Quantitative Pupillometry in the Intensive Care Unit.

Quantitative pupillometry provides a noninvasive and objective assessment within the neurological examination. This review details the physiology of the pupillary light response, the clinical significance of changes in pupillary reactivity, and the variables that compose the Neurological Pupil index or NPi are discussed. This article reviews the most recent applications and advances in quantitative pupillometry for noninvasive intracranial pressure monitoring, postcardiac arrest prognostication, and subarachnoid hemorrhage. Also discussed are the limitations and confounders of quantitative pupillometry in the modern neurological intensive care unit.

Treatment of adults with intracranial hemorrhage on apixaban or rivaroxaban with prothrombin complex concentrate products.

To analyze the efficacy and safety of activated prothrombin complex concentrates (aPCC) and four-factor prothrombin complex concentrates (4F-PCC) to prevent hematoma expansion in patients taking apixaban or rivaroxaban with intracranial hemorrhage (ICH). In this multicenter, retrospective study, sixty-seven ICH patients who received aPCC or 4F-PCC for known use of apixaban or rivaroxaban between February 2014 and September 2018 were included. The primary outcome was the percentage of patients who achieved excellent/good or poor hemostasis after administration of aPCC or 4F-PCC. Secondary outcomes included hospital mortality, thromboembolic events during admission, and transfusion requirements. Excellent/good hemostasis was achieved in 87% of aPCC patients, 89% of low-dose 4F-PCC [< 30 units per kilogram (kg)], and 89% of high-dose 4F-PCC (≥ 30 units per kg). There were no significant differences in excellent/good or poor hemostatic efficacy (p = 0.362). No differences were identified in transfusions 6 h prior (p = 0.087) or 12 h after (p = 0.178) the reversal agent. Mortality occurred in five patients, with no differences among the groups (p = 0.838). There were no inpatient thromboembolic events. Both aPCC and 4F-PCC appear safe and equally associated with hematoma stability in patients taking apixaban or rivaroxaban who present with ICH. Prospective studies are needed to identify a superior reversal agent when comparing andexanet alfa to hospital standard of care (4F-PCC or aPCC) and to further explore the optimal dosing strategy for patients with ICH associated with apixaban or rivaroxaban use.

Intracerebral hemorrhage: who gets tested for methamphetamine use and why might it matter?

BACKGROUND: Methamphetamine use is an emerging risk factor for intracerebral hemorrhage (ICH). The aim of this study was to investigate the use of urine drug screen (UDS) for identifying methamphetamine-associated ICH. METHODS: This is a retrospective, single-center study of consecutive patients hospitalized with spontaneous ICH from January 2013 to December 2017. Patients were divided into groups based on presence of UDS. The characteristics of patients with and without UDS were compared. Factors associated with getting UDS were explored using multivariable analyses. RESULTS: Five hundred ninety-six patients with ICH were included. UDS was performed in 357 (60%), and positive for methamphetamine in 44 (12.3%). In contrast, only 19 of the 357 patients (5.3%) had a documented history of methamphetamine use. Multivariable analysis demonstrated that patients screened with UDS were more likely to be younger than 45 (OR, 2.24; 95% CI, 0.26-0.78; p = 0.004), male (OR, 1.65; 95% CI, 0.44-0.84; p = 0.003), smokers (OR, 1.74; 95% CI, 1.09-2.77; p <  0.001), with history of methamphetamine use (OR, 10.48; 95% CI, 2.48-44.34; p <  0.001), without diabetes (OR 1.47; 95% CI, 0.471-0.975; p = 0.036), not on anticoagulant (OR, 2.20; 95% CI, 0.26-0.78; p = 0.004), with National Institutes of Health Stroke Scale (NIHSS) > 4 (OR, 1.92; 95%CI, 1.34-2.75; p <  0.001), or require external ventricular drain (EVD) (OR, 1.63; 95%CI, 1.07-2.47; p = 0.021. There was no significant difference in race (p = 0.319). Reported history of methamphetamine use was the strongest predictor of obtaining a UDS (OR,10.48). Five percent of patients without UDS admitted history of use. CONCLUSION: UDS identified 12.3% of ICH patients with methamphetamine use as compared to 5.3% per documented history of drug use. There was no racial bias in ordering UDS. However, it was more often ordered in younger, male, smokers, with history of methamphetamine use, without diabetes or anticoagulant use.

Early Initiation of Oral Antihypertensives Reduces Intensive Care Unit Stay and Hospital Cost for Patients with Hypertensive Intracerebral Hemorrhage.

