Adverse Events in Pediatric Critical Care Nonsurvivors With a Low Predicted Mortality Risk: A Multicenter Case Control Study.

OBJECTIVES: Some patients with a low predicted mortality risk in the PICU die. The contribution of adverse events to mortality in this group is unknown. The aim of this study was to estimate the occurrence of adverse events in low-risk nonsurvivors (LN), compared with low-risk survivors (LS) and high-risk PICU survivors and nonsurvivors, and the contribution of adverse events to mortality. DESIGN: Case control study. Admissions were selected from the national Dutch PICU registry, containing 53,789 PICU admissions between 2006 and 2017, in seven PICUs. PICU admissions were stratified into four groups, based on mortality risk (low/high) and outcome (death/survival). Random samples were selected from the four groups. Cases were "LN." Control groups were as follows: "LS," "high-risk nonsurvivors" (HN), and "high-risk survivors" (HS). Adverse events were identified using the validated trigger tool method. SETTING: Patient chart review study. PATIENTS: Children admitted to the PICU with either a low predicted mortality risk (< 1%) or high predicted mortality risk (≥ 30%). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In total, 419 patients were included (102 LN, 107 LS, 104 HN, and 106 HS). LN had more complex chronic conditions (93.1%) than LS (72.9%; p < 0.01), HN (49.0%; p < 0.001), and HS (48.1%; p < 0.001). The occurrence of adverse events in LN (76.5%) was higher than in LS (13.1%) and HN (47.1%) ( p < 0.001). The most frequent adverse events in LN were hospital-acquired infections and drug/fluid-related adverse events. LN suffered from more severe adverse events compared with LS and HS ( p < 0.001). In 30.4% of LN, an adverse event contributed to death. In 8.8%, this adverse event was considered preventable. CONCLUSIONS: Significant and preventable adverse events were found in low-risk PICU nonsurvivors. 76.5% of LN had one or more adverse events. In 30.4% of LN, an adverse event contributed to mortality.

Neurocognitive, Psychosocial, and Quality of Life Outcomes After Multisystem Inflammatory Syndrome in Children Admitted to the PICU.

OBJECTIVES: To investigate neurocognitive, psychosocial, and quality of life (QoL) outcomes in children with Multisystem Inflammatory Syndrome in Children (MIS-C) seen 3-6 months after PICU admission. DESIGN: National prospective cohort study March 2020 to November 2021. SETTING: Seven PICUs in the Netherlands. PATIENTS: Children with MIS-C (0-17 yr) admitted to a PICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Children and/or parents were seen median (interquartile range [IQR] 4 mo [3-5 mo]) after PICU admission. Testing included assessment of neurocognitive, psychosocial, and QoL outcomes with reference to Dutch pre-COVID-19 general population norms. Effect sizes (Hedges' g ) were used to indicate the strengths and clinical relevance of differences: 0.2 small, 0.5 medium, and 0.8 and above large. Of 69 children with MIS-C, 49 (median age 11.6 yr [IQR 9.3-15.6 yr]) attended follow-up. General intelligence and verbal memory scores were normal compared with population norms. Twenty-nine of the 49 followed-up (59%) underwent extensive testing with worse function in domains such as visual memory, g = 1.0 (95% CI, 0.6-1.4), sustained attention, g = 2.0 (95% CI 1.4-2.4), and planning, g = 0.5 (95% CI, 0.1-0.9). The children also had more emotional and behavioral problems, g = 0.4 (95% CI 0.1-0.7), and had lower QoL scores in domains such as physical functioning g = 1.3 (95% CI 0.9-1.6), school functioning g = 1.1 (95% CI 0.7-1.4), and increased fatigue g = 0.5 (95% CI 0.1-0.9) compared with population norms. Elevated risk for posttraumatic stress disorder (PTSD) was seen in 10 of 30 children (33%) with MIS-C. Last, in the 32 parents, no elevated risk for PTSD was found. CONCLUSIONS: Children with MIS-C requiring PICU admission had normal overall intelligence 4 months after PICU discharge. Nevertheless, these children reported more emotional and behavioral problems, more PTSD, and worse QoL compared with general population norms. In a subset undergoing more extensive testing, we also identified irregularities in neurocognitive functions. Whether these impairments are caused by the viral or inflammatory response, the PICU admission, or COVID-19 restrictions remains to be investigated.

