Parviz Habibi

A myocardial cytotoxic process is involved in the cardiac dysfunction of meningococcal septic shock.

ObjectiveMyocardial dysfunction is a characteristic component of meningococcal septic shock and contributes to the persisting high mortality from the disease. Specific treatment of the myocardial failure has been hampered by the lack of understanding of its pathophysiology. We were interested to determine whether myocardial cell death was occurring in the presence of meningococcal septicemia and whether it correlated with the degree of left ventricular dysfunction and disease severity. We therefore investigated the release of cardiac troponin I (cTnI), a sensitive and specific marker of myocardial cell death, and related this to the severity of disease and cardiac dysfunction. DesignProspective study SettingPediatric intensive care unit SubjectsPatients admitted to the pediatric intensive care unit with a diagnosis of meningococcal septicemia. InterventionsSerum concentrations of cTnI were determined at admission to intensive care in 101 children with meningococcal septicemia and serially in 37 children. Changes in cTnI were related to disease severity as measured by the Pediatric Risk of Mortality score and two markers of cardiac dysfunction. Measurements and Main ResultsSerum concentrations of cTnI were elevated above the range for healthy children in 24% of children with meningococcal septicemia at admission and in 62% of patients within 48 hrs. The peak concentrations occurred between 12 and 36 hrs after admission. There were significant correlations between cTnI levels and disease severity and between cTnI levels and the degree of myocardial depression measured by quantitative transthoracic echocardiography and peak inotrope requirements. ConclusionsThe elevated serum concentrations of cTnI indicate that myocardial cell death is occurring in meningococcal septicemia. The relationship between cTnI and markers of myocardial function suggest that the cell death may have a role in the pathogenesis of myocardial dysfunction in meningococcal septicemia. Elucidation of the mechanism responsible for myocardial injury may lead to the development of therapeutic interventions to prevent or limit this cardiac damage.

Avoidable deficiencies in the delivery of health care to children with meningococcal disease.

OBJECTIVES: It is apparent that delays and inadequate or inappropriate management occur frequently and may contribute to the continued high mortality seen in meningococcal disease. An attempt has been made to define the major sources of delay or inappropriate treatment. METHODS: A prospective, descriptive study of children with meningococcal disease referred to a tertiary centre paediatric intensive care and infectious disease unit. Definitions of optimal care were established at three stages: parental; general practitioner (GP)/accident and emergency (A&E) department; and hospital. Duration of symptoms and management were recorded from direct questioning of parents and carers, and from hospital records. RESULTS: 54 consecutive children with meningococcal disease were recruited to the study. Delayed parental recognition occurred in 16 children. GPs correctly diagnosed 19 of 35 children. Delay of 2.5-21 hours occurred in those who were incorrectly diagnosed. Two of 15 children who presented to the A&E department with specific features were incorrectly diagnosed. Hospital treatment was suboptimal in 71%. Shock was not recognised or treated in 50%, 20% of children had unnecessary lumbar punctures. Time from illness onset to treatment was longer in fatal disease (median 18.3, range 8-24 hours), compared with survivors (median 12, range 2-48 hours; p < 0.01, Mann-Whitney U test). CONCLUSION: Suboptimal treatment in meningococcal disease is due to failure of parents, GPs, and hospital doctors to recognise specific features of the illness. Improvement by public education and better training of clinicians in recognition, resuscitation, and stabilisation of seriously ill children.

Pertussis is increasing in unimmunised infants: is a change in policy needed?

The proportion and trend in absolute number of pertussis notifications in young infants has increased each year in England and Wales since the accelerated immunisation schedule was introduced. We report five infants all less than 3 months of age admitted with life threatening pertussis infection to two paediatric intensive care units. Despite aggressive cardiorespiratory support measures, three of the infants died. Pertussis remains a significant cause of morbidity and mortality in unimmunised infants. In this age group presentation is likely to be atypical and infection more severe. Public health measures to prevent the disease could be strengthened. Chemoprophylaxis should be offered to susceptible contacts and booster vaccinations against pertussis considered.

