Use of hyperbaric oxygen therapy for preventing delayed neurological sequelae in patients with carbon monoxide poisoning: A multicenter, prospective, observational study in Japan.

BACKGROUND: The purpose of this study was to clarify the practical clinical treatment for acute carbon monoxide (CO) poisoning in Japan and to investigate the efficacy of hyperbaric oxygen (HBO2) therapy in preventing delayed neurological sequelae (DNS) in the acute phase of CO poisoning. METHODS: We conducted a multicenter, prospective, observational study of acute CO poisoning in Japan. Patients with acute CO poisoning were enrolled and their treatment details were recorded. The primary endpoint was the onset of DNS within 2 months of CO exposure. Factors associated with DNS were assessed with logistic regression analysis. RESULTS: A total of 311 patients from 57 institutions were registered and 255 were analyzed: 171 received HBO2 therapy (HBO2 group) and 84 did not (normobaric oxygen [NBO2] group). HBO2 therapy was performed zero, once, twice, or three times within the first 24 h in 1.8%, 55.9%, 30.9%, and 11.3% of the HBO2 group, respectively. The treatment pressure in the first HBO2 session was 2.8 ATA (47.9% of the HBO2 group), 2.0 ATA (41.8%), 2.5 ATA (7.9%), or another pressure (2.4%). The incidence of DNS was 13/171 (7.6%) in the HBO2 group and 3/84 (3.6%) in the NBO2 group (P = 0.212). The number of HBO2 sessions in the first 24 h was one of the factors associated with the incidence of DNS (odds ratio, 2.082; 95% confidence interval, 1.101-3.937; P = 0.024). CONCLUSIONS: The practical clinical treatment for acute CO poisoning, including HBO2 therapy, varied among the institutions participating in Japan. HBO2 therapy with inconsistent protocols showed no advantage over NBO2 therapy in preventing DNS. Multiple HBO2 sessions was associated with the incidence of DNS.

Immediate Surgery in Acute Type A Dissection and Neurologic Dysfunction: Fighting the Inevitable?

BACKGROUND: Neurologic dysfunction remains an ongoing challenge in the diagnosis of type A aortic dissection (AAD). Our study analyzed the impact of preoperative neurologic dysfunction (PND) on outcome and assessed a potential link between PND and specific patterns of postoperative neurologic injury. METHODS: Medical records of 338 patients (70.1% men; mean age, 59.3 ± 13.7 years) undergoing surgical repair for AAD were screened for the presence of PND. Preoperative characteristics, surgical treatment, and hospital and neurologic outcomes were analyzed according to patients with PND (PND+) and without PND (PND-) RESULTS: There were 50 patients (14.8%) admitted with PND. PND+ patients showed significantly higher rates of postoperative neurologic injury (44.4%) than PND- patients (14.3%; P < .001) with a specific pattern of ischemic lesions in accordance with preoperative neurologic status. While PND+ patients suffered mainly from right hemispheric strokes (66.7% vs 32.4% in PND- patients, P = .024), PND- patients more frequently presented with bilateral cerebral ischemia (56.8% vs 13.3% in PND+ patients, P = .004). Multivariable analysis identified presence of PND (odds ratio, 2.977; 95% confidence interval, 1.357-6.545) as an independent predictor for new postoperative neurologic injury. PND was associated with impaired survival (P = .005). CONCLUSIONS: This study identified an association of preoperative neurologic status and specific stroke patterns after surgical repair of AAD. Irrespective of timing of surgery and reperfusion strategies, preoperative neurologic dysfunction is strongly associated with impaired neurologic outcome.

Predicting medication-associated altered mental status in hospitalized patients: Development and validation of a risk model.

