Perioperative Opioid Administration: A Critical Review of Opioid-free Versus Opioid-sparing Approaches

Harsha Shanthanna, M.D., Ph.D., F.R.C.P.C.; Karim S. Ladha, M.D., M.Sc., F.R.C.P.C.; Henrik Kehlet, M.D., Ph.D.; Girish P. Joshi, M.B.B.S., M.D., F.F.A.R.C.S.I.


Anesthesiology. 2021;134(4):645-659. 

In This Article

Abstract and Introduction


Opioids form an important component of general anesthesia and perioperative analgesia. Discharge opioid prescriptions are identified as a contributor for persistent opioid use and diversion. In parallel, there is increased enthusiasm to advocate opioid-free strategies, which include a combination of known analgesics and adjuvants, many of which are in the form of continuous infusions. This article critically reviews perioperative opioid use, especially in view of opioid-sparing versus opioid-free strategies. The data indicate that opioid-free strategies, however noble in their cause, do not fully acknowledge the limitations and gaps within the existing evidence and clinical practice considerations. Moreover, they do not allow analgesic titration based on patient needs; are unclear about optimal components and their role in different surgical settings and perioperative phases; and do not serve to decrease the risk of persistent opioid use, thereby distracting us from optimizing pain and minimizing realistic long-term harms.


Opioids are an integral part of perioperative care because of their high analgesic efficacy.[1–3] They have well-known short-term adverse effects and the potential for long-term adverse effects for patients and society.[3–5] The long-term harms are specifically responsible for the ongoing opioid epidemic in North America, as well as in some other parts of the world, and are related primarily to oral opioids prescribed for chronic pain.[6] In the United States, Congress declared 2001 to 2011 the "Decade of Pain Control and Research."[7] Liberal opioid use was encouraged in an effort to gain higher patient satisfaction along with misguided efforts by the pharmaceutical industry acting as driving forces.[8] This resulted in practice patterns favoring opioid overprescription with limited oversight. Several observational studies have demonstrated a clear disconnect between the prescriptions provided to the patients and opioids needed to manage pain.[9,10] This increases the risk for persistent opioid use and opioid use disorder,[11] and the unused pills represent a reservoir feeding the opioid diversion market, leading to societal harms.[12,13] Because a large proportion of literature clearly indicates inappropriate physician prescriptions as the contributing factor,[10,11,14] interventions encouraging safer opioid prescriptions have a direct role to play. These interventions have the potential to decrease opioid utilization and overprescription without affecting the satisfaction of postdischarge analgesia.[15–17] However, imposing strict opioid limits alone may not to lead to appreciable reductions.[18]

At the same time, this seems to have precipitated a rethinking around the use of opioids during the perioperative period, and anesthesiologists are identifying the role they can play in decreasing the burden of the opioid crisis. With good intent, backed by strong enthusiasm but uncertain evidence, there is advocacy toward opioid-free perioperative care strategies, with ever more increasing publications.[2,19–21] A quick search of PubMed indicates over 300 publications in the last 10 yr, of which more than 200 were published in the past 5 yr. Many suggest these strategies as a new paradigm that might help to solve the problem.[2] Others have quoted that there are alternative approaches to pain management that do not rely on opioids,[22] without clarifying what these methods are and how they operate. There is a lack of understanding around these alternative approaches, their limitations and applicability, phases of care in which they can be effectively introduced and operate, and whether they truly lead to opioid-free care throughout the perioperative course, including after discharge from the surgical facility.[21,23] The bigger and more relevant questions are whether these strategies influence overall opioid needs and pain resolution and whether this has any bearing on the potential for persistent opioid use after surgery.[24]

Our review was informed by the existing literature around the theme of rational opioid use in the perioperative period, more specifically as it applies to opioid-reduction and -minimizing strategies. Because this is not a systematic review, we did not consider a specific methodologic criteria for study selection or analysis. However, a conscious attempt was made to keep the review current and comprehensive by searching within Medline and Embase databases via OVID platform using the terms "opioid-sparing" and "opioid-free" to look for studies and reviews focused on intraoperative anesthesia and postoperative analgesia. In addition, we looked into practice guidelines and recommendations published by recognized anesthesia societies and organization, relevant to this review. Keeping in mind the common anesthesia practitioner, we will review the feasibility, challenges, and practical considerations with the use of opioid-sparing and opioid-free techniques in different phases of perioperative care. Because a clear distinction needs to be made, we will separate the terms "opioid-free anesthesia" to denote avoidance of opioids in the intraoperative period and "opioid-free analgesia" to further extend opioid avoidance to the postoperative phase. We conclude by summarizing the important questions and the potential role for anesthesiologists in optimizing perioperative pain, opioid utilization and surgical recovery.