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Modalities to maintain normothermia include using warm intravenous fluids, heat exchangers in the anesthesia circuit, forced-warm-air covers, and new technology involving water-filled garments with microprocessor feedback control to a core temperature set point.

Nausea and Vomiting Nausea and vomiting in the postoperative period continue to be significant problems following general anesthesia and are caused by an action of anesthetics on the chemoreceptor trigger zone and the brainstem vomiting center, which are modulated by serotonin (5-HT), histamine, acetylcholine, and dopamine. The 5-HT3 receptor antagonist ondansetron (see Chapter 37) is very effective in suppressing nausea and vomiting. Common treatments also include droperidol, metoclopramide, dexamethasone, and avoidance of N2O. The use of propofol as an induction agent and the nonsteroidal anti-inflammatory drug ketorolac as a substitute for opioids may decrease the incidence and severity of postoperative nausea and vomiting.

Other Emergence and Postoperative Phenomena Physiological changes accompanying emergence from general anesthesia can be profound. Hypertension and tachycardia are common as the sympathetic nervous system regains its tone, which is enhanced by pain. Myocardial ischemia can appear or markedly worsen during emergence in patients with coronary artery disease. Emergence excitement occurs in 5-30% of patients and is characterized by tachycardia, restlessness, crying, moaning and thrashing, and various neurological signs. Postanesthesia shivering occurs frequently because of core hypothermia. A small dose of meperidine (12.5 mg) lowers the shivering trigger temperature and effectively stops the activity. The incidence of these emergence phenomena is greatly reduced when opioids are employed as part of the intraoperative regimen.

Airway obstruction may occur during the postoperative period because residual anesthetic effects continue to partially obtund consciousness and reflexes (especially in patients who normally snore or who have sleep apnea). Strong inspiratory efforts against a closed glottis can lead to negative-pressure pulmonary edema. Pulmonary function is reduced postoperatively following all types of anesthesia and surgery, and hypoxemia may occur. Hypertension can be prodigious, often requiring aggressive treatment.

Pain control can be complicated in the immediate postoperative period. Respiratory suppression associated with opioids can be problematic among postoperative patients with a substantial residual anesthetic effect. Patients can alternate between screaming in apparent agony and being deeply somnolent with airway obstruction, all in a matter of moments. The nonsteroidal antiinflammatory agent ketorolac (30-60 mg intravenously) frequently is effective, and the development of injectable cyclooxygenase-2 inhibitors (see Chapter 26) holds promise for analgesia without respiratory depression. In addition, regional anesthetic techniques are an important part of a perioperative multimodal approach that employs local anesthetic wound infiltration; epidural, spinal, and plexus blocks; and nonsteroidal anti-inflammatory drugs, opioids, a2 adrenergic receptor agonists, and NMDA receptor antagonists. Patient-controlled administration of intravenous and epidural analgesics makes use of small, computerized pumps activated on demand but programmed with safety limits to prevent overdose. Agents used are intravenous opioids (frequently morphine), and opioid, local anesthetic, or both, by the epidural route. These techniques have revolutionized postoperative pain management, can be continued for hours or days, and promote ambulation and improved bowel function until oral pain medications are initiated.

ACTIONS AND MECHANISMS OF GENERALANESTHETICS The Anesthetic State

General anesthetics produce a behavioral state referred to as general anesthesia, which can be defined as a global but reversible depression of CNS function resulting in the loss of response to and perception of all external stimuli. However, anesthesia is not simply a deafferented state (e.g., amnesia is an important aspect of the anesthetic state), and not all general anesthetics produce identical patterns of deafferentation.

Components of the anesthetic state include amnesia, immobility in response to noxious stimulation, attenuation of autonomic responses to noxious stimulation, analgesia, and unconsciousness. General anesthesia is useful only insofar as it facilitates the performance of surgery or other noxious procedures. The performance of surgery usually requires an immobilized patient who does not have an excessive autonomic response to surgery (blood pressure and heart rate) and who has amnesia for the procedure. Thus, the essential components of the anesthetic state are immobilization, amnesia, and attenuation of autonomic responses to noxious stimulation. If an anesthetic produces profound amnesia, it can be difficult in principle to determine if it also produces either analgesia or unconsciousness.

Anesthetic Potency

The potency of general anesthetics usually is measured by determining the concentration of drug that prevents movement in response to surgical stimulation. For inhalational anesthetics, anesthetic potency is measured in MAC units, with 1 MAC defined as the minimum alveolar concentration that prevents movement in response to surgical stimulation in 50% of subjects. The strengths of MAC as a measurement are that (1) alveolar concentrations can be monitored continuously by measuring end-tidal anesthetic concentration using infrared spectroscopy or mass spectrometry; (2) it provides a direct correlate of the free concentration of the anesthetic at its site(s) of action in the CNS; (3) it is a simple-to-measure end point that reflects an important clinical goal. End points other than immobilization also can be used to measure anesthetic potency (e.g., the ability to respond to verbal commands [MACawake] or to form memories; both are suppressed at a fraction of MAC) (Table 13-1). Potency of intravenous anesthetic agents is defined as the free plasma concentration (at equilibrium) that produces loss of response to surgical incision (or other end points) in 50% of subjects.

Sites and Mechanisms of Anesthesia

The molecular and cellular mechanisms by which general anesthetics produce their effects have remained one of the great mysteries of pharmacology.

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