BACKGROUND/OBJECTIVE: Intravenous nicardipine infusion is effective for rapid blood pressure control. However, its use requires hemodynamic monitoring in the intensive care unit (ICU) and is associated with high hospital cost. This study aimed to examine the effect of early versus late initiation of oral antihypertensives on ICU length of stay (LOS) and cost of hospitalization in patients with hypertensive intracerebral hemorrhage (ICH). METHODS: This is a single-center retrospective study of patients with hypertensive ICH treated with nicardipine infusion from January 1, 2013, to December 31, 2017. Patients were dichotomized into study and control groups, based on receiving oral antihypertensives within 24 h versus after 24 h of emergency department arrival. Baseline characteristics, duration of nicardipine infusion, LOS in the ICU and hospital, functional outcome at discharge, and hospital cost were compared between the two groups using univariate and multivariate analysis. RESULTS: A total of 90 patients in the study group and 76 in the control group were identified. There was no significant difference in demographics, past medical history, and initial SBP between the two groups. After adjusting for confounding factors with multivariate regression models, early initiation of oral antihypertensives was associated with significant reductions in duration of nicardipine infusion (55.5 ± 60.1 vs 121.6 ± 141.3 h, p <0.005), nicardipine cost ($14,207 vs $29,299, p < 0.01), ICU LOS (2 vs 5 days, p < 0.005), and cost of hospitalization ($24,564 vs $47,366, p < 0.01). There was no significant difference in adversary renal events, favorable outcomes, and mortality between the two groups. CONCLUSIONS: Early initiation of oral antihypertensives is safe and may have a significant financial impact on patients with hypertensive ICH.

A multicenter retrospective study evaluating the impact of desmopressin on hematoma expansion in patients with antiplatelet-associated intracranial hemorrhage.

INTRODUCTION: Antiplatelet medications interfere with hemostasis which can contribute to increased risk of hematoma expansion and potentially worse outcomes in patients presenting with intracranial hemorrhages (ICH). Current Neurocritical Care Society guidelines recommend desmopressin (DDAVP) in patients with antiplatelet-associated ICH with evidence limited by small cohorts. MATERIALS AND METHODS: Patients were included in our multi-center, retrospective study if they had computed tomographic (CT) scan confirmed ICH and were taking antiplatelet medications. Patients were excluded if hospital length of stay was <24 h, administered DDAVP dose was <0.3 µg/kg, no follow-up head CT scan was performed within the first 24 h after baseline, major neurosurgical intervention was performed in between CT scans, or the injury was an acute on chronic ICH. The primary outcome was incidence of hematoma expansion (defined as >20 % increase from baseline). Secondary outcomes were incidence of thrombotic complications within 7 days, largest absolute decrease in serum sodium within the first 24 h, and patient disposition. RESULTS: Among the 209 patients included in the study, 118 patients received DDAVP while 91 did not. The frequency of hematoma expansion was similar between patients who received DDAVP and those who did not (16.1 % vs 17.6 %; P = 0.78). No difference in secondary outcomes was observed between the two groups. CONCLUSIONS: These findings in conjunction with recently published literature may suggest minimal benefit or harm with DDAVP treatment. However, further study could elucidate any potential impact on long-term function outcomes.

Polymerase Chain Reaction (PCR)-Negative Herpes Simplex Virus (HSV) Encephalitis in a 62-Year-Old Woman With p-ANCA Vasculitis.

We present the case of a 62-year-old woman with a past medical history significant for p-ANCA vasculitis (on immunosuppression) who was found to have polymerase chain reaction (PCR)-negative herpes simplex virus (HSV) encephalitis. We also present a review of all identifiable reports of PCR-negative HSV encephalitis in the past 20 years. To our knowledge, this is the first case of PCR-negative HSV encephalitis in a patient with p-ANCA vasculitis and the thirteenth overall in this timeframe. The patient presented with new-onset fever, encephalopathy, and a first-in-lifetime focal motor seizure progressing to status epilepticus. Cerebrospinal fluid (CSF) PCR was negative for HSV on three separate instances between the first and thirteenth days since symptom onset, and the CSF profile was not typical for HSV encephalitis. The patient underwent a brain biopsy, which confirmed the presence of HSV. She continued to worsen despite aggressive seizure control and six days of empiric acyclovir. Unfortunately, she expired despite the reinitiation of acyclovir. When faced with the classical features of encephalitis in the immunocompromised, the suspicion of HSV should remain high despite negative PCR results. The completion of a full course of acyclovir in the absence of clinical improvement should be considered.

Maxillofacial Injuries Sustained by Riders of Electric-Powered Bikes and Electric-Powered Scooters.

