Inadequate pain control during surgery can lead to decreased patient satisfaction, development of chronic postoperative pain, and increased morbidity and mortality (1). In general, pain management involves the use of either opioid or non-opioid medications. Although opioids are still widely used, more information on their misuse, limitations, and side effects is available, including the risk of dependence and opioid-induced hyperalgesia (OIH). Based on current clinical knowledge, a balanced multimodal analgesic regimen with limited opioid use appears to be the best way of ensuring patient comfort with anesthesia.
Multimodal analgesia involves the use of 2 or more analgesics that target different pathways in the nociceptive (pain) system. Appropriate combination of different analgesics allows for lower doses of each individual drug, thereby lowering the side effects of each drug, while preserving overall efficacy. In recent years, the American Society of Anesthesiologists (ASA) and the American Pain Society (APS) have strongly recommended the use of multimodal analgesia in the management of pain in the intraoperative setting (1).
Opioids have been used for centuries to treat acute pain, and unfortunately, they still play an important role in the management of acute pain. Their potent pain-relieving effects make them a key component of anesthesia for ensuring patient comfort. However, physicians must understand the many caveats that exist with this drug class in order to use opioids in an appropriate manner while being sensitive to the potential pitfalls. Namely, physicians must understand that all opioids are addictive, which is contrary to prior false assumptions contributing to the current opioid epidemic (1). An example of an opioid that is widely used to prevent pain under anesthesia is fentanyl. Some advantages of this drug is that overdose is rare in clinical settings, it does not cause myocardial depression, and it is a short-acting agent that is safe in the management of critically ill patients (2).
Ketamine was first developed in the 1960s as an anesthetic agent with analgesic properties. Ketamine exerts its effect via inhibition of NMDA receptors in the central nervous system (1). At lower doses (slow bolus of 0.1 mg/kg, typically followed by low-dose infusion of 0.1 mg/kg/h), ketamine has predominantly analgesic effects. At higher doses (bolus of 0.5–1 mg/kg), it acts more like an anesthetic agent. As a result of the opioid crisis, use of ketamine has been steadily increasing in clinical settings. A 2010 study by Loftus and colleagues (N = 102) 55 and a more recent 2019 study by Boenigk and colleagues (N = 129) 56 both demonstrated that postoperative opioid consumption was reduced in opioid-dependent and opioid-tolerant patients that received ketamine infusions during surgery (3,4). Continuing to be able to provide pain relief and safeguard patient comfort is the necessary caveat to reducing opioid use. Results such as these demonstrate promising alternatives. Contraindications to ketamine administration include uncontrolled cardiovascular disease, pregnancy, and psychosis. Additionally, elevated intracranial pressure or intraocular pressure also precludes the safe use of ketamine from the available evidence, but these recommendations most often refer to high-dose administration (1).
Dexmedetomidine, a highly selective α-2 agonist, was approved by the FDA in 1999 as an analgesic and sedative medication in the intensive care setting (ICU) setting. It can be included in an anesthesia regimen to provide pain relief and reduce the need for opioids, improving patient comfort while decreasing risk. Several meta-analyses have examined the effectiveness of this drug in both intraoperative and postoperative analgesia. One such meta-analysis included 30 studies (N = 1792), with 933 patients receiving either clonidine or dexmedetomidine, and the authors concluded that perioperative systemic alpha-2 agonists reduced postoperative opioid consumption (down 30% compared with placebo), pain intensity, and nausea without prolonging recovery times, while the most common adverse effects noted were bradycardia and arterial hypotension (1). IV administration of dexmedetomidine is most common, and dosing typically consists of a bolus dose between 0.25 and 1 mcg/kg given over 10 minutes and infusion rates between 0.2 and 0.6 mcg/kg/h. However, due to risk of hypotension, dexmedetomidine should only be administered in monitored settings, such as the OR, PACU, or ICU.
References
1. O’Neill A, Lirk P. Multimodal Analgesia. Anesthesiol Clin. 2022;40(3):455-468. doi:10.1016/j.anclin.2022.04.002
2. Chikwe J, Cooke DA, Weiss A, Goldstone A. Cardiothoracic Surgery. 2nd ed. London, England: Oxford University Press; 2013.
3. Loftus RW, Yeager MP, Clark JA, et al. Intraoperative ketamine reduces perioperative opiate consumption in opiate-dependent patients with chronic back pain undergoing back surgery. Anesthesiology. 2010;113(3):639-646. doi:10.1097/ALN.0b013e3181e90914
4. Boenigk K, Echevarria GC, Nisimov E, et al. Low-dose ketamine infusion reduces postoperative hydromorphone requirements in opioid-tolerant patients following spinal fusion: A randomised controlled trial. Eur J Anaesthesiol. 2019;36(1):8-15. doi:10.1097/EJA.0000000000000877