Headache Management in the Neuroscience Intensive Care Unit.

PURPOSE OF REVIEW: Headache is a common symptom in the Neuroscience Intensive Care Unit (NeuroICU). Our goal is to provide an overview of approaches to headache management for common neurocritical care conditions. RECENT FINDINGS: Headache disorders afflict nearly half of patients admitted to the NICU. Commonly encountered disorders featuring headache include cerebrovascular disease, trauma, and intracranial infection. Approaches to pain are highly variable, and multimodal pain regimens are commonly employed. The overall body of evidence supporting therapeutic strategies to manage headache in the critical care setting is slim, and pain control remains suboptimal in many cases with persistent reliance on opioids. Headache is a complex, frequently occurring phenomenon in the NeuroICU care setting. At present, literature on evidence-based practice for management of headache in the critical care setting remains scarce, and despite multimodal approaches, reliance on opioids is commonplace.

Major Publications in the Critical Care Pharmacotherapy Literature: 2022.

OBJECTIVES: A number of trials related to critical care pharmacotherapy were published in 2022. We aimed to summarize the most influential publications related to the pharmacotherapeutic care of critically ill patients in 2022. DATA SOURCES: PubMed/Medical Literature Analysis and Retrieval System Online and the Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update. STUDY SELECTION: Randomized controlled trials, prospective studies, or systematic review/meta-analyses of adult critically ill patients assessing a pharmacotherapeutic intervention and reporting clinical endpoints published between January 1, 2022, and December 31, 2022, were included in this article. DATA EXTRACTION: Articles from a systematic search and the Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update were included and stratified into clinical domains based upon consistent themes. Consensus was obtained on the most influential publication within each clinical domain utilizing an a priori defined three-round modified Delphi process with the following considerations: 1) overall contribution to scientific knowledge and 2) novelty to the literature. DATA SYNTHESIS: The systematic search and Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update yielded a total of 704 articles, of which 660 were excluded. The remaining 44 articles were stratified into the following clinical domains: emergency/neurology, cardiovascular, gastroenterology/fluids/nutrition, hematology, infectious diseases/immunomodulation, and endocrine/metabolic. The final article selected from each clinical domain was summarized following a three-round modified Delphi process and included three randomized controlled trials and three systematic review/meta-analyses. Article topics summarized included dexmedetomidine versus other sedatives during mechanical ventilation, beta-blocker treatment in the critically ill, restriction of IV fluids in septic shock, venous thromboembolism prophylaxis in critically ill adults, duration of antibiotic therapy for Pseudomonas aeruginosa ventilator-associated pneumonia, and low-dose methylprednisolone treatment in severe community-acquired pneumonia. CONCLUSIONS: This concise review provides a perspective on articles published in 2022 that are relevant to the pharmacotherapeutic care of critically ill patients and their potential impact on clinical practice.

Caring for two in the ICU: Pharmacologic management of pregnancy-related complications.

Maternal mortality continues to be an issue globally despite advances in technology and pharmacotherapy. Pregnancy can lead to complications that necessitate immediate action to prevent severe morbidity and mortality. Patients may need escalation to the ICU setting for close monitoring and administration of advanced therapies not available elsewhere. Obstetric emergencies are rare but high-stakes events that require clinicians to have prompt identification and management. The purpose of this review is to describe complications of pregnancy and provide a focused resource of pharmacotherapy considerations that clinicians may encounter. For each disease state, the epidemiology, pathophysiology, and management are summarized. Brief descriptions of non-pharmacological (e.g., cesarean or vaginal delivery of the baby) interventions are provided. Mainstays of pharmacotherapy highlighted include oxytocin for obstetric hemorrhage, methotrexate for ectopic pregnancy, magnesium and antihypertensive agents for preeclampsia and eclampsia, eculizumab for atypical hemolytic uremic syndrome, corticosteroids, and immunosuppressive agents for thrombotic thrombocytopenic purpura, diuretics, metoprolol, and anticoagulation for peripartum cardiomyopathy, and pulmonary vasodilators for amniotic fluid embolism.

