Browsing by Author "Puskarich, Michael A."
Now showing 1 - 10 of 10
Results Per Page
Sort Options
Item Association Between Early Hyperoxia Exposure After Resuscitation From Cardiac Arrest and Neurological Disability: Prospective Multicenter Protocol-Directed Cohort Study(American Heart Association, 2018-05-15) Roberts, Brian W.; Kilgannon, J. Hope; Hunter, Benton R.; Puskarich, Michael A.; Pierce, Lisa; Donnino, Michael; Leary, Marion; Kline, Jeffrey A.; Jones, Alan E.; Shapiro, Nathan I.; Abella, Benjamin S.; Trzeciak, Stephen; Emergency Medicine, School of MedicineBACKGROUND: Studies examining the association between hyperoxia exposure after resuscitation from cardiac arrest and clinical outcomes have reported conflicting results. Our objective was to test the hypothesis that early postresuscitation hyperoxia is associated with poor neurological outcome. METHODS: This was a multicenter prospective cohort study. We included adult patients with cardiac arrest who were mechanically ventilated and received targeted temperature management after return of spontaneous circulation. We excluded patients with cardiac arrest caused by trauma or sepsis. Per protocol, partial pressure of arterial oxygen (Pao2) was measured at 1 and 6 hours after return of spontaneous circulation. Hyperoxia was defined as a Pao2 >300 mm Hg during the initial 6 hours after return of spontaneous circulation. The primary outcome was poor neurological function at hospital discharge, defined as a modified Rankin Scale score >3. Multivariable generalized linear regression with a log link was used to test the association between Pao2 and poor neurological outcome. To assess whether there was an association between other supranormal Pao2 levels and poor neurological outcome, we used other Pao2 cut points to define hyperoxia (ie, 100, 150, 200, 250, 350, 400 mm Hg). RESULTS: Of the 280 patients included, 105 (38%) had exposure to hyperoxia. Poor neurological function at hospital discharge occurred in 70% of patients in the entire cohort and in 77% versus 65% among patients with versus without exposure to hyperoxia respectively (absolute risk difference, 12%; 95% confidence interval, 1-23). Hyperoxia was independently associated with poor neurological function (relative risk, 1.23; 95% confidence interval, 1.11-1.35). On multivariable analysis, a 1-hour-longer duration of hyperoxia exposure was associated with a 3% increase in risk of poor neurological outcome (relative risk, 1.03; 95% confidence interval, 1.02-1.05). We found that the association with poor neurological outcome began at ≥300 mm Hg. CONCLUSIONS: Early hyperoxia exposure after resuscitation from cardiac arrest was independently associated with poor neurological function at hospital discharge.Item Association Between Elevated Mean Arterial Blood Pressure and Neurologic Outcome After Resuscitation From Cardiac Arrest: Results From a Multicenter Prospective Cohort Study(Wolters Kluwer, 2019-01) Roberts, Brian W.; Kilgannon, J. Hope; Hunter, Benton R.; Puskarich, Michael A.; Shea, Lisa; Donnino, Michael; Jones, Christopher; Fuller, Brian M.; Kline, Jeffrey A.; Jones, Alan E.; Shapiro, Nathan I.; Abella, Benjamin S.; Trzeciak, Stephen; Department of Emergency MedicineObjective: Laboratory studies suggest elevated blood pressure after resuscitation from cardiac arrest may be protective; however, clinical data are limited. We sought to test the hypothesis that elevated post-resuscitation mean arterial blood pressure (MAP) is associated with neurological outcome. Design: Pre-planned analysis of a prospective cohort study. Setting: Six academic hospitals in the United States. Patients: Adult, non-traumatic cardiac arrest patients treated with targeted temperature management after return of spontaneous circulation (ROSC). Interventions: MAP was measured non-invasively after ROSC and every hour during the initial six hours after ROSC. Measures and Main Results: We calculated the mean MAP and a priori dichotomized subjects into two groups: mean MAP 70–90 and > 90 