Prospective, randomized trial of higher goal hemoglobin after subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: In patients with subarachnoid hemorrhage (SAH), higher hemoglobin (HGB) has been associated with better outcomes, but packed red blood cell (PRBC) transfusions with worse outcomes. We performed a prospective pilot trial of goal HGB after SAH. METHODS: Forty-four patients with SAH and high risk for vasospasm were randomized to goal HGB concentration of at least 10 or 11.5 g/dl. We obtained blinded clinical outcomes at 14 days (NIH Stroke Scale and modified Rankin Scale, mRS), 28 days (mRS), and 3 months (mRS), and blinded interpretation of brain MRI for cerebral infarction at 14 days. This trial is registered at www.stroketrials.org. RESULTS: Forty-four patients were randomized. Patients with goal HGB 11.5 g/dl received more PRBC units per transfusion [1 (1-2) vs. 1 (1-1), P < 0.001] and more total PRBC units [3 (2-4) vs. 2 (1-3), P = 0.045]. Prospectively defined safety endpoints were not different between groups. HGB concentration was different between study groups from day 4 onwards. The number of cerebral infarctions on MRI (6 of 20 vs. 9 of 22), NIH Stroke Scale scores at 14 days [1 (0-9.75) vs. 2 (0-16)], and rates of independence on the mRS at 14 days (65% vs. 44%) and 28 days (80% vs. 67%) were similar, but favored higher goal HGB (P > 0.1 for all). CONCLUSIONS: Higher goal hemoglobin in patients with SAH seems to be safe and feasible. A phase III trial of goal HGB after SAH is warranted.

Intensive versus conventional insulin therapy in critically ill neurologic patients.

BACKGROUND: Previous studies of glycemic control in non-neurologic ICU patients have shown conflicting results. The purpose was to investigate whether intensive insulin therapy (IIT) to keep blood glucose levels from 80 to 110 mg/dl or conventional treatment to keep levels less than 151 mg/dl was associated with a reduction of mortality and improved functional outcome in critically ill neurologic patients. METHODS: Within 24 h of ICU admission, mechanically ventilated adult neurologic patients were enrolled after written informed consent and randomized to intensive or conventional control of blood glucose levels with insulin. Primary outcome measure was death within 3 months. Secondary outcome measures included 90-day modified Rankin scale (mRS) score, ICU, and hospital LOS. RESULTS: 81 patients were enrolled. The proportion of deaths was higher among IIT patients but this was not statistically significant (36 vs. 25%, P = 0.34). When good versus poor outcome at 3 months was dichotomized to mRS score 0-2 versus 3-6, respectively, there was no difference in outcome between the two groups (76.2 vs. 75% had a poor 3-month outcome, P = 1.0). There was also no difference in ICU or hospital LOS. Hypoglycemia (<60 mg/dl) and severe hypoglycemia (<40 mg/dl) were more common in the intensive arm (48 vs. 11%, P = 0.0006; and 4 vs. 0%, P = 0.5, respectively). CONCLUSION: There was no benefit to IIT in this small critically ill neurologic population. This is the first glycemic control study to specifically examine both critically ill stroke and traumatic brain injury (TBI) patients and functional outcome. Given these results, IIT cannot be recommended over conventional control.

Use of Conivaptan (Vaprisol) for hyponatremic neuro-ICU patients.

