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The use of intravenous (IV) acetaminophen (APAP) for fever has not been thoroughly studied in neurocritical care (NCC) patients, in whom a temperature of ≥38°C is associated with poor outcomes and treatment to normothermia is common practice. This retrospective study evaluated NCC patients admitted between May 1, 2012, and April 30, 2013, and received at least one dose of IV or oral (PO) APAP for a body temperature of ≥38°C. The primary aim of this study was to compare the reduction in body temperature (RIT) between IV and PO APAP, calculated as the change in temperature before and 0.5, 1, 2, 3, and 6 hours after administration. Descriptive statistics were used to assess use characteristics, and Kruskal-Wallis and Mann-Whitney

Pharmacologic interventions are commonly used to support rehabilitation efforts of patients with disorders of consciousness (DoC). The 2018 practice guidelines recommend amantadine in adults with traumatic DoC to promote functional recovery, though several other stimulants are used off-label in clinical practice and trials, such as methylphenidate, bromocriptine, levodopa, and zolpidem. Differences in the mechanisms of action, adverse effects, pharmacokinetics, and drug–drug interactions should be considered when selecting the best agent for each individual patient. Overall, pharmacologic stimulants may provide a safe and inexpensive pathway to increased functionality and participation in rehabilitation. This article provides a concise summary of scientific evidence supporting the use of pharmacologic therapies to stimulate recovery of consciousness in patients with DoC.

Levetiracetam is an antiseizure medication commonly used in neurocritical care(NCC) patients to prevent or treat seizures. Behavioral adverse events(BAE) have been reported to occur in approximately 10% of patients taking levetiracetam; however, the incidence of these BAEs in NCC patients is unknown. The objective of this study was to identify the incidence of levetiracetam-associated BAEs in NCC patients.Adult NCC patients admitted between November 1, 2014 and October 31, 2018 and diagnosed with traumatic brain injury(TBI), subarachnoid or intracerebral hemorrhage(SAH/ICH), or cerebral infarction(CI) were included in this study. Levetiracetam-associated BAEs were identified by: 1) agitation/restlessness, delirium, or anxiety; 2) administration of haloperidol, quetiapine, ziprasidone, olanzapine, or risperidone; 3) positive CAM-ICU and/or 4) implementation of physical restraints. Patients were considered to have a levetiracetam-associated BAE if one of these criteria were met while receiving levetiracetam.There were 965 patients included; 52% males with a median GCS of 13. Injury types included TBI (43.1%), ICH (21.8%), SAH (20.5%), and CI (14.6%). BAEs were identified in 46% of patients. Of these, 60% had documentation of agitation/restlessness, delirium, or anxiety while receiving levetiracetam, only 25% had a positive CAM-ICU, 13% had restraints ordered, and 42% received antipsychotics. Patients with TBI had the highest incidence of BAEs (52.4%). The median time to initiation of levetiracetam after hospital admission was 6.4 hours and BAEs occurred after 1.3 days of levetiracetam initiation.In this study, we found that almost half of our NCC population experienced levetiracetam associated BAEs which were mostly hyperactive in nature. We believe that the incidence of BAEs in our specific patient population cannot solely be attributed to ICU delirium given the lower risk of developing hyperactive delirium in ICU patients as compared to other subtypes. Therefore, monitoring and determination of the benefit versus risk in those experiencing BAEs is highly encouraged.

Stress-related mucosal bleeding (SRMB) occurs in approximately 2-4% of critically ill patients. Patients with aneurysmal subarachnoid hemorrhage (aSAH) have a (diffuse) space-occupying lesion, are critically ill, often require mechanical ventilation, and frequently receive anticoagulation or antiplatelet therapy after aneurysm embolization, all of which may be risk factors for SRMB. However, no studies have evaluated SRMB in patients with aSAH. Aims of the study were to determine the incidence of SRMB in aSAH patients, evaluate the effect of acid suppression on SRMB, and identify specific risk factors for SRMB.This was a multicenter, retrospective, observational study conducted across 17 centers. Each center reviewed up to 50 of the most recent cases of aSAH. Patients with length of stay (LOS) 48 h or active GI bleeding on admission were excluded. Variables related to demographics, aSAH severity, gastrointestinal (GI) bleeding, provision of SRMB prophylaxis, adverse events, intensive care unit (ICU), and hospital LOS were collected for the first 21 days of admission or until hospital discharge, whichever came first. Descriptive statistics were used to analyze the data. A multivariate logistic regression modeling was utilized to examine the relationship between specific risk factors and the incidence of clinically important GI bleeding in patients with aSAH.A total of 627 patients were included. The overall incidence of clinically important GI bleeding was 4.9%. Of the patients with clinically important GI bleeding, 19 (61%) received pharmacologic prophylaxis prior to evidence of GI bleeding, while 12 (39%) were not on pharmacologic prophylaxis at the onset of GI bleeding. Patients who received an acid suppressant agent were less likely to experience GI bleeding than patients who did not receive pharmacologic prophylaxis prior to evidence of bleeding (OR 0.39, 95% CI 0.18-0.83). The multivariate regression analysis identified any instance of elevated intracranial pressure, creatinine clearance 60 ml/min and the incidence of cerebral vasospasm as specific risk factors associated with GI bleeding. Cerebral vasospasm has not previously been described as a risk for GI bleeding (OR 2.5 95% CI 1.09-5.79).Clinically important GI bleeding occurred in 4.9% of patients with aSAH, similar to the general critical care population. Risk factors associated with GI bleeding were prolonged mechanical ventilation ( 48 h), creatinine clearance 60 ml/min, presence of coagulopathy, elevation of intracranial pressure, and cerebral vasospasm. Further prospective research is needed to confirm this observation within this patient population.

