Association of Blood Pressure Variability with Delirium in Patients with Critical Illness.

BACKGROUND: The objective was to examine the association of blood pressure variability (BPV) during the first 24 h after intensive care unit admission with the likelihood of delirium and depressed alertness without delirium ("depressed alertness"). METHODS: This retrospective, observational, cohort study included all consecutive adult patients admitted to an intensive care unit at Mayo Clinic, Rochester, Minnesota, from July 1, 2004, through October 31, 2015. The primary outcomes were delirium and delirium-free days, and the secondary outcomes included depressed alertness and depressed alertness-free days. Logistic regression was performed to determine the association of BPV with delirium and depressed alertness. Proportional odds regression was used to assess the association of BPV with delirium-free days and depressed alertness-free days. RESULTS: Among 66,549 intensive care unit admissions, delirium was documented in 20.2% and depressed alertness was documented in 24.4%. Preserved cognition was documented in 55.4% of intensive care unit admissions. Increased systolic and diastolic BPV was associated with an increased odds of delirium and depressed alertness. The magnitude of the association per 5-mm Hg increase in systolic average real variability (the average of absolute value of changes between consecutive systolic blood pressure readings) was greater for delirium (odds ratio 1.34; 95% confidence interval 1.29-1.40; P < 0.001) than for depressed alertness (odds ratio 1.06; 95% confidence interval 1.02-1.10; P = 0.004). Increased systolic and diastolic BPV was associated with fewer delirium-free days but not with depressed alertness-free days. CONCLUSIONS: BPV in the first 24 h after intensive care unit admission is associated with an increased likelihood of delirium and fewer delirium-free days.

SMART syndrome: retrospective review of a rare delayed complication of radiation.

BACKGROUND: SMART (stroke-like migraine attacks after radiation therapy) is a rare, delayed complication of brain radiation. In this study, we wanted to review the spectrum of symptoms, neuroradiological findings, autoimmune status, and outcomes in SMART syndrome patients. METHODS: We conducted a retrospective cohort study of all consecutive adult patients (≥18 years) diagnosed with SMART syndrome at Mayo Clinic, Rochester between January 1995 and December 2018. RESULTS: We identified 25 unique patients with SMART syndrome and a total of 31 episodes and 15 (60%) patients were male. The median age at onset was 46 (interquartile range [IQR] 43-55) years and the median latency of onset after the initial radiation was 21.6 (IQR 14.4-28.2) years. Magnetic resonance imaging (MRI) showed gyral edema and enhancement in all cases with the temporal (25, 80.6%) and parietal (23, 74.2%) lobes being the most commonly affected. The median follow-up of the patients in our cohort was 10 (IQR 6-32) weeks. On univariate analysis, factors associated with an increased risk of recurrent SMART episodes were female gender (odds ratio [OR] 8.1, 95% confidence interval [95% CI] 1.1-52.6, p = 0.019) and absence of electrographic seizure discharges during initial symptoms (OR 7.4, 95% CI 1.1-45.9, p = 0.032). We could not identify an autoimmune etiology. Longer duration of symptoms (>10 weeks) correlated with an older age (p = 0.049), temporal lobe involvement (p < 0.001), and diffusion restriction (p = 0.043). CONCLUSIONS: SMART is a syndrome with characteristic imaging findings and clinical features. Incomplete recovery by 10 weeks occurred in one-third of individuals and was associated with older age, temporal lobe involvement, and restricted diffusion on MRI.

Outcomes of adult patients supported by extracorporeal membrane oxygenation (ECMO) following cardiopulmonary arrest. The Mayo Clinic experience.

