Skip to main content
    • Aa
    • Aa

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

  • T. Bouillon (a1), J. Bruhn (a1), H. Roepcke (a1) and A. Hoeft (a1)


Background and objective: μ-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 μg kg−1 min−1, 14 patients) or pirinitramide (piritramide) (17.9 μg kg−1 min−1, nine patients) until either a cumulative dose of 70 μg kg−1 for alfentanil or 500 μg 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 (Qeff20VT).

Results: Both the decrease of minute volume and the increase of Qeff20VT 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 Qeff20VT (P = 0.034, t-test) than those who received the complete dose. Changes in the regularity of breathing measured as Qeff20VT 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, Qeff20VT appears to predict the severity of opioid-induced respiratory depression.

Corresponding author
Correspondence to: Thomas Bouillon, Department of Anaesthesiology, LUMC, P5-Q, Albinusdreef 2, 2300 RC Leiden, The Netherlands. E-mail:; Tel: +31 71 526 2301; Fax: +31 71 526 6953
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

BellvilleW, SeedJC. The effect of drugs on the respiratory response to carbon dioxide.Anesthesiology1960; 21: 727741.

RomagnoliA, KeatsAS. Comparative respiratory depression of tillidine and morphine.Clin Pharmacol Ther1975; 17: 523528.

RomagnoliA, KeatsAS. Ceiling effect for respiratory depression by nalbuphine.Clin Pharmacol Ther1980; 27: 478485.

ScammanFL, GhoneimMM, KorttilaK. Ventilatory and mental effects of alfentanil and fentanyl.Acta Anaesthesiol Scand1984; 28: 6367.

SkatrudJB, BegleRL, BuschMA. Ventilatory effects of single, high-dose triazolam in awake human subjects.Clin Pharmacol Ther1988; 44: 684689.

GlassPS, Iselin-ChavesIA, GoodmanD, DelongE, HermannDJ. Determination of the potency of remifentanil compared with alfentanil using ventilatory depression as the measure of opioid effect.Anesthesiology1999; 90: 15561563.

AlexanderCM, GrossJB. Sedative doses of midazolam depress hypoxic ventilatory responses in humans.Anesth Analg1988; 67: 377382.

BlouinRT, SeifertHA, BabencoHD, ConardPF, GrossJB. Propofol depresses the hypoxic ventilatory response during conscious sedation and isohypercapnia.Anesthesiology1993; 79: 11771182.

AlexanderCM, SeifertHA, BlouinRT, ConardPF, GrossJB. Diphenhydramine enhances the interaction of hypercapnic and hypoxic ventilatory drive.Anesthesiology1994; 80: 789795.

JordanC. Assessment of the effects of drugs on respiration.Br J Anaesth1982; 54: 763782.

BouillonT, SchmidtC, GarstkaG, et al. Pharmacokinetic– pharmacodynamic modeling of the respiratory depressant effect of alfentanil.Anesthesiology1999; 91: 144155.

BouillonT, SchmidtC, GarstkaG, et al. Comparison of the respiratory depressant effect of alfentanil and piritramide with a pharmacokinetic/pharmacodynamic model.Anesthesiology1998; 89: A153.

AusemsME, HugCCJr, StanskiDR, BurmAG. Plasma concentrations of alfentanil required to supplement nitrous oxide anesthesia for general surgery.Anesthesiology1986; 65: 362373.

JennettS. Assessment of respiratory effects of analgesic drugs.Br J Anaesth1968; 40: 746755.

JaffeRS, FungDL. Constructing a heart rate variability analysis system.J Clin Monit1994; 10: 4558.

Task Force of the European Society and the North American Society of Pacing and Electrophysiology. Heart rate variability.Circulation1996; 93: 10431065.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

European Journal of Anaesthesiology
  • ISSN: 0265-0215
  • EISSN: 1365-2346
  • URL: /core/journals/european-journal-of-anaesthesiology
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Abstract views

Total abstract views: 185 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 22nd September 2017. This data will be updated every 24 hours.