Propofol: A Sedative-Hypnotic Anesthetic Agent for Use in Ambulatory Procedures: DOSAGE

In: Anesthesia

14 Jan 2010

The effective induction dose of 1% propofol in healthy nonpremedicated adults is 2-2.5 mgAg IV. For individuals over 60, 1.5 mgAg is generally adequate. This induction dose is also reduced by premedication with benzodiazepines or opioids. In children, the dose requirement is increased by 1.5 times due to the shorter elimination half-life in the pediatric patient.

There are two major administration techniques for maintenance of anesthesia: manual bolus and continuous infusion. Both the manual bolus infusion and continuous infusion methods have been shown to provide satisfactory sedation for oral and maxillofacial surgery. However, repeated bolus administration of propofol often produces fluctuating plasma concentrations. This results in a greater likelihood of hypotension and respiratory depression in addition to increasing the amount of drug that needs to be administered. In contrast, the continuous infusion mode of delivery steadies the plasma propofol concentration. This decreases the amount of drug given, permits better control of anesthetic depth, and allows for a swifter recovery time. Also, the risks of adverse effects like hypotension and bradycardia are minimized and hemodynamic stability is more readily achieved. This property is especially advantageous in elderly patients because of their heightened propensity for an exaggerated response to hypotension.

In order to maintain general anesthesia, propofol should be delivered at a rate of 80-150 ixgAg/min. Administration regimens can include propofol alone or concurrently with an opioid and/or nitrous oxide or volatile anesthetic. For conscious sedation, propofol should be administered at 10-50 |xgAg/min, alone or in com­bination with an opioid. When administered with 60-70% nitrous oxide in oxygen, a propofol infusion rate of about 6-8 mgAg/h (100-130 |xgAg/min) is required. When nitrous oxide is undesirable (eg, jet ventilation or pneumothorax), anesthesia can be adequately maintained with propofol alone (usually with benzodiazepine or opioid premedication) at infusion rates of up to 12 mgAg/h (200 |ULgAg/min). More often, however, total IV anesthesia is achieved by simultaneous infusions of propofol and an opioid. Both fentanyl and alfentanil have been found suitable in this context. The characteristic rapid, smooth recovery after propofol maintenance still occurs as long as opioid infusion is discontinued 10-20 minutes before propofol infusion. If this lag time is not implemented, opioid-in-duced respiratory depression may be a problem. Because of the high lipophilicity of propofol, a prolonged effect may be observed in patients with high proportions of adipose tissue compared with overall body weight.

Recently, computer-driven infusion systems have been developed with the salient aspects of propofol’s pharmacokinetic profile in mind. These allow the desired blood propofol concentration to be attained very rapidly with little overshoot. The plasma levels are maintained over long periods by calculating and exponentially decreasing the infusion rate to match the decreasing rate at which the drug leaves the central compartment by distribution and elimination. Remarkably stable hemodynamics can be achieved with such a system.
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Another delivery mechanism, termed patient-controlled sedation, has also been reported as safe and effective. Patients can establish and maintain their own desired level of sedation. This entails self-administration of a predetermined dose, usually over a 5-second period, and a delay mechanism prevents oversedation. Patient-controlled sedation provides a compensatory mechanism for individual pharmacokinetic and pharmacodynamic differences.

RECOVERY CHARACTERISTICS

A major advantage of propofol is the expected rapid emergence from anesthesia. The fastest reported recovery times after general anesthesia with propofol are 5 minutes and 30 minutes. These recovery rates resemble those of some volatile anesthetics. The swift recovery time is more obvious when propofol is used for both induction and maintenance. It has been shown that patients recover faster from propofol compared with methohexital and all of the other major alternatives after deep sedation. In addition, propofol elicits a lower incidence of postoperative shivering than methohexital or halothane. Following propofol an esthesia and sedation, patients are cognizant and clear headed with low occurrences of depression, tremulous-ness, nausea, and vomiting. These aforementioned characteristics make propofol especially beneficial for ambulatory surgery. canadian antibiotics


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