INTRODUCTION: To describe our experience in use of extracorporeal life support (ECLS) as a rescue strategy in patients following cardiopulmonary resuscitation. METHODS: A retrospective analysis was performed for patients (n = 101) who received ECLS after cardiorespiratory arrest between May 2001 and December 2014. The primary outcome was survival to hospital discharge. RESULTS: In this cohort median (IQR) age was 56 (37-67) years, 53 (53%) were male, and 90 (89%) were Caucasian. Ventricular tachycardia or ventricular fibrillations were the initial cardiac rhythm in 49 (48.5%) and asystole/pulseless electrical activity in 37 (36.8%). Median (IQR) time to initiation of extracorporeal support from arrest time was 72 (43-170) min. The median (IQR) duration of support was 100 (47-157) hours. Renal failure (66%) and bleeding (66%) were the two most commonly observed complications during ECLS support. The survival to hospital discharge was seen in 47 (47%) patients, and good neurologic outcome (mRs 0-3) was seen in 29%. Acidosis, lactate and continuous renal replacement therapy were independent predictors of mortality. The median (IQR) intensive care unit stay was 14 (4-28) days and hospital stay was 17 (4-35) days. CONCLUSION: Our institutional experience with ECLS as a rescue measure following cardiac arrest is associated with improvement in mortality, and favorable neurologic status at hospital discharge.

Cefepime is Associated with Acute Encephalopathy in Critically Ill Patients: A Retrospective Case-Control Study.

BACKGROUND: Acute encephalopathy (AE) is a common complication of critical illness and is associated with increased short and long-term mortality. In this study, we evaluated the role of cefepime in causing AE. METHODS: Retrospective case-control study involving consecutive patients enrolled in the intensive care units (ICUs) of Mayo Clinic Rochester, MN between July 1, 2004 and December 31, 2015. AE was defined by the presence of delirium or depressed level of consciousness in the absence of deep sedation. Controls were identified as patients not developing AE and were matched by propensity score for age, Charlson Comorbidity Index, 24-h Apache III score and invasive ventilation use. RESULTS: The total number of eligible ICU admissions during our study period was 152,999. AE was present in 57,726 (37.7%) with a median AE duration of 17 (interquartile range [IQR] 4.0-51.8) hours. We matched 14,645 cases with AE with the same number of controls. Cefepime was used in 1241 (4.2%) patients and its use was associated with greater incidence of AE [713 (4.9%) vs 528 (3.6%), p < 0.001] and duration [unit estimate 0.73; (95% CI 0.542-0.918)]. On multivariate analysis, cefepime was associated with an increased likelihood of AE after controlling for shock, midazolam infusion and acute kidney injury [OR 1.24 (95% CI 1.10-1.27)]. These associations were also present after controlling for prior chronic kidney disease. CONCLUSION: The use of cefepime is associated with increased likelihood and duration of AE. These associations are stronger among patients with impaired renal function, but can also occur in patients without renal impairment.

Risk Factors for Persistent Cognitive Impairment After Critical Illness, Nested Case-Control Study.

OBJECTIVES: Persistent cognitive impairment after critical illness is an important healthcare problem forecasted to worsen in the near future. However, the epidemiology is insufficiently explored. We aimed to determine potentially modifiable risk factors during ICU hospitalization that play a significant role in developing persistent cognitive impairment. DESIGN: An observational case-control study. SETTINGS: Mayo Clinic ICUs between July 1, 2004, and November 20, 2015. PATIENTS: We conducted a study nested in a large cohort of 98,227 adult critically ill patients. Using previously validated computable phenotypes for dementia and cognitive impairment, we determined the onset of cognitive impairment relative to ICU hospitalization and associated risk factors. The primary endpoint of the study was new and persistent cognitive impairment documented between 3 and 24 months after ICU discharge. INTERVENTIONS: Unadjusted and adjusted analyses were performed to identify potentially modifiable risk factors during ICU hospitalization. MEASUREMENTS AND MAIN RESULTS: Among 21,923 unique patients identified as cognitively impaired (22% of the entire ICU cohort), 2,428 (2.5%) developed incident new and persistent cognitive dysfunction after the index ICU admission. Compared with age- and sex-matched ICU controls (2,401 pairs), cases had higher chronic illness burden (Charlson Comorbidity Index, 6.2 vs 5.1; p < 0.01), and were more likely to have multiple ICU stays (22% vs 14%; p < 0.01). After adjustment for baseline differences, new and persistent cognitive dysfunction was associated with higher frequency of acute brain failure in the ICU, a higher exposure to severe hypotension, hypoxemia, hyperthermia, fluctuations in serum glucose, and treatment with quinolones or vancomycin. Association with sepsis observed in univariate analysis did not persist after adjustment. CONCLUSIONS: Cognitive dysfunction is highly prevalent in ICU patients. Incident new and persistent cognitive impairment is less common but important, potentially preventable problem after critical illness. Chronic comorbidities and number of ICU stays increase the risk of post-ICU cognitive dysfunction irrespective of age. Modifiable ICU exposures were identified as potential targets for future prevention trials.