mmHg. The primary outcome was good neurological function, defined as a modified Rankin Scale (mRS) ≤ 3. The mRS was prospectively determined at hospital discharge. Of the 269 patients included, 159 (59%) had a mean MAP > 90 mmHg. Good neurological function at hospital discharge occurred in 30% of patients in the entire cohort, and was significantly higher in patients with a mean MAP > 90 mmHg (42%) as compared to MAP 70–90 mmHg (15%) [absolute risk difference 27% (95% CI 17%−37%)]. In a multivariable Poisson regression model adjusting for potential confounders, mean MAP > 90 mmHg was associated with good neurological function, adjusted relative risk 2.46 (95% CI 2.09–2.88). Over ascending ranges of mean MAP, there was a dose-response increase in probability of good neurological outcome, with mean MAP > 110 mmHg having the strongest association, adjusted relative risk 2.97 (95% CI 1.86 – 4.76). Conclusions: Elevated blood pressure during the initial six hours after resuscitation from cardiac arrest was independently associated with good neurological function at hospital discharge. Further investigation is warranted to determine if targeting an elevated MAP would improve neurologic outcome after cardiac arrest.Item Clinical prediction rule for SARS-CoV-2 infection from 116 U.S. emergency departments 2-22-2021(PloS, 2021-03) Kline, Jeffrey A.; Camargo, Carlos A.; Courtney, D. Mark; Kabrhel, Christopher; Nordenholz, Kristen E.; Aufderheide, Thomas; Baugh, Joshua J.; Beiser, David G.; Bennett, Christopher L.; Bledsoe, Joseph; Castillo, Edward; Chisolm-Straker, Makini; Goldberg, Elizabeth M.; House, Hans; House, Stacey; Jang, Timothy; Lim, Stephen C.; Madsen, Troy E.; McCarthy, Danielle M.; Meltzer, Andrew; Moore, Stephen; Newgard, Craig; Pagenhardt, Justine; Pettit, Katherine L.; Pulia, Michael S.; Puskarich, Michael A.; Southerland, Lauren T.; Sparks, Scott; Turner-Lawrence, Danielle; Vrablik, Marie; Wang, Alfred; Weekes, Anthony J.; Westafer, Lauren; Wilburn, John; Emergency Medicine, School of MedicineObjectives Accurate and reliable criteria to rapidly estimate the probability of infection with the novel coronavirus-2 that causes the severe acute respiratory syndrome (SARS-CoV-2) and associated disease (COVID-19) remain an urgent unmet need, especially in emergency care. The objective was to derive and validate a clinical prediction score for SARS-CoV-2 infection that uses simple criteria widely available at the point of care. Methods Data came from the registry data from the national REgistry of suspected COVID-19 in EmeRgency care (RECOVER network) comprising 116 hospitals from 25 states in the US. Clinical variables and 30-day outcomes were abstracted from medical records of 19,850 emergency department (ED) patients tested for SARS-CoV-2. The criterion standard for diagnosis of SARS-CoV-2 required a positive molecular test from a swabbed sample or positive antibody testing within 30 days. The prediction score was derived from a 50% random sample (n = 9,925) using unadjusted analysis of 107 candidate variables as a screening step, followed by stepwise forward logistic regression on 72 variables. Results Multivariable regression yielded a 13-variable score, which was simplified to a 13-point score: +1 point each for age>50 years, measured temperature>37.5°C, oxygen saturation<95%, Black race, Hispanic or Latino ethnicity, household contact with known or suspected COVID-19, patient reported history of dry cough, anosmia/dysgeusia, myalgias or fever; and -1 point each for White race, no direct contact with infected person, or smoking. In the validation sample (n = 9,975), the probability from logistic regression score produced an area under the receiver operating characteristic curve of 0.80 (95% CI: 0.79–0.81), and this level of accuracy was retained across patients enrolled from the early spring to summer of 2020. In the simplified score, a score of zero produced a sensitivity of 95.6% (94.8–96.3%), specificity of 20.0% (19.0–21.0%), negative likelihood ratio of 0.22 (0.19–0.26). Increasing points on the simplified score predicted higher probability of infection (e.g., >75% probability with +5 or more points). Conclusion Criteria that are available at the point of care can accurately predict the probability of SARS-CoV-2 infection. These criteria could assist with decisions about isolation and testing at high throughput checkpoints.Item Effect of Levocarnitine vs Placebo as an Adjunctive Treatment for Septic Shock: The Rapid Administration of Carnitine in Sepsis (RACE) Randomized Clinical Trial(American Medical Association, 2018-12-07) Jones, Alan E.; Puskarich, Michael A.; Shapiro, Nathan I.; Guirgis, Faheem W.; Runyon, Michael; Adams, Jason Y.; Sherwin, Robert; Arnold, Ryan; Roberts, Brian W.; Kurz, Michael C.; Wang, Henry E.; Kline, Jeffrey A.; Courtney, D. Mark; Trzeciak, Stephen; Sterling, Sarah A.; Nandi, Utsav; Patki, Deepti; Viele, Kert; Emergency Medicine, School of MedicineImportance: Sepsis induces profound metabolic derangements, while exogenous levocarnitine mitigates metabolic dysfunction by enhancing glucose and lactate oxidation and increasing fatty acid shuttling. Previous trials in sepsis suggest beneficial effects of levocarnitine on patient-centered outcomes. Objectives: To test the hypothesis that levocarnitine reduces cumulative organ failure in patients with septic shock at 48 hours and, if present, to estimate the probability that the most efficacious dose will decrease 28-day mortality in a pivotal phase 3 clinical trial. Design, Setting, and Participants: Multicenter adaptive, randomized, blinded, dose-finding, phase 2 clinical trial (Rapid Administration of Carnitine in Sepsis [RACE]). The setting was 16 urban US medical centers. Participants were patients aged 18 years or older admitted from March 5, 2013, to February 5, 2018, with septic shock and moderate organ dysfunction. Interventions: Within 24 hours of identification, patients were assigned to 1 of the following 4 treatments: low (6 g), medium (12 g), or high (18 g) doses of levocarnitine or an equivalent volume of saline placebo administered as a 12-hour infusion. Main Outcomes and Measures: The primary outcome required, first, a greater than 90% posterior probability that the most promising levocarnitine dose decreases the Sequential Organ Failure Assessment (SOFA) score at 48 hours and, second (given having met the first condition), at least a 30% predictive probability of success in reducing 28-day mortality in a subsequent traditional superiority trial to test efficacy. Results: Of the 250 enrolled participants (mean [SD] age, 61.7 [14.8] years; 56.8% male), 35, 34, and 106 patients were adaptively randomized to the low, medium, and high levocarnitine doses, respectively, while 75 patients were randomized to placebo. In the intent-to-treat analysis, the fitted mean (SD) changes in the SOFA score for the low, medium, and high levocarnitine groups were -1.27 (0.49), -1.66 (0.38), and -1.97 (0.32), respectively, vs -1.63 (0.35) in the placebo group. The posterior probability that the 18-g dose is superior to placebo was 0.78, which did not meet the a priori threshold of 0.90. Mortality at 28 days was 45.9% (34 of 74) in the placebo group compared with 43.3% (45 of 104) for the most promising levocarnitine dose (18 g). Similar findings were noted in the per-protocol analysis. Conclusions and Relevance: In this dose-finding, phase 2 adaptive randomized trial, the most efficacious dose of levocarnitine (18 g) did not meaningfully reduce cumulative organ failure at 48 hours.Item Inhaled nitric oxide to control platelet hyper-reactivity in patients with acute submassive pulmonary embolism(Elsevier, 2020-03-01) Kline, Jeffrey A.; Puskarich, Michael A.; Pike, Jonathan; Zagorski, John; Alves, Nathan J.; Emergency Medicine, School of MedicineBackground: We test if inhaled nitric oxide (NO) attenuates platelet functional and metabolic hyper-reactivity in subjects with submassive pulmonary embolism (PE). Methods: Participants with PE were randomized to either 50 ppm NO + O2 