Search

Background The relationship between intraoperative physiology and postoperative stroke is incompletely understood. Preliminary data suggest that either hypo- or hypercapnia coupled with reduced cerebrovascular inflow (e.g., due to hypotension) can lead to ischemia. This study tested the hypothesis that the combination of intraoperative hypotension and either hypo- or hypercarbia is associated with postoperative ischemic stroke. Methods We conducted a retrospective, case–control study via the Multicenter Perioperative Outcomes Group. Noncardiac, nonintracranial, and nonmajor vascular surgical cases (18 yr or older) were extracted from five major academic centers between January 2004 and December 2015. Ischemic stroke cases were identified via manual chart review and matched to controls (1:4). Time and reduction below key mean arterial blood pressure thresholds (less than 55 mmHg, less than 60 mmHg, less than 65 mmHg) and outside of specific end-tidal carbon dioxide thresholds (30 mmHg or less, 35 mmHg or less, 45 mmHg or greater) were calculated based on total area under the curve. The association between stroke and total area under the curve values was then tested while adjusting for relevant confounders. Results In total, 1,244,881 cases were analyzed. Among the cases that screened positive for stroke (n = 1,702), 126 were confirmed and successfully matched with 500 corresponding controls. Total area under the curve was significantly associated with stroke for all thresholds tested, with the strongest combination observed with mean arterial pressure less than 55 mmHg (adjusted odds ratio per 10 mmHg-min, 1.17 [95% CI, 1.10 to 1.23], P < 0.0001) and end-tidal carbon dioxide 45 mmHg or greater (adjusted odds ratio per 10 mmHg-min, 1.11 [95% CI, 1.10 to 1.11], P < 0.0001). There was no interaction effect observed between blood pressure and carbon dioxide. Conclusions Intraoperative hypotension and carbon dioxide dysregulation may each independently increase postoperative stroke risk. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

BACKGROUND Mechanisms of postoperative stroke are poorly understood, particularly for strokes occurring after uneventful emergence from anesthesia. We sought to create a model to study retrospectively the timing and associations for stroke in a high-risk surgery population. METHODS Using a large prospective database containing detailed information on the occurrence and timing of stroke, we identified patients undergoing procedures involving the distal vascular (DV) and the cerebral vascular (CV) to assess the association between perioperative factors and stroke. We used separate Cox regressions with time-varying coefficients, one for each cohort, to assess the association between baseline factors and the timing of postoperative stroke within the DV and CV cohorts. Using time-varying coefficients allows hazard ratios to vary over time rather than assuming that the hazard ratio remains constant with time. Propensity score matching was used to compare the timing of stroke between DV and CV groups. RESULTS Among the 80,185 patients with qualifying procedures, there were 711 strokes (0.9%) in the first 30 days after surgery. Stroke incidence was lower for DV patients (0.5%, 306/57,553; P < .001) than CV (1.8%, 405/21,940) and the majority of strokes in the DV group were delayed, occurring between postoperative (POD) days 2 and 30 (236/306, 77%). Among the 711 patients who had a stroke, the proportion of strokes that occurred on day 0 was 8% (n = 24 of 306 strokes) in the DV group compared to 35% in the CV group (n = 140 of 405 strokes). Factors associated with stroke on POD 1 for both groups were preoperative mechanical ventilation and emergent procedures. Acute renal failure and female sex were highly associated with delayed stroke (POD 2-30). Perioperative blood transfusion was associated with an increased hazard of delayed stroke in the DV group and a hazard ratio that increased with time in the CV group. CONCLUSIONS After adjusting for confounding, stroke was more common and occurred earlier in the CV group. Factors associated with delayed postoperative stroke include acute renal failure, emergent procedures, female sex, preoperative mechanical ventilation, and perioperative transfusion.

Stroke is associated with substantial morbidity and mortality. The aim of this review is to provide an evidence-based synthesis of the literature related to perioperative stroke, including its etiology, common risk factors, and potential risk reduction strategies. In addition, the authors will discuss screening methods for the detection of postoperative cerebral ischemia and how multidisciplinary collaborations, including endovascular interventions, should be considered to improve patient outcomes. Lastly, the authors will discuss the clinical and scientific knowledge gaps that need to be addressed to reduce the incidence and improve outcomes after perioperative stroke.

Perioperative stroke is associated with considerable morbidity and mortality. Stroke recognition and diagnosis are challenging perioperatively, and surgical patients receive therapeutic interventions less frequently compared with stroke patients in the outpatient setting. These updated guidelines from the Society for Neuroscience in Anesthesiology and Critical Care provide evidence-based recommendations regarding perioperative care of patients at high risk for stroke. Recommended areas for future investigation are also proposed.