Caring for two in the ICU: Pharmacotherapy in the critically ill pregnant patient.

Safe and thoughtful medication management of pregnant patients requiring intensive care unit (ICU) level of care is key to optimizing outcomes for both mother and fetus. Pregnancy induces physiologic alterations that closely mirror the changes expected in a critically ill patient. These changes can be predictable depending on the gestational age and trimester and will directly impact the pharmacokinetic profile of medications commonly used in the ICU; examples include decreased gastric emptying, increased blood and plasma volume, increased glomerular filtration, and increased cardiac output. When pregnant patients require ICU care, the resulting impact on drug absorption, distribution, metabolism, and elimination can be difficult to predict. In addition, there are many nuances of medication metabolism and interface with the placental barrier that should be considered when selecting pharmacotherapy for the pregnant patient. Critical care clinicians need to be aware of medication interactions with the placenta and weigh the risk versus benefit profile of medication use in this patient population. Obstetric critical care admissions have increased over the years, especially during the coronavirus waves. Therefore, understanding the interplay between pregnancy and critical illness to optimize pharmacotherapy selection is crucial to improving health outcomes of mother and fetus. This review highlights pharmacotherapy considerations in the pregnant ICU patient for the following topics: physiologic alterations, categorizing medication risk, supportive care, sepsis, cardiogenic shock, acute respiratory distress syndrome, and venous thromboembolism.

Temperature Control After Cardiac Arrest: A Narrative Review.

Cardiac arrest (CA) is a critical public health issue affecting more than half a million Americans annually. The main determinant of outcome post-CA is hypoxic-ischemic brain injury (HIBI), and temperature control is currently the only evidence-based, guideline-recommended intervention targeting secondary brain injury. Temperature control is a key component of a post-CA care bundle; however, conflicting evidence challenges its wide implementation across the vastly heterogeneous population of CA survivors. Here, we critically appraise the available literature on temperature control in HIBI, detail how the evidence has been integrated into clinical practice, and highlight the complications associated with its use and the timing of neuroprognostication after CA. Future clinical trials evaluating different temperature targets, rates of rewarming, duration of cooling, and identifying which patient phenotype benefits from different temperature control methods are needed to address these prevailing knowledge gaps.

Acute Headache Management for Patients with Subarachnoid Hemorrhage: An International Survey of Health Care Providers.

BACKGROUND: Severe headaches are common after subarachnoid hemorrhage. Guidelines recommend treatment with acetaminophen and opioids, but patient data show that headaches often persist despite multimodal treatment approaches. Considering an overall slim body of data for a common complaint affecting patients with SAH during their intensive care stay, we set out to assess practice patterns in headache management among clinicians who treat patients with SAH. METHODS: We conducted an international cross-sectional study through a 37-question Web-based survey distributed to members of five professional societies relevant to intensive and neurocritical care from November 2021 to January 2022. Responses were characterized through descriptive analyses. Fisher's exact test was used to test associations. RESULTS: Of 516 respondents, 329 of 497 (66%) were from North America and 121 of 497 (24%) from Europe. Of 435 respondents, 379 (87%) reported headache as a major management concern for patients with SAH. Intensive care teams were primarily responsible for analgesia during hospitalization (249 of 435, 57%), whereas responsibility shifted to neurosurgery at discharge (233 of 501, 47%). Most used medications were acetaminophen (90%), opioids (66%), corticosteroids (28%), and antiseizure medications (28%). Opioids or medication combinations including opioids were most frequently perceived as most effective by 169 of 433 respondents (39%, predominantly intensivists), followed by corticosteroids or combinations with corticosteroids (96 of 433, 22%, predominantly neurologists). Of medications prescribed at discharge, acetaminophen was most common (303 of 381, 80%), followed by opioids (175 of 381, 46%) and antiseizure medications (173 of 381, 45%). Opioids during hospitalization were significantly more prescribed by intensivists, by providers managing higher numbers of patients with SAH, and in Europe. At discharge, opioids were more frequently prescribed in North America. Of 435 respondents, 299 (69%) indicated no change in prescription practice of opioids with the opioid crisis. Additional differences in prescription patterns between continents and providers and while inpatient versus at discharge were found. CONCLUSIONS: Post-SAH headache in the intensive care setting is a major clinical concern. Analgesia heavily relies on opioids both in use and in perception of efficacy, with no reported change in prescription patterns for opioids for most providers despite the significant drawbacks of opioids. Responsibility for analgesia shifts between hospitalization and discharge. International and provider-related differences are evident. Novel treatment strategies and alignment of prescription between providers are urgently needed.