Features of Adult Hyperammonemia Not Due to Liver Failure in the ICU.

OBJECTIVES: To evaluate the epidemiology of hyperammonemia unrelated to liver failure in the critical care setting. DESIGN: Retrospective case series. SETTING: Critically ill patients admitted to ICUs at Mayo Clinic, Rochester, MN (medical ICU, two mixed medical-surgical ICUs, coronary care unit, or the cardiosurgical ICU) between July 1, 2004, and October 31, 2015. PATIENTS: Adult critically ill patients with hyperammonemia not related to acute or chronic liver failure. We excluded patients with diagnosis of moderate or severe liver disease, hyperbilirubinemia, and patients who denied the use of their medical records. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 3,908 ICU patients with hyperammonemia, 167 (4.5%) had no evidence of acute or chronic liver failure. One-hundred one patients (60.5%) were male with median age of 65.7 years (interquartile range, 50-74.5 yr) and median serum ammonia level of 68 µg/dL (interquartile range, 58-87 µg/dL). Acute encephalopathy was present in 119 patients (71%). Predisposing conditions included malnutrition 27 (16%), gastric bypass six (3.6%), total parenteral nutrition four (2.4%); exposure to valproic acid 17 (10%); status epilepticus 11 (6.6%), high tumour burden 19 (11.3%), and renal failure 82 (49.1%). Urea cycle defects were diagnosed in seven patients (4.1%). Hospital mortality was high (30%), and median ammonia level was higher among the nonsurvivors (74 vs 67 µg/dL; p = 0.05). Deaths were more likely in hyperammonemic patients who were older (p = 0.016), had greater illness severity (higher Acute Physiology and Chronic Health Evaluation III score, p < 0.01), malignancy (p < 0.01), and solid organ transplantation (p = 0.04), whereas seizure disorder was more common in survivors (p = 0.02). After adjustment, serum ammonia level was not associated with increased mortality. CONCLUSIONS: Hyperammonemia occurs in a substantial minority of critically ill patients without liver failure. These patients have a poor prognosis, although ammonia level per se is not independently associated with mortality. Serum ammonia should be measured when risk factors are present, such as nutritional deficiencies and protein refeeding, treatment with valproic acid, high tumour burden, and known or suspected urea cycle abnormalities.

Episodic status migrainosus: A novel migraine subtype.

Objective To report a case series of a novel migraine subtype, which we term as episodic status migrainosus (ESM), characterized by attacks of migraine exclusively lasting more than 72 hours. We hypothesized that this would represent a novel nosologic entity, possibly an unstable migraine phenotype with a high conversion rate to chronic migraine (CM). Methods We conducted a retrospective review of patients diagnosed with status migrainosus at the Mayo Clinic, Rochester, between January 2005 and December 2015. All the records were then manually reviewed for patients with migraine headaches exclusively lasting more than 72 hours. Results We identified 18 patients with ESM, with a female predominance (15(83.3%)) and a median age of onset of 16.5 (IQR 13-19) years. The median monthly attack frequency was two (IQR 1-3), with each attack lasting a median duration of seven (IQR 4-12.5) days. Stress was the most commonly reported precipitant (11 (61.1%)). Migraine with aura was common (10 (55.6%)), as was comorbid depression (10 (55.6%)). Fifteen (83.3%) patients developed CM at a median of 7.8 (IQR 2.6-21.9) years from their first attack. There was no significant association between the time to the development of chronic migraine with either attack frequency or duration. Conclusions and relevance We report the existence of a novel migraine subtype, episodic status migrainosus. This migraine subtype appears to have similar clinical characteristics to episodic migraine with or without aura, except for a notably high tendency to progress to chronic migraine.