BACKGROUND: Hyponatremia is common in neurocritical care and is associated with poor outcome, but the optimal treatment is not known. We wished to test the hypothesis that for neurocritical care patients with severe hyponatremia (Na < 130 mmol/l) or hyponatremia (Na < 135 mmol/l) with depressed Glasgow Coma Scale (GCS) that conivaptan use would lead to increased serum sodium compared to usual care. METHODS: We prospectively screened 249 neurocritical care patients with hyponatremia for a prospective, randomized pilot (goal N = 20) trial. Study interventions were usual care, or usual care plus conivaptan 20 mg IV as a bolus followed by 20 mg IV over 24 h, the lower FDA-approved dose. Patients were prospectively followed for changes in serum and urine electrolytes and clinical examinations with a blinded examiner. This study is registered at www.clinicaltrials.gov (NCT00727090). RESULTS: Despite the prevalence of hyponatremia, recruitment was difficult, and the study was terminated after six patients were enrolled, three in each group. Most hyponatremia in screened but non-randomized patients was transient or not associated with depressed GCS. Conivaptan led to higher serum sodium compared to usual care. The change in serum sodium from baseline, the pre-specified endpoint, was significantly different between groups at six (7.0 +/- 1.7 vs. -0.6 +/- 2.1 mmol/l, P = 0.008), 24 (9.7 +/- 3.2 vs. 0 +/- 1.0 mmol/l), and 36 h (8.0 +/- 5.6 vs. -1.7 +/- 2.1 mmol/l, P = 0.05). There were no apparent differences in clinical examination as a result of treatment. Adverse events were similar, and all randomized patients completed the protocol. CONCLUSIONS: Despite an inclusive protocol, most patients were not candidates for conivaptan therapy for hyponatremia. The role of conivaptan in the Neuro-ICU remains to be defined.

Classification of cerebral infarction after subarachnoid hemorrhage impacts outcome.

OBJECTIVE: Cerebral infarction (CI) after subarachnoid hemorrhage (SAH) is well described, but there is no validated classification. METHODS: We prospectively enrolled 119 consecutive patients with SAH. We recorded admission World Federation of Neurological Societies grade and Columbia computed tomographic scores. Vasospasm was defined as transcranial Doppler of greater than 120 cm/second or typical clinical symptoms. CI was defined by computed tomographic or magnetic resonance imaging scan, and the date of discovery was recorded. CI was classified by a previously published method (single versus multiple, cortical versus deep versus combined). Outcomes were assessed at 14 days or discharge with the National Institutes of Health Stroke Scale and modified Rankin Scale (mRS), and at 28 days and 3 months with the mRS. RESULTS: Vasospasm was associated with a higher risk of CI (odds ratio, 2.6; 95% confidence interval, 1.3-5.6; P = 0.01). The median time to detection was 4.2 days (interquartile range, 1.6-7.6 days) after SAH onset. CI classification was associated with the National Institutes of Health Stroke Scale score at 14 days (P = 0.002) and intensive care unit length of stay (P = 0.001). CI location (cortical, deep, or combined) was associated with National Institutes of Health Stroke Scale and mRS score at 14 days, and mRS score at 28 days and 3 months (P

Cardiac troponin I and acute lung injury after subarachnoid hemorrhage.

INTRODUCTION: There are few predictors of acute lung injury (ALI) or the acute respiratory distress syndrome (ARDS) after subarachnoid hemorrhage (SAH). We hypothesized that cardiac troponin I, which is associated with cardiovascular morbidity, would also predict ALI. METHODS: We prospectively enrolled 171 consecutive patients with SAH. Troponin was routinely measured on admission and the next day and subsequently if abnormal. We prospectively recorded the maximum troponin, in-hospital events, and clinical endpoints. ALI and ARDS were defined by standard criteria. RESULTS: Acute lung injury was found in 10 patients (6%), ARDS in an additional 14 (8%), and pulmonary edema without lung injury in 9 (5%). Maximum troponin was different in patients without lung injury or pulmonary edema (0.03 [0.02-0.12] mcg/l), ALI (0.17 [0.04-1.4]), or ARDS (0.31 [0.9-1.8], P < 0.001). In ROC analysis, a cutoff of 0.04 mcg/l had 91% sensitivity and 42% specificity for ALI or ARDS (AUC = 0.75, P < 0.001). Troponin was associated with ALI or ARDS after accounting for neurologic grade in multivariate models without further contribution from pneumonia, packed red cell transfusion, gender, tobacco use, coronary artery disease, vasospasm, depressed ejection fraction on echocardiography, or CT grade. Lung injury was associated with worse functional outcome at 14 days, but not at 28 days or 3 months. CONCLUSION: Troponin I is associated with the development of ALI after SAH.

