Multimodal General Anesthesia: Theory and Practice

Emery N. Brown, MD, PhD; Kara J. Pavone, BS, BSN, RN; Marusa Naranjo, MD

Disclosures

Anesth Analg. 2018;127(5):1246-1258. 

In This Article

Abstract and Introduction

Abstract

Balanced general anesthesia, the most common management strategy used in anesthesia care, entails the administration of different drugs together to create the anesthetic state. Anesthesiologists developed this approach to avoid sole reliance on ether for general anesthesia maintenance. Balanced general anesthesia uses less of each drug than if the drug were administered alone, thereby increasing the likelihood of its desired effects and reducing the likelihood of its side effects. To manage nociception intraoperatively and pain postoperatively, the current practice of balanced general anesthesia relies almost exclusively on opioids. While opioids are the most effective antinociceptive agents, they have undesirable side effects. Moreover, overreliance on opioids has contributed to the opioid epidemic in the United States. Spurred by concern of opioid overuse, balanced general anesthesia strategies are now using more agents to create the anesthetic state. Under these approaches, called "multimodal general anesthesia," the additional drugs may include agents with specific central nervous system targets such as dexmedetomidine and ones with less specific targets, such as magnesium. It is postulated that use of more agents at smaller doses further maximizes desired effects while minimizing side effects. Although this approach appears to maximize the benefit-to-side effect ratio, no rational strategy has been provided for choosing the drug combinations. Nociception induced by surgery is the primary reason for placing a patient in a state of general anesthesia. Hence, any rational strategy should focus on nociception control intraoperatively and pain control postoperatively. In this Special Article, we review the anatomy and physiology of the nociceptive and arousal circuits, and the mechanisms through which commonly used anesthetics and anesthetic adjuncts act in these systems. We propose a rational strategy for multimodal general anesthesia predicated on choosing a combination of agents that act at different targets in the nociceptive system to control nociception intraoperatively and pain postoperatively. Because these agents also decrease arousal, the doses of hypnotics and/or inhaled ethers needed to control unconsciousness are reduced. Effective use of this strategy requires simultaneous monitoring of antinociception and level of unconsciousness. We illustrate the application of this strategy by summarizing anesthetic management for 4 representative surgeries.

Introduction

General anesthesia is a drug-induced reversible state consisting of unconsciousness, amnesia, antinociception, and immobility, with maintenance of physiological stability.[1] Balanced general anesthesia, the most common management strategy used in anesthesia care, entails administering a combination of different agents to create the anesthetic state. Anesthesiologists developed this approach to avoid sole reliance on ether for maintenance of general anesthesia.[2] There is evidence that balanced general anesthesia uses less of each drug than if the drug were administered alone.[3] This approach is believed to increase the likelihood of a drug's desired effects and reduce the likelihood of its side effects.

Current practice of balanced general anesthesia relies on a hypnotic, such as propofol, for induction and on an inhaled ether or on a hypnotic infusion to maintain unconsciousness. Although midazolam is often administered before induction to treat anxiety, amnesia is managed implicitly by rendering the patient unconscious. And while muscle relaxants are administered to produce immobility, administration of propofol and of inhaled ethers also contributes to muscle relaxation. To date, balanced general anesthesia has relied almost exclusively on opioids administered as intermittent boluses or as continuous infusions to manage nociception intraoperatively and pain postoperatively.

We distinguish here between nociception and pain. Nociception is the propagation through the sensory system of potentially noxious and harmful stimuli, whereas pain is the conscious perception of nociceptive information.[4] For example, if a patient is unconscious after receiving only propofol and has an increase in heart rate and blood pressure in response to the surgical incision, then this is an example of nociception. If a surgeon makes an incision to create a dialysis fistula after an inadequate administration of local anesthesia for a field block and the patient says, "Ouch," then this is pain. The heart rate and blood pressure most certainly would go up as a physiological response. Someone monitoring the vital signs but unable to hear the patient would appreciate the patient's nociceptive response.

Nociception induced by surgery, due to tearing of tissue and inflammation, is the primary reason for placing a patient in a state of general anesthesia.[5] If not controlled, nociceptive perturbations are also the primary source of hemodynamic and stress responses intraoperatively and of chronic pain syndromes postoperatively. While opioids are the most effective antinociceptive agents, they have undesirable side effects, including respiratory depression, nausea, vomiting, urinary retention, constipation, ileus, and pruritus.[6] Overreliance on opioids has certainly contributed to the opioid epidemic in the United States.[7] Propofol and the inhaled ethers also contribute to antinociception by maintaining unconsciousness, and thereby altering perception of nociceptive stimuli.

Spurred by concerns about opioid overuse and their undesirable side effects, strategies for balanced general anesthesia are now using multiple agents in addition to or in lieu of opioids to manage the nociceptive component of the anesthetic state. Under this approach, called "multimodal general anesthesia," the additional drugs may include agents with specific central nervous system targets such as dexmedetomidine[8] as well as ones whose targets are less specific such as lidocaine.[9] It is postulated that the use of more agents at smaller doses further maximizes desired effects while minimizing side effects.[10] And while the multimodal approach appears to maximize the benefit-to-side effect ratio, no rational strategy for choosing the drug combinations has been proposed.

We propose that a rational strategy for multimodal general anesthesia should: (1) administer combinations of antinociceptive agents chosen so that each one targets a different circuit in the nociceptive system; (2) monitor continuously levels of antinociception and unconsciousness; (3) use explicitly the sedative effects of the antinociceptive agents to reduce the doses of hypnotic agents and inhaled anesthetics administered to maintain unconsciousness; and (4) continue multimodal pain control during the in-hospital postoperative period and after discharge.

We review the anatomy and physiology of the parts of nociceptive and arousal systems, and the mechanisms through which commonly used anesthetic and nonanesthetic drugs act in these systems. We show that understanding these systems can be used to formulate a rational strategy for multimodal general anesthesia management. We illustrate the new strategy by summarizing anesthetic management for 4 representative surgeries.

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