scholarly journals Pediatric Multi-Organ Dysfunction Syndrome: Analysis by an Untargeted “Shotgun” Lipidomic Approach Reveals Low-Abundance Plasma Phospholipids and Dynamic Recovery over 8-Day Period, a Single-Center Observational Study

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 774
Author(s):  
Mara L. Leimanis-Laurens ◽  
Karen Ferguson ◽  
Emily Wolfrum ◽  
Brian Boville ◽  
Dominic Sanfilippo ◽  
...  

Lipids are molecules involved in metabolism and inflammation. This study investigates the plasma lipidome for markers of severity and nutritional status in critically ill children. Children with multi-organ dysfunction syndrome (MODS) (n = 24) are analyzed at three time-points and cross-referenced to sedation controls (n = 4) for a total of N = 28. Eight of the patients with MODS, needed veno-arterial extracorporeal membrane oxygenation (VA ECMO) support to survive. Blood plasma lipid profiles are quantified by nano-electrospray (nESI), direct infusion high resolution/accurate mass spectrometry (MS), and tandem mass spectrometry (MS/MS), and compared to nutritional profiles and pediatric logistic organ dysfunction (PELOD) scores. Our results show that PELOD scores were not significantly different between MODS and ECMO cases across time-points (p = 0.66). Lipid profiling provides stratification between sedation controls and all MODS patients for total lysophosphatidylserine (lysoPS) (p-value = 0.004), total phosphatidylserine (PS) (p-value = 0.015), and total ether-linked phosphatidylethanolamine (ether-PE) (p-value = 0.03) after adjusting for sex and age. Nutrition intake over time did not correlate with changes in lipid profiles, as measured by caloric and protein intake. Lipid measurement in the intensive care environment shows dynamic changes over an 8-day pediatric intensive care unit (PICU) course, suggesting novel metabolic indicators for defining critically ill children.

Author(s):  
Mara L. Leimanis Laurens ◽  
Karen Ferguson ◽  
Emily Wolfrum ◽  
Brian Boville ◽  
Dominic Sanfilippo ◽  
...  

AbstractLipids are stable molecules involved in metabolism and inflammation. We investigated the plasma lipidome for markers of severity and nutritional status in critically ill children. Children with multi-organ dysfunction syndrome (MODS) (n=24) were analyzed at three time points and cross referenced to sedation controls (n = 4) for a total of N=28. Eight of the patients with MODS, needed veno-arterial extracorporeal membrane oxygenation (VA ECMO) support to survive. Blood plasma lipid profiles were quantified by nano-electrospray (nESI), direct infusion high resolution/accurate mass spectrometry (MS), and tandem mass spectrometry (MS/MS) and compared to nutritional profiles and PEdiatric Logistic Organ Dysfunction (PELOD) scores. PELOD scores were not significantly different between MODS and ECMO cases across time-points (p = 0.66). Lipid profiling provided stratification between sedation controls and all MODS patients for lysophosphatidylserine (lysoPS) (p-value = 0.004), total phosphatidylserine (PS) (p-value = 0.015), and total ether-linked phosphatidylethanolamine (PE) (p-value = 0.03). Phospholipids in patients needing ECMO were observably closer to sedation controls than other MODS patients. Nutrition intake revealed changes in lipid profiles that corresponded to calorie and protein intake. Lipid measurement in the intensive care environment shows dynamic changes over an 8-day PICU course, suggesting novel indicators for defining critically ill children.


2021 ◽  
Author(s):  
Mara L. Leimanis-Laurens ◽  
Emily Wolfrum ◽  
Karen Ferguson ◽  
Jocelyn R. Grunwell ◽  
Dominic Sanfilippo ◽  
...  

AbstractGlycero- and sphingo-lipids are important in plasma membrane structure, caloric storage and signaling. An un-targeted lipidomics approach for a cohort of critically ill pediatric intensive care unit (PICU) patients, undergoing multi-organ dysfunction syndrome (MODS) was compared to sedation controls. After IRB approval, patients meeting criteria for MODS were screened, consented (n=24), and blood samples were collected from the PICU at HDVCH, Michigan; eight patients needed veno-arterial extracorporeal membrane oxygenation (VA ECMO). Sedation controls were presenting for routine sedation (n=4). Plasma lipid profiles were determined by nano-electrospray (nESI) direct infusion high resolution/accurate mass spectrometry (MS) and tandem mass spectrometry (MS/MS). Biostatistics analysis was performed using R v 3.6.0. 61 patient samples over 3 time points revealed a ceramide metabolite, hexosylceramide (Hex-Cer) was high across all time points (mean 1.63% - 3.19%; vs. controls 0.22%). Fourteen species statistically differentiated from sedation controls (P-value ≤0.05); sphingomyelin (SM) [SM(d18:1/23:0), SM(d18:1/22:0), SM(d18:1/23:1), SM(d18:1/21:0), SM(d18:1/24:0)]; and glycerophosphotidylcholine (GPC) [GPC(36:01), GPC(18:00), GPC(O:34:02), GPC(18:02), GPC(38:05), GPC(O:34:03), GPC(16:00), GPC(40:05), GPC(O:36:03)]. Hex-Cer has been shown to be involved in viral infection and may be at play during acute illness. GPC(36:01) was elevated in all MODS patients at all time points and is associated with inflammation and brain injury.