Recent reviews of interprofessional education (IPE) highlight the need for innovative curricula focused on longitudinal clinical learning. We describe the development and early outcomes of the initial clinical experience (ICE), a longitudinal practice-based course for first-year medical students. While IPE courses focus on student-to-student interaction, ICE focuses on introducing students to interprofessional collaboration. Students attend 14 sessions at one of 18 different clinical sites. They work directly with different health professionals from among 17 possible professions, including nurses, pharmacists, social workers, and respiratory, occupational, and physical therapists. Between 2015 and 2016, 167 students completed the course, and 81 completed the end-of-course evaluation. Students agreed or strongly agreed that ICE meaningfully contributed to their understanding of healthcare teams and different professional roles (86%), improved their understanding of healthcare systems (84%), improved their ability to communicate with healthcare professionals (61%), and improved their ability to work on interprofessional teams (65%). Select themes from narrative comments suggest that clinical immersion improves understanding of professional roles, helps students understand their own future roles in healthcare teams, and increases awareness of and respect for other professionals, with the potential to change future practice. ICE may be a template for other schools wishing to expand their current educational offerings, by engaging learners in more authentic, longitudinal clinical experiences with practicing healthcare professionals.

Neurosurgical intensive care unit (NICU) patients often require multiple transports for diagnostic studies and interventions over the course of their hospitalizations. While the majority of these transports proceed uneventfully, they are fraught with risk, particularly in the context of a rapidly deteriorating patient. Urgent transports are frequently required at night when staff experience and numbers may be less robust than during daytime shifts. Given the potential for patient injury, many institutions are now moving toward the establishment of a team of professionals who provide both scheduled and emergent transport and continued care during invasive studies. These teams represent an entirely new (and thus far under-recognized) specialty of transport medicine.

Purpose of Review The significance of stroke in the noncardiac, nonneurologic, and nonvascular perioperative setting has been routinely underestimated. A complex interplay of multiple perioperative, patient, and surgical factors is involved in the pathogenesis of perioperative stroke. Multiple risk reduction strategies are required to decrease the incidence of this devastating complication.

Stroke is the leading cause of disability in the United States, and in terms of mortality is second only to ischemic heart disease worldwide. Medical management for acute ischemic stroke (AIS) was limited to supportive care until 1995, when the National Institute of Neurological Disorders and Stroke (NINDS) trial demonstrated improved outcomes with systemic thrombolysis for AIS. Since December 2014, four major articles have been published in support of endovascular intervention for AIS, making this a central focus of this chapter. Other related topics for this chapter include the timing of elective surgery following stroke, how to assess perioperative risk for patients having a history of remote stroke, and implications for postoperative morbidity and mortality associated with perioperative stroke in noncardiac surgery.

Perioperative stroke is associated with considerable morbidity and mortality. Stroke recognition and diagnosis are challenging perioperatively, and surgical patients receive therapeutic interventions less frequently compared with stroke patients in the outpatient setting. These updated guidelines from the Society for Neuroscience in Anesthesiology and Critical Care provide evidence-based recommendations regarding perioperative care of patients at high risk for stroke. Recommended areas for future investigation are also proposed.

Perioperative stroke is a potentially catastrophic complication of surgery. Patients undergoing vascular surgery suffer from systemic atherosclerosis and are expected to be at increased risk for this complication. We studied the incidence, predictors, and outcomes of perioperative stroke after noncarotid major vascular surgery using the American College of Surgeons National Quality Improvement Program database.Forty-seven thousand seven hundred fifty patients undergoing noncarotid vascular surgery from 2005 to 2009 at nonVeterans Administration hospitals were identified from the American College of Surgeons National Quality Improvement Program database. An analysis of patients undergoing elective lower extremity amputation, lower extremity revascularization, or open aortic procedures was performed to determine the incidence, independent predictors, and 30-day mortality of perioperative stroke.The overall incidence of perioperative stroke within 30 days of surgery (n=37,927) was 0.6%. Multivariate analysis revealed that each 1-year increase in age [odds ratio 1.02, 95% confidence interval (CI) (1.01 to 1.04)], cardiac history [1.42, (1.07 to 1.87)], female sex [1.47, (1.12 to 1.93)], history of cerebrovascular disease [1.72, (1.29 to 2.29)], and acute renal failure or dialysis dependence [2.03, (1.39 to 2.97)] were independent predictors of stroke. Only 15% (95% CI, 11%-20%) of strokes occurred on postoperative day 0 or 1. Perioperative stroke was associated with a 3-fold increase in 30-day all-cause mortality [3.36, (1.77 to 6.36)] and an increased median surgical length of stay from 6 (95% CI, 2 to 28) to 13 (95% CI, 3 to 43) days (P0.001, WMWodds 2.5, 95% CI, 2.0 to 3.2) in a matched-cohort assessment.Perioperative stroke is an important source of morbidity and mortality, as reflected by significant increases in median surgical length of stay and all-cause 30-day mortality. The independent predictors of stroke that we have identified in this population are not readily modifiable and the majority of strokes occurred after postoperative day 1. Additional studies are required to identify potentially modifiable intraoperative or postoperative risk factors of perioperative stroke.

