Similar Metabolic, Innate Immunity, and Adipokine Profiles in Adult and Pediatric Sepsis Versus Systemic Inflammatory Response Syndrome-A Pilot Study.

OBJECTIVES: To examine whether the septic profiles of heat shock protein 72, heat shock protein 90α, resistin, adiponectin, oxygen consumption, CO2 production, energy expenditure, and metabolic pattern, along with illness severity, nutritional, and inflammatory indices, differ between adult and pediatric patients compared with systemic inflammatory response syndrome and healthy controls. To evaluate whether these biomolecules may discriminate sepsis from systemic inflammatory response syndrome in adult and pediatric patients. DESIGN: Prospective cohort study. SETTING: University ICU and PICU. PATIENTS: Seventy-eight adults (sepsis/23; systemic inflammatory response syndrome/23; healthy controls/33), 67 children (sepsis/18; systemic inflammatory response syndrome/23; controls/27), mechanically ventilated. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Flow cytometry determined mean fluorescence intensity for monocyte or neutrophil heat shock protein expression. Resistin, adiponectin, and extracellular heat shock proteins were measured using enzyme-linked immunosorbent assay; energy expenditure by E-COVX (GE Healthcare). Genomic DNA was extracted with PureLink Genomic DNA kit (Invitrogen, Carlsbad, CA) to detect heat shock protein 72 single nucleotide polymorphisms. Similarly, in adult and pediatric patients, Acute Physiology and Chronic Evaluation-II/Acute Physiology and Pediatric Risk of Mortality-III, Simplified Acute Physiology Score-III, C-reactive protein, lactate, and resistin were higher and myocardial contractility, monocyte heat shock protein 72, oxygen consumption, CO2 production, energy expenditure, metabolic pattern, glucose, and albumin lower in sepsis compared with systemic inflammatory response syndrome or controls (p < 0.05). For discriminating sepsis from systemic inflammatory response syndrome, resistin, extracellular heat shock protein 90α, and lactate achieved a receiver operating characteristic curve greater than 0.80 in children and greater than 0.75 in adults (p < 0.05). In both, adults and children, genotype heat shock protein 72 analysis did not disclose any diagnosis or mortality group differences regarding either rs6457452 or rs1061581 haplotypes. CONCLUSIONS: Sepsis presents with similar profiles in adult and pediatric patients, characterized by enhanced inflammatory hormonal response and by repressed innate immunity, metabolism, and myocardial contractility. These features early distinguish sepsis from systemic inflammatory response syndrome across all age groups.

Acute coagulopathy in children with multiple trauma: a retrospective study.

BACKGROUND: Acute coagulopathy associated with trauma has been recognized for decades and is a constituent of the "triad of death" together with hypothermia and acidosis. STUDY OBJECTIVE: The aim of this study was to determine to what extent coagulopathy is already established upon emergency department (ED) admission and the association with the severity of injury, impaired outcome, and mortality. METHODS: Ninety-one injured children were admitted to the ED in our hospital. Pediatric Trauma Score (PTS), Injury Severity Score (ISS), and Glasgow Coma Scale (GCS) score were used to estimate injury severity, and organ function was assessed by the Sequential Organ Failure Assessment (SOFA) score. RESULTS: Coagulopathy upon pediatric intensive care unit admission was present in 33 children (39.3%): 21 males and 12 females. PTS ranged from 1 to 12 (mean 8.2) in 51 children without coagulopathy and from -1 to +11 (mean 6.8) in 33 children with coagulopathy (p = 0.087). ISS and GCS ranged from 4 to 57 (mean 28) and from 3 to 11 (mean 7.3), respectively, in the coagulopathy group, whereas in the group without coagulopathy, ISS score ranged from 4 to 41 (mean 20.5; p = 0.08) and GCS from 8 to 15 (mean 12.8; p = 0.01). SOFA ranged from 0 to 10 (mean 3.4) in children without coagulopathy and from 0 to 15 (mean 5.4) in the coagulopathy group (p = 0.002). Among 33 children with coagulopathy, 7 did not survive (21%), all with parenchymal brain damage, whereas all trauma patients without coagulopathy survived (p < 0.001). CONCLUSION: Acute coagulopathy is present on admission to the ED and is associated with injury severity and significantly higher mortality.

Severe and Atypical Presentation of Takotsubo Cardiomyopathy in a Pediatric Patient after a Serious Crash Injury-Case Report and Literature Review.

