Rabinstein, Alejandro A.

ImportanceUnderstanding the relationship between patients’ clinical characteristics and outcomes is fundamental to medicine. When critically ill patients die after withdrawal of life-sustaining therapy (WLST), the inability to observe the potential for recovery with continued aggressive care could bias future clinical decisions and research.ObjectiveTo quantify the frequency with which experts consider patients who died after WLST following resuscitated cardiac arrest to have had recovery potential if life-sustaining therapy had been continued.Design, Setting, and ParticipantsThis prospective cohort study included comatose adult patients (aged ≥18 years) treated following resuscitation from cardiac arrest at a single academic medical center between January 1, 2010, and July 31, 2022. Patients with advanced directives limiting critical care or who experienced cardiac arrest of traumatic or neurologic etiology were excluded. An international cohort of experts in post-arrest care based on clinical experience and academic productivity was identified. Experts reviewed the cases between August 24, 2022, and February 11, 2024.ExposurePatients who died after WLST.Main Outcome and MeasuresThree or more experts independently estimated recovery potential for each patient had life-sustaining treatment been continued, using a 7-point numerical ordinal scale. In the primary analysis, which involved the patient cases with death after WLST, a 1% or greater estimated recovery potential was considered to be clinically meaningful. In secondary analyses, thresholds of 5% and 10% estimated recovery probability were explored.ResultsA total of 2391 patients (median [IQR] age, 59 [48-69] years; 1455 men [60.9%]) were included, of whom 714 (29.9%) survived to discharge. Cases of uncertain outcome (1431 patients [59.8%]) in which WLST preceded death were reviewed by 38 experts who rendered 4381 estimates of recovery potential. In 518 cases (36.2%; 95% CI, 33.7%-38.7%), all experts believed that recovery potential was less than 1% if life-sustaining therapies had been continued. In the remaining 913 cases (63.8%; 95% CI, 61.3%-66.3%), at least 1 expert believed that recovery potential was at least 1%. In 227 cases (15.9%; 95% CI, 14.0%-17.9%), all experts agreed that recovery potential was at least 1%, and in 686 cases (47.9%; 95% CI, 45.3%-50.6%), expert estimates differed at this threshold.Conclusions and RelevanceIn this cohort study of comatose patients resuscitated from cardiac arrest, most who died after WLST were considered by experts to have had recovery potential. These findings suggest that novel solutions to avoiding deaths based on biased prognostication or incomplete information are needed.

Abstract A collection of patients are seen in the neurointensive care unit and other medical and surgical intensive care units. Diagnosis, neuroimaging, and management in acute conditions are discussed in detail. In this new edition, we place more emphasis on how diagnostic and management decisions can go awry. When pertinent, we discuss new care paradigms, the latest support modalities, and new therapies, interventions, and technologies, but the main purpose is to convey a sense of what our specialty is all about. The book is useful for all health care professionals, essential material for learners and fellows in intensive care specialties and informational for staff attending physicians and hospitalists.

Background: Systolic blood pressure (SBP) fluctuation is linked to increased death or disability in intracerebral hemorrhage (ICH) patients. We analyzed data from the Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH)-2 trial to explore whether the association between SBP fluctuation and 90-day outcomes varies with time from randomization. Methods: We calculated hourly SBP fluctuation based on the difference between maximum and minimum SBP during the first 24 hours post-randomization. Logistic regression models assessed the impact of SBP fluctuation on: 1) death or disability (modified Rankin scale [mRS] 4-6 at 90 days); 2) hematoma expansion (>33% increase in volume on 24-hour CT scan); 3) neurological deterioration within 24 hours (defined as ≥2-point decrease on Glasgow Coma Scale or ≥4-point increase on NIH Stroke Scale); and 4) acute kidney injury (AKI) within 72 hours. Adjustments were made for baseline Glasgow Coma Scale score, intraventricular hemorrhage, hematoma volume, and maximum SBP. Results: The hourly SBP fluctuations according to 90-day outcomes (dichotomized into good outcome, mRS 0-3, and poor outcome, mRS 4-6) in 961 patients with ICH are presented in Figure. The SBP fluctuation at 5 hours (p=0.014) and 6 hours (p=0.014) post randomization were significantly associated with death or disability at 90 days, with positive, but not statistically significant associations observed at all other points up to 13 hours after randomization. Risk of neurological deterioration within 24 hours was highly associated with SBP fluctuation, with the largest association observed between 1 (p<0.001) and 5 (p<0.001) hours following randomization, with significant associations observed up to 22 hours following randomization. Risk of hematoma expansion was associated with SBP fluctuation between 3 (p=0.015) and 8 (p=0.002) hours post randomization. Statistically significant associations between SPB fluctuations and risk of AKI were not observed. Conclusions: The first 8 hours following randomization are critical for reducing SBP fluctuations, as this period most strongly influences both short- and long-term outcomes in ICH patients. These findings suggest this time window is crucial for future interventions aimed at controlling SBP in ICH patients.

