis was conducted after further exclusion of patients who failed to meet eligibility criteria or deviated from the protocol. An exploratory analysis compared the primary end-point length of ICU stay and length of hospital stay between patients receiving and not receiving intubation.


  • Adult patients ≥ 18 who presented with a clinical suspicion of acute poisoning (alcohol, drug, or medication) and a decreased level of consciousness with a GCS score ≤ 8 as assessed by the treating physician


  • Patients known to be pregnant, incarcerated, involuntarily detained, or who had an immediate need for tracheal intubation (as defined by respiratory distress, suspicion of brain injury, seizure, or shock)
  • Suspicion of cardiotropic drug poisoning including: beta blockers, calcium channel blockers, or angiotensin-converting enzyme inhibitors. Poisoning with signs of QRS or QT prolongation on ECG
  • Intoxication with a single toxic substance that could be reversed (ie, opioids or benzodiazepines)


  • In-hospital death
  • Length of ICU stay
  • Length of hospital stay, truncated to 28 days. Discharge included transfer to a psychiatric facility


  • The proportion of patients, number of days on mechanical ventilation until hospital discharge or day through 28 days
  • The proportion of patients admitted to the ICU
  • The portion of patients with rapid-onset pneumonia. Pneumonia diagnostic criteria included:
    • 2 or more serial chest x-rays or CT scans showing new/progressive infiltrates, consolidation, cavitation with at least one of: fever, leukopenia/leukocytosis, and/or an adult greater than 70 years of age with altered mental status
    • 2 or more of the following: new purulent sputum/change in sputum production/increased suctioning requirements, new onset of worsening cough/dyspnea/tachypnea, rales or bronchial breath sounds, and/or worsening gas exchange via increasing oxygen requirements or ventilator demands
  • Adverse events from intubation; defined as any of the following during the peri-intubation period:
    • Peripheral oxygen saturation <90%
    • Dental trauma
    • Vomiting
    • Cardiac arrest
    • Systolic blood pressure < 65 mmHg
    • Esophageal intubation
    • Intubation Difficulty Scale score of 5 or more


  • From May 16, 2021 - April 12, 2023: 237 patients were randomized
    • 225 were analyzed (116 in the intervention group)
      • Mean age: 33 years old
      • 38% were female
      • Median GCS: 6
      • Main source of poisoning: Alcohol
    • The intervention group had 19 intubations (16.4% of patients)
      • 16 had at least 1 criteria for emergency intubation
    • The control group had 63 intubations (57.8% of patients)

Primary Outcomes

  • No deaths were reported in either group
  • The median length of stay in the ICU resulted in 0 hours in the intervention vs. 24 hours for the control group (RR 0.39; 95% CI 0.24-0.66)
  • The median length of stay in the hospital was 21.5 hours in the intervention vs. 37.0 hours in the control group (RR 0.74; 95% CI 0.53-1.03)
  • From their exploratory analysis of the above: Clinical benefit for patients who were not intubated with a win ratio of 12.76  (95% CI 7.92-20.57)

Secondary Outcomes

  • The percentage of patients admitted to the ICU was 39.7% in the intervention vs. 66.1% for the control group (Absolute risk difference -29.2 percentage points; 95% CI -41.0 to -17.4)
  • The percentage of patients receiving mechanical ventilation was 18.1% in the intervention vs. 59.6% in the control group (absolute risk difference -42.5 percentage points; 95% CI -54.1 to -30.9)
  • The adverse events from intubation were 6.0% in the intervention group vs. 14.7% in the control group (absolute risk difference -8.6 percentage points; 95% CI -16.6 to -0.7)
  • Pneumonia after intubation occurred in 6.9% of the intervention vs. 14.7% of the control group (absolute risk difference -7.8 percentage points; 95% CI -15.9 to 0.3)

Among intubated patients, there was no difference between the groups in: Risk of adverse events from intubation, first pass failure, or the median length of ICU stay or hospital stay.


  • The trial was unblinded as physicians were aware of their group assignment
  • A per-protocol analysis can undermine randomization
  • There were no deaths in the study population and the choice of this as the primary outcome is therefore questionable
  • Only 1 in 5 patients were admitted to the ICU. This resulted in the main benefit being reduced rates of pneumonia, reduction in length of stay and reduced ICU admissions–none of which reached statistical significance
  • Intubation occurred in a variety of settings including prehospital, the ED, and ICU which may have contributed to differences in findings
  • Patients were included if there was a suspicion of acute poisoning which could not always be confirmed
  • The use of a bougie and/or video laryngoscope was not recorded
  • GCS was not explicitly designed to guide decisions or make clinical predictions for aspiration risk or need for intubation in this patient population


A conservative airway approach for patients suspected of acute poisoning was associated with greater patient benefit including reduced length of stay in the hospital, ICU admissions, and reduced risk of pneumonia. Given these results, it would be reasonable to not reflexively proceed to intubation for patients with suspected acute poisoning and a GCS ≤ 8 who otherwise show no signs of acute respiratory failure.

However, some instances of acute poisoning will likely require intubation as demonstrated by the intervention group. It is important to continuously weigh the risks/benefits, perform serial examinations, and use clinical judgment when treating these patients.


  1. Beaune S, Juvin P, Beauchet A, Casalino E, Megarbane B. Deliberate drug poisonings admitted to an emergency department in Paris area - a descriptive study and assessment of risk factors for intensive care admission. Eur Rev Med Pharmacol Sci. 2016;20(6):1174-1179.
  2. Teasdale G, Jennett B. Assessment of coma and impaired consciousness. A practical scale. Lancet. 1974;2(7872):81-84.
  3. Burket GA, Horowitz BZ, Hendrickson RG, Beauchamp GA. Endotracheal Intubation in the Pharmaceutical-Poisoned Patient: a Narrative Review of the Literature. J Med Toxicol. 2021;17(1):61-69.
  4. Orso D, Vetrugno L, Federici N, D'Andrea N, Bove T. Endotracheal intubation to reduce aspiration events in acutely comatose patients: a systematic review. Scand J Trauma Resusc Emerg Med. 2020;28(1):116.
  5. Eizadi-Mood N, Saghaei M, Alfred S, et al. Comparative evaluation of Glasgow Coma Score and gag reflex in predicting aspiration pneumonitis in acute poisoning. J Crit Care. 2009;24(3):470.e9-470.e4.7E15.
  6. Van Helmond LPFM, Gresnigt FMJ. Safety of withholding intubation in gamma-hydroxybutyrate- and gamma-butyrolactone-intoxicated coma patients in the emergency department. Eur J Emerg Med. 2020;27(3):223-227.

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