Background: Since the approval of the oral factor Xa inhibitors, there have been concerns regarding the ability to neutralize their anticoagulant effects after intracranial hemorrhage (ICH). Multiple guidelines suggest using prothrombin complex concentrates (PCCs) in these patients on the basis of research that includes a limited number of patients with ICH. Given this, we aimed to evaluate the safety and efficacy of PCCs for factor Xa inhibitor–related ICH in a large, multicenter cohort of patients. Methods: This was a multicenter, retrospective, observational cohort study of patients with apixaban- or rivaroxaban-related ICH who received PCCs between January 1, 2015, and March 1, 2019. The study had 2 primary analysis groups: safety and hemostatic efficacy. The safety analysis evaluated all patients meeting inclusion criteria for the occurrence of a thrombotic event, which were censored at hospital discharge or 30 days after PCC administration. Patients with intracerebral, subarachnoid, or subdural hemorrhages who had at least 1 follow-up image within 24 hours of PCC administration were assessed for hemostatic efficacy. The primary efficacy outcome was the percentage of patients with excellent or good hemostasis on the basis of the modified Sarode criteria. Secondary outcomes included an evaluation of in-hospital mortality, length of stay, infusion-related reactions, and thrombotic event occurrence during multiple predefined periods. Results: A total of 663 patients were included and assessed for safety outcomes. Of these, 433 patients met criteria for hemostatic efficacy evaluation. We observed excellent or good hemostasis in 354 patients (81.8% [95% CI, 77.9–85.2]). Twenty-five (3.8%) patients had a total of 26 thrombotic events, of which 22 occurred in the first 14 days after PCC administration. One patient had documentation of an infusion-related reaction. For the full cohort of patients, in-hospital mortality was 19.0%, and the median intensive care unit and hospital lengths of stay were 2.0 and 6.0 days, respectively. Conclusions: Administration of PCCs after apixaban- and rivaroxaban-related ICH provided a high rate of excellent or good hemostasis (81.8%) coupled with a 3.8% thrombosis rate. Randomized, controlled trials evaluating the clinical efficacy of PCCs in patients with factor Xa inhibitor–related ICH are needed.

Patients with neurological injuries have many complicating factors that may impact outcomes. This includes medications used to treat acute and chronic illnesses that also affect systemic and central vasoactivity and may complicate neurological testing and recovery. Unfortunately, there is a lack of data to help guide clinicians on the cerebrovascular effects of medications. Multimodality monitoring techniques are used for neurocritical care patients, including transcranial Doppler, cerebral blood flow, and intracranial pressure monitoring devices. Some medications may affect cerebral autoregulation and blood flow and cause abrupt hemodynamic changes. Comorbid conditions may also contribute to pharmacokinetic changes for certain medications, causing unwanted effects. The use of monitoring techniques can serve as a tool for determining therapeutic responses to pharmacologic treatments and may be useful for guiding therapy. This chapter will focus on how the use of neurosonographic devices may help guide medication management in neurocritical care patients.

