NICO: Noninvasive Airway Management in Comatose Poisoned Patients (2023)

“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.”

— The NICO Trial Investigators

1. Publication Details

  • Trial Title: Effect of Noninvasive Airway Management of Comatose Patients With Acute Poisoning: A Randomized Clinical Trial.
  • Citation: Freund Y, Viglino D, Cachanado M, et al; for the NICO Trial Investigators. Effect of Noninvasive Airway Management of Comatose Patients With Acute Poisoning: A Randomized Clinical Trial. JAMA. 2023;330(23):2267–2274. doi:10.1001/jama.2023.24391.
  • Published: December 19, 2023, in the Journal of the American Medical Association (JAMA).
  • Author: Yonathan Freund, M.D., Ph.D.
  • Funding: French Ministry of Health.

2. Keywords

Poisoning, Overdose, Coma, Glasgow Coma Scale (GCS), Airway Management, Intubation, Noninvasive Management.

3. The Clinical Question

In comatose adult patients with suspected acute poisoning (GCS < 9) (Population), does a conservative strategy of withholding intubation (Intervention) compared to routine practice (discretionary intubation) (Comparison) improve the composite outcome of in-hospital death, ICU length of stay, and hospital length of stay (Outcome)?

4. Background and Rationale

  • Existing Knowledge: The practice of intubating comatose patients with a Glasgow Coma Scale (GCS) score of 8 or less (“GCS less than 8, intubate”) is a long-standing dogma in emergency medicine, originally developed for patients with traumatic brain injury to protect the airway.
  • Knowledge Gap: It was unclear if this aggressive approach was necessary or beneficial for patients with transient coma from poisoning. Intubation itself carries risks (e.g., hemodynamic instability, pneumonia, trauma), and many poisoned patients recover consciousness quickly. There was no high-quality randomized evidence to guide this common clinical decision.
  • Proposed Hypothesis: The authors hypothesized that a conservative strategy of withholding immediate intubation in comatose poisoned patients would be safe and associated with better clinical outcomes (fewer complications, shorter hospital stays) compared to routine practice.

5. Study Design and Methods

  • Design: A multicenter, open-label, randomized, parallel-group clinical trial.
  • Setting: 20 emergency departments and 1 ICU in France.
  • Trial Period: Enrollment from May 2021 to April 2023.
  • Population:
    • Inclusion Criteria: Adult patients (≥18 years) with suspected acute poisoning and a GCS score less than 9.
    • Exclusion Criteria: Patients with a clear immediate need for intubation (e.g., shock, respiratory distress, seizure, witnessed aspiration) or intoxication with cardiotropic drugs.
  • Intervention: Conservative Group: Intubation was withheld unless specific emergency criteria developed (shock, respiratory distress, seizure, witnessed aspiration). Patients were closely monitored.
  • Control: Routine Practice Group: The decision to intubate was left to the discretion of the treating physician, as per usual care.
  • Management Common to Both Groups: All other aspects of care were standard for poisoned patients.

6. Key Results

  • Enrollment and Baseline: 225 patients were randomized (116 to the conservative group, 109 to the routine practice group). The groups were well-matched, with a median GCS of 6. Alcohol was the most common toxin (~67%).
  • Trial Status: The trial was completed as planned.
  • Primary Outcome: The conservative strategy was associated with a significant clinical benefit for the hierarchical composite primary endpoint (in-hospital death, ICU length of stay, and hospital length of stay), with a win ratio of 1.85 (95% CI, 1.33 to 2.58; P < .001). This benefit was driven by shorter ICU and hospital stays, as there were no deaths in either group.
  • Secondary Outcomes: The rate of intubation was dramatically lower in the conservative group (16%) compared to the routine practice group (58%). The conservative group also had fewer adverse events (6.0% vs. 14.7%) and a trend toward less pneumonia (6.9% vs. 14.7%).

