Anesthesia and analgesia
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Anesthesia and analgesia · Aug 2005
ReviewNitric oxide synthase inhibition in sepsis? Lessons learned from large-animal studies.
Nitric Oxide (NO) plays a controversial role in the pathophysiology of sepsis and septic shock. Its vasodilatory effects are well known, but it also has pro- and antiinflammatory properties, assumes crucial importance in antimicrobial host defense, may act as an oxidant as well as an antioxidant, and is said to be a "vital poison" for the immune and inflammatory network. Large amounts of NO and peroxynitrite are responsible for hypotension, vasoplegia, cellular suffocation, apoptosis, lactic acidosis, and ultimately multiorgan failure. ⋯ Thus, the issue of NOS inhibition in sepsis remains a matter of debate. Several publications have emphasized the differences concerning clinical applicability of data obtained from unresuscitated, hypodynamic rodent models using a pretreatment approach versus resuscitated, hyperdynamic models in high-order species using posttreatment approaches. Therefore, the present review focuses on clinically relevant large-animal studies of endotoxin or living bacteria-induced, hyperdynamic models of sepsis that integrate standard day-to-day care resuscitative measures.
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Anesthesia and analgesia · Aug 2005
ReviewIntraoperative fluid restriction improves outcome after major elective gastrointestinal surgery.
Fluid therapy is one of the most controversial topics in perioperative management. There is continuing debate with regard to the quantity and the type of fluid resuscitation during elective major surgery. However, there are increasing reports of perioperative excessive intravascular volume leading to increased postoperative morbidity and mortality. ⋯ Furthermore, predetermined algorithms that suggest replacement of third space losses and losses through diuresis are unnecessary. Significant reduction in crystalloid volume can be achieved without encountering intraoperative hemodynamic instability or reduced (i.e., < 0.5 mL x kg(-1) x h(-1)) urinary output just by avoiding replacement of third space losses and preloading. Finally, there is a need for well-controlled studies in a well-defined patient population using clear criteria or end-points for perioperative fluid therapy.
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Anesthesia and analgesia · Aug 2005
Review Meta AnalysisRevising a dogma: ketamine for patients with neurological injury?
We evaluated reports of randomized clinical trials in the perioperative and intensive care setting concerning ketamine's effects on the brain in patients with, or at risk for, neurological injury. We also reviewed other studies in humans on the drug's effects on the brain, and reports that examined ketamine in experimental brain injury. In the clinical setting, level II evidence indicates that ketamine does not increase intracranial pressure when used under conditions of controlled ventilation, coadministration of a gamma-aminobutyric acid (GABA) receptor agonist, and without nitrous oxide. Ketamine may thus safely be used in neurologically impaired patients. Compared with other anesthetics or sedatives, level II and III evidence indicates that hemodynamic stimulation induced by ketamine may improve cerebral perfusion; this could make the drug a preferred choice in sedative regimes after brain injury. In the laboratory, ketamine has neuroprotective, and S(+)-ketamine additional neuroregenerative effects, even when administered after onset of a cerebral insult. However, improved outcomes were only reported in studies with brief recovery observation intervals. In developing animals, and in certain brain areas of adult rats without cerebral injury, neurotoxic effects were noted after large-dose ketamine. These were prevented by coadministration of GABA receptor agonists. ⋯ Ketamine can be used safely in neurologically impaired patients under conditions of controlled ventilation, coadministration of a {gamma}-aminobutyric acid receptor agonist, and avoidance of nitrous oxide. Its beneficial circulatory effects and preclinical data demonstrating neuroprotection merit further animal and patient investigation.