Society of Critical Care Medicine Clinical Practice Guidelines for Rapid Sequence Intubation in the Critically Ill Adult Patient.

RATIONALE: Controversies and practice variations exist related to the pharmacologic and nonpharmacologic management of the airway during rapid sequence intubation (RSI). OBJECTIVES: To develop evidence-based recommendations on pharmacologic and nonpharmacologic topics related to RSI. DESIGN: A guideline panel of 20 Society of Critical Care Medicine members with experience with RSI and emergency airway management met virtually at least monthly from the panel's inception in 2018 through 2020 and face-to-face at the 2020 Critical Care Congress. The guideline panel included pharmacists, physicians, a nurse practitioner, and a respiratory therapist with experience in emergency medicine, critical care medicine, anesthesiology, and prehospital medicine; consultation with a methodologist and librarian was available. A formal conflict of interest policy was followed and enforced throughout the guidelines-development process. METHODS: Panelists created Population, Intervention, Comparison, and Outcome (PICO) questions and voted to select the most clinically relevant questions for inclusion in the guideline. Each question was assigned to a pair of panelists, who refined the PICO wording and reviewed the best available evidence using predetermined search terms. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework was used throughout and recommendations of "strong" or "conditional" were made for each PICO question based on quality of evidence and panel consensus. Recommendations were provided when evidence was actionable; suggestions, when evidence was equivocal; and best practice statements, when the benefits of the intervention outweighed the risks, but direct evidence to support the intervention did not exist. RESULTS: From the original 35 proposed PICO questions, 10 were selected. The RSI guideline panel issued one recommendation (strong, low-quality evidence), seven suggestions (all conditional recommendations with moderate-, low-, or very low-quality evidence), and two best practice statements. The panel made two suggestions for a single PICO question and did not make any suggestions for one PICO question due to lack of evidence. CONCLUSIONS: Using GRADE principles, the interdisciplinary panel found substantial agreement with respect to the evidence supporting recommendations for RSI. The panel also identified literature gaps that might be addressed by future research.

Elevated Cerebrospinal Fluid Protein Is Associated with Unfavorable Functional Outcome in Spontaneous Subarachnoid Hemorrhage.

BACKGROUND/OBJECTIVE: Subarachnoid hemorrhage (SAH) is a devastating neurologic event for which markers to assess poor outcome are needed. Elevated cerebrospinal fluid (CSF) protein may result from inflammation and blood-brain barrier (BBB) disruption that occurs during SAH. We sought to determine if CSF protein level is associated with functional outcome after SAH. METHODS: We prospectively collected single-center demographic and clinical data for consecutive patients admitted with spontaneous SAH. Inclusion required an external ventricular drain and daily CSF protein and cellular counts starting within 48 hours of symptom onset and extending through 7 days after onset. Seven-day average CSF protein was determined from daily measured values after correcting for contemporaneous CSF red blood cell (RBC) count. Three-month functional outcome was assessed by telephone interview with good outcome defined as modified Rankin score 0-3. Variables univariately associated with outcome at P less than .25 and measures of hemorrhage volume were included for binary logistic regression model development. RESULTS: The study included 130 patients (88% aneurysmal SAH, 69% female, 54.8 ± 14.8 years, Glasgow Coma Scale [GCS] 14 [7-15]). Three-month outcome assessment was complete in 112 (86%) patients with good functional outcome in 74 (66%). CSF protein was lower in good outcome (35.3 [20.4-49.7] versus 80.5 [40.5-115.5] mg/dL; P < .001). CSF protein was not associated with cerebral vasospasm, but delayed radiographic infarction on 3 to 12-month neuroimaging was associated with higher CSF protein (46.3 [32.0-75.0] versus 30.2 [20.4-47.8] mg/dL; P = .023). Good 3-month outcome was independently associated with lower CSF protein (odds ratios [OR] .39 [.23-.70] for 75th versus 25th percentile of protein; P = .001) and higher admission GCS (OR 1.23 [1.10-1.37] for good outcome per GCS point increase; P < .001). Parenchymal hematoma predicted worse outcome (OR 6.31 [1.58-25.25]; P = .009). Results were similar after excluding nonaneurysmal SAH and after including CSF RBC count, CT score, and intraventricular hemorrhage volume in models. CONCLUSIONS: Elevated average CSF protein is associated with poor outcome after spontaneous SAH. Further research should investigate if elevated CSF protein identifies patients in whom mechanisms such as BBB disruption contribute to poor outcome.