Severe traumatic brain injury (TBI) is a major contributor to disability and mortality in the industrialized world. Outcomes of severe TBI are profoundly heterogeneous, complicating outcome prognostication. Several prognostic models have been validated for acute prediction of 6-month global outcomes following TBI (e.g., morbidity/mortality). In this preliminary observational prognostic study, we assess the utility of the International Mission on Prognosis and Analysis of Clinical Trials in TBI (IMPACT) Lab model in predicting longer term global and cognitive outcomes (7-10 years post injury) and the extent to which cerebrospinal fluid (CSF) biomarkers enhance outcome prediction.Very long-term global outcome was assessed in a total of 59 participants (41 of whom did not survive their injuries) using the Glasgow Outcome Scale-Extended and Disability Rating Scale. More detailed outcome information regarding cognitive functioning in daily life was collected from 18 participants surviving to 7-10 years post injury using the Cognitive Subscale of the Functional Independence Measure. A subset (n = 10) of these participants also completed performance-based cognitive testing (Digit Span Test) by telephone. The IMPACT lab model was applied to determine its prognostic value in relation to very long-term outcomes as well as the additive effects of acute CSF ubiquitin C-terminal hydrolase-L1 (UCH-L1) and microtubule associated protein 2 (MAP-2) concentrations.The IMPACT lab model discriminated favorable versus unfavorable 7- to 10-year outcome with an area under the receiver operating characteristic curve of 0.80. Higher IMPACT lab model risk scores predicted greater extent of very long-term morbidity (β = 0.488 p = 0.000) as well as reduced cognitive independence (β = - 0.515, p = 0.034). Acute elevations in UCH-L1 levels were also predictive of lesser independence in cognitive activities in daily life at very long-term follow-up (β = 0.286, p = 0.048). Addition of two CSF biomarkers significantly improved prediction of very long-term neuropsychological performance among survivors, with the overall model (including IMPACT lab score, UCH-L1, and MAP-2) explaining 89.6% of variance in cognitive performance 7-10 years post injury (p = 0.008). Higher acute UCH-L1 concentrations were predictive of poorer cognitive performance (β = - 0.496, p = 0.029), whereas higher acute MAP-2 concentrations demonstrated a strong cognitive protective effect (β = 0.679, p = 0.010).Although preliminary, results suggest that existing prognostic models, including models with incorporation of CSF markers, may be applied to predict outcome of severe TBI years after injury. Continued research is needed examining early predictors of longer-term outcomes following TBI to identify potential targets for clinical trials that could impact long-ranging functional and cognitive outcomes.

Time plays a major role in seizure evaluation and treatment. Acute repetitive seizures and status epilepticus are medical emergencies that require immediate assessment and treatment for optimal therapeutic response. Benzodiazepines are considered the first-line agent for rapid seizure control. Thus, various routes of administration of benzodiazepines have been studied to facilitate a quick, effective, and easy therapy administration. Choosing the right agent may vary based on the drug and route properties, patient’s environment, caregiver’s skills, and drug accessibility. The pharmacokinetic and pharmacodynamic aspects of benzodiazepines are essential in the decision-making process. Ultimately, agents and routes that give the highest bioavailability, fastest absorption, and a modest duration are preferred. In the outpatient setting, intranasal and buccal routes appear to be equally effective and more rapidly administered than rectal diazepam. On the other hand, in the inpatient setting, if available, the IV route is ideal for benzodiazepine administration to avoid any potential absorption delay. In this article, we will provide an overview and comparison of the various routes of benzodiazepine administration for acute control of repetitive seizures and status epilepticus.

Traumatic brain injury (TBI) is one of the leading public health problems in the USA and worldwide. It is the number one cause of death and disability in children and adults between ages 1-44. Despite efforts to prevent TBIs, the incidence continues to rise. Secondary brain injury occurs in the first hours and days after the initial impact and is the most effective target for intervention. Inflammatory processes and oxidative stress play an important role in the pathomechanism of TBI and are exacerbated by impaired endogenous defense mechanisms, including depletion of antioxidants. As a reducing agent, free radical scavenger, and co-factor in numerous biosynthetic reactions, ascorbic acid (AA, vitamin C) is an essential nutrient that rapidly becomes depleted in states of critical illness. The administration of high-dose intravenous (IV) AA has demonstrated benefits in numerous preclinical models in the areas of trauma, critical care, wound healing, and hematology. A safe and inexpensive treatment, high-dose IV AA administration gained recent attention in studies demonstrating an associated mortality reduction in septic shock patients. High-quality data on the effects of high-dose IV AA on TBI are lacking. Historic data in a small number of patients demonstrate acute and profound AA deficiency in patients with central nervous system pathology, particularly TBI, and a strong correlation between low AA concentrations and poor outcomes. While replenishing deficient AA stores in TBI patients should improve the brain's ability to tolerate oxidative stress, high-dose IV AA may prove an effective strategy to prevent or mitigate secondary brain injury due to its ability to impede lipid peroxidation, scavenge reactive oxygen species, suppress inflammatory mediators, stabilize the endothelium, and reduce brain edema. The existing preclinical data and limited clinical data suggest that high-dose IV AA may be effective in lowering oxidative stress and decreasing cerebral edema. Whether this translates into improved clinical outcomes will depend on identifying the ideal target patient population and possible treatment combinations, factors that need to be evaluated in future clinical studies. With its excellent safety profile and low cost, high-dose IV AA is ready to be evaluated in the early treatment of TBI patients to mitigate secondary brain injury and improve outcomes.