Takotsubo cardiomyopathy is an uncommon clinical entity in children, resulting in severe but sometimes reversible systolic dysfunction of the left ventricle. This condition is triggered by multiple emotional or physical stressors, while neurogenic stress cardiomyopathy after brain injuries has become increasingly recognized in children over the past few years. We report the case of an 11-year-old child with an atypical clinical presentation after a serious car crash accident. An initial computed tomography scan revealed an acute epidural hematoma, which was immediately treated by an emergency craniotomy. During the patient's following pediatric intensive care unit hospitalization, severe hemodynamic instability was observed, leading to gradually higher doses of vasopressors for circulatory support. On echocardiography, the patient had signs of severe cardiac contractility compromise, with characteristic pattern of regional wall motion abnormalities of the left ventricle, which, in combination with seriously elevated cardiac enzymes, electrocardiographic (ECG) abnormalities and continuous thermodilution hemodynamic monitoring (PICCO) findings, led to intensification of inotropic support and to the diagnosis of takotsubo cardiomyopathy. Despite supportive measures, the patient developed multiorgan failure and succumbed to their serious illness. For this atypical case, extracorporeal membrane oxygenation (ECMO) was addressed as an option for the seriously failing heart, but due to the extremely high risk of intracranial bleeding, it could not be used for this patient's treatment. In conclusion, Takotsubo cardiomyopathy should be suspected in pediatric cases of cardiac dysfunction after serious injuries or stress conditions.

Oxidant/Antioxidant Status Is Impaired in Sepsis and Is Related to Anti-Apoptotic, Inflammatory, and Innate Immunity Alterations.

Oxidative stress is considered pivotal in the pathophysiology of sepsis. Oxidants modulate heat shock proteins (Hsp), interleukins (IL), and cell death pathways, including apoptosis. This multicenter prospective observational study was designed to ascertain whether an oxidant/antioxidant imbalance is an independent sepsis discriminator and mortality predictor in intensive care unit (ICU) patients with sepsis (n = 145), compared to non-infectious critically ill patients (n = 112) and healthy individuals (n = 89). Serum total oxidative status (TOS) and total antioxidant capacity (TAC) were measured by photometric testing. IL-6, -8, -10, -27, Hsp72/90 (ELISA), and selected antioxidant biomolecules (Ζn, glutathione) were correlated with apoptotic mediators (caspase-3, capsase-9) and the central anti-apoptotic survivin protein (ELISA, real-time PCR). A wide scattering of TOS, TAC, and TOS/TAC in all three groups was demonstrated. Septic patients had an elevated TOS/TAC, compared to non-infectious critically ill patients and healthy individuals (p = 0.001). TOS/TAC was associated with severity scores, procalcitonin, IL-6, -10, -27, IFN-γ, Hsp72, Hsp90, survivin protein, and survivin isoforms -2B, -ΔΕx3, -WT (p < 0.001). In a propensity probability (age-sex-adjusted) logistic regression model, only sepsis was independently associated with TOS/TAC (Exp(B) 25.4, p < 0.001). The AUCTOS/TAC (0.96 (95% CI = 0.93-0.99)) was higher than AUCTAC (z = 20, p < 0.001) or AUCTOS (z = 3.1, p = 0.002) in distinguishing sepsis. TOS/TAC, TOS, survivin isoforms -WT and -2B, Hsp90, IL-6, survivin protein, and repressed TAC were strong predictors of mortality (p < 0.01). Oxidant/antioxidant status is impaired in septic compared to critically ill patients with trauma or surgery and is related to anti-apoptotic, inflammatory, and innate immunity alterations. The unpredicted TOS/TAC imbalance might be related to undefined phenotypes in patients and healthy individuals.

Survivin and caspases serum protein levels and survivin variants mRNA expression in sepsis.

Sepsis is a dysregulated host response to infection related to devastating outcomes. Recently, interest has been shifted towards apoptotic and antiapoptotic pathobiology. Apoptosis is executed through the activation of caspases regulated by a number of antiapoptotic proteins, such as survivin. The survivin and caspases' responses to sepsis have not yet been elucidated. This is a multicenter prospective observational study concerning patients with sepsis (n = 107) compared to patients with traumatic systemic inflammatory response syndrome (SIRS) (n = 75) and to healthy controls (n = 89). The expression of survivin was quantified through real-time quantitative polymerase chain reaction for the different survivin splice variants (wild type-WT, ΔEx3, 2B, 3B) in peripheral blood leukocytes. The apoptotic or antiapoptotic tendency was specified by measuring survivin-WT, caspase-3, and -9 serum protein concentrations through enzyme-linked immunosorbent assay. The survivin-WT, -2B, -ΔΕx3 mRNA, survivin protein, and caspases showed an escalated increase in SIRS and sepsis, whereas survivin-3B was repressed in sepsis (p < 0.05). Survivin correlated with IL-8 and caspase-9 (p < 0.01). For discriminating sepsis, caspase-9 achieved the best receiver operating characteristic curve (AUROC) of 0.95. In predicting mortality, caspase-9 and survivin protein achieved an AUROC of 0.70. In conclusion, specific apoptotic and antiapoptotic pathways might represent attractive targets for future research in sepsis.

