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SUJAY DESHPANDE, BA
Drexel University College of Medicine
SUMMARY POINTS
Intraoperative opioids have had a predominant role in anesthesia management despite the large side effect profile and contribution to the opioids epidemic.
Opioid free anesthesia is a recently emerging anesthetic technique with possible amelioration of opioid side effects while maintaining desired anesthetic effect.
Many alternative medications to opioids have been studied in the literature.
Dexmedetomidine or Precedex, ketamine, and magnesium have proven to be viable alternatives to opioids in anesthesia management.
ANALYSIS
Background
Opioids are a specific class of drugs that are often associated with pain reduction. While opioids may primarily serve this function, they also serve a critical role in surgical and operative anesthesia management. Anesthesia involving opioids, primarily fentanyl, are effective in maintaining cardiovascular stability during anesthesia induction as the operation (1). One study investigated the role of opioids in maintaining cardiovascular stability in patients with severely impaired cardiac function. Opioids were found to lower the incidence of severe hypertension and reduce the patient's respiratory response when intubated (1). However, large doses of opioids were associated with prolonged postoperative respiratory depression (1). Furthermore, there are different types of opioids with different effects; newer opioids like sufentanil or remifentanil can be suitable alternatives to morphine or fentanyl.
The drawbacks to intraoperative opioid use are largely associated with effects that happen in the postoperative period. One aspect of opioid use not often thought about, given the current opioid epidemic and the focus of addiction, is the presence of adverse side effects that may occur after use. There is strong evidence that opioid-inclusive anesthesia is associated with more postoperative nausea and vomiting as opposed to opioid-free anesthesia (2). Furthermore, anesthesia involving opioids have been shown to lead to increased rates of hypotension and shivering (2). Additionally, the opioid crisis in the United States has continued to worsen year by year. Short-term solutions that can reduce opioid use include alternative medications and implementation of prescription guidelines (3).
Figure 1. The conventional goals of general anesthesia. ANS- autonomic nervous system. SEE ARTICLE from Frauenknecht J, Kirkham KR, Jacot‐Guillarmod A, Albrecht E. Analgesic impact of intra‐operative opioids vs. opioid‐free anaesthesia: a systematic review and meta‐analysis. Anaesthesia. 2019;74(5):651-662. doi:https://doi.org/10.1111/anae.14582
Analysis
There is increasing interest in further understanding and possibly implementing an opioid-free anesthetic plan or opioid free anesthesia (OFA). The basis for these changes include reducing negative postoperative outcomes caused by intraoperative opioid use. However, implementing these changes are difficult due to the long history of anesthesia combination with opioids intraoperatively (4). Oftentimes, using a single anesthetic agent like propofol or an inhaled vapor like sevoflurane may be challenging due to the need for higher doses and longer recovery time. Therefore, the idea of multimodal general anesthesia or “balanced anesthesia” emerged as a new alternative in anesthesia management (4). Opioid free anesthesia plans involve using alternatives to reach a similar effect without the adverse side effects and greater postoperative discomfort that opioids may cause. One study cites that there is potential for benefit in OFA for obstructive sleep apnea, obesity, and chronic opioid use disorder (5).
Some alternatives that are gaining popularity and are being evaluated in clinical studies are NMDA antagonists including ketamine, anti-inflammatories, alpha-2 agonists including dexmedetomidine, and sodium channel blockers including lidocaine and magnesium sulfate (6). Most of these drugs are associated with maintaining hemodynamic stability and reducing pain. One study investigated the role of ketamine and magnesium in hemodynamic control and found that ketamine was effective in maintaining a consistent blood pressure while magnesium was effective for maintaining a consistent heart rate (7). These drugs can also be used as complements for pain control and for a balanced and stable anesthesia during a procedure (7). Furthermore, sodium channel blockers, specifically lidocaine, are often used in nerve blocks either pre or post operatively and can be effective tools to lessen pain. For joint surgeries like total knee arthroplasties, the use of supplementary adductor canal blocks can provide superior analgesia to prior standards of care (8).