PURPOSE: This study presents a medication-associated altered mental status (AMS) risk model for real-time implementation in inpatient electronic health record (EHR) systems. METHODS: We utilized a retrospective cohort of patients admitted to 2 large hospitals between January 2012 and October 2013. The study population included admitted patients aged ≥18 years with exposure to an AMS risk-inducing medication within the first 5 hospitalization days. AMS events were identified by a measurable mental status change documented in the EHR in conjunction with the administration of an atypical antipsychotic or haloperidol. AMS risk factors and AMS risk-inducing medications were identified from the literature, drug information databases, and expert opinion. We used multivariate logistic regression with a full and backward eliminated set of risk factors to predict AMS. The final model was validated with 100 bootstrap samples. RESULTS: During 194,156 at-risk days for 66,875 admissions, 262 medication-associated AMS events occurred (an event rate of 0.13%). The strongest predictors included a history of AMS (odds ratio [OR], 9.55; 95% confidence interval [CI], 5.64-16.17), alcohol withdrawal (OR, 3.34; 95% CI, 2.18-5.13), history of delirium or psychosis (OR, 3.25; 95% CI, 2.39-4.40), presence in the intensive care unit (OR, 2.53; 95% CI, 1.89-3.39), and hypernatremia (OR, 2.40; 95% CI, 1.61-3.56). With a C statistic of 0.85, among patients scoring in the 90th percentile, our model captured 159 AMS events (60.7%). CONCLUSION: The risk model was demonstrated to have good predictive ability, with all risk factors operationalized from discrete EHR fields. The real-time identification of higher-risk patients would allow pharmacists to prioritize surveillance, thus allowing early management of precipitating factors.

Detection of delayed cerebral ischemia using objective pupillometry in patients with aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Cerebral vasospasm causing delayed cerebral ischemia (DCI) is a source of significant morbidity after subarachnoid hemorrhage (SAH). Transcranial Doppler is used at most institutions to detect sonographic vasospasm but has poor positive predictive value for DCI. Automated assessment of the pupillary light reflex has been increasingly used as a reliable way of assessing pupillary reactivity, and the Neurological Pupil Index (NPi) has been shown to decrease hours prior to the clinical manifestation of ischemic injury or herniation syndromes. The aim of this study was to investigate the role of automated pupillometry in the setting of SAH, as a potential adjunct to TCD. METHODS: Our analysis included patients that had been diagnosed with aneurysmal SAH and admitted to the neuro-intensive care unit of the University of Texas Southwestern Medical Center between November 2015 and June 2017. A dynamic infrared pupillometer was used for all pupillary measurements. An NPi value ranging from 3 to 5 was considered normal, and from 0 to 2.9 abnormal. Sonographic vasospasm was defined as middle cerebral artery velocities greater than 100 cm/sec with a Lindegaard ratio greater than 3 on either side on transcranial Doppler. Most patients had multiple NPi readings daily and we retained the lowest value for our analysis. We aimed to study the association between DCI and sonographic vasospasm, and DCI and NPi readings. RESULTS: A total of 56 patients were included in the final analysis with 635 paired observations of daily TCD and NPi data. There was no statistically significant association between the NPi value and the presence of sonographic vasospasm. There was a significant association between DCI and sonographic vasospasm, χ2(1) = 6.4112, p = 0.0113, OR 1.6419 (95% CI 1.1163-2.4150), and between DCI and an abnormal decrease in NPi, χ2(1) = 38.4456, p < 0.001, OR 3.3930 (95% CI 2.2789-5.0517). Twelve patients experienced DCI, with 7 showing a decrease of their NPi to an abnormal range. This change occurred > 8 hours prior to the clinical decline 71.4% of the time. The NPi normalized in all patients after treatment of their vasospasm. CONCLUSIONS: Isolated sonographic vasospasm does not seem to correlate with NPi changes, as the latter likely reflects an ischemic neurological injury. NPi changes are strongly associated with the advent of DCI and could be an early herald of clinical deterioration.

Neurosurgical Care in the Elderly: Increasing Demands Necessitate Future Healthcare Planning.

OBJECTIVES: The worldwide elderly population is steadily increasing. It has been recommended that age-appropriate information should be available for older patients, but little exists in neurosurgery. We aim to better understand the clinical characteristics, bed occupancy and outcomes of elderly patients admitted to a UK neurosurgical unit. METHODS: Retrospective review of medical records of all patients aged 75 years and older admitted for at least 1 night to the Southwest Neurosurgery Centre from 2007 to 2010. Mortality data up to 31 December 2012 were obtained from a national registry. RESULTS: Eight hundred and eighty-six elderly patients were admitted, for whom 877 records were available. Three hundred and eighty-nine patients were admitted electively; 488 were emergency or urgent; 48.8% had cranial pathology and 50.7% had spinal disease. Emergency cases were significantly older and more likely to be male than elective patients. The median length of stay for emergency patients was significantly longer than that of elective patients (P < 0.0001, 3 vs. 8 days). One elective patient died as an inpatient, compared with 46 emergency patients. Of emergency and elective patients, 25.6% and 3.6%, respectively, had died by 6 months after discharge. Age and length of stay were not associated with early death. CONCLUSIONS: The demographics and outcomes of the elderly admitted to a UK neurosurgical center are discussed. Differences between elective and emergency groups are attributable to both the pathologic processes and case selection. Neurosurgical treatment should not be denied based on age, however the high risks of emergency surgery in this age group should be acknowledged.

