Hostname: page-component-cd9895bd7-mkpzs Total loading time: 0 Render date: 2024-12-17T11:03:55.506Z Has data issue: false hasContentIssue false

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

Published online by Cambridge University Press:  02 June 2005

T. Bouillon
Affiliation:
University of Bonn, Department of Anaesthesia and Critical Care Medicine, Bonn, Germany
J. Bruhn
Affiliation:
University of Bonn, Department of Anaesthesia and Critical Care Medicine, Bonn, Germany
H. Roepcke
Affiliation:
University of Bonn, Department of Anaesthesia and Critical Care Medicine, Bonn, Germany
A. Hoeft
Affiliation:
University of Bonn, Department of Anaesthesia and Critical Care Medicine, Bonn, Germany
Get access

Abstract

Summary

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.

Type
Original Article
Copyright
2003 European Society of Anaesthesiology

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Bellville W, Seed JC. The effect of drugs on the respiratory response to carbon dioxide. Anesthesiology 1960; 21: 727741.Google Scholar
Heitmann HB, Drechsel U, Herpfer G, Zindler M. Die Wirkung von Piritramid (Dipidolor) auf die Regulation der Atmung und die orthostatische Stabilitat des Kreislaufs. Anaesthesist 1970; 19: 152155.Google Scholar
Romagnoli A, Keats AS. Comparative respiratory depression of tillidine and morphine. Clin Pharmacol Ther 1975; 17: 523528.Google Scholar
Romagnoli A, Keats AS. Ceiling effect for respiratory depression by nalbuphine. Clin Pharmacol Ther 1980; 27: 478485.Google Scholar
Scamman FL, Ghoneim MM, Korttila K. Ventilatory and mental effects of alfentanil and fentanyl. Acta Anaesthesiol Scand 1984; 28: 6367.Google Scholar
Skatrud JB, Begle RL, Busch MA. Ventilatory effects of single, high-dose triazolam in awake human subjects. Clin Pharmacol Ther 1988; 44: 684689.Google Scholar
Bragg P, Zwass MS, Lau M, Fisher DM. Opioid pharmacodynamics in neonatal dogs: differences between morphine and fentanyl. J Appl Physiol 1995; 79: 15191524.Google Scholar
Glass PS, Iselin-Chaves IA, Goodman D, Delong E, Hermann DJ. Determination of the potency of remifentanil compared with alfentanil using ventilatory depression as the measure of opioid effect. Anesthesiology 1999; 90: 15561563.Google Scholar
Alexander CM, Gross JB. Sedative doses of midazolam depress hypoxic ventilatory responses in humans. Anesth Analg 1988; 67: 377382.Google Scholar
Blouin RT, Seifert HA, Babenco HD, Conard PF, Gross JB. Propofol depresses the hypoxic ventilatory response during conscious sedation and isohypercapnia. Anesthesiology 1993; 79: 11771182.Google Scholar
Alexander CM, Seifert HA, Blouin RT, Conard PF, Gross JB. Diphenhydramine enhances the interaction of hypercapnic and hypoxic ventilatory drive. Anesthesiology 1994; 80: 789795.Google Scholar
Jordan C. Assessment of the effects of drugs on respiration. Br J Anaesth 1982; 54: 763782.Google Scholar
Bouillon T, Schmidt C, Garstka G, et al. Pharmacokinetic– pharmacodynamic modeling of the respiratory depressant effect of alfentanil. Anesthesiology 1999; 91: 144155.Google Scholar
Murphy MR. Opioids. In: Barash PG, Cullen BF, Stoelting RK, eds. Clinical Anesthesia.Philadelphia, USA: J. B. Lippincott, 1989: 255279.
Bailey PL, Stanley TH. Narcotic intravenous anesthetics. In: Miller RD, ed. Anesthesia.New York, USA: Churchill Livingstone, 1990: 281366.
Gutstein HB, Akil H. Opioid analgesics. In: Hardman JG, Limbird LE, eds. Goodman & Gilman's The Pharmacological Basis of Therapeutics, 10th edn. New York, USA: McGraw-Hill, 2001: 569621.
Bouillon T, Schmidt C, Garstka G, et al. Comparison of the respiratory depressant effect of alfentanil and piritramide with a pharmacokinetic/pharmacodynamic model. Anesthesiology 1998; 89: A153.Google Scholar
Ausems ME, Hug CC Jr, Stanski DR, Burm AG. Plasma concentrations of alfentanil required to supplement nitrous oxide anesthesia for general surgery. Anesthesiology 1986; 65: 362373.Google Scholar
Jennett S. Assessment of respiratory effects of analgesic drugs. Br J Anaesth 1968; 40: 746755.Google Scholar
Jaffe RS, Fung DL. Constructing a heart rate variability analysis system. J Clin Monit 1994; 10: 4558.Google Scholar
Task Force of the European Society and the North American Society of Pacing and Electrophysiology. Heart rate variability. Circulation 1996; 93: 10431065.