2021 ◽  
Vol 11 (5) ◽  
pp. 339
Author(s):  
Mara Leimanis-Laurens ◽  
Emily Wolfrum ◽  
Karen Ferguson ◽  
Jocelyn R. Grunwell ◽  
Dominic Sanfilippo ◽  
...  

Glycero- and sphingo-lipids are important in plasma membrane structure, caloric storage and signaling. An un-targeted lipidomics approach for a cohort of critically ill pediatric intensive care unit (PICU) patients undergoing multi-organ dysfunction syndrome (MODS) was compared to sedation controls. After IRB approval, patients meeting the criteria for MODS were screened, consented (n = 24), and blood samples were collected from the PICU at HDVCH, Michigan; eight patients needed veno-arterial extracorporeal membrane oxygenation (VA ECMO). Sedation controls were presenting for routine sedation (n = 4). Plasma lipid profiles were determined by nano-electrospray (nESI) direct infusion high resolution/accurate mass spectrometry (MS) and tandem mass spectrometry (MS/MS). Biostatistics analysis was performed using R v 3.6.0. Sixty-one patient samples over three time points revealed a ceramide metabolite, hexosylceramide (Hex-Cer) was high across all time points (mean 1.63–3.19%; vs. controls 0.22%). Fourteen species statistically differentiated from sedation controls (p-value ≤ 0.05); sphingomyelin (SM) [SM(d18:1/23:0), SM(d18:1/22:0), SM(d18:1/23:1), SM(d18:1/21:0), SM(d18:1/24:0)]; and glycerophosphotidylcholine (GPC) [GPC(36:01), GPC(18:00), GPC(O:34:02), GPC(18:02), GPC(38:05), GPC(O:34:03), GPC(16:00), GPC(40:05), GPC(O:36:03)]. Hex-Cer has been shown to be involved in viral infection and may be at play during acute illness. GPC(36:01) was elevated in all MODS patients at all time points and is associated with inflammation and brain injury.


2019 ◽  
Vol 59 (6) ◽  
pp. 318-24
Author(s):  
Anindita Wulandari ◽  
Pudjiastuti Pudjiastuti ◽  
Sri Martuti

Background Sepsis is one of the main causes of death in infants and children. Currently, it is defined as a life-threatening organ dysfunction, caused by an inflammatory response of infection. Several organ dysfunction assessment methods are available, but they are not uniformly used. Objective To compare the accuracy of three mortality predictor tools: severe sepsis criteria, pediatric logistic organ dysfunction (PELOD)-2, and pediatric sequential organ failure assessment (pSOFA), in critically ill children with sepsis. Methods This prospective cohort study was conducted in the pediatric intensive care unit (PICU) and pediatric high care unit (HCU) of dr. Moewardi Hospital, Surakarta, Central of Java. All patients who met the systemic inflammatory response syndrome (SIRS) criteria were included in our study. The exclusion criteria were congenital anomalies of heart or kidney, malignancy, or hematological abnormalities. The data were taken from laboratory and physical examinations by the physicians on duty. The outcome assessed was mortality. Results Of 30 subjects, the mean age was 22.22 (SD 29.36) months; the most common infection source was the respiratory tract, followed by gastrointestinal tract and central nervous system. Most subjects were treated in the PICU and had a mean length of stay of 8.70 (SD 11.91) days. Severe sepsis and PELOD-2 were not significant predictors of death. However, pSOFA score was a statistically significant predictor of mortality, with odds ratio 10.11 (95%CI 1.054 to 97.002; P=0.039). Conclusion Pediatric SOFA (pSOFA) is a better predictor of mortality compared to PELOD-2 and SIRS-severe sepsis. A pSOFA score ≥ 2 increases the risk of mortality by 10.11-fold.


2020 ◽  
Vol 21 (4) ◽  
pp. e160-e169
Author(s):  
Michaël Sauthier ◽  
Florence Landry-Hould ◽  
Stéphane Leteurtre ◽  
Atsushi Kawaguchi ◽  
Guillaume Emeriaud ◽  
...  

2021 ◽  
pp. 1-8
Author(s):  
Gabriella Bottari ◽  
Manuel Murciano ◽  
Pietro Merli ◽  
Claudia Bracaglia ◽  
Isabella Guzzo ◽  
...  