SSRI/SNRI Use is Not Associated with Increased Risk of Delayed Cerebral Ischemia After aSAH.

BACKGROUND: To determine the effect of selective serotonin reuptake inhibitor (SSRI)/selective norepinephrine reuptake inhibitor (SNRI) use on the risk of symptomatic vasospasm and delayed cerebral ischemia (DCI) in patients hospitalized with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: Retrospective review of consecutive patients with aSAH at Mayo Clinic, Rochester from January 2001 to December 2013. The variables collected and analyzed included age, sex, SSRI/SNRI use, active smoking, transfusion, modified Fisher score, WFNS grade, and outcome at discharge. Multivariate logistic regression analysis was used to evaluate factors associated with DCI, symptomatic vasospasm, and poor outcome (modified Rankin score 3-6) within 1 year. RESULTS: 579 [females 363 (62.7%)] patients with a median age of 55 (IQR 47-65) years were admitted with aSAH during the study period. WFNS at nadir was IV-V in 240 (41.5%), and modified Fisher score was 3-4 in 434 (75.0%). 81 (13.9%) patients had been prescribed an SSRI or SNRI prior to admission and all continued to receive these medications during hospitalization. Symptomatic vasospasm was present in 154 (26.4%), radiological infarction in 172 (29.5%), and DCI in 250 (42.9%) patients. SSRI/SNRI use was not associated with the occurrence of DCI (p = 0.458), symptomatic vasospasm (p = 0.097), radiological infarction (p = 0.972), or poor functional outcome at 3 months (p = 0.376). CONCLUSIONS: The use of SSRI/SNRI prior to and during hospitalization is not associated with DCI or functional outcome in patients with aSAH.

Predictors of Extubation Success in Patients with Posterior Fossa Strokes.

OBJECTIVE: Posterior fossa stroke is unique in its presentation and outcomes, and mechanical ventilation is commonly used in the management of these patients. We aimed to identify predictors of extubation success in patients with posterior fossa stroke, who require mechanical ventilation. DESIGN: We included consecutive adult patients admitted to the neurosciences ICU from January 2003 to December 2012. Extubation failure was defined as re-intubation within 7 days of extubation. A modified Rankin Scale score of 0-3 was considered a good outcome. MEASUREMENTS AND MAIN RESULTS: We identified 150 patients with mean age of 65 ± 15.7 years with posterior fossa strokes; 77 (51 %) were hemorrhagic, and 73 (49 %) were ischemic. The most common reason for intubation was depressed consciousness (54 %). Fifty-two (35 %) were successfully extubated, 18 (12 %) failed extubation, 17 (11 %) patients had tracheostomy without attempted extubation, and 63 (42 %) were transitioned to palliative care prior to extubation. In the logistic regression analysis, controlling for transition to palliative care, Glasgow Coma Score (GCS) score >6 at the time of intubation (p = 0.020), mechanical ventilation for less than 7 days (p = 0.004), and surgical evacuation of a hematoma (p = 0.058) were independently associated with successful extubation. The presence of cough, gag reflex, and absence of pneumonia/atelectasis were not associated with successful extubation. Success of extubation predicted a good outcome at hospital discharge. CONCLUSIONS: In posterior fossa stroke patients with a GCS ≤ 6 at the time of intubation and who remain intubated for more than 1 week, extubation is less likely to be successful, and tracheostomy should be considered.

Postencephalitic epilepsy: clinical characteristics and predictors.

