Chapter 76: The Role of Nonopioid Analgesic Infusions in the Management of Postoperative Pain

INTRODUCTION

Opioids are the most commonly used medications for perioperative pain control. However, opioid-related side effects such as constipation, nausea, vomiting, and respiratory depression often accompany the use opioids. Many studies have evaluated the efficacy of nonopioids such as ketamine, lidocaine, naloxone, and magnesium as perioperative infusions to decrease postoperative pain and minimize the use of opioids after surgery. Infusions of the short-acting beta-blocker esmolol and the α₂ agonist dexmedetomidine have also been investigated as adjuvants to reduce the postoperative opioid requirement. In this chapter, the results of the studies on infusions of ketamine, lidocaine, naloxone, esmolol, α₂ agonists, and magnesium will be summarized, and recommendations on their clinical applicability as part of perioperative pain management will be made.

INTRAVENOUS KETAMINE INFUSION

Ketamine is a noncompetitive N-methyl-D-aspartate glutamate (NMDA) receptor antagonist and a sodium channel blocker.¹ The drug is available as racemic ketamine which contains the S (+) and R (–) stereoisomers. The S (+) ketamine has four times greater affinity for the NMDA receptor than the R (–) ketamine. Ketamine has a half-life of 80–180 minutes. Its metabolite norketamine has a longer half-life life and is one third as potent as the parent compound.² Early studies showed ketamine to have analgesic properties at low doses.^3,4,5,6,7

Ketamine has many qualities as an analgesic. It does not suppress cardiovascular function in the presence of an intact nervous system,⁸ does not depress the laryngeal protective reflexes and causes less depression of ventilation compared to opioids,⁹ and may even stimulate respiration.¹⁰

Ketamine has been used in subanesthetic doses as an analgesic.⁶ The analgesic effects of ketamine occur at plasma concentrations of 100–150 ng.mL^–1,11 The undesirable characteristics of ketamine include postoperative malaise,¹² accumulation of metabolites,¹³ development of tolerance,¹⁴ cardiovascular excitation, and the occurrence of psychotomimetic side effects.^15,16 Psychotomimetic effects are the most common feared complication by clinical practitioners but few studies have formally evaluated these side effects.^4,5,6,7

Randomized controlled clinical studies on perioperative IV ketamine showed some beneficial effect. In a study in patients who underwent cervical and lumbar spine surgery, ketamine (1–mg/kg bolus followed by 83 mcg/kg^–1/h^–1) resulted in lower pain scores, less analgesic requirements, and better satisfaction than patients who had saline infusions or those who had lower doses of ketamine infusions (same bolus but with an infusion rate of 42 mcg/kg^–1/h^-1).¹⁷ The same salutary effects were seen in patients who had major abdominal surgery. Perioperative ketamine infusion (0.5–mg/kg bolus followed by 2 mcg/kg^–1/min^–1) for 48 hours after surgery resulted in lower morphine consumption than patients who had saline infusion or those who had the same infusion given intraoperatively.¹⁸ The pain ...