Atención a pacientes con estados alterados de conciencia en un hospital de pacientes crónicos y larga estancia / Care for patients with altered states of consciousness in a hospital for chronic and long-stay patients

Introducción. Un 30-40% de los pacientes con daño cerebral presenta alteraciones del nivel de conciencia, y algunos casos, estados alterados de conciencia: síndrome de vigilia sin respuesta (SVSR) o estado de mínima conciencia (EMC). La recuperación es variable y la supervivencia está amenazada por múltiples complicaciones. Objetivos. Presentar la metodología de trabajo del Hospital La Pedrera (HLP) para pacientes en SVSR o EMC y analizar las características clínicas de los pacientes atendidos, la evolución, y la situación funcional y cognitiva en el momento del alta. Pacientes y métodos. Estudio descriptivo prospectivo de pacientes atendidos en el HLP durante el período 2009-2013, con diagnóstico de SVSR o EMC. Resultados. El HLP trabaja mediante el método gestión de caso, ofreciendo una atención integral por un equipo multidisciplinar. Los pacientes se clasifican según objetivos asistenciales. Los pacientes con SVSR o EMC se incluyen en el programa de cuidados integrales y adaptación. Se atendió a 23 pacientes (86,9% varones), con una edad media de 54,9 años. Etiología: hemorragia cerebral, 30,4%; encefalopatía anóxica, 26,6%; encefalopatía metabólica, 17,3%; y otras causas, 17,3%. El 73,9% ingresó en SVSR y el resto en EMC. Evolución: el 43,4% mejoró su situación cognitiva inicial y el 88,8% presentaba una situación de dependencia total en el momento del alta. Las complicaciones más frecuentes fueron infecciones respiratorias y urinarias (53,6%). El 65,2% de los casos fueron exitus. Conclusiones. La asistencia en SVSR o EMC es compleja y precisa cuidados multidisciplinares. Casi la mitad de los pacientes mejoró su situación cognitiva, lo que justifica una actitud proactiva que intente mejorar la calidad de vida de los pacientes y sus familias (AU)

Introduction. Between 30% and 40% of patients with brain damage present alterations in their level of consciousness and, in some cases, altered states of consciousness: unresponsive wakefulness syndrome (UWS) or minimally conscious state (MCS). Recovery varies and survival is threatened by a number of complications. Aims. The purpose of this study is to present the working methodology used at the Hospital La Pedrera (HLP) for patients in UWS or MCS and to analyse the clinical characteristics of the patients attended to, their progress, and the functional and cognitive situation at the time of their discharge from hospital. Patients and methods. The work consisted in a prospective descriptive study of patients seen at the HLP over the period 2009-2013, who had been diagnosed with UWS or MCS. Results. The HLP uses the case management method, offering integrated care dispensed by a multidisciplinary team. Patients are classified according to healthcare goals. Patients with UWS or MCS are included in the integrated care and adaptation programme. A total of 23 patients (86.9% males) were attended to, the mean age being 54.9 years. Aetiology: brain haemorrhage, 30.4%; anoxic encephalopathy, 26.6%; metabolic encephalopathy, 17.3%; and other causes, 17.3%. Altogether 73.9% were admitted in UWS and the rest in MCS. Course: 43.4% improved their initial cognitive situation and 88.8% presented a situation of total dependence at the time of discharge. The most frequent complications were respiratory and urinary infections (53.6%). Death occurred in 65.2% of cases. Conclusions. Medical attention in UWS or MCS is complex and requires multidisciplinary care. Almost half of the patients improved their cognitive situation, which justifies a proactive attitude that attempts to improve the quality of life of both patients and their families (AU)

[A 43-year-old patient with character changes, recurrent impaired consciousness and retrograde amnesia]. / 43-jähriger Patient mit Wesensveränderung, rezidivierenden Bewusstseinsstörungen und retrograder Amnesie.