Admission Heart Rate Variability is Associated with Fever Development in Patients with Intracerebral Hemorrhage.

BACKGROUND: Fever is associated with worse outcome after intracerebral hemorrhage (ICH). Autonomic dysfunction, commonly seen after brain injury, results in reduced heart rate variability (HRV). We sought to investigate whether HRV was associated with the development of fever in patients with ICH. METHODS: We prospectively enrolled consecutive patients with spontaneous ICH in a single-center observational study. We included patients who presented directly to our emergency department after symptom onset, had a 10-second electrocardiogram (EKG) performed within 24 h of admission, and were in sinus rhythm. Patient temperature was recorded every 1-4 h. We defined being febrile as having a temperature of ≥ 38 °C within the first 14 days, and fever burden as the number of febrile days. HRV was defined by the standard deviation of the R-R interval (SDNN) measured on the admission EKG. Univariate associations were determined by Fisher's exact, Mann-Whitney U, or Spearman's rho correlation tests. Variables associated with fever at p ≤ 0.2 were entered in a logistic regression model of being febrile within 14 days. RESULTS: There were 248 patients (median age 63 [54-74] years, 125 [50.4%] female, median ICH Score 1 [0-2]) who met the inclusion criteria. Febrile patients had lower HRV (median SDNN: 1.72 [1.08-3.60] vs. 2.55 [1.58-5.72] msec, p = 0.001). Lower HRV was associated with more febrile days (R = - 0.22, p < 0.001). After adjustment, lower HRV was independently associated with greater odds of fever occurrence (OR 0.92 [95% CI 0.87-0.97] with each msec increase in SDNN, p = 0.002). CONCLUSIONS: HRV measured on 10-second EKGs is a potential early marker of parasympathetic nervous system dysfunction and is associated with subsequent fever occurrence after ICH. Detecting early parasympathetic dysfunction may afford opportunities to improve ICH outcome by targeting therapies at fever prevention.

Medication History versus Point-of-Care Platelet Activity Testing in Patients with Intracerebral Hemorrhage.

OBJECTIVE: We evaluated whether reduced platelet activity detected by point-of-care (POC) testing is a better predictor of hematoma expansion and poor functional outcomes in patients with intracerebral hemorrhage (ICH) than a history of antiplatelet medication exposure. METHODS: Patients presenting with spontaneous ICH were enrolled in a prospective observational cohort study that collected demographic, clinical, laboratory, and radiographic data. We measured platelet activity using the PFA-100 (Siemens AG, Germany) and VerifyNow-ASA (Accumetrics, CA) systems on admission. We performed univariate and adjusted multivariate analyses to assess the strength of association between those measures and (1) hematoma growth at 24 hours and (2) functional outcomes measured by the modified Rankin Scale (mRS) at 3 months. RESULTS: We identified 278 patients for analysis (mean age 65 ± 15, median ICH score 1 [interquartile range 0-2]), among whom 164 underwent initial neuroimaging within 6 hours of symptom onset. Univariate association with hematoma growth was stronger for antiplatelet medication history than POC measures, which was confirmed in multivariable models (ß 3.64 [95% confidence interval [CI] 1.02-6.26], P = .007), with a larger effect size measured in the under 6-hour subgroup (ß 7.20 [95% CI 3.35-11.1], P < .001). Moreover, antiplatelet medication history, but not POC measures of platelet activity, was independently associated with poor outcome at 3 months (mRS 4-6) in the under 6-hour subgroup (adjusted OR 3.6 [95% CI 1.2-11], P = .023). CONCLUSION: A history of antiplatelet medication use better identifies patients at risk for hematoma growth and poor functional outcomes than POC measures of platelet activity after spontaneous ICH.

Predictors of neurologic outcome in hypothermia after cardiac arrest.

