J. Michael Schmidt

Impact of medical complications on outcome after subarachnoid hemorrhage.

Objective:Medical complications occur frequently after subarachnoid hemorrhage (SAH). Their impact on outcome remains poorly defined. Design:Inception cohort study. Patients:Five-hundred eighty patients enrolled in the Columbia University SAH Outcomes Project between July 1996 and May 2002. Setting:Neurologic intensive care unit. Interventions:Patients were treated according to standard management protocols. Measurements and Main Results:Poor outcome was defined as death or severe disability (modified Rankin score, 4–6) at 3 months. We calculated the frequency of medical complications according to prespecified criteria and evaluated their impact on outcome, using forward stepwise multiple logistic regression after adjusting for known predictors of poor outcome. Thirty-eight% had a poor outcome; mortality was 21%. The most frequent complications were temperature >38.3°C (54%), followed by anemia treated with transfusion (36%), hyperglycemia >11.1 mmol/L (30%), treated hypertension (>160 mm Hg systolic; 27%), hypernatremia >150 mmol/L (22%), pneumonia (20%), hypotension (<90 mm Hg systolic) treated with vasopressors (18%), pulmonary edema (14%), and hyponatremia <130 mmol/L (14%). Fever (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.1–3.4; p = .02), anemia (OR, 1.8; 95% CI, 1.1–2.9; p = .02), and hyperglycemia (OR, 1.8; 95% CI, 1.1–3.0; p = .02) significantly predicted poor outcome after adjustment for age, Hunt-Hess grade, aneurysm size, rebleeding, and cerebral infarction due to vasospasm. Conclusions:Fever, anemia, and hyperglycemia affect 30% to 54% of patients with SAH and are significantly associated with mortality and poor functional outcome. Critical care strategies directed at maintaining normothermia, normoglycemia, and prevention of anemia may improve outcome after SAH. LEARNING OBJECTIVESOn completion of this article, the reader should be able to: Identify common medical complications after subarachnoid hemorrhage. Describe complications that influence outcome. Use this inofrmation in a clinical setting. Dr. Connolly has disclosed that he is/was the recipient of direct grant/research funds from the National Institutes of Health. The remaining authors have disclosed that they have no financial relationships with or interests in any commercial companies pertaining to the educational activity. Wolters Kluwer has identified and resolved all faculty conflicts of interest regarding the educational activity. Visit the Critical Care Medicine Web site (www.ccmjournal.org) for information on obtaining continuing medical education credit.

Prediction of symptomatic vasospasm after subarachnoid hemorrhage: the modified fisher scale.

OBJECTIVE We developed a modification of the Fisher computed tomographic rating scale and compared it with the original Fisher scale to determine which scale best predicts symptomatic vasospasm after subarachnoid hemorrhage. METHODS We analyzed data from 1355 subarachnoid hemorrhage patients in the placebo arm of four randomized, double-blind, placebo-controlled studies of tirilazad. Modified Fisher computed tomographic grades were calculated on the basis of the presence of cisternal blood and intraventricular hemorrhage. Crude odds ratios (OR) reflecting the risk of developing symptomatic vasospasm were calculated for each scale level, and adjusted ORs expressing the incremental risk were calculated after controlling for known predictors of vasospasm. RESULTS Of 1355 patients, 451 (33%) developed symptomatic vasospasm. For the modified Fisher scale, compared with Grade 0 to 1 patients, the crude OR for vasospasm was 1.6 (95% confidence interval [CI], 1.0-2.5) for Grade 2, 1.6 (95% CI, 1.1-2.2) for Grade 3, and 2.2 (95% CI, 1.6-3.1) for Grade 4. For the original Fisher scale, referenced to Grade 1, the OR for vasospasm was 1.3 (95% CI, 0.7-2.2) for Grade 2, 2.2 (95% CI, 1.4-3.5) for Grade 3, and 1.7 (95% CI, 1.0-3.0) for Grade 4. Early angiographic vasospasm, history of hypertension, neurological grade, and elevated admission mean arterial pressure were identified as risk factors for symptomatic vasospasm. After adjusting for these variables, the modified Fisher scale remained a significant predictor of vasospasm (adjusted OR, 1.28; 95% CI, 1.06-1.54), whereas the original Fisher scale was not. CONCLUSION The modified Fisher scale, which accounts for thick cisternal and ventricular blood, predicts symptomatic vasospasm after subarachnoid hemorrhage more accurately than original Fisher scale.

