Cyclooxygenase 2 Inhibitors for Headache After Elective Cranial Neurosurgery: Results from a Systematic Review of Efficacy of Cyclooxygenase 2 Inhibitors for Headache After Acute Brain Injury.

Headache management after acute brain injury (ABI) is challenging. Although opioids are commonly used, selective cyclooxygenase 2 inhibitors (COXIBs) may be promising alternatives. However, concerns about cardiovascular effects and bleeding risk have limited their use. We aimed at summarizing available data on efficacy of COXIBs for headache management following ABI. A systematic review was conducted through MEDLINE and Embase for articles published through September 2023 (PROSPERO identifier: CRD42022320453). No language filters were applied to the initial searches. Interventional or observational studies and systematic reviews assessing efficacy of COXIBs for headache in adults with ABI were eligible. Article selection was performed by two independent reviewers using DistillerSR. Descriptive statistics were used for data analysis, and meta-analysis was unfeasible because of study heterogeneity. Of 3190 articles identified, 6 studies met inclusion criteria: 4 randomized controlled trials and 2 retrospective cohort studies, all conducted in elective cranial neurosurgical patients (total N = 738) between 2006 and 2022. Five studies used COXIBs in the intervention group only. Of the six studies, four found a reduction in overall pain scores in the intervention group, whereas one showed improvement only at 6 h postoperatively, and one did not find significant differences. Pain scores decreased between 4 and 15%, the largest shift being from moderate to mild severity. Three studies found an overall opioid use reduction throughout hospitalization in the intervention group, whereas one reported a reduction at 12 h postoperatively only. Opioid consumption decreased between 9 and 90%. Two studies found a decrease in hospital length of stay by ~ 1 day in the intervention group. The one study reporting postoperative hemorrhage found a statistically nonsignificant 3% reduction in the intervention group. COXIBs may serve as opioid-sparing adjunctive analgesics for headache control after elective cranial surgery. Limited or no literature exists for other forms of ABI, and additional safety data remain to be elucidated.

Rationale and Design for the BLOCK-SAH Study (Pterygopalatine Fossa Block as an Opioid-Sparing Treatment for Acute Headache in Aneurysmal Subarachnoid Hemorrhage): A Phase II, Multicenter, Randomized, Double-Blinded, Placebo-Controlled Clinical Trial with a Sequential Parallel Comparison Design.

BACKGROUND: Acute post-subarachnoid hemorrhage (SAH) headaches are common and severe. Management strategies for post-SAH headaches are limited, with heavy reliance on opioids, and pain control is overall poor. Pterygopalatine fossa (PPF) nerve blocks have shown promising results in treatment of acute headache, including our preliminary and published experience with PPF-blocks for refractory post-SAH headache during hospitalization. The BLOCK-SAH trial was designed to assess the efficacy and safety of bilateral PPF-blocks in awake patients with severe headaches from aneurysmal SAH who require opioids for pain control and are able to verbalize pain scores. METHODS: BLOCK-SAH is a phase II, multicenter, randomized, double-blinded, placebo-controlled clinical trial using the sequential parallel comparison design (SPCD), followed by an open-label phase. RESULTS: Across 12 sites in the United States, 195 eligible study participants will be randomized into three groups to receive bilateral active or placebo PPF-injections for 2 consecutive days with periprocedural monitoring of intracranial arterial mean flow velocities with transcranial Doppler, according to SPCD (group 1: active block followed by placebo; group 2: placebo followed by active block; group 3: placebo followed by placebo). PPF-injections will be delivered under ultrasound guidance and will comprise 5-mL injectates of 20 mg of ropivacaine plus 4 mg of dexamethasone (active PPF-block) or saline solution (placebo PPF-injection). CONCLUSIONS: The trial has a primary efficacy end point (oral morphine equivalent/day use within 24 h after each PPF-injection), a primary safety end point (incidence of radiographic vasospasm at 48 h from first PPF-injection), and a primary tolerability end point (rate of acceptance of second PPF-injection following the first PPF-injection). BLOCK-SAH will inform the design of a phase III trial to establish the efficacy of PPF-block, accounting for different headache phenotypes.

