Opioid analgesics have always been important for the control of pain in the preoperative and postoperative periods. They are also used to supplement anesthesia when other anesthetic drugs do not adequately control pain reactions. Recently, the more potent and rapidly acting phenylpiperidine opioids have been used as induction agents or as the primary drug for the maintenance of anesthesia (opioid anesthesia), particularly when hemodynamic stability is essential. The high doses required to produce unconsciousness do not depress the myocardium, nor do they cause a significant reduction in blood pressure. Doses must be at least 10 times those used for the control of pain in ambulatory patients; thus, the anesthetic approach is often referred to as highdose opioid. The opioids most commonly used are the highly potent, short-acting phenylpiperidine compounds (see Chapter 26), such as fentanyl (Sublimaze), sufentanil citrate (Sufenta), alfentanil (Alfenta) and remifentanil (Ultiva). Compared to fentanyl and sufen-tanil, alfentanil has a shorter duration of action because of pharmacokinetic characteristics that favor its sequestration in plasma (i.e., high protein binding and relatively low lipid solubility).
Remifentanil, recently approved for use in the United States and Europe, is the first truly ultra-short-acting opioid. Remifentanil's unique ester linkage allows it to be rapidly degraded to an inactive carboxylic acid metabolite by nonspecific esterases found in tissue and red blood cells. Since it is not a good substrate for plasma pseudocholinesterase, deficiency of the enzyme does not influence its duration of action. Also, hepatic and renal insufficiencies do not influence remifentanil's pharmacokinetics, so it is useful when liver or kidney failure is a factor. Because of its rapid clearance following infusion, remifentanil has gained popularity as an agent for maintenance of anesthesia when an IV technique is practical.
Although opioid anesthesia is particularly useful in patients with compromised myocardial function, the opioids depress respiration by inhibiting the responsiveness of the medullary respiratory center to Pco2 and alter the rhythm of breathing. Consequently, it is necessary to assist ventilation intraoperatively. Since respiratory depression may extend into the postoperative period as a result of drug accumulation in the tissues, the use of opioids whose clearances are slow, remain most appropriate for patients who are expected to require postoperative ventilatory care.
Less potent opioids have fallen into disfavor because of the prominence of the untoward effects they produce when given in high doses. Meperidine hy-drochloride (Demerol) causes tachycardia, while morphine produces hypotension and bronchoconstriction as a consequence of its histamine-releasing action.
opioid-induced muscle rigidity is a frequent complication of this form of anesthesia. It is most common with phenylpiperidine drugs and occurs even after low doses of fentanyl, such as those used in certain diagnostic or minor surgical procedures where a pain-free but communicative patient is required (i.e., neurolep-tanalgesia; conscious sedation). Rigidity affects the chest wall and abdomen and thus significantly interferes with breathing. The problem may result from an opioid-induced stimulation of spinal reflexes or interference with basal ganglia integration; the rigidity can be controlled through the use of neuromuscular blocking agents (e.g., pancuronium) and ventilatory support.
one of the most serious drawbacks of opioid anesthesia is the possibility of inadequate anesthetic depth. Signs of inadequate anesthesia include sweating, pupillary dilation, wrinkling of the forehead, and opening of the eyes. Most important, however, awareness or incomplete amnesia may occur. Consequently, additional doses of the opioids are appropriate when signs of light anesthesia manifest. Furthermore, many clinicians supplement the high-dose opioid technique with inhala-tional anesthetics or hypnotics, such as benzodiazepines (midazolam for shorter cases; the longer-acting drug lo-razepam for cases longer than 4 hours) or more recently, propofol. Unfortunately, the use of many of these supplemental drugs may result in some loss of cardiovascular stability.
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