scholarly journals Sepsis-3: new edition — old problems. analysis from the perspective of general pathology

2021 ◽  
Vol 11 (4) ◽  
pp. 649-662
Author(s):  
E. Yu. Gusev ◽  
N. V. Zotova ◽  
V. A. Chereshnev
Keyword(s):  
Intensive Care ◽  
Organ Dysfunction ◽  
Systemic Inflammation ◽  
Intensive Therapy ◽  
Clinical Manifestations ◽  
Critical Conditions ◽  
Low Grade ◽  
Proinflammatory Response ◽  
Shock Condition ◽  
General Pathology

Sepsis-3 Guidelines defines sepsis as an organ dysfunction caused by dysregulated host response to infection. To record organ dysfunction, the SOFA/quick SOFA scales were recommended. In fact, in medical practice, sepsis is considered nothing more than a critical infection that requires intensive care. Therefore, sepsis is pathogenetically a nonhomogeneous condition manifested by diverse nosologies and syndromes. Unlike the previous two editions, Sepsis-1 and Sepsis-2 Guidelines, the formal criteria provided in the Sepsis-3 are closer to the de facto position, describe more specific, but less sensitive features to predict mortality. However, the initial, latent manifestations of critical conditions, which can be relatively effectively controlled by intensive therapy, remain outside the Sepsis-3 criteria. Not all signs of multiple organ dysfunctions (according to the Sepsis-3 criteria) will require intensive care. Hence, obviously the presence or absence of formal criteria of Sepsis-3 will not be always taken into account while verifying sepsis. The only relatively pathogenetically homogeneous definition in Sepsis-3 is “septic shock”. However, it also does not fully consider the staging (according to the degree of compensation of hemodynamic disturbances) and the phasing (according to the severity of the proinflammatory response) of the dynamics of the shock condition. From our point of view, a positive result of the Sepsis-3 consensus would be in transition of the systemic inflammatory response syndrome (SIRS) from the main to additional (optional) verifying sepsis criteria. We also believe that the weak side of the Sepsis-3 Guidelines is in underestimated mechanisms of systemic inflammation as a general pathological process in the genesis of developing critical conditions of various origins. From the perspective of general pathology, sepsis is a combination of the three common fundamental pathological processes: classical (canonical) and systemic inflammation (SI), as well as chronic systemic low-grade inflammation (parainflammation), the latter can be considered as an unfavorable background for development of the former two processes. All three processes are characterized by any SIR signs and require to be differentiated on the basis of integral criteria, which reflect specific blocks of the SI complex process. The pathogenesis of the SARS-CoV-2 infection (COVID-19) is a relevant example underlying inevitability of such approach. The systemic microvascular vasculitis, and its main clinical manifestations such as systemic microcirculatory disorders in the form of shockogenic conditions is the SI pathogenetic basis. Apparently, one of the modalities for further evolution of critical care medicine will be coupled to development of a more multilayered but effective methods for assessing pathogenesis of critical states and more differentiated methods of pathogenetic therapy. Therefore, it will require to modernize a number of fundamental premises in our knowledge about pathobiology, pathophysiology, and general pathology.

scholarly journals Intramucosal pH as a criterion for the organism emergency from hepatospanchnic ischemia, or centralization of blood flow

2021 ◽  
Vol 17 (3) ◽  
pp. 10-14
Author(s):  
L.O. Maltseva ◽  
V.M. Lisnycha ◽  
I.A. Malsev ◽  
N.A. Kazimirova
Keyword(s):  
Blood Pressure ◽  
Intensive Care ◽  
Intensive Therapy ◽  
Tissue Perfusion ◽  
Regional Perfusion ◽  
Critical Conditions ◽  
Intramucosal Ph ◽  
Arterial Blood ◽  
The Difference ◽  
Splanchnic Hypoperfusion