Leveraging machine learning to develop a postoperative predictive model for postoperative urinary retention following lumbar spine surgery.

Introduction: Postoperative urinary retention (POUR) is the inability to urinate after a surgical procedure despite having a full bladder. It is a common complication following lumbar spine surgery which has been extensively linked to increased patient morbidity and hospital costs. This study hopes to development and validate a predictive model for POUR following lumbar spine surgery using patient demographics, surgical and anesthesia variables. Methods: This is a retrospective observational cohort study of 903 patients who underwent lumbar spine surgery over the period of June 2017 to June 2019 in a tertiary academic medical center. Four hundred and nineteen variables were collected including patient demographics, ICD-10 codes, and intraoperative factors. Least absolute shrinkage and selection operation (LASSO) regression and logistic regression models were compared. A decision tree model was fitted to the optimal model to classify each patient's risk of developing POUR as high, intermediate, or low risk. Predictive performance of POUR was assessed by area under the receiver operating characteristic curve (AUC-ROC). Results: 903 patients were included with average age 60 ± 15 years, body mass index of 30.5 ± 6.4 kg/m2, 476 (53%) male, 785 (87%) white, 446 (49%) involving fusions, with average 2.1 ± 2.0 levels. The incidence of POUR was 235 (26%) with 63 (7%) requiring indwelling catheter placement. A decision tree was constructed with an accuracy of 87.8%. Conclusion: We present a highly accurate and easy to implement decision tree model which predicts POUR following lumbar spine surgery using preoperative and intraoperative variables.

Neuro-oncologic Emergencies.

OBJECTIVE: Neuro-oncologic emergencies have become more frequent as cancer remains one of the leading causes of death in the United States, second only to heart disease. This article highlights key aspects of epidemiology, diagnosis, and management of acute neurologic complications in primary central nervous system malignancies and systemic cancer, following three thematic classifications: (1) complications that are anatomically or intrinsically tumor-related, (2) complications that are tumor-mediated, and (3) complications that are treatment-related. LATEST DEVELOPMENTS: The main driver of mortality in patients with brain metastasis is systemic disease progression; however, intracranial hypertension, treatment-resistant seizures, and overall decline due to increased intracranial burden of disease are the main factors underlying neurologic-related deaths. Advances in the understanding of tumor-specific characteristics can better inform risk stratification of neurologic complications. Following standardized grading and management algorithms for neurotoxic syndromes related to newer immunologic therapies is paramount to achieving favorable outcomes. ESSENTIAL POINTS: Neuro-oncologic emergencies span the boundaries of subspecialties in neurology and require a broad understanding of neuroimmunology, neuronal hyperexcitability, CSF flow dynamics, intracranial compliance, and neuroanatomy.

Efficacy of Cyclooxygenase-2 Inhibitors for Headache in Acute Brain Injury: A Systematic Review.

Background: Headache management after acute brain injury (ABI) is challenging. While opioids are commonly used, selective cyclooxygenase-2 inhibitors (COXIBs) may be promising alternatives. However, concerns about cardiovascular effects and bleeding risk have limited their use. We aimed at summarizing available data on efficacy of COXIBs for headache management following ABI. Methods: A systematic review was conducted through MEDLINE and Embase for articles published through 09/2023 (PROSPERO CRD42022320453). No language filters were applied to the initial searches. Interventional or observational studies and systematic reviews assessing efficacy of COXIBs for headache in adults with ABI were eligible. Article selection was performed by two independent reviewers using Distiller SR®. Descriptive statistics were used for data analysis, while meta-analysis was unfeasible due to study heterogeneity. Results: Of 3190 articles identified, six studies met inclusion criteria: four randomized controlled trials and two retrospective cohort studies, all conducted in neurosurgical patients (total n=738) between 2006-2022. Five studies used COXIBs in the intervention group only. Of the six studies, four found a reduction in overall pain scores in the intervention group, while one showed improvement only at 6 hours postoperative, and one did not find significant differences. Pain scores decreased between 4-15%, the largest shift being from moderate to mild severity. Three studies found an overall opioid use reduction throughout hospitalization in the intervention group, while one reported a reduction at 12 hours postoperative only. Opioid consumption decreased between 9-90%. Two studies found a decrease in hospital-length-of-stay by ~1 day in the intervention group. The one study reporting postoperative hemorrhage found a statistically non-significant 3% reduction in the intervention group. Conclusions: In adults with ABI, COXIBs may serve as opioid-sparing adjunctive analgesics for headache control, with limited but pointed data to indicate efficacy in the post-neurosurgical setting. However, further safety data remains to be elucidated.