OBJECTIVE: To describe the etiologies, clinical presentations, outcomes, and predictors of postencephalitic epilepsy (PE) in a large series of adult patients with acute encephalitis. METHODS: We conducted a retrospective review of patients diagnosed with acute encephalitis at Mayo Clinic, Rochester, between January 2000 and December 2012. The patients were categorized into two groups based on the presence or absence of PE at last follow-up. Multivariate logistic regression analysis was used to analyze factors associated with PE. RESULTS: We identified 198 consecutive patients (100 [50.5%] male and 98 [49.5%] female) with a median age of 58 years (range 41.8-69). Etiologies included viral infection (n=95, 48%), autoimmune (n=44, 22%), and unknown/others (n=59, 30%). During hospitalization, seizures were seen in patients with autoimmune encephalitis (n=24, 54.5%), unknown/others (n=20, 33.9%), and viral encephalitis (n=23, 24.2%). Interictal epileptiform discharges on electroencephalography (EEG) were present in 34 (54%), whereas periodic lateralized epileptiform discharges (PLEDs) and generalized periodic discharges (GPDs) were seen in 14 (41.2%) and 2 (5.9%) patients. Forty-six patients with seizures (70.8%) had fluid-attenuated inversion recovery (FLAIR)/T2 abnormalities, 20 (31.3%) diffusion abnormalities, and 43 (66.2%) cortical involvement. Good outcome at discharge among patients with seizures was seen in 8/23 patients with viral etiology (34.8%), 10/24 patients with autoimmune encephalitis (45.5%), and 12/20 patients with unknown cause (60%). PE was present in 43 patients (29.9%). On multivariate regression analysis, the factors associated with PE were generalized seizures during hospitalization (p=0.03), focal seizures (p≤0.001), and the presence of FLAIR/T2 abnormalities on brain magnetic resonance imaging (MRI) (p=0.003). SIGNIFICANCE: The presence of seizures during hospitalization and an abnormal brain MRI are the strongest predictors of the development of PE. The etiology of encephalitis, presence of focal neurologic deficits, and interictal EEG abnormalities did not influence the development of PE.

Asymptomatic Carotid Stenosis: Risk of Progression and Development of Symptoms.

BACKGROUND: The aim of this study is to evaluate the rate of progression of stenosis and development of symptoms in patients with asymptomatic carotid artery stenosis (aCAS) treated with contemporary medical therapy over a prolonged time interval. METHODS: This study is a retrospective review of consecutive patients diagnosed with moderate or severe aCAS at our institution between 2000 and 2001. Data were gathered from both carotid arteries for each patient excluding vessels operated within 1 year of diagnosis and occlusions. Multivariate analysis was performed to analyze factors associated with ipsilateral transient ischemic attack (TIA)/stroke. RESULTS: We identified 214 patients (58.8% men; median age 70 years) and collected data on 349 vessels. Degree of stenosis was severe (>70%) upon diagnosis in 92 (26.4%) vessels. Median length of follow-up was 13 years (interquartile range 10-14), and mean number of time points for follow-up imaging were 8.1 ± 3.9. Progression of stenosis was observed in 237 (67.9%) vessels, and 72 (20.6%) patients developed symptoms ipsilateral to the stenosis (TIA in 14.4%, non-disabling stroke in 4%, disabling stroke in 2.2%). Median time to appearance of first symptom was 6 years (range 1-13). On multivariate analysis, degree of baseline stenosis, intracranial stenosis >50%, plaque ulceration, silent infarction and previous history of TIA/stroke were associated with ipsilateral TIA/stroke, but progression of stenosis was not. CONCLUSIONS: There was a substantial rate of progression of stenosis in patients with aCAS over time despite adequate medical therapy, but progression of stenosis did not increase the risk of ipsilateral TIA/stroke. Over long-term follow-up, 1 in 5 patients with aCAS developed ipsilateral TIA/stroke, though most events were either transient or non-disabling.

Neuropsychiatric symptoms in primary progressive aphasia and apraxia of speech.

