Arterial to end-tidal carbon dioxide gap and its characterization in mechanically ventilated adults in the emergency department.

PURPOSE: To evaluate early measurement of the arterial to end-tidal carbon dioxide (PaCO2-PetCO2) gap, a surrogate for physiologic dead space, and its association with clinical outcomes in intubated adults in the emergency department (ED). MATERIALS AND METHODS: Observational cohort study of invasively mechanically ventilated adults in an academic medical center (years 2009 to 2016). The association of the PaCO2-PetCO2 gap was evaluated with respect to clinical outcomes; the primary outcome was in-hospital mortality. RESULTS: 519 patients were included. 325 (63%) patients had an elevated (>5 mmHg) PaCO2-PetCO2. Patients with an elevated PaCO2-PetCO2 were significantly older, had higher APACHE II scores, more frequently had chronic obstructive pulmonary disease (COPD), had lower arterial oxygen to fraction of inspired oxygen (P:F) ratios, and were more likely to be intubated for exacerbation of COPD or sepsis. There was no difference in mortality for patients with an elevated PaCO2-PetCO2 (25% vs 26%) in unadjusted analysis (p = 0.829) or adjusted analysis (aOR = 0.81 [95% CI: 0.53-1.26]), as compared to a non-elevated PaCO2-PetCO2. CONCLUSIONS: An elevated PaCO2-PetCO2 gap is common in the post-intubation period in the ED, but not significantly associated with clinical outcomes.

Intermittent complete heart block with ventricular standstill after Pfizer COVID-19 booster vaccination: A case report.

As the COVID-19 pandemic continues around the globe, vaccines are undoubtedly central to the fight to control the spread of the virus. However, as with any therapy, these vaccines are not without side effects. Documented cardiac complications of COVID-19 vaccination include myocarditis, pericarditis, and cardiac conduction abnormalities. Here, we report a novel case of intermittent complete heart block with ventricular standstill occurring within 24 hours of administration of a Pfizer-BioNTech COVID-19 booster vaccine. The patient presented to the emergency department (ED) via ambulance for evaluation of syncope. On arrival, the patient lost pulses as a result of intermittent complete heart block with ventricular standstill. He required cardiopulmonary resuscitation (CPR) with intubation, transcutaneous pacing, and subsequent transvenous pacing in the ED. After stabilization and extensive workup, the patient was diagnosed with lymphocytic myocarditis and complete heart block that is suspected to be secondary to COVID-19 booster vaccination. Ultimately, the patient's complete heart block resolved spontaneously, and he was discharged home with ambulatory rhythm monitoring.

Extracorporeal membrane oxygenation use in poisoning: a narrative review with clinical recommendations.