In critical conditions, despite the restoration of systemic hemodynamics and overall oxygen delivery, tissue hypoxia and reduced oxygen extraction remain. One of the important tasks of intensive care for critical conditions is the early diagnosis of tissue perfusion disorders. In clinical circumstances, signs of hypoperfusion are arterial hypotension, tachycardia, oliguria, encephalopathy, low body temperature, the disappearance of skin capillary pattern, metabolic lactate acidosis. However, blood pressure is an insensitive indicator of tissue hypoperfusion itself. Experimental clinical trials have repeatedly documented that local perfusion pressure in critical conditions does not directly depend on systemic blood pressure. Lactate is not a specific marker of anaerobic metabolism, but rather impaired microcirculation seems to be one of the possible mechanisms of hyperlactatemia. Reliable markers of tissue perfusion and the effectiveness of early targeted therapy are regional capnometry (gastric intramucosal pH, sublingual pCO2), a saturation of mixed venous blood, etc. Intramucosal pH is of particular practical importance as a marker of regional capnometry. The aim of the study is the analysis of literature sources devoted to the effectiveness and diagnostic significance of intramucosal pH as a marker of regional perfusion. The value of intramucosal pH was evaluated: 1) during abdominal operations and the development of postoperative complications in comparison against IL-6 and IL-8; 2) during and after surgical interventions in conditions of prolonged cardiopulmonary bypass to assess the adequacy of blood supply to the abdominal organs; 3) in experimental septic shock compared to the values of lactate and hypoxanthine concentration in the liver and arterial blood; 4) the correlation between intramucosal pH va-lues, indices of the pediatric mortality risk scale, forming of great (cardiac arrest, shock) and minor (hypotension, hypovolemia, arrhythmia) hemodynamic complications and duration of staying in intensive care unit and intensive therapy; 5) during laparoscopic cholecystectomy in apparently healthy patients with the simultaneous calculation of the difference between arterial and intramucosal pH. Intramuscular pH-controlled intensive therapy is a separate fragment: an intramucosal pH of less than 7.3 reflects splanchnic hypoperfusion and is an indicator of the unfavorable outcomes; intramucousal pH of more than 7.3 is a criterion for the emergency of the organism from hepatosplanchic ischemia, i.e. centralization of blood circulation. Therefore, the intramucosal pH is valuable in the clinical picture of critical conditions as a marker of regional perfusion measured by capnometry, which allows monitoring that reflects the perfusion of the intestinal wall. The lower threshold is 7.35 (the sensitivity of the method is 67 %, specificity is 74 %). An intramucosal pH of < 7.3 reflects splanchnic hypoperfusion and is an indicator of an adverse outcome. An alternative measurement of intramucosal pCO2, pCO2 in arterial blood and the difference [P (1-a) CO2] is a more reliable index of intestinal oxygenation than single intramucosal pH, but rather pH (1-a) makes it possible to adequately assess the acid-base state of arterial blood. The improvement and widespread use of capnometry and capnography for monitoring during general anaesthesia and intensive care, on the one hand, and modern knowledge of the pathophysiology of gas exchange, on the other hand, stimulate the wider use of less invasive and more affordable methods of regional capnometry and aerial tonometry.

scholarly journals Effect of additional neuroprotection with Gliatilin on the course of the septic process and the severity of encephalopathy in the structure of multiple organ dysfunction syndrome

2021 ◽  
Vol 17 (2) ◽  
pp. 34-41
Author(s):  
L.O. Maltseva ◽  
V.M. Lisnycha ◽  
Yu.Yu. Kobelatskyy ◽  
N.A. Kazimirova
Keyword(s):  
Intensive Care ◽  
Organ Failure ◽  
Organ Dysfunction ◽  
Multiple Organ Dysfunction Syndrome ◽  
Clinical Manifestations ◽  
Multiple Organ ◽  
Interferon Α ◽  
Multiple Organ Dysfunction ◽  
Cerebral Dysfunction ◽  
Factor Α