A 43-year-old male patient with recurring impaired consciousness and retrograde amnesia was admitted to the department of neurology. During the neurological evaluation no pathological findings could initially be revealed but one day the patient was confused again and presented with inadequate behavior: at this time a blood glucose value of 40 mg/dl was measured. For further evaluation the patient was transferred to our department. As the reason for the impaired consciousness was suspected to be of neuroglucopenic origin a rapid adrenocorticotropic hormone (ACTH) stimulation test was first performed to rule out adrenal insufficiency. For further evaluation a fasting test was conducted: after 48 h an episode with neuroglucopenic symptoms occurred again which disappeared after intravenous administration of glucose. The laboratory results of glucose, insulin and c-peptide determined at this point in time led to the diagnosis of an insulinoma. By ultrasound examination a hypoechogenic lesion 1.5 cm in size could be shown in the head of the pancreas and was confirmed by magnetic resonance imaging (MRI). After duodenum-preserving partial pancreatic head resection with enucleation of the insulinoma no further neuroglucopenic symptoms occurred.

LIPAEMIC report: results of clinical use of intravenous lipid emulsion in drug toxicity reported to an online lipid registry.

The use of intravenous lipid emulsion (ILE) as an antidote has prompted significant academic and clinical interest. Between August 2009 and August 2012, data from cases of ILE use in intoxicated patients in different hospitals on different continents were voluntarily entered into a registry based on the world wide web (www.lipidregistry.org). Here, we report data from this project. Participating centers were given access to the registry following institutional subscription. Specifically sought were details of the individual patients' presenting condition, indications for ILE use, ILE administration regimen, potential complications, and of clinical outcome. Forty-eight uses of ILE were reported from 61 participating centers. Ten cases of local anesthetic systemic toxicity were reported; all (10/10) survived. Thirty-eight cases of intoxication by other agents were reported [30 decreased conscious state, 8 cardiovascular collapse (3 deaths)]. There was an elevation in GCS (p < 0.0001) and increased systolic blood pressure (p = 0.012) from immediately prior to ILE administration to 30 min after use. One serious and two minor adverse effects of ILE use were recorded in 48 reported cases (one case of bronchospastic reaction, one case of hyperamylasemia and one case of interference with laboratory testing). In this series of cases reported to the registry, improvements were seen for GCS in patients with central nervous system toxicity and in systolic blood pressure in shocked patients over a short time frame after the injection of ILE. Few adverse effects were recorded. Clinical trials and the reporting of drug concentrations after ILE use are necessary to further elucidate the role of ILE in clinical toxicology.

Severe stroke: which medicine for which results?

In face of any severe stroke, the questions for health professionals in charge of the patient are: will the handicap be acceptable for the patient? But can we predict an acceptable handicap for the patient? For his family? When we know that the cognitive disorders, consequences of severe stroke often modify, in a major way, the behaviour of these patients? Given these difficulties for estimate vital and functional prognosis and even more the quality of life of patients with severe stroke, collective reflexions between physicians and nurses are essential, reflexions taking into account preferences and values of patients. Use of resuscitation resources for severe stroke patients implies to offer them the best rehabilitation. So, questions about health pathways for severe stroke are essential: which structures for these patients, which technologies, which medical, medico-social and social supports, which human accompaniment the society can propose to the patients and to their family, so that they have an acceptable quality of life.

[24-hour work: the interaction of stress and changes in the sleep-wake cycle in the police force]. / II lavoro H24: I'interazione stress e alterazione del ritmo sonno-veglia nelle forze di polizia.

Disruption in police officers. In recent years there has been a widespread growth in services, available regardless of time or day organization (24/7 service) and a diffuse increase in their use, both in work and private lives, generally ignoring the importance of a regular sleep organization. Police officers - often need to work extended shifts and long hours under highly stressful conditions, which results in reduced levels of safety and operational effectiveness. In numerous studies, perceived stress has been found to correlate with both subjective and objective disturbances in sleep. Consequently, excessive daytime sleepiness is one of the most frequent health and safety hazards that police officers have to deal with. Sleep deprivation affects performance outcomes through a wide range of cognitive domains. Sleepiness and fatigue, caused by sleep loss, extended work and wakefulness, circadian misalignment and sleep disorders are major causes of workplace human errors, incidents, and accidents. Therefore, prevention of sleep loss, high levels of stress and fatigue is a key factor to consider when assessing emergency intervention. In order to combat fatigue and sleepiness, a 30-90 minutes nap before night shift could be a viable option.

