Pharmacotherapy
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The reported incidence of adrenal insufficiency varies greatly depending on the population of critically ill patients studied, the test and cutoff levels used, and the severity of illness. Several studies have shown increased mortality in patients with very low or very high baseline cortisol levels. Manifestations of adrenal insufficiency in the critically ill patient are numerous and nonspecific, so clinicians are urged to have a high index of suspicion and be alert to important diagnostic clues, such as hyponatremia, hyperkalemia, and hypotension, that are refractory to fluids and vasopressors without any clear causation. ⋯ Although diagnosing adrenal insufficiency continues to be difficult in the critically ill patient, administration of high-dose corticosteroids, defined as methylprednisolone 30 mg/kg/day or more (or its equivalent), over a short period of time provides no overall benefit and may even be harmful; however, administration of low-dose corticosteroids for a longer duration decreases both the amount of the time that vasopressors are required and mortality at 28 days. Hydrocortisone 200-300 mg/day, administered in divided doses or as a continuous infusion, is the preferred corticosteroid in patients with septic shock and should be started as early as possible. For patients in whom the ACTH stimulation test cannot be given immediately, clinicians are urged to consider using dexamethasone until such time that the test can be administered, since, unlike hydrocortisone, it does not interfere with the cortisol test.
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The combination of ketamine and propofol for procedural sedation and analgesia theoretically may be beneficial, with the rationale being that using lower doses of each agent may result in a reduction of the undesirable adverse effects of both agents while maintaining optimal conditions for performing procedures. To examine the current evidence for the efficacy and safety of ketamine and propofol in combination for procedural sedation and analgesia, we searched the MEDLINE (1966-March 2007), EMBASE (1980-March 2007), and Cochrane Database of Systematic Reviews (through the first quarter of 2007) databases for reports describing the use of ketamine and propofol in combination for procedural sedation and analgesia. Additional published reports were identified through a manual search of references from retrieved articles. ⋯ Compatibility data for the two agents combined in a syringe are limited. The available evidence does not support the use of a fixed-dose ketamine-propofol combination for procedural sedation and analgesia. Further research is needed to elucidate the role, if any, of this combination for procedural sedation and analgesia.
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Infections caused by multidrug-resistant Acinetobacter baumannii have become a therapeutic challenge for clinicians worldwide. Although colistin and tigecycline have been successful in treating patients with these infections, these agents are not available on a worldwide basis. ⋯ We also conducted an in vitro study using isolates from these patients that showed that this drug combination had a synergistic effect with enhanced antibacterial activity against the isolates. Thus, a carbapenem-sulbactam combination may be a therapeutic alternative for multidrug-resistant Acinetobacter baumannii bacteremia in countries where colistin and tigecycline are not available for clinical use.
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To compare conventional intermittent dosing regimens of piperacillin-tazobactam with prolonged and continuous infusions to determine the optimal dosing scheme against a local Pseudomonas aeruginosa population. ⋯ Both prolonged- and continuous-infusion strategies improved the pharmacodynamics of piperacillin-tazobactam over those of traditional 30-minute intermittent-infusion regimens. Prolonged- and continuous infusion regimens that contained the same daily doses of piperacillin had similar likelihoods of bactericidal exposure. Thus, the selection of dosing strategy depends on the availability of intravenous access versus the convenience of once-daily administration.