Patients undergoing neuroendovascular procedures such as cerebral aneurysm coiling and intracranial stent deployment are frequently treated with antiplatelet agents to prevent thrombotic complications. The combination of aspirin and a P2Y12 inhibitor such as clopidogrel is often initiated days before elective procedures or as loading doses for emergent procedures; however, some patients may still experience thrombotic complications. Patients identified as clopidogrel hyporesponders are more likely to experience poor outcomes and may require changes to their regimens. Historically, high-dose clopidogrel regimens were used in response to subtherapeutic results of platelet function assays and point-of-care testing despite limited supporting data. Recently, more data have emerged using alternative P2Y12 inhibitors such as prasugrel and ticagrelor. Dosing for neuroendovascular conditions is often extrapolated from the cardiac literature, although outcomes in cardiac patients may not be relevant to neurologic patients, making prophylactic treatment recommendations challenging for these patients. This review summarizes the literature for antiplatelet prophylaxis in patients undergoing neuroendovascular device placement, focusing on alternative regimens for clopidogrel hyporesponders.

Central nervous system (CNS) infections are particularly prevalent in the adult neurocritical care patient population and are associated with significant morbidity and mortality. Factors relevant to the nature of CNS infections pose significant challenges to clinicians treating afflicted patients. Intraventricular (IVT) administration of antibiotics may offer several benefits over systemic therapy; however, the outcomes and current practices of such treatments are poorly described in the literature. To describe current practices and outcomes of patients receiving intraventricular antibiotic treatment for CNS infections in neurological intensive care units of academic medical centers nationwide. A retrospective cohort study was conducted on patients admitted to intensive care units who received IVT antibiotic treatment at participating centers in the USA between January 01, 2003, and December 31, 2013. Clinical and laboratory parameters, microbiology, surgical and antimicrobial management, and treatment outcomes were collected and described. Of the 105 patients included, all received systemic antimicrobial therapy along with at least one dose of IVT antimicrobial agents. Intraventricular vancomycin was used in 52.4% of patients. The average dose was 12.2 mg/day for a median duration of 5 days. Intraventricular aminoglycosides were used in 47.5% of the patients, either alone or in combination with IVT vancomycin. The average dose of gentamicin/tobramycin was 6.7 mg/day with a median duration of 6 days. Overall mortality was 18.1%. Cerebrospinal fluid (CSF) culture sterilization occurred in 88.4% of the patients with a rate of recurrence or persistence of positive cultures of 9.5%. Intraventricular antimicrobial agents resulted in a high CSF sterilization rate. Contemporary use of this route typically results in a treatment duration of less than a week. Prospective studies are needed to establish the optimal patient population, as well as the efficacy and safety of this route of administration.

Pharmacological management of intracerebral hemorrhage in adult patients over 65 years of age requires special considerations due to differing clinical presentations, underlying organ dysfunction, and more complex medical histories and medication profiles. A literature review of articles focusing on the age-specific pharmacological management of intracerebral hemorrhage was conducted. Treatment approaches and clinical outcomes specific to older adults were evaluated and therapeutic considerations for this population are summarized. Older adults were commonly included in trials regarding reversal of anticoagulants and antiplatelet agents and these results are generalizable to older adults. Underlying organ dysfunction should frequently be considered throughout the treatment of intracerebral hemorrhage in older adults. Older adults with intracerebral hemorrhage should be managed similarly to younger adult patients; however, consideration of age-related comorbidities and physiological differences is critically important for optimizing patient care.

Status epilepticus is a neurological emergency with an outcome that is highly associated with the initial pharmacotherapy management that must be administered in a timely fashion. Beyond first-line therapy of status epilepticus, treatment is not guided by robust evidence. Optimal pharmacotherapy selection for individual patients is essential in the management of seizures and status epilepticus with careful evaluation of pharmacokinetic and pharmacodynamic factors. With the addition of newer antiseizure agents to the market, understanding their role in the management of status epilepticus is critical. Etiology-guided therapy should be considered in certain patients with drug-induced seizures, alcohol withdrawal, or autoimmune encephalitis. Some patient populations warrant special consideration, such as pediatric, pregnant, elderly, and the critically ill. Seizure prophylaxis is indicated in select patients with acute neurological injury and should be limited to the acute postinjury period.

Purpose of review This review focuses on recent relevant literature that examines the reversal of direct oral anticoagulants (DOACs) in patients with intracranial hemorrhage (ICH). The aim of this review is to provide an insightful description of available reversal agents and their clinical utility. Recent findings Increases in prescribing of DOACs has led to the introduction of drug-specific reversal agents. The clinical trials that evaluated these agents did not include a comparator arm making it difficult to determine if they are clinically superior to nonspecific reversal agents. Summary Numerous options for reversal of DOAC-associated ICH are currently available. Recent clinical trials have demonstrated drug-specific reversal agents are effective in this setting, but additional research is needed to determine whether these agents should be routinely preferred over nonspecific reversal agents.

