Publications by Year: 2020

2020

Holmberg, Mathias J, Amy Uber, Nikola Stankovic, C-Y Oliver Chen, Anne Grossestreuer V, Michael W Donnino, Lars W Andersen, and Xiaowen Liu. (2020) 2020. “Ubiquinol (Reduced Coenzyme Q10) and Cellular Oxygen Consumption in Patients Undergoing Coronary Artery Bypass Grafting.”. Journal of Intensive Care Medicine 35 (8): 797-804. https://doi.org/10.1177/0885066618789114.

Ubiquinol is a fundamental component of cellular metabolism. Low ubiquinol levels have been associated with mortality. This was a substudy of a randomized trial in patients undergoing coronary artery bypass grafting. We drew blood before and after surgery. Ubiquinol or placebo was added to peripheral blood mononuclear cells for oxygen consumption (OCR) measurements. In vivo ubiquinol levels were lower postsurgery compared to presurgery (0.16 μmol/L [quartiles: 0.02-0.39], P = .01), although the difference disappeared when adjusting for hemoglobin levels (P = .30). There was no difference in presurgical basal (1.0 mL/min/mg [95% confidence interval [CI]: -0.9 to 2.2], P = .08) and maximal (0.5 mL/min/mg [95% CI: -4.3 to 7.3], P = .56) OCR in cells receiving ubiquinol or placebo. There was a difference in postsurgical basal (1.1 mL/min/mg [95% CI: 0.9-1.6], P < .001) and maximal (4.2 mL/min/mg [95% CI: 0.3-7.0], P = .01) OCR between the groups. We found no association between ubiquinol and OCR levels (all P > .05).

Gardner, Ryan, Xiaowen Liu, Yanbo Wang, Andrew Cole, Stanley Heydrick, Michael W Donnino, and Ari Moskowitz. (2020) 2020. “Vitamin C Levels Amongst Initial Survivors of Out of Hospital Cardiac Arrest.”. Resuscitation 156: 190-93. https://doi.org/10.1016/j.resuscitation.2020.09.005.

INTRODUCTION: Vitamin C deficiency has been described in patients with sepsis. The post-cardiac arrest syndrome shares similarities to sepsis, however vitamin C levels in post-arrest patients have been incompletely characterized. We assessed vitamin C levels in a post-arrest population.

METHODS: This was a retrospective observational study at a tertiary care center. A convenience sample of post-arrest, sepsis, and healthy control patients was selected from prior studies. Vitamin C levels were measured from samples obtained within 6-h of emergency department admission. A subset of cardiac arrest patients had vitamin C levels additionally measured 24-h later.

RESULTS: A total of 84 patients (34 healthy controls, 25 post-arrest, and 25 septic patients) were included. The median baseline vitamin C level in cardiac arrest patients was 0.33 mg/dL (0.05-0.83), as compared to 0.91 mg/dL (0.69-1.48) in the healthy control group (p < 0.01) and 0.28 mg/dL (0.11-0.59) in the septic group (p = 0.36). Vitamin C levels for cardiac arrest patients fell between the two time points, but the change was not statistically significant (median decrease 0.26 mg/dL, p = 0.08).

CONCLUSIONS: Serum vitamin C levels were lower in post-arrest patients compared to controls and were similar to patients with sepsis. Future studies of vitamin C levels and supplementation following cardiac arrest may be warranted.

Moskowitz, Ari, Lars W Andersen, Jon C Rittenberger, Robert Swor, Raghu R Seethala, Michael C Kurz, Katherine M Berg, et al. (2020) 2020. “Continuous Neuromuscular Blockade Following Successful Resuscitation From Cardiac Arrest: A Randomized Trial.”. Journal of the American Heart Association 9 (17): e017171. https://doi.org/10.1161/JAHA.120.017171.

Background Neuromuscular blockade (NMB) agents are often administered to control shivering during targeted temperature management following cardiac arrest. In this study, we hypothesized that early, continuous NMB would result in a greater reduction in serum lactate levels among comatose patients after cardiac arrest. Methods and Results Randomized trial of continuous NMB for 24 hours versus usual care following cardiac arrest conducted at 5 urban centers in the United States. Adult patients who achieved return of spontaneous circulation, remained unresponsive, and underwent targeted temperature management after cardiac arrest were included. The primary outcome was change in lactate over 24 hours. A total of 83 patients were randomized, and 80 were analyzed (37 and 43 in the NMB and usual care arms, respectively). There was no significant interaction between time and treatment group with respect to change in lactate over 24 hours (median lactate change from 4.2 to 2.0 mmol/L [-2.2 mmol/L] in the NMB arm versus 4.0 to 1.7 mmol/L [-2.3 mmol/L] in the usual care arm; geometric mean difference, 1.3 [95% CI, 1.0-1.8]; P=0.07 for the interaction term). There was no difference in hospital survival (38% [NMB] versus 33% [usual care]; P=0.63) or survival with good functional outcome (30% [NMB] versus 21% [usual care]; P=0.35). There were no adverse events in either arm attributed to study interventions. Conclusions Continuous NMB compared with usual care did not reduce lactate over the first 24 hours after enrollment compared with usual care. There was no difference in overall hospital survival, hospital survival with good neurologic outcome, or adverse events. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02260258.

Cocchi, Michael N, Justin Salciccioli, Tuyen Yankama, Maureen Chase, Parth Patel V, Xiaowen Liu, Timothy J Mader, and Michael W Donnino. (2020) 2020. “Predicting Outcome After Out-of-Hospital Cardiac Arrest: Lactate, Need for Vasopressors, and Cytochrome C.”. Journal of Intensive Care Medicine 35 (12): 1483-89. https://doi.org/10.1177/0885066619873315.

BACKGROUND: Outcome prediction after out-of-hospital cardiac arrest (OHCA) is difficult. We hypothesized that lactate and need for vasopressors would predict outcome, and that addition of a mitochondrial biomarker would enhance performance of the tool.

METHODS: Prospective observational study of OHCA patients presenting to an academic medical center September 2008 to April 2016. We conducted univariate and multivariate logistic regressions.

RESULTS: Patients were divided based on 2 variables: vasopressor status and initial lactate (<5 mmol/L, 5-10, ≥10). Three hundred fifty-two patients were evaluated; 249 had a lactate within 3 hours and were included. Patients on vasopressors had higher mortality (74% vs 40%; P < .001). A stepwise increase in mortality is associated with increasing lactate (45% lactate <5, 66% 5-10, and 83% ≥10; P < 001). Multivariable models with lactate group and vasopressors as predictors demonstrated excellent discrimination (area under the receiver operating curve [AUC]: 0.73 [95% confidence interval, CI: 0.66-0.79]; adjusted for additional covariates: AUC: 0.81 [95% CI: 0.75-0.86]). Thirty-six patients had cytochrome c levels available; among these 36, when comparing models with and without cytochrome c, there was no difference (AUC: 0.88 [95% CI: 0.76-1.00] vs AUC: 0.85 [95% CI: 0.73-0.98], respectively; P = .30).

CONCLUSION: In this prospective validation, the combination of lactate and vasopressors in the immediate postarrest period is predictive of mortality. Cytochrome c offered minimal additional predictive power.