AIM: To conduct a prospective analysis of the neuropsychiatric symptoms (NPS) across the three categories of primary progressive aphasia (PPA) and progressive apraxia of speech (PAOS), compare the prevalence and nature of the symptoms, and look at which symptoms could be helpful to better differentiate these PPA and PAOS categories. METHODS: A total of 106 consecutive patients with a diagnosis of semantic variant (n = 13), logopenic variant (n = 37), agrammatic variant (n = 15) or PAOS (n = 41) were included in this prospective study. The NPS were measured by the Neuropsychiatric Inventory Questionnaire. RESULTS: There were 65 patients with PPA and 41 with PAOS diagnosis. The most distinguishing features between the two groups were anxiety, apathy, aberrant motor behavior and appetite, while among the subtypes of PPA they were disinhibition and appetite changes. PPA and PAOS patients initially exhibited depression, but with increased disease duration, PAOS patients showed apathy (55.5%) while PPA patients showed disinhibition (28.6%) and aberrant motor behavior (14.3%). CONCLUSION: Mood symptoms like anxiety and appetite changes are more likely to be present at initial stages of PPA, whereas behavioral symptoms like aberrant motor behavior and apathy are likely to occur early in PAOS. The NPS seem to evolve with the progression of the disease in both PPA and PAOS.

Compound Muscle Action Potential and Myosin-Loss Pathology in Patients With Critical Illness Myopathy: Correlation and Prognostication.

BACKGROUND AND OBJECTIVES: Prolonged compound muscle action potential (CMAP) duration and preferential loss of myosin are considered the diagnostic hallmarks of critical illness myopathy (CIM); however, their correlation and prognostic values have not been studied. We aimed to investigate the correlation between CMAP duration and myosin loss and their effect on mortality by comparing between patients with CIM with and without myosin loss. METHODS: We searched the Mayo Clinic Electromyography Laboratory databases (1986-2021) for patients diagnosed with CIM on the basis of prolonged distal CMAP durations (>15 msec in fibular motor nerve studies recording over the tibialis anterior or >8 msec in other motor nerves) and needle EMG findings compatible with myopathy. Electrodiagnostic studies were generally performed within 24 hours after weakness became noticeable. We included only patients who underwent muscle biopsy. Clinical, electrophysiologic, and myopathologic data were reviewed. We conducted myosin/actin ratio analysis when muscle tissue was available. We used the Fisher exact test for categorical data comparisons and the Mann-Whitney 2-tailed test for continuous data. We applied the Kaplan-Meier technique to analyze survival rates. RESULTS: Twenty patients (13 female patients) were identified [median age at diagnosis of 62.5 years (range: 19-80 years)]. The median onset of weakness was 24 days (range: 1-128) from the first day of intensive care unit admission. Muscle biopsy showed myosin loss in 14 patients, 9 of whom had >50% of myofibers affected (high grade). Type 2 fiber atrophy was observed in 19 patients, 13 of whom also had myosin loss. Patients with myosin loss had higher frequency of steroid exposure (14 vs 3; p = 0.004); higher median number of necrotic fibers per low-power field (2.5 vs 1, p = 0.04); and longer median CMAP duration (msec) of fibular (13.4 vs 8.75, p = 0.02), tibial (10 vs 7.8, p = 0.01), and ulnar (11.1 vs 7.95, p = 0.002) nerves compared with those without. Only patients with high-grade myosin loss had reduced myosin/actin ratios (<1.7). Ten patients died during median follow-up of 3 months. The mortality rate was similar between patients with and without myosin loss. Patients with high-grade myosin loss had a lower overall survival rate than those with low-grade or no myosin loss, but this was not statistically significant (p = 0.05). DISCUSSION: Myosin loss occurred in 70% of the patients with CIM with prolonged CMAP duration. Longer CMAP duration predicts myosin-loss pathology. The extent of myosin loss marginally correlates with the mortality rate. Our findings highlight the potential prognostic values of CMAP duration and myosin loss severity in predicting disease outcome.