We sought to characterize stroke management and outcomes in a postoperative population. By using the electronic medical records, we identified 39 patients suffering perioperative stroke after noncardiac and nonneurosurgical procedures for whom documentation of management and outcomes was available. Thirty-three strokes occurred during admission, whereas 6 occurred after discharge and were recognized upon return to the hospital. Perioperative stroke was associated with delayed recognition, infrequent intervention, and significant rates of morbidity and mortality, suggesting the need for improved screening and more rapid treatment. There may be disparities in care and outcomes between in-hospital and out-of hospital stroke patients, though further study is warranted.

BACKGROUND Maintaining adequate cerebral perfusion pressure (CPP) is of clinical concern in patients with neurological injury. Although there are extensive data on CPP in the ICU setting, there has been little quantitative study of CPP in the intraoperative setting. METHODS We retrospectively analyzed the electronic intraoperative records of neurosurgical and trauma patients with concurrent intracranial and arterial pressure monitoring devices in continuous use for ≥45 minutes to calculate CPP (=mean arterial pressure-intracranial pressure). We assessed the total minutes and frequency of 5-minute epochs, during which the median CPP was

Background Perioperative hypothermia has been reported to increase the occurrence of cardiovascular complications. By increasing the activity of sympathetic nervous system, perioperative hypothermia also has the potential to increase cardiac injury and dysfunction associated with subarachnoid hemorrhage. Methods The Intraoperative Hypothermia for Aneurysm Surgery Trial randomized patients undergoing cerebral aneurysm surgery to intraoperative hypothermia (n = 499, 33.3 degrees +/- 0.8 degrees C) or normothermia (n = 501, 36.7 degrees +/- 0.5 degrees C). Cardiovascular events (hypotension, arrhythmias, vasopressor use, myocardial infarction, and others) were prospectively followed until 3-month follow-up and were compared in hypothermic and normothermic patients. A subset of 62 patients (hypothermia, n = 33; normothermia, n = 29) also had preoperative and postoperative (within 24 h) measurement of cardiac troponin-I and echocardiography to explore the association between perioperative hypothermia and subarachnoid hemorrhage-associated myocardial injury and left ventricular function. Results There was no difference between hypothermic and normothermic patients in the occurrence of any single cardiovascular event or in composite cardiovascular events. There was no difference in mortality (6%) between groups, and there was only a single primary cardiovascular death (normothermia). There was no difference between hypothermic and normothermic patients in postoperative versus preoperative left ventricular regional wall motion or ejection fraction. Compared with preoperative values, hypothermic patients had no postoperative increase in cardiac troponin-I (median change 0.00 microg/l), whereas normothermic patients had a small postoperative increase (median change + 0.01 microg/l, P = 0.038). Conclusion In patients undergoing cerebral aneurysm surgery, perioperative hypothermia was not associated with an increased occurrence of cardiovascular events.

Background Although hypothermia and barbiturates improve neurologic outcomes in animal temporary focal ischemia models, the clinical efficacy of these interventions during temporary occlusion of the cerebral vasculature during intracranial aneurysm surgery (temporary clipping) is not established. Methods A post hoc analysis of patients from the Intraoperative Hypothermia for Aneurysm Surgery Trial who underwent temporary clipping was performed. Univariate and multivariate logistic regression methods were used to test for associations between hypothermia, supplemental protective drug, and short- (24-h) and long-term (3-month) neurologic outcomes. An odds ratio more than 1 denotes better outcome. Results Patients undergoing temporary clipping (n = 441) were assigned to intraoperative hypothermia (33.3 degrees +/- 0.8 degrees C, n = 208) or normothermia (36.7 degrees +/- 0.5 degrees C, n = 233), with 178 patients also receiving supplemental protective drug (thiopental or etomidate) during temporary clipping. Three months after surgery, 278 patients (63%) had good outcome (Glasgow Outcome Score = 1). Neither hypothermia (P = 0.847; odds ratio = 1.043, 95% CI = 0.678-1.606) nor supplemental protective drug (P = 0.835; odds ratio = 1.048, 95% CI = 0.674-1.631) were associated with 3-month Glasgow Outcome Score. The effect of supplemental protective drug did not significantly vary with temperature. The effects of hypothermia and protective drug did not significantly vary with temporary clip duration. Similar findings were made for 24-h neurologic status and 3-month Neuropsychological Composite Score. Conclusion In the Intraoperative Hypothermia for Aneurysm Surgery Trial, neither systemic hypothermia nor supplemental protective drug affected short- or long-term neurologic outcomes of patients undergoing temporary clipping.