After the storm: Extracorporeal membrane oxygenation after hemicraniectomy in a child.

Ventricular arrhythmias following neurological injury have been attributed to sympathetic surge in subarachnoid hemorrhage and traumatic brain injury. Despite associated risks of bleeding and thrombosis, veno-arterial extracorporeal membrane oxygenation (ECMO) in critically ill, clinically unstable postoperative neurosurgical patients can be lifesaving. In the context of neurological injury and the neurosurgical population, the literature available regarding ECMO utilization is limited, especially in children. We report a case of successful ECMO utilization in a child with malignant ventricular tachycardia after decompressive craniectomy for refractory intracranial hypertension following evacuation of extensive subdural empyema.

Wolf Creek XVII part 9: Wolf Creek Innovator in Cardiac Arrest and Resuscitation Science Award.

The Wolf Creek Conferences on Cardiac Arrest Resuscitation began in 1975, and have served as an important forum for thought leaders and scientists from industry and academia to come together with the common goal of advancing the field of cardiac arrest resuscitation. The Wolf Creek XVII Conference was hosted by the Max Harry Weil Institute of Critical Care Research and Innovation in Ann Arbor, Michigan on June 14-17, 2023. A new component of the conference was the Wolf Creek Innovator in Cardiac Arrest and Resuscitation Science Award competition. The competition was designed to recognize early career investigators from around the world who's science is challenging the current paradigms in the field. Finalists were selected by a panel of international experts and invited to present in-person at the conference. The winner was chosen by electronic vote of conference participants and awarded a $10,0000 cash prize. Finalists included Carolina Barbosa Maciel from the University of Florida, Adam Gottula from the University of Michigan, Rajat Kalra from the University of Minnesota, Ryan Morgan from the Children's Hospital of Philadelphia, Mitsuaki Nishikimi form Hiroshima University, and Jacob Sunshine from the University of Washington. Ryan Morgan from the Children's Hospital of Philadelphia was selected as the 2023 Wolf Creek Innovator Awardee. This manuscript provides a summary of the work presented by each of the finalists and provides a preview of the future of resuscitation science.

2023 American Heart Association Focused Update on Adult Advanced Cardiovascular Life Support: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.

Cardiac arrest is common and deadly, affecting up to 700 000 people in the United States annually. Advanced cardiac life support measures are commonly used to improve outcomes. This "2023 American Heart Association Focused Update on Adult Advanced Cardiovascular Life Support" summarizes the most recent published evidence for and recommendations on the use of medications, temperature management, percutaneous coronary angiography, extracorporeal cardiopulmonary resuscitation, and seizure management in this population. We discuss the lack of data in recent cardiac arrest literature that limits our ability to evaluate diversity, equity, and inclusion in this population. Last, we consider how the cardiac arrest population may make up an important pool of organ donors for those awaiting organ transplantation.

Electroencephalography as a Biomarker of Prognosis in Acute Brain Injury.

Electroencephalography (EEG) is a noninvasive tool that allows the monitoring of cerebral brain function in critically ill patients, aiding with diagnosis, management, and prognostication. Specific EEG features have shown utility in the prediction of outcomes in critically ill patients with status epilepticus, acute brain injury (ischemic stroke, intracranial hemorrhage, subarachnoid hemorrhage, and traumatic brain injury), anoxic brain injury, and toxic-metabolic encephalopathy. Studies have also found an association between particular EEG patterns and long-term functional and cognitive outcomes as well as prediction of recovery of consciousness following acute brain injury. This review summarizes these findings and demonstrates the value of utilizing EEG findings in the determination of prognosis.

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.

Pre-operative prediction of post-operative urinary retention in lumbar surgery: a prospective validation of machine learning model.

