Emily J. Gilmore

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.

Seizures and CNS hemorrhage: spontaneous intracerebral and aneurysmal subarachnoid hemorrhage.

Background:Convulsive and nonconvulsive seizures frequently complicate acute brain injury particularly central nervous system hemorrhages and both have been associated with poor outcome. No randomized controlled trials have been conducted to guide decisions on seizure prophylaxis or treatment. The magnitude of additional injury from nonconvulsive seizures remains controversial and some argue that these epileptiform patterns primarily represent surrogate markers of severely injured brain. The deleterious effects of seizures on brain recovering from a recent injury have to be weighed against the deleterious effects of antiepileptic medications when making decisions on prophylaxis and treatment. Review Summary:Currently seizure prophylaxis is not generally recommended for patients with spontaneous intracerebral hemorrhage (ICH) or aneurysmal subarachnoid hemorrhage (aSAH). However, short-term prophylaxis (during the acute critical illness) is commonly instituted for patients in whom seizures would likely lead to additional injury such as herniation or rebleeding. ICH or aSAH patients with seizures at the onset of their hemorrhage, patients with ICH in close proximity to the cortical surface, and aSAH patients with a poor clinical grade (poor neurologic examination and/or thick cisternal blood) are at high risk of seizures, especially nonconvulsive, and are frequently kept on short-term prophylaxis. Convulsive seizures occur in 7% to 17% of patients with spontaneous ICH and in between 6% and 26% of those with aneurysmal aSAH. These should be treated as soon as possible regardless of the underlying causative factors. Nonconvulsive seizures are seen in about 20% of patients with ICH and in 8% to 18% of those with aSAH. It is controversial how aggressively to treat nonconvulsive seizures. Conclusion:Convulsive and nonconvulsive seizures are frequent after central nervous system hemorrhage and treatment is controversial, particularly for nonconvulsive seizures. Randomized controlled trials need to be conducted to better allow evidence-based guidelines for these common neurologic conditions.

Association of periodic and rhythmic electroencephalographic patterns with seizures in critically ill patients

Importance Periodic and rhythmic electroencephalographic patterns have been associated with risk of seizures in critically ill patients. However, specific features that confer higher seizure risk remain unclear. Objective To analyze the association of distinct characteristics of periodic and rhythmic patterns with seizures. Design, Setting, and Participants We reviewed electroencephalographic recordings from 4772 critically ill adults in 3 academic medical centers from February 2013 to September 2015 and performed a multivariate analysis to determine features associated with seizures. Interventions Continuous electroencephalography. Main Outcomes and Measures Association of periodic and rhythmic patterns and specific characteristics, such as pattern frequency (hertz), Plus modifier, prevalence, and stimulation-induced patterns, and the risk for seizures. Results Of the 4772 patients included in our study, 2868 were men and 1904 were women. Lateralized periodic discharges (LPDs) had the highest association with seizures regardless of frequency and the association was greater when the Plus modifier was present (58%; odds ratio [OR], 2.00, P < .001). Generalized periodic discharges (GPDs) and lateralized rhythmic delta activity (LRDA) were associated with seizures in a frequency-dependent manner (1.5-2 Hz: GPDs, 24%,OR, 2.31, P = .02; LRDA, 24%, OR, 1.79, P = .05; ≥ 2 Hz: GPDs, 32%, OR, 3.30, P < .001; LRDA, 40%, OR, 3.98, P < .001) as was the association with Plus (GPDs, 28%, OR, 3.57, P < .001; LRDA, 40%, P < .001). There was no difference in seizure incidence in patients with generalized rhythmic delta activity compared with no periodic or rhythmic pattern (13%, OR, 1.18, P = .26). Higher prevalence of LPDs and GPDs also conferred increased seizure risk (37% frequent vs 45% abundant/continuous, OR, 1.64, P = .03 for difference; 8% rare/occasional vs 15% frequent, OR, 2.71, P = .03, vs 23% abundant/continuous, OR, 1.95, P = .04). Patterns associated with stimulation did not show an additional risk for seizures from the underlying pattern risk (P > .10). Conclusions and Relevance In this study, LPDs, LRDA, and GPDs were associated with seizures while generalized rhythmic delta activity was not. Lateralized periodic discharges were associated with seizures at all frequencies with and without Plus modifier, but LRDA and GPDs were associated with seizures when the frequency was 1.5 Hz or faster or when associated with a Plus modifier. Increased pattern prevalence was associated with increased risk for seizures in LPDs and GPDs. Stimulus-induced patterns were not associated with such risk. These findings highlight the importance of detailed electroencephalographic interpretation using standardized nomenclature for seizure risk stratification and clinical decision making.

