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Opioid Free Anesthesia – Here’s What We Know

Opioid free anesthesia continues to be a hot topic due to potentially reducing complications related to opioids, but more research is needed to fully understand its role in the operating room.

Three clinicians performing surgery on a patien

Opioids have been used during surgery since the 1960s due to its effective pain management, minimal cardiovascular impact, and being relatively cost effective. Since then, opioid use has become a mainstay in the operating room1.

Unfortunately, opioids are not consequence free. Respiratory depression and excess sedation are a common concern with intraoperative opioid use, especially when patients have comorbidities like obesity or sleep apnea2, Other consequences of opioid use include gastrointestinal issues such as nausea, vomiting, and constipation3.

Nausea and constipation are quite common post-operatively due to intraoperative opioid use and are often difficult to manage.3 In addition to respiratory and gastrointestinal side effects, there is also the concern of opioid abuse post-operatively which has become a growing concern, specifically in the United States4.

Due to the potential side effects associated with intraoperative opioid use, researchers are exploring the potential role opioid-free anesthesia may have in the operating room. While more research is needed to fully understand its efficacy during anesthesia as well as its ability to deter abuse – opioid-free anesthesia is a hot topic in many hospitals.

Today’s article reviews opioid-free anesthesia, research on the practice, and how nociceptive monitoring can play a key role in opioid-free anesthesia.

Why are People Interested in Opioid-Free Anesthesia?

While opioids are an effective way to manage pain and sedation in the operating room, there are many common side effects that impact patient recovery. Patients who are obese or who have pre-existing respiratory issues including sleep apnea or chronic obstructive pulmonary disease are at an increased risk of respiratory failure post-operatively5. This is due to the inherent respiratory depression caused by opioids as well as a risk for pharyngeal muscle weakness6.

Decreased gastrointestinal function caused by intraoperative opioids can lead to nausea and constipation. The increase in abdominal pressure and distention caused by this impairment can interfere with wound healing, especially with bowel surgery.

Additionally, if a patient is having excessive episodes of nausea and vomiting this can increase bleeding risk for patients undergoing eye surgery or head and neck surgeries (due to the Valsalva maneuver initiated with vomiting).3 Other concerns related to post-operative nausea and vomiting (PONV) include decreased nutritional intake and risk for dehydration which can also impact wound healing and recovery.  

Although less severe, itching from opioid use is common and can be difficult to treat. Treatment options tend to be limited to antihistamines which can cause further unwanted sedation. 3

Cognitive change such as delirium and sleep disturbances are also a risk of intra-operative and post-operative opioid use. 3

Many of these complications can be managed, but patients often struggle with side effects of opioids despite efforts to prevent or manage common complications associated with opioids. These side effects can often be worse than the surgery recovery itself, which is why researchers are exploring the potential for reducing or eliminating opioid use in the operating room.  

Potential Opioid Alternatives

Multimodal anesthesia has been a common practice for decades, and this presents the opportunity for substituting and re-arranging the combinations of anesthesia in an attempt to reduce or remove opioids.

Additionally, there have been advances in the class of hypnotics and muscle relaxers which previously carried a high risk of cardiovascular complications.

Lidocaine works well as an analgesic and anti-inflammatory drug. Metabolized in the liver and excreted by the kidneys, lidocaine must be used with caution in elderly or patients with organ dysfunction7.

Dexmedetomidine works as an alpha-2 agonist and is thought to be up to ten times more potent than clonidine. While a powerful hypnotic and sedative, dexmedetomidine affects ventilation very little, however, loading doses can cause hypotension or bradycardia.7

Ketamine is a powerful amnesiac and analgesic.7 Another benefit of ketamine is in small doses, ketamine has the potential for reducing post-operative morphine consumption without inducing any psychotic effects8.

There are also medications often used outside of the operating room that are being used as part of an opioid-free anesthesia method. Ketorolac, intravenous ibuprofen and acetaminophen to name a few, have all been used intraoperatively and are noted to have analgesic effects.7

What Does the Research Say?

When exploring options for opioid-free anesthesia, several different methods have been formulated. A 2015 study in Brazil used propofol, dexmedetomidine, and lidocaine infusions to assess efficacy compared to a control group receiving opioid-based anesthesia with remifentanil and propofol9.

The patients in the study were undergoing a laparoscopic cholecystectomy and researchers found the opioid-free protocol to be an effective alternative approach. PONV was reduced in the opioid-free group and the use of fentanyl in the second hour post-operative setting was statistically less than the opioid-based group.9

Pain scores were also much lower in the opioid-free group, however, there was a longer recovery time in this group. As far as differences in intraoperative events, there were more hypotensive events in the opioid-free group while the opioid-based group had more hypertensive events.9

While this study was small with only 80 participants, and they all received the same surgical procedure, this study shows the potential benefit and efficacy of using opioid-free anesthesia, especially in patients at a high risk of PONV.9

Another small study (54 participants) found opioid-free anesthesia to have similar subjective pain scores, and there was no ‘catch up’ effect post-operatively in patients who did not receive opioid-based anesthesia10.

