Halinder S. Mangat

Efficacy spectrum of antishivering medications: Meta-analysis of randomized controlled trials.

Objectives:Shivering after anesthesia or in the critical care setting is frequent, can be prolonged, and has the potential for serious adverse events and worsening outcomes. Furthermore, there are conflicting published data and clinical protocols on how to best treat shivering. In this study, we aimed to critically analyze the published evidence of antishivering medications. Data Sources:We systematically reviewed, categorized, and analyzed all literature on antishivering medications published in English. Target key words and study types were determined and major scientific databases (PubMed, EMBASE, the Cochrane Controlled Trials Register, Ovid-Medline, and JAMA Evidence) and individual target journals were systematically searched up to August 1, 2011. Study Selection:Publications were categorized by the pharmacological intervention used, regardless of whether the subjects were ventilated, underwent surgery, received anesthesia, or received additional medications. Randomized, double-blinded, placebo-controlled trials investigating antishivering treatment were extracted and evaluated for clinical and statistical homogeneity and, if suitable, included in a subsequent meta-analysis using linear comparisons calculating shivering risk-reduction ratios. Data Extraction:A total of 41 individual and eight combination antishivering medications were tested in 124 publications containing 208 substudies and recruiting a total of 9,668 subjects. Among those, 80 publications containing 119 substudies were identified as randomized, double-blinded, placebo-controlled of which 94 substudies were subjected to linear comparison analysis. Data Synthesis:Study drug frequencies, calculated pooled risk benefits, and pooled numbers needed to treat of the five most frequently studied and efficacious medications were clonidine (22 studies; risk ratio: 1.6, numbers needed to treat: 4), meperidine (16; 2.2, 2), tramadol (8; 2.2, 2), nefopam (7; 2.1, 2), and ketamine (7; 1.8, 3). Conclusions:There is significant heterogeneity in the literature with respect to study methods and efficacy testing of antishivering treatments. Clonidine, meperidine, tramadol, nefopam, and ketamine were the most frequently reported pharmacological interventions and showed a variable degree of efficacy in randomized, double-blinded, placebo-controlled trials.

Hypertonic saline reduces cumulative and daily intracranial pressure burdens after severe traumatic brain injury

TO THE EDITOR: After publication of our article, “Hypertonic saline reduces cumulative and daily intracranial pressure burdens after severe traumatic brain injury” (J Neurosurg 122:202–210, 2015), we discovered errors in Table 4. These errors occurred after data analysis and during preparation of the table. They do not impact the content or results of the publication in any way. In the original version of Table 4, the values given for the characteristics “Abnormal pupils (no. [%]),” “Hypotension (no. [%]),” and “Craniotomy (no. [%])” were listed as 6 (17.1), 8 (23.5), and 7 (20.6), respectively. These values should have been 4 (16.0), 4 (16.0), and 6 (24.0), respectively. We apologize for the error and appreciate the opportunity to set the record straight by publishing this erratum. The figure has been corrected online as of October 30, 2015, and appears below.

Neutrophil–Lymphocyte Ratio and Perihematomal Edema Growth in Intracerebral Hemorrhage

Background and Purpose— Although preclinical studies have shown inflammation to mediate perihematomal edema (PHE) after intracerebral hemorrhage, clinical data are lacking. Leukocyte count, often used to gauge serum inflammation, has been correlated with poor outcome but its relationship with PHE remains unknown. Our aim was to test the hypothesis that leukocyte count is associated with PHE growth. Methods— We included patients with intracerebral hemorrhage admitted to a tertiary-care stroke center between 2011 and 2015. The primary outcome was absolute PHE growth during 24 hours, calculated using semiautomated planimetry. Linear regression models were constructed to study the relationship between absolute and differential leukocyte counts (monocyte count and neutrophil–lymphocyte ratio) and 24-hour PHE growth. Results— A total of 153 patients were included. Median hematoma and PHE volumes at baseline were 14.4 (interquartile range, 6.3–36.3) and 14.0 (interquartile range, 5.9–27.8), respectively. In linear regression analysis adjusted for demographics and intracerebral hemorrhage characteristics, absolute leukocyte count was not associated with PHE growth (&bgr;, 0.07; standard error, 0.15; P=0.09). In secondary analyses, neutrophil–lymphocyte ratio was correlated with PHE growth (&bgr;, 0.22; standard error, 0.08; P=0.005). Conclusions— Higher neutrophil–lymphocyte ratio is independently associated with PHE growth. This suggests that PHE growth can be predicted using differential leukocyte counts on admission.