Reduced platelet activity is associated with early clot growth and worse 3-month outcome after intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Antiplatelet medication use and reduced platelet activity may be associated with mortality after intracerebral hemorrhage (ICH). We tested the hypothesis that reduced platelet activity is associated with early ICH clot growth and worse outcomes. METHODS: We prospectively identified patients with spontaneous ICH, measured platelet activity (VerifyNow-ASA, Accumetrics) on admission, and recorded antiplatelet medication use. ICH volume was calculated using computerized volumetric analysis. Data were analyzed with nonparametric statistics and repeated measures ANOVA as appropriate. Patients were prospectively followed for functional outcomes. Data are presented as mean+/-SD or median [Q1 to Q3]. RESULTS: Reduced platelet activity (

Platelet activity and outcome after intracerebral hemorrhage.

There are few data on platelet function in intracerebral hemorrhage (ICH). We prospectively enrolled 69 patients with ICH and measured platelet function on admission. Aspirin use before ICH was associated with reduced platelet activity. Less platelet activity was associated with intraventricular hemorrhage (516.5 [interquartile range (IQR), 454-629.25] vs 637 [IQR, 493-654] aspirin reaction units; p = 0.04) and death at 14 days (480.5 [IQR, 444.5-632.5] vs 626 [IQR, 494-652] aspirin reaction units; p = 0.04). Objective measures of platelet function on admission are associated with intraventricular hemorrhage and death after ICH.

Reduced platelet activity is more common than reported anti-platelet medication use in patients with intracerebral hemorrhage.

BACKGROUND: Anti-platelet medication and reduced platelet activity are associated with an increased risk of death after intracerebral hemorrhage (ICH). The optimal assay for assessing platelet activity is not defined. We hypothesized that reduced platelet activity would be common after ICH. PATIENTS AND METHODS: We prospectively enrolled 72 consecutive patients with ICH and routinely measured platelet activity with both the PFA-100 (Siemens AG, Germany) and the VerifyNow-ASA (Accumetrics, CA, USA) systems on admission. We prospectively recorded anti-platelet medication use prior to ICH. RESULTS: VerifyNow-ASA measurements were associated with aspirin (P = 0.001) and clopidogrel (P = 0.01) use prior to ICH. Combined clopidogrel and aspirin therapy was more potent than either alone. Of 33 patients with reduced platelet activity on the VerifyNow-ASA assay, 14 (42%) were not known to take anti-platelet agents. Of 27 patients with reduced platelet activity on the PFA-100, a related but different 14 (52%) were not known to take anti-platelet agents. There was a poor agreement between the assays (κ = 0.26, P = 0.07) on which patients had reduced platelet activity among the patients not known to take aspirin. CONCLUSIONS: A medication history does not reliably identify patients with reduced platelet activity after ICH, and this may explain studies that found no association between known aspirin use and outcomes. Future studies should screen for unknown use of anti-platelet medications after ICH. Neither assay perfectly identified patients who reportedly used anti-platelet medication before ICH.

How patients die after intracerebral hemorrhage.

INTRODUCTION: Severity of illness scores predict all-cause mortality after intracerebral hemorrhage (ICH), but do not differentiate between proximate mechanisms or predict the timing. We hypothesized that death by neurologic criteria [brain death (BD)], withdrawal of life support, and cardiovascular death would be distinct after ICH. METHODS: We prospectively enrolled patients with spontaneous ICH without underlying vascular malformation or neoplasm. We recorded clinical data and the proximate mechanism of death (BD, withdrawal of life support, cardiovascular death, or other cause). Time to death was compared with Kaplan-Meier methods (log-rank test). Data are median (IQR). RESULTS: Among 89 patients, 15 had withdrawal of life support, 5 had BD, 2 died from cardiac arrest, and 3 died from other causes. Among patients who died, ICH score, age, Glasgow Coma Scale, NIH Stroke Scale, and proximate cause were not associated with the proximate mechanism of death. The time to death was different (P < 0.001) depending on the proximate mechanism. Patients with BD died 1 [0-1] 1 day after ICH, withdrawal of life support led to death 5 [1-13] days after ICH, cardiac death occurred 35 [35-85] days after ICH, and other causes led to death 33 [26-33] days after ICH. Among patients where life support was withdrawn, a higher ICH score on admission was related to earlier death (P = 0.002). CONCLUSIONS: Proximate mechanisms of death after ICH occur at distinct times. Withdrawal of life support leads to earlier death in patients with a higher severity of injury. Medical causes of death can be effectively prevented after ICH.