or O2 only for 24 h with blood sampling at enrollment and after treatment; results were compared with healthy controls. Platelet metabolic activity was assessed by oxygen consumption (basal and uncoupled) and reactivity was assessed with agonist-stimulated thromboelastography (TEG) and fluorometric measurement of agonist-stimulated cytosolic [Ca++] without and with pharmacological soluble guanylate (sGC) modulation. Results: Participants (N = 38 per group) were well-matched at enrollment for PE severity, comorbidities as well as TEG parameters and platelet O2 consumption. NO treatment doubled the mean plasma [NO3-] (P < 0.001) indicating successful delivery, but placebo treatment produced no change. After 24 h, neither TEG nor O2 consumption parameters differed significantly between treatment groups. Platelet cytosolic [Ca++] was elevated with PE versus controls, and was decreased by treatment with cinaciguat (an sGC activator), but not riociguat (an sGC stimulator). Stimulated platelet lysate sGC activity was increased with PE compared with controls. Conclusions: In patients with acute submassive PE, despite evidence of adequate drug delivery, inhaled NO had no major effect on platelet O2 consumption or agonist-stimulated parameters on TEG. Pharmacological activation, but not stimulation, of sGC effectively decreased platelet cytosolic [Ca++], and platelet sGC activity was increased with PE, confirming the viability of sGC as a therapeutic target.Item Inhaled nitric oxide to treat intermediate risk pulmonary embolism: A multicenter randomized controlled trial(Elsevier, 2019-03) Kline, Jeffrey A.; Puskarich, Michael A.; Jones, Alan E.; Mastouri, Ronald A.; Hall, Cassandra L.; Perkins, Anthony; Gundert, Emily; Lahm, Tim; Emergency Medicine, School of MedicineObjective To test the hypothesis that adjunctive inhaled NO would improve RV function and viability in acute PE. Methods This was a randomized, placebo-controlled, double blind trial conducted at four academic hospitals. Eligible patients had acute PE without systemic arterial hypotension but had RV dysfunction and a treatment plan of standard anticoagulation. Subjects received either oxygen plus 50 parts per million nitrogen (placebo) or oxygen plus 50 ppm NO for 24 h. The primary composite endpoint required a normal RV on echocardiography and a plasma troponin T concentration <14 pg/mL. The secondary endpoint required a blood brain natriuretic peptide concentration <90 pg/mL and a Borg dyspnea score ≤ 2. The sample size of N = 76 tested if 30% more patients treated with NO would achieve the primary endpoint with 80% power and alpha = 5%. Results We randomized 78 patients and after two withdrawals, 38 were treated per protocol in each group. Patients were well matched for baseline conditions. At 24 h, 5/38 (13%) of patients treated with placebo and 9/38 (24%) of patients treated with NO reached the primary endpoint (P = 0.375). The secondary endpoint was reached in 34% with placebo and 13% of the NO (P = 0.11). In a pre-planned post-hoc analysis, we examined how many patients with RV hypokinesis or dilation at enrollment resolved these abnormalities; 29% more patients treated with NO resolved both abnormalities at 24 h (P = 0.010, Cochrane's Q test). Conclusions In patients with severe submassive PE, inhaled nitric oxide failed to increase the proportion of patients with a normal troponin and echocardiogram but increased the probability of eliminating RV hypokinesis and dilation on echocardiography.Item Partial pressure of arterial carbon dioxide after resuscitation from cardiac arrest and neurological outcome: A prospective multi-center protocol-directed cohort study(Elsevier, 2018) Hope Kilgannon, J.; Hunter, Benton R.; Puskarich, Michael A.; Shea, Lisa; Fuller, Brian M.; Jones, Christopher; Donnino, Michael; Kline, Jeffrey A.; Jones, Alan E.; Shapiro, Nathan I.; Abella, Benjamin S.; Trzeciak, Stephen; Roberts, Brian W.; Emergency Medicine, School of MedicineAims Partial pressure of arterial carbon dioxide (PaCO2) is a