Impact of tight glycemic control on cerebral glucose metabolism after severe brain injury: A microdialysis study*

Objectives:To analyze the effect of tight glycemic control with the use of intensive insulin therapy on cerebral glucose metabolism in patients with severe brain injury. Design:Retrospective analysis of a prospective observational cohort. Setting:University hospital neurologic intensive care unit. Patients:Twenty patients (median age 59 yrs) monitored with cerebral microdialysis as part of their clinical care. Interventions:Intensive insulin therapy (systemic glucose target: 4.4–6.7 mmol/L [80–120 mg/dL]). Measurements and Main Results:Brain tissue markers of glucose metabolism (cerebral microdialysis glucose and lactate/pyruvate ratio) and systemic glucose were collected hourly. Systemic glucose levels were categorized as within the target “tight” (4.4–6.7 mmol/L [80–120 mg/dL]) vs. “intermediate” (6.8–10.0 mmol/L [121–180 mg/dL]) range. Brain energy crisis was defined as a cerebral microdialysis glucose <0.7 mmol/L with a lactate/pyruvate ratio >40. We analyzed 2131 cerebral microdialysis samples: tight systemic glucose levels were associated with a greater prevalence of low cerebral microdialysis glucose (65% vs. 36%, p < 0.01) and brain energy crisis (25% vs.17%, p < 0.01) than intermediate levels. Using multivariable analysis, and adjusting for intracranial pressure and cerebral perfusion pressure, systemic glucose concentration (adjusted odds ratio 1.23, 95% confidence interval [CI] 1.10–1.37, for each 1 mmol/L decrease, p < 0.001) and insulin dose (adjusted odds ratio 1.10, 95% CI 1.04–1.17, for each 1 U/hr increase, p = 0.02) independently predicted brain energy crisis. Cerebral microdialysis glucose was lower in nonsurvivors than in survivors (0.46 ± 0.23 vs. 1.04 ± 0.56 mmol/L, p < 0.05). Brain energy crisis was associated with increased mortality at hospital discharge (adjusted odds ratio 7.36, 95% CI 1.37–39.51, p = 0.02). Conclusions:In patients with severe brain injury, tight systemic glucose control is associated with reduced cerebral extracellular glucose availability and increased prevalence of brain energy crisis, which in turn correlates with increased mortality. Intensive insulin therapy may impair cerebral glucose metabolism after severe brain injury.

Metabolic Impact of Shivering During Therapeutic Temperature Modulation The Bedside Shivering Assessment Scale

Background and Purpose— Therapeutic temperature modulation is widely used in neurocritical care but commonly causes shivering, which can hamper the cooling process and result in increases in systemic metabolism. We sought to validate a grading scale to assist in the monitoring and control of shivering. Methods— A simple 4-point Bedside Shivering Assessment Scale was validated against continuous assessments of resting energy expenditure, oxygen consumption, and carbon dioxide production as measured by indirect calorimetry. Therapeutic temperature modulation for fever control or the induction of hypothermia was achieved with the use of a surface or endovascular device. Expected energy expenditure was calculated using the Harris–Benedict equation. A hypermetabolic index was calculated from the ratio of resting of energy expenditure to energy expenditure. Results— Fifty consecutive cerebrovascular patients underwent indirect calorimetry between January 2006 and June 2007. Fifty-six percent were women, and mean age 63±16 years. The majority underwent fever control (n=40 [80%]) with a surface cooling device (n=44 [87%]) and had signs of shivering (Bedside Shivering Assessment Scale >0, 64% [n=34 of 50]). Low serum magnesium was independently associated with the presence of shivering (Bedside Shivering Assessment Scale >0; OR, 6.8; 95% CI, 1.7 to 28.0; P=0.01). The Bedside Shivering Assessment Scale was independently associated with the hypermetabolic index (W=16.3, P<0.001), oxygen consumption (W=26.3, P<0.001), resting energy expenditure (W=27.2, P<0.001), and carbon dioxide production (W=18.2, P<0.001) with a high level of interobserver reliability (&kgr;w=0.84, 95% CI, 0.81 to 0.86). Conclusion— The Bedside Shivering Assessment Scale is a simple and reliable tool for evaluating the metabolic stress of shivering.

Transcranial Doppler for predicting delayed cerebral ischemia after subarachnoid hemorrhage.