Background. Sepsis as the response to an infection includes such a developmental stage as multiple organ dysfunction syndrome. In 70 % of cases, cerebral dysfunction is one of the first symptoms of sepsis-associated multiple organ dysfunction syndrome before clinical manifestations in other life support systems. Sepsis-associated encephalopathy is a multifocal dysfunction of the brain in the presence of an infection, accompanied by manifestations of systemic inflammation, but without clinical and laboratory evidence of a direct involvement of the infection in brain damage. Depending on the criteria on which the diagnosis is based, cerebral dysfunction-insufficiency can be detected in all patients with sepsis. The degree of its severity correlates with an increase in the severity of the septic process. Sepsis-associated dysfunction-failure may be an independent predictor of morta­lity. The severity of cerebral dysfunction-failure ranges from lethargy and/or disorientation to coma. The purpose was to study the effect of the main provisions of the International Guidelines for Ma­nagement of Sepsis and Septic Shock: 2016 with additional neuroprotection with Gliatilin on the course of the septic process and the severity of encephalopathy in the structure of multiple organ dysfunction syndrome. Materials and methods. In 2010–2015, we conducted a controlled prospective randomized cohort study at the clinical base of the Department of Anesthesiology and Intensive Care of the State Institution “Dnipropetrovsk Medical Academy of the Ministry of Health of Ukraine” and the Department of Intensive Care of Sepsis at Mechnikov Dnipropetrovsk Regional Clinical Hospital. The study included 22 patients. All of them underwent routine laboratory tests to determine the level of clinical and biochemical markers of systemic inflammation and organ dysfunction according to the Sequential Organ Failure Assessment score and Lausanne Intestinal Failure Estimation. The Glasgow Coma Scale was used to assess the level of consciousness. The concentration of cytokines (tumor necrosis factor α, interleukins 1, 4, interferon α) in the blood serum was studied by the enzyme immunoassay. Basic intensive care was carried out using the main provisions of the International Guidelines for Management of Sepsis and Septic Shock: 2016 with the additional use of the neuroprotective drug Gliatilin (choline alfoscerate) — 1,000–3,000 mg/day, which is dissolved in 0.9% sodium chloride solution, for 5–10 days. The study of indicators was carried out in four stages, on days 1, 3, 5, 7. Results. Summarizing the results of the study, we can say that on the fifth and seventh days, there were no clinical manifestations of the systemic inflammatory response syndrome in more than 75 % of patients; the severity of the condition according to Acute Physiology And Chronic Health Evaluation II system decreased by 72.5 and 74.5 % (p < 0.001) and the severity of the syndrome of multiple organ failure according to Sequential Organ Failure Assessment score decreased 9 times (p < 0.001), according to the stages of the study. Cerebral insufficiency assessed by the Glasgow Coma Scale was 15 points on the fifth and seventh days of the study, which corresponded to the level of clear consciousness in more than 75 % of patients. The above was observed against the background of a trend towards balanced activity of pro-inflammatory and anti-inflammatory links of the cytokine system, as evidenced by the maximum levels of tumor necrosis factor α and interferon α on the fifth day of observation with a decrease in the concentration of interleukin 1 by 55.8 % compared to baseline. The predicted mortality in patients of the second group was 51 %, the actual mortality was 7.5 %. So, carrying out this intensive care helped reduce the estimated mortality by 43.5 %.

scholarly journals Modern Approaches to Intensive Therapy of Patients with Thoracic Trauma in Politrauma

2021 ◽  
Vol 6 (1) ◽  
pp. 10-17
Author(s):  
E. V. Boyko ◽  
◽  
Yu. V. Volkova ◽  
N. V. Baranova
Keyword(s):  
Intensive Care ◽  
Thoracic Trauma ◽  
Intensive Therapy ◽  
Clinical Manifestations ◽  
Practical Interest ◽  
Intensive Care Patients ◽  
Leading Role ◽  
Results Of Treatment ◽  
Vital Functions ◽  
Number Of Patients

