PHARMACOKINETICS AND PHARMACODYNAMICS OF SEDATIVES AND ANALGESICS IN THE TREATMENT OF AGITATED CRITICALLY-ILL PATIENTS

The pharmacokinetics and pharmacodynamics of sedatives and analgesics are significantly altered in the critically ill. These changes may acc ount for the large differences in drug dosage requirements compared wi th other patient populations. Drugs that in other settings may be cons idered short-acting often have significantly altered onset and duratio n of action in critically ill patients, necessitating a change in dosa ge. Of the benzodiazepines, lorazepam is the drug whose parameters are the least likely to be altered in critical illness. The presence of a ctive metabolites with other benzodiazepines complicates their use dur ing periods of prolonged use. Similarly, the presence of active metabo lites of morphine and pethidine (meperidine) warrants caution in patie nts with renal insufficiency. The fewer cardiovascular effects seen wi th high-potency opioids, such as fentanyl and sufentanil, increase the ir usefulness in haemodynamically compromised patients. The pharmacody namics of propofol are not significantly altered in the critically ill . Ketamine should be used with a benzodiazepine to prevent the emergen ce of psychomimetic reactions. Lower sedative doses of benzodiazepines and anaesthetics may not provide reliable amnesia. Barbiturates and p ropofol probably do not induce hyperalgesia and lack intrinsic analges ic activity. The antipsychotic agent haloperidol has a calming effect on patients and administration to the point of sedation is generally n ot necessary. Combinations of sedatives and analgesics are synergistic in producing sedation. The costs of sedation and analgesia are very v ariable and closely linked to the pharmacokinetics and pharmacodynamic s of the drug. Monitoring of sedation and analgesia is difficult in un cooperative patients in the intensive care unit. In the future, specif ic monitoring tools may assist clinicians in the regulation of infusio ns of sedative and analgesic agents.