Un modelo explicativo de la calidad de vida en la esquizofrenia: el papel de la velocidad de procesamiento y los síntomas negativos / An explanatory model of quality of life in schizophrenia: the role of processing speed and negative symptoms

Introducción. Mejorar la calidad de vida de los pacientes con esquizofrenia es un objetivo fundamental en una enfermedad que resulta devastadora, pero no hay acuerdo sobre qué factores predicen la calidad de vida (CV) en el curso de la enfermedad. Metodología. En el presente estudio se examinaron a165 pacientes hospitalizados con esquizofrenia. Se incluyeron medidas de síntomas psiquiátricos (PANSS, insight y síntomas afectivos) y cognitivas. Un análisis factorial confirmatorio estableció una estructura cognitiva compuesta de seis factores, que incluyen atención, velocidad de procesamiento, memoria verbal, fluidez, memoria de trabajo y funciones ejecutivas. La calidad de vida fue medida mediante la Escala de Calidad de Vida de Heinrichs-Hanlon-Carpenter. Resultados. La edad, tiempo de duración de la enfermedad, mayor gravedad de síntomas negativos y la mayoría de factores cognitivos correlacionaron significativamente con los indicadores de CV. Los análisis de regresión mostraron que, muy por encima de los demás factores cognitivos, la velocidad de procesamiento (VP) es un importante predictor de la CV. Además, la interacción de la VP con los síntomas negativos, la edad del paciente y el nivel de deterioro en funciones ejecutivas modificaron el efecto de la VP sobre la CV. Finalmente, los síntomas positivos y otros datos sociodemográficos no guardaron relación con la CV en nuestro estudio. Conclusiones. Nuestros hallazgos sugieren que la VP y los síntomas negativos predicen la CV en la esquizofrenia (AU)

Introduction. Improving the quality of life of patients with schizophrenia is a major goal in managing this devastating disorder, but agreement is lacking about the factors that predict quality of life (QoL) over the course of the disorder. Methods. We examined 165 hospitalized patients with schizophrenia in this study. We included measures for psychiatric (PANSS, insight and affective symptoms) and cognitive symptoms. Confirmatory factor analysis established a cognitive structure composed of the following six factors: attention, processing speed, verbal memory, fluency, working memory and executive functioning. Quality of life was assessed using the Heinrichs-Hanlon-Carpenter Scale. Results. Age, duration of illness, presence of more severe negative symptoms and most cognitive factors correlated significantly with QoL indicators. Regression analysis showed that processing speed (PS) was by far the most important cognitive factor that predicted QoL. Moreover, the interaction between PS and negative symptoms, patient age and executive functions modified the effect of PS on QoL. Finally, positive symptoms and other socio-demographic data were not related to QoL in the current study. Conclusions. Our findings suggest that PS and negative symptoms predict QoL in schizophrenia (AU)

Managing hyponatremia in patients with syndrome of inappropriate antidiuretic hormone secretion.

Disorders of sodium [Na+] and water metabolism are commonly encountered in the hospital setting due to the wide range of disease states that can disrupt the balanced control of water and solute intake and output. In particular, the prompt identification and appropriate management of abnormally low serum [Na+] is critical if we are to reduce the increased morbidity and mortality that accompany hyponatremia in hospitalized patients. Use of an algorithm that is based primarily on the symptomatology of hyponatremic patients, rather than the serum [Na+] or the chronicity of the hyponatremia, will help to choose the correct initial therapy in hospitalized hyponatremic patients. However, careful monitoring of serum [Na+] responses is required in all cases to adjust therapy appropriately in response to changing clinical conditions. Although this approach will enable efficacious and safe treatment of hyponatremic patients with syndrome of inappropriate antidiuretic hormone secretion (SIADH) at the present time, evolving knowledge of the consequences of chronic hyponatremia will likely alter treatment indications and guidelines in the future.

[Complications of the hemodialysis procedure in acute renal failure patients: nursing interventions]. / Complicações do procedimento hemodialítico em pacientes com insuficiência renal aguda: intervenções de enfermagem.

