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 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.

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.

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.

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.

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.

Crying with depressed affect induced by electrical stimulation of the anterior insula: A stereo EEG case study.

Stereo-EEG (sEEG) is an invasive recording technique used to localize the seizure-onset zone for epilepsy surgery in people with drug-resistant focal seizures. Pathological crying reflects disordered emotional expression and the anterior insula is known to play a role in empathy and socio-emotional processing. We describe a patient where electrical stimulation mapping (ESM) of the anterior insula during sEEG generated pathological crying and profound sadness that was time-locked to the electrical stimulus. We evaluated a 35-year-old left-handed female for repeat epilepsy surgery. The patient had drug resistant focal impaired awareness seizures despite a previous left temporal neocortical resection informed by an invasive study using subdural grid and strip electrodes seven years earlier. She was studied invasively with 10 sEEG electrodes sampling temporal, occipital, and insular targets. In the process of functional mapping, stimulation of the anterior insular cortex provoked tearful crying with sad affect, reproducible upon repeat stimulation. Our case is unique in demonstrating transitory pathological crying with profound sadness provoked by ESM of the left anterior insula. Furthermore we demonstrate repeated time-synched crying from electrical stimulation, which supports the hypothesis that the anterior insula in the brain plays an important role in the biology of emotion, as implicated by previous studies.

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.

Functional outcome after critical illness in older patients: a population-based study.

PURPOSE: To determine the prevalence of disability among ICU survivors one year after admission, and which factors influence functional outcome. METHODS: We examined consecutive patients enrolled in the population-based Mayo Clinic Olmsted Study of Aging and then admitted to medical or surgical adult ICUs at Mayo Clinic, Rochester between January 1, 2006, and December 31, 2014 to determine one-year functional outcomes. RESULTS: 831cases were included. Mean age was 84 years (IQR 79-88). 569 (68.5%) patients were alive one year after ICU admission. Of them, 546 patients had functional assessment at one year and 367 (67.2%) had good functional outcome. On multivariable analysis, poor one-year functional outcome (death or disability) was more common among women, older patients, and patients with baseline cognitive impairment (mild cognitive impairment or dementia), higher Carlson scores, and longer ICU stay (all P <.01). After excluding deceased patients, these associations remained unchanged. In addition, 120 (32.3%) of 372 patients who had post-ICU cognitive evaluation experienced cognitive decline after the ICU admission. CONCLUSIONS: On a population-based cohort of older, predominantly elderly patients, approximately two-thirds of survivors maintained or regained good functional status 1 year after ICU hospitalization. However, older age, female sex, greater comorbidities, abnormal baseline cognition, and longer ICU stay were associated with poor functional recovery and cognitive decline was common.

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.

Association of septic shock definitions and standardized mortality ratio in a contemporary cohort of critically ill patients.

PURPOSE: The newly proposed septic shock definition has provoked a substantial controversy in the emergency and critical care communities. We aim to compare new (SEPSIS-III) versus old (SEPSIS-II) definitions for septic shock in a contemporary cohort of critically ill patients. MATERIAL AND METHODS: Retrospective cohort of consecutive patients, age ≥ 18 years admitted to intensive care units at the Mayo Clinic between January 2009 and October 2015. We compared patients who met old, new, both, or neither definition of sepsis shock. SMR were calculated using APACHE IV predicted mortality. RESULTS: The initial cohort consisted of 16,720 patients who had suspicion of infection, 7463 required vasopressor support. The median (IQR) age was 65(54-75) years and 4167(55.8%) were male. Compared to patients with old definition, the patients with new definition had higher APACHE III score (median IQR); (73 (57-92) vs. 70 (56-89), p < .01); SOFA score; (6 (4-10) vs. 6 (4-9), p < .01), were older (70 (59-79) vs. 64 (54-74) years, p = .03). They also had higher hospital mortality, N (%) 71, (19.7%) vs. 40 (12.6%), p < .01) and a higher SMR (0.66 vs. 0.45, p < .01). CONCLUSIONS: Compared to SEPSIS-II, SEPSIS-III definition of septic shock identifies patients further along disease trajectory with higher likelihood of poor outcome.