OBJECTIVE: To evaluate the predictive value of neurologic prognostic indicators for patients treated with hypothermia after surviving cardiopulmonary arrest. METHODS: Patients who survived cardiopulmonary arrest were prospectively collected from June 2006 to October 2009. Detailed neurologic examinations were performed. Serum neuron specific enolase (NSE) measurements, brain imaging findings, somatosensory evoked potentials, and electroencephalogram (EEG) results were recorded. EEG patterns were blindly dichotomized with malignant patterns consisting of burst-suppression, generalized suppression, status epilepticus, and nonreactivity. Outcome measure of in-hospital mortality was assessed. RESULTS: A total of 192 patients (103 hypothermic, 89 nonhypothermic) were studied. The absence of pupillary light responses, corneal reflexes, and an extensor or absent motor response at Day 3 after cardiac arrest remained accurate predictors of poor outcome after therapeutic hypothermia (p < 0.0001 for all). Myoclonic status epilepticus was invariably associated with death (p = 0.0002). Malignant EEG patterns and global cerebral edema on head computed tomography (CT) were associated with death in both populations (p < 0.001). NSE > 33 ng/ml levels measured 1-3 days after cardiac arrest remained associated with poor outcome (p = 0.017), but had a false-positive rate of 29.3% (95% confidence interval [CI] 0.164-0.361). INTERPRETATION: Clinical examination (brainstem reflexes, motor response, and presence of myoclonus) at Day 3 after cardiac arrest remains an accurate predictor of outcome after therapeutic hypothermia. Sedative medications in both hypothermic and nonhypothermic patients may confound the clinical exam. NSE > 33 ng/ml has a high false-positive rate in patients treated with hypothermia and should be interpreted with caution.

Clinical spectrum of reversible posterior leukoencephalopathy syndrome.

BACKGROUND: Reversible posterior leukoencephalopathy syndrome (RPLS) is characterized by neuroimaging findings of reversible vasogenic subcortical edema without infarction. The clinical syndrome of RPLS typically involves headache, encephalopathy, visual symptoms, and seizures. OBJECTIVE: To retrospectively identify patients with RPLS with a characteristic clinical presentation and neuroimaging abnormalities and documented improvement on repeated neuroimaging. DESIGN: Retrospective. SETTING: Mayo Clinic. PATIENTS: Thirty-six patients with RPLS. MAIN OUTCOME MEASURES: Associated comorbid medical conditions, presenting clinical symptoms, duration of clinical symptoms, diagnostic test results (magnetic resonance imaging, electroencephalography, and lumbar puncture), and time to clinical and neuroimaging recovery. RESULTS: We identified 38 episodes of RPLS in 36 patients (20 females and 16 males) with a mean age of 44.7 years. Comorbid conditions included hypertension (53%), renal disease (45%), dialysis dependency (21%), malignancy (32%), and transplantation (24%). Presenting symptoms included clinical seizures (87%), encephalopathy (92%), visual symptoms (39%), and headache (53%). Mean peak systolic blood pressure at presentation was 187 mm Hg. Clinical symptoms resolved after a mean of 5.3 days. Atypical neuroimaging features included significant frontal involvement in 22 episodes (58%), gray matter lesions in 16 (42%), unilateral lesions in 2 (5%), hemorrhage in 2 (5%), recurrent RPLS in 2 (5%), confluent lesions in 2 (5%), and foci of permanent injury in 10 (26%). Twenty-two episodes (58%) had brainstem/cerebellar involvement on neuroimaging. CONCLUSIONS: This is the largest clinical series to date of RPLS with confirmed neuroimaging improvement. Clinical recovery occurred in most patients within days. The condition was rarely isolated to the parieto-occipital white matter, and atypical neuroimaging features were frequent.

A prospective trial of elective extubation in brain injured patients meeting extubation criteria for ventilatory support: a feasibility study.

