Critical care and emergency medicine.
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Biomedical subjects
Publications and source records attributed to Stephan A Mayer.
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BACKGROUND: While efforts have been made to document short-term outcomes following poor grade aneurysmal subarachnoid hemorrhage (aSAH), no data exist concerning the degree of delayed improvement in neurological function. Here we assess cognitive function, level of independence, and quality of life (QoL) over 12 months following poor grade aSAH. METHODS: Data on definitively treated poor grade patients (Hunt and Hess grade IV or V) surviving 12 months post-aSAH were obtained through a prospectively maintained SAH database. Demographic information, medical history, and clinical course were analyzed. Health outcomes assessments completed by surviving patients at discharge (DC), three months (3 M) and 12 months (12 M) follow-up, including the Telephone Interview for Cognitive Status (TICS), Barthel Index (BI), and Sickness Impact Profile (SIP), were used to evaluate cognitive function, level of independence, and QoL. FINDINGS: Fifty-six poor grade patients underwent aneurysm-securing intervention and survived at least 12 months post-aSAH. Thirty-five (63%) surviving patients underwent health outcomes assessments at DC, 3 M and 12 M post-aSAH. A majority of patients had improved scores on the TICS (DC to 3 M: 91%; 3 M to 12 M: 82%), BI (DC to 3 M: 96%; 3 M to 12 M: 92%), and SIP (3 M to 12 M: 80%) following aSAH. Using paired-sample analyses, significant improvement on each test was observed. CONCLUSION: A substantial portion of patients experience cognitive recovery, increased independence, and improved QoL following poor grade aSAH. Delayed follow-up assessments are necessary when evaluating functional recovery in this population. These findings have the potential to impact poor grade aSAH management and prognosis.
Despite the highest mortality and morbidity of all forms of stroke, few advances have been made in the management of intracerebral hemorrhage (ICH). Besides specialized care in the stroke or neurologic intensive care unit, until very recently no specific therapies have been shown to improve outcome after ICH. Ventilatory support, blood pressure reduction, intracranial pressure monitoring, osmotherapy, fever control, seizure prophylaxis, and nutritional supplementation are the cornerstones of supportive care in the intensive care unit. Recently, a phase II trial of recombinant activated factor VII (NovoSeven; Novo Nordisk, Bagsvaerd, Denmark) reduced hematoma expansion, mortality, and disability when given within 3 hours of ICH onset. A phase III trial to confirm these results is now in progress.
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Intracerebral hemorrhage (ICH) is the least treatable form of stroke, and causes high mortality, severe disability, and a staggering economic burden. ICH accounts for 15% of stroke cases in the United States and Europe, and up to 30% in Asian populations. Computed tomography-based studies suggest that ICH growth within the first few hours of onset is common, and the principal cause of early neurological deterioration. Hematoma volume is also a well-established predictor of 30-day mortality. Intervention with ultra-early hemostatic therapy could minimize or prevent this early dynamic bleeding process, and might improve outcome. Recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark) is approved for the treatment of bleeding in patients with hemophilia and inhibitors, but it may also promote hemostasis in patients with normal coagulation by acting locally at the bleeding site without activation of systemic coagulation. In a randomized, double-blind, placebo-controlled trial of 399 ICH patients treated with a single dose of 40, 80, or 160 microg/kg of rFVIIa or placebo within 4 hours of onset, subsequent hematoma growth was reduced by approximately 50% with rFVIIa. This was associated with a significant reduction (38%) in mortality, and improved functional outcomes among survivors. A phase III trial comparing 20 and 80 microg/kg rFVIIa with placebo is now in progress to confirm these results.
Morbidity and mortality in patients successfully resuscitated from cardiac arrest primarily depends on neurological outcome. Clinical trials of therapies directed toward reducing the extent of neuronal damage by means of pharmacological agents have been disappointing. To date, the only clinically effective tool for amelioration of brain damage by ischemia and reperfusion is mild to moderate induced hypothermia. The pathophysiology of global hypoxic-ischemic brain injury, the mechanisms by which hypothermia confers neuroprotection, and the encouraging beneficial effects of mild to moderate hypothermia in experimental studies and clinical trials are discussed.
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 degreesC (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.