Background: Symptomatic intracranial hemorrhage (sICH) is the most dreaded complication after reperfusion therapy for acute ischemic stroke. We performed a meta-analysis of randomized controlled trials to estimate and compare risks of sICH after mechanical thrombectomy (MT) depending on the location of the large vessel occlusion, concomitant use of intravenous thrombolysis, timing of treatment, and core size. Methods: Randomized controlled trials were included following a comprehensive search strategy on different databases from inception to March 1, 2024. Random-effect models in a meta-analysis were employed to get the pooled risk ratios (RRs) and their corresponding 95% confidence intervals (95% CI) for sICH with MT, compared to other reperfusion treatment regimens, including best medical treatment and intravenous thrombolysis (IVT). Results: MT in the anterior circulation was associated with a significantly higher risk of sICH as compared with no-MT (RR: 1.46; 95%CI: 1.03-2.07; P = 0.037). Risk of sICH was comparable between the MT and MT+IVT groups (RR: 0.77; 95%CI: 0.57-1.03; P = 0.079). There was no difference in sICH risk with MT as compared with no-MT within 6 hours of last known well (RR: 1.14; 95%CI: 0.78-1.66; P = 0.485) and beyond that time (RR: 1.29; 95%CI: 0.80-2.08; P = 0.252); the risk of sICH was also comparable between MT conducted within 6 hours of last known well and MT conducted beyond that time (P = 0.512). The sICH risk for MT in the posterior circulation (RR: 7.48; 95%CI: 2.27-24.61) was significantly higher than for MT in the anterior circulation (RR: 1.18; 95%CI: 0.90-1.56) (P = 0.003). MT was also associated with a significantly higher sICH risk than no-MT among patients with large-core strokes (RR: 1.71; 95%CI: 1.09-2.66, P = 0.018). Conclusion: When evaluating cumulative evidence from randomized controlled trials, the risk of sICH is increased after MT compared with patients not treated with MT. Yet, the difference is largely driven by the greater risk of sICH in patients treated with MT for posterior circulation occlusions and, to a lesser degree, large core strokes. Concomitant use of intravenous thrombolysis and the use of MT in the extended therapeutic window do not raise the risk of sICH.

Introduction: Posterior reversible encephalopathy syndrome (PRES) has been defined based on classic risk factors, clinical characteristics, and evidence of reversibility. Radiographic evidence of vasogenic edema, which is best seen on MRI, is considered a cornerstone of the diagnosis. Yet, severity of clinical presentation does not correlate with extent of edema on MRI. We sought to explore whether PRES can present with negative MRI by comparing clinical features between cases of PRES with classic MRI findings and cases of hypertensive encephalopathy without MRI changes. Methods: Patients diagnosed with hypertensive encephalopathy from August 1, 2008 to December 31, 2017 were identified retrospectively and matched by age (+/- 5 years) and sex in a 2:1 ratio to patients retrospectively identified as having PRES from January 1 st , 2002 to November 30 th , 2017. All patients had undergone MRI, and images were reviewed. A detailed review of clinical information from the medical records was performed and included analysis of presenting symptoms, risk factors, and medical history. Results: We identified 16 cases of hypertensive encephalopathy and 32 age and sex matched controls with PRES on MRI. There were no statistically significant differences in the odds of presentation with headache (OR=1.372, 95% CI [0.458, 4.106]), encephalopathy (OR=2.303, 95% CI [0.433, 12.236]), visual disturbance (OR= 0.826, 95% CI [0.185, 3.697]), or focal neurologic deficit (OR=4.000, 95% CI [0.767, 20.872]). Seizures were more common at presentation in patients with typical PRES with vasogenic edema (OR=0.082, 95% CI [0.010, 0.664]). There was no significant difference in baseline creatine (OR= 0.874, 95% CI [0.424, 1.799]), admission creatine (OR= 1.215, 95% CI [0.819, 1.803]), or odds of acute kidney injury (OR=2.90, 95% CI [0.679, 12.449]). There were no statistically significant differences in the odds of having a past medical history of malignancy (OR= 0.295, 95% CI [0.076, 1.152]), transplant (OR= 3.347, 95% CI [0.594, 18.880]), or autoimmune disease (OR= 0.400, 95% CI [0.104, 1.532]). Resolution to baseline was the norm and occurred similarly in both groups. Conclusions: Most presenting symptoms and key risk factors were not significantly different between cases of hypertensive encephalopathy without vasogenic edema on MRI and typical PRES, arguing that the diagnosis of PRES, at least in the setting of acute severe hypertension, should not depend on MRI confirmation.