Electrolyte considerations in targeted temperature management.

PURPOSE: Targeted temperature management (TTM), including normothermia and therapeutic hypothermia, is used primarily for comatose patients with return of spontaneous circulation after cardiac arrest or following neurological injury. Despite the potential benefits of TTM, risks associated with physiological alterations, including electrolyte shifts, may require intervention. SUMMARY: This review describes the normal physiological balance of electrolytes and temperature-related alterations as well as the impact of derangements on patient outcomes, providing general recommendations for repletion and monitoring of key electrolytes, including potassium, phosphate, and magnesium. CONCLUSION: Frequent monitoring and consideration of patient variables such as renal function and other risk factors for adverse effects are important areas of awareness for clinicians caring for patients undergoing TTM.

Targeting the gut microbiome in the management of sepsis-associated encephalopathy.

Brain injury resulting from sepsis, or sepsis-associated encephalopathy (SAE), occurs due to impaired end-organ perfusion, dysregulated inflammation affecting the central nervous system (CNS), blood-brain barrier (BBB) disruption, mitochondrial dysfunction, oxidative stress, accumulation of toxic neuropeptides and impaired toxin clearance secondary to sepsis-induced hepatic and renal dysfunction. The gut microbiome becomes pathologically altered in sepsis, which likely contributes to the pathogenesis of SAE. Herein, we review the literature detailing dysregulation of microbiota-gut-brain axis (MGBA) in SAE and highlight potential therapeutic strategies to modulate the gut microbiome to mitigate sepsis-induced brain injury.

Meropenem Population Pharmacokinetics and Simulations in Plasma, Cerebrospinal Fluid, and Brain Tissue.

Meropenem is a broad spectrum carbapenem used for the treatment of cerebral infections. There is a need for data describing meropenem pharmacokinetics (PK) in the brain tissue to optimize therapy in these infections. Here, we present a meropenem PK model in the central nervous system and simulate dosing regimens. This was a population PK analysis of a previously published prospective study of patients admitted to the neurointesive care unit between 2016 and 2019 who received 2 g of meropenem intravenously every 8 h. Meropenem concentration was determined in blood, cerebrospinal fluid (CSF), and brain microdialysate. Meropenem was described by a six-compartment model: two compartments in the blood, two in the CSF, and two in the brain tissue. Creatinine clearance and brain glucose were included as covariates. The median elimination rate constant was 1.26 h-1, the central plasma volume was 5.38 L, and the transfer rate constants from the blood to the CSF and from the blood to the brain were 0.001 h-1 and 0.02 h-1, respectively. In the first 24 h, meropenem 2 g, administered every 8 h via intermittent and extended infusions achieved good target attainment in the CSF and brain, but continuous infusion (CI) was better at steady-state. Administering a 3 g loading dose (LD) followed by 8 g CI was beneficial for early target attainment. In conclusion, a meropenem PK model was developed using blood, CSF, and brain microdialysate samples. An 8 g CI may be needed for good target attainment in the CSF and brain. Giving a LD prior to the CI improved the probability of early target attainment.

The Digital Classroom: How to Leverage Social Media for Infectious Diseases Education.