Background: Web-based delivery of educational material by scientific societies appears to have increased recently. However, the utilization of such efforts by the members of professional societies is unknown. We report the experience with delivery of educational resources on the Web site of the Society for Neuroscience in Anesthesiology and Critical Care (SNACC), and utilization of those resources by members. Methods: Three web-based educational initiatives were developed over 1 year to be disseminated through the SNACC Web site (http://www.snacc.org) for society members: (1) The SNACC Bibliography; (2) “Chat with the Author”; and (3) Clinical Case Discussions. Content experts and authors of important new research publications were invited to contribute. Member utilization data were abstracted with the help of the webmaster. Results: For the bibliography, there were 1175 page requests during the 6-month period after its launch by 122/664 (19%) distinct SNACC members. The bibliography was utilized by 107/553 (19%) of the active members and 15/91 (16.5%) of the trainee members. The “Chats with the Authors” were viewed by 56 (9%) members and the Clinical Case Discussions by 51 (8%) members. Conclusions: Educational resources can be developed in a timely manner utilizing member contributions without additional financial implications. However, the member utilization of these resources was lower than expected. These are first estimates of utilization of web-based educational resources by members of a scientific society. Further evaluation of such utilization by members of other societies as well as measures of the effectiveness and impact of such activities is needed.

We tested the hypothesis that Paco2 would be more tightly controlled if end-tidal CO2 monitoring was used during hand ventilation for transport of intubated patients.Randomized, prospective analysis of the no-monitor and monitor-blind groups (the monitor was on the bed during transport but only the investigator was aware of the end-tidal CO2 values). Nonrandomized, prospective analysis of the monitor group (ventilation controlled using end-tidal CO2 value from monitor).University hospital operating room and intensive care unit (ICU).Fifty intubated patients who were transported from the operating room to the ICU or from the ICU to the neuroradiology suite were assigned randomly to one of two groups: a) no-monitor group (n = 25); and b) monitor-blind group (n = 25). An additional group (monitor group, n = 10) was subsequently added to the study.Capnography was instituted in all patients in a blocked fashion.Arterial blood gases and end-tidal CO2 values were measured before and after transport. When comparing overall group data, pre- and post-Paco2 values were similar: monitor 39 +/- 2 vs. 41 +/- 2 torr (5.2 +/- 0.3 vs. 5.5 +/- 0.3 no-monitor 39 +/- 1 vs. 37 +/- torr (5.2 +/- 0.1 vs. 5.0 +/- 0.1 kPa). However, when comparing Paco2 values for individual patients, we found that there was significantly greater variability for Paco2 after transport when end-tidal CO2 was not used for control of ventilation during transport.These data do not support routine monitoring of end-tidal CO2 during short transport times in adult patients requiring mechanical ventilation. However, the monitor may prevent morbidity in patients requiring tight control of Paco2.

