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Background Mild hypothermia is neuroprotective following cerebral ischemia but surgery involving profound hypothermia (PH, temperature <18 °C) is associated with neurological complications. Rewarming (RW) from PH injures hippocampal neurons by glutamate excitotoxicity, N-methyl-D-aspartate receptors and intracellular calcium. Because neurons are protected from hypoxia-ischemia by anesthetics that inhibit N-methyl-D-aspartic acid receptors, we tested whether anesthetics protect neurons from damage caused by PH/RW. Methods Organotypic cultures of rat hippocampus were used to model PH/RW injury, with hypothermia at 4°C followed by RW to 37°C and assessment of cell death 1 or 24 h later. Cell death and intracellular Ca2+ were assessed with fluorescent dye imaging and histology. Anesthetics were present in the culture media during PH and RW or only RW. Results Injury to hippocampal CA1, CA3, and dentate neurons following PH and RW involved cell swelling, cell rupture, and adenosine triphosphate loss; this injury was similar for 4 through 10 h of PH. Isoflurane (1 and 2%), sevoflurane (3%) and xenon (60%) reduced cell loss but propofol (3 μM) and pentobarbital (100 μM) did not. Isoflurane protection involved reduction in N-methyl-D-aspartate receptor-mediated Ca2+ influx during RW but did not involve γ-amino butyric acid receptors or KATP channels. However, cell death increased over the next day. Conclusions Anesthetic protection of neurons rewarmed from 4°C involves suppression of N-methyl-D-aspartate receptor-mediated Ca2+ overload in neurons undergoing adenosine triphosphate loss and excitotoxicity. Unlike during hypoxia/ischemia, anesthetics acting predominately on γ-amino butyric acid receptors do not protect against PH/RW. The durability of anesthetic protection against cold injury may be limited.

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Serotonin syndrome (SS) is a potentially life-threatening adverse drug reaction that may occur in patients treated with serotonin agonist medications. Medications responsible for serotonin syndrome include commonly prescribed antidepressants, anxiolytics, analgesics, and antiemetics. Veterans with post-traumatic stress disorder (PTSD) are at risk for polypharmacy with serotoninergic medications, given their psychological comorbidities and service-related musculoskeletal injuries. The perioperative period is a particularly vulnerable time owing to the use of high-dose anxiolytics and antiemetics frequently administered in this period, and places PTSD patients at higher risk of SS. Herein, we present the first case of SS in a young veteran with combat-related PTSD following an uncomplicated L5-S1 revision discectomy that highlights the unique set of clinical challenges and dilemmas faced when treating SS in a patient with severe postsurgical pain. As we are likely to encounter increasing numbers of veterans treated for PTSD who require multiple surgical procedures to treat their service-related injuries, health care providers need to be familiar with prevention, recognition, and the clinical challenges in the management of SS in the postoperative period.