A comparison of four different models of acute respiratory distress syndrome in sheep.

BACKGROUND: Acute respiratory distress syndrome (ARDS) can have various causes. The study objective was to investigate whether different pathophysiologic models of ARDS would show different respiratory, cardiovascular and inflammatory outcomes. METHODS: We performed a prospective, randomized study in 27 ventilated ewes inducing ARDS using three different techniques to mimic the pulmonary causes of ARDS (ARDSp): warm saline lavage (n = 6), intratracheal hydrochloric acid (HCl; n = 6), intratracheal albumin (n = 10), and one technique to mimic an extrapulmonary cause of ARDS (ARDSexp): intravenous lipopolysaccharide (LPS iv; n = 5). ARDS was defined when PaO2 was < 15 kPa (112 mmHg) when ventilated with PEEP 10 cm H2O and FiO2 = 1.0. The effects on gas exchange were investigated by calculating the oxygenation index (OI) and the ventilation efficacy index (VEI) every 30 min for a period of 4 h. Post mortem lung lavage was performed to obtain broncho-alveolar lavage fluid (BALF) to assess lung injury and inflammation. Lung injury and inflammation were assessed by measuring the total number and differentiation of leukocytes, the concentration of protein and disaturated phospholipids, and interleukine-6 and -8 in the BALF. Histology of the lung was evaluated by measuring the mean alveolar size, alveolar wall thickness and the lung injury score system by Matute-Bello et al., as markers of lung injury. The concentration of interleukin-6 was determined in plasma, as a marker of systematic inflammation. RESULTS: The OI and VEI were most affected in the LPS iv group and thereafter the HCl group, after meeting the ARDS criteria. Diastolic blood pressure was lowest in the LPS iv group. There were no significant differences found in the total number and differentiation of leukocytes, the concentration of protein and disaturated phospholipids, or interleukin-8 in the BALF, histology of the lung and the lung injury score. IL-6 in BALF and plasma was highest in the LPS iv group, but no significant differences were found between the other groups. It took a significantly longer period of time to meet the ARDS criteria in the LPS iv group. CONCLUSIONS: The LPS model caused the most severe pulmonary and cardiovascular insufficiency. Surprisingly, there were limited significant differences in lung injury and inflammatory markers, despite the different pathophysiological models, when the clinical definition of ARDS was applied.

ERS statement on obstructive sleep disordered breathing in 1- to 23-month-old children.

The present statement was produced by a European Respiratory Society Task Force to summarise the evidence and current practice on the diagnosis and management of obstructive sleep disordered breathing (SDB) in children aged 1-23 months. A systematic literature search was completed and 159 articles were summarised to answer clinically relevant questions. SDB is suspected when symptoms or abnormalities related to upper airway obstruction are identified. Morbidity (pulmonary hypertension, growth delay, behavioural problems) and coexisting conditions (feeding difficulties, recurrent otitis media) may be present. SDB severity is measured objectively, preferably by polysomnography, or alternatively polygraphy or nocturnal oximetry. Children with apparent upper airway obstruction during wakefulness, those with abnormal sleep study in combination with SDB symptoms (e.g. snoring) and/or conditions predisposing to SDB (e.g. mandibular hypoplasia) as well as children with SDB and complex conditions (e.g. Down syndrome, Prader-Willi syndrome) will benefit from treatment. Adenotonsillectomy and continuous positive airway pressure are the most frequently used treatment measures along with interventions targeting specific conditions (e.g. supraglottoplasty for laryngomalacia or nasopharyngeal airway for mandibular hypoplasia). Hence, obstructive SDB in children aged 1-23 months is a multifactorial disorder that requires objective assessment and treatment of all underlying abnormalities that contribute to upper airway obstruction during sleep.

Factors Associated With Mortality in Low-Risk Pediatric Critical Care Patients in The Netherlands.