A systematic review explored the differences between opioid-free anesthesia and opioid-based anesthesia among 33 randomized controlled trials11. Patients who received opioid-free anesthesia had lower pain scores and required less morphine at 2 and 24 hours post-operative, but these changes were not large.11

Opioid-free anesthesia also appeared to reduce the frequency of post-operative sedation and shivering. PONV was also reduced when patients did not receive opioid-based anesthesia.11

A study of 110 patients undergoing cardiopulmonary bypass were divided into two groups – one received opioid anesthesia and the other had opioid-free anesthesia12. The opioid-free group had lower morphine consumption and had shorter intubation times. These patients spent less time in the ICU compared to those who received opioid anesthesia.12

While these studies show promise and benefit related to side effects associated with opioids, notable PONV and sedation – there is still a need for additional research. Research with larger numbers of patients undergoing a variety of surgical options is needed to get a bigger picture of the benefits of opioid-free anesthesia.

Looking Ahead with Opioid-Free Anesthesia

While there is a compelling argument to reduce the use of any medication that causes harmful effects, there is still more research and evidence needed to fully understand the role opioid-free anesthesia can play in the operating room.

In addition to adverse effect reduction, there will have to be additional advancements in patient monitoring to ensure adequate pain and stress management intraoperatively. While post-operative pain can be assessed by the patient, objective measures must be used intraoperatively.

Current nociception monitors have limitations and their utility in opioid-free anesthesia needs to be studied further13.

Systems are needed that can quantify nociception if opioid-free anesthesia will be used, and this can help determine if a patient’s pain is being managed properly and opens the door to more personalized medicine.


  • Opioids have been used in the operating room for half a century and are considered standard practice in multimodal anesthesia
  • Due to the adverse effects noted with opioid use, researchers are exploring the benefits of minimal use or opioid-free anesthesia
  • Many different medications are available and when used, appear to reduce the prevalence of PONV, sedation, and need for additional respiratory support
  • Advanced nociceptive monitoring technology is being used and being explored in OR to accompany the reduction of opioids for an individualized anesthesia care
  • More research is needed to fully understand the role of opioid-free anesthesia as well as the need for continued development of monitoring systems to accurately assess patient pain during anesthesia


[1] Stanley, T. (2014). The fentanyl story. The Journal of Pain. 15(12). P1215-1226.

[2] Funk, R, Hilliard, P, Ramachandran, S. (2014). Perioperative opioid usage. Plastic and Reconstructive Surgery. 134(45-2). 32S-39S.

[3] Benyamin, R. et al. (2008). Opioid complications and side effects. Pain Physician Journal. 11. S105-S120.

[4] Harper, S, Riddell, C, & King, N. (2020). Declining life expectancy in the United States: missing the trees for the forest. Annual Review of Public Health. 42. 381-403.

[5] Bohringer, C, Astorga, C, & Liu, H. (2020). The benefits of opioid free anesthesia and the precautions necessary when employing it. Transl Perioper Pain Med. 7(1). 152-157.

[6] Mulier, J. (2017). Opioid free general anesthesia: a paradigm shift? Rev Esp Anestesiol Reanim. 64(8). 427-430.

[7] Boysen, P, Pappas, M, & Evans, B. (2018). An evidence-based opioid-free anesthetic technique to manage perioperative and periprocedural pain. The Ochsner Journal. 18(2). 121-125.

[8] Guillou, N et al. (2003). The effects of small-dose ketamine on morphine consumption in surgical intensive care unit patients after major abdominal surgery. Anesthesia & Analgesia. 97(3). 843-847.

[9] Bakan, M et al. (2015). Opioid-free total intravenous anesthesia with propofol, dexmedetomidine and lidocaine infusions for laparoscopic cholecystectomy: a prospective, randomized, double-blinded study. Brazilian Journal of Anesthesiology. 65(3). 191-199.

[10] Bell, A. et al. (2020). Opioid-free anesthesia in the perioperative setting- a preliminary retrospective matched cohort study. Military Medicine. Usaa570.

[11] Salome, A. (2021). Opioid-Free Anesthesia Benefit–Risk Balance: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Journal of Clinical Medicine. 10(10). 2069.

[12] Guinot, P. et al. (2019). Effects of opioid-free anesthesia on post-operative period in cardiac surgery: a retrospectice matched case-control study. BMC Anesthesiology. 19(1). 136.

[13] Chia, P, Cannasson, M, & Bui, C. (2021). Opioid free anesthesia: feasible? Current Opinion Anesthesiology. 33(4). 512-517.

  • Neurology
  • Perioperative care