Sedation & immunomodulation.

As the armamentarium for sedation in the critically ill expands, opportunities will develop to modulate the immune responses of patients by way of the direct immune and neural-immune interactions of the sedatives. Control of autonomic activity through the use of appropriate sedation may be critical in this matter. Likewise analgesic-based sedation, with increased opioid dosage, may not prove beneficial in the setting of infection; whether avoidance of morphine in preference for a fentanyl derivative will help is unclear. However, as the immune effects seem dependent on the m receptor, it is improbable that a significant difference would be uncovered. Similarly, the present evidence suggests benzodiazepines are deleterious in infection; further studies are required urgently to evaluate this evidence. As an alternative to benzodiazepine-based sedation, dexmedetomidine has shown a remarkable 70% mortality benefit in a small secondary analysis of septic patients from the MENDS trial. Further powered clinical studies should now be undertaken to investigate the potential benefit of the α2-adrenoceptor agonist in this setting, with comparisons with propofol.