OBJECTIVE: To determine differences between survivors and nonsurvivors and factors associated with mortality in pediatric intensive care patients with low risk of mortality. DESIGN: Retrospective cohort study. SETTING: Patients were selected from a national database including all admissions to the PICUs in The Netherlands between 2006 and 2012. PATIENTS: Patients less than 18 years old admitted to the PICU with a predicted mortality risk lower than 1% according to either the recalibrated Pediatric Risk of Mortality or the Pediatric Index of Mortality 2 were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In total, 16,874 low-risk admissions were included of which 86 patients (0.5%) died. Nonsurvivors had more unplanned admissions (74.4% vs 38.5%; p < 0.001), had more complex chronic conditions (76.7% vs 58.8%; p = 0.001), were more often mechanically ventilated (88.1% vs 34.9%; p < 0.001), and had a longer length of stay (median, 11 [interquartile range, 5-32] d vs median, 3 [interquartile range, 2-5] d; p < 0.001) when compared with survivors. Factors significantly associated with mortality were complex chronic conditions (odds ratio, 3.29; 95% CI, 1.97-5.50), unplanned admissions (odds ratio, 5.78; 95% CI, 3.40-9.81), and admissions in spring/summer (odds ratio, 1.67; 95% CI, 1.08-2.58). CONCLUSIONS: Nonsurvivors in the PICU with a low predicted mortality risk have recognizable risk factors including complex chronic condition and unplanned admissions.

Obstructive sleep disordered breathing in 2- to 18-year-old children: diagnosis and management.

This document summarises the conclusions of a European Respiratory Society Task Force on the diagnosis and management of obstructive sleep disordered breathing (SDB) in childhood and refers to children aged 2-18 years. Prospective cohort studies describing the natural history of SDB or randomised, double-blind, placebo-controlled trials regarding its management are scarce. Selected evidence (362 articles) can be consolidated into seven management steps. SDB is suspected when symptoms or abnormalities related to upper airway obstruction are present (step 1). Central nervous or cardiovascular system morbidity, growth failure or enuresis and predictors of SDB persistence in the long-term are recognised (steps 2 and 3), and SDB severity is determined objectively preferably using polysomnography (step 4). Children with an apnoea-hypopnoea index (AHI) >5 episodes·h(-1), those with an AHI of 1-5 episodes·h(-1) and the presence of morbidity or factors predicting SDB persistence, and children with complex conditions (e.g. Down syndrome and Prader-Willi syndrome) all appear to benefit from treatment (step 5). Treatment interventions are usually implemented in a stepwise fashion addressing all abnormalities that predispose to SDB (step 6) with re-evaluation after each intervention to detect residual disease and to determine the need for additional treatment (step 7).

Characteristics and Outcome of Children with Wilms Tumor Requiring Intensive Care Admission in First Line Therapy.

Survival rates are excellent for children with Wilms tumor (WT), yet tumor and treatment-related complications may require pediatric intensive care unit (PICU) admission. We assessed the frequency, clinical characteristics, and outcome of children with WT requiring PICU admissions in a multicenter, retrospective study in the Netherlands. Admission reasons of unplanned PICU admissions were described in relation to treatment phase. Unplanned PICU admissions were compared to a control group of no or planned PICU admissions, with regard to patient characteristics and short and long term outcomes. In a multicenter cohort of 175 children with an underlying WT, 50 unplanned PICU admissions were registered in 33 patients. Reasons for admission were diverse and varied per treatment phase. Younger age at diagnosis, intensive chemotherapy regimens, and bilateral tumor surgery were observed in children with unplanned PICU admission versus the other WT patients. Three children required renal replacement therapy, two of which continued dialysis after PICU discharge (both with bilateral disease). Two children died during their PICU stay. During follow-up, hypertension and chronic kidney disease (18.2 vs. 4.2% and 15.2 vs. 0.7%) were more frequently observed in unplanned PICU admitted patients compared to the other patients. No significant differences in cardiac morbidity, relapse, or progression were observed. Almost 20% of children with WT required unplanned PICU admission, with young age and treatment intensity as potential risk factors. Hypertension and renal impairment were frequently observed in these patients, warranting special attention at presentation and during treatment and follow-up.

Gut mucosal cell damage in meningococcal sepsis in children: relation with clinical outcome.