OBJECTIVETranscranial Doppler (TCD) is widely used to monitor the temporal course of vasospasm after subarachnoid hemorrhage (SAH), but its ability to predict clinical deterioration or infarction from delayed cerebral ischemia (DCI) remains controversial. We sought to determine the prognostic utility of serial TCD examination after SAH. METHODSWe analyzed 1877 TCD examinations in 441 aneurysmal SAH patients within 14 days of onset. The highest mean blood flow velocity (mBFV) value in any vessel before DCI onset was recorded. DCI was defined as clinical deterioration or computed tomographic evidence of infarction caused by vasospasm, with adjudication by consensus of the study team. Logistic regression was used to calculate adjusted odds ratios for DCI risk after controlling for other risk factors. RESULTSDCI occurred in 21% of patients (n = 92). Multivariate predictors of DCI included modified Fisher computed tomographic score (P = 0.001), poor clinical grade (P = 0.04), and female sex (P = 0.008). After controlling for these variables, all TCD mBFV thresholds between 120 and 180 cm/s added a modest degree of incremental predictive value for DCI at nearly all time points, with maximal sensitivity by SAH day 8. However, the sensitivity of any mBFV more than 120 cm/s for subsequent DCI was only 63%, with a positive predictive value of 22% among patients with Hunt and Hess grades I to III and 36% in patients with Hunt and Hess grades IV and V. Positive predictive value was only slightly higher if mBFV exceeded 180 cm/s. CONCLUSIONIncreased TCD flow velocities imply only a mild incremental risk of DCI after SAH, with maximal sensitivity by day 8. Nearly 40% of patients with DCI never attained an mBFV more than 120 cm/s during the course of monitoring. Given the poor overall sensitivity of TCD, improved methods for identifying patients at high risk for DCI after SAH are needed.

Frequency and clinical impact of asymptomatic cerebral infarction due to vasospasm after subarachnoid hemorrhage : Clinical article

OBJECT The authors sought to determine frequency, risk factors, and impact on outcome of asymptomatic cerebral infarction due to vasospasm after subarachnoid hemorrhage (SAH). METHODS The authors prospectively studied 580 patients with SAH admitted to their center between July 1996 and May 2002. Delayed cerebral ischemia (DCI) from vasospasm was defined as 1) a new focal neurological deficit or decrease in level of consciousness, 2) a new infarct revealed by follow-up CT imaging, or both, after excluding causes other than vasospasm. Outcome at 3 months was assessed using the modified Rankin Scale. RESULTS Delayed cerebral ischemia occurred in 121 (21%) of 580 patients. Of those with DCI, 36% (44 patients) experienced neurological deterioration without a corresponding infarct, 42% (51 patients) developed an infarct in conjunction with neurological deterioration, and 21% (26 patients) had a new infarct on CT without concurrent neurological deterioration. In a multivariate analysis, risk factors for asymptomatic DCI included coma on admission, placement of an external ventricular drain, and smaller volumes of SAH (all p < or = 0.03). Patients with asymptomatic DCI were less likely to be treated with vasopressor agents than those with symptomatic DCI (64 vs 86%, p = 0.01). After adjusting for clinical grade, age, and aneurysm size, the authors found that there was a higher frequency of death or moderate-to-severe disability at 3 months (modified Rankin Scale Score 4-6) in patients with asymptomatic DCI than in patients with symptomatic DCI (73 vs 40%, adjusted odds ratio 3.9, 95% confidence interval 1.3-12.0, p = 0.017). CONCLUSIONS Approximately 20% of episodes of DCI after SAH are characterized by cerebral infarction in the absence of clinical symptoms. Asymptomatic DCI is particularly common in comatose patients and is associated with poor outcome. Strategies directed at diagnosing and preventing asymptomatic infarction from vasospasm in patients with poor-grade SAH are needed.

Resuscitation and critical care of poor-grade subarachnoid hemorrhage.

As outcomes have improved for patients with aneurysmal subarachnoid hemorrhage, most mortality and morbidity that occur today are the result of severe diffuse brain injury in poor-grade patients. The premise of this review is that aggressive emergency cardiopulmonary and neurological resuscitation, coupled with early aneurysm repair and advanced multimodality monitoring in a specialized neurocritical care unit, offers the best approach for achieving further improvements in subarachnoid hemorrhage outcomes. Emergency care should focus on control of elevated intracranial pressure, optimization of cerebral perfusion and oxygenation, and medical and surgical therapy to prevent rebleeding. In the postoperative period, advanced monitoring techniques such as continuous electroencephalography, brain tissue oxygen monitoring, and microdialysis can detect harmful secondary insults, and may eventually be used as end points for goal-directed therapy, with the aim of creating an optimal physiological environment for the comatose injured brain. As part of this paradigm shift, it is essential that aggressive surgical and medical support be linked to compassionate end-of-life care. As neurosurgeons become confident that comfort care can be implemented in a straightforward fashion after a failed trial of early maximal intervention, the usual justification for withholding treatment (survival with neurological devastation) becomes less relevant, and lives may be saved as more patients recover beyond expectations.

