The pharmacokinetics and pharmacodynamics of sedatives and analgesics are significantly altered in the critically ill. These changes may account for the large differences in drug dosage requirements compared with other patient populations. Drugs that in other settings may be considered short-acting often have significantly altered onset and duration of action in critically ill patients, necessitating a change in dosage. Of the benzodiazepines, lorazepam is the drug whose parameters are the least likely to be altered in critical illness. The presence of active metabolites with other benzodiazepines complicates their use during periods of prolonged use. Similarly, the presence of active metabolites of morphine and pethidine (meperidine) warrants caution in patients with renal insufficiency. The fewer cardiovascular effects seen with high-potency opioids, such as fentanyl and sufentanil, increase their usefulness in haemodynamically compromised patients. The pharmacodynamics of propofol are not significantly altered in the critically ill. Ketamine should be used with a benzodiazepine to prevent the emergence of psychomimetic reactions. Lower sedative doses of benzodiazepines and anaesthetics may not provide reliable amnesia. Barbiturates and propofol probably do not induce hyperalgesia and lack intrinsic analgesic activity. The antipsychotic agent haloperidol has a calming effect on patients and administration to the point of sedation is generally not necessary. Combinations of sedatives and analgesics are synergistic in producing sedation. The costs of sedation and analgesia are very variable and closely linked to the pharmacokinetics and pharmacodynamics of the drug. Monitoring of sedation and analgesia is difficult in uncooperative patients in the intensive care unit. In the future, specific monitoring tools may assist clinicians in the regulation of infusions of sedative and analgesic agents.

Both intranasal midazolam and sufentanil provide rapid, safe, and effective sedation in small children before anesthesia for ambulatory surgery. Sufentanil provided somewhat better conditions for induction and emergence. Midazolam causes more nasal irritation during instillation, and sufentanil causes more postoperative nausea and vomiting. Both drugs enabled patients to be separated from their parents with a minimum of distress. Patients in the midazolam group were discharged approximately 40 minutes earlier (p <0.005).

PCA is safe and effective for morbidly obese patients following RYGBP.

OBJECTIVE: This review focuses on how patients' recall of their stay in the ICU can be modified pharmacologically. DATA SOURCES: Computerized MEDLINE and PAPERCHASE searches of English- and foreign-language published research from 1966 to 1995, bibliographies, pharmaceutical and personal files, and conference abstract reports. STUDY SELECTION: All abstracts from uncontrolled and controlled clinical trials were reviewed. DATA EXTRACTION: Study design, population, results, and safety information were retained. Efficacy conclusions were drawn from controlled trials. DATA SYNTHESIS: Patients without cerebral injury may recall mental and physical discomfort during their stay in the ICU. All benzodiazepines produce amnestic effects, but the short duration of action, lack of long-acting metabolites, and potent amnestic effects make lorazepam and midazolam preferable in this setting. Infusions of propofol for conscious sedation produce concentrations below those required for consistent amnesia. Opioids generally do not produce amnesia; however, end-organ failure and use of high doses of opioids may increase plasma concentrations to levels that produce impairment of learning and various degrees of amnesia. High infusion rates of ketamine may be required for satisfactory amnesia and pain control (with coadministration of benzodiazepine). Barbiturates and haloperidol do not impair memory in patients who are not critically ill. Antihistamines and anticholinergics that do not penetrate the central nervous system do not produce amnesia. Flumazenil may induce recall. CONCLUSIONS: Patients may remember their stay in the ICU, depending on the type of injury and the drug therapy. Of the drugs presented, benzodiazepines most reliably provide anterograde amnesia, whereas ketamine and propofol exhibit dose-dependent effects on memory.