OBJECTIVE: The pathophysiological sequelae of meningococcal sepsis are mainly caused by deregulated microvasculature function, leading to impaired tissue blood flow. Because mature enterocytes are known to be susceptible to altered perfusion, we aimed to investigate: (1) the development of enterocyte damage; and (2) the relation between enterocyte damage and severity of disease and outcome in children with meningococcal sepsis. DESIGN: Retrospective human study. SETTING: Pediatric intensive care unit at a university hospital. PATIENTS: Nineteen consecutive children with meningococcal sepsis were studied during their pediatric intensive care unit stay. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS Circulating levels of intestinal fatty acid binding protein, a small cytosolic protein constitutively present in mature enterocytes and released on cell injury, were assessed. Severity of disease was represented by meningococcal-specific Rotterdam Score, generic Pediatric Risk of Mortality II score, and circulating interleukin-6. Clinical outcome was measured by length of pediatric intensive care unit stay and number of ventilator days. Highest plasma intestinal fatty acid binding protein values were measured on pediatric intensive care unit stay admission. At the time of admission, eight of 19 patients had higher intestinal fatty acid binding protein plasma levels than the upper reference limit of 30 healthy volunteers. In all survivors, intestinal fatty acid binding protein levels declined to normal values within 12 hrs after starting intensive treatment, whereas the three nonsurvivors maintained elevated intestinal fatty acid binding protein plasma levels. A significant correlation was found among intestinal fatty acid binding protein and Rotterdam Score, Pediatric Risk of Mortality II, interleukin-6 at admission (Spearman's r = 0.402, p = .006; r = 0.243, p = .045; r = 0.687, p < .001, respectively). Next, a significant correlation was found between intestinal fatty acid binding protein and clinical outcome. CONCLUSIONS: Elevated plasma intestinal fatty acid binding protein is found in eight of 19 children with severe pediatric intensive care unit stay at the time of clinical presentation, suggesting the presence of enterocyte damage. Furthermore, prolonged enterocyte damage is found in nonsurvivors. Further studies are needed to clarify the potential role for assessment of plasma intestinal fatty acid binding protein in monitoring treatment of pediatric intensive care unit stay.

Influenza A-associated acute necrotising encephalopathy in a 10-year-old child.

We report an otherwise healthy 10-year-old boy who was brought to the emergency department with altered mental status, vomiting, diarrhoea and fever (39.5°C), without signs of meningitis. The CT scan revealed bilateral hypodensities of the thalamus and cerebellum, with diffuse oedema and slight compression of the brainstem and a triventricular hydrocephalus. Lumbar puncture and blood examination revealed markedly elevated protein level of 2.4 g/L in cerebrospinal fluid and high serum aminotransferase, characteristic of acute necrotising encephalopathy (ANE). The PCR of the nasopharyngeal swab was influenza A positive. Because of signs of high intracranial pressure, mannitol was given, an external ventricular drain was placed and subsequently, a posterior fossa craniectomy was performed. Postoperatively, he showed signs of cerebellar mutism with emotional instability and diminished speech. Six months after presentation, he showed full recovery. This case illustrates ANE as a rare complication of influenza A infection.

Obstructive sleep apnea in obese adolescents referred for bariatric surgery: association with metabolic and cardiovascular variables.

BACKGROUND: obstructive sleep apnea syndrome (OSA) is a well-described disease entity in adults, with a higher prevalence in severely obese individuals, while at the same time associated with several comorbidities independently of BMI. Literature regarding OSA in severely obese adolescents is qualitatively and quantitatively limited, possibly resulting in suboptimal diagnosis and treatment. METHODS: polysomnographic, demographic, anthropometric, and comorbidity-related data were prospectively collected in 56 adolescents with morbid obesity refractory to conservative treatment who presented for surgical therapy. Differences between adolescents with no/mild (apnea-hypopnea index (AHI) 0-4.9) and moderate/severe OSA (AHI ≥ 5.0) were evaluated using independent-samples t, chi-square or Fisher's exact tests. Multivariable linear regression analysis was performed to evaluate the association of several variables with AHI, corrected for BMI z-score. RESULTS: of the 53 included subjects, 48 (90.6%) showed some degree of sleep disordered breathing and 20 (37.7%) had moderate/severe OSA. Patients with moderate/severe OSA had on average a higher neck circumference (42.4 versus 40.1 cm, p = 0.008), higher BMI z-score (3.7 versus 3.4, p = 0.003), higher plasma triglyceride level (2.2 versus 1.5 mmol/L, p = 0.012), and lower IGF (29.6 versus 40.2 mmol/L, p = 0.010) than those with no/mild OSA. BMI z-score and plasma triglyceride levels were independently related to AHI. CONCLUSIONS: OSA is highly prevalent amongst morbidly obese adolescents and is strongly associated with BMI z-score. Elevated plasma triglyceride levels are associated with AHI, independent of BMI z-score.

