Anesthetic protection of neurons injured by hypothermia and rewarming: roles of intracellular Ca2+ and excitotoxicity.

BACKGROUND: Mild hypothermia is neuroprotective after cerebral ischemia but surgery involving profound hypothermia (PH, temperature less than 18°C) is associated with neurologic 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 anesthetic agents 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 Ca were assessed with fluorescent dye imaging and histology. Anesthetic agents were present in the culture media during PH and RW or only RW. RESULTS: Injury to hippocampal CA1, CA3, and dentate neurons after PH and RW involved cell swelling, cell rupture, and adenosine triphosphate (ATP) 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 Ca influx during RW but did not involve γ-amino butyric acid receptors or KATP channels. However, cell death increased over the next day. CONCLUSION: Anesthetic protection of neurons rewarmed from 4°C involves suppression of N-methyl-D-aspartate receptor-mediated Ca overload in neurons undergoing ATP loss and excitotoxicity. Unlike during hypoxia/ischemia, anesthetic agents acting predominantly on γ-aminobutyric acid receptors do not protect against PH/RW. The durability of anesthetic protection against cold injury may be limited.

An Analysis of Successful Features of Anesthesiology Journal Clubs.

BACKGROUND: No studies have examined how journal clubs (JCs) are implemented in anesthesiology residency training programs. The goal of the study was to close this gap by (1) examining the format, content, and goals of JCs; (2) identifying features associated with higher resident attendance and JC success; and (3) examining program directors' perspectives on JCs. METHODS: A 41-question survey was sent to anesthesiology program directors. Answers were analyzed using multivariable logistic regression, multivariable linear regression, and exploratory factor analysis. RESULTS: Out of 117 surveys sent across the United States, 80 program directors responded (68.4% response rate). Of the 80 programs, 77 (96.3%) programs have a JC, with 93.2% of them existing for more than 2 years. Most JCs (62.5%) neither formally appraised articles before meetings, nor formally evaluated their JC (59.7%). Faculty alone organized 44.4% and moderated 69.9% of the JCs. The role of residents was primarily limited to presenting selected articles with faculty guidance (83.3%). The average resident attendance was 49.7%. A multivariable linear regression analysis identified mandatory resident attendance, faculty turnout of >5 members, and longer intervals between JC meetings as features associated with higher resident attendance. Only 49.3% of JCs were successful as defined a priori by resident attendance >50% and longevity of ≥2 years. Features associated with JC success based on multivariable logistic regression included mandatory resident attendance and complimentary food. CONCLUSIONS: This largest survey of JCs in anesthesiology found that while JCs are widely established, half of them could be improved.

Discharge against Medical Advice in Surgical Patients with Posttraumatic Stress Disorder: A Case Report Series Illustrating Unique Challenges.

Discharge against medical advice (DAMA) can have detrimental effects on patient outcomes. Recently, the diagnosis of posttraumatic stress disorder (PTSD) has been linked with DAMA in the mental health setting. However, PTSD as a risk factor for DAMA in surgical patients has not received much consideration, although such patients may be at risk for triggering or amplification of PTSD symptoms perioperatively. We present the first case report series of three surgical patients with PTSD who left the hospital AMA. These cases differ markedly from DAMA in non-PTSD patients. In all three subjects, the stress of feeling misunderstood by clinicians and the distress of public detainment by hospital security in the setting of chronic PTSD led to aggressive and risky behavior. All three subjects represented a risk to themselves and to others at the time of DAMA. Finally, all three subjects were difficult to contact for follow-up or medical care and missed appointments.

Serotonin Syndrome Following an Uncomplicated Orthopedic Surgery in a Patient With Post-Traumatic Stress Disorder.

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.

Limitations of Mild, Moderate, and Profound Hypothermia in Protecting Developing Hippocampal Neurons After Simulated Ischemia.

Mild hypothermia (33°C-34°C) after cerebral ischemia in intact animals or ischemia-like conditions in vitro reduces neuron death. However, it is now clear that more profound hypothermia or delayed hypothermia may not provide significant protection. To further define the limitations of hypothermia after cerebral ischemia, we used hippocampal slice cultures to examine the effects of various degrees, durations, and delays of hypothermia on neuron death after an ischemia-like insult. Organotypic cultures of the hippocampus from 7- to 8 day-old rat pups were cooled to 32°C, 23°C, 17°C, or 4°C immediately or after a 2-4 hour delay from an injurious insult of oxygen and glucose deprivation (OGD). Cell death in CA1, CA3 and dentate regions of the cultures was assessed 24 hours later with SYTOX® or propidium iodide, both of which are fluorescent markers labeling damaged cells. OGD caused extensive cell death in CA1, CA3, and dentate regions of the hippocampal cultures. Hypothermia (32°C, 23°C and 17°C) for 4-6 hours immediately after OGD was protective at 24 hours, but when hypothermia was applied for longer periods or delayed after OGD, no protection or increased death was seen. Ultra-profound hypothermia (4°C) increased cell death in all cell areas of the hippocampus even when after a milder insult of only hypoxia. In an in vitro model of recovery after an ischemia-like insult, mild to profound hypothermia is protective only when applied without delay and for limited periods of time (6-8 hours). Longer durations of hypothermia, or delayed application of the hypothermia can increase neuron death. These findings may have implications for clinical uses of therapeutic hypothermia after hypoxic or ischemic insults, and suggest that further work is needed to elucidate the limitations of hypothermia as a protective treatment after ischemic stress.