BACKGROUND The mechanism of isoflurane-induced cerebral hyperemia is poorly understood. Data from studies in vitro suggest that volatile anesthetics release a vasodilator prostanoid. We hypothesized that prostanoids and nitric oxide (NO) are mediators of this response in vivo. If true, inhibition of cyclooxygenase by indomethacin (5 mg/kg intravenously) or of nitric oxide synthase by N omega-nitro-L-arginine methyl ester (L-NAME; 40 mg/kg intravenously) should attenuate isoflurane-induced hyperemia. Any response to L-NAME occurring via nitric oxide should be competitively reversed by L-arginine. METHODS The cerebral blood flow (microsphere) response to 1 MAC isoflurane was tested at three time points (0, 90, and 180 min) in pentobarbital-anesthetized pigs. Isoflurane challenges were separated by 60-min periods of continuous intravenous pentobarbital alone. Control animals (n = 7) received no additional pharmacologic intervention. Experimental animals were randomized to receive L-NAME before the second and indomethacin before the third isoflurane challenge (n = 7); L-NAME before the second and L-arginine (400 mg/kg intravenously) before the third isoflurane challenge (n = 9); or indomethacin before the second and L-NAME before the third isoflurane challenge (n = 8). RESULTS In control animals, isoflurane reproducibly increased cerebral blood flow (whole brain; 113 +/- 18%, 120 +/- 18%, and 103 +/- 19% increase above baseline at each time point, respectively). Both indomethacin and L-NAME attenuated (10 +/- 10% and 52 +/- 11% increase, respectively) the hyperemic response to isoflurane. The effect of L-NAME was reversed by L-arginine. CONCLUSIONS We conclude that both prostanoids and nitric oxide contribute to isoflurane-induced hyperemia. We are unable to determine from our data what, if any, interaction exists between these two mechanisms.

OBJECTIVE We tested the hypothesis that, in piglets, the intravenous administration of the reversible inhibitor of nitric oxide synthase, NG-mono-methyl-L-arginine, decreases cerebral blood flow via a mechanism unrelated to cerebral oxygen consumption. DESIGN Prospective, randomized, controlled animal study. SETTING Animal laboratory at a university. SUBJECTS Pentobarbital-anesthetized piglets (1 to 2 wks of age; 2.6 to 4.0 kg). INTERVENTIONS Piglets were treated with either 50 mg of NG-mono-methyl-L-arginine, 100 mg of NG-mono-methyl-L-arginine, or an equal volume of saline by intravenous infusion over 10 mins. MEASUREMENTS AND MAIN RESULTS Mean arterial pressure increased after NG-mono-methyl-L-arginine (50 mg dose: 84 +/- 6 to 100 +/- 7 mmHg; 100 mg dose: 82 +/- 4 to 107 +/- 4 mmHg; p < .001). Forebrain blood flow (microspheres) decreased (37 +/- 2 to 30 +/- 2 mL/min/100 g; p < .05) and cerebrovascular resistance increased (2.1 +/- 0.2 to 3.5 +/- 0.3 mmHg/mL/min/100 g; p < .05) only after 100 mg of NG-mono-methyl-L-arginine. Neurohypophysis blood flow decreased to 56 +/- 9% of the control value, while forebrain blood flow decreased only to 81 +/- 4% of the control value after 100 mg of NG-mono-methyl-L-arginine administration. Blood flow returned to control values by 30 mins after infusion. NG-mono-methyl-L-arginine administration had no effect on cerebral oxygen consumption at either dose. Intravenous administration of L-arginine (300 mg) immediately after the infusion of 100 mg of NG-mono-methyl-L-arginine was associated with prompt (by 3 mins) recovery of blood flow to all brain regions that were affected by NG-mono-methyl-L-arginine. CONCLUSIONS These data suggest that nitric oxide and/or a nitric oxide-containing substance is an important mediator of cerebrovascular tone in piglets, acting via a mechanism unrelated to altering cerebral oxygen consumption.

Neurosurgical intensive care unit (NICU) patients require multiple transports for diagnostic studies and interventions over the course of their hospitalization. While the majority of these transports proceed uneventfully, they are fraught with potential risk, particularly in the setting of a rapidly deteriorating patient. Urgent transports are frequently required at night when staffing numbers and the experience of staff doing the transport may be less than during daytime shifts. Given the potential for patient injury, many institutions are now moving toward the establishment of a team of professionals who provide scheduled and emergent transport and continued care during invasive studies, an entirely new (and yet unrecognized) specialty of transport medicine.

This article outlines some of the concerns and considerations in the anesthetic management of critically ill patients with chest trauma during their initial resuscitation and intraoperative course. The management decisions made during this critical period have clear implications for patient care once the patient arrives in the intensive care unit. It is the goal of this article to outline the rationale for these management decisions in order to facilitate the transfer of the patient from the operating room or trauma bay to the intensive care unit and allow the critical care nurse to establish effectively the expectations for postoperative recovery.

