Low Plasma Sphingomyelin Levels Show a Weak Association with Poor Neurological Outcome in Cardiac Arrest Patients: Results from the Prospective, Observational COMMUNICATE Trial.

Aurelio Boerlin,Kai Tisljar,Emanuel Thommen,Katharina Beck,Sebastian Perrig,Alessia Vincent,Christoph Becker,Luca Bernasconi,Stephan Marsch,Raoul Sutter,Tanja Luescher,Sabina Hunziker,Peter Neyer,Philipp Schuetz,Madlaina Widmer

doi:10.3390/jcm9040897

Abstract

There is interest in novel blood markers to improve risk stratification in patients presenting with cardiac arrest. We assessed associations of different plasma sphingomyelin concentrations and neurological outcome in patients with cardiac arrest. In this prospective observational study, adult patients with cardiac arrest were included upon admission to the intensive care unit (ICU). We studied associations of admission plasma levels of 15 different sphingomyelin species with neurological outcome at hospital discharge (primary endpoint) defined by the modified Rankin Scale by the calculation of univariable and multivariable logistic regression models adjusted for age, gender, and clinical shock markers. We included 290 patients (72% males, median age 65 years) with 162 (56%) having poor neurological outcome at hospital discharge. The three sphingomyelin species SM C24:0, SM(OH) C22:1, and SM(OH) C24:1 were significantly lower in patients with poor neurological outcome compared to patients with favorable outcome with areas under the curve (AUC) of 0.58, 0.59, and 0.59. SM(OH) C24:1 was independently associated with poor neurological outcome in a fully-adjusted regression model (adjusted odds ratio per log-transformed unit increase in SM(OH) C24:1 blood level 0.18, 95% CI 0.04 to 0.87, p = 0.033). Results were similar for 1-year mortality. Low admission sphingomyelin levels showed a weak association with poor neurological outcome in patients after cardiac arrest. If validated in future studies, a better understanding of biological sphingomyelin function during cardiac arrest may help to further advance the therapeutic approach and risk stratification in this vulnerable patient group.

Highlights

Cardiac arrest remains a severe condition with high mortality and morbidity [1]
The regulation of SM content in a cell is directed by two main groups of enzymes: sphingomyelin synthases (SMSs), which catalyse the SM synthesis from ceramides and sphingomyelinases (SMases), which are responsible for SM hydrolysis to generate ceramides and phosphocholine [18]
From October 2012 until June 2018, 406 adult patients were admitted to the intensive care unit (ICU) at the University hospital of Basel following cardiac arrest, of which 290 (71.4%) had an admission blood sample available and were included in this study

Summary

Introduction

Cardiac arrest remains a severe condition with high mortality and morbidity [1]. Among survivors, risk for irreversible brain injury is high, leading to severe disability [2]. The discussion of therapeutic options in this context is often challenging, since patients are usually unconscious upon arrival to the intensive care unit (ICU), and isolated prognostic markers are not reliable. Research investigating prognostic blood markers in this patient group has the potential to improve the prediction of clinical outcomes and may help to define new therapeutic opportunities [4,5]. In the field of metabolomics—the analysis of a subset of metabolites under a defined clinical condition [6,7]—sphingolipids (SLs) have been linked to atherosclerosis, coronary artery disease (CAD), Alzheimer’s disease, and sepsis [8,9,10,11,12,13,14,15,16]. The regulation of SM content in a cell is directed by two main groups of enzymes: sphingomyelin synthases (SMSs), which catalyse the SM synthesis from ceramides and sphingomyelinases (SMases), which are responsible for SM hydrolysis to generate ceramides and phosphocholine [18]

Results

Discussion

Conclusion