Septic shock definitions and associated outcomes in blood culture positive critically ill patients.

Background: The proposed definition of septic shock in the Sepsis-3 consensus statement has been previously validated in critically ill patients. However, the subset of critically ill patients with sepsis and positive blood cultures needs further evaluation. To compare the combined (old and new septic shock) versus old definition of septic shock in sepsis patients that have positive blood cultures and are critically ill. Methods: A retrospective cohort study of adult patients (age ≥18 years), who had evidence of positive blood cultures, requiring intensive care unit (ICU) admission at a large tertiary care academic center from January 2009 through October 2015. Eligible subjects who opted out of research participation, those requiring intensive care admission after elective surgery, and those who were deemed to have a low probability of infection were excluded. Basic demographics data, clinical and laboratory parameters, and outcomes of interest were pulled from the validated institutional database/repository and contrasted between the patients who qualified the new and old definitions criteria (combined) of septic shock versus the group meeting the old septic shock criteria only. Results: We included a total of 477 patients in the final analysis who qualified for old and new septic shock definitions. For the entire cohort, median age was 65.6 (IQR, 55-75) years, with male predominance (N=258, 54%). When compared to patients in the group who only met the old definition (N=206), the patients who met the combined (new or both new and old, N=271) definition had a higher APACHE III scores, 92 (IQR, 76-112) vs. 76 (IQR, 61-95), P<0.001; a higher SOFA day-1 score of 10 (IQR, 8-13) vs. 7 (IQR, 4-10), P<0.001, but did not differ significantly in age 65.5 years (IQR, 55-74) vs. 66 years (IQR, 55-76) years, P=0.47. The patients who met the combined (new or both new and old) definition had higher chances of having conservative resuscitation preferences (DNI/DNR); 77 (28.4) vs. 22 (10.7), P<0.001. The same group also had worse outcomes in terms of hospital mortality (34.3% vs. 18%, P<0.001) and standardized mortality ratio (0.76 vs. 0.52, P<0.04). Conclusions: In patients with sepsis with positive blood cultures, the group of patients meeting the combined definition (new or both new and old) have higher severity of illness, higher mortality, and a worse standardized mortality ratio as compared to patients meeting the old definition of septic shock.

Association of blood pressure variability with short- and long-term cognitive outcomes in patients with critical illness.

BACKGROUND: Blood pressure variability (BPV), a modifiable risk factor, can compromise cerebral perfusion in critically ill patients. We studied the association between BPV in the intensive care unit (ICU) and short- and long-term cognitive outcomes. METHODS: All patients were ≥50 years old. The short-term cognitive end points were delirium and depressed alertness without delirium. The long-term outcome was change in the slope of longitudinal cognitive scores. Primary BPV measure was average real variability (ARV) of systolic blood pressure. Associations were assessed with multivariable multinominal logistic regression and linear mixed effects models. RESULTS: Of 794 patients (1130 admissions) 185 developed delirium and 274 developed depressed alertness. There was a dose-response association of 24-h systolic ARV with delirium (adjusted OR, 95% CI 2.15 per 5 mm Hg increase, 1.31-3.06, P < 0.017) and with depressed alertness (OR 1.89, 95% CI 1.18-3.03, P < 0.008). For 371 patients with available longitudinal cognitive scores, the decline in cognitive trajectory was accelerated after discharge (annual change OR -0.097, 95% CI -0.122 to -0.073). This acceleration increased with delirium (additional decline -0.132 [-0.233 to 0.030], P = 0.011). We found no significant association between BPV and post-ICU cognitive trajectory. CONCLUSIONS: BPV was associated with increased likelihood of delirium in the ICU. Delirium, but not BPV, was associated with long-term cognitive decline.

Neurologic Manifestations of Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Hospitalized Patients During the First Year of the COVID-19 Pandemic.

