Opioid-induced respiratory depression is associated with increased tidal volume variability

Eur J Anaesthesiol. 2003 Feb;20(2):127-33. doi: 10.1017/s0265021503000243.


Background and objective: mu-agonistic opioids cause concentration-dependent hypoventilation and increased irregularity of breathing. The aim was to quantify opioid-induced irregularity of breathing and to investigate its time-course during and after an opioid infusion, and its ability to predict the severity of respiratory depression.

Methods: Twenty-three patients breathing spontaneously via a continuous positive airway pressure (CPAP) mask received an intravenous (i.v.) infusion of alfentanil (2.3 microg kg(-1) min(-1), 14 patients) or pirinitramide (piritramide) (17.9 microg kg(-1) min(-1), nine patients) until either a cumulative dose of 70 microg kg(-1) for alfentanil or 500 microg kg(-1) for pirinitramide had been achieved or the infusion had to be stopped for safety reasons. Tidal volumes (VT) and minute ventilation were measured with an anaesthesia workstation. For every 20 breaths, the quartile coefficient was calculated (Qeff20V(T)).

Results: Both the decrease of minute volume and the increase of Qeff20V(T) during and after opioid infusion were highly significant (P < 0.001, ANOVA). Patients in which the alfentanil infusion had to be terminated prematurely had lower minute volumes (P = 0.002, t-test) and higher Qeff20V(T) (P = 0.034, t-test) than those who received the complete dose. Changes in the regularity of breathing measured as Qeff20V(T) parallel those of minute ventilation during and after opioid infusion.

Conclusions: Opioids cause a more complicated disturbance of the control of respiration than a mere resetting to higher PCO2. Furthermore, Qeff20V(T) appears to predict the severity of opioid-induced respiratory depression.

MeSH terms

  • Adult
  • Aged
  • Alfentanil / administration & dosage*
  • Alfentanil / adverse effects*
  • Analgesics, Opioid / administration & dosage*
  • Analgesics, Opioid / adverse effects*
  • Analysis of Variance
  • Female
  • Humans
  • Infusions, Intravenous
  • Laryngeal Masks
  • Male
  • Middle Aged
  • Pirinitramide / administration & dosage*
  • Pirinitramide / adverse effects*
  • Respiratory Insufficiency / chemically induced*
  • Tidal Volume / drug effects
  • Time Factors


  • Analgesics, Opioid
  • Alfentanil
  • Pirinitramide