INTRODUCTION: To assess the safety and feasibility of recruiting mechanically ventilated patients with brain injury who are solely intubated for airway protection and randomising them into early or delayed extubation, and to obtain estimates to refine sample-size calculations for a larger study. The design is a single-blinded block randomised controlled trial. A single large academic medical centre is the setting. METHODS: Sixteen neurologically stable but severely brain injured patients with a Glasgow Coma Score (GCS) of 8 or less were randomised to early or delayed extubation until their neurological examination improved. Eligible patients met standard respiratory criteria for extubation and passed a modified Airway Care Score (ACS) to ensure adequate control of respiratory secretions. The primary outcome measured between groups was the functional status of the patient at hospital discharge as measured by a Modified Rankin Score (MRS) and Functional Independence Measure (FIM). Secondary measurements included the number of nosocomial pneumonias and re-intubations, and intensive care unit (ICU) and hospital length of stay. Standard statistical assessments were employed for analysis. RESULTS: Five female and eleven male patients ranging in age from 30 to 93 years were enrolled. Aetiologies responsible for the neurological injury included six head traumas, three brain tumours, two intracerebral haemorrhages, two subarachnoid haemorrhages and three ischaemic strokes. There were no demographic differences between the groups. There were no unexpected deaths and no significant differences in secondary measures. The difference in means between the MRS and FIM were small (0.25 and 5.62, respectively). These results suggest that between 64 and 110 patients are needed in each treatment arm to detect a treatment effect with 80% power. CONCLUSIONS: Recruitment and randomisation of severely brain injured patients appears to be safe and feasible. A large multicentre trial will be needed to determine if stable, severely brain injured patients who meet respiratory and airway control criteria for extubation need to remain intubated.

Primary intracerebral hemorrhage: update on epidemiology, pathophysiology, and treatment strategies.

Intracerebral hemorrhage (ICH) is a common and devastating condition. Its incidence is expected to increase as the population ages, and its epidemiology is changing. Advances in understanding the pathogenesis of ICH have recently been made. A number of recently completed and ongoing trials suggest that new treatments that limit the mortality and morbidity of ICH may be on the horizon.

Magnesium, hemostasis, and outcomes in patients with intracerebral hemorrhage.

OBJECTIVE: We tested the hypothesis that admission serum magnesium levels are associated with hematoma volume, hematoma growth, and functional outcomes in patients with intracerebral hemorrhage (ICH). METHODS: Patients presenting with spontaneous ICH were enrolled in an observational cohort study that prospectively collected demographic, clinical, laboratory, radiographic, and outcome data. We performed univariate and adjusted multivariate analyses to assess for associations between serum magnesium levels and initial hematoma volume, final hematoma volume, and in-hospital hematoma growth as radiographic measures of hemostasis, and functional outcome measured by the modified Rankin Scale (mRS) at 3 months. RESULTS: We included 290 patients for analysis. Admission serum magnesium was 2.0 ± 0.3 mg/dL. Lower admission magnesium levels were associated with larger initial hematoma volumes on univariate (p = 0.02), parsimoniously adjusted (p = 0.002), and fully adjusted models (p = 0.006), as well as greater hematoma growth (p = 0.004, p = 0.005, and p = 0.008, respectively) and larger final hematoma volumes (p = 0.02, p = 0.001, and p = 0.002, respectively). Lower admission magnesium level was associated with worse functional outcomes at 3 months (i.e., higher mRS; odds ratio 0.14, 95% confidence interval 0.03-0.64, p = 0.011) after adjustment for age, admission Glasgow Coma Scale score, initial hematoma volume, time from symptom onset to initial CT, and hematoma growth, with evidence that the effect of magnesium is mediated through hematoma growth. CONCLUSIONS: These data support the hypothesis that magnesium exerts a clinically meaningful influence on hemostasis in patients with ICH.

A Multifaceted Approach to Reduction of Catheter-Associated Urinary Tract Infections in the Intensive Care Unit With an Emphasis on "Stewardship of Culturing".