Background Left ventricular assist devices (LVADs) are used as definitive therapy or as a bridge to heart transplant in patients with advanced heart failure. Thromboembolic complications such as acute ischemic stroke (AIS) are common among patients with LVAD support. This study aims to evaluate the current evidence on the efficacy and safety of mechanical thrombectomy (MT) in patients with AIS due to large vessel occlusions (LVO) and LVAD-support. Methods A comprehensive systematic review was conducted in PubMed, Embase, and Scopus to find observational studies with reports of ≥5 MTs in adult patients with LVAD support (PROSPERO registration code CRD42024597541). Rates of successful and complete reperfusion, favorable functional outcomes at 90 days (modified Rankin Scale (mRS) 0–2 or equal to pre-stroke mRS), mortality at 90 days, any intracerebral hemorrhage (ICH) and symptomatic ICH (sICH) were pooled using generalized linear mixed models. Results Eight studies were included with data from 51 patients and 62 MTs. The rate of successful reperfusion was 87.4% (95% CI 62.5% to 96.6%) and complete reperfusion rate was 57.3% (95% CI 35.1% to 76.9%). Rate of favorable functional recovery was 62.5% (95% CI 42.2% to 79.2%). Rate of sICH was 6.4% (95% CI 0.9% to 34.0%). Mortality rate was 16.7% (95% CI 7.1% to 34.7%). Between 25–40% of patients who were waiting for a heart transplant before their stroke received a heart transplant after MT. Conclusions MT for the emergent treatment of AIS in the setting of LVAD is relatively safe and efficacious for achieving successful reperfusion and good functional recovery.

Background: A vast amount of literature is available on the burden of acute ischemic stroke (AIS). Yet, most information on AIS burden does not stratify by stroke severity, and the inclusion of mild strokes (National Institute of Health Stroke Scale < 5) might obscure the true impact of moderate-to-severe AIS. Therefore, it is important to understand the literature as it pertains to the epidemiological, clinical, humanistic, and economic burden of moderate-to-severe AIS from a global perspective. Methods: A systematic literature review (SLR) was conducted, including articles published between January 2015 and June 2023. The clinical burden search focused on patients with moderate or severe AIS. Due to the paucity of evidence, the humanistic and economic burdens were evaluated based on overall AIS studies. Abstract and full-text screening were conducted by 2 reviewers, with data extraction completed by 1 reviewer. In all, 136 studies were included in the SLR. Results: AIS caused a substantial burden for patients and the healthcare system. The clinical burden of AIS (specifically severe AIS) resulted in high mortality and worse functional outcomes across multiple demographics (female sex, older age, and patients with comorbidities). The economic burden of overall AIS was substantial, with inpatient costs as the primary driver (a mean or median stay of 7 days). The highest inpatient costs were reported in South Korea ($45,180) and the United States ($38,470). Conclusions: The review highlighted the huge burden of moderate-to-severe AIS, with patients experiencing worse outcomes with increased stroke severity. Further focus is needed on outcomes relating to moderate-to-severe AIS to fully understand the burden of stroke in this patient population.

Background The impact of certain comorbidities on mechanical thrombectomy (MT) outcomes remains largely unexplored. Diabetes mellitus (DM) and admission hyperglycemia have been associated with poor clinical outcomes for patients treated with MT. In this study, we sought to investigate the effects of DM and admission hyperglycemia on MT outcomes. Methods Following PRISMA guidelines, a systematic literature search was conducted in Medline, Embase, Scopus, and Web of Science databases. Data regarding successful recanalization (modified Thrombolysis in Cerebral Infarction [mTICI] ≥2b), functional independence (modified Rankin Scale [mRS] 0–2), excellent outcomes (mRS 0–1), symptomatic intracranial hemorrhage (sICH), and mortality were extracted from the included studies. The pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were calculated using random effects model. Results Twenty-one studies comprising 9708 patients were included. A total of 2311 patients (24%) had a history of DM, and 2026 patients (21%) had admission hyperglycemia. Admission hyperglycemia was associated with significantly lower odds of mTICI ≥2b (OR = 0.7, 95% CI = 0.55–0.89), mRS 0–2 (OR = 0.47, 95% CI = 0.41–0.53), and mRS 0–1 (OR = 0.43, 95% CI = 0.34–0.55) as compared to normoglycemic state. Patients with hyperglycemia had significantly higher rates of sICH (OR = 2.05, 95% CI = 1.66–2.54) and mortality (OR = 1.99, 95% CI = 1.58–2.52) than normoglycemic patients. Diabetes mellitus was associated with significantly high rates of mortality (OR = 1.74, 95% CI = 1.31–2.3) and lower rates of mRS 0–2 (OR = 0.60, 95% CI = 0.48–0.76) in sensitivity analyses. Conclusion Our results indicate that admission blood glucose levels and DM can negatively affect MT outcomes. Further research should focus on optimizing MT outcomes for these patients.