Noninvasive Measurement of Cardiac Output in Critically Ill Children

This study was performed to evaluate the hemodynamic status of children admitted to the intensive care unit, using suprasternal and transesophageal Doppler ultrasound, and to establish a suitable noninvasive technique to monitor trends in cardiac output in critically ill children. Twenty children were studied over a period of 6 months. The median age was 32.5 months and weight 14.5 kg. Minute distance (MD), which is a linear cardiac output parameter, was assessed. Seven simultaneous pairs of measurements of MD were made using transesophageal Doppler (TED) and suprasternal Doppler (SSD) by the same operator. Following a fluid challenge, seven repeat pairs of measurements were made. The mean percentage changes for MD by TED and SSD were 21.84 (SD 9.97) and 5.75 (SD 7.32). The average coefficients of variation for measurements of MD by TED and SSD were 2.34% and 15.98%, respectively. The mean difference in percentage change between MD, measured by TED and SSD, was 27.59 with a 95% confidence interval and wide limits of agreement. The repeatability of TED measurements was good, but the measurements by SSD were wide and erratic with poor reproducibility. Our study shows that TED is easy to use, reliable, and very useful for monitoring hemodynamic changes in critically ill children.

The challenge of developing a new predictive formula to estimate energy requirements in ventilated critically ill children.

BACKGROUND Traditionally, energy requirements have been calculated using predictive equations. These methods have failed to calculate energy expenditure accurately. Routine indirect calorimetry has been suggested, but this method is technically demanding and costly. This study aimed to develop a new predictive equation to estimate energy requirements for critically ill children. METHODS This prospective, observational study on ventilated children included patients with an endotracheal tube leak of < 10% and fractional inspired oxygen of < 60%. An indirect calorimetry energy expenditure measurement was performed and polynomial regression analysis was used to develop new predictive equations. The new formulas were then compared with existing prediction equations. RESULTS Data from 369 measurements were included in the formula design. Only weight and diagnosis influenced energy expenditure significantly. Three formulas (A, B, C) with an R² > 0.8 were developed. When we compared the new formulas with commonly used equations (Schofield, Food and Agriculture Organization/World Health Organization/United Nations University, and White equation), all formulas performed very similar, but the Schofield equation seemed to have the lowest SD. CONCLUSIONS All 3 new pediatric intensive care unit equations have R² values of > 0.8; however, the Schofield equation still performed better than other predictive methods in predicting energy expenditure in these patients. Still, none of the predictive equations, including the new equations, predicted energy expenditure within a clinically accepted range, and further research is required, particularly for patients outside the technical scope of indirect calorimetry.

Heliox Therapy in Bronchiolitis: Phase III Multicenter Double-Blind Randomized Controlled Trial

BACKGROUND AND OBJECTIVE: Supportive care remains the mainstay of therapy in bronchiolitis. Earlier studies suggest that helium-oxygen therapy may be beneficial, but evidence is limited. We aimed to compare efficacy of 2 treatment gases, Heliox and Airox (21% oxygen + 79% helium or nitrogen, respectively), on length of hospital treatment for bronchiolitis. METHODS: This was a multicenter randomized blinded controlled trial of 319 bronchiolitic infant subjects randomly assigned to either gas; 281 subjects completed the study (140 Heliox, 141 Airox), whose data was analyzed. Treatment was delivered via facemask (nasal cannula, if the facemask intolerant) ± continuous positive airway pressure (CPAP). Severe bronchiolitics received CPAP from the start. Primary end point was length of treatment (LoT) required to alleviate hypoxia and respiratory distress. Secondary end-points were proportion of subjects needing CPAP; CPAP (LoT); and change in respiratory distress score. RESULTS: Analysis by intention to treat (all subjects); median LoT (inter-quartile range, days): Heliox 1.90 (1.08–3.17), Airox 1.87 (1.11–3.34), P = .41. Facemask tolerant subgroup: Heliox 1.46 (0.85–1.95), Airox 2.01 (0.93–2.86), P = .03. Nasal cannula subgroup: Heliox 2.51 (1.21–4.32), Airox 2.81 (1.45–4.78), P = .53. Subgroup started on CPAP: Heliox 1.55 (1.38–2.01), Airox 2.26 (1.84–2.73), P = .02. Proportion of subjects needing CPAP: Heliox 17%, Airox 19%, O.R. 0.87 (0.47–1.60), P = .76. Heliox reduced respiratory distress score after 8 hours (mixed models estimate, −0.1298; P < .001). The effect was greater for facemask compared with nasal cannula (mixed models estimate, 0.093; P = .04). CONCLUSIONS: Heliox therapy does not reduce LoT unless given via a tight-fitting facemask or CPAP. Nasal cannula heliox therapy is ineffective.