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition characterized by a state of hyperinflammation. Blood purification techniques can blunt the inflammatory process with a rapidly relevant nonselective effect on the cytokine storm, thus potentially translating into survival benefit for these patients. In this cohort, we evaluated the impact of hemoadsorption with CytoSorb combined with continuous kidney replacement therapy used as adjunctive therapy in 6 critically ill children with multiple organ dysfunction due to HLH. In our series, we found a reduction in inflammatory biomarkers in patients with HLH secondary to infection. Ferritin, one of the most important bedside biomarkers of HLH, showed a reduction in most of the treated patients. The same results were found measuring interleukin-6 and interleukin-10. The same patients showed hemodynamic stabilization measured by the Vasopressor-Inotropic-Score, and reduction in the organ disease score measured with the Pediatric Logistic Organ Dysfunction score. In our cohort, mortality was less than expected based on the Pediatric Index of Mortality 3 score at pediatric intensive care unit admission. Our study shows that hemoperfusion could be a valuable therapeutic option in HLH: stronger scientific evidence is needed to confirm our preliminary experience.


2014 ◽  
Vol 54 (5) ◽  
pp. 251
Author(s):  
Putri Amelia ◽  
Munar Lubis ◽  
Ema Mutiara ◽  
Yunnie Trisnawati

Background Mortality from acute kidney injury (AKI) can be ashigh as 60% in critically ill children. This high mortality rate isinfluenced by the severity of primary diseases, organ dysfunction,and the stage of acute kidney injury.Objective To assess for an as sedation between AKI and mortalityin critically ill children hospitalized in the pediatric intensive careunit (PICU).Methods A cross-sectional study was conducted from Aprilto July 2012. All patients aged 1 month to 18 years who werehospitalized in the PICU for more than 24 hours were included.Urine output and serum creatinine levels were evaluated daily.Patients were categorized according to the pediatric risk, injury,failure, loss, and end stage renal disease (pRIFLE) criteria. Chisquare, Fisher's exact, Mann-\X'hitney U, and Kruskal-Wallis testswere used to assess for an association between AKI, mortality,pediatric logistic organ dysfunction (PELOD) score, and lengthof PICU stay. AP value of < 0.05 was considered as statisticallysignificant.Results During the study period, 57 children were admitted,consisting of 25 (43.9%) females and 32 (56.1 %) males, witha median age of 43 months. The prevalance of AKI was 31.5%(18/57) and classified into stages: risk 13/18, injury 3/18, andfailure 2/18. The mortality rate for AKI was 16. 7%. There was noassociation between AKI and mortality (P=0.592). The PELODscores were found to be similar among patients (SD 11.3 2 vs. SD12.23; P=0.830), and there was no association between AKI andlength of PICU stay (P=0.819).Conclusion There is no association between AKI and mortalityin critically ill children admitted in PICU.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Hiroyuki Nagafuchi ◽  
Hiroyuki Shimizu ◽  
Kaori Yamada ◽  
Kenta Shono ◽  
Tetsuya Ogawa

Abstract Background Multiple organ dysfunction syndrome is the leading cause of death in pediatric intensive care units and can be very critical when combined with shock and disseminated intravascular coagulation (DIC). Currently, there is no effective treatment. We developed a new hemodiafiltration (HDF) method called plasma HDF (PHDF) that uses fresh frozen plasma as replacement fluid and investigated the safety and efficacy of this treatment. Methods We enrolled critically ill children with (1) a Pediatric Logistic Organ Dysfunction 2 (PELOD-2) score ≥ 14, (2) a Japanese Ministry of Health and Welfare (JMHW) DIC score ≥ 7, (3) a vasoactive inotropic score (VIS) ≥ 10, and (4) a serum total protein concentration ≤ 5.0 g/dL. PHDF was performed for 5 h and then switched to continuous HDF. The primary endpoint was the 28-day mortality rate. Secondary endpoints included assessment of vital signs, blood test data, and fluid balance from PHDF start to day 7. Results Nine patients (four males and five females) between 3 days and 40 months of age, weighing 2.1–13 kg, met the inclusion criteria. Although the median PMR was 0.94 (0.71–0.96), the 28-day mortality rate was 22.2% (2/9). One hour after the start of PHDF, there was an increase in mean arterial pressure and central venous pressure and a decrease in heart rate; by day 7, there was a significant decrease in the PELOD-2 score, the JMHW DIC score, and the VIS. Hypoproteinemia also improved the day after PHDF. Water balance was able to remain negative after day 2. Conclusions PHDF was found to be effective in the treatment of DIC and circulatory failure by supplementing coagulation and antithrombotic factors as well as by raising colloid osmotic pressure to increase circulating blood volume. PHDF has been shown to be a safe and useful treatment for critically ill children and has the potential to improve 28-day survival.


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