Approximately 795 000 people in the United States experience stroke annually, with 610 000 initial and 185 000 recurrent events.1 The majority of these events (87%) are ischemic in nature.1 Stroke ranks fifth among all causes of death in the United States, although rates of mortality due to stroke have decreased overall by 2.3% between 2005 and 2015.1 Given the aging population of the United States, it is likely that the incidence of stroke will continue to rise. The management of patients with acute ischemic stroke (AIS) continues to evolve, with the recent publication of several trials evaluating fibrinolytic, interventional, and medical management of critically ill patients presenting with occlusions of the cerebral vasculature. Recently published American Heart Association and American Stroke Association (AHA/ASA) guidelines on the early management of these patients have provided updated recommendations for a variety of pharmacotherapeutic interventions for the treatment of AIS.2 The primary focus of this article will be the early pharmacologic management of patients presenting with AIS. Pharmacists should be aware of medical and surgical interventions available to patients presenting with AIS to effectively manage and monitor therapy.

Trauma is a major problem in the United States. Mortality from trauma is the number one cause of death under the age of 45 in the United States and is the third leading cause of death for all age groups. There are approximately 200,000 deaths per year due to trauma in the United States at a cost of over $671 billion in combined healthcare costs and lost productivity. Unsurprisingly, trauma accounts for approximately 30% of all life-years lost in the United States. Due to immense development of trauma systems, a large majority of trauma patients survive the injury, but then go on to die from complications arising from the injury. These complications are marked by early and significant metabolic changes accompanied by inflammatory responses that lead to progressive organ failure and, ultimately, death. Early resuscitative and surgical interventions followed by close monitoring to identify and rescue treatment failures are key to successful outcomes. Currently, the adequacy of resuscitation is measured using vital signs, noninvasive methods such as bedside echocardiography or stroke volume variation, and other laboratory endpoints of resuscitation, such as lactate and base deficit. However, these methods may be too crude to understand cellular and subcellular changes that may be occurring in trauma patients. Better diagnostic and therapeutic markers are needed to assess the adequacy of interventions and monitor responses at a cellular and subcellular level and inform clinical decision-making before complications are clinically apparent. The developing field of metabolomics holds great promise in the identification and application of biochemical markers toward the clinical decision-making process.

Currently, a lack of published literature exists regarding the use of clevidipine in the neuroscience population. This agent may be preferred in some patients because of its short half-life, potentially leading to more narrow blood pressure (BP) control in comparison with other agents. The purpose of this study was to compare the difference in time to achieve target systolic blood pressure (SBP) goals with clevidipine versus nicardipine infusions in patients admitted to the neuroscience intensive care unit (NSICU) at our institution. A retrospective review was performed on patients receiving clevidipine or nicardipine infusions while in the NSICU between July 1, 2011 and June 30, 2014. Patients were matched based on indication for BP lowering and target SBP. Primary endpoints included time to target SBP and percentage of time within target BP range. Of the 57 patients included in the study, the median time to target SBP was 30 min in the clevidipine group and 46 min in the nicardipine group (p = 0.13). The percentage of time spent within target BP range was 79 versus 78% (p = 0.64). Clevidipine administration resulted in significantly less volume administered per patient versus nicardipine (530 vs. 1254 mL, p = 0.02). There were no statistically significant differences in acute BP management between the two agents; however, there was a trend toward shorter time to target and significantly less volume administered in the clevidipine group. Either agent should be considered a viable option in a NSICU population.

Traumatic brain injury (TBI) is one of the leading public health problems in the USA and worldwide. It is the number one cause of death and disability in children and adults between ages 1-44. Despite efforts to prevent TBIs, the incidence continues to rise. Secondary brain injury occurs in the first hours and days after the initial impact and is the most effective target for intervention. Inflammatory processes and oxidative stress play an important role in the pathomechanism of TBI and are exacerbated by impaired endogenous defense mechanisms, including depletion of antioxidants. As a reducing agent, free radical scavenger, and co-factor in numerous biosynthetic reactions, ascorbic acid (AA, vitamin C) is an essential nutrient that rapidly becomes depleted in states of critical illness. The administration of high-dose intravenous (IV) AA has demonstrated benefits in numerous preclinical models in the areas of trauma, critical care, wound healing, and hematology. A safe and inexpensive treatment, high-dose IV AA administration gained recent attention in studies demonstrating an associated mortality reduction in septic shock patients. High-quality data on the effects of high-dose IV AA on TBI are lacking. Historic data in a small number of patients demonstrate acute and profound AA deficiency in patients with central nervous system pathology, particularly TBI, and a strong correlation between low AA concentrations and poor outcomes. While replenishing deficient AA stores in TBI patients should improve the brain's ability to tolerate oxidative stress, high-dose IV AA may prove an effective strategy to prevent or mitigate secondary brain injury due to its ability to impede lipid peroxidation, scavenge reactive oxygen species, suppress inflammatory mediators, stabilize the endothelium, and reduce brain edema. The existing preclinical data and limited clinical data suggest that high-dose IV AA may be effective in lowering oxidative stress and decreasing cerebral edema. Whether this translates into improved clinical outcomes will depend on identifying the ideal target patient population and possible treatment combinations, factors that need to be evaluated in future clinical studies. With its excellent safety profile and low cost, high-dose IV AA is ready to be evaluated in the early treatment of TBI patients to mitigate secondary brain injury and improve outcomes.

