Amra Sakusic

Efficacy of Antitoxin Therapy in Treating Patients With Foodborne Botulism: A Systematic Review and Meta-analysis of Cases, 1923–2016

Background Botulism is a rare, potentially severe illness, often fatal if not appropriately treated. Data on treatment are sparse. We systematically evaluated the literature on botulinum antitoxin and other treatments. Methods We conducted a systematic literature review of published articles in PubMed via Medline, Web of Science, Embase, Ovid, and Cumulative Index to Nursing and Allied Health Literature, and included all studies that reported on the clinical course and treatment for foodborne botulism. Articles were reviewed by 2 independent reviewers and independently abstracted for treatment type and toxin exposure. We conducted a meta-analysis on the effect of timing of antitoxin administration, antitoxin type, and toxin exposure type. Results We identified 235 articles that met the inclusion criteria, published between 1923 and 2016. Study quality was variable. Few (27%) case series reported sufficient data for inclusion in meta-analysis. Reduced mortality was associated with any antitoxin treatment (odds ratio [OR], 0.16; 95% confidence interval [CI], .09-.30) and antitoxin treatment within 48 hours of illness onset (OR, 0.12; 95% CI, .03-.41). Data did not allow assessment of critical care impact, including ventilator support, on survival. Therapeutic agents other than antitoxin offered no clear benefit. Patient characteristics did not predict poor outcomes. We did not identify an interval beyond which antitoxin was not beneficial. Conclusions Published studies on botulism treatment are relatively sparse and of low quality. Timely administration of antitoxin reduces mortality; despite appropriate treatment with antitoxin, some patients suffer respiratory failure. Prompt antitoxin administration and meticulous intensive care are essential for optimal outcome.

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

&NA; 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.

Identification of acute brain failure using electronic medical records.

PURPOSE Up to 80% of critically ill patients have acute neurologic dysfunction syndromes. We evaluated interrater reliability between the examination by the investigator and the charted assessment by the nurse because the accuracy and reliability of detailed data sets extracted from the electronic medical records represents a keystone for creating EMR-based definitions. MATERIALS AND METHODS We conducted a prospective observational study of intensive care unit (ICU) patients to assess the reliability of charted Confusion Assessment Method for the ICU, Glasgow Coma Scale (GSC), Full Outline of Unresponsiveness, and Richmond Agitation Sedation Scale (RASS) scores, and a composite measure of ABF defined as new-onset coma or delirium. Trained investigator blinded to nursing assessments performed the neurologic evaluations that were compared with nursing documentation. RESULTS A total of 202 observations were performed in 55 ICU patients. Excellent correlation was noted for GCS and Full Outline of Unresponsiveness scores on Bland-Altman plots (Pearson correlation 0.87 and 0.92, respectively). Correlation for Confusion Assessment Method for the ICU was also high (κ= 0.86; 95% confidence interval [CI], 0.70-1.01). Richmond Agitation Sedation Scale had good agreement when scores were dichotomized as oversedated (less than -2) vs not oversedated, with κ= 0.76 (95% CI, 0.54-0.98). Investigator assessment and nurse charting were highly concordant (κ= 0.84; 95% CI, 0.71-0.99). CONCLUSION Neurologic assessments documented on the EMR are reliable.

Risk factors and outcomes of critically ill patients with acute brain failure: A novel end point

Objective: To determine the incidence, risk factors and outcomes of acute brain failure (ABF) in a mixed medical and surgical cohort of critically ill patients and its effect on ICU & hospital mortality. Design: Observational electronic medical record (EMR) based retrospective cohort study of critically ill patients admitted to the ICU between 2006 and 2013. Setting: Tertiary academic medical center. Patients: Consecutive adult (>18 years) critically ill patients admitted to medical and surgical ICUs. Patients admitted to the Neuroscience, Pediatric and Neonatal ICUs were excluded. Interventions: None. Measurements and main results: ABF was defined by the presence of delirium (positive CAM‐ICU) or depressed level of consciousness (by abnormal GCS and FOUR scores) in the absence of deep sedation (RASS < −3). Severity of ABF was categorized as grade I if there was delirium with GCS consistently >8 and grade II if the GCS was ≤8 with or without delirium during the ICU hospitalization. ABF duration was not used for this study. Univariate and multivariable analyses were used to access the factors associated with the development of ABF and its effect on short and long term mortality. Of 67,333 ICU patients included in the analysis, ABF was present in 30,610 (44.6%). Patients with ABF had an isolated delirium in 1985 (6.5%) patients, isolated depressed consciousness in 18,323 (59.9%), and both delirium and depressed consciousness in 10,302 (33.6%) patients. When adjusted for comorbidities and severity of illness ABF was associated with increased hospital (OR 3.47; 95% CI 3.19–3.79), and at one year (OR 2.36; 95% CI 2.24–2.50) mortality. Both hospital and one year mortality correlated with the increased severity of ABF. The factors most strongly associated with ABF were pre‐admission dementia (OR 7.86; 95% CI 6.15–10.19) and invasive ventilation (OR 2.32; 95% CI 2.24–2.40) but older age, female sex, presence of liver disease, renal failure, diabetes mellitus, malignancy and COPD were also associated with increased risk of ABF. Conclusions: ABF is a common complication of critical illness and is associated with increased short and long term mortality. The risk of ABF was particularly high in older patients with baseline dementia, COPD, diabetes, liver and renal disease and those treated with invasive mechanical ventilation. Highlights:ABF has a high incidence among critically ill patients.ABF is associated with poor clinical outcome including hospital and 1 year mortality.Clinical outcomes worsen with increasing severity of ABF.Pre‐existing dementia and invasive ventilation are strongly associated with ABF.