The effects of endotracheal suctioning on the accuracy of oxygen consumption and carbon dioxide production measurements and pulmonary mechanics calculated by a compact metabolic monitor.

BACKGROUND: Open endotracheal suctioning (ETS), which is performed regularly in mechanically ventilated patients to remove obstructive secretions, can cause an immediate decrease in dynamic compliance and expired tidal volume and result in inadequate or inaccurate sidestream respiratory monitoring, necessitating prolonged periods of stabilization of connected metabolic monitors. We investigated the immediate effect of open ETS on the accuracy of oxygen consumption (VO2) and carbon dioxide production (VCO2) measurements and calculated lung mechanics, respiratory quotient, and resting energy expenditure in mechanically ventilated children without severe lung pathology, when using a compact modular metabolic monitor (E-COVX) continuously recording patient spirometry and gas exchange measurements. METHODS: Open ETS was performed when clinically indicated in 11 children mechanically ventilated for sepsis or head injury. A total of 2800 pulmonary 1-min gas exchange measurements were recorded in 28 ETS instances for 50 consecutive minutes before and 50 min after the standardized procedure. RESULTS: Pulmonary mechanics and indirect calorimetry did not differ between pre- and postsuction sets of measurements. Pre- and postsuction VO2, VCO2, dynamic airway resistance, dynamic compliance, and expiratory minute ventilation remained stable from 5 to 55 min after tracheal suctioning and did not differ among different ventilatory modes. Average paired differences of sequential pre- and postsuction VO2, VCO2, respiratory quotient, and resting energy expenditure were -0.6%, -1%, -0.1%, and -0.3%. Ratio differences between the first and the second periods of measurements (1-25 vs 26-50 sets of 1-min measurements) did not differ in the two groups. CONCLUSIONS: Pulmonary mechanics and indirect calorimetry measurements are not influenced after uneventful open ETS in well-sedated patients. The E-COVX is able to reliably record spirometry and metabolic indices as early as 5 min after suctioning at different ventilator modes.

Longitudinal Profiles of Metabolism and Bioenergetics Associated with Innate Immune Hormonal Inflammatory Responses and Amino-Acid Kinetics in Severe Sepsis and Systemic Inflammatory Response Syndrome in Children.

BACKGROUND: Experimental data indicate that sepsis influences the mitochondrial function and metabolism. We aim to investigate longitudinal bioenergetic, metabolic, hormonal, amino-acid, and innate immunity changes in children with sepsis. METHODS: Sixty-eight children (sepsis, 18; systemic inflammatory response syndrome [SIRS], 23; healthy controls, 27) were enrolled. Plasma amino acids were determined by high-performance liquid chromatography (HPLC); flow-cytometry expressed as mean fluorescence intensity (MFI) of heat shock protein (HSP) levels from monocytes (m) and neutrophils (n); resistin, adiponectin, and extracellular (e) HSPs evaluated by ELISA; ATP levels in white blood cells by luciferase luminescent assay; lipid peroxidation products (TBARS) by colorimetric test; nitrite and nitrate levels by chemiluminescent assay; biliverdin reductase (BVR) activity by enzymatic assay; and energy-expenditure (EE) by E-COVX. RESULTS: Resistin, eHSP72, eHSP90α, and nitrate were longitudinally higher in sepsis compared with SIRS (p<0.05); mHSP72, nHSP72, VO2 , VCO2 , EE, and metabolic pattern were repressed in sepsis compared with SIRS (p<0.05). Septic patients had lower ATP and TBARS compared with controls on day 1, lower ATP compared with SIRS on day 3 (p<0.05), but higher levels of BVR activity. Sepsis exhibited higher phenylalanine levels on day 1, serine on day 3; lower glutamine concentrations on days 3 and 5 (p<0.05). Resistin, inversely related to ATP, was independently associated with sepsis, along with mHSP72 and eHSP90α (p<0.05); TBARS and VO2 were independently associated with organ failure (p<0.05)). Septic nonsurvivors had malnutrition, persistently repressed metabolism, mHSP72, and induced resistin and adiponectin (p<0.05). CONCLUSIONS: A pattern of early longitudinal induction of metabolic-hormones and eHSP72/HSP90α, repression of bioenergetics and innate immunity, hypo-metabolism, and amino-acid kinetics changes discriminate sepsis from SIRS; malnutrition, hypo-metabolism, and persistently increased resistin and adiponectin are associated with poor outcome.

