Amanda M. Carpenter

Prevention of Shivering During Therapeutic Temperature Modulation: The Columbia Anti-Shivering Protocol

BackgroundAs the practice of aggressive temperature control has become more commonplace, new clinical problems are arising, of which shivering is the most common. Treatment for shivering while avoiding the negative consequences of many anti-shivering therapies is often difficult. We have developed a stepwise protocol that emphasizes use of the least sedating regimen to achieve adequate shiver control.MethodsAll patients treated with temperature modulating devices in the neurological intensive care unit were prospectively entered into a database. Baseline demographic information, daily temperature goals, best daily GCS, and type and cumulative dose of anti-shivering agents were recorded.ResultsWe collected 213 patients who underwent 1388 patient days of temperature modulation. Eighty-nine patients underwent hypothermia and 124 patients underwent induced normothermia. In 18% of patients and 33% of the total patient days only none-sedating baseline interventions were needed. The first agent used was most commonly dexmeditomidine at 50% of the time, followed by an opiate and increased doses of propofol. Younger patients, men, and decreased BSA were factors associated with increased number of anti-shivering interventions.ConclusionsA significant proportion of patients undergoing temperature modulation can be effectively treated for shivering without over-sedation and paralysis. Patients at higher risk for needing more interventions are younger men with decreased BSA.

Quantitative Analysis of Hemorrhage Volume for Predicting Delayed Cerebral Ischemia After Subarachnoid Hemorrhage

Background and Purpose— Delayed cerebral ischemia (DCI) is an important complication after subarachnoid hemorrhage and appears to be associated with clot burden on CT. Quantification of hemorrhage on digitized images may be a more accurate method for predicting DCI than qualitative scales. Methods— Quantitative analysis of clot burden on CT was performed in 160 subarachnoid hemorrhage patients who were scanned within 24 hours from the symptom onset between June 25, 2005 and July 19, 2009. Cisternal plus intraventricular hemorrhage volumes (CIHV) were classified into quartiles to evaluate their association with DCI. DCI was defined as neurological deterioration or cerebral infarction, or both attributable to vasospasm. Results— DCI occurred in 25% of the patients included (age, 55.4±14.5; male, 36.3%). Compared to the lowest quartile of CIHV (<9.6 mL), the higher quartile (9.6 mL–16.5 mL, 16.5 mL–31.0 mL, and ≥31.0 mL) was associated with a greater risk of DCI (odds ratio, 2.6, 4.1, and 6.1, respectively; P=0.01). Receiver-operating characteristic curve analysis showed that quantitative CIHV performed equivalently to the modified Fisher scale. Patients who had DCI develop in a specific vascular territory had higher amounts of blood volume in the corresponding cisterns. Patients in the highest quartile of CIHV also had a higher risk of death or severe disability at 3 months (71%) compared to other groups (23%, 19%, and 40% for first, second, and third quartiles, respectively). Conclusions— CIHV is a reasonable predictor for DCI and 3-month functional outcome in subarachnoid hemorrhage patients.

Evaluation of intraventricular hemorrhage assessment methods for predicting outcome following intracerebral hemorrhage

OBJECT Intraventricular hemorrhage (IVH) associated with intracerebral hemorrhage (ICH) is an independent predictor of poor outcome. Clinical methods for evaluating IVH, however, are not well established. This study sought to determine the best IVH grading scale by evaluating the predictive accuracies of IVH, Graeb, and LeRoux scores in an independent cohort of ICH patients with IVH. Subacute IVH dynamics as well as the impact of external ventricular drain (EVD) placement on IVH and outcome were also investigated. METHODS A consecutive cohort of 142 primary ICH patients with IVH was admitted to Columbia University Medical Center between February 2009 and February 2011. Baseline demographics, clinical presentation, and hospital course were prospectively recorded. Admission CT scans performed within 24 hours of onset were reviewed for ICH location, hematoma volume, and presence of IVH. Intraventricular hemorrhage was categorized according to IVH, Graeb, and LeRoux scores. For each patient, the last scan performed within 6 days of ictus was similarly evaluated. Outcomes at discharge were assessed using the modified Rankin Scale (mRS). Receiver operating characteristic analysis was used to determine the predictive accuracies of the grading scales for poor outcome (mRS score ≥ 3). RESULTS Seventy-three primary ICH patients (51%) had IVH. Median admission IVH, Graeb, and LeRoux scores were 13, 6, and 8, respectively. Median IVH, Graeb and LeRoux scores decreased to 9 (p = 0.005), 4 (p = 0.002), and 4 (p = 0.003), respectively, within 6 days of ictus. Poor outcome was noted in 55 patients (75%). Areas under the receiver operating characteristic curve were similar among the IVH, Graeb, and LeRoux scores (0.745, 0.743, and 0.744, respectively) and within 6 days postictus (0.765, 0.722, 0.723, respectively). Moreover, the IVH, Graeb, and LeRoux scores had similar maximum Youden Indices both at admission (0.515 vs 0.477 vs 0.440, respectively) and within 6 days postictus (0.515 vs 0.339 vs 0.365, respectively). Patients who received EVDs had higher mean IVH volumes (23 ± 26 ml vs 9 ± 11 ml, p = 0.003) and increased incidence of Glasgow Coma Scale scores < 8 (67% vs 38%, p = 0.015) and hydrocephalus (82% vs 50%, p = 0.004) at admission but had similar outcome as those who did not receive an EVD. CONCLUSIONS The IVH, Graeb, and LeRoux scores predict outcome well with similarly good accuracy in ICH patients with IVH when assessed at admission and within 6 days after hemorrhage. Therefore, any of one of the scores would be equally useful for assessing IVH severity and risk-stratifying ICH patients with regard to outcome. These results suggest that EVD placement may be beneficial for patients with severe IVH, who have particularly poor prognosis at admission, but a randomized clinical trial is needed to conclusively demonstrate its therapeutic value.