7. Medical Statistics

  • Analysis Principle: An intention-to-treat analysis was performed.
  • Statistical Tests Used: The primary outcome was analyzed using the win ratio method, a statistical approach for hierarchical composite endpoints.
  • Key Statistic(s) Reported:
    • Primary Outcome: Win Ratio 1.85 (95% CI, 1.33 to 2.58; P < .001).
  • Interpretation of Key Statistic(s):
    • Win Ratio:
      • Formula: Conceptually, Win Ratio = (Total Wins) / (Total Losses) across all paired comparisons.
      • Calculation: The paper reports the Win Ratio as 1.85.
      • Clinical Meaning: A win ratio of 1.85 means that for any randomly selected pair of patients (one from each group), the patient in the conservative strategy group was 85% more likely to have a better outcome (i.e., “win”) on the hierarchical composite endpoint (survival, then shorter ICU stay, then shorter hospital stay) than the patient in the routine practice group.
    • Confidence Interval (CI):
      • Formula: Conceptually, CI = (Point Estimate) ± (Margin of Error).
      • Calculation: The reported 95% CI was 1.33 to 2.58.
      • Clinical Meaning: Since the entire range of the 95% CI is above 1.0, it indicates that the result is statistically significant and the true effect is very unlikely to be one of no benefit or harm.
    • P-value:
      • Calculation: The reported p-value was < .001.
      • Clinical Meaning: The very low p-value indicates that the observed difference is highly unlikely to be due to chance, strongly supporting the conclusion that the conservative strategy is superior.

8. Strengths of the Study

  • First RCT: This was the first randomized controlled trial to directly challenge the “GCS < 8, intubate” dogma in poisoned patients.
  • Pragmatic Design: The study addressed a common and important clinical question with a design that is applicable to real-world emergency department practice.
  • Patient-Centered Outcomes: The primary outcome included length of stay, which is an important patient-centered and health-system outcome.

9. Limitations and Weaknesses

  • Unblinded Design: The open-label nature could have led to performance bias (a Hawthorne effect), where clinicians in the routine practice group felt more pressure to intubate.
  • Single Country: The study was conducted entirely in France, which may limit generalizability to healthcare systems with different ICU admission practices or pre-hospital care.
  • Dominant Toxin: The high prevalence of alcohol intoxication may limit the applicability of the findings to poisonings with other substances that have different clinical courses.

10. Conclusion of the Authors

“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.”

11. To Summarize

  • Impact on Current Practice: This is a landmark, practice-changing trial that provides strong evidence to abandon the reflexive intubation of all comatose poisoned patients based solely on a GCS score. It demonstrates that a “watchful waiting” approach is not only safe but superior for patient-centered outcomes in this specific population.
  • Specific Recommendations:
    • Patient Selection: For adult patients with coma (GCS < 9) due to suspected poisoning, who do not have immediate indications for intubation (like shock or respiratory failure).
    • Actionable Intervention: Adopt a conservative airway strategy. Do not intubate based on GCS score alone. Instead, monitor the patient closely and intubate only if specific indications arise.
    • Expected Benefit: A significant reduction in the need for mechanical ventilation, shorter ICU and hospital stays, and fewer adverse events.
  • What This Trial Does NOT Mean: This trial does not mean that comatose poisoned patients should never be intubated. It means the decision should be based on physiological parameters (shock, hypoxia, etc.) rather than just the GCS score. The findings do not apply to patients with traumatic brain injury.

12. Context and Related Studies

  • Building on Previous Evidence: This trial was designed to provide high-quality evidence to address a long-standing clinical dogma that was based on principles derived from a different patient population (traumatic brain injury) and supported by limited, low-quality observational data.
  • Influence on Subsequent Research: The NICO trial will likely lead to major changes in international guidelines for the management of poisoned patients. It will shift the focus from prophylactic intubation to careful clinical monitoring and selective airway intervention.

13. Unresolved Questions & Future Directions

  • Unresolved Questions: What is the optimal monitoring strategy for non-intubated comatose patients? Do these findings apply to poisonings with substances other than alcohol that may have a more prolonged or unpredictable course?
  • Future Directions: Future research may focus on developing better risk-stratification tools to identify which poisoned patients are at highest risk of deterioration and may still benefit from early intubation.

14. External Links

15. Framework for Critical Appraisal

  • Clinical Question: The question was of fundamental importance, challenging a deeply ingrained medical dogma with significant implications for patient safety and resource utilization.
  • Methods: The randomized trial design was appropriate. While the open-label nature is a limitation, the objective components of the primary outcome (length of stay) are less susceptible to bias.
  • Results: The trial had a clear and statistically robust positive result for its primary outcome, driven by clinically meaningful reductions in ICU and hospital length of stay. The large reduction in intubation rates and adverse events further strengthens the findings.
  • Conclusions and Applicability: The authors’ conclusion is strongly supported by the data. The results are highly applicable to emergency departments and ICUs worldwide and should lead to a direct change in the management of comatose poisoned patients.

16. Disclaimer and Contact

This summary is provided by the Academic Committee of ESBICM (ACE) to facilitate the understanding of this study; readers are advised to refer to the original trial document for a deeper understanding. If you find any information incorrect, or missing, or it needs an update or have a request for a specific critical care trial summary, kindly write to us at academics[at]esbicm.org.

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