OBJECTIVES: The purpose of our study is to retrospectively analyze and compare the patterns of maxillofacial-related injuries among rides of electric-powered bikes (E-bikes) and electric-powered scooters (E-scooters), the associated risk factors, and the required treatment. MATERIALS AND METHODS: The medical files of all riders presenting to the emergency department at the Tel Aviv Sourasky Medical Center between 2019 and 2020 with oral- and maxillofacial-related injuries due to E-bike and E-scooter accidents were reviewed. RESULTS: A total of 320 riders sustained oral- and maxillofacial-related injuries due to trauma involving E-bikes and E-scooters during the study period. E-scooter riders were involved in 238 accidents (74.5%) while E-bike riders accounted for the remaining 82 accidents (27.5%). Eighty-four out of 320 riders (26.25%) were hospitalized and required surgical interventions. Most of the 232 riders (72.5%) who reported not wearing a protective helmet during the index accident were E-scooter riders. In addition, 39 riders (18.66%) were riding either of these electric-powered vehicles under the influence of alcohol. CONCLUSIONS: E-bike riders are more likely to sustain a maxillofacial fracture than E-scooter riders. Not wearing a protective helmet and riding under the influence of alcohol are major risk factors for maxillofacial injuries.

Therapeutic hypothermia in acute ischemic stroke.

Induced hypothermia has been used for neuroprotection in cardiac and neurovascular procedures. Experimental and translational studies provide evidence for its utility in the treatment of ischemic cerebrovascular disease. Over the past decade, these principles have been applied to the clinical management of acute stroke. Varying induction methods, time windows, clinical indications, and adjuvant therapies have been studied. In this article the authors review the mechanisms and techniques for achieving therapeutic hypothermia in the setting of acute stroke, and they outline pertinent side effects and complications. The manuscript summarizes and examines the relevant clinical trials to date. Despite a reasonable amount of existing data, this review suggests that additional trials are warranted to define the optimal time window, temperature regimen, and precise clinical indications for induction of therapeutic hypothermia in the setting of acute stroke.

Coagulopathy reversal in intracerebral haemorrhage.

As intracerebral hemorrahge becomes more frequent as a result of an aging population with greater comorbidities, rapid identification and reversal of precipitators becomes increasingly paramount. The aformentioned population will ever more likely be on some form of anticoagulant therapy. Understanding the mechanisms of these agents and means by which to reverse them early on is critical in managing the acute intracerebral hemorrhage.

Refractory Central Neurogenic Hyperventilation: A Novel Approach Utilizing Mechanical Dead Space.

This report describes the successful management of a case of central neurogenic hyperventilation (CNH) refractory to high dose sedation by increasing the mechanical dead space. A 46-year-old male presented with a history of multiple neurological symptoms. Following an extensive evaluation, he was diagnosed with primary diffuse CNS lymphoma and started on high dose steroids. After initial symptomatic improvement, the patient developed increasing respiratory distress and tachypnea. He was intubated and transferred to the neurointensive care unit (neuro ICU). While in the ICU the patient remained ventilator dependent with significant tachypnea and respiratory alkalosis resistant to fentanyl and propofol. This prompted an attempt to normalize the PaCO2 via an increase of the mechanical dead space. This approach successfully increased PaCO2 and bridged the patient until ongoing therapy for the underlying disease resolved the pervasive breathing pattern typical of CNH. Further investigation is warranted to evaluate this strategy, which upon review of the literature appears underused.

Platelet Dysfunction and Intracerebral Hemorrhage in a Patient Treated with Empiric Piperacillin-Tazobactam in the Neurocritical Care Unit.

BACKGROUND: Piperacillin-tazobactam is common empiric antibiotic therapy. Hematologic laboratory test abnormalities were documented but rare in premarketing studies, and whether these alterations are of clinical significance has been studied little. Very few cases of piperacillin-induced bleeding, thrombocytopenia, or both have been reported; aberrations in platelet function have not been implicated. CASE DESCRIPTION: A 55-year old Vietnamese man with hypertension presented for treatment of an Intracranial hemorrhage. Platelet function assays (PFAs) at the time of external ventricular drain and quad-lumen bolt placement were normal, and imaging showed no hemorrhage after placement. The patient was later started on empiric piperacillin-tazobactam due to high suspicion for aspiration pneumonia. After removal of the quad-lumen bolt and external ventricular drain on separate days, both follow-up computed tomography scans showed new hematomas in the devices' tracts, with significant intraventricular hemorrhage. Repeat PFAs were abnormally prolonged, representing a distinct change from baseline. A trend toward normalization of PFAs was observed 6 hours after discontinuation of piperacillin-tazobactam with progression toward baseline thereafter. CONCLUSIONS: This is unique in that the significant bleeding that occurred was attributable to platelet dysfunction rather than thrombocytopenia. This is the first reported case of intracranial (periprocedural) hemorrhage potentially related to piperacillin-tazobactam; further research into this drug's impact upon qualitative platelet function is needed.

Resistant Hypertension after Hypertensive Intracerebral Hemorrhage Is Associated with More Medical Interventions and Longer Hospital Stays without Affecting Outcome.