The review article presents data on the modern possibilities of intensive care for patients with thoracic trauma in case of polytrauma. It should be noted that over the past 5 years, the number of patients with thoracic injuries in polytrauma who require intensive care in the intensive care unit has increased by 10 times. For their treatment, advanced intensive care methods are used, but, despite this, the mortality rate of this category of patients remains one of the highest, reaching 80%. Moreover, it is combined thoracic trauma that plays a leading role in thanatogenesis. Studying the clinical manifestations of thoracic trauma in patients with polytrauma will help to improve the quality of medical care and the results of treatment of such patients. One of the reasons for the high mortality and disability of patients with thoracic trauma during polytrauma is the lack of a single integrated pathogenetic approach to assessing the severity of the condition of patients and the tactics of intensive care. The values of direct damage to internal organs, the main vessels of the chest and mediastinum in the development of a number of formidable complications are not fully defined, and it is not clearly stated in which cases support for vital functions is needed or their replacement. In the practice of conducting intensive care with thoracic trauma on the background of software in different institutions, often opposite methods and approaches to tactics of conducting intensive care are used. This indicates that the problem of intensive care patients of this contingent is far from being solved and is of certain scientific and practical interest. The role of primary and secondary injuries in combined thoracic trauma has not been studied, the boundaries of compensatory and adaptive reactions have not been determined. Moreover, there is no single concept for intensive care patients with thoracic trauma during polytrauma. This type of damage is accompanied by deep disorders of homeostasis systems, which determine the severity of the clinical course and cause a high level of complications and disability. Unsatisfactory results of intensive care are often associated with insufficient ideas about the pathogenesis of the early post-traumatic period in patients with polytrauma, which leads to errors in determining the volume, timing, feasibility and sequence of intensive care. Conclusion. We believe that the improvement of treatment outcomes for this category of patients can be achieved only with a comprehensive, objectively substantiated approach to the choice of intensive care tactics, focused on the clinical features of thoracic trauma on the background of polytrauma

scholarly journals Modified PIRO (predisposition, insult, response, organ dysfunction) severity score as a predictor for mortality of children with pneumonia in Hasan Sadikin Hospital, Bandung, Indonesia

2021 ◽  
Vol 16 ◽  
Author(s):  
Vebri Valentania ◽  
Dadang H. Somasetia ◽  
Dany Hilmanto ◽  
Djatnika Setiabudi ◽  
Heda Melinda N. Nataprawira
Keyword(s):  
Intensive Care ◽  
Organ Dysfunction ◽  
Severity Score ◽  
Clinical Manifestations ◽  
Bivariate Analysis ◽  
Significant Variable ◽  
Operating Characteristics ◽  
A Value ◽  
Interval Variables ◽  
Care Capacity

Background: Clinical manifestations for pneumonia vary from mild to severe. The PIRO model (predisposition, insult, response, organ dysfunction) was used as scoring system to determine severity of sepsis and pneumonia in adult patients. The PIRO model was modified for sorting the severity of pneumonia in children and predicting its risk of mortality.Methods: An ambispective cohort study of pneumonia patients aged 1 month ≤18 years admitted over the period from May to September 2020. Data were collected from history, physical examination, laboratory examination, and chest radiography. Based on bivariate analysis (p<0.05 and relative risk (RR) with 95% confidence interval), variables of each PIRO component that were significant for mortality were assigned a value of 1. The cut-off score for predictor of mortality was calculated using the receiver operating characteristics (ROC) curve. Stratify the score into three degrees of risk based on interquartile range. Score ≤Q1 is categorized as low risk; Q1-Q3 is categorized as moderate risk; and score >Q3 is categorized as high risk.Results: Out of the 80 subjects subjects enrolled, 6 months-5 years was the largest age group (56.3%). The observed mortality was 15/80 (18.8%). The modified PIRO severity score was compiled from significant variable of predisposition (malnutrition), insult (chest radiograph), response (hypoxemia, hypotension, CRP >0.5 mg/dL, PCT >0.5 ng/dL) and organ dysfunction, with range of score 0-7. Score >3 as a cutoff point score for predictor of mortality with AUC 0.919 (95% CI 0.836–0.968), sensitivity of 80%, and specificity of 84.62%. Subjects with score >3 have RR of 10.544 compared to those with score ≤3. The stratification of score level was low (≤2), moderate (3-4), and high (5-7). The mortality levels were 0%, 46.7%, and 53.3%, respectively.Conclusions: Modified PIRO severity score can be used as a sorting tool and predictor of mortality risk in children with pneumonia. This score can also be used to select candidates for intensive care, especially in health facilities with limited intensive care capacity.

