Acid Sphingomyelinase Serum Activity Predicts Mortality in Intensive Care Unit Patients after Systemic Inflammation: A Prospective Cohort Study

Abstract

IntroductionAcid sphingomyelinase is involved in lipid signalling pathways and regulation of apoptosis by the generation of ceramide and plays an important role during the host response to infectious stimuli. It thus has the potential to be used as a novel diagnostic marker in the management of critically ill patients. The objective of our study was to evaluate acid sphingomyelinase serum activity (ASM) as a diagnostic and prognostic marker in a mixed intensive care unit population before, during, and after systemic inflammation.Methods40 patients admitted to the intensive care unit at risk for developing systemic inflammation (defined as systemic inflammatory response syndrome plus a significant procalcitonin [PCT] increase) were included. ASM was analysed on ICU admission, before (PCTbefore), during (PCTpeak) and after (PCTlow) onset of SIRS. Patients undergoing elective surgery served as control (N = 8). Receiver-operating characteristics curves were computed.ResultsASM significantly increased after surgery in the eight control patients. Patients from the intensive care unit had significantly higher ASM on admission than control patients after surgery. 19 out of 40 patients admitted to the intensive care unit developed systemic inflammation and 21 did not, with no differences in ASM between these two groups on admission. In patients with SIRS and PCT peak, ASM between admission and PCTbefore was not different, but further increased at PCTpeak in non-survivors and was significantly higher at PCTlow compared to survivors. Survivors exhibited decreased ASM at PCTpeak and PCTlow. Receiver operating curve analysis on discrimination of ICU mortality showed an area under the curve of 0.79 for ASM at PCTlow.ConclusionsIn summary, ASM was generally higher in patients admitted to the intensive care unit compared to patients undergoing uncomplicated surgery. ASM did not indicate onset of systemic inflammation. In contrast to PCT however, it remained high in non-surviving ICU patients after systemic inflammation.

Secretory sphingomyelinase in health and disease

“…In the context of elevated S-ASM levels in sepsis (Claus et al, 2005;Kott et al, 2014), the resulting enhanced erythrocyte clearance is likely to contribute to anemia. The sensitivity of erythrocytes increases further during blood bank storage and physiological aging (Dinkla et al, 2012).…”

“…SIRS, systemic inflammatory response syndrome; NPD, Niemann-Pick disease. Literature (in alphabetical order of the description in the Figure): acute myocardial infarction (Pan et al, 2014), alcohol detoxification , allergy ), Alzheimer's disease (Lee et al, 2014), chronic heart failure (Pan et al, 2014), diabetes mellitus II (Górska et al, 2003), hepatitis C (Grammatikos et al, 2014), inflammatory renal disease (Kiprianos et al, 2012), lymphohistiocytosis (Takahashi et al, 2002;Jenkins et al, 2013), non-alcoholic fatty liver (Grammatikos et al, 2014), NPD-B (Abe et al, 1999;He et al, 2003), NPD-B carrier (He et al, 2003), post-operative (Kott et al, 2014), post-traumatic stress disorder , rs1050239 , rs141641266 (Rhein et al, 2013), sepsis (Claus et al, 2005), signal peptide repeat 4/4 , SIRS (Kott et al, 2014), stable angina pectoris (Pan et al, 2014), systemic vasculitis ( Kiprianos et al, 2012), unstable angina pectoris (Pan et al, 2014), and Wilson disease (Lang et al, 2007).…”

“…Mildly elevated activities are observed in Alzheimer's disease (Lee et al, 2014), type II diabetes mellitus (Górska et al, 2003), stable angina pectoris, acute myocardial infarction (Pan et al, 2014), chronic heart failure (Doehner et al, 2007), post-traumatic stress disorder and in response to ionizing radiation treatment in cancer patients (Sathishkumar et al, 2005). Marked increases in activity ( > 200%) are observed in unstable angina pectoris (Pan et al, 2014), Wilson disease (Lang et al, 2007), sepsis (Claus et al, 2005), systemic inflammatory response syndrome (Kott et al, 2014), lymphohistiocytosis (Takahashi et al, 2002;Jenkins et al, 2013), non-alcoholic fatty liver, hepatitis C (Grammatikos et al, 2014), systemic vasculitis, inflammatory renal disease (Kiprianos et al, 2012) and in patients with alcohol dependency undergoing withdrawal . In sepsis, lymphohistiocytosis, systemic inflammatory response syndrome and chronic heart failure, high S-ASM activity is associated with higher mortality (Claus et al, 2005;Doehner et al, 2007;Jenkins et al, 2013;Kott et al, 2014).…”

Elevation of Serum Acid Sphingomyelinase Activity in Children with Acute Respiratory Syncytial Virus Bronchiolitis

“…Mild elevations of blood S-ASM activity were observed in Alzheimer's disease (Lee et al 2014), type 2 diabetes mellitus (Górska et al 2003), stable angina pectoris (Pan et al 2014), acute myocardial infarction (Pan et al 2014), chronic heart failure (Doehner et al 2007), post-traumatic stress disorder (Hammad et al 2012), and in response to ionizing radiation treatment in cancer patients (Sathishkumar et al 2005). Marked elevations of blood S-ASM activity were observed in unstable angina pectoris (Pan et al 2014), Wilson disease (Lang et al 2007), sepsis (Claus et al 2005), systemic inflammatory response syndrome (Kott et al 2014), lymphohistiocytosis (Takahashi et al 2002;Jenkins et al 2013), non-alcoholic fatty liver (Grammatikos et al 2014), hepatitis C (Grammatikos et al 2014), systemic vasculitis inflammatory renal disease (Kiprianos et al 2012), and in patients with alcohol dependency undergoing withdrawal . Thus, ASM has a potential pathophysiological role in these diseases.…”

Acid Sphingomyelinase Promotes Endothelial Stress Response in Systemic Inflammation and Sepsis

“…An altered biological function, including sphingomyelin-breakdown and ceramidegeneration, may play an important role in systemic inflammatory response syndrome (SIRS) and sepsis. In sepsis, both enhanced monocytic ceramide content and threshold levels of SMPD1 activity help to predict outcome (19)(20)(21). Further evidence suggests a beneficial role of using functional inhibitors of acid sphingomyelinase (FIASMA) in systemic inflammation, which reduced inflammatory response and improved outcome in an endotoxemia mice model (20,22).…”