Volume-dependent effect of perihaematomal oedema on outcome for spontaneous intracerebral haemorrhages

Introduction It is still unknown whether subsequent perihaematomal oedema (PHE) formation further increases the odds of an unfavourable outcome. Methods Demographic, clinical, radiographic and outcome data were prospectively collected in a single large academic centre. A multiple logistic regression model was then developed to determine the effect of admission oedema volume on outcome. Results 133 patients were analysed in this study. While there was no significant association between relative PHE volume and discharge outcome (p=0.713), a strong relationship was observed between absolute PHE volume and discharge outcome (p=0.009). In a multivariate model incorporating known predictors of outcome, as well as other factors found to be significant in our univariate analysis, absolute PHE volume remained a significant predictor of poor outcome only in patients with intracerebral haemorrhage (ICH) volumes ≤30 cm3 (OR 1.123, 95% CI 1.021 to 1.273, p=0.034). An increase in absolute PHE volume of 10 cm3 in these patients was found to increase the odds of poor outcome on discharge by a factor of 3.19. Conclusions Our findings suggest that the effect of absolute PHE volume on functional outcome following ICH is dependent on haematoma size, with only patients with smaller haemorrhages exhibiting poorer outcome with worse PHE. Further studies are needed to define the precise role of PHE in driving outcome following ICH.

Inflammation, negative nitrogen balance, and outcome after aneurysmal subarachnoid hemorrhage.

Objective: To analyze the impact of inflammation and negative nitrogen balance (NBAL) on nutritional status and outcomes after subarachnoid hemorrhage (SAH). Methods: This was a prospective observational study of SAH patients admitted between May 2008 and June 2012. Measurements of C-reactive protein (CRP), transthyretin (TTR), resting energy expenditure (REE), and NBAL (g/day) were performed over 4 preset time periods during the first 14 postbleed days (PBD) in addition to daily caloric intake. Factors associated with REE and NBAL were analyzed with multivariable linear regression. Hospital-acquired infections (HAI) were tracked daily for time-to-event analyses. Poor outcome at 3 months was defined as a modified Rankin Scale score ≥4 and assessed by multivariable logistic regression. Results: There were 229 patients with an average age of 55 ± 15 years. Higher REE was associated with younger age (p = 0.02), male sex (p < 0.001), higher Hunt Hess grade (p = 0.001), and higher modified Fisher score (p = 0.01). Negative NBAL was associated with lower caloric intake (p < 0.001), higher body mass index (p < 0.001), aneurysm clipping (p = 0.03), and higher CRP:TTR ratio (p = 0.03). HAIs developed in 53 (23%) patients on mean PBD 8 ± 3. Older age (p = 0.002), higher Hunt Hess (p < 0.001), lower caloric intake (p = 0.001), and negative NBAL (p = 0.04) predicted time to first HAI. Poor outcome at 3 months was associated with higher Hunt Hess grade (p < 0.001), older age (p < 0.001), negative NBAL (p = 0.01), HAI (p = 0.03), higher CRP:TTR ratio (p = 0.04), higher body mass index (p = 0.03), and delayed cerebral ischemia (p = 0.04). Conclusions: Negative NBAL after SAH is influenced by inflammation and associated with an increased risk of HAI and poor outcome. Underfeeding and systemic inflammation are potential modifiable risk factors for negative NBAL and poor outcome after SAH.