We tested the hypothesis that differential sympathetic innervation explains the attenuated cerebral blood flow (CBF) response to hypercapnia (hyper) in fore-brain (fb) compared with brain stem in 1- to 2-wk-old piglets. In pentobarbital sodium-anesthetized piglets, CBF (microspheres) was measured during hypocapnia, normocapnia (normo), and hypercapnia [arterial CO2 partial pressure (PaCO2) of 25, 40, and 65 mmHg, respectively] in random sequence. After pretreatment values were obtained, piglets were randomized to undergo sham treatment (n = 5), high cervical spinal cord transection (n = 6), or pharmacological alpha-adrenergic blockade (prazosin 1 mg/kg + yohimbine 1 mg/kg, n = 6). After each experimental treatment, CO2 reactivity was again measured. Before experimental manipulation, hypercapnic reactivity [(CBFhyper - CBFnormo)/(PaCO2hyper - PaCO2normo)] in brain stem was approximately three times greater than in forebrain (e.g., sham; 3.6 +/- 0.8 vs. 1.2 +/- 0.3 ml.min-1.100 g-1.mmHg-1). Hypercapnic reactivity in forebrain was not increased by cord transection (1.4 +/- 0.3 vs. 1.1 +/- 0.2 ml.min-1.100 g-1.mmHg-1) or alpha-blockade (1.6 +/- 0.6 vs. 1.2 +/- 0.4 ml.min-1.100 g-1.mmHg-1). Likewise, hypercapnic cerebral vascular resistance (CVR) was unchanged by experimental treatment (e.g., CVRfb; cord transection 1.1 +/- 0.1 vs. 1.0 +/- 0.1; alpha-blockade 1.1 +/- 0.2 vs. 1.0 +/- 0.1 mmHg.ml-1.min-1.100 g-1). Hypocapnic vasoconstriction, however, was attenuated by both cord transection and alpha-blockade in forebrain and brain stem. We conclude that physiological stimulation of the noradrenergic component of the sympathetic nervous system does not explain regional differences in CBF reactivity during hypercapnia in 1- to 2-wk-old piglets.(ABSTRACT TRUNCATED AT 250 WORDS)

OBJECTIVE: We examined the incidence of perioperative fever and its relationship to outcome among patients enrolled in the Intraoperative Hypothermia for Aneurysm Surgery Trial. METHODS: One thousand patients with initial World Federation of Neurological Surgeons grades of I to III undergoing clipping of intracranial aneurysms after subarachnoid hemorrhage were randomized to intraoperative normothermia (36 degrees C-37 degrees C) or hypothermia (32.5 degrees C-33.5 degrees C). Fever (> or =38.5 degrees C) and other complications (including infections) occurring between admission and discharge (or death) were recorded. Functional and neuropsychologic outcomes were assessed 3 months postoperatively. The primary outcome variable for the trial was dichotomized Glasgow Outcome Scale (good outcome versus all others). RESULTS: Fever was reported in 41% of patients. In 97% of these, fever occurred in the postoperative period. The median time from surgery to first fever was 3 days. All measures of outcome were worse in patients who developed fever, even in those without infections or who were World Federation of Neurological Surgeons grade I. Logistic regression analyses were performed to adjust for differences in preoperative factors (e.g., age, Fisher grade, initial neurological status). This demonstrated that fever continued to be significantly associated with most outcome measures, even when infection was added to the model. An alternative stepwise model selection process including all fever-related measures from the preoperative and intraoperative period (e.g., hydrocephalus, duration of surgery, intraoperative blood loss) resulted in the loss of significance for dichotomized Glasgow Outcome Scale, but significant associations between fever and several other outcome measures remained. After adding postoperative delayed ischemic neurological deficits to the model, only worsened National Institutes of Health Stroke Scale score, Barthel Activities of Daily Living index, and discharge destination (home versus other) remained independently associated with fever. CONCLUSION: These findings suggest that fever is associated with worsened outcome in surgical subarachnoid hemorrhage patients, although, because the association between fever and the primary outcome measure for the trial is dependent on the covariates used in the analysis (particularly operative events and delayed ischemic neurological deficits), we cannot rule out the possibility that fever is a marker for other events. Only a formal trial of fever treatment or prevention can address this issue.

This case report presents a patient suffering acute fatal intracranial-intratumoral hemorrhage during a gamma knife treatment session. Acute hemorrhage during a radiosurgery session is extremely rare and a plausible cause for this case is discussed along with a literature review of previously reported incidents. The patient was a 71-year-old male presenting with three large intracranial lesions and an underlying primary renal cell carcinoma malignancy. Because of a severe kyphotic deformity resulting from ankylosing spondylitis, the patient was placed in a moderate Trendelenburg position to allow his head to fit into the gamma knife unit during the radiosurgery session. The two left-sided lesions were to be treated with 20 Gy to the 50% isodose line, and the right-sided lesion with 16 Gy to the 40% isodose line. Anesthesia was available throughout the treatment session to aid with pain control. The gamma knife treatment was aborted because the patient suffered a generalized seizure while in the unit. Immediate head CT of the patient revealed large acute hemorrhages into all three intracranial masses. This proved to be a fatal complication. It is likely that this positioning contributed to the hemorrhage. The clinical history of this patient is provided as well as a review of the literature on acute intracranial hemorrhage associated with radiosurgical therapy.