regulator of cerebral blood flow after brain injury. We sought to test the association between PaCO2 after resuscitation from cardiac arrest and neurological outcome. Methods A prospective protocol-directed cohort study across six hospitals. Inclusion criteria: age ≥ 18, non-traumatic cardiac arrest, mechanically ventilated after return of spontaneous circulation (ROSC), and receipt of targeted temperature management. Per protocol, PaCO2 was measured by arterial blood gas analyses at one and six hours after ROSC. We determined the mean PaCO2 over this initial six hours after ROSC. The primary outcome was good neurological function at hospital discharge, defined a priori as a modified Rankin Scale ≤ 3. Multivariable Poisson regression analysis was used to test the association between PaCO2 and neurological outcome. Results Of the 280 patients included, the median (interquartile range) PaCO2 was 44 (37-52) mmHg and 30% had good neurological function. We found mean PaCO2 had a quadratic (inverted “U” shaped) association with good neurological outcome, with a mean PaCO2 of 68 mmHg having the highest predictive probability of good neurological outcome, and worse neurological outcome at higher and lower PaCO2. Presence of metabolic acidosis attenuated the association between PaCO2 and good neurological outcome, with a PaCO2 of 51 mmHg having the highest predictive probability of good neurological outcome among patients with metabolic acidosis. Conclusion PaCO2 has a “U” shaped association with neurological outcome, with mild to moderate hypercapnia having the highest probability of good neurological outcome.Item Perception of Physician Empathy Varies With Educational Level and Gender of Patients Undergoing Low-Yield Computerized Tomographic Imaging(SAGE, 2020-06-01) Kline, Jeffrey A.; Lin, Michelle P.; Hall, Cassandra L.; Puskarich, Michael A.; Dehon, Erin.; Kuehl, Damon R.; Wang, Ralph C.; Hess, Erik P.; Runyon, Michael S.; Wang, Hao; Courtney, D Mark.; Emergency Medicine, School of MedicineObjective: Lack of empathic communication between providers and patients may contribute to low value diagnostic testing in emergency care. Accordingly, we measured the perception of physician empathy and trust in patients undergoing low-value computed tomography (CT) in the emergency department (ED). Methods: Multicenter study of ED patients undergoing CT scanning, acknowledged by ordering physicians as unlikely to show an emergent condition. Near the end of their visit, patients completed the Jefferson Scale of Patient Perception of Physician Empathy (JSPPPE), Trust in Physicians Survey (TIPS), and the Group Based Medical Mistrust Scale (GBMMS). We stratified results by patient demographics including gender, race, and education. Results: We enrolled 305 participants across 9 sites with diverse geographic, racial, and ethnic representation. The median scores (interquartile ranges) for the JSPPPE, TIPS, and GBMMS for all patients were 29 (24-33.5), 55 (47-62), and 18 (12-29). Compared with white patients, nonwhite patients had similar JSPPPE and TIPS scores but had higher (worse) GBMMS scores. Females had significantly lower JSPPPE and TIPS scores than males, and scores were lower (worse) in females with college degrees. Patients in the lowest tier of educational status had the highest (better) JSPPPE and TIPS scores. Scores were invariant with physician characteristics. Conclusion: Among patients undergoing low-value CT scanning in the ED, the degree of patient perception of physician empathy and trust varied based on the patients’ level of education and gender. Given this variation, an intervention to increase patient perception of physician empathy should contain individualized strategies to address these subgroups, rather than a one-size-fits-all approach.Item Predicting 30-day return hospital admissions in patients with COVID-19 discharged from the emergency department: A national retrospective cohort study(Wiley, 2021) Beiser, David G.; Jarou, Zachary J.; Kassir, Alaa A.; Puskarich, Michael