Social media (SoMe) platforms have been increasingly used by infectious diseases (ID) learners and educators in recent years. This trend has only accelerated with the changes brought to our educational spaces by the coronavirus disease 2019 pandemic. Given the increasingly diverse SoMe landscape, educators may find themselves struggling with how to effectively use these tools. In this Viewpoint we describe how to use SoMe platforms (e.g., Twitter, podcasts, and open-access online content portals) in medical education, highlight medical education theories supporting their use, and discuss how educators can engage with these learning tools effectively. We focus on how these platforms harness key principles of adult learning and provide a guide for educators in the effective use of SoMe tools in educating ID learners. Finally, we suggest how to effectively interact with and leverage these increasingly important digital platforms.

Severe headache trajectory following aneurysmal subarachnoid hemorrhage: the association with lower sodium levels.

BACKGROUND: A clinical hallmark of aneurysmal SAH (aSAH) is headache. Little is known about post-aSAH headache factors which may point to underlying mechanisms. In this study, we aimed to characterize the severity and trajectory of headaches in relation to clinical features of patients with aSAH. METHODS: This is a retrospective longitudinal study of adult patients admitted to an academic tertiary care center between 2012 and 2019 with aSAH who could verbalize pain scores. Factors recorded included demographics, aneurysm characteristics, analgesia, daily morning serum sodium concentration, and occurrence of vasospasm. Group-based trajectory modeling was used to identify headache pain trajectories, and clinical factors were compared between trajectories. RESULTS: Of 91 patients included in the analysis, mean age was 57 years and 20 (22%) were male. Headache score trajectories clustered into two groups: patients with mild-moderate and moderate-severe pain. Patients in the moderate-severe pain group were younger (P<0.05), received more opioid analgesia (P<0.001), and had lower sodium concentrations (P<0.001) than patients in the mild-moderate pain group. CONCLUSION: We identified two distinct post-aSAH headache pain trajectory cohorts and identified an association with age, analgesia, and sodium levels. Future prospective studies considering sodium homeostasis and volume status under standardized analgesic regimens are warranted.

Pharmacotherapy in Coronavirus Disease 2019 and Risk of Secondary Infections: A Single-Center Case Series and Narrative Review.

Since the onset of the coronavirus disease 2019 pandemic, immune modulators have been considered front-line candidates for the management of patients presenting with clinical symptoms secondary to severe acute respiratory syndrome coronavirus 2 infection. Although heavy emphasis has been placed on early clinical efficacy, we sought to evaluate the impact of pharmacologic approach to coronavirus disease 2019 within the ICU on secondary infections and clinical outcomes. DATA SOURCES: PubMed (inception to March 2021) database search and manual selection of bibliographies from selected articles. STUDY SELECTION AND DATA EXTRACTION: Articles relevant to coronavirus disease 2019, management of severe acute respiratory syndrome coronavirus 2-associated respiratory failure, and prevalence of secondary infections with pharmacotherapies were selected. The MeSH terms "COVID-19," "secondary infection," "SARS-CoV-2," "tocilizumab," and "corticosteroids" were used for article identification. Articles were narratively synthesized for this review. DATA SYNTHESIS: Current data surrounding the use of tocilizumab and/or corticosteroids for coronavirus disease 2019 management are limited given the short follow-up period and conflicting results between studies. Further complicating the understanding of immune modulator role is the lack of definitive understanding of clinical impact of the immune response in coronavirus disease 2019. CONCLUSIONS: Based on the current available literature, we suggest prolonged trials and follow-up intervals for those patients managed with immune modulating agents for the management of coronavirus disease 2019.

Pulmonary arterial hypertension in the emergency department: A focus on medication management.