PURPOSE OF REVIEW: To summarize new concepts regarding the occurrence, prevention, and management of medical complications following subarachnoid hemorrhage. RECENT FINDINGS: Data regarding the impact of common medical complications after subarachnoid hemorrhage on delayed cerebral ischemia and neurological outcome after subarachnoid hemorrhage are available from recent outcomes studies. Fever, anemia requiring transfusion, hyperglycemia, electrolyte abnormalities, pneumonia, hypertension, and neurogenic stunned myocardium and pulmonary edema occur frequently after subarachnoid hemorrhage. Fever, anemia, hyperglycemia, and acute hypoxia and hypotension related to neurogenic stunned myocardium have the greatest impact on mortality and functional outcome after subarachnoid hemorrhage. Potential treatment interventions for these complications include the development of acute resuscitation strategies to optimize cerebral perfusion in poor-grade patients, maintaining normothermia with systemic cooling devices, administration of erythropoietin to prevent severe anemia, preserving normoglycemia with continuous insulin infusions, and goal-directed hemodynamic support guided by brain tissue oxygenation. SUMMARY: Clinical trials to investigate interventions targeted at preventing or treating common medical complications after subarachnoid hemorrhage are needed.
OBJECTIVE: Critical cerebrospinal fluid (CSF) hypovolemia may cause acute postoperative clinical deterioration in aneurysmal subarachnoid hemorrhage patients after craniotomy for microsurgical aneurysm clipping. We sought to identify risk factors for critical CSF hypovolemia and determine this syndrome's effect on clinical outcome. METHODS: Between April 2001 and June 2004 at Columbia University Medical Center, 16 aneurysmal subarachnoid hemorrhage patients were diagnosed with postoperative critical CSF hypovolemia, whereas 151 patients who underwent craniotomy for clipping were not. The demographics, as well as the presenting radiographic and clinical characteristics, of these groups were evaluated. In addition, a 2:1 matched case-control comparison of patients with and without critical CSF hypovolemia was completed using clinical data, operative variables, and outcome data. Outcome analysis was performed with a battery of tests designed to assess global outcome, cognitive function, independence, and quality of life. RESULTS: There was no difference in clinical grade, Fisher score, age, and sex distribution between patients diagnosed with critical CSF hypovolemia and the general aneurysmal subarachnoid hemorrhage population at Columbia University Medical Center. Subsequent 2:1 matched case-control comparison demonstrated a higher incidence of global cerebral edema on admission computed tomographic scans (75 versus 31%; P < 0.01) and a significantly longer operative time for patients with critical CSF hypovolemia (5 h 18 min versus 4 h 22 min; P < 0.03). No significant differences were observed between groups in outcome assessments at the time of hospital discharge or the 3-month follow-up examination. CONCLUSION: Risk factors associated with an increased incidence of critical CSF hypovolemia after aneurysm surgery include the presence of global cerebral edema on admission head computed tomographic scans and prolonged operative time. In such patients, heightened suspicion of CSF hypovolemia is crucial because rapid and appropriate management obviates excess morbidity and mortality.
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.
OBJECTIVE: To evaluate predictors of intraventricular hemorrhage (IVH) and IVH growth, impact of IVH growth on outcome, and impact of recombinant activated factor VII (rFVIIa) in patients with intracerebral hemorrhage (ICH). METHODS: We analyzed 374 patients out of 399 who were randomized to rFVIIa (40, 80, or 160 mug/kg) or placebo for ICH (diagnosed within 3 h of symptoms). Risk factors for IVH growth (>2 ml increase in IVH volume at 24 h), and death or severe disability (modified Rankin scale score 4-6) at 3 months were identified (logistic regression). RESULTS: IVH was present in 38% (n = 141) of patients at baseline and 45% (n = 169) by 24 hours. IVH growth, by 24 hours, occurred in 17 and 10% of placebo- and rFVIIa-treated patients, respectively (P = 0.037). Risk factors for IVH growth included baseline mean arterial pressure greater than 120 mmHg, larger baseline ICH volume, IVH present at baseline, shorter time from symptom onset to baseline computed tomographic scan, and treatment (rFVIIa versus placebo) (all, P < or = 0.037). Predictors of death or severe disability included older age, lower baseline Glasgow Coma Score, larger baseline ICH volume, IVH growth greater than 2 ml, IVH present at baseline or 24 hours, and treatment (rFVIIa versus placebo) (all, P < or = 0.0405). CONCLUSION: Presence of IVH at any time and early IVH growth worsen clinical outcome and increase mortality. Elevated mean arterial pressure at baseline may be a modifiable risk factor for IVH growth. Beneficial effects of rFVIIa on ICH outcome may be mediated, at least in part, by reducing IVH growth.
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.