Encephalopathy complicated by Guillain-Barre syndrome and hydrocephalus and associated with acute Bartonella quintana infection.

We describe a 16-month-old girl who suffered from encephalopathy leading to intensive care unit hospitalization, complicated by Guillain-Barre syndrome and hydrocephalus, and who had serologic and molecular evidence of central nervous system infection by B. quintana. The possible association of B. quintana with Guillain-Barre syndrome and hydrocephalus has not been previously described and demonstrates the growing spectrum of neurologic complications of Bartonella spp. infections.

Heat shock protein 72 expressing stress in sepsis: unbridgeable gap between animal and human studies--a hypothetical "comparative" study.

Heat shock protein 72 (Hsp72) exhibits a protective role during times of increased risk of pathogenic challenge and/or tissue damage. The aim of the study was to ascertain Hsp72 protective effect differences between animal and human studies in sepsis using a hypothetical "comparative study" model. Forty-one in vivo (56.1%), in vitro (17.1%), or combined (26.8%) animal and 14 in vivo (2) or in vitro (12) human Hsp72 studies (P < 0.0001) were enrolled in the analysis. Of the 14 human studies, 50% showed a protective Hsp72 effect compared to 95.8% protection shown in septic animal studies (P < 0.0001). Only human studies reported Hsp72-associated mortality (21.4%) or infection (7.1%) or reported results (14.3%) to be nonprotective (P < 0.001). In animal models, any Hsp72 induction method tried increased intracellular Hsp72 (100%), compared to 57.1% of human studies (P < 0.02), reduced proinflammatory cytokines (28/29), and enhanced survival (18/18). Animal studies show a clear Hsp72 protective effect in sepsis. Human studies are inconclusive, showing either protection or a possible relation to mortality and infections. This might be due to the fact that using evermore purified target cell populations in animal models, a lot of clinical information regarding the net response that occurs in sepsis is missing.

The sweet lung: Chewing gummi bear aspiration.

Inhalation of foreign bodies, a leading cause of accidental death, is most common in preschool children. In this article we report our experience with a 5-year-old Greek girl who presented with a 24-hour history of sore throat, chest pain, and shortness of breath. Emergency bronchoscopy was performed and multiple small chewing gummi bear (HARIBO) particles impacted in the orifices of the right main bronchus and right lobar and segmentalinic bronchi were successfully removed and aspirated. Aspiration of gummi bears, which is for the first time reported, may cause a silent choking episode leading to life-threatening bronchi obstruction at multiple sites, even in children older than 4 years.

Unusual exanthema combined with cerebral vasculitis in pneumococcal meningitis: a case report.

INTRODUCTION: Bacterial meningitis is a complex, rapidly progressive disease in which neurological injury is caused in part by the causative organism and in part by the host's own inflammatory responses. CASE PRESENTATION: We present the case of a two-year-old Greek girl with pneumococcal meningitis and an atypical curvilinear-like skin eruption, chronologically associated with cerebral vasculitis. A diffusion-weighted MRI scan showed lesions with restricted diffusion, reflecting local areas of immunologically mediated necrotizing vasculitis. CONCLUSIONS: Atypical presentations of bacterial meningitis may occur, and they can be accompanied by serious unexpected complications.

Influence of different ventilator modes on Vo(2) and Vco(2) measurements using a compact metabolic monitor.

OBJECTIVE: We assessed the influence of different ventilator modes on carbon dioxide elimination (Vco(2)) and oxygen uptake (Vo(2)) using a new compact modular metabolic monitor (E-COVX) and its impact on calculated respiratory quotient (RQ) and resting energy expenditure (REE) in critically ill children. METHODS: Sequential 30-min ventilation by pressure-regulated volume controlled ventilation (PRVC), synchronized intermittent mandatory ventilation (SIMV), and biphasic intermittent positive airway pressure/airway pressure release ventilation (BiVent) in mechanically ventilated critically-ill children was assessed. To determine within- or between-day variations, 30-min Vo(2) and Vco(2) measurements were repeated at four separate occasions. RESULTS: A total of 3960pulmonary 1-min gas exchange measurements were recorded in the 44 sessions for the three ventilator modes. Vo(2), Vco(2), and REE did not differ significantly among the PRVC, SIMV, and BiVent sequence of measurements. RQ (0.86+/-0.1) in the SIMV and Vco(2) (113+/-55mL/min) in the BiVent mode had a higher trend compared with PRVC (0.82+/-0.01, P<0.05, and 103+/-49mL/min, P<0.2, respectively). All three modes displayed good agreement and there were no significant differences between the first and second same-day or between the first- and second-day measurements or sequentially changed ventilator modes. Bland-Altman plots comparing the means of sequential REE, Vo(2), Vco(2), and RQ during the PRVC, SIMV, and BiVent modes of ventilation indicated that the average paired differences were <-5.5%. CONCLUSION: The influence of different ventilator modes on Vo(2) and Vco(2) measurements in adequately sedated critically ill children is not significant. The E-COVX metabolic module is suitable for repeated measurements in well-sedated mechanically ventilated children with stable respiratory patterns using the PRVC, SIMV, or BiVent modes of ventilation.

