It serves as evidence of compassionate concern for patients and dedication to improving practice that several letters1–3  were received in response to the articles by Beloeil et al.4  and Shanthanna et al.5  on opioid-free anesthesia, and to our accompanying editorial.6  The topic of opioid-free anesthesia is one of intense interest to the field, and these articles are commended to the reader. Those points made in the letters specific to our editorial are addressed briefly below.

The letter by Chelly1  reminds us that we are perioperative physicians and that optimal postoperative analgesia might begin with a preoperative intervention. Addressing psychological factors linked to pain and elevated analgesic requirements is suggested, proposing complementary strategies such as acupuncture, music therapy and others. We agree that any potential opportunity for early intervention is not to be squandered, although preemptive analgesia has not been conceptually substantiated. The general call to address pain management comprehensively is important. Caution is suggested, however, in placing too much faith in strategies that currently have relatively little data supporting them.

Forget et al.2  provide a more extensive set of concerns over some of the particulars of the opioid-free dexmedetomidine anesthetic investigated by Beloeil et al.4  Regrettably, Forget et al. “strongly disagree” that opioid-free anesthesia can do more harm than good, despite the study by Beloeil et al. being stopped early over major safety concerns (five episodes of bradycardia and three cases of asystole in the opioid-free dexmedetomidine group). We do agree, however, that safer and perhaps more effective protocols could potentially be designed, but they must also be rigorously tested and show benefit to patients. Such benefit must not be limited to intermediate outcomes of opioid consumption but also extend to more important, patient-centric outcomes, including pain, adverse events, recovery, function, and quality of life.7  We reiterate the thrust of our editorial comments, which were that balance may be the best approach to anesthetic and analgesic management rather than fashion, dogma, or the challenging concept that powerful opioid analgesics should be eliminated as a class for no particularly compelling reason.

Finally, Ingrande and Drummond3  succinctly comment on the lack of evidence supporting the sometimes-bewildering combinations of analgesics and adjuncts used in the name of eliminating opioids. They point out that the downsides of poorly evaluated but aggressive multi-modal analgesic strategies might be unexpected drug interactions and unclear safety profiles. The point is well taken.

This work was supported by National Institutes of Health grant No. R01 DA042985 (Bethesda, Maryland; to Dr. Kharasch) and Department of Veterans Affairs grant No. I01 BX000881 (Washington, D.C.; to Dr. Clark).

Dr. Clark has a consulting agreement with Teikoku Pharma USA (San Jose, California). Dr. Kharasch declares no competing interests.

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