Understanding and Managing the Ictal-Interictal Continuum in Neurocritical Care

Opinion statementContinuous electroencephalographic (EEG) monitoring has become an invaluable tool for the assessment of brain function in critically ill patients. However, interpretation of EEG waveforms, especially in the intensive care unit (ICU) setting is fraught with ambiguity. The term ictal-interictal continuum encompasses EEG patterns that are potentially harmful and can cause neuronal injury. There are no clear guidelines on how to treat EEG patterns that lie on this continuum. We advocate the following approaches in a step wise manner: (1) identify and exclude clear electrographic seizures and status epilepticus (SE), i.e., generalized spike-wave discharges at 3/s or faster; and clearly evolving discharges of any type (rhythmic, periodic, fast activity), whether focal or generalized; (2) exclude clear interictal patterns, i.e., spike-wave discharges, periodic discharges, and rhythmic patterns at 1/s or slower with no evolution, unless accompanied by a clear clinical correlate, which would make them ictal regardless of the frequency; (3) consider any EEG patterns that lie in between the above two categories as being on the ictal-interictal continuum; (4) compare the electrographic pattern of the ictal-incterictal continuum to the normal background and unequivocal seizures (if present) from the same patient; (5) when available, correlate ictal-interictal continuum pattern with other markers of neuronal injury such as neuronal specific enolase (NSE) levels, brain imaging findings, depth electrode recordings, data from microdialysis, intracranial pressure fluctuations, and brain oxygen measurement; and (6) perform a diagnostic trial with preferably a nonsedating antiepileptic drug with the endpoint being both clinical and electrographic improvement. Minimize the use of anesthetics or multiple AEDs unless there is clear supporting evidence from ancillary tests or worsening of the EEG patterns over time, which could indicate possible neuronal injury.

Time Course and Predictors of Neurological Deterioration After Intracerebral Hemorrhage

Background and Purpose— Neurological deterioration (ND) is a devastating complication after intracerebral hemorrhage but little is known about time course and predictors. Methods— We performed a retrospective cohort study of placebo patients in intracerebral hemorrhage trials. We performed computed tomographic scans within 3 hours of symptoms and at 24 and 72 hours; and clinical evaluations at baseline, 1-hour, and days 1, 2, 3, and 15. Timing of ND was predefined as follows: hyperacute (within 1 hour), acute (1–24 hours), subacute (1–3 days), and delayed (3–15 days). Results— We enrolled 376 patients and 176 (47%) had ND within 15 days. In multivariate analyses of ND by category, hyperacute ND was associated with hematoma expansion (odds ratio [OR], 3.6; 95% confidence interval [CI], 1.7–7.6) and baseline intracerebral hemorrhage volume (OR, 1.04 per mL; 95% CI 1.02–1.06); acute ND with hematoma expansion (OR, 7.59; 95% CI, 3.91–14.74), baseline intracerebral hemorrhage volume (OR, 1.02 per mL; 95% CI, 1.01–1.04), admission Glasgow Coma Scale (OR, 0.77 per point; 95% CI, 0.65–0.91), and interventricular hemorrhage (OR, 2.14; 95% CI, 1.05–4.35); subacute ND with 72-hour edema (OR, 1.03 per mL; 95% CI, 1.02–1.05) and fever (OR, 2.49; 95% CI, 1.01–6.14); and delayed ND with age (OR, 1.11 per year; 95% CI, 1.04–1.18), troponin (OR, 4.30 per point; 95% CI, 1.71–10.77), and infections (OR, 3.69; 95% CI, 1.11–12.23). Patients with ND had worse 90-day modified Rankin scores (5 versus 3; P<0.001). Conclusions— ND occurs frequently and predicts poor outcomes. Our results implicate hematoma expansion and interventricular hemorrhage in early ND, and cerebral edema, fever, and medical complications in later ND.

Clinical Correlates and Prognostic Significance of Lateralized Periodic Discharges in Patients Without Acute or Progressive Brain Injury: A Case-Control Study.

Purpose: Lateralized periodic discharges (LPDs, also known as periodic lateralized epileptiform discharges) in conjunction with acute brain injuries are known to be associated with worse prognosis but little is known about their importance in absence of such acute injuries. We studied the clinical correlates and outcome of patients with LPDs in the absence of acute or progressive brain injury. Methods: This is a case–control study of 74 patients with no acute brain injury undergoing continuous EEG monitoring, half with LPDs and half without, matched for age and etiology of remote brain injury, if any, or history of epilepsy. Results: Lateralized periodic discharges were found in 145/1785 (8.1%) of subjects; 37/145 (26%) had no radiologic evidence of acute or progressive brain injury. Those with LPDs were more likely to have abnormal consciousness (86% vs. 57%; P = 0.005), seizures (70% vs. 24%; P = 0.0002), and functional decline (62% vs. 27%; P = 0.005), and were less likely to be discharged home (24% vs. 62%; P = 0.002). On multivariate analysis, LPDs and status epilepticus were associated with abnormal consciousness (P = 0.009; odds ratio = 5.2, 95% CI = 1.60–20.00 and P = 0.017; odds ratio = 5.0, 95% CI = 1.4–21.4); and LPDs were independently associated with functional decline (P = 0.001; odds ratio = 4.8, 95% CI = 1.6–15.4) and lower likelihood of being discharged home (P = 0.009; odds ratio = 0.2, 95% CI = 0.04–0.6). Conclusions: Despite absence of acute or progressive brain injury, LPDs were independently associated with abnormal consciousness and worse outcome at hospital discharge.