CONTEXT: Poisoning may lead to respiratory failure, shock, cardiac arrest, or death. Extracorporeal membrane oxygenation (ECMO) may be used to provide circulatory support, termed venoarterial (VA) ECMO; or respiratory support termed venovenous (VV) ECMO. The clinical utility of ECMO in poisoned patients remains unclear and guidelines on its use in this setting are lacking. OBJECTIVES: To perform a literature search and narrative review on the use of ECMO in poisonings. Additionally, to provide recommendations on the use of ECMO in poisonings from physicians with expertise in ECMO, medical toxicology, critical care, and emergency medicine. METHODS: A literature search in Ovid MEDLINE from 1946 to October 14, 2020, was performed to identify relevant articles with a strategy utilizing both MeSH terms and adjacency searching that encompassed both extracorporeal life support/ECMO/Membrane Oxygenation concepts and chemically-induced disorders/toxicity/poisoning concepts, which identified 318 unique records. Twelve additional manuscripts were identified by the authors for a total of 330 articles for screening, of which 156 were included for this report. NARRATIVE LITERATURE REVIEW: The use of ECMO in poisoned patients is significantly increasing over time. Available retrospective data suggest that patients receiving VA ECMO for refractory shock or cardiac arrest due to poisoning have lower mortality as compared to those who receive VA ECMO for non-poisoning-related indications. Poisoned patients treated with ECMO have reduced mortality as compared to those treated without ECMO with similar severity of illness and after adjusted analyses, regardless of the type of ingestion. This is especially evident for poisoned patients with refractory cardiac arrest placed on VA ECMO (termed extracorporeal cardiopulmonary resuscitation [ECPR]). INDICATIONS: We suggest VA ECMO be considered for poisoned patients with refractory cardiogenic shock (continued shock with myocardial dysfunction despite fluid resuscitation, vasoactive support, and indicated toxicologic therapies such as glucagon, intravenous lipid emulsion, hyperinsulinemia euglycemia therapy, or others), and strongly considered for patients with cardiac arrest in institutions which are structured to deliver effective ECPR. VV ECMO should be considered in poisoned patients with ARDS or severe respiratory failure according to traditional indications for ECMO in this setting. CONTRAINDICATIONS: Patients with pre-existing comorbidities with low expected survival or recovery. Relative contraindications vary based on each center's experience but often include: severe brain injury; advanced age; unrepaired aortic dissection or severe aortic regurgitation in VA ECMO; irreversible organ injury; contraindication to systemic anticoagulation, such as severe hemorrhage. CONCLUSIONS: ECMO may provide hemodynamic or respiratory support to poisoned patients while they recover from the toxic exposure and metabolize or eliminate the toxic agent. Available literature suggests a potential benefit for ECMO use in selected poisoned patients with refractory shock, cardiac arrest, or respiratory failure. Future studies may help to further our understanding of the use and complications of ECMO in poisoned patients.

Symptomatic Cholelithiasis of a Remnant Gallbladder after Open Cholecystectomy.

BACKGROUND: Recurrent abdominal pain, particularly in the right upper quadrant (RUQ) in a patient with a history of cholecystectomy, known as postcholecystectomy syndrome, requires a broad differential diagnosis. Pathology of a retained gallbladder remnant is an exceedingly rare etiology of this pain. CASE REPORT: A 49-year-old woman who had previously undergone an open cholecystectomy presented to the emergency department with several hours of postprandial RUQ pain and emesis. Liver function tests and lipase were not significantly elevated. RUQ ultrasonography revealed a cystic structure containing a stone with mild prominence of the common bile duct at 7 mm, and magnetic resonance cholangiopancreatography confirmed the presence of a remnant gallbladder without common bile duct obstruction. Her pain subsided, she tolerated a diet, and was discharged with a referral for an elective cholecystectomy. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Abdominal pain is the most common chief complaint of patients presenting to the emergency department in the United States, and emergency physicians routinely encounter patients with postcholecystectomy syndrome. Emergency physicians should not exclude the possibility of remnant gallbladder pathology, such as symptomatic cholelithiasis or cholecystitis, in patients presenting with symptoms concerning for biliary colic, even if the patient has undergone previous cholecystectomy.

Community-Acquired Pneumonia Visualized on CT Scans but Not Chest Radiographs: Pathogens, Severity, and Clinical Outcomes.

BACKGROUND: The clinical significance of pneumonia visualized on CT scan in the setting of a normal chest radiograph is uncertain. METHODS: In a multicenter prospective surveillance study of adults hospitalized with community-acquired pneumonia (CAP), we compared the presenting clinical features, pathogens present, and outcomes of patients with pneumonia visualized on a CT scan but not on a concurrent chest radiograph (CT-only pneumonia) and those with pneumonia visualized on a chest radiograph. All patients underwent chest radiography; the decision to obtain CT imaging was determined by the treating clinicians. Chest radiographs and CT images were interpreted by study-dedicated thoracic radiologists blinded to the clinical data. RESULTS: The study population included 2,251 adults with CAP; 2,185 patients (97%) had pneumonia visualized on chest radiography, whereas 66 patients (3%) had pneumonia visualized on CT scan but not on concurrent chest radiography. Overall, these patients with CT-only pneumonia had a clinical profile similar to those with pneumonia visualized on chest radiography, including comorbidities, vital signs, hospital length of stay, prevalence of viral (30% vs 26%) and bacterial (12% vs 14%) pathogens, ICU admission (23% vs 21%), use of mechanical ventilation (6% vs 5%), septic shock (5% vs 4%), and inhospital mortality (0 vs 2%). CONCLUSIONS: Adults hospitalized with CAP who had radiological evidence of pneumonia on CT scan but not on concurrent chest radiograph had pathogens, disease severity, and outcomes similar to patients who had signs of pneumonia on chest radiography. These findings support using the same management principles for patients with CT-only pneumonia and those with pneumonia seen on chest radiography.

