Table 1 Summary of Studies with evaluation of lipid biomarkers

Drobnik et al., 2003 [37]

Prospective Experimental

102 patients with sepsis and 56 control

Analyses by mass spectrometry. The samples were collected as soon as sepsis criteria were met and mortality analyzed at 30 days.

Most Cer species were increased in sepsis patients, while all LPC species were markedly decreased. Species-specific as well as total Cer-SPM ratios were increased, whereas LPC-PC ratios were decreased in sepsis patients. The increased Cer-SPM ratios as well as the decreased LPC-PC ratios showed a strong predictive power for sepsis-related mortality.

Total cholesterol, HDL-C, and LDL-C in sepsis patients were markedly reduced compared with a healthy population.

Cho et al., 2012 [59]

Prospective

Not randomized

Patients meeting sepsis criteria (105) and control – healthy blood donors (21)

Blood samples collected on the first day.

Samples were analyzed using the ANZWELL LPC Assay commercial kit (Alfresa Pharma Corporation, Osaka, Japan).

Mean of serum concentration of LPC was significantly lower in patients with sepsis than in healthy individuals.

No differences were observed between survivors and non-survivors in septic patients.

Schmerler et al., 2012 [69]

Prospective

Not randomized

161 patients (74 with SIRS, 69 with sepsis and 18 control – patients in ICU without SIRS)

Samples of blood samples were collected within the first 24 h of admission of patients with SIRS. For patients with sepsis, samples were collected at 24 h after the onset of organ dysfunction.

Analyzes were performed by mass spectrometry.

Acylcarnitine (C10:1) and Phosphatidylcholine (PCaaC32:0) were significantly higher in patients with sepsis compared to patients with non-infectious SIRS.

Cho et al., 2014 [65]

Prospective

Not randomized

A total of 56 patients with community-acquired pneumonia (CAP)

Blood samples were collected from patients with CAP on days 1 and 7 and analyzed for their plasma LPC concentrations. Blood samples were analyzed using an Anzwell LPC Assay Kit commercial (Alfresa Pharma, Osaka, Japan).

24 (42.9%) of patients required intubation and 15 (26.8%) died. The mean LPC concentrations on days 1 and 7 were significantly lower in the non-survivors. LPC levels < 29.6 μmol/L at day 1 were associated with outcomes such as the need for mechanical ventilation, vasopressors, ICU admission and hospital mortality.

Park et al., 2014 [67]

Prospective, observational

A total of 74 patients with confirmed diagnosis of infection with at least two criteria of SIRS, within 24 h of admission in ICU

Blood sample analyzed on day 1 and day 7.

Blood samples were analyzed using an Anzwell LPC Assay Kit commercial (Alfresa Pharma, Osaka, Japan).

The LPC concentration on day 7 was significantly lower in non-survivors. A decreased LPC concentration on day 7 and sustained high concentration of procalcitonin on day 7 were related to 28-day mortality. LPC concentrations increased over time in patients with appropriate antibiotics.

Liang et al., 2016 [70]

Prospective

ICU patients with sepsis induced lung injury - SLI (80) and healthy volunteers (82)

Plasma samples were collected in the morning at ICU with 10 h of fasting and analyzed by chromatography/mass spectrometry.

Significant changes were found in 7 metabolites, with an increase in concentration in SLI patients in 5 of them and a decrease in 2. Lipid metabolites include PE (P-19: 1 (12Z) / 0: 0), PE (22: 2 13Z, 16Z) / 15: 0), PC (17: 0/0: 0), LPC (P-16: 0), PE (20: 3 (8Z, 11Z, 14Z) / 0: 16: 0/0: 0) and PC (17: 1 (10Z) / 0: 0). PE (P-19: 1 (12Z) / 0: 0) showed sensitivity of 98.1% and specificity of 97.3%. Three lipids (PE (P-19: 1 (12Z) / 0: 0), PE (22: 2 (13Z, 16Z) / 15: 0), PC (17: 0/0: 0)) were selected to form a group of biomarkers to improve risk discrimination among SIL patients and healthy cases.

Retrospective

Plasma of 20 patients with severe septic shock (SOFA score > 8) enrolled in a multicenter Study (Albumin Italian Outcome Sepsis Study)

Plasma samples were analyzed by spectrometry that included quantitative measurements of

acylcarnitines, aminoacids, biogenicamines, glycerophospholipids, sphingolipids, and sugars.

Unsaturated long-chain phosphatidylcholines and LPC species were associated to the event at 28-days and 90-days in combination with clinical variables such as cardiovascular SOFA score (28-day mortality model) or renal replacement therapy (90-day mortality model).

Mecatti et al., 2018 [39]

Prospective

Not randomized

Septic patients (n = 20) and healthy controls (n = 20)

Samples were collected in the first 36 h of admission to the ICU and analyzed by gas chromatography and mass spectrometry.

LPCs and SMs were downregulated, whereas the saturated and unsaturated phosphatidylcholines (PCs) were upregulated in the plasma and erythrocytes of septic patients.

Prospective

Controlled

Patients with severe sepsis and septic shock (n = 143), with pneumonia (n = 12), and healthy individuals (n = 31)

Quantitative analyses of LPC 16:0 were performed in samples of sera using a matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry on a parylene-matrix chip.

Sensitivity of 97.9% and selectivity of 95.5% in sepsis diagnosis as compared to healthy individuals and patients with pneumonia.

Experimental

Controlled

Swine model (n = 9)

Induced peritonitis was performed in a swine model, and changes in hemodynamic, blood chemistry, and inflammatory markers were monitored. Quantitative mass spectrometry-based targeted metabolomic analyses were performed.

Marked decrease in phosphatidylcholines and LPC species, altered alanine-glucose cycle and inter-organ amino acid metabolism.

Prospective

Controlled

Patients with community-acquired pneumonia (n = 29) and with chronic obstructive pulmonary disease exacerbation with infection (n = 13) and control group (n = 33)

105 phospholipids, 40 acylcarnitines, and 4 ceramides, as well as acid sphingomyelinase activity were analysed in plasma using a triple-quadrupole mass spectrometer.

Phospholipid concentrations were greatly decreased in community-acquired pneumonia and normalized in the course of clinical improvement. The changes in COPD were less pronounced, but also differed qualitatively.