Background and Purpose The purpose of the present study was to measure cortical nitric oxide synthase (NOS) activity and determine the appropriate doses of N ω -nitro -l- arginine methyl ester (L-NAME) or N ω -nitro -l- arginine (L-NNA) for near-complete enzyme inhibition in dogs, cats, and pigs. We anticipated that NOS inhibition was dose- and time-dependent and questioned if the dose-response relationship was related to the specific drug or animal species. Methods Saline or L-NAME or L-NNA in escalating doses was administered to pentobarbital-anesthetized pigs, dogs, and cats. Brain temperature and arterial blood gas, hemoglobin, and blood pressure levels were maintained within the physiological range. Cortical tissue was biopsied at baseline and 30, 120, and 360 minutes after agent administration for measurement of NOS activity by isotopic assay of the conversion of [ 14 C]arginine to [ 14 C]citrulline. Results L-NAME produced >70% enzyme inhibition at a dose of 20 mg/kg across the species tested. Arterial blood pressure was elevated at 30 minutes after L-NAME treatment. However, consistent decreases in brain NOS activity required a longer period of time. Near-complete inhibition was apparent in most animals by 120 minutes and persisted for 6 hours after administration. A smaller dose of L-NNA was required for >70% enzyme inhibition in the cats and dogs (10 mg/kg). Near-complete NOS inhibition was evident in most animals at 30 minutes after L-NNA administration, which also persisted for 6 hours. In pigs, this same level of inhibition required 20 mg/kg. Conclusions These results suggest that administration of L-NAME and L-NNA diminishes brain NOS activity in a dose- and time-dependent manner and that the duration of effect is at least 6 hours.

Publisher Summary This chapter discusses the known pathophysiology of reperfusion injury and outlines some current areas of research that attempt to therapeutically minimize cerebral ischemia and reperfusion injury. There are several possible mechanisms for free radical formation during ischemia and reperfusion. In the absence of oxygen to serve as a terminal electron acceptor, the electron transport chain within mitochondria becomes significantly reduced. In this reduced state oxygen radical formation may result, particularly when oxygen is resupplied. Furthermore, during ischemia the release of excitatory amino acids can stimulate N -methyl- D-aspartate (NMDA) receptors within brain to produce nitric oxide (NO). NO with its unpaired electron is able to initiate free radical chain reactions in the presence of superoxide anion. Cerebral ischemia is associated with the rapid failure of adenosine triphosphate (ATP)-dependent ionic pumps. In an ATP-deficient environment, phospholipase A may also cause the breakdown of phospholipid in cell membranes. As a result, ischemia produces a rapid increase in free fatty acids. The concentrations of fatty acids and arachidonic acid correlate with the duration of ischemia. During ischemia, in addition to the rapid increase in arachidonic acid, there is also an increase in interstitial adenosine and hypoxanthine. Lipid peroxidation appears to be a major mechanism by which radicals produce brain injury. Because of the high concentration of polyunsaturated fats in brain, this organ may be particularly susceptible to insult. Several endogenous free radical scavengers or antioxidants have been tested for their efficacy in reducing neurological, biochemical, metabolic, or histological injury from cerebral ischemia. α -Tocopherol, an endogenous antioxidant, reduces lipid peroxidation when administered prior to ischemia. Deferoxamine, an iron-chelating agent, presumably acts to decrease the amount of free iron available during reperfusion for hydroxyl radical formation. Superoxide dismutase (SOD) and catalase are endogenous free radical scavengers that may act to scavenge tonically produced free radicals under normal conditions.