Time Trends in Outcomes After Aneurysmal Subarachnoid Hemorrhage Over the Past 30 Years.

OBJECTIVE: To analyze trends in mortality rates, functional outcomes, and treatment in patients with aneurysmal subarachnoid hemorrhage (aSAH) over the past 3 decades. PATIENTS AND METHODS: We conducted a retrospective review of consecutive patients with aSAH treated at Mayo Clinic in Rochester, Minnesota, between January 1, 1985, and December 31, 2014. RESULTS: A total of 1173 patients identified were grouped by decade of treatment: 1985 to 1994, n=274; 1995 to 2004, n=461; and 2005 to 2014, n=438. Overall, the use of endovascular techniques increased progressively from 5.1% (14) in 1985 to 1994 to 65.5% (287) in 2005 to 2014. This corresponded to a progressive decrease in the rate of clipping from 78.8% (216) in 1985 to 2004 to 21.5% (94) in 2005 to 2014 (P<.001). The percentage of patients admitted with poor clinical grade also increased from 22.3% (61) in 1985 to 1994 to 24.1% (111) in 1995 to 2004 and 29.5% (129) in 2005 to 2014 (P=.06). The in-hospital mortality rate decreased from 22.6% (62) in 1985 to 1994 to 16.3% (75) in 1995 to 2004 and remained relatively constant at 16.7% (73) in 2005 to 2014. Good functional outcome at 3- to 6-month follow-up improved significantly from 64.8% (173) in 1985 to 1994 to 72% (332) in 1995 to 2004 and 78.8% (345) in 2005 to 2014 (P<.001). CONCLUSION: Outcomes in patients with aSAH have markedly improved over the past 3 decades, in terms of both in-hospital survival and functional recovery of survivors. Higher rates of endovascular coiling over time paralleled these improvements in clinical outcomes. More detailed investigation is necessary to determine whether this or other factors may directly explain the favorable trends in survival and functional recovery over time.

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.

Potentially Modifiable Risk Factors for Long-Term Cognitive Impairment After Critical Illness: A Systematic Review.

Long-term cognitive impairment is common in survivors of critical illness. Little is known about the etiology of this serious complication. We sought to summarize current scientific knowledge about potentially modifiable risk factors during intensive care unit (ICU) treatment that may play a substantial role in the development of long-term cognitive impairment. All searches were run on October 1, 2017. The search strategy included Ovid MEDLINE, Ovid Embase, Ovid CDR, Cochrane Central Register of Controlled Trials and Database of Abstracts of Reviews of Effect, Scopus, and Web of Science, and included MeSH headings and keywords related to intensive care, critical care, and cognitive disorders. Searches were restricted to adult subjects. Inclusion required follow-up cognitive evaluation at least 2 months after ICU discharge. Studies assessing patients with cardiac arrest, traumatic brain injury, and cardiac surgery history were excluded. The search strategy resulted in 3180 studies. Of these, 28 studies (.88%) met our inclusion criteria and were analyzed. Delirium and duration of delirium were associated with long-term cognitive impairment after ICU admission in 6 of 9 studies in which this factor was analyzed. Weaker and more inconsistent associations have been reported with hypoglycemia, hyperglycemia, fluctuations in serum glucose levels, and in-hospital acute stress symptoms. Instead, most of the studies did not find significant associations between long-term cognitive impairment and mechanical ventilation; use of sedatives, vasopressors, or analgesic medications; enteral feeding; hypoxia; extracorporeal membrane oxygenation; systolic blood pressure; pulse rate; or length of ICU stay. Prolonged delirium may be a risk factor for long-term cognitive impairment after critical illness, though this association has not been entirely consistent across studies. Other potentially preventable factors have not been shown to have strong or consistent associations with long-term cognitive dysfunction in survivors of critical illness.

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.