Preoperative prediction of long-term outcome in poor-grade aneurysmal subarachnoid hemorrhage

OBJECTIVE:To evaluate which presentation indices, demographics, and clinical information predict 12-month outcome in poor-grade aneurysmal subarachnoid hemorrhage (SAH), and to provide a preoperative index of prognosis. METHODS:Data were obtained on all patients with poor-grade (Hunt and Hess Grades IV and V) aneurysmal SAH from a prospectively maintained SAH database and health outcomes project. Demographics, medical history, presenting clinical condition, and health outcomes were analyzed. Survival analysis was performed and Kaplan-Meier curves were generated. Multivariable logistic regression analysis was used to identify significant predictors of poor outcome at 12 months after hemorrhage, as measured by the modified Rankin disability scale. RESULTS:Survival curves for open surgery and endovascular treatment did not differ significantly. Overall, 40% of the 98 definitively treated patients had a favorable outcome at 12 months. Multivariable analysis identified patient age older than 65 years (P < 0.001), hyperglycemia (P < 0.03), worst preoperative Hunt and Hess Grade V (P < 0.0001), and aneurysm size of at least 13 mm (P < 0.002) as significant predictors of poor outcome. These variables were weighted and used to compute a poor-grade aneurysmal SAH Prognosis Score (hereafter, Prognosis Score) for each patient. A Prognosis Score of 0 was associated with a 90% favorable outcome; Prognosis Score of 1 with 83%; Prognosis Score of 2 with 43%; Prognosis Score of 3 with 8%; Prognosis Score of 4 with 7%; and a Prognosis Score of 5 with 0%. CONCLUSION:Outcome in poor-grade aneurysmal SAH is strongly predicted by patient age, worst preoperative Hunt and Hess clinical grade, and aneurysm size. Hyperglycemia on admission after poor-grade aneurysmal SAH increases the likelihood of poor outcome, and is a potentially modifiable risk factor. The Prognosis Score is a useful tool for preoperatively assessing the likelihood of a favorable outcome for poor-grade aneurysmal SAH patients.

Impact of nosocomial infectious complications after subarachnoid hemorrhage

OBJECTIVECritically ill neurological patients are susceptible to infections that may be distinct from other intensive care patients. The aim of this study is to quantify the prevalence, risk factors, and effect on the outcome of nosocomial infectious complications in patients with subarachnoid hemorrhage (SAH). METHODSWe studied 573 consecutive patients with SAH, identified the most prevalent infectious complications, and performed univariate analyses to determine risk factors for each complication. Multiple logistic regression models were constructed to calculate adjusted odds ratios for associated risk factors and to assess the impact of infectious complications on 3-month outcome as evaluated with the modified Rankin Scale. RESULTSThe most prevalent nosocomial infections were pneumonia (n = 114, 20%), urinary tract infection (n = 77, 13%), bloodstream infection (BSI) (n = 48, 8%), and meningitis/ventriculitis (n = 28, 5%). Significant independent associations with pneumonia included older age, poor Hunt and Hess grade, intubation/mechanical ventilation, and loss of consciousness at ictus. Urinary tract infection was associated with female sex and central line use. BSI was also associated with central line use, and meningitis/ventriculitis was associated with the presence of intraventricular hemorrhage and external ventricular drainage (all P < 0.05). After adjustment for Hunt and Hess grade, aneurysm size, and age, pneumonia (adjusted odds ratio, 2.04; 95% confidence interval, 1.12–3.71; P = 0.020) and BSI (adjusted odds ratio, 2.51; 95% confidence interval, 1.14–5.56; P = 0.023) independently predicted death or severe disability at 3 months. Prolonged length of stay was significantly associated with all infection types (P < 0.001). CONCLUSIONPneumonia and BSI are common infectious complications of SAH and independently predict poor outcome. The implementation of infection-control measures may be needed to improve outcome after SAH.

NONCONVULSIVE SEIZURES AFTER SUBARACHNOID HEMORRHAGE: MULTIMODAL DETECTION AND OUTCOMES

Seizures have been implicated as a cause of secondary brain injury, but the systemic and cerebral physiologic effects of seizures after acute brain injury are poorly understood.