Proposed consensus definitions for new-onset refractory status epilepticus (NORSE), febrile infection-related epilepsy syndrome (FIRES), and related conditions.

We convened an international group of experts to standardize definitions of New‐Onset Refractory Status Epilepticus (NORSE), Febrile Infection‐Related Epilepsy Syndrome (FIRES), and related conditions. This was done to enable improved communication for investigators, physicians, families, patients, and other caregivers. Consensus definitions were achieved via email messages, phone calls, an in‐person consensus conference, and collaborative manuscript preparation. Panel members were from 8 countries and included adult and pediatric experts in epilepsy, electroencephalography (EEG), and neurocritical care. The proposed consensus definitions are as follows: NORSE is a clinical presentation, not a specific diagnosis, in a patient without active epilepsy or other preexisting relevant neurological disorder, with new onset of refractory status epilepticus without a clear acute or active structural, toxic or metabolic cause. FIRES is a subcategory of NORSE, applicable for all ages, that requires a prior febrile infection starting between 2 weeks and 24 hours prior to onset of refractory status epilepticus, with or without fever at onset of status epilepticus. Proposed consensus definitions are also provided for Infantile Hemiconvulsion‐Hemiplegia and Epilepsy syndrome (IHHE) and for prolonged, refractory and super‐refractory status epilepticus. This document has been endorsed by the Critical Care EEG Monitoring Research Consortium. We hope these consensus definitions will promote improved communication, permit multicenter research, and ultimately improve understanding and treatment of these conditions.

Assessment of Brain Death in the Neurocritical Care Unit

This article reviews current guidelines for death by neurologic criteria and addresses topics relevant to the determination of brain death in the intensive care unit. The history of brain death as a concept leads into a discussion of the evolution of practice parameters, focusing on the most recent 2010 update from the American Academy of Neurology and the practice variability that exists worldwide. Proper transition from brain death determination to possible organ donation is reviewed. This review concludes with a discussion regarding ethical and religious concerns and suggestions on how families of patients who may be brain dead might be optimally approached.

Review of the Utility of Prophylactic Anticonvulsant Use in Critically Ill Patients With Intracerebral Hemorrhage

Spontaneous atraumatic intracerebral hemorrhage (sICH) accounts for 10% to 15% of strokes a year and results in significant morbidity and mortality for survivors. The sICH-related, 30-day mortality is 30% to 50% with a significant proportion occurring in the acute phase, often in the first 48 hours,1 which may be a reflection of early withdrawal of life-sustaining therapy based on perceived poor neurological prognosis.2,3 Cerebrovascular disease, including sICH, is the most common cause of acute symptomatic seizures and localization-related epilepsy in adults, accounting for ≈3.2% to 10.7% of epilepsy.4–6 Spontaneous ICH patients typically develop seizures early after their hemorrhage,7–9 but the association between early seizures and late seizures/epilepsy remains uncertain. Our understanding of risk factors for developing seizures and epilepsy, and the role of antiseizure medications in preventing poststroke seizures and epilepsy, is based mainly on retrospective analyses. To date, there are limited data on the impact of seizures, epilepsy, and antiseizure medications on functional and cognitive outcomes in patients with sICH. The goal of this nonsystematic review is to summarize the available literature, focusing on the role of seizure prophylaxis in the immediate and long-term post-sICH periods. To identify key articles for inclusion, MEDLINE on the Ovid platform (through February 14, 2016) and Embase and newer (unindexed/in process) articles from PubMed were searched using the following terms or combination of terms Anticonvulsants, Seizures, Cerebral Hemorrhage, Intracranial Hemorrhage, Nontraumatic, Spontaneous and Critical Care. All identified references were then cross-referenced to select further articles for inclusion. Non-English studies and studies isolated to infants and children were excluded. ### Definitions Seizures occur at various time points after sICH, from onset to weeks, months, and years afterward. Onset or immediate seizures occur either at ictus or within 24 hours of injury and may in fact be …

Seizures and Epileptiform Patterns in SAH and Their Relation to Outcomes.

Summary: In subarachnoid hemorrhage (SAH), seizures are frequent and occur at different time points, likely reflecting heterogeneous pathophysiology. Young patients, those with more severe SAH (by clot burden or presence of severe mental status changes at onset or focal neurologic deficits at any time), those with associated increased cortical irritation (by infarction or presence of underlying hematoma), and patients undergoing craniotomy are at higher risk. Advanced neurophysiologic monitoring allows for seizure burden quantification, identification of subclinical seizures, and interictal patterns as well as neurovascular complications that may have an independent impact on the outcome in this population. Practice regarding seizure prophylaxis varies widely; its institution is often guided by the risk–benefit ratio of seizures and medication side effects. Newer anticonvulsants seem to be equally effective and may have a more favorable profile. However, questions regarding the association of seizures and vasospasm, the therapeutic dosing, timing, and duration of antiepileptic treatment and the impact of seizures and antiepileptics on the outcome remain unanswered. In this review, we provide a broad overview of the work in this area and offer a diagnostic and therapeutic approach based on our own expert opinion.