Regulators of Lysosome Function and Dynamics in Caenorhabditis elegans.

Lysosomes, the major membrane-bound degradative organelles, have a multitude of functions in eukaryotic cells. Lysosomes are the terminal compartments in the endocytic pathway, though they display highly dynamic behaviors, fusing with each other and with late endosomes in the endocytic pathway, and with the plasma membrane during regulated exocytosis and for wound repair. After fusing with late endosomes, lysosomes are reformed from the resulting hybrid organelles through a process that involves budding of a nascent lysosome, extension of the nascent lysosome from the hybrid organelle, while remaining connected by a membrane bridge, and scission of the membrane bridge to release the newly formed lysosome. The newly formed lysosomes undergo cycles of homotypic fusion and fission reactions to form mature lysosomes. In this study, we used a forward genetic screen in Caenorhabditis elegans to identify six regulators of lysosome biology. We show that these proteins function in different steps of lysosome biology, regulating lysosome formation, lysosome fusion, and lysosome degradation.

Comparison of Etomidate and Ketamine for Induction During Rapid Sequence Intubation of Adult Trauma Patients.

STUDY OBJECTIVE: Induction doses of etomidate during rapid sequence intubation cause transient adrenal dysfunction, but its clinical significance on trauma patients is uncertain. Ketamine has emerged as an alternative for rapid sequence intubation induction. Among adult trauma patients intubated in the emergency department, we compare clinical outcomes among those induced with etomidate and ketamine. METHODS: The study entailed a retrospective evaluation of a 4-year (January 2011 to December 2014) period spanning an institutional protocol switch from etomidate to ketamine as the standard induction agent for adult trauma patients undergoing rapid sequence intubation in the emergency department of an academic Level I trauma center. The primary outcome was hospital mortality evaluated with multivariable logistic regression, adjusted for age, vital signs, and injury severity and mechanism. Secondary outcomes included ICU-free days and ventilator-free days evaluated with multivariable ordered logistic regression using the same covariates. RESULTS: The analysis included 968 patients, including 526 with etomidate and 442 with ketamine. Hospital mortality was 20.4% among patients induced with ketamine compared with 17.3% among those induced with etomidate (adjusted odds ratio [OR] 1.41; 95% confidence interval [CI] 0.92 to 2.16). Patients induced with ketamine had ICU-free days (adjusted OR 0.80; 95% CI 0.63 to 1.00) and ventilator-free days (adjusted OR 0.96; 95% CI 0.76 to 1.20) similar to those of patients induced with etomidate. CONCLUSION: In this analysis spanning an institutional protocol switch from etomidate to ketamine as the standard rapid sequence intubation induction agent for adult trauma patients, patient-centered outcomes were similar for patients who received etomidate and ketamine.

Cell-free hemoglobin: a novel mediator of acute lung injury.

