Increased tidal volume variability in children is a better marker of opioid-induced respiratory depression than decreased respiratory rate

J Clin Monit Comput. 2004 Jun;18(3):171-8. doi: 10.1023/b:jocm.0000042922.63647.b9.


Objective: During opioid administration, decreasing respiratory rate is typically used as a predictor of respiratory depression. Prior to opioid-induced apnea, progressively irregular breathing patterns have been noticed. We hypothesize that opioid administration to children will increase tidal volume variability (TV(var)) and that this will be a better predictor of respiratory depression than a decrease in respiratory rate.

Methods: We recruited 32 children aged 2-8 years scheduled to undergo surgery. During spontaneous ventilation, flow rates and respiratory rates were continuously recorded, while remifentanil was infused at stepwise increasing doses each lasting 10 min. The infusion was continued until the patient showed signs of respiratory depression. Flow data from each dose was used to calculate tidal volumes, from which TV(var) was calculated. The respiratory rate and TV(var) during the last (D(last)), second to last (D-2), and third to last (D-3), administered doses were compared to those during baseline (fourth to last dose). We chose a threshold of TV(var) increase and compared it to a decrease in respiratory rate below 10 breaths per min as predictors of respiratory depression.

Results: Compared to baseline, the TV(var) increased by 336% and 668% during D(-2) and D(last), respectively, whereas respiratory rate decreased by 14.3%, 31.7%, and 55.5% during D(-3), D(-2), and D(last), respectively. A threshold increase in TV(var) of 150% over baseline correctly predicted respiratory depression in 41% of patients, compared to a drop in respiratory rate correctly predicting 22% of patients.

Conclusions: TV(var) increases as children approach opioid-induced respiratory depression. This is a more useful predictor of respiratory depression than a fall in respiratory rate because the TV(var) increase is 10 times the drop in respiratory rate. A TV(var) increase also correctly predicts respiratory depression twice as often as decreased respiratory rate and is independent of age-related alterations in physiologic respiratory rates.

MeSH terms

  • Analgesics, Opioid / pharmacology*
  • Anesthetics, Intravenous*
  • Body Size
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Male
  • Piperidines / pharmacology*
  • Remifentanil
  • Respiration / drug effects*
  • Respiratory Insufficiency / chemically induced
  • Tidal Volume / drug effects*


  • Analgesics, Opioid
  • Anesthetics, Intravenous
  • Piperidines
  • Remifentanil