Case Studies in Neurocritical Care

The practice of neurocritical care encompasses multiple acute neurologic and neurosurgical diseases and requires detailed knowledge of neurology and critical care. This article presents 5 cases that illustrate just some of the conditions encountered in the daily practice of neurocritical care and exemplify some of the common diagnostic, therapeutic, and prognostic challenges facing the neurointensivist. Life-threatening medical complications after severe acute ischemic stroke, seizures and extreme agitation from autoimmune encephalitis, refractory seizures after subdural hemorrhage, neurologic and systemic complications related to aneurysmal subarachnoid hemorrhage, and status epilepticus after cardiac arrest are discussed in this article.

1689: REFRACTORY HYPERAMMONEMIA IN A POST-GASTRIC BYPASS SURGERY PATIENT

Crit Care Med 2016 • Volume 44 • Number 12 (Suppl.) to the emergency department where he was diaphoretic and agitated. He was hypertensive, tachycardic, tachypneic, and febrile. He was in atrial fibrillation with rapid ventricular response. Multiple prescription bottles were found in his apartment including several bottles of liothyronine (T3) and levothyroxine (T4). Approximately 180 pills of each were missing. Initial TSH was 0.064 (ref 0.340– 5.600 uIU/mL), free T3 was >30 (ref 2.50–3.90 pg/mL), free T4 4.46 (ref 0.61– 1.12 ng/dL). In the ICU he was treated with dexamethasone, cholestyramine, carnitine and propranolol. He required mechanical ventilation due to respiratory distress. His hospital course was complicated by aspiration pneumonia, bilateral pulmonary embolism and severe epistaxis. He eventually converted to normal sinus rhythm after 20 days., His mental status gradually improved with normal TSH and free T4 levels by hospital day 27 and discharged on hospital day 34 (T3 remained below normal at time of discharge). Results: We used dexamethasone to decrease T4 to T3 conversion, cholestyramine to decrease the resorption of thyroid hormone, carnitine to inhibit thyroid hormone action and propranolol to block the toxic adrenergic effects. This case illustrates the dangers and complications of combined intentional overdose of exogenous T3 and T4 using various interventions to manage thyrotoxicosis.

Timing of ARDS Onset. A Neglected Confounder.

Accurate interpretation of the relationship between the specific risk factors (exposures) and outcomes in epidemiological studies is critically dependent on a reliable definition of timing for both the exposures and outcomes of interest. Unreliable or imprecise onset-time definitions may lead to false conclusions, resulting in wrong understanding of epidemiology, biology, and the implementation of faulty prevention strategies. Clinical research in emergency and critical care medicine is particularly vulnerable, as the exposures and outcomes often develop rapidly over minutes to hours, rather than over days. Yet, the time resolution of research observations in most clinical studies on acute respiratory distress syndrome (ARDS) and related critical care syndromes is low (Day 1, Day 2, Day 3, etc.), thereby amplifying the possibility of biased observations based on imprecise onset-time definitions. The Canadian Consensus Conference and the National Heart, Lung and Blood Institute working group have both proposed standardized definitions for transfusion-related acute lung Injury (TRALI) (1–3). Both define TRALI as new-onset ARDS occurring within 6 hours of a blood component transfusion. The possibility that blood component transfusions contribute to lung injury in patients with preexisting risk factors is implied in both definitions, but neither definition specifies how ARDS onset time should be defined. Applying different methods to define ARDS onset time could reduce the validity and reliability of the TRALI definition and lead to false conclusions. In this month’s issue of AnnalsATS, Vande Vusse and colleagues (pp. 1328– 1335) (4) describe the influence of ARDS onset-time definition on the epidemiology TRALI in patients who suffered blunt trauma. In this single-center, prospective cohort study, the authors compared characteristics of TRALI cases and transfusion risk factors implicated in TRALI between the two ARDS onset-time definitions (onset based on meeting the single vs. both definition criteria: arterial blood gas PaO2/FIO2 ratio and edema on a chest radiograph). The authors hypothesized that the use of different definitions for ARDS onset time would affect the epidemiology of consensus-defined TRALI, including the distribution of cases, characteristics of implicated blood components, and clinical risk factors. Of 316 patients enrolled, 113 met ARDS criteria; among them, 42 patients met TRALI criteria when applying the first onset-time definition, and 63 patients met TRALI criteria when applying the second ARDS onset-time definition. Only 28 patients met TRALI criteria under both ARDS onset-time definitions. The median time to TRALI onset also differed by ARDS onset-time definition (5.9 vs. 7.0 hours after the injury). There was no significant difference in mortality rate. What is particularly interesting is that the age, injury severity score, high-plasma-volume components, and transfused plasma volume were risk factors for TRALI when the second ARDS onset-time definition was applied, but not when the first onset time was used. This clearly stresses the importance of accurately defining the time of ARDS onset. However, only one among the seven contemporary studies examining patient-related TRALI risk factors details how the investigators determined ARDS onset time (5). These issues are not peculiar to ARDS andmay apply to other critical care syndromes (e.g., acute kidney injury). For example, the risk factors for acute kidney injury are likely to differ if acute kidney injury onset is defined by creatinine versus urine output. In summary, the study by Vande Vusse and colleagues (5) is a sobering reminder of the vulnerability of clinical research in the emergency and critical care medicine. Epidemiology of critical care syndromes critically depends on the accurate and precise timing definitions. Introduction of novel tools for real-time electronic data capture will hopefully make this task easier in the future increasing the quality of clinical research in this area. n