Fever and Infection in the Neurosurgical Intensive Care Unit

Fever is an adaptive response to a variety of infectious, inflammatory, and foreign stimuli. The “febrile response” confers an immunological advantage to the host over invading microorganisms – bacterial, fungal and viral. Fever results from a cytokine-mediated reaction that results in the generation of acute phase reactants and controlled elevation of core body temperature. The anterior hypothalamus coordinates the “febrile response” in reaction to the release of endogenous pyrogenes and subsequent up-regulation of prostaglandin synthesis. An ensuing change in the hypothalamic set point for temperature regulation advances a synchronized physiologic response from CNS to periphery, on a microscopic and macroscopic level, throughout the entire human organism. This differs from hyperthermia which refers to heat retention attributable to unregulated readjustment of the thermoregulatory mechanism. Clinically, an elevation of core body temperature, whether in fever or hyperthermia, is only the most apparent manifestation of an intricate mechanism that orchestrates activation of autonomic, immunologic, neurologic, hematologic, endocrine and behavioral responses

The Intensivist

The intensivist is the primary care physician of the ICU. Critically ill patients often have multiple acute and chronic illnesses requiring the careful integration of information and recommendations from multiple consultants. In addition to acting as a physician, intensivists commonly are administrators of an ICU. In 1992, the Society of Critical Care Medicine1 published its guidelines for the definition of an intensivist and the intensivist’s role in an ICU (Table 1)

Nociceptive neuropeptide increases and periorbital allodynia in a model of traumatic brain injury.

OBJECTIVE: This study tests the hypothesis that injury to the somatosensory cortex is associated with periorbital allodynia and increases in nociceptive neuropeptides in the brainstem in a mouse model of controlled cortical impact (CCI) injury. METHODS: Male C57BL/6 mice received either CCI or craniotomy-only followed by weekly periorbital von Frey (mechanical) sensory testing for up to 28 days post-injury. Mice receiving an incision only and naïve mice were included as control groups. Changes in calcitonin gene-related peptide (CGRP) and substance P (SP) within the brainstem were determined using enzyme-linked immunosorbent assay and immunohistochemistry, respectively. Activation of ionized calcium-binding adaptor molecule-1-labeled macrophages/microglia and glial fibrillary acidic protein (GFAP)-positive astrocytes were evaluated using immunohistochemistry because of their potential involvement in nociceptor sensitization. RESULTS: Incision-only control mice showed no changes from baseline periorbital von Frey mechanical thresholds. CCI significantly reduced mean periorbital von Frey thresholds (periorbital allodynia) compared with baseline and craniotomy-only at each endpoint, analysis of variance P \u3c .0001. Craniotomy significantly reduced periorbital threshold at 14 days but not 7, 21, or 28 days compared with baseline threshold, P \u3c .01. CCI significantly increased SP immunoreactivity in the brainstem at 7 and 14 days but not 28 days compared with craniotomy-only and controls, P \u3c .001. CGRP levels in brainstem tissues were significantly increased in CCI groups compared with controls (incision-only and naïve mice) or craniotomy-only mice at each endpoint examined, P \u3c .0001. There was a significant correlation between CGRP and periorbital allodynia (P \u3c .0001, r = -0.65) but not for SP (r = 0.20). CCI significantly increased the number of macrophage/microglia in the injured cortex at each endpoint up to 28 days, although cell numbers declined over weeks post-injury, P \u3c .001. GFAP(+) immunoreactivity was significantly increased at 7 but not 14 or 28 days after CCI, P \u3c .001. Craniotomy resulted in transient periorbital allodynia accompanied by transient increases in SP, CGRP, and GFAP immunoreactivity compared with control mice. There was no increase in the number of macrophage/microglia cells compared with controls after craniotomy. CONCLUSION: Injury to the somatosensory cortex results in persistent periorbital allodynia and increases in brainstem nociceptive neuropeptides. Findings suggest that persistent allodynia and increased neuropeptides are maintained by mechanisms other than activation of macrophage/microglia or astrocyte in the injured somatosensory cortex

Thoracolumbar spine trauma: review of the evidence.