PURPOSE: Predicting urinary retention is difficult. The aim of this study is to prospectively validate a previously developed model using machine learning techniques. METHODS: Patients were recruited from pre-operative clinic. Prediction of urinary retention was completed pre-operatively by 4 individuals and compared to ground truth POUR outcomes. Inter-rater reliability was calculated with intercorrelation coefficient (2,1). RESULTS: 171 patients were included with age 63 ± 14 years, 58.5% (100/171) male, BMI 30.4 ± 5.9 kg/m2, American Society of Anesthesiologists class 2.6 ± 0.5, 1.7 ± 1.0 levels, 56% (96/171) fusions. The observed rate of POUR was 25.7%. The model's performance was found to be 0.663 (0.567-0.759). With a regression model probability cutoff of 0.24 and a neural network cutoff of 0.23, the following predictive power was achieved: specificity 90.6%, sensitivity 22.7%, negative predictive value 77.2%, positive predictive value 45.5%, and accuracy 73.1%. Intercorrelation coefficient for the regression aspect of the model was found to be 0.889 and intercorrelation coefficient for the neural network aspect of the model was found to be 0.874. CONCLUSIONS: This prospective study confirms performance of the prediction model for POUR developed with retrospective data, showing great correlation. This supports the use of machine learning techniques in the prediction of postoperative complications such as urinary retention.

Evaluating analgesic medications utilized in the treatment of aneurysmal subarachnoid hemorrhage and association with delayed cerebral ischemia.

BACKGROUND: Spontaneous aneurysmal subarachnoid hemorrhage (aSAH) recovery may be hampered by delayed cerebral ischemia (DCI). Herein, we sought to identify whether frequently administered medications in the intensive care unit (ICU) are associated with DCI. METHODS: In this retrospective study, patients admitted to a tertiary care center neuro-ICU between 2012 and 2019 with aSAH who could verbalize pain intensity scores were included. Medication dosages and clinical characteristics were abstracted from the medical record. Both paired and unpaired analyses were utilized to measure individual DCI risk for a given patient in relation to drug dosages. RESULTS: 119 patients were included; average age was 61.7 ± 15.2 (SD) years, 89 (74.7%) were female, and 32 (26.9%) experienced DCI during admission. Patients with DCI had longer length of stay (19.3 ± 7.4 vs 12.7 ± 5.3 days, p < 0.0001). The combination medication of acetaminophen 325 mg/butalbital 50 mg/caffeine 40 mg (A/B/C) was associated with decreased DCI on paired (2.3 ± 2.0 vs 3.1 ± 1.9 tabs, p = 0.034) and unpaired analysis (1.84 ± 2.4 vs 2.6 ± 2.4 tabs, p < 0.001). No associations were found between DCI and opioids, dexamethasone, levetiracetam, or acetaminophen. Max and mean daily headache pain was not associated with DCI occurrence. CONCLUSION: We identified an association between a commonly administered analgesic and DCI. A/B/C is associated with decreased DCI in this study, while other medications are not associated with DCI risk.

Practice Standards for the Use of Multimodality Neuromonitoring: A Delphi Consensus Process.

OBJECTIVES: To address areas in which there is no consensus for the technologies, effort, and training necessary to integrate and interpret information from multimodality neuromonitoring (MNM). DESIGN: A three-round Delphi consensus process. SETTING: Electronic surveys and virtual meeting. SUBJECTS: Participants with broad MNM expertise from adult and pediatric intensive care backgrounds. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two rounds of surveys were completed followed by a virtual meeting to resolve areas without consensus and a final survey to conclude the Delphi process. With 35 participants consensus was achieved on 49% statements concerning MNM. Neurologic impairment and the potential for MNM to guide management were important clinical considerations. Experts reached consensus for the use of MNM-both invasive and noninvasive-for patients in coma with traumatic brain injury, aneurysmal subarachnoid hemorrhage, and intracranial hemorrhage. There was consensus that effort to integrate and interpret MNM requires time independent of daily clinical duties, along with specific skills and expertise. Consensus was reached that training and educational platforms are necessary to develop this expertise and to provide clinical correlation. CONCLUSIONS: We provide expert consensus in the clinical considerations, minimum necessary technologies, implementation, and training/education to provide practice standards for the use of MNM to individualize clinical care.