BACKGROUND Catheter-associated urinary tract infections (CAUTIs) are among the most common hospital-acquired infections (HAIs). Reducing CAUTI rates has become a major focus of attention due to increasing public health concerns and reimbursement implications. OBJECTIVE To implement and describe a multifaceted intervention to decrease CAUTIs in our ICUs with an emphasis on indications for obtaining a urine culture. METHODS A project team composed of all critical care disciplines was assembled to address an institutional goal of decreasing CAUTIs. Interventions implemented between year 1 and year 2 included protocols recommended by the Centers for Disease Control and Prevention for placement, maintenance, and removal of catheters. Leaders from all critical care disciplines agreed to align routine culturing practice with American College of Critical Care Medicine (ACCCM) and Infectious Disease Society of America (IDSA) guidelines for evaluating a fever in a critically ill patient. Surveillance data for CAUTI and hospital-acquired bloodstream infection (HABSI) were recorded prospectively according to National Healthcare Safety Network (NHSN) protocols. Device utilization ratios (DURs), rates of CAUTI, HABSI, and urine cultures were calculated and compared. RESULTS The CAUTI rate decreased from 3.0 per 1,000 catheter days in 2013 to 1.9 in 2014. The DUR was 0.7 in 2013 and 0.68 in 2014. The HABSI rates per 1,000 patient days decreased from 2.8 in 2013 to 2.4 in 2014. CONCLUSIONS Effectively reducing ICU CAUTI rates requires a multifaceted and collaborative approach; stewardship of culturing was a key and safe component of our successful reduction efforts. Infect Control Hosp Epidemiol 2017;38:186-188.

Clinical importance of cardiac troponin release and cardiac abnormalities in patients with supratentorial cerebral hemorrhages.

OBJECTIVE: To determine the Incidence of cardiac troponin T (cTnT) elevation, electrocardiographic (ECG) changes, and arrhythmias in supratentorial intracerebral hemorrhage (ICH) and their association with early mortality. PATIENTS AND METHODS: Patients with supratentorial ICHs admitted to Mayo Clinic, Rochester, Minn, from March 1998 to October 2003 were studied. We excluded moribund patients with ICHs who died within 12 hours of hospital admission. Cardiac troponin T levels measured on admission and day 2 were determined by a third-generation enzyme-linked immunosorbent assay. Continuous ECG monitoring was performed In all patients. Computed tomographic scans were graded and correlated with abnormal cardiac variables. RESULTS: Peak levels of cTnT were elevated at 0.035 to 1.2 microg/L (mean +/- SD, 0.27 +/- 0.38 microg/L) in 10 (20%) of 49 patients and were not associated with changes in creatine kinase MB fraction or ECG results. The cTnT levels did not correlate with location or side of hemorrhage or mortality at 30 days. Seventy (64%) of 110 patients displayed ECG abnormalities. The ECG changes did not correlate with the location or side of ICH, hydrocephalus, midline shift, or extension to the ventricles. CONCLUSION: The cTnT elevations in survivors of acute ICH are frequent but without confirmatory ECG changes that suggest mild myocardial injury. One-month mortality is not influenced by such cTnT elevations. In addition, ECG abnormalities are common but likely benign in patients with supratentorial ICH who survive the initial insult.

Tako-tsubo cardiomyopathy in aneurysmal subarachnoid hemorrhage: an underappreciated ventricular dysfunction.

OBJECT: Neurogenic stunned myocardium in aneurysmal subarachnoid hemorrhage (SAH) is associated with a wide spectrum of reversible left ventricular wall motion abnormalities and includes a subset of patients with a pattern of apical akinesia and concomitant sparing of basal segments called "tako-tsubo cardiomyopathy". METHODS: After obtaining institutional review board approval, the authors retrospectively identified among all patients admitted to the Mayo Clinic's Neurological Intensive Care Unit between January 1990 and January 2005 those with aneurysmal SAH who had met the echocardiographic criteria for tako-tsubo cardiomyopathy. Among 24 patients with SAH-induced reversible cardiac dysfunction, the authors identified eight with SAH-induced tako-tsubo cardiomyopathy. All eight patients were women with a mean age of 55.5 years (range 38.6-71.1). Seven patients presented with a poor-grade SAH, reflected by a Hunt and Hess grade of III or IV. Four patients underwent aneurysm clip application, and four underwent endovascular coil occlusion. The initial mean ejection fraction (EF) was 38% (range 25-55%), and the mean EF at recovery was 55% (range 40-68%). Cerebral vasospasm developed in six patients, but cerebral infarction developed in only three patients. CONCLUSIONS: The authors describe the largest cohort with aneurysmal SAH-induced tako-tsubo cardiomyopathy. In the SAH population, tako-tsubo cardiomyopathy predominates in postmenopausal women and is often associated with pulmonary edema, prolonged intubation, and cerebral vasospasm. Additional studies are warranted to understand the complex mechanism involved in tako-tsubo cardiomyopathy and its intriguing relationship to neurogenic stunned myocardium.