Risk factors for intensive care admission in children with severe acute asthma in the Netherlands: a prospective multicentre study.

RATIONALE: Severe acute asthma (SAA) can be fatal, but is often preventable. We previously observed in a retrospective cohort study, a three-fold increase in SAA paediatric intensive care (PICU) admissions between 2003 and 2013 in the Netherlands, with a significant increase during those years of numbers of children without treatment of inhaled corticosteroids (ICS). OBJECTIVES: To determine whether steroid-naïve children are at higher risk of PICU admission among those hospitalised for SAA. Furthermore, we included the secondary risk factors tobacco smoke exposure, allergic sensitisation, previous admissions and viral infections. METHODS: A prospective, nationwide multicentre study of children with SAA (2-18 years) admitted to all Dutch PICUs and four general wards between 2016 and 2018. Potential risk factors for PICU admission were assessed using logistic regression analyses. MEASUREMENTS AND MAIN RESULTS: 110 PICU and 111 general ward patients were included. The proportion of steroid-naïve children did not differ significantly between PICU and ward patients. PICU children were significantly older and more exposed to tobacco smoke, with symptoms >1 week prior to admission. Viral susceptibility was not a significant risk factor for PICU admission. CONCLUSIONS: Children with SAA admitted to a PICU were comparable to those admitted to a general ward with respect to ICS treatment prior to admission. Preventable risk factors for PICU admission were >7 days of symptoms without adjustment of therapy and exposure to tobacco smoke. Physicians who treat children with asthma must be aware of these risk factors.

Severe hemolysis and methemoglobinemia following fava beans ingestion in glucose-6-phosphatase dehydrogenase deficiency: case report and literature review.

INTRODUCTION: Reduced concentrations of glucose-6-phospate dehydrogenase (G6PD) render erythrocytes susceptible to hemolysis under conditions of oxidative stress. In favism, the ingestion of fava beans induces an oxidative stress to erythrocytes, leading to acute hemolysis. DISCUSSION: The simultaneous occurrence of methemoglobinemia has been reported only scarcely, despite the fact that both phenomena are the consequence of a common pathophysiologic mechanism. The presence of methemoglobinemia has important diagnostic and therapeutic consequences. We report a previously healthy boy who presented with combined severe hemolytic anemia and cyanosis due to methemoglobinemia, following the ingestion of fava beans. His condition was complicated by the development of transient acute renal failure. A G6PD-deficiency was diagnosed. We review the literature on the combination of acute hemolysis and methemoglobinemia in favism. Pathophysiologic, diagnostic, and therapeutic aspects of this disorder are discussed.

Plasma arginine and citrulline concentrations in critically ill children: strong relation with inflammation.

BACKGROUND: The amino acid arginine plays a key role in many metabolic processes in health and disease. Low arginine concentrations are found in various illnesses in children. OBJECTIVE: The objective was to investigate the relation between plasma concentrations of arginine (and precursor amino acids) and severity of inflammation in critically ill children. DESIGN: This was an observational cohort study in children with viral respiratory disease (n = 21; control group), accidental or surgical trauma (n = 19), or sepsis (n = 19) who were admitted to a pediatric intensive care unit. RESULTS: Plasma arginine and citrulline concentrations were lower in subjects with sepsis and trauma than in those with viral disease (arginine: 33 +/- 4, 37 +/- 4, and 69 +/- 8 micromol/L, respectively, P < 0.01 for both; citrulline: 10 +/- 1, 14 +/- 1, and 23 +/- 2 micromol/L, respectively, P < 0.01 for both) and correlated strongly and inversely with severity of inflammation as indicated by plasma CRP concentration (r = -0.645 and r = -0.660, respectively; P < 0.001 for both). During recovery, plasma arginine and citrulline concentrations increased and were strongly related to the reduction in inflammation as shown by the inverse correlation between arginine and citrulline concentrations and the CRP concentration on days 3 (r = -0.832 and r = -0.756, P < 0.001 for both) and 7 (r = -0.784 and r = -0.694, P < 0.001 for both). CONCLUSIONS: Plasma concentrations of arginine and citrulline are low during the acute phase of critical illness in children and normalize again during recovery. Plasma arginine and citrulline are strongly related to the severity of inflammation indicated by plasma CRP concentrations.