Relationship Between C-Reactive Protein, Systemic Oxygen Consumption, and Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage

Background and Purpose— Subarachnoid hemorrhage (SAH) is known to result in elevated systemic oxygen consumption (VO2) and increases in high-sensitivity C-reactive protein (hsCRP), although the relationship among hsCRP, VO2, and delayed cerebral ischemia (DCI) after SAH remains unknown. We hypothesized that hsCRP is directly associated with VO2 and that elevated VO2 is a predictor of DCI after SAH. Methods— Prospective serial assessments of VO2 and hsCRP over 4 prespecified time periods during the first 14 days after bleed in consecutive SAH patients admitted to a single academic medical center for a 2-year period. Results— One hundred ten SAH patients met study criteria (mean age, 55±16 years; 62% women), with a median admission Hunt Hess grade of 3 (interquartile range, 2–4). In multivariate generalized estimating equation model of the first 14 days after bleed, VO2 was associated with younger age (P=0.01), male gender (P=0.01), and hsCRP levels (P=0.03). Twenty-four (22%) patients had DCI develop, with a median onset on day 7 after bleed (interquartile range, 5–11). The mean VO2 (291±65 mL/min versus 226±55 mL/min; P=0.003) was higher in DCI patients. In a multivariable Cox proportional hazards model, younger age (hazard ratio, 1.2 per 5 years; 95% CI, 1.1–1.3), a higher modified Fisher scale score (hazard ratio, 3.4 per 1-point increase; 95% CI, 1.7–6.9), and higher VO2 (HR, 1.2 per 50-mL/min increase; 95% CI, 1.1–1.3) were predictive of DCI. Conclusions— Systemic oxygen consumption is associated with hsCRP levels in the first 14 days after SAH and is an independent predictor of DCI.

Variability in Outcome After Elective Cerebral Aneurysm Repair in High-Volume Academic Medical Centers

Background and Purpose— Unruptured intracranial aneurysm repair is the most commonly performed procedure for the prevention of hemorrhagic stroke. Despite efforts to regionalize care in high-volume centers, overall results have improved little. This study aims to determine the effectiveness in improving outcomes of previous efforts to regionalize unruptured intracranial aneurysm repair to high-volume centers and to recommend future steps toward that goal. Methods— Using data obtained via the New York Statewide Planning and Research Cooperative System, this study included all patients admitted to any of the 10 highest volume centers in New York state between 2005 and 2010 with a principal diagnosis of unruptured intracranial aneurysm who were treated either by microsurgical or endovascular repair. Mixed-effects logistic regression was used to determine the degree to which hospital-level and patient-level variables contributed to observed variation in good outcome, defined as discharge to home, between hospitals. Results— Of 3499 patients treated during the study period, 2692 (76.9%) were treated at the 10 highest volume centers, with 2198 (81.6%) experiencing a good outcome. Good outcomes varied widely between centers, with 44.6% to 91.1% of clipped patients and 75.4% to 92.1% of coiled patients discharged home. Mixed-effects logistic regression revealed that procedural volume accounts for 85.8% of the between-hospital variation in outcome. Conclusions— There is notable interhospital heterogeneity in outcomes among even the largest volume unruptured intracranial aneurysm referral centers. Although further regionalization may be needed, mandatory participation in prospective, adjudicated registries will be necessary to reliably identify factors associated with superior outcomes.

Severity of Intraventricular Extension Correlates With Level of Admission Glucose After Intracerebral Hemorrhage