AIM: The aim of this paper was to provide a comprehensive review of literature regarding the classification systems and surgical management of thoracolumbar spine trauma. METHODS: A Pubmed search of thoracolumbar , spine , fracture was used on January 05, 2013. Exclusionary criteria included non-Human studies, case reports, and non-clinical papers. RESULTS. One thousand five hundred twenty manuscripts were initially returned for the combined search string; 150 were carefully reviewed, and 48 manuscripts were included in the review. DISCUSSION: Traumatic spinal cord injury (SCI) has a high prevalence in North America. The thoracolumbar junction is a point of high kinetic energy transfer and often results in thoracolumbar fractures. New classification systems for thoracolumbar spine fractures are being developed in an attempt to standardize evaluation, diagnosis, and treatment as well as reporting in the literature. Earlier classifications such as the Denis 3-column model emphasized anatomic divisions to guide surgical planning. More modern classification systems such as the Thoracolumbar injury classification system (TLICS) emphasize initial neurologic status and structural integrity of the posterior ligamentous complex as a guide for surgical decision making and have demonstrated a high intra- and interobserver reliability. Other systems such as the Load-Sharing Classification aid as a useful tool in planning the extent of instrumentation and fusion. CONCLUSION: There is still much controversy over the surgical management of various thoracolumbar fractures. Level I data exists supporting the nonsurgical management of thoracolumbar burst fractures without neurologic compromise. However, for the majority of fracture types in this region, more randomized controlled trials are necessary to establish standards of care

Etiology and Surgical Management of Cervical Spinal Epidural Abscess (SEA):: A Systematic Review.

Study Design: Systematic analysis and review. Objective: Evaluation of the presentation, etiology, management strategies (including both surgical and nonsurgical options), and neurological functional outcomes in patients with cervical spinal epidural abscess (SEA). Methods: The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria were used to create a framework based on which articles pertaining to cervical SEA were chosen for review following a search of the Ovid and PubMed databases using the search terms epidural abscess and cervical. Included studies needed to have at least 4 patients aged 18 years or older, and to have been published within the past 20 years. Results: Database searches yielded 521 potential articles in PubMed and 974 potential articles in Ovid. After review, 11 studies were ultimately identified for inclusion in this systematic review. Surgery appears to be a well-tolerated management strategy with limited complications for patients with cervical SEA. However, the quantity of data comparing medical and surgical treatment of cervical SEA is limited and the bulk of the data is derived from low quality studies. Conclusion: Data reporting was heterogeneous among studies making it difficult to draw discrete conclusions. Early surgical intervention may be appropriate in selected patients with cervical epidural abscess, but it is not clear what distinguishes these patients from those who are successfully managed nonoperatively

Acute effects of a selective cannabinoid-2 receptor agonist on neuroinflammation in a model of traumatic brain injury.

Proposed therapeutic strategies for attenuating secondary traumatic brain injury (TBI) include modulation of acute neuroimmune responses. The goal of this study was to examine the acute effects of cannabinoid-2 receptor (CB(2)R) modulation on behavioral deficits, cerebral edema, perivascular substance P, and macrophage/microglial activation in a murine model of TBI. Thirty male C57BL/6 mice underwent sham surgery, or cortical contusion impact injury (CCI). CCI mice received vehicle or the CB(2)R agonist 0-1966 at 1 and 24 h after injury. Performance on the rotarod, forelimb cylinder, and open-field tests were evaluated before and at 48 h after sham or CCI surgery. Cerebral edema was evaluated using the wet-dry weight technique. Immunohistochemical analysis was used to examine changes in substance P and macrophage/microglia-specific Iba1 protein immunoreactivity. Locomotor performance and exploratory behavior were significantly improved in mice receiving 0-1966 (CB(2)R agonist) compared to vehicle-treated mice. Significant reductions were found for cerebral edema, number of perivascular areas of substance P immunoreactivity, and number of activated macrophages/microglial cells in the injured brains of 0-1966-treated mice compared to vehicle-treated mice. The findings show that the effects of the CB(2)R agonist 0-1966 on edema, substance P immunoreactivity, and macrophage/microglial activation, were associated with recovery of acute motor and exploratory deficits. This study provides evidence of acute neuroprotective effects derived from selective CB(2)R activation that may represent an avenue for further development of novel therapeutic agents in the treatment of TBI

Outcomes in Traumatic Brain Injury Patients on Preinjury Anticoagulation and Antiplatelet Agents

Traumatic brain injury (TBI) affects an estimated 1.7 million people a year. Around 75% of these cases are mild. Falls and motor vehicle accidents are among the leading causes for TBI, with falls accounting for 60.7% of occurrences in populations 65 years or older1. As the general population continues to expand both in age and in size, the risk of falls will increase. This poses a problem particularly in light of the pervasive use of anticoagulants and antiplatelet agents for this population, both of which increase the bleeding risk. Anticoagulants and antiplatelet agents are used for a variety of conditions, including deep venous thrombosis, atrial fibrillation, pulmonary embolism and coronary artery disease. They are also given postoperatively for prosthetic heart valves or stent placement. An estimated 597,689 deaths in 2010 were due to cardiovascular disease, with 80% above the age of 652. Stroke caused 129,476 deaths. The use of anticoagulants and antiplatelet agents for prevention of cardiovascular and cerebrovascular events is irrefutable, but little literature has touched on its effects on morbidity and mortality in those with traumatic brain injury. This article summarizes the current literature on the pre-TBI use of anticoagulants and antiplatelet agents and the associated morbidity and mortality

Duration of Posttraumatic Amnesia Predicts Neuropsychological and Global Outcome in Complicated Mild Traumatic Brain Injury.