Pulmonary arterial hypertension (PAH) is a chronic progressive incurable condition associated with a high degree of morbidity and mortality. With over five drug classes FDA approved in the last decade, the significant advancements in the pharmacologic management of PAH has improved long-term outcomes. Drug therapies have been developed to directly target the underlying pathogenesis of PAH including phosphodiesterase type-5 inhibitors (PDE-5i), endothelin-receptor antagonists (ERAs), guanylyl-cyclase inhibitors, prostacyclin analogues, and prostacyclin receptor agonists. Although these agents offer remarkable benefits, there are significant challenges with their use such as complexities in medication dosing, administration, and adverse effects. Given these consequences, PAH medications are classified as high-risk, and the transitions of care process to and from the hospital setting are a vulnerable area for medication errors in this population. Thus, it is crucial for the emergency department provider to appropriately identify, manage, and triage these patients through close collaboration with a multidisciplinary team to ensure safe and effective medication management for PAH patients in the acute care setting.

Evaluation of Evidence, Pharmacology, and Interplay of Fluid Resuscitation and Vasoactive Therapy in Sepsis and Septic Shock.

ABSTRACT: We sought to review the pharmacology of vasoactive therapy and fluid administration in sepsis and septic shock, with specific insight into the physiologic interplay of these agents. A PubMed/MEDLINE search was conducted using the following terms (vasopressor OR vasoactive OR inotrope) AND (crystalloid OR colloid OR fluid) AND (sepsis) AND (shock OR septic shock) from 1965 to October 2020. A total of 1,022 citations were reviewed with only relevant clinical data extracted. While physiologic rationale provides a hypothetical foundation for interaction between fluid and vasopressor administration, few studies have sought to evaluate the clinical impact of this synergy. Current guidelines are not in alignment with the data available, which suggests a potential benefit from low-dose fluid administration and early vasopressor exposure. Future data must account for the impact of both of these pharmacotherapies when assessing clinical outcomes and should assess personalization of therapy based on the possible interaction.

Clinical strategies for optimizing infusion center care through a pandemic.

The national pandemic resulting from the novel coronavirus, COVID-19, has made the delivery of care for patients with cancer a challenge. There are competing risks of mortality from cancer versus serious complications and higher risk of death from COVID-19 in immunocompromised hosts. Furthermore, compounding these concerns is the inadequate supply of personal protective equipment, decreased hospital capacity, and paucity of effective treatments or vaccines to date for COVID-19. Guidance measures and recommendations have been published by national organizations aiming to facilitate the delivery of care in a safe and effective manner, many of which, are permanently adoptable interventions. Given the critical importance to continue chemotherapy, there remains additional interventions to further enhance patient safety while conserving healthcare resources such as adjustments in medication administration, reduction in laboratory or drug monitoring, and home delivery of specialty infusions. In this manuscript, we outline how to implement these actionable interventions of chemotherapy and supportive care delivery to further enhance the current precautionary measures while maintaining safe and effective patient care. Coupled with current published standards, these strategies can help alleviate the numerous challenges associated with this pandemic.

Interventions to reduce polypharmacy and optimize medication use in older adults with cancer.

The use of polypharmacy and potentially inappropriate medications (PIMs) is an increasingly common, concerning public health issue in older adults, and a concurrent cancer diagnosis only further escalates the prevalence and complexity. Polypharmacy and PIM use has been associated with negative patient outcomes, including falls, chemotherapy toxicities and other adverse events, postoperative complications, frailty, functional impairment, and shortened survival. Despite the recognition of the harms, the prevalence of polypharmacy and PIM use continues to rise due to a lack of standardized identification and intervention methods. Efforts to reduce the prevalence have included use of explicit PIM screening tools (e.g., Beers criteria), comprehensive medication reviews, and deprescribing algorithms. However, these efforts are not widespread and the research on the effectiveness of such interventions is limited. To better understand what is known, this paper summarized available studies evaluating the effect of interventions on reducing the burden of polypharmacy/PIMs and provided recommendations to guide further practice models to reduce the negative consequences associated with polypharmacy and PIM use. Furthermore, we aim to establish a framework for clinical practice and to highlight areas for future intervention-based research to improve outcomes for older adults with cancer.