By Betty Tran, MD, MSc
Associate Professor of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago
SYNOPSIS: In this unblinded, randomized trial of adults presenting with acute poisoning and a Glasgow Coma Scale score less than 9, those for whom intubation was withheld unless emergently indicated had decreased intensive care unit and hospital lengths of stay and a lower rate of pneumonia.
SOURCE: 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;330:2267-2274.
The Non-Invasive Airway Management of Comatose Poisoned Emergency Patients (NICO) was a multicenter, unblinded, randomized, parallel-group trial based in France comparing a strategy of withholding intubation in comatose patients presenting with acute toxic ingestion to routine practice. Adults with suspected acute poisoning and a Glasgow Coma Scale (GCS) score of less than 9 were eligible for enrollment. Exclusion criteria included pregnancy, incarceration, an immediate need for intubation (i.e., respiratory distress, brain injury, seizure, shock), suspected cardiotropic drug poisoning (beta-blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors), or the presence of a single toxin that could be easily reversed. Patients were randomized in a 1:1 ratio to usual care/control or the intervention group. In the control group, intubation was at the discretion of the emergency physician. In the intervention group, intubation was purposefully withheld unless specific emergency intubation criteria were met. These included seizure, peripheral oxygen saturation (SpO2) < 90% despite nasal cannula, vomiting, and shock (systolic blood pressure < 90 mmHg despite 1 L crystalloid). The window for intervention was up to four hours, after which the patient was managed per routine practice.
The primary outcome was a hierarchical composite end point of in-hospital death, intensive care unit (ICU) length of stay (LOS), and hospital LOS determined at day 28. Secondary outcomes included each of these components, mechanical ventilation days, proportion of patients admitted to the ICU, proportion of patients with pneumonia, and adverse events related to intubation. For the primary analysis, the Finkelstein-Schoenfeld method was used to compare each patient in the intervention group with each patient in the control group by denoting a win, loss, or tie hierarchically by clinical importance (death, then ICU LOS, then hospital LOS) for each pairwise comparison; win ratios were subsequently calculated.
Overall, 225 patients were analyzed (116 in the intervention group and 109 in the control group). The mean age was 33 years (interquartile range [IQR], 25-49 years), 38% were female, and median GCS score was 6 (IQR, 3-7). The main toxin was alcohol, followed by benzodiazepines. In terms of the primary outcome, the intervention strategy of withholding intubation resulted in a win ratio of 1.85 (95% confidence interval [CI], 1.33-2.58; P < 0.001) consistent with clinical benefit in terms of the composite end point. However, no patients died in either the intervention group or the control group. In terms of secondary outcomes, compared to the control group, fewer patients in the intervention group were admitted to the ICU (39.7% vs. 66.1%, respectively), received mechanical ventilation (18.1% vs. 59.6%), and had any adverse effects related to intubation (6.0% vs. 14.7%). In addition, there was a trend toward fewer patients in the intervention group developing pneumonia compared to the control group (6.9% vs. 14.7%, respectively; absolute risk difference, -7.8 percentage points, 95% CI, -15.9 to 0.3). There was no difference between groups in terms of median ICU LOS or hospital LOS.
COMMENTARY
Airway protection is a common response to the question of why an ICU patient presenting with acute intoxication/poisoning was intubated in the emergency department. The presumption is that we are protecting the patient’s airway from aspiration of gastric contents and subsequent pneumonia in addition to clearing respiratory secretions with the act of intubation. Historically, however, the data supporting this tenet are limited. The NICO trial addresses this knowledge gap.
Based on the trial results, the take-home points from this study include the findings that a strategy of withholding intubation unless emergently indicated in patients with acute poisoning/intoxication leads to fewer ICU admissions and possibly a lower rate of pneumonia with no increased mortality.
The trial findings are helpful in clinical decision-making, although the results should be applied with caution in non-selected patient populations. The trial population excluded patients with acute hypoxemia requiring more than 4 liters/minute of supplemental oxygen, shock (defined as a systolic blood pressure < 90 mmHg after 1 L of crystalloid), vomiting, cardiotropic ingestion, and seizure or other acute cerebral insults. Ultimately, the results give medical providers the latitude to not intubate all or even most patients presenting with acute toxic ingestions based on the strong argument that more harm may come rather than benefit. It certainly challenges the predominant bias that mental status, as measured by GCS, should be the sole criterion to determine the need for intubation to prevent aspiration. Furthermore, it challenges the notion that doing more is better; in this case, the intervention group actually is withholding an intervention, with resultant clinical benefits. These are critical lessons. The long-standing mantra, “GCS less than 8, intubate,” may need to be rethought in additional robust, prospective, randomized trials in different patient populations.