A.; Vrablik, Marie C.; Rosenman, Elizabeth D.; McDonald, Samuel A.; Meltzer, Andrew C.; Courtney, D. Mark; Kabrhel, Christopher; Kline, Jeffrey A.; RECOVER Investigators; Emergency Medicine, School of MedicineObjectives: Identification of patients with coronavirus disease 2019 (COVID-19) at risk for deterioration after discharge from the emergency department (ED) remains a clinical challenge. Our objective was to develop a prediction model that identifies patients with COVID-19 at risk for return and hospital admission within 30 days of ED discharge. Methods: We performed a retrospective cohort study of discharged adult ED patients (n = 7529) with SARS-CoV-2 infection from 116 unique hospitals contributing to the National Registry of Suspected COVID-19 in Emergency Care. The primary outcome was return hospital admission within 30 days. Models were developed using classification and regression tree (CART), gradient boosted machine (GBM), random forest (RF), and least absolute shrinkage and selection (LASSO) approaches. Results: Among patients with COVID-19 discharged from the ED on their index encounter, 571 (7.6%) returned for hospital admission within 30 days. The machine-learning (ML) models (GBM, RF, and LASSO) performed similarly. The RF model yielded a test area under the receiver operating characteristic curve of 0.74 (95% confidence interval [CI], 0.71–0.78), with a sensitivity of 0.46 (95% CI, 0.39–0.54) and a specificity of 0.84 (95% CI, 0.82–0.85). Predictive variables, including lowest oxygen saturation, temperature, or history of hypertension, diabetes, hyperlipidemia, or obesity, were common to all ML models. Conclusions: A predictive model identifying adult ED patients with COVID-19 at risk for return for return hospital admission within 30 days is feasible. Ensemble/boot-strapped classification methods (eg, GBM, RF, and LASSO) outperform the single-tree CART method. Future efforts may focus on the application of ML models in the hospital setting to optimize the allocation of follow-up resources.Item Randomized trial of inhaled nitric oxide to treat acute pulmonary embolism: The iNOPE trial(Elsevier, 2017-04) Kline, Jeffrey A.; Hall, Cassandra L.; Jones, Alan E.; Puskarich, Michael A.; Mastouri, Ronald; Lahm, Tim; Emergency Medicine, School of MedicineBACKGROUND: The study hypothesis is that administration of inhaled nitric oxide (NO) plus oxygen to subjects with submassive pulmonary embolism (PE) will improve right ventricular (RV) systolic function and reduce RV strain and necrosis, while improving patient dyspnea, more than treatment with oxygen alone. METHODS: This article describes the rationale and protocol for a registered (NCT01939301), nearly completed phase II, 3-center, randomized, double-blind, controlled trial. Eligible patients have pulmonary imaging-proven acute PE. Subjects must be normotensive, and have RV dysfunction on echocardiography or elevated troponin or brain natriuretic peptide and no fibrinolytics. Subjects receive NO plus oxygen or placebo for 24 hours (±3 hours) with blood sampling before and after treatment, and mandatory echocardiography and high-sensitivity troponin posttreatment to assess the composite primary end point. The sample size of N=78 was predicated on 30% more NO-treated patients having a normal high-sensitivity troponin (<14 pg/mL) and a normal RV on echocardiography at 24 hours with α=.05 and β=.20. Safety was ensured by continuous spectrophotometric monitoring of percentage of methemoglobinemia and a predefined protocol to respond to emergent changes in condition. Blinding was ensured by identical tanks, software, and physical shielding of the device display and query of the clinical care team to assess blinding efficacy. RESULTS: We have enrolled 78 patients over a 31-month period. No patient has been withdrawn as a result of a safety concern, and no patient has had a serious adverse event related to NO. CONCLUSIONS: We present methods and a protocol for the first double-blinded, randomized trial of inhaled NO to treat PE.