The diagnosis and management of seizures in the critically ill patient can sometimes present a unique challenge for practitioners due to lack of exposure and complex patient comorbidities. The reported incidence varies between 8% and 34% of critically ill patients, with many patients often showing no overt clinical signs of seizures. Outcomes in patients with unidentified seizure activity tend to be poor, and mortality significantly increases in those who have seizure activity longer than 30 min. Prompt diagnosis and provision of medical therapy are crucial in order to attain successful seizure termination and prevent poor outcomes. In this article, we review the epidemiology and pathophysiology of seizures in the critically ill, various seizure monitoring modalities, and recommended medical therapy.

Providers encounter unique challenges in the sedation of neurocritically ill patients. Sedative selection requires thoughtful consideration of the risks and benefits of specific pharmacologic agents. Sedative agents should provide enough sedation to maintain patient comfort while allowing frequent and accurate neurologic examinations during sedation interruption. The ideal sedative agent is patient-specific, taking into account the pharmacokinetic and pharmacodynamic characteristics of the drug and patient, drug interactions, and comorbid conditions. While analgosedation is preferred by critical care guidelines, more traditional sedatives that have been used for the routine sedation of brain-injured patients include propofol, dexmedetomidine, benzodiazepines, and ketamine. Butyrophenones such as haloperidol have a limited place in the management of neurocritical patients. A working knowledge of available sedatives and significant neurocritical care sedative concepts are essential for ensuring safety while optimizing patient outcomes.

Central nervous system (CNS) infections are particularly prevalent in the adult neurocritical care patient population and are associated with significant morbidity and mortality. Factors relevant to the nature of CNS infections pose significant challenges to clinicians treating afflicted patients. Intraventricular (IVT) administration of antibiotics may offer several benefits over systemic therapy; however, the outcomes and current practices of such treatments are poorly described in the literature.To describe current practices and outcomes of patients receiving intraventricular antibiotic treatment for CNS infections in neurological intensive care units of academic medical centers nationwide.A retrospective cohort study was conducted on patients admitted to intensive care units who received IVT antibiotic treatment at participating centers in the USA between January 01, 2003, and December 31, 2013. Clinical and laboratory parameters, microbiology, surgical and antimicrobial management, and treatment outcomes were collected and described.Of the 105 patients included, all received systemic antimicrobial therapy along with at least one dose of IVT antimicrobial agents. Intraventricular vancomycin was used in 52.4% of patients. The average dose was 12.2 mg/day for a median duration of 5 days. Intraventricular aminoglycosides were used in 47.5% of the patients, either alone or in combination with IVT vancomycin. The average dose of gentamicin/tobramycin was 6.7 mg/day with a median duration of 6 days. Overall mortality was 18.1%. Cerebrospinal fluid (CSF) culture sterilization occurred in 88.4% of the patients with a rate of recurrence or persistence of positive cultures of 9.5%.Intraventricular antimicrobial agents resulted in a high CSF sterilization rate. Contemporary use of this route typically results in a treatment duration of less than a week. Prospective studies are needed to establish the optimal patient population, as well as the efficacy and safety of this route of administration.