Medical complications drive length of stay after brain hemorrhage: a cohort study.

INTRODUCTION: Longer length of stay (LOS) is associated with higher complications and costs in ICU patients, while hospital protocols may decrease complications and LOS. We hypothesized that medical complications would increase LOS after spontaneous subarachnoid (SAH) and intracerebral (ICH) hemorrhage after accounting for severity of neurologic injury in a cohort of consecutively admitted patients. METHODS: We prospectively recorded admission characteristics, hospital complications, and LOS for 122 patients with SAH and 56 patients with ICH from February 2006 through March 2008. A multidisciplinary Neuro-ICU team included a dedicated pharmacist and intensivist on daily rounds. Hospital protocols set glucose control with intravenous insulin, ventilator bundles, pharmacist involvement, and hand hygiene. Associations were explored with univariate statistics (t-tests, ANOVA, or non-parametric statistics as appropriate) and linear regression (repeated after log transformation of ICU and hospital LOS). RESULTS: Factors associated with longer LOS after SAH and ICH were similar. In both SAH and ICH the strongest drivers of LOS were infection, fever, and acute lung injury. For SAH, vasospasm and Glasgow Coma Scale were also significant in some models, while in patients with ICH the volume of the initial bleed was significant in some models. CONCLUSION: LOS after spontaneous brain hemorrhage is driven by medical complications even after the adoption of dedicated intensive care medical staff, pharmacist involvement, and evidence-based protocols for ICU care. Further alterations in care will be necessary to eliminate "preventable" complications and minimize LOS after brain hemorrhage.

Barbiturates for the treatment of intracranial hypertension after traumatic brain injury.

In their article on the use of barbiturates for the treatment of intracranial hypertension after traumatic brain injury, Perez-Barcena and colleagues conclude that thiopental was more effective than pentobarbital in decreasing intracranial pressure. Here we discuss the limitations of this study and review areas of controversy surrounding barbiturate use in neurocritical care.

Intravascular temperature control system to maintain normothermia in organ donors.

INTRODUCTION: Temperature regulation in humans is controlled by the hypothalamus. After death by neurological criteria, the hypothalamus ceases to function and poikilothermia ensues. Preservation of normothermia in those patients destined to become organ donors is an important part of maintaining the normal physiology of the organs and organ systems. Typical means of achieving normothermia include increasing the temperature of the ambient air, infrared warming lights, instillation of warmed intravenous fluids, and warm air or water blankets. METHODS: In this prospective case series of five organ donors, we used an intravascular temperature modulation catheter (Alsius, Irvine, CA) to maintain normothermia in organ donors declared dead by neurological criteria. Data on accuracy of temperature maintenance at 37 degrees C and nursing ease of use were collected. RESULTS: This intravascular temperature modulation catheter provided an accurate method of temperature regulation in brain death donor and easier to use from a nursing workload perspective. CONCLUSIONS: Intravascular warming is a viable method for the maintenance of normothermia in organ donors. The experience here provides some insight into the ability of these devices to warm patients in other clinical situations.

Tetanus.

Tetanus is a potentially lethal disease that is preventable with appropriate vaccination. The diagnosis is made exclusively on clinical criteria, and early recognition and treatment are essential for positive outcome. Patients should be monitored in the intensive care unit immediately on diagnosis. Early intubation and mechanical ventilation have drastically reduced the mortality from tetanus. Autonomic instability is associated with a high fatality rate and therefore must be aggressively treated. Metronidazole, human tetanus immunoglobulin, and active immunization should also be initiated on presentation. Because of extremely high metabolic demands in patients with tetanus, care must be taken to provide adequate nutrition and fluids. Prevention of sequelae of long-term critical illness, such as nosocomial pneumonia and deep venous thrombosis, are also important for achieving good outcomes.