scholarly journals Study of the effectiveness of using decamethoxin-based antiseptic compositions for treating endotracheal tubes in order to prevent the development of ventilator-associated pneumonia in intensive care patients

2020 ◽  
Vol 24 (1) ◽  
pp. 17-19
Author(s):  
Y. Y. Trofimenko ◽  
O. I. Zhorniak ◽  
N. S. Fomina ◽  
V. M. Burkot ◽  
A. V. Kulik ◽  
...  
Keyword(s):  
Intensive Care ◽  
Endotracheal Intubation ◽  
Film Formation ◽  
Clinical Manifestations ◽  
Antimicrobial Properties ◽  
Lung Ventilation ◽  
Critical Conditions ◽  
Ventilator Associated Pneumonia ◽  
Adhesive Film ◽  
Endotracheal Tubes

Annotation. The use of artificial lung ventilation in patients of intensive care unit often leads to airway contamination of conditionally pathogenic microorganisms and the development of ventilator-associated pneumonia. The clinical manifestations of ventilator-associated pneumonia can vary widely from mild to development of critical conditions accompanied by septic shock. This significantly worsens the patient's condition and prognosis for effective treatment. The paper presents the results of the study of the use of adhesive antiseptic compositions based on the domestic antiseptic drug decamethoxin in order to give antimicrobial properties to intubation tubes. An antibacterial adhesive was applied to the surface of segments of the endotracheal intubation tube, after which the samples were dried in a sterile box. The sensitivity of the microorganisms to the components of the antiseptic compositions was studied by the diameter of the growth retardation zone around the studied fragments of endotracheal intubation tubes placed in the thickness of the pre-seeded microorganism’s dense nutrient medium. The results were statistically analyzed using standard application package for biomedical research “STATISTICA 5.5”. It has been proved that adhesive film-forming compositions based on decamethoxin confer pronounced antimicrobial properties to endotracheal intubation tubes. The most susceptible to antimicrobial activity were gram-positive microorganisms of the genus Staphylococcus, and the most resistant were representatives of gram-negative bacteria of the genus Acinetobacter. The obtained research results allow us to predict the effectiveness of the use of adhesive hydrophilic and hydrophobic antiseptic compositions based on the domestic antiseptic decamethoxin to provide protective properties of the surface of endotracheal tubes, prevent the process of bacterial film formation and prevention of ventilator-associated patients.

STUDY OF HS-CRP AND TNF-A LEVELS IN COPD PATIENTS ACCOMPANIED WITH CORONARY ARTERY DISEASE

2014 ◽  
pp. 48-56
Author(s):  
Van Thi Tran ◽  
Van Bang Le ◽  
Thị Thu Huong Hoang
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Systemic Inflammation ◽  
Chronic Obstructive ◽  
Low Grade ◽  
Cross Sectional ◽  
Copd Patients ◽  
Coronary Artery Angiography ◽  
Hs Crp ◽  
Artery Disease

