Mechanism of respiratory insufficiency in pure or mixed drug-induced coma involving benzodiazepines

J Toxicol Clin Toxicol. 2002;40(1):35-47. doi: 10.1081/clt-120002884.


Objective: We tested the hypothesis that the mechanism of respiratory insufficiency in drug-induced coma involving benzodiazepines is an increase in upper airway resistance.

Methods: Eighteen nonintubated and seven intubated (control) patients were poisoned with hypnotic sedatives involving benzodiazepines. Neurological and respiratory parameters were measured by polysomnography before and after flumazenil. Flumazenil was administered as escalating bolus doses followed by a continuous infusion.

Results: Upon entry, Glasgow Coma Score was 7 +/- 1 in nonintubated and 5 +/- 1 in intubated patients. Snoring with flow limitation and obstructive apnea were recorded in 16 and 5 among the 18 nonintubated patients, respectively. Central apnea was not observed. Total pulmonary resistance was 2.5-fold higher in nonintubated patients than in intubated patients. Total and resistive work of breathing (WOB) was significantly greater in the nonintubated group. Flumazenil bolus administration was associated with an improvement in Glasgow Coma Score from 7 +/- 1 to 13 +/- 1 in the nonintubatedpatients, and from 5 +/- 1 to 11 +/- in the intubated patients. Mean effective bolus doses were 0.3 +/- 0.1 mg in nonintubated patients and 0.6 +/- 0.1 mg in intubated patients. Tidal and minute volumes increased significantly, and WOB decreased significantly in nonintubated patients. In nonintubated patients, the decrease in total WOB resulted from a significant decrease in resistive WOB.

Conclusion: Drug-induced coma involving benzodiazepines is characterized by snoring with flow limitation and obstructive apnea. The mechanism of respiratory insufficiency in nonintubated patients with drug-induced coma involving benzodiazepines is an increase in upper airway resistance and WOB.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Airway Resistance / drug effects
  • Anti-Anxiety Agents / poisoning*
  • Antidotes / therapeutic use
  • Coma / chemically induced
  • Coma / complications*
  • Drug Overdose
  • Esophagus
  • Female
  • Flumazenil / therapeutic use
  • Glasgow Coma Scale
  • Humans
  • Intubation
  • Male
  • Middle Aged
  • Oximetry
  • Polysomnography
  • Respiratory Insufficiency / etiology*
  • Respiratory Insufficiency / physiopathology
  • Respiratory Muscles / drug effects
  • Sleep Apnea, Obstructive / etiology
  • Snoring / etiology
  • Tidal Volume / drug effects
  • Work of Breathing / drug effects


  • Anti-Anxiety Agents
  • Antidotes
  • Flumazenil