How do we recognize the child with OSAS?

Obstructive sleep-disordered breathing includes a spectrum of clinical entities with variable severity ranging from primary snoring to obstructive sleep apnea syndrome (OSAS). The clinical suspicion for OSAS is most often raised by parental report of specific symptoms and/or abnormalities identified by the physical examination which predispose to upper airway obstruction (e.g., adenotonsillar hypertrophy, obesity, craniofacial abnormalities, neuromuscular disorders). Symptoms and signs of OSAS are classified into those directly related to the intermittent pharyngeal airway obstruction (e.g., parental report of snoring, apneic events) and into morbidity resulting from the upper airway obstruction (e.g., increased daytime sleepiness, hyperactivity, poor school performance, inadequate somatic growth rate or enuresis). History of premature birth and a family history of OSAS as well as obesity and African American ethnicity are associated with increased risk of sleep-disordered breathing in childhood. Polysomnography is the gold standard method for the diagnosis of OSAS but may not be always feasible, especially in low-income countries or non-tertiary hospitals. Nocturnal oximetry and/or sleep questionnaires may be used to identify the child at high risk of OSAS when polysomnography is not an option. Endoscopy and MRI of the upper airway may help to identify the level(s) of upper airway obstruction and to evaluate the dynamic mechanics of the upper airway, especially in children with combined abnormalities. Pediatr Pulmonol. 2017;52:260-271. © 2016 Wiley Periodicals, Inc.

24-Hour protein, arginine and citrulline metabolism in fed critically ill children - A stable isotope tracer study.

BACKGROUND & AIMS: The reference method to study protein and arginine metabolism in critically ill children is measuring plasma amino acid appearances with stable isotopes during a short (4-8 h) time period and extrapolate results to 24-h. However, 24-h measurements may be variable due to critical illness related factors and a circadian rhythm could be present. Since only short duration stable isotope studies in critically ill children have been conducted before, the aim of this study was to investigate 24-h appearance of specific amino acids representing protein and arginine metabolism, with stable isotope techniques in continuously fed critically ill children. METHODS: In eight critically ill children, admitted to the pediatric (n = 4) or cardiovascular (n = 4) intensive care unit, aged 0-10 years, receiving continuous (par)enteral nutrition with protein intake 1.0-3.7 g/kg/day, a 24-h stable isotope tracer protocol was carried out. L-[ring-2H5]-phenylalanine, L-[3,3-2H2]-tyrosine, L-[5,5,5-2H3]-leucine, L-[guanido-15N2]-arginine and L-[5-13C-3,3,4,4-2H4]-citrulline were infused intravenously and L-[15N]-phenylalanine and L-[1-13C]leucine enterally. Arterial blood was sampled every hour. RESULTS: Coefficients of variation, representing intra-individual variability, of the amino acid appearances of phenylalanine, tyrosine, leucine, arginine and citrulline were high, on average 14-19% for intravenous tracers and 23-26% for enteral tracers. No evident circadian rhythm was present. The pattern and overall 24-h level of whole body protein balance differed per individual. CONCLUSIONS: In continuously fed stable critically ill children, the amino acid appearances of phenylalanine, tyrosine, leucine, arginine and citrulline show high variability. This should be kept in mind when performing stable isotope studies in this population. There was no apparent circadian rhythm. CLINICAL TRIAL REGISTER: NCT01511354 on clinicaltrials.gov.

Hyperglycemia in children with meningococcal sepsis and septic shock: the relation between plasma levels of insulin and inflammatory mediators.