This retrospective study has identified both the prevalence of complications during hemodialitic treatment in patients carrying acute renal failure (ARF) in an intensive care unit of a university hospital and the nursing conduct performed during those episodes. We have assessed sixty-five (282 sessions) records of ARF patients who underwent renal replacement therapy and presented complications during hemodialysis sessions. We have noticed that the most prevalent intradialitic complications were: arterial hypotension (35%), hypothermia (29%), and lack of flow in the vascular access (24.1%). The nursing interventions prioritized during episodes of clinical complications involved clinical assessment (66.8%) and evaluation of patients' consciousness level (59.9%). The search for nursing procedures that are suitable to different situations experienced by patients during hemodialysis, as well as the continuing education of the nursing team are actions that may minimize the intercurrence rate.

Addendum to "Personal and public safety issues related to arrhythmias that may affect consciousness: implications for regulation and physician recommendations: a medical/scientific statement from the American Heart Association and the North American Society of Pacing and Electrophysiology": public safety issues in patients with implantable defibrillators: a scientific statement from the American Heart Association and the Heart Rhythm Society.

OVERVIEW: In 1996, the American Heart Association developed a scientific statement entitled "Personal and Public Safety Issues Related to Arrhythmias That May Affect Consciousness: Implications for Regulation and Physician Recommendations." Since then, multiple trials have established the role of implantable cardioverter-defibrillators (ICDs) for the primary prevention of sudden cardiac death in patients at risk for life-threatening ventricular arrhythmias. OBJECTIVE: The issue of driving for patients with ICDs implanted for primary prevention was briefly discussed in the original statement, with the recommendation that such patients not be restricted from driving beyond the initial phase of healing. This scientific statement has been developed to extend the original 1996 recommendations and to provide specific recommendations on driving for individuals with ICDs implanted for primary prevention. SUMMARY OF RECOMMENDATIONS: (1) Patients receiving ICDs for primary prevention should be restricted from driving a private automobile for at least 1 week to allow for recovery from implantation of the defibrillator. Thereafter, these driving privileges should not be restricted in the absence of symptoms potentially related to an arrhythmia. (2) Patients who have received an ICD for primary prevention who subsequently receive an appropriate therapy for ventricular tachycardia or ventricular fibrillation, especially with symptoms of cerebral hypoperfusion, should then be considered to be subject to the driving guidelines previously published for patients who received an ICD for secondary prevention. (3) Patients with ICDs for primary prevention must be instructed that impairment of consciousness is a possible future event. (4) These recommendations do not apply to the licensing of commercial drivers.

Valproic acid prevents brain injury in a canine model of hypothermic circulatory arrest: a promising new approach to neuroprotection during cardiac surgery.

BACKGROUND: The anticonvulsant valproic acid (sodium valproate, Depacon) acts as a neuroprotectant in rodents, but has never been tested in larger animals. We used valproate in our canine model of hypothermic circulatory arrest to evaluate its neuroprotective benefit in complex cardiac surgical cases. METHODS: Thirteen dogs pretreated with valproate before 2 hours of hypothermic circulatory arrest survived for 24 hours (n = 7) or 72 hours (n = 6). Thirteen control animals (placebo only) also survived for 24 hours (n = 7) or 72 hours (n = 6) after hypothermic circulatory arrest. Blinded clinical neurologic evaluation was performed daily until sacrifice using the Pittsburgh Canine Neurologic Scoring System. Brains were harvested for blinded histopathologic analysis by a neuropathologist to determine the extent of apoptosis and necrosis in 11 brain regions (Total Brain Cell Death Score: 0 = normal, 99 = extensive neuronal death in all regions). Quantification of N-acetyl-aspartate, an established marker for brain injury, was performed with mass spectrometry. RESULTS: Valproate dogs scored significantly better than control animals on clinical neurologic evaluation. Histopathologic examination revealed that valproate animals demonstrated less neuronal damage (by Total Brain Cell Death Score) than control animals at both 24 hours (16.4 versus 11.4; p = 0.03) and 72 hours (21.7 versus 17.7; p = 0.07). At 72 hours, the entorhinal cortex, an area involved with learning and memory, was significantly protected in valproate dogs (p < 0.05). Furthermore, the cortex, hippocampus, and cerebellum demonstrated preservation of near-normal N-acetyl-aspartate levels after valproate pretreatment. CONCLUSIONS: These data demonstrate clinical, histologic, and biochemical improvements in dogs pretreated with valproate before hypothermic circulatory arrest. This commonly used drug may offer a promising new approach to neuroprotection during cardiac surgery.