One specific medication showing promise as a more all-encompassing alternative to opioids is dexmedetomidine, also known as Precedex. Dexmedetomidine was recently approved by the Food Drug Association (FDA) and has a similar effect to benzodiazepines with reduction in side effect profile (9). One study compared opioid free anesthesia with dexmedetomidine versus opioid based anesthesia involving remifentanil and found lower pain scores, lower anti-nausea medication use, and lower fentanyl consumption 2 hours postoperatively in OFA patients (10). However, more hypertensive events were found in the OFA patients while more hypotensive events occurred in patients receiving opioid based anesthesia (10). A meta-analysis compared general anesthesia cases with dexmedetomidine versus remifentanil and found pain scores two hours postop to be better in the dexmedetomidine group (11). Furthermore, secondary side effects including rates of hypotension, shivering, and post-op nausea and vomiting were twice as frequent for patients receiving remifentanil (11).
Discussion
Based on this analysis, it is important to first recognize the role and importance that opioids have in an anesthetic care plan. Opioids are very effective in maintaining balanced anesthesia and ensuring the patient is hemodynamically stable while also dampening the patient’s own breathing response while intubated. However, given the side effects that opioids can present post operatively, risk of developing opioid dependence, and the current opioid epidemic; opioids should be reconsidered as standard of care. Fortunately, many alternatives exist that can provide similar anesthetic effects with improved postoperative outcomes. More objective comparisons should be performed to better understand current medication alternatives. Anti-inflammatories seem to have a much lower impact on pain reduction compared to opioids, however there is room for literature to investigate further.
REFERENCES:
Bovill JG, Sebel PS, Stanley TH. Opioid analgesics in anesthesia: with special reference to their use in cardiovascular anesthesia. Anesthesiology. 1984;61(6):731-755. https://pubmed.ncbi.nlm.nih.gov/6150663/
Frauenknecht J, Kirkham KR, Jacot‐Guillarmod A, Albrecht E. Analgesic impact of intra‐operative opioids vs. opioid‐free anaesthesia: a systematic review and meta‐analysis. Anaesthesia. 2019;74(5):651-662. doi:https://doi.org/10.1111/anae.14582
Skolnick P. The Opioid Epidemic: Crisis and Solutions. Annual Review of Pharmacology and Toxicology. 2018;58(1):143-159. doi:https://doi.org/10.1146/annurev-pharmtox-010617-052534
Egan TD. Are opioids indispensable for general anaesthesia? British Journal of Anaesthesia. 2019;122(6):e127-e135. doi:https://doi.org/10.1016/j.bja.2019.02.018
Sultana A, Torres D, Schumann R. Special indications for Opioid Free Anaesthesia and Analgesia, patient and procedure related: Including obesity, sleep apnoea, chronic obstructive pulmonary disease, complex regional pain syndromes, opioid addiction and cancer surgery. Best Practice & Research Clinical Anaesthesiology. 2017;31(4):547-560. doi:https://doi.org/10.1016/j.bpa.2017.11.002
BUGADA D, LORINI LF, LAVAND’HOMME P. Opioid free anesthesia: evidence for short and long-term outcome. Minerva Anestesiologica. 2021;87(2). doi:https://doi.org/10.23736/s0375-9393.20.14515-2
Forget P, Cata J. Stable anesthesia with alternative to opioids: Are ketamine and magnesium helpful in stabilizing hemodynamics during surgery? A systematic review and meta-analyses of randomized controlled trials. Best Practice & Research Clinical Anaesthesiology. 2017;31(4):523-531. doi:https://doi.org/10.1016/j.bpa.2017.07.001
Hussain N, Brull R, Vannabouathong C, et al. The analgesic effectiveness of motor-sparing nerve blocks for total knee arthroplasty: A network meta-analysis. Anesthesiology. Published online June 26, 2023. doi:https://doi.org/10.1097/ALN.0000000000004667
Gertler R, Brown HC, Mitchell DH, Silvius EN. Dexmedetomidine: a novel sedative-analgesic agent. Proceedings (Baylor University Medical Center). 2001;14(1):13-21. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1291306/
Bakan M, Umutoglu T, Topuz U, et al. Opioid-free total intravenous anesthesia with propofol, dexmedetomidine and lidocaine infusions for laparoscopic cholecystectomy: a prospective, randomized, double-blinded study. Brazilian Journal of Anesthesiology (English Edition). 2015;65(3):191-199. doi:https://doi.org/10.1016/j.bjane.2014.05.001
Grape S, Kirkham KR, Frauenknecht J, Albrecht E. Intra‐operative analgesia with remifentanil vs. dexmedetomidine: a systematic review and meta‐analysis with trial sequential analysis. Anaesthesia. 2019;74(6):793-800. doi:https://doi.org/10.1111/anae.14657
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