Patients with the acute respiratory distress syndrome (ARDS) have elevated levels of cell-free hemoglobin (CFH) in the air space, but the contribution of CFH to the pathogenesis of acute lung injury is unknown. In the present study, we demonstrate that levels of CFH in the air space correlate with measures of alveolar-capillary barrier dysfunction in humans with ARDS (r = 0.89, P < 0.001) and in mice with ventilator-induced acute lung injury (r = 0.89, P < 0.001). To investigate the specific contribution of CFH to ARDS, we studied the impact of purified CFH in the mouse lung and on cultured mouse lung epithelial (MLE-12) cells. Intratracheal delivery of CFH in mice causes acute lung injury with air space inflammation and alveolar-capillary barrier disruption. Similarly, in MLE-12 cells, CFH increases proinflammatory cytokine expression and increases paracellular permeability as measured by electrical cell-substrate impedance sensing. Next, to determine whether these effects are mediated by the iron-containing heme moiety of CFH, we treated mice with intratracheal hemin, the chloride salt of heme, and found that hemin was sufficient to increase alveolar permeability but failed to induce proinflammatory cytokine expression or epithelial cell injury. Together, these data identify CFH in the air space as a previously unrecognized driver of lung epithelial injury in human and experimental ARDS and suggest that CFH and hemin may contribute to ARDS through different mechanisms. Interventions targeting CFH and heme in the air space could provide a new therapeutic approach for ARDS.

Mucolipidosis type IV protein TRPML1-dependent lysosome formation.

Lysosomes are dynamic organelles that undergo cycles of fusion and fission with themselves and with other organelles. Following fusion with late endosomes to form hybrid organelles, lysosomes are reformed as discrete organelles. This lysosome reformation or formation is a poorly understood process that has not been systematically analyzed and that lacks known regulators. In this study, we quantitatively define the multiple steps of lysosome formation and identify the first regulator of this process.

Discharge instructions for youth sports-related concussions in the emergency department, 2004 to 2012.

OBJECTIVE: To evaluate the effect of the Centers for Disease Control and Prevention (CDC) Heads-Up concussion campaign on appropriateness of discharge instructions for youth sports-related concussion (SRC) patients presenting to a pediatric emergency department (ED). DESIGN: Retrospective cohort study. SETTING: Pediatric ED. PATIENTS: Children up to 18 years. ASSESSMENT OF RISK FACTORS: A retrospective chart review was conducted on patients evaluated from 2004 to 2012. Patients were selected by ICD-9 code for having a concussion during a sporting activity. MAIN OUTCOME MEASURES: Discharge instructions were reviewed for recommendations for cognitive rest, physical rest, primary care physician follow-up, and referral to a concussion specialist or center. RESULTS: There were 497 youth SRCs from 392 908 total ED visits. Overall, only 66% had appropriate discharge recommendations. This improved to 75% after 2010, which was not statistically significant (odds ratio = 1.02, P = 0.179). Only 4% of patients received a recommendation of cognitive rest, which only increased to 12% of the patients seen after 2010. Finally, referrals to a sports concussion specialist or center dramatically increased from an average of 8% to 43% after 2010. CONCLUSIONS: Even with the CDC Heads-Up campaign on concussion education, there is still need to improve appropriateness of discharge instructions for youth SRCs. There have been dramatic increases in referrals to sports concussion specialists and centers after 2010.

Systematic screens for proteins that interact with the mucolipidosis type IV protein TRPML1.

Mucolipidosis type IV is a lysosomal storage disorder resulting from mutations in the MCOLN1 gene, which encodes the endosomal/lysosomal Transient Receptor Potential channel protein mucolipin-1/TRPML1. Cells isolated from Mucolipidosis type IV patients and grown in vitro and in in vivo models of this disease both show several lysosome-associated defects. However, it is still unclear how TRPML1 regulates the transport steps implicated by these defects. Identifying proteins that associate with TRPML1 will facilitate the elucidation of its cellular and biochemical functions. We report here two saturation screens for proteins that interact with TRPML1: one that is based on immunoprecipitation/mass spectrometry and the other using a genetic yeast two-hybrid approach. From these screens, we identified largely non-overlapping proteins, which represent potential TRPML1-interactors., Using additional interaction assays on some of the potential interactors from each screen, we validated some proteins as candidate TRPML1 interactors In addition, our analysis indicates that each of the two screens not only identified some false-positive interactors, as expected from any screen, but also failed to uncover potential TRPML1 interactors. Future studies on the true interactors, first identified in these screens, will help elucidate the structure and function of protein complexes containing TRPML1.