BACKGROUND: Hypertension (HTN) is the most common cause of spontaneous intracerebral hemorrhage (ICH). The aim of this study is to investigate the role of resistant HTN in patients with ICH. METHODS AND RESULTS: We conducted a retrospective study of all consecutive ICH admissions at our medical center from November 2013 to October 2015. The clinical features of patients with resistant HTN (requiring four or more antihypertensive agents to keep systolic blood pressure <140 mm Hg) were compared with those with responsive HTN (requiring three or fewer agents). Of the 152 patients with hypertensive ICH, 48 (31.6%) had resistant HTN. Resistant HTN was independently associated with higher body mass index and proteinuria. Compared to the responsive group, patients with resistant HTN had higher initial blood pressures and greater requirement for ventilator support, hematoma evacuation, hypertonic saline therapy, and nicardipine infusion. Resistant HTN increases length of stay (LOS) in the intensive care unit (ICU) (4.2 vs 2.1 days; p = 0.007) and in the hospital (11.5 vs 7.0 days; p = 0.003). Multivariate regression analysis showed that the rate of systolic blood pressure >140 mm Hg and duration of nicardipine infusion were independently associated with LOS in the ICU. There was no significant difference in hematoma expansion and functional outcome at hospital discharge between the two groups. CONCLUSION: Resistant HTN in patients with ICH is associated with more medical interventions and longer LOS without effecting outcome at hospital discharge.

Effect of caffeine on cerebral blood flow response to somatosensory stimulation.

Despite caffeine's wide consumption and well-documented psychoactive effects, little is known regarding the effects of caffeine on neurovascular coupling. In the present study, we evaluated the effects of caffeine, an adenosine receptor antagonist, on intracerebral arterioles in vitro and subsequently, on the pial circulation in vivo during cortical activation induced by contralateral sciatic nerve stimulation (SNS). In our in vitro studies, we utilized isolated intracerebral arterioles to determine the effects of caffeine (10 or 50 micromol/L) on adenosine-induced vasodilatation. At the lower concentration, caffeine was without effect, but at the higher concentration, caffeine produced significant attenuation. In our in vivo studies, we determined the cerebrospinal fluid (CSF) caffeine concentrations at 15, 30, and 60 mins after intravenous administration of 5, 10 and 40 mg/kg. At the latter two concentrations, CSF levels exceeded 10 micromol/L. We then evaluated the pial arteriolar response during cortical activation caused by contralateral SNS after administering caffeine intravenously (0, 5, 10, 20 30, and 40 mg/kg). The pial circulation was observed through a closed cranial window in chloralose-anesthetized Sprague-Dawley rats. The contralateral sciatic nerve was isolated, positioned on silver electrodes and stimulated for 20 secs (0.20 V, 0.5 ms, and 5 Hz). Arteriolar diameter was quantified using an automated video dimension analyzer. Contralateral SNS resulted in a 23.8% +/-3.9% increase in pial arteriolar diameter in the hindlimb sensory cortex under control conditions. Intravenous administration of caffeine at the lowest dose studied (5 mg/kg) had no effect on either resting arteriolar diameter or SNS-induced vasodilatation. However, at higher doses (10, 20, 30, and 40 mg/kg, intravenously), caffeine significantly (P < 0.05; n = 6) attenuated both resting diameter and cerebral blood flow (CBF) responses to somatosensory stimulation. Intravenous administration of theophylline (10, 20, and 40 mg/kg), another adenosine receptor antagonist, also significantly reduced SNS-induced vasodilatation in a dose-dependent manner. Hypercarbic vasodilatation was unaffected by either caffeine or theophylline. The results of the present study show that caffeine significantly reduces cerebrovascular responses to both adenosine and to somatosensory stimulation and supports a role of adenosine in the regulation of CBF during functional neuronal activity.

White matter injury due to experimental chronic cerebral hypoperfusion is associated with C5 deposition.

The C5 complement protein is a potent inflammatory mediator that has been implicated in the pathogenesis of both stroke and neurodegenerative disease. Microvascular failure is proposed as a potential mechanism of injury. Along these lines, this investigation examines the role of C5 in the setting of chronic cerebral hypoperfusion. Following experimental bilateral carotid artery stenosis, C5 protein deposition increases in the corpus callosum over thirty days (p<0.05). The time course is temporally consistent with the appearance of white matter injury. Concurrently, systemic serum C5 levels do not appear to differ between bilateral carotid artery stenosis and sham-operated mice, implicating a local cerebral process. Following bilateral carotid artery stenosis, C5 deficient mice demonstrate decreased white matter ischemia in the corpus callosum when compared to C5 sufficient controls (p<0.05). Further, the C5 deficient mice exhibit fewer reactive astrocytes and microglia (p<0.01). This study reveals that the C5 complement protein may play a critical role in mediating white matter injury through inflammation in the setting of chronic cerebral hypoperfusion.