INTRODUCTION: Predicting outcome in patients with poor-grade subarachnoid hemorrhage (SAH) may help guide therapy and assist in family discussions. The objective of this study was to determine if continuous electroencephalogram (cEEG) monitoring results are predictive of 3-month outcome in critically ill patients with SAH. METHODS: We prospectively studied 756 patients with SAH over a 7-year period. Functional outcome was assessed at 3 months with the modified Rankin Scale (mRS). Patients that underwent cEEG monitoring were retrospectively identified and EEG findings were collected. Multivariate logistic regression analysis was performed to identify EEG findings associated with poor outcome, defined as mRS 4 to 6 (dead or moderately to severely disabled). RESULTS: In 116 patients with SAH, cEEG monitoring and 3-month mRS were available. Of these patients, 88% had a Hunt & Hess grade of 3 or worse on admission. After controlling for age, Hunt & Hess grade, and presence of intraventricular hemorrhage on admission CT scan, poor outcome was associated with the absence of sleep architecture (80 versus 47%; odds ratio [OR] 4.3, 95%-confidence interval [CI] 1.1-17.2) and the presence of periodic lateralized epileptiform discharges (PLEDS) (91 versus 66% OR 18.8, 95%-CI 1.6-214.6). In addition, outcome was poor in all patients with absent EEG reactivity (n = 8), generalized periodic epileptiform discharges (n = 12), or bilateral independent PLEDs (n = 5), and in 92% (11 of 12) of patients with nonconvulsive status epilepticus. CONCLUSIONS: cEEG monitoring provides independent prognostic information in patients with poor-grade SAH, even after controlling for clinical and radiological findings. Unfavorable findings include periodic epileptiform discharges, electrographic status epilepticus, and the absence of sleep architecture.
BACKGROUND AND PURPOSE: Ultra-early hemostatic therapy may improve outcome after intracerebral hemorrhage (ICH) by preventing rebleeding and hematoma expansion. We conducted this trial to evaluate the safety of activated recombinant factor VII (rFVIIa; NovoSeven) for preventing early hematoma growth in acute ICH. METHODS: In this multicenter, randomized, double-blind, placebo-controlled, dose-escalation trial, 40 patients diagnosed with ICH by computed tomography within 3 hours of onset were treated with placebo or 5, 20, 40, or 80 microg/kg of rFVIIa ( n = 8 per group). Patients with any history of thromboembolic or vaso-occlusive disease were excluded. The primary endpoint was the frequency of adverse events (AEs). RESULTS: Mean age was 65 years (range 34 - 91) and the median admission Glasgow Coma Scale score was 14.5 (range 6 to 15). Mean ICH volume was 17 +/- 19 mL; nearly three-quarters were located in the basal ganglia ( n = 29). The mean interval from onset to treatment was 178 +/- 41 minutes. Thirty-three patients experienced 186 AEs, which occurred with similar frequency in the five groups. There were 10 thromboembolic AEs, including one case of deep vein thrombosis (20 microg g/kg group); one case of cerebral infarction (placebo); two cases of pulmonary embolism (20 and 40 microg g/kg groups); and six instances of ischemic ECG changes or cardiac enzyme elevation (placebo [ n = 2], 20 microg g/kg [ n = 1], 40 microg g/kg [ n = 1], and 80 microg g/kg [ n = 2] groups). No consumption coagulopathy or dose-related increase in edema-to-ICH volume ratio occurred. CONCLUSIONS: Ultra-early rFVIIa treatment for ICH was associated with a reasonable safety profile in this preliminary study across a wide range of dosages. Further research is warranted to investigate the safety and potential efficacy of rFVIIa for minimizing ICH growth.
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BACKGROUND AND PURPOSE: Hyperglycemia is common after subarachnoid hemorrhage (SAH). The extent to which prolonged hyperglycemia contributes to in-hospital complications and poor outcome after SAH is unknown. METHODS: We studied an inception cohort of 281 SAH patients with an initial serum glucose level obtained within 3 days of SAH onset and who had at least 7 daily glucose measurements between SAH days 0 and 10. We defined mean glucose burden (GB) as the average peak daily glucose level >5.8 mmol/L (105 mg/dL). Hospital complications were recorded prospectively, and 3-month outcome was assessed with the modified Rankin scale. RESULTS: The median GB was 1.8 mmol/L (33 mg/dL). Predictors of high-GB included age > or =54 years, Hunt and Hess grade III-V, poor Acute Physiology and Chronic Health Evaluation (APACHE)-2 physiological subscores, and a history of diabetes mellitus (all P< or =0.001). In a multivariate analysis, GB was associated with increased intensive care unit length of stay (P=0.003) and the following complications: congestive heart failure, respiratory failure, pneumonia, and brain stem compression from herniation (all P<0.05). After adjusting for Hunt-Hess grade, aneurysm size, and age, GB was an independent predictor of death (odds ratio, 1.10 per mmol/L; 95% CI, 1.01 to 1.21; P=0.027) and death or severe disability (modified Rankin scale score of 4 to 6; odds ratio, 1.17 per mmol/L; 95% CI 1.07 to 1.28, P<0.001). CONCLUSIONS: Hyperglycemia after SAH is associated with serious hospital complications, increased intensive care unit length of stay, and an increased risk of death or severe disability.