We tested the hypothesis that superoxide dismutase (SOD) conjugated with polyethylene glycol (PEG-SOD) would alter hyperemia following complete global cerebral ischemia. Thirty minutes before ischemia pentobarbital-anesthetized piglets were assigned to receive 3 ml of either PEG-SOD (10,000 U/ml; n = 10), an equivalent concentration of PEG (n = 10), or saline (n = 10) in a randomized and blinded manner. Cerebral ischemia was sustained for 10 min by cross-clamping the ascending aorta. Measurements of cerebral blood flow (radiolabeled microspheres) and oxygen consumption were made before ischemia and at 2, 4, 8, 12, and 15 min of reperfusion. Plasma SOD activity was higher in PEG-SOD-treated piglets (134 +/- 8 U/ml) than in PEG or saline-treated piglets (less than 5 U/ml). All groups and all brain regions demonstrated postischemic hyperemia. There were no differences in blood flow between groups at any time point in any region. At 2 min of reperfusion, blood flow to cerebrum rose from 31 +/- 4 to 88 +/- 9 ml.min-1.100 g-1 (saline), 44 +/- 6 to 102 +/- 17 ml.min-1.100 g-1 (PEG), and 31 +/- 3 to 83 +/- 16 ml.min-1.100 g-1 (PEG-SOD). During reperfusion cerebral oxygen consumption was not different from preischemic values in any group. In conclusion, we demonstrated that exogenously administered PEG-SOD raises serum SOD activity but does not alter the patterns of early cerebral blood flow or metabolic recovery after 10 min of complete global cerebral ischemia in piglets.

We tested whether the cerebral blood flow (CBF) response to the cholinergic agonist oxotremorine (OXO) is affected by the choice of anesthetics in dogs. We studied two anesthetics, pentobarbital and isoflurane, which produce similar levels of cerebral metabolic depression but have opposing effects on CBF. We also tested the contribution of nitric oxide (NO, or a NO-containing compound) in mediating the CBF response to OXO by determining whether NO synthase inhibition with N omega-nitro-L-arginine methyl ester (L-NAME) would attenuate OXO-induced hyperemia in both anesthetic groups. CBF (microspheres) was measured before and after OXO administration (50 micrograms.kg-1.min-1 intravenously [i.v.] for 10 min). Animals were divided randomly to receive OXO alone (n = 10) or L-NAME (40 mg/kg i.v.) followed by OXO (n = 10). Within each group, half of the animals received pentobarbital anesthesia (30 mg/kg i.v.) and half received isoflurane (1.4% end-tidal). In pentobarbital-anesthetized animals OXO produced no change in blood flow to cerebrum, caudate, diencephalon, neurohypophysis, or cerebellum in the absence (e.g., cerebrum 37 +/- 2 vs 42 +/- 5 mL/min/100 g) or presence of L-NAME (e.g., cerebrum, 29 +/- 4 vs 30 +/- 3 mL.min-1 x 100 g-1). In isoflurane-anesthetized animals, however, blood flow to forebrain regions increased after OXO (e.g., cerebrum 108 +/- 10 vs 232 +/- 15 mL.min-1 x 100 g-1; P < 0.05) without alteration in oxygen consumption in cerebrum (CMRO2) or blood flow to hindbrain regions. In isoflurane-anesthetized animals, L-NAME decreased baseline blood flow to cerebrum, caudate, diencephalon, cerebellum, and neurohypophysis (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

The mechanism by which halothane, isoflurane, and nitrous oxide increase cerebral blood flow (CBF) is unknown. We assessed the cerebrovascular effects of nitrous oxide (70%; n = 6), isoflurane (1 minimum alveolar anesthetic concentration: 1.4%; n = 6) or halothane (1 minimum alveolar anesthetic concentration: 0.8%; n = 6) before and after blockade of nitric oxide (NO) synthase with 40 mg/kg N omega-nitro-L-arginine methyl ester (L-NAME) intravenously in dogs with baseline pentobarbital anesthesia. Baseline CBF (microspheres) was determined after 1 h of pentobarbital anesthesia. Cerebral perfusion pressure (CPP) was maintained during inhaled anesthetic or L-NAME by either hemorrhage or inflation of an intra-aortic balloon. Before L-NAME, halothane and isoflurane increased CBF (40 +/- 4 to 56 +/- 6 mL.min-1 x 100 g-1 and 43 +/- 6 to 78 +/- 12 mL.min-1 x 100 g-1, respectively) with no change in cerebral oxygen consumption (baseline: halothane, 2.6 +/- 0.2; isoflurane, 2.0 +/- 0.2 mL.min-1 x 100 g-1). On the contrary, nitrous oxide increased CBF similarly (40 +/- 6 to 57 +/- 8 mL.min-1 x 100 g-1), but increased cerebral oxygen consumption (2.2 +/- 0.3 to 3.0 +/- 0.3 mL.min-1 x 100 g-1). L-NAME decreased blood flow in the neurohypophysis by 80% with no change in blood flow in other brain regions. After L-NAME, reexposure to nitrous oxide, halothane, or isoflurane resulted in no change in CBF.(ABSTRACT TRUNCATED AT 250 WORDS)