Outcomes after intracerebral hemorrhage from arteriovenous malformations

Objective: To compare outcomes after intracerebral hemorrhage (ICH) from cerebral arteriovenous malformation (AVM) rupture and other causes of ICH. Methods: We performed a retrospective population-based study using data from the Nationwide Inpatient Sample. We used standard diagnosis codes to identify ICH cases from 2002 to 2011. Our predictor variable was cerebral AVM. Our primary outcomes were inpatient mortality and home discharge. We used logistic regression to compare outcomes between patients with ICH with and without AVM while adjusting for demographics, comorbidities, and hospital characteristics. In a confirmatory analysis using a prospective cohort of patients hospitalized with ICH at our institution, we additionally adjusted for hematoma characteristics and the Glasgow Coma Scale score. Results: Among 619,167 ICH hospitalizations, the 4,485 patients (0.7%, 95% confidence interval [CI] 0.6–0.8) with an AVM were younger and had fewer medical comorbidities than patients without AVM. After adjustment for confounders, patients with AVM had lower odds of death (odds ratio [OR] 0.5, 95% CI 0.4–0.7) and higher odds of home discharge (OR 2.0, 95% CI 1.4–3.0) than patients without AVM. In a confirmatory analysis of 342 patients with ICH at our institution, the 34 patients (9.9%, 95% CI 7.2–13.6) with a ruptured AVM had higher odds of ambulatory independence at discharge (OR 4.4, 95% CI 1.4–13.1) compared to patients without AVM. Conclusions: Patients with ICH due to ruptured AVM have more favorable outcomes than patients with ICH from other causes.

Appropriate Use of CT Perfusion following Aneurysmal Subarachnoid Hemorrhage: A Bayesian Analysis Approach

These investigators evaluated the test characteristics of CTP in patients with SAH for detection of delayed cerebral ischemia. Ninety-seven patients were assessed with CTP for ischemia and with DSA for vasospasm. The authors concluded that positive CTP findings identified patients who should be carefully considered for induced hypertension, hypervolemia, and hemodilution and/or intra-arterial therapy while negative CTP findings are useful in guiding a no-treatment decision. BACKGROUND AND PURPOSE: In recent years CTP has been used as a complementary diagnostic tool in the evaluation of delayed cerebral ischemia and vasospasm. Our aim was to determine the test characteristics of CTP for detecting delayed cerebral ischemia and vasospasm in SAH, and then to apply Bayesian analysis to identify subgroups for its appropriate use. MATERIALS AND METHODS: Our retrospective cohort comprised consecutive patients with SAH and CTP performed between days 6 and 8 following aneurysm rupture. Delayed cerebral ischemia was determined according to primary outcome measures of infarction and/or permanent neurologic deficits. Vasospasm was determined by using DSA. The test characteristics of CTP and its 95% CIs were calculated. Graphs of conditional probabilities were constructed by using Bayesian techniques. Local treatment thresholds (posttest probability of delayed cerebral ischemia needed to initiate induced hypertension, hypervolemia, and hemodilution or intra-arterial therapy) were determined via a survey of 6 independent neurologists. RESULTS: Ninety-seven patients with SAH were included in the study; 39% (38/97) developed delayed cerebral ischemia. Qualitative CTP deficits were seen in 49% (48/97), occurring in 84% (32/38) with delayed cerebral ischemia and 27% (16/59) without. The sensitivity, specificity, and positive and negative predictive values (95% CI) for CTP were 0.84 (0.73–0.96), 0.73 (0.62–0.84), 0.67 (0.51–0.79), and 0.88 (0.74–0.94), respectively. A subgroup of 57 patients underwent DSA; 63% (36/57) developed vasospasm. Qualitative CTP deficits were seen in 70% (40/57), occurring in 97% (35/36) with vasospasm and 23% (5/21) without. The sensitivity, specificity, and positive and negative predictive values (95% CI) for CTP were 0.97 (0.92–1.0), 0.76 (0.58–0.94), 0.88 (0.72–0.95), and 0.94 (0.69–0.99), respectively. Treatment thresholds were determined as 30% for induced hypertension, hypervolemia, and hemodilution and 70% for intra-arterial therapy. CONCLUSIONS: Positive CTP findings identify patients who should be carefully considered for induced hypertension, hypervolemia, and hemodilution and/or intra-arterial therapy while negative CTP findings are useful in guiding a no-treatment decision.

