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INTRODUCTION

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Perioperative pain control remains one of the primary concerns for surgical patients, surgeons, and anesthesiologists. Traditionally, opiates have been the medications used for the treatment of perioperative pain. However, as our knowledge of molecular nociception has expanded, it has become apparent that multiple receptor subtypes are involved in the neurochemical basis for pain (Figure 11–1). As perioperative physicians, anesthesiologists exploit this knowledge by using pharmacologic agents in addition to opiates to control surgical pain.

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Figure 11–1

Schematic representation of the various receptor subtypes present on nociceptive neurons. AMPA, -amino-3-hydroxyl-5-methyl-4-isoxazole-propionate; GABA, γ-aminobutyric acid; NMDA, N-methyl-d-aspartate.

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This multimodal approach to perioperative pain control has gained popularity. Common perioperative pain adjuncts include ketamine, gabapentin, pregabalin, clonidine, and dexmedetomidine, neuraxial blocks, peripheral nerve blocks, systemic nonsteroidal anti-inflammatory drugs, tricyclic antidepressants, and local anesthetics.

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In addition to opiate-sparing effects, adjuncts may be useful in 2 clinical scenarios: (1) achieving safe and effective analgesia for the opiate tolerant surgical patient, and (2) reducing patients’ risk of having chronic postsurgical pain syndromes after undergoing procedures that place them at risk for chronic pain.

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Opiate-Tolerant Surgical Patients

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The recent increased interest in multimodal pain control is in part a consequence of the steady rise in opiate use since the late 1990s. A review examining the trends of opiate use in the United States from 1997 to 2007 revealed some alarming trends.1 While constituting only 4.6% of the world's total population in 2007, Americans were consuming 80% of the global prescription opioid supply. The average sale of opioids per person in the United States increased 402% from 1997 to 2007. Opiate use, both prescribed and illicit, may be more prevalent in surgical patients than these numbers suggest.

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In tolerant patients, opiates used to treat surgical pain are less effective and potentially more dangerous, because patients often require excessive doses to achieve analgesia that are associated with adverse effects in opioid-naive patients. Thus, the benefits of pain control adjuncts are of particular interest to perioperative physicians. The evidence regarding the use of these agents in opiate-tolerant surgical patients will be discussed below.

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Prevention of Chronic Pain

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There is evidence that perioperative pain adjuncts may aid in the prevention of chronic postsurgical pain. Certain surgeries, such as thoracotomies and limb amputations, can produce chronic pain syndromes in as many as 30% to 50% of patients who undergo these procedures.2 The limited data pertaining to the use of pain control adjuncts for the prevention of chronic pain syndromes after surgery will be reviewed for selected agents.

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KETAMINE

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History of Development

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Ketamine was invented in the early 1960s as part of an effort to find a safer alternative to phencyclidine for the ...

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