Essentials Platelets in trauma-induced coagulopathy (TIC) are impaired, but the mechanism is not known. We performed comprehensive longitudinal platelet function testing in trauma patient samples. Platelets in TIC are widely impaired early after injury, but platelet activatability is intact. This suggests a mechanism of transient platelet cytoskeletal/integrin dysfunction during TIC. SUMMARY: Background Trauma-induced coagulopathy (TIC) is a common and deadly bleeding disorder. Platelet dysfunction is present during TIC, but its mechanisms remain unclear. Platelets are currently thought to become "exhausted," a state in which they have released their granule contents and can no longer aggregate or contract. Methods This prospective observational cohort study tested the hypothesis that platelet exhaustion is present during TIC and characterized the early time course of platelet dysfunction. Blood was collected from 95 adult trauma patients at a Level I trauma center at time of Emergency Department arrival and several time points over 72 h. Platelet activation state and function were characterized using CD62P (P-selectin) and PAC-1 surface membrane staining, platelet function analyzer (PFA-100), aggregometry, viscoelastic platelet mapping, and, to test for exhaustion, their ability to express CD62P after ex vivo adenosine diphosphate (ADP) agonism. Platelet function was compared between patients with and without TIC, defined by prothrombin time ≥18 s. Results Platelets in TIC showed no initial increase in their level of surface activation markers or impairment of their capacity to express CD62P in response to ADP stimulation. However, TIC platelets were impaired in nearly all functional assays, spanning adhesion, aggregation, and contraction. These effects largely remained after controlling for platelet count and fibrinogen concentration and resolved after 8 h. Conclusion The TIC platelets exhibit early impairment of adhesion, aggregation, and contraction with retained alpha granule secretion ability, suggesting a specific mechanism of cytoskeletal or integrin dysfunction that is not a result of more general platelet exhaustion.

In the neurologically injured patient, it is extremely important to optimize and individualize pharmacotherapeutic strategies to improve patient outcomes. Therefore, understanding the pharmacology, pharmacokinetics, and pharmacodynamics of medications used in neurocritical care patients, as well as the impact of the acute illness and comorbid states on these characteristics, is essential. This chapter provides practical information on medications and treatment strategies commonly used in patients with neurological injuries, including recommendations to optimize therapeutic strategies and avoid unwanted adverse effects and drug interactions. Specific medications and treatment strategies discussed include hyperosmolar therapy with mannitol and hypertonic saline for management of intracranial pressure, anticonvulsant treatments for status epilepticus and refractory status epilepticus, reversal strategies for oral anticoagulant agents, , shivering control agents for use during therapeutic temperature management and induced hypothermia, and vasoactive therapies to maintain hemodynamic control. The pharmacology, pharmacokinetic and pharmacodynamic characteristics, and clinical pearls of these commonly used treatments in neurocritical care patients will also be highlighted.

The appropriate use of medications during Emergency Neurological Life Support (ENLS) is essential to optimize patient care. Important considerations when choosing the appropriate agent include the patient's organ function and medication allergies, potential adverse drug effects, drug interactions, and critical illness and aging pathophysiologic changes. Critical medications used during ENLS include hyperosmolar therapy, anticonvulsants, antithrombotics, anticoagulant reversal and hemostatic agents, anti-shivering agents, neuromuscular blockers, antihypertensive agents, sedatives, vasopressors and inotropes, and antimicrobials. This article focuses on the important pharmacokinetic and pharmacodynamics characteristics, advantages and disadvantages, and clinical pearls of these therapies, providing practitioners with essential drug information to optimize pharmacotherapy in acutely ill neurocritical care patients.

This study compared cerebrospinal fluid (CSF) levels of microtubule-associated protein 2 (MAP-2) from adult patients with severe traumatic brain injury (TBI) with uninjured controls over 10 days, and examined the relationship between MAP-2 concentrations and acute clinical and radiologic measures of injury severity along with mortality at 2 weeks and over 6 months. This prospective study, conducted at two Level 1 trauma centers, enrolled adults with severe TBI (Glasgow Coma Scale [GCS] score ≤8) requiring a ventriculostomy, as well as controls. Ventricular CSF was sampled from each patient at 6, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 h following TBI and analyzed via enzyme-linked immunosorbent assay for MAP-2 (ng/mL). Injury severity was assessed by the GCS score, Marshall Classification on computed tomography (CT), Rotterdam CT score, and mortality. There were 151 patients enrolled—130 TBI and 21 control patients. MAP-2 was detectable within 6 h of injury and was significantly elevated compared with controls (p

Traumatic brain injury (TBI) is associated with both hypercoagulable and hypocoagulable states; however, the causes of each are still not well understood. These coagulopathies are further complicated by TBI patients who are injured while on antithrombotic medications. This chapter compiles data from the most recent peer-reviewed publications and drug references on the pathophysiology of coagulopathy in TBI patients, predictors of outcomes, the impact of preinjury antithrombotic medication use, reversal agents, monitoring parameters, and when to restart antithrombotic medications post-TBI. Direct-acting oral anticoagulants (DOACs) and their impact on TBI management are discussed in detail.