To describe the prevalence, associated risk factors, and outcomes of serious neurologic manifestations (encephalopathy, stroke, seizure, and meningitis/encephalitis) among patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. DESIGN: Prospective observational study. SETTING: One hundred seventy-nine hospitals in 24 countries within the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study COVID-19 Registry. PATIENTS: Hospitalized adults with laboratory-confirmed SARS-CoV-2 infection. INTERVENTIONS: None. RESULTS: Of 16,225 patients enrolled in the registry with hospital discharge status available, 2,092 (12.9%) developed serious neurologic manifestations including 1,656 (10.2%) with encephalopathy at admission, 331 (2.0%) with stroke, 243 (1.5%) with seizure, and 73 (0.5%) with meningitis/encephalitis at admission or during hospitalization. Patients with serious neurologic manifestations of COVID-19 were older with median (interquartile range) age 72 years (61.0-81.0 yr) versus 61 years (48.0-72.0 yr) and had higher prevalence of chronic medical conditions, including vascular risk factors. Adjusting for age, sex, and time since the onset of the pandemic, serious neurologic manifestations were associated with more severe disease (odds ratio [OR], 1.49; p < 0.001) as defined by the World Health Organization ordinal disease severity scale for COVID-19 infection. Patients with neurologic manifestations were more likely to be admitted to the ICU (OR, 1.45; p < 0.001) and require critical care interventions (extracorporeal membrane oxygenation: OR, 1.78; p = 0.009 and renal replacement therapy: OR, 1.99; p < 0.001). Hospital, ICU, and 28-day mortality for patients with neurologic manifestations was higher (OR, 1.51, 1.37, and 1.58; p < 0.001), and patients had fewer ICU-free, hospital-free, and ventilator-free days (estimated difference in days, -0.84, -1.34, and -0.84; p < 0.001). CONCLUSIONS: Encephalopathy at admission is common in hospitalized patients with SARS-CoV-2 infection and is associated with worse outcomes. While serious neurologic manifestations including stroke, seizure, and meningitis/encephalitis were less common, all were associated with increased ICU support utilization, more severe disease, and worse outcomes.

Neuromuscular Respiratory Failure.

Neuromuscular respiratory failure can result from any disease that causes weakness of bulbar and/or respiratory muscles. Once compensatory mechanisms are overwhelmed, hypoxemic and hypercapnic respiratory failure ensues. The diagnosis of neuromuscular respiratory failure is primarily clinical, but arterial blood gases, bedside spirometry, and diaphragmatic ultrasonography can help in early assessment. Intensive care unit (ICU) admission is indicated for patients with severe bulbar weakness or rapidly progressing appendicular weakness. Intubation should be performed electively, particularly in patients with dysautonomia. Patients with an underlying treatable cause have the potential to regain functional independence with meticulous ICU care.

Antiseizure Medication use in Gastric Bypass Patients and Other Post-Surgical Malabsorptive States.

Healthcare professionals are encountering an increasing number of patients who have undergone bariatric surgeries. Antiseizure medications (ASM) have a narrow therapeutic window, and patients with malabsorptive states receiving ASM present a complex situation as the pharmacokinetics of these drugs have only been studied in patients with a normal functioning gastrointestinal tract. Patients with malabsorptive states may have altered pharmacokinetics, and there is limited literature to guide drug selection and dosage adjustment in patients with malabsorptive states. This review highlights pharmacokinetic parameters of common ASM, and considerations when managing patients on them. The effect of pH, lipophilicity, absorption, and metabolism should be taken into account when selecting and managing ASMs in this patient population. Based on these parameters, levetiracetam, and topiramate have fewer issues referable to absorption related to bariatric surgery while oral formulations of phenytoin, carbamazepine, oxcarbamazepine and valproic acid have reduced absorption due to effects of bariatric surgery based on the pharmacokinetic properties of these medications. Extended formulations should be avoided and ASM serum concentrations should be checked before and after surgery. The care of patients with epilepsy who are scheduled to undergo bariatric surgery should be guided by a multidisciplinary team including a pharmacist and a neurologist who should be involved in the adjustment of the ASMs throughout the pre-surgical and post-surgical periods.