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Chapter: Modern Pharmacology with Clinical Applications: General Anesthesia: Intravenous and Inhalational Agents

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Intravenous Anesthetic Techniques Managed with Opioids

Opioid analgesics have always been important for the control of pain in the preoperative and postoperative periods.

Intravenous Anesthetic Techniques Managed with Opioids

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 in-duction agents or as the primary drug for the mainte-nance 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 high-dose opioid. The opioids most commonly used are the highly potent, short-acting phenylpiperidine com-pounds , 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 seques-tration in plasma (i.e., high protein binding and rela-tively 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 al-lows 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 follow-ing infusion, remifentanil has gained popularity as an agent for maintenance of anesthesia when an IV tech-nique is practical.

Although opioid anesthesia is particularly useful in patients with compromised myocardial function, the opioids depress respiration by inhibiting the respon-siveness of the medullary respiratory center to PCO2 and alter the rhythm of breathing. Consequently, it is neces-sary to assist ventilation intraoperatively. Since respira-tory depression may extend into the postoperative pe-riod 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 be-cause of the prominence of the untoward effects they produce when given in high doses. Meperidine hy-drochloride (Demerol) causes tachycardia, while mor-phine produces hypotension and bronchoconstriction as a consequence of its histamine-releasing action.

Opioid-induced muscle rigidity is a frequent com-plication 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 diag-nostic 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 inter-feres with breathing. The problem may result from an opioid-induced stimulation of spinal reflexes or inter-ference with basal ganglia integration; the rigidity can be controlled through the use of neuromuscular block-ing agents (e.g., pancuronium) and ventilatory support.

One of the most serious drawbacks of opioid anes-thesia is the possibility of inadequate anesthetic depth. Signs of inadequate anesthesia include sweating, pupil-lary dilation, wrinkling of the forehead, and opening of the eyes. Most important, however, awareness or in-complete amnesia may occur. Consequently, additional doses of the opioids are appropriate when signs of light anesthesia manifest. Furthermore, many clinicians sup-plement 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 re-cently, propofol. Unfortunately, the use of many of these supplemental drugs may result in some loss of cardio-vascular stability.

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