Midline shift following severe traumatic brain injury (sTBI) detected on computed tomography (CT) scans is an established predictor of poor outcome. We hypothesized that lateral ventricular volume (LVV) asymmetry is an earlier sign of developing asymmetric intracranial pathology than midline shift. This retrospective analysis was performed on data from 84 adults with blunt sTBI requiring a ventriculostomy who presented to a Level I trauma center. Seventy-six patients underwent serial CTs within 3 h and an average of three scans within the first 10 d of sTBI. Left and right LVVs were quantified by computer-assisted manual volumetric measurements. LVV ratios (LVR) were determined on the admission CT to evaluate ventricular asymmetry. The relationship between the admission LVR value and subsequent midline shift development was tested using receiver operating characteristic (ROC) analysis, and odds ratio (OR) and relative risk tests. Sixty patients had no >5 mm midline shift on the initial admission scan. Of these, 15 patients developed it subsequently (16 patients already had >5 mm midline shift on admission scans). For >5 mm midline shift development, admission LVR of >1.67 was shown to have a sensitivity of 73.3% and a specificity of 73.3% (area under the curve=0.782; p1.67 as exposure yielded an OR of 7.56 (p

Anticoagulation, fibrinogen consumption, fibrinolytic activation, and platelet dysfunction all interact to produce different clot formation responses after trauma. However, the relative contributions of these coagulation components to overall clot formation remain poorly defined. We examined for sources of heterogeneity in clot formation responses after trauma.Blood was sampled in the emergency department from patients meeting trauma team activation criteria at an urban trauma center. Plasma prothrombin time of 18 s or longer was used to define traumatic coagulopathy. Mean kaolin-activated thrombelastography (TEG) parameters were calculated and tested for heterogeneity using analysis of means. Discriminant analysis and forward stepwise variable selection with linear regression were used to determine if prothrombin time, fibrinogen, platelet contractile force (PCF), and D-dimer concentration, representing key mechanistic components of coagulopathy, each contribute to heterogeneous TEG responses after trauma.Of 95 subjects, 16% met criteria for coagulopathy. Coagulopathic subjects were more severely injured with greater shock and received more blood products in the first 8 h compared with noncoagulopathic subjects. Mean (SD) TEG maximal amplitude (MA) was significantly decreased in the coagulopathic group (57.5 [SD, 4.7] mm vs. 62.7 [SD, 4.7], t test P0.001). The MA also exceeded the ANOM predicted upper decision limit for the noncoagulopathic group and the lower decision limit for the coagulopathic group at α = 0.05, suggesting significant heterogeneity from the overall cohort mean. Fibrinogen and PCF best discriminated TEG MA using discriminant analysis. Fibrinogen, PCF, and D-dimer were primary covariates for TEG MA using regression analysis.Heterogeneity in TEG-based clot formation in emergency department trauma patients was linked to changes in MA. Individual parameters representing fibrin polymerization, PCFs, and fibrinolysis were primarily associated with TEG MA after trauma and should be the focus of early hemostatic therapies.

A variety of technologies have been developed to assist decision-making during the management of patients with acute brain injury who require intensive care. A large body of research has been generated describing these various technologies. The Neurocritical Care Society (NCS) in collaboration with the European Society of Intensive Care Medicine (ESICM), the Society for Critical Care Medicine (SCCM), and the Latin America Brain Injury Consortium (LABIC) organized an international, multidisciplinary consensus conference to perform a systematic review of the published literature to help develop evidence-based practice recommendations on bedside physiologic monitoring. This supplement contains a Consensus Summary Statement with recommendations and individual topic reviews on physiologic processes important in the care of acute brain injury. In this article we provide the evidentiary tables for select topics including systemic hemodynamics, intracranial pressure, brain and systemic oxygenation, EEG, brain metabolism, biomarkers, processes of care and monitoring in emerging economies to provide the clinician ready access to evidence that supports recommendations about neuromonitoring.

Adverse drug effects often complicate the care of critically ill patients. Therefore, each patient's medical history, maintenance medication, and new therapies administered in the intensive care unit must be evaluated to prevent unwanted neurologic adverse effects. Optimization of pharmacotherapy in critically ill patients can be achieved by considering the need to reinitiate home medications, and avoiding drugs that can decrease the seizure threshold, increase sedation and cognitive deficits, induce delirium, increase intracranial pressure, or induce fever. Avoiding medication-induced neurologic adverse effects is essential in critically ill patients, especially those with neurologic injury.

The appropriate use of medications during Emergency Neurological Life Support (ENLS) is essential to optimize patient care. Important considerations when choosing the appropriate agent include the patient’s organ function and medication allergies, potential adverse drug effects, drug interactions and critical illness and aging pathophysiologic changes. Critical medications used during ENLS include hyperosmolar therapy, anticonvulsants, antithrombotics, anticoagulant reversal and hemostatic agents, anti-shivering agents, neuromuscular blockers, antihypertensive agents, sedatives, vasopressors and inotropes, and antimicrobials. This article focuses on the important pharmacokinetic and pharmacodynamics characteristics, advantages and disadvantages and clinical pearls of these therapies, providing practitioners with essential drug information to optimize pharmacotherapy in acutely ill neurocritical care patients.