CONTEXT: Hyperglycemia and insulin resistance are common findings in critically ill adult patients and are associated with increased morbidity and mortality. OBJECTIVES: The objective of this study was to investigate the hyperglycemic response to critical illness in children. DESIGN: The study was designed as an observational cohort study. SETTING: The study was set in a university-affiliated pediatric intensive care unit. PATIENTS: Six children with meningococcal sepsis (MS) without shock and 10 children with meningococcal septic shock (MSS) were patients. MAIN OUTCOME MEASURES: Differences in blood glucose levels (measured during 72 h after admission) and differences in plasma levels of glucoregulatory hormones (insulin, GH, IGF-I, cortisol, glucagons, leptin), soluble cytokine receptors (sTNF-R55, R75, sIL-1R2), and IL-6 (measured on d 3) between MS and MSS patients were assessed. RESULTS: Blood glucose levels on d 2 and 3 were higher in MSS patients than in MS patients [7.5 (3.9-13.0) vs. 5.1 (4.0-6.0) and 6.5 (4.0-9.9) vs. 5.5 (4.8-6.8) mmol/liter, both P < 0.05]. Maximum blood glucose values recorded in individual patients were higher in MSS patients [9.3 (6.5-13) vs. 7.2 (6.2-9.9), P < 0.05] and correlated with severity of illness (r = 0.833, P < 0.001). Insulin levels in MSS patients were significantly lower (7.2 vs. 19.0 mU/liter, P < 0.001), compatible with insufficient insulin response to hyperglycemia, whereas MS patients showed insulin resistance. Insulin levels correlated inversely with levels of sTNF-R55 and R75 (r = -0.814 and -0.878, both P < 0.001), suggesting suppression of the proinflammatory response on insulin secretion. CONCLUSION: Hyperglycemia associated with hypoinsulinemia rather than insulin resistance may be the normal pathophysiological response in acute MSS in children. Our study emphasizes that application of intensive insulin therapy in critically ill children demands further investigation.

Management of a severe forceful breather with Rett syndrome using carbogen.

We have used a novel neurophysiological technique in the NeuroScope system in combination with conventional electroencephalography (EEG) to monitor both brainstem and cortical activity simultaneously in real-time in a girl with Rett syndrome. The presenting clinical features in our patient were severe sleep disturbances, irregular breathing in the awake state dominated by Valsalva's type of breathing followed by tachypnoea and very frequent attacks of seizures and vacant spells. Our novel neurophysiological data showed that the patient was a Forceful Breather according to the breathing categories in Rett syndrome. She had frequent abnormal spontaneous brainstem activation (ASBA) preceded by severe attacks of hypocapnoea, which was caused by a combination of Valsalva's type of breathing and tachypnoea and all these together were responsible for the seizures and non-epileptic vacant spells. The ASBA was not detectable in conventional EEG and there were no epileptiform changes in the EEG during the seizures and vacant spells caused by the hypocapnic attacks, therefore these were pseudo-seizures. The record of brainstem activity confirmed that these were autonomic events, a kind of "brainstem epilepsy". We successfully treated the sleep disturbance with Pipamperone, a 5-hydroxytryptophan antagonist of receptor type 2 and we prevented the severe hypocapnoea during Valsalva's type of breathing and during tachypnoea using carbogen (a mixture of 5% carbon dioxide and 95% oxygen), which we gave by inhalation. Our treatment drastically reduced the autonomic events, promoted whole night sleep and significantly improved the quality of life in our patient. She can now participate in normal family activity which was previously impossible before treatment.

Point-of-care blood analyzer during the interhospital transport of critically ill children.