Temperature Management for Comatose Adult Survivors of Cardiac Arrest: A Science Advisory From the American Heart Association.

Targeted temperature management has been a cornerstone of post-cardiac arrest care for patients remaining unresponsive after return of spontaneous circulation since the initial trials in 2002 found that mild therapeutic hypothermia improves neurological outcome. The suggested temperature range expanded in 2015 in response to a large trial finding that outcomes were not better with treatment at 33° C compared with 36° C. In 2021, another large trial was published in which outcomes with temperature control at 33° C were not better than those of patients treated with a strategy of strict normothermia. On the basis of these new data, the International Liaison Committee on Resuscitation and other organizations have altered their treatment recommendations for temperature management after cardiac arrest. The new American Heart Association guidelines on this topic will be introduced in a 2023 focused update. To provide guidance to clinicians while this focused update is forthcoming, the American Heart Association's Emergency Cardiovascular Care Committee convened a writing group to review the TTM2 trial (Hypothermia Versus Normothermia After Out-of-Hospital Cardiac Arrest) in the context of other recent evidence and to present an opinion on how this trial may influence clinical practice. This science advisory was informed by review of the TTM2 trial, consideration of other recent influential studies, and discussion between cardiac arrest experts in the fields of cardiology, critical care, emergency medicine, and neurology. Conclusions presented in this advisory statement do not replace current guidelines but are intended to provide an expert opinion on novel literature that will be incorporated into future guidelines and suggest the opportunity for reassessment of current clinical practice.

Sedation and shivering management after cardiac arrest.

Management of sedation and shivering during targeted temperature management (TTM) after cardiac arrest is limited by a dearth of high-quality evidence to guide clinicians. Data from general intensive care unit (ICU) populations can likely be extrapolated to post-cardiac arrest patients, but clinicians should be mindful of key differences that exist between these populations. Most importantly, the goals of sedation after cardiac arrest are distinct from other ICU patients and may also involve suppression of shivering during TTM. Drug metabolism and clearance are altered considerably during TTM when a low goal temperature is used, which can delay accurate neuroprognostication. When neuromuscular blockade is used to prevent shivering, sedation should be deep enough to prevent awareness and providers should be aware that this can mask clinical manifestations of seizures. However, excessively deep or prolonged sedation is associated with complications including delirium, infections, increased duration of ventilatory support, prolonged ICU length of stay, and delays in neuroprognostication. In this manuscript, we review sedation and shivering management best practices in the post-cardiac arrest patient population.

Do Neuroprognostic Studies Account for Self-Fulfilling Prophecy Bias in Their Methodology? The SPIN Protocol for a Systematic Review.

Self-fulfilling prophecy bias occurs when a perceived prognosis leads to treatment decisions that inherently modify outcomes of a patient, and thus, overinflate the prediction performance of prognostic methods. The goal of this series of systematic reviews is to characterize the extent to which neuroprognostic studies account for the potential impact of self-fulfilling prophecy bias in their methodology by assessing their adequacy of disclosing factors relevant to this bias. Methods: Studies evaluating the prediction performance of neuroprognostic tools in cardiac arrest, malignant ischemic stroke, traumatic brain injury, subarachnoid hemorrhage, and spontaneous intracerebral hemorrhage will be identified through PubMed, Cochrane, and Embase database searches. Two reviewers blinded to each other's assessment will perform screening and data extraction of included studies using Distiller SR and following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We will abstract data pertinent to the methodology of the studies relevant to self-fulfilling prophecy bias. Results: We will conduct a descriptive analysis of the data. We will summarize the reporting of mortality according to timing and mode of death, rates of exposure to withdrawal of life-sustaining therapy, reasoning behind limitations of supportive care, systematic use of standardized neuroprognostication algorithms and whether the tool being investigated is part of such assessments, and blinding of treatment team to results of neuroprognostic test being evaluated. CONCLUSIONS: We will identify if neuroprognostic studies have been transparent in their methodology to factors that affect the self-fulfilling prophecy bias. Our results will serve as the foundation for standardization of neuroprognostic study methodologies by refining the quality of the data derived from such studies.