Background and Purpose— Hyperglycemia after spontaneous intracerebral hemorrhage (ICH) is associated with poor outcome, but the pathophysiology of ICH-induced glucose dysregulation remains unclear. We sought to identify clinical and radiographic parameters of ICH that are associated with admission hyperglycemia. Methods— Patients admitted to the Columbia University Medical Center Neurological Intensive Care Unit with spontaneous ICH between January 2009 and September 2010 were prospectively enrolled in the ICH Outcomes Project. Clinical, radiographic, and laboratory data were collected prospectively. Receiver operating characteristic analysis was used to identify the glucose level with optimal sensitivity and specificity for in-hospital mortality. Logistic and linear regression analyses were used to identify independent predictors of outcome measures where appropriate. Results— One hundred four patients admitted during the study period were included in the analysis. Mean admission glucose level was 8.23±3.15 mmol/L (3.83 to 18.89 mmol/L) and 23.2% had a history of diabetes mellitus. Admission glucose was significantly associated with discharge (P=0.003) and 3-month mortality (P=0.002). Critical hyperglycemia defined at 10 mmol/L independently predicted discharge mortality (P=0.027; OR, 4.381; 95% CI, 1.186 to 16.174) and 3-month mortality (P=0.011; OR, 10.95; 95% CI, 1.886 to 62.41). Admission intraventricular extension score (P=0.038; OR, 1.117; 95% CI, 1.043 to 1.197) and diabetes mellitus (P=0.002; OR, 5.530; 95% CI, 1.833 to 16.689) were independent predictors of critical hyperglycemia. The intraventricular extension score (B=0.115, P=0.001) linearly correlated with admission glucose level (R=0.612, P=0.001) after adjusting for other clinical variables. Conclusions— Admission hyperglycemia after spontaneous ICH is associated with poor outcome and potentially related to the presence and severity of intraventricular extension.

Predictors of long-term shunt-dependent hydrocephalus in patients with intracerebral hemorrhage requiring emergency cerebrospinal fluid diversion.

OBJECT Intracerebral hemorrhage (ICH) is frequently complicated by acute hydrocephalus, necessitating emergency CSF diversion with a subset of patients, ultimately requiring long-term treatment via placement of permanent ventricular shunts. It is unclear what factors may predict the need for ventricular shunt placement in this patient population. METHODS The authors performed a retrospective analysis of a prospective database (ICH Outcomes Project) containing patients with nontraumatic ICH admitted to the neurological ICU at Columbia University Medical Center between January 2009 and September 2011. A multiple logistic regression model was developed to identify independent predictors of shunt-dependent hydrocephalus after ICH. The following variables were included: patient age, admission Glasgow Coma Scale score, temporal horn diameter on admission CT imaging, bicaudate index, admission ICH volume and location, intraventricular hemorrhage volume, Graeb score, LeRoux score, third or fourth ventricle hemorrhage, and intracranial pressure (ICP) and ventriculitis during hospital stay. RESULTS Of 210 patients prospectively enrolled in the ICH Outcomes Project, 64 required emergency CSF diversion via placement of an external ventricular drain and were included in the final cohort. Thirteen of these patients underwent permanent ventricular CSF shunting prior to discharge. In univariate analysis, only thalamic hemorrhage and elevated ICP were significantly associated with the requirement for permanent CSF diversion, with p values of 0.008 and 0.033, respectively. Each remained significant in a multiple logistic regression model in which both variables were present. CONCLUSIONS Of patients with ICH requiring emergency CSF diversion, those with persistently elevated ICP and thalamic location of their hemorrhage are at increased odds of developing persistent hydrocephalus, necessitating permanent ventricular shunt placement. These factors may assist in predicting which patients will require permanent CSF diversion and could ultimately lead to improvements in the management of this disorder and the outcome in patients with ICH.

Free Fatty Acids and Delayed Cerebral Ischemia After Subarachnoid Hemorrhage

Background and Purpose— The purpose of this study was to understand factors related to increases in serum free fatty acid (FFA) levels and association with delayed cerebral ischemia (DCI) after subarachnoid hemorrhage. Methods— We performed serial measurement of systemic oxygen consumption by indirect calorimetry and FFA levels by liquid chromatography/mass spectrometry in the first 14 days after ictus in 50 consecutive patients with subarachnoid hemorrhage. Multivariable generalized estimating equation models identified associations with FFA levels in the first 14 days after SAH and Cox proportional hazards model used to identified associations with time to DCI. Results— There were 187 measurements in 50 patients with subarachnoid hemorrhage (mean age, 56±14 years old; 66% women) with a median Hunt–Hess score of 3. Adjusting for Hunt–Hess grade and daily caloric intake, n-6 and n-3 FFA levels were both associated with oxygen consumption and the modified Fisher score. Fourteen (28%) patients developed DCI on median postbleed Day 7. The modified Fisher score (P=0.01), mean n-6:n-3 FFA ratio (P=0.02), and mean oxygen consumption level (P=0.04) were higher in patients who developed DCI. In a Cox proportional hazards model, the mean n-6:n-3 FFA ratio (P<0.001), younger age (P=0.05), and modified Fisher scale (P=0.004) were associated with time to DCI. Conclusions— Injury severity and oxygen consumption hypermetabolism are associated with higher n-FFA levels and an increased n-6:n-3 FFA ratio is associated with DCI. This may indicate a role for interventions that modulate both oxygen consumption and FFA levels to reduce the occurrence of DCI.