OBJECTIVES: To investigate the influence of point-of-care laboratory results (arterial blood gases, ionized calcium, potassium, sodium, glucose, hematocrit and hemoglobin) on therapeutic interventions during interhospital pediatric intensive care transport. DESIGN: Prospective observational study. SETTINGS: Specialist pediatric intensive care retrieval team of a university hospital. PARTICIPANTS: Critically ill pediatric patients who were referred from a community hospital to a pediatric intensive care of a tertiary center. The retrieval team sampled arterial blood during the time of stabilization in the referring hospital and during transport. All results were recorded and for each result the physician of the specialist retrieval team wrote down the influence on the treatment (none, partly, only). The physician specified the kind of intervention. RESULTS: Point-of-care blood analyses influenced the therapeutic management in 76.5% of all blood samples and in 86.2% of the referred patients. Of all interventions, 42.9% were based only on the laboratory results. The majority of interventions were adjustments of the mechanical ventilation. Point-of-care blood analyses reduced the delay in treatment of potentially life-threatening abnormalities of laboratory results (severe hypokalemia and low hematocrit). CONCLUSIONS: During interhospital pediatric intensive care transport, point-of-care blood analyses frequently led to therapeutic interventions. Some abnormal blood results were potentially life threatening and could not have been discovered without point-of-care measurement. We therefore recommend the use of a point-of-care blood analyzer during interhospital intensive care transports, not only for blood gases but also for electrolytes, glucose and hematocrit.

Comparison of interhospital pediatric intensive care transport accompanied by a referring specialist or a specialist retrieval team.

OBJECTIVE: Interhospital transfers of critically ill pediatric patients in The Netherlands are accompanied by referring specialists or by specialist retrieval teams. We compared the interventions before and directly after transports and the complications and the equipment available during transports in the two groups. DESIGN AND SETTING: Prospective observational clinical study in pediatric intensive care units of Dutch university hospitals. PATIENTS: 249 pediatric patients requiring interhospital intensive care transport. METHODS: Data were collected on interhospital pediatric intensive care transports. We compared patient characteristics, interventions before and directly after transport, complications and equipment available during transport (137 accompanied by referring specialists, 112 by specialist retrieval teams). RESULTS: Interhospital transports accompanied by referring specialists had a longer average transport time (74.6 vs. 60.2 min), higher incidence of respiratory insufficiency (56.9% vs. 41.1%), and lower incidence of circulatory insufficiency (27.0% vs. 41.1%) than primary admission diagnoses. These transports had a lower percentage of ventilatory support (47.4% vs. 72.3%), higher need for acute interventions directly upon arrival on the pediatric ICU, and higher incidence of critical and serious complications. In 75% of the transfers accompanied by retrieval teams interventions before the transport were deemed to be necessary. During the transports accompanied by referring specialists the equipment and materials available proved rather limited. CONCLUSIONS: During pediatric intensive care transports accompanied by nontrained referring specialists there appears to be a higher incidence of complications, specialized equipment is more often not available, and more acute interventions are required upon arrival in the pediatric ICU.

Assessment of whole body protein metabolism in critically ill children: can we use the [15N]glycine single oral dose method?

BACKGROUND & AIMS: Most stable-isotope methods to evaluate whole body protein metabolism in patients are invasive and difficult to use in children. In this study protein metabolism was evaluated with the non-invasive [15N]glycine single oral dose method in critically ill children and the value of the method is discussed. METHODS: [15N]glycine (100mg) was given orally to children (mean age 5.5 years; range 0.6-15.5 years) with meningococcal septic shock (MSS, n = 8), pneumonia (n = 5), and to healthy, fed and post-absorptive children (n = 10). Urine was collected during 9h, total amount of NH(3), labelled NH(3) and nitrogen were measured, and protein turnover, synthesis and breakdown were calculated using urinary NH(3) as end-product. RESULTS: Mean protein turnover in children with MSS, pneumonia and fed and post-absorptive healthy children was 0.63+/-0.13, 0.38+/-0.10, 0.28+/-0.03 and 0.28+/-0.02g N/kg/9h, respectively. Mean protein synthesis was 0.55+/-0.12, 0.29+/-0.09, 0.18+/-0.02, 0.20+/-0.02g N/kg/9h, respectively. Mean protein breakdown was 0.56+/-0.14, 0.28+/-0.12, 0.08+/-0.03, 0.28+/-0.02g N/kg/9h, respectively. Protein turnover, synthesis and breakdown were significantly increased in MSS patients compared to fed healthy children (P <0.01) and post-absorptive children (P <0.05). Protein turnover, protein synthesis, protein breakdown were significantly correlated with disease severity and body temperature (P <0.05). CONCLUSION: Results of whole body protein metabolism measured with the [15N]glycine single oral dose method in children with MSS and in healthy children were in line with expectations based on results obtained in earlier reports and with different methods.