Critical care : the official journal of the Critical Care Forum
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Appropriate antibiotic therapy in patients with severe sepsis and septic shock should mean prompt achievement and maintenance of optimal exposure at the infection site with broad-spectrum antimicrobial agents administered in a timely manner. Once the causative pathogens have been identified and tested for in vitro susceptibility, subsequent de-escalation of antimicrobial therapy should be applied whenever feasible. The goal of appropriate antibiotic therapy must be pursued resolutely and with continuity, in view of the ongoing explosion of antibiotic-resistant infections that plague the intensive care unit setting and of the continued decrease in new antibiotics emerging. This article provides some principles for the correct handling of antimicrobial dosing regimens in patients with severe sepsis and septic shock, in whom various pathophysiological conditions may significantly alter the pharmacokinetic behaviour of drugs.
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Comment Review
Understanding the cognitive consequences of critical illness through experimental animal models.
Tuon and colleagues have developed an animal model to examine the impact of sepsis on memory in rats. They report important data that expand the understanding of the cognitive consequences of critical illness. Future research should follow this path of inquiry and extend animal models beyond aversive conditioning to include recently developed paradigms that will permit assessment of complex and cognitive processes, such as attention, episodic memory and orientation to time and place. This has the potential to greatly increase the putative understanding of the homologous neurocognitive dysfunctions acquired during critical illness.
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Multicenter Study
Incidence of propofol-related infusion syndrome in critically ill adults: a prospective, multicenter study.
While propofol is associated with an infusion syndrome (PRIS) that may cause death, the incidence of PRIS is unknown. Determining the incidence of PRIS and the frequency of PRIS-related clinical manifestations are key steps prior to the completion of any controlled studies investigating PRIS. This prospective, multicenter study sought to determine the incidence of PRIS and PRIS-related clinical manifestations in a large cohort of critically ill adults prescribed propofol. ⋯ Despite using a conservative definition for PRIS, and only considering new-onset PRIS clinical manifestations, the incidence of PRIS slightly exceeds 1%. Future controlled studies focusing on evaluating whether propofol manifests the derangements of critical illness more frequently than other sedatives will need to be large. These studies should also investigate the mechanism(s) and risk factors for PRIS.
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Many studies have demonstrated that closed intensive care units (ICUs), staffed by trained intensivists, are associated with improved patient outcomes. However, the mechanisms by which ICU organizational factors, such as physician staffing, influence patient outcomes are unclear. One potential mechanism is the increased utilization of evidence-based practices in closed ICUs. ⋯ Although closed ICUs were independently associated with a modestly lower mean tidal volume, this finding did not explain the mortality benefit associated with a closed ICU model in this patient cohort. Future studies should evaluate other potential mechanisms by which closed ICUs improve patient outcomes. An improved understanding of these mechanisms may yield new targets for improving the quality of medical care for all ICU patients.
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Critically ill patients may require mechanical ventilatory support and short-term high-dose corticosteroid to treat some specific underlying disease processes. Diaphragm muscle inactivity induced by controlled mechanical ventilation produces dramatic alterations in diaphragm muscle structure and significant losses in function. Although the exact mechanisms responsible for losses in diaphragm muscle function are still unknown, recent studies have highlighted the importance of proteolysis and oxidative stress. ⋯ In animal models, studies on the influence of combined controlled mechanical ventilation and short-term high-dose methylprednisolone have given inconsistent results in regard to the effects on diaphragm muscle function. In the critically ill patient, further research is needed to establish the prevalence and mechanisms of ventilator-induced diaphragm muscle dysfunction, and the possible interaction between mechanical ventilation and the administration of high-dose corticosteroid. Until then, in caring for these patients, it is imperative to allow partial activation of the diaphragm, and to administer the lowest dose of corticosteroid for the shortest duration possible.