The NICO Trial: NIV in Comatose Patients with Acute Poisoning

Background:  Patients with decreased level of consciousness due to alcohol, drugs, or medications commonly present to the ED. These patients can be at risk of vomiting and aspiration and often prompts clinicians to pursue definitive airway management to avoid pneumonia and other complications. It is unclear, though, if the risks of intubation (including ventilator associated pneumonia) outweighs the benefits. Additionally, intubation can risk hemodynamic instability as well as hypoxemia from the procedure itself.  There has been no high level evidence to help guide practice until now…the Non-Invasive Airway Management of Comatose Poisoned Emergency Patients (NICO) trial.

Paper: Freund Y et al. Effect of Noninvasive Airway management of Comatose Patients with Acute Poisoning: A Randomized Clinical Trial. JAMA 2023. PMID: 38019968

Clinical Question: In patients with suspected acute poisoning and GCS <9, is a conservative airway strategy of withholding intubation associated with a reduction in death, ICU LOS, and hospital LOS compared with routine practice of intubation?

What They Did: 

• Multicenter, unblinded, randomized, parallel-group clinical trial
• 20 EDs and 1 ICU in France
• Comatose patients with suspected acute poisoning and GCS <9
• Randomized 1:1 to
  • Standard Practice : Intubation Group
    • Seizure
    • Respiratory distress (SpO2 <90% persisted after nasal cannula)
    • Vomiting
    • Shock (SBP <90mmHg persisted after 1L crystalloid)
  • Conservative Practice: No Intubation Group
    • Intubation left to discretion of treating physician
  • In patients where intubation required
    • Induction drug: Either etomidate or ketamine
    • Paralytic drug: Either succinylcholine or rocuronium
    • Preoxygenation: Maintaining SpO2 100% for 2min; If patient remained hypoxemic, NIV was permitted
    • Laryngoscopy: Use of DL or VL and use of bougie or stylet left to the discretion of the physician
    • Waveform capnography was recommended to confirm ETT position

Outcomes:

• Primary: Hierarchal composite endpoint of in-hospital death, length of ICU stay, and length of hospital stay
• Key Secondary:
  • Adverse events resulting from intubation
  • Pneumonia within 48 hours

Inclusion:

• Adult patients ≥18 years of age
• Clinical suspicion of acute poisoning
• Decreased level of consciousness (GCS <9)

Exclusion:

• Pregnant
• Incarcerated or Involuntarily detained
• Immediate need for tracheal intubation (Defined by signs of respiratory distress, clinical suspicion of any brain injury, seizure, or shock)
• Any suspicion of cardiotropic drug poisoning (Beta blockers, calcium channel inhibitors, or angiotensin-converting enzyme inhibitors)
• Intoxication with a single toxic substance that could be reversed (opioids and benzodiazepines)

Results:

• 225 patients
  • Mean age: 33 years
  • Median GCS: 6 (Range 3 to 7)
  • Alcohol was the implicated toxin in 67% of cases
  • 116 intervention group (16% intubation rate)
  • 109 in the control group (58% intubation rate)
• Hierarchical Composite Primary End Point was improved in the avoid intubation group compared to the intubation group: Win ratio 1.85; 95% CI 1.33 to 2.58; p < 0.001

Strengths:

• Asks a clinically important question
• Groups well balanced at baseline
• Randomization appropriately performed to avoid bias
• Multicenter increasing external validity
• Only RCT to date comparing conservative to standard practice of intubation in patients with decreased GCS due to acute poisoning

Limitations:

• Unblinded study could lead to a Hawthorne effect that may have influenced physician behavior on the decision to intubate
• Primary outcome driven by reduction in ICU LOS (i.e. not a patient oriented outcome)
• Single country study which may limit generalizability
• Excluded pregnancy where risk of emesis is increased due to gravid uterus
• Alcohol was the implicated in the overwhelming majority of patients. This decreases generalizability to other substances.
• Unclear monitoring strategy for patients not intubated or in the conservative arm

Discussion:

• No patient was treated with gastric evacuation nor activated charcoal in this trial
• In this trial there was an absolute reduction of 7.8% of the risk of pneumonia by not intubating patients (NNT = 13)
• Additionally there was an absolute reduction of 12.2% of the risk of first pass failure by not intubating patients as well (NNT = 8)

Author Conclusion: “Among comatose patients with suspected acute poisoning, a conservative strategy of withholding intubation was associated with a greater clinical benefit for the composite end point of in-hospital death, length of ICU stay, and length of hospital stay.”

Clinical Take Home Point: In patients with decreased level of consciousness due to acute poisoning a conservative strategy of withholding intubation leads to less ICU admissions, median length of ICU/hospital stay, and a lower risk of adverse events.

References:

1. Freund Y et al. Effect of Noninvasive Airway management of Comatose Patients with Acute Poisoning: A Randomized Clinical Trial. JAMA 2023. PMID: 38019968

Post Peer Reviewed By: Anand Swaminathan, MD (Twitter/X: @EMSwami)