Aim: Some studies have linked the present of chronic obstructive oulmonary disease (COPD) to coronary artery disease (CAD). Low grade systemic inflammation occurs in patients with COPD as well as patients with CAD. This study was designed to find out the concentration differences of hs-CRP and TNF-a in patients having both chronic obstructive pulmonary and coronary artery diseases with those having either. Methods: A cross - sectional descriptive study was conducted in 200 patients undergoing a coronary artery angiography in the Heart Institute, Thong Nhat Hospital and 115 People Hospital. COPD was diagnosed using GOLD classification. Result: Our study had shown that the levels of hs-CRP and TNF-a were statistically increased in patients with COPD, CAD as well as in patients who had COPD with CAD (p<0,05). The levels of hs-CRP were higher in CAD than in COPD nad the levels of TNF-a were higher in COPD than in CAD. In patients with COPD and CAD, there were increased the levels of both hs-CRP and TNF-a in serum. Conclusion: Systemic inflammation presents in both COPD and CAD. Key words: hs-CRP, TNF-a, coronary artery disease (CAD).

Presepsin - New Marker of Sepsis Romanian Neonatal Intensive Care Unit Experience

2019 ◽  
Vol 70 (8) ◽  
pp. 3008-3013
Author(s):  
Silvia Maria Stoicescu ◽  
Ramona Mohora ◽  
Monica Luminos ◽  
Madalina Maria Merisescu ◽  
Gheorghita Jugulete ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Neonatal Intensive Care Unit ◽  
Neonatal Sepsis ◽  
Predictive Value ◽  
Neonatal Intensive Care ◽  
Complete Blood Count ◽  
Clinical Manifestations ◽  
Receiver Operating Curve ◽  
Predictive Values

Difficulties in establishing the onset of neonatal sepsis has directed the medical research in recent years to the possibility of identifying early biological markers of diagnosis. Overdiagnosing neonatal sepsis leads to a higher rate and duration in the usage of antibiotics in the Neonatal Intensive Care Unit (NICU), which in term leads to a rise in bacterial resistance, antibiotherapy complications, duration of hospitalization and costs.Concomitant analysis of CRP (C Reactive Protein), procalcitonin, complete blood count, presepsin in newborn babies with suspicion of early or late neonatal sepsis. Presepsin sensibility and specificity in diagnosing neonatal sepsis. The study group consists of newborns admitted to Polizu Neonatology Clinic between 15th February- 15th July 2017, with suspected neonatal sepsis. We analyzed: clinical manifestations and biochemical markers values used for diagnosis of sepsis, namely the value of CRP, presepsin and procalcitonin on the onset day of the disease and later, according to evolution. CRP values may be influenced by clinical pathology. Procalcitonin values were mainly influenced by the presence of jaundice. Presepsin is the biochemical marker with the fastest predictive values of positive infection. Presepsin can be a useful tool for early diagnosis of neonatal sepsis and can guide the antibiotic treatment. Presepsin value is significantly higher in neonatal sepsis compared to healthy newborns (939 vs 368 ng/mL, p [ 0.0001); area under receiver operating curve (AUC) for presepsine was 0.931 (95% confidence interval 0.86-1.0). PSP has a greater sensibility and specificity compared to classical sepsis markers, CRP and PCT respectively (AUC 0.931 vs 0.857 vs 0.819, p [ 0.001). The cut off value for presepsin was established at 538 ng/mLwith a sensibility of 79.5% and a specificity of 87.2 %. The positive predictive value (PPV) is 83.8 % and negative predictive value (NPV) is 83.3%.

Limitation and withdrawal of intensive therapy at the end of life: Practices in intensive care units in Mumbai, India*

2005 ◽  
Vol 33 (6) ◽  
pp. 1272-1275 ◽  
Author(s):  
Farhad Kapadia ◽  
Manoj Singh ◽  
Jigeeshu Divatia ◽  
Priya Vaidyanathan ◽  
Farokh E. Udwadia ◽  
...  
Keyword(s):  
Intensive Care ◽  
End Of Life ◽  
Intensive Care Units ◽  
Intensive Therapy

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 ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Intensive Care ◽  
Critically Ill ◽  
Organ Dysfunction ◽  
Lipid Profiles ◽  
Critically Ill Children ◽  
P Value ◽  
Time Points ◽  
Logistic Organ Dysfunction ◽  
Multi Organ Dysfunction Syndrome

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.

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