Multiple injuries in vital organs in a child from a gunshot: a case report.

INTRODUCTION: Many people in rural and urban areas own a gun legally or illegally. It is a social phenomenon that apart from the adults, the children become familiar with the guns in early age. CASE PRESENTATION: A nine year old boy was shot by accident by his uncle, who was cleaning his gun (carbine) close to where the child was playing. More than 200 pellets were counted in the boy's x-rays. The boy was hospitalised in pediatric intensive care unit with many injuries in thorax, abdomen, and limbs, clearly shown by the x-rays. He developed multiple injuries in lungs and liver, bilateral haemothorax and pneumothorax, subcutaneous emphysema, injury of pericardium, perirenal hematoma, choloperitoneum, injuries in the intestine and in the limbs. Initial level of lead in the boy's body was measured as a reference value. Thereafter, frequent monitoring for lead levels was scheduled to prevent a potential lead poisoning from the pellets' absorption. After the appropriate treatment the boy left the hospital in a month in good health. CONCLUSION: The consequences from gun use in places where children are exposed could be fatal. The appropriate co-operation of different medical sub-specialities in Pediatrics and the presence of pediatric intensive care unit can save the life of a child with multiple injuries.

Near demise of a child with Prader-Willi syndrome during elective orchidopexy.

The case of a morbidly obese 3.5-year-old boy, with Prader-Willi syndrome (PWS), who experienced a life-threatening episode of pulmonary edema soon after induction of general anesthesia with sevoflurane and intubation for orchidopexy is presented. The patient who had history of sleep apnea and who had an uneventful laparoscopy under general anesthesia 6 months previously was supported with mechanical ventilation with positive end expiratory pressure but developed hyperthermia, pneumonia, sepsis, and Acute Respiratory Distress Syndrome in the intensive care unit. He recovered fully 11 days after surgery. The possible contributing factors for the development of pulmonary edema are discussed. Arrangements for monitoring in an intensive care setting after surgery are highly recommended for patients with PWS.

Fulminant hepatitis due to varicella zoster virus in a girl with acute lymphoblastic leukemia in remission: report of a case and review.

The authors describe a 4-year-old girl with acute lymphoblastic leukemia in remission who developed fulminant hepatic failure due to varicella-zoster virus (VZV). Diagnosing VZV visceral infection in immunocompromised patients is often difficult due to atypical clinical presentation with few or no skin lesions and severe abdominal or back pain. Prompt initiation of empirical treatment with acyclovir and VZV immunoglobulin pending results of the serum polymerase chain reaction for VZV is warranted in this clinical setting.

Life-threatening hypercalcemia complicated by pancreatitis in a child with acute lymphoblastic leukemia.

The authors describe a 9-year-old girl with precursor-B acute lymphoblastic leukemia (ALL) who presented with dehydration and severe hypercalcemia. She had received oral vitamin D and calcium supplementation for 4 days, the last dose 48 hours prior to admission, and required pediatric intensive care unit (PICU) hospitalization for management of the hypercalcemia and safe initiation of induction chemotherapy. Her clinical course was complicated by pancreatitis, disseminated intravascular coagulation, pleural effusion, and focal seizures. Although the exact mechanism of hypercalcemia was not elucidated, it was likely related to the underlying ALL, without dismissing the prior vitamin D and calcium supplementation as a possible contributing factor. The hypercalcemia resolved with specific antileukemic therapy along with supportive care and administration of calcitonin. Hypercalcemia is an uncommon metabolic abnormality in children with ALL, but it can be life-threatening. Children with ALL should be referred to tertiary-care institutions with PICU and subspecialty support because serious metabolic and other complications can occur before or after the administration of chemotherapy.