Hypertonic saline for the management of raised intracranial pressure after severe traumatic brain injury

Hyperosmolar agents are commonly used as an initial treatment for the management of raised intracranial pressure (ICP) after severe traumatic brain injury (TBI). They have an excellent adverse‐effect profile compared to other therapies, such as hyperventilation and barbiturates, which carry the risk of reducing cerebral perfusion. The hyperosmolar agent mannitol has been used for several decades to reduce raised ICP, and there is accumulating evidence from pilot studies suggesting beneficial effects of hypertonic saline (HTS) for similar purposes. An ideal therapeutic agent for ICP reduction should reduce ICP while maintaining cerebral perfusion (pressure). While mannitol can cause dehydration over time, HTS helps maintain normovolemia and cerebral perfusion, a finding that has led to a large amount of pilot data being published on the benefits of HTS, albeit in small cohorts. Prophylactic therapy is not recommended with mannitol, although it may be beneficial with HTS. To date, no large clinical trial has been performed to directly compare the two agents. The best current evidence suggests that mannitol is effective in reducing ICP in the management of traumatic intracranial hypertension and carries mortality benefit compared to barbiturates. Current evidence regarding the use of HTS in severe TBI is limited to smaller studies, which illustrate a benefit in ICP reduction and perhaps mortality.

Neurosurgery in East Africa: Foundations

This article is the first in a series of 3 articles that seek to provide readers with an understanding of the development of neurosurgery in East Africa (Foundations), the challenges that arise in providing neurosurgical care in developing countries (Challenges), and an overview of traditional and novel approaches to overcoming these challenges to improve healthcare in the region (Innovations). We review the history and evolution of neurosurgery as a clinical specialty in East Africa. We also review Kenya, Uganda, and Tanzania in some detail and highlight contributions of individuals and local and regional organizations that helped to develop and shape neurosurgical care in East Africa. Neurosurgery has developed steadily as advanced techniques have been adopted by local surgeons who trained abroad, and foreign surgeons who have dedicated part of their careers in local hospitals. New medical schools and surgical training programs have been established through regional and international partnerships, and the era of regional specialty surgical training has just begun. As more surgical specialists complete training, a comprehensive estimation of disease burden facing the neurosurgical field is important. We present an overview with specific reference to neurotrauma and neural tube defects, both of which are of epidemiologic importance as they gain not only greater recognition, but increased diagnoses and demands for treatment. Neurosurgery in East Africa is poised to blossom as it seeks to address the growing needs of a growing subspecialty.

Hypertonic saline infusion for treating intracranial hypertension after severe traumatic brain injury

Traumatic brain injury (TBI) remains a major cause of mortality and disability. Post-traumatic intracranial hypertension (ICH) further complicates the care of patients. Hyperosmolar agents are recommended for the treatment of ICH, but no consensus or high-level data exist on the use of any particular agent or the route of administration. The two agents used commonly are hypertonic saline (HTS) and mannitol given as bolus therapy. Smaller studies suggest that HTS may be a superior agent in reducing the ICH burden, but neither agent has been shown to improve mortality or functional outcome. In a recently published analysis of pooled data from three prospective clinical trials, continuous infusion of HTS correlated with serum hypernatremia and reduced ICH burden in addition to improving 90-day mortality and functional outcome. This lays the foundation for the upcoming continuous hyperosmolar therapy for traumatic brain-injured patients (COBI) randomized controlled trial to study the outcome benefit of continuous HTS infusion to treat ICH after severe TBI. This is much anticipated and will be a high impact trial should the results be replicated. However, this would still leave a question over the use of mannitol bolus therapy which will need to be studied.

Emergency Neurological Life Support: Severe Traumatic Brain Injury

Severe traumatic brain injury (TBI) causes substantial morbidity and mortality, and is a leading cause of death in both the developed and developing world. The need for a systematic evidence-based approach to the care of severe TBI patients within the emergency setting has led to its inclusion as an Emergency Neurological Life Support topic. This protocol was designed to enumerate the practice steps that should be considered within the first critical hours of neurological injury from severe TBI.