Correspondence  |   October 2019
Opioid-induced Ventilatory Depression in Sleep Apnea: Comment
Author Notes
  • Trident Medical Center, Charleston, South Carolina (F.J.O.).
  • (Accepted for publication May 20, 2019.)
    (Accepted for publication May 20, 2019.)×
Article Information
Correspondence   |   October 2019
Opioid-induced Ventilatory Depression in Sleep Apnea: Comment
Anesthesiology 10 2019, Vol.131, 936-937. doi:
Anesthesiology 10 2019, Vol.131, 936-937. doi:
To the Editor:
On the front page of the February 2019 issue of Anesthesiology, the article by Doufas et al. was encapsulated as, “Adults with Obstructive Sleep Apnea Do Not Have Increased Sensitivity to Opioid-induced Ventilatory Depression.”1  This is potentially misleading.
The complexity of the study design, pharmacokinetic/pharmacodynamic modeling, and the assumptions and limitations of the study may be beyond the understanding of the average reader. In their accompanying editorial, Henthorn and Olofsen did an admirable job explaining the many limitations.2  They stated, “...we should be very cautious drawing conclusions in the language of pharmacokinetics–pharmacodynamics when there are no drug concentrations (pharmacokinetics) data and when there is non–steady-state effect data and either the onset effect or offset effect is missing.”
The front page title, however, suggests the study endpoint of Doufas et al. can be broadly interpreted as applicable to all opioids in all clinical situations encountered by obstructive sleep apnea patients, which is overly simplistic. Is a target-controlled infusion of 4 ng/ml of remifentanil for 10 min in a well-lit and noisy operating room in a patient anticipating surgery an appropriate surrogate for the level of consciousness, airway, and respiratory dynamics of patients with obstructive sleep apnea on morphine patient-controlled analgesia in a quiet hospital ward at nighttime? Even the study authors acknowledge this in their “Discussion” section: “...our findings pertain to awake patients with obstructive sleep apnea and exercise caution when opioids are administered to patients with decreased state of arousal.”
Cases of patients with moderate to severe sleep apnea suffering fatal opioid-induced ventilatory depression postoperatively are increasingly reported, and the evidence of worse outcomes in this cohort is undisputed.3–5  Additionally, the occurrence of apneic events in postoperative patients on opioids is a consistent finding in both retrospective and prospective cohort studies.6  More than 10 yr of work by the Anesthesia Patient Safety Foundation (Rochester, Minnesota), Society for Anesthesia and Sleep Medicine (Milwaukee, Wisconsin), American Society of Anesthesiologists (Schaumburg, Illinois), Institute of Safe Medication Practices (Horsham, Pennsylvania), and others to advocate guidelines for safer parenteral opioid use in these patients are finally bearing fruit. Yet the reluctance to adopt these guidelines by skeptics may be emboldened by cursory attention to the title of this edition of the Journal. We sincerely hope the editors can rectify this potential for confusion, which is critical to the safety of these patients.
Competing Interests
Dr. Overdyk received consulting fees from Medtronic (Dublin, Ireland). Dr. Dahan has received speaker and consultancy fees from Grunenthal (Aachen, Germany), Medasense (Ramat Gan, Israel), MSD (Kenilworth, New Jersey), and Philips (Eindhoven, The Netherlands). His research unit received grants from Medasense, Bedrocan (Veendam, The Netherlands), and MSD. Dr. Chung received research support from the Ontario Ministry of Health and Long-Term Care (Toronto, Canada), University Health Network Foundation (Toronto, Canada), Medtronics grants to the institution, Up-to-Date royalties, and STOP-Bang proprietary to the University Health Network. Dr. Warner is president of the Anesthesia Patient Safety Foundation (Rochester, Minnesota).
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Henthorn, TK, Olofsen, E . Where’s the beef?: How much can we skimp on pharmacokinetic-pharmacodynamic data? Anesthesiology. 2019; 130:186–8 [Article] [PubMed]
Opperer, M, Cozowicz, C, Bugada, D, Mokhlesi, B, Kaw, R, Auckley, D, Chung, F, Memtsoudis, SG . Does obstructive sleep apnea influence perioperative outcome? A qualitative systematic review for the Society of Anesthesia and Sleep Medicine Task Force on Preoperative Preparation of Patients with Sleep-Disordered Breathing. Anesth Analg. 2016; 122:1321–34 [Article] [PubMed]
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Khanna, A, Buhre, W, Saager, L, Di Stefano, P, Weingarten, T, Dahan, A, Brazzi, L, Overdyk, F . Derivation and validation of a novel opioid-induced respiratory depression risk prediction tool Crit Care Med. 2019; 47:18 [Article]