The declaration of death and the withdrawal of care in the neurologic patient.

Intensive care technologies have led to an increase in patients who are neurologically devastated and deceased. The practical, moral, and ethical situations encountered can be varied and challenging to manage. Decisions and discussions surrounding withdrawal of care, death by neurologic criteria, and organ donation require significant knowledge of the prognosis, ancillary testing, and definitions of these processes. Experience and skill are often required on the part of physicians and staff to guide families through these most difficult of circumstances.

Subarachnoid hemorrhage: neurointensive care and aneurysm repair.

Aneurysmal subarachnoid hemorrhage (SAH) is often a neurologic catastrophe. Diagnosing SAH can be challenging, and treatment is complex, sophisticated, multidisciplinary, and rarely routine. This review emphasizes treatment in the intensive care unit, surgical and endovascular therapeutic options, and the current state of treatment of major complications such as cerebral vasospasm, acute hydrocephalus, and rebleeding. Outcome assessment in survivors of SAH and controversies in screening of family members are discussed.

Emerging medical and surgical management strategies in the evaluation and treatment of intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) accounts for approximately 10% of all strokes and causes high morbidity and mortality. Rupture of the small perforating vessels of the cerebral arteries is caused by chronic hypertension, which induces pathologic changes in the small vessels and accounts for most cases of ICH; however, amyloid angiopathy and other secondary causes are being seen more frequently with the increasing age of the population. Recent computed tomographic studies have revealed that ICH is a dynamic process with up to one third of initial hemorrhages expanding within the first several hours of ictus. Secondary injury is believed to result from the development of cerebral edema and the release of specific neurotoxins associated with the breakdown products of hemoglobin. Treatment is primarily supportive. Surgical evacuation is the treatment of choice for patients with neurologic deterioration from infratentorial hematomas. Randomized trials comparing surgical evacuation to medical management have shown no benefit of surgical removal of supratentorial hemorrhages. New strategies focusing on early hemostasis, improved critical care management, and less invasive surgical techniques for clot evacuation are promising to decrease secondary neurologic injury. We review the pathophysiology of ICH, its medical management, and new treatment strategies for improving patient outcome.

Coital hemorrhage of an arteriovenous malformation after premedication with tadalafil (Cialis).

Phosphodiesterase type 5 (PDE 5) inhibitors are widely used in the treatment of erectile dysfunction. However, the results on the cerebral vasculature are unknown. Several cases of intraparenchymal hemorrhage in the setting of PDE 5 inhibitor use have been reported. The effect of these agents on the risk of arteriovenous malformation (AVM) hemorrhage is speculative. This report illustrates a possible association between tadalafil (Cialis, Lilly ICOS, Indianapolis, IN), a new long-acting PDE 5 inhibitor, and AVM hemorrhage during coitus. A 59-year-old male suffered a coital intraparenchymal hemorrhage after premedication with tadalafil. Angiography and magnetic resonance imaging demonstrated an underlying right temporoparital AVM. The AVM was excised, and the patient made an uneventful recovery. AVMs are felt to be dynamic lesions that evolve in response to changes in blood flow. Repeated use of PDE 5 inhibitors could induce changes in an AVM that would make it more likely to hemorrhage, particularly in the setting of additional stress from coitus and elevated blood pressure. The potential for risk of devastating neurovascular complications related to PDE 5 inhibitors should be monitored.

The management of large hemispheric cerebral infarcts.

Large hemispheric cerebral infarcts have significant morbidity and mortality. Our understanding of this pathophysiological process involved with secondary neurological deterioration in large hemispheric infarctions has increased in the past few decades. New experimental strategies designed to improve outcome are reviewed.

Treatment of malignant brain edema and increased intracranial pressure after stroke.

OPINION STATEMENT: The management of patients with large territory ischemic strokes and the subsequent development of malignant brain edema and increased intracranial pressure is a significant challenge in modern neurology and neurocritical care. These patients are at high risk of subsequent neurologic decline and are best cared for in an intensive care unit or a comprehensive stroke center with access to neurosurgical support. Risks include hemorrhagic conversion, herniation, poor functional outcome, and death. This review discusses recent advances in understanding the pathophysiology of edema formation, identifying patients at risk, current management strategies, and emerging therapies.