OBJECTIVES: Examine the effects of posttraumatic amnesia (PTA) duration on neuropsychological and global recovery from 1 to 6 months after complicated mild traumatic brain injury (cmTBI). PARTICIPANTS: A total of 330 persons with cmTBI defined as Glasgow Coma Scale score of 13 to 15 in emergency department, with well-defined abnormalities on neuroimaging. METHODS: Enrollment within 24 hours of injury with follow-up at 1, 3, and 6 months. MEASURES: Glasgow Outcome Scale-Extended, California Verbal Learning Test II, and Controlled Oral Word Association Test. Duration of PTA was retrospectively measured with structured interview at 30 days postinjury. RESULTS: Despite all having a Glasgow Coma Scale Score of 13 to 15, a quarter of the sample had a PTA duration of greater than 7 days; half had PTA duration of 1 of 7 days. Both cognitive performance and Extended Glasgow Outcome Scale outcomes were strongly associated with time since injury and PTA duration, with those with PTA duration of greater than 1 week showing residual moderate disability at 6-month assessment. CONCLUSIONS: Findings reinforce importance of careful measurement of duration of PTA to refine outcome prediction and allocation of resources to those with cmTBI. Future research would benefit from standardization in computed tomographic criteria and use of severity indices beyond Glasgow Coma Scale to characterize cmTBI

Emergency reversal of antiplatelet agents in patients presenting with an intracranial hemorrhage: A clinical review

Abstract Objective: Prehospital use of antiplatelet agents has been associated with an increased risk for ICH as well as a secondary increase in ICH volume after the initial hemorrhage. Strategies to reestablish platelet aggregation are used in clinical practice, but without any established guidelines or recommendations. This article serves to evaluate the literature regarding “reversal” of antiplatelet agents in neurosurgical populations. Methods: PUBMED and MEDLINE databases were searched for publications from 1966 to 2009 relating to intracranial hemorrhage and antiplatelet agents. The reference sections of recent articles, guidelines and reviews were reviewed and pertinent articles identified. Studies were classified by two broad subsets; those describing intracranial hemorrhage relatable to a traumatic mechanism and those with a spontaneous intracranial hemorrhage. Two independent auditors recorded and analyzed study design and the reported outcome measures. Results: For the spontaneous intracranial hemorrhage group, 9 reports assessing antiplatelet effects on various outcome measures were identified. Eleven studies evaluating the use of prehospital antiplatlets prior to a traumatic intracranial hemorrhage were examined. Conclusion: The data assessing the relationship between outcome and prehospital antiplatelet agents in the setting of ICH is conflicting in both the trauma and the stroke literature. Only one retrospective review specifically addressed outcomes after attempted reversal with platelet transfusion. Further study is needed to determine whether platelet transfusion ameliorates hematoma enlargement and/or improves outcome in the setting of acute ICH

Complications of Decompressive Craniectomy

Introduction: Persistent elevation of intracranial pressure (ICP), if untreated, may lead to brain ischemia or lack of brain oxygen and even brain death.1-6,10 When standard treatments for elevated ICP are exhausted without any signs of improvement, decompressive craniectomy can be an effective alternative solution.7,19 Decompressive craniectomies (DC) have been used as a method of controlling intracranial pressure in patients with cerebral edema secondary to cerebral ischemia, subarachnoid hemorrhage (SAH), and traumatic brain injury (TBI), among others. 8-10 Several studies over the years have demonstrated the efficacy of this procedure.7-9,11,35,36 However, consensus is still lacking in the utility of DC as an effective first tier treatment for intractable intracranial pressure due to the rudimentary neurological outcome assessments, and the many complications associated with this procedure.11,12,59 There are a limited number of studies that have looked at complications secondary to the procedure itself.13-18 The majority of these studies only investigated the impact of this procedure in patients with traumatic brain injury. The purpose of this study is to investigate the rates of various complications associated with the decompressive craniectomy procedure in patients that did not suffer from traumatic brain injury, and to determine whether the same associations between preoperative parameters and development of complications can be made