Distribution and pathophysiology of acute lobar collapse in the pediatric intensive care unit.

OBJECTIVE The high incidence of lower lobe collapse in adult intensive care patients is well described. We aimed to document the incidence and distribution of acute lobar collapse in the pediatric intensive care setting. The influence of anatomical and pathophysiological differences between the adult and pediatric respiratory tract will be considered. DESIGN Retrospective review of chest radiograph series. SETTING Tertiary referral center for pediatric intensive care and the Department of Diagnostic Radiology in a large teaching hospital in England. PATIENTS Cohort of 160 patients receiving intensive care during a 2-yr period (age range, 6 days-18 yrs; median, 23 months). INTERVENTIONS None MEASUREMENTS AND MAIN RESULTS Twenty-four of 160 children (15%) developed acute lobar collapse during their intensive care unit admission. Isolated right upper lobe collapse occurred in 14 patients, right upper lobe in association with one or more other lobes in five patients, and lobar collapse other than the right upper lobe in five patients. The development of lobar collapse and, in particular, right upper lobe collapse was associated with a lower median age (no collapse, 26 months; lobar collapse, 8 months; right upper lobe collapse, 4 months). Lobar collapse was significantly associated with the requirement for mechanical ventilation during admission (chi-square, 12.18; p = .005). It was observed in association with both high and low endotracheal tube positions. CONCLUSION The predominance of upper lobe and, in particular, right upper lobe collapse observed in pediatric intensive care patients contrasts with the high incidence of lower lobe collapse in their adult counterparts. Multiple interrelated factors are likely to be contributory and include the following: a) anatomical and physiological differences between adults and children; b) the pathophysiology of childhood respiratory disease; c) more critical positioning of endotracheal tubes in younger patients and their movement with patient positioning.

Emergency cranial computed tomography in the management of acute febrile encephalopathy in children.

OBJECTIVE: Evaluation of the influence of emergency cranial computed tomography on the management of acute febrile encephalopathy in children. METHODS: A retrospective study in children with acute febrile encephalopathy who underwent emergency cranial computed tomography within 12 hours of admission to the paediatric intensive care unit. All scans were evaluated by two independent radiologists. RESULTS: Thirty nine children were included. Fourteen scans were abnormal and two had clinically insignificant incidental findings. Four children with focal neurological signs had scans demonstrating extra-axial collections. None required neurosurgical intervention. Clinically, raised intracranial pressure was present in 10 patients. Only five had cerebral oedema on computed tomography; these five children died. Emergency cranial computed tomography influenced subsequent management in no child without focal neurological signs and in only one child with focal neurology. CONCLUSION: Emergency cranial computed tomography in acute febrile encephalopathy in children without focal neurological signs has little influence on subsequent management. Where cranial computed tomography is thought to be necessary, it should be carried out when the childs clinical condition has been stabilised.

The effect of 2 mMol glutamine supplementation on HSP70 and TNF-α release by LPS stimulated blood from healthy children

OBJECTIVE Glutamine has been shown to promote heat shock protein 70 (HSP70) release both within experimental in vitro models of sepsis (2-10 mM) and in adults post trauma (0.5 g/kg), although the efficacy varies and is dependent on the model used. The effect of glutamine supplementation on HSP70 release in children is less clear. Therefore, the aim of this study was to investigate the effect of 2 mM glutamine added to incubation media on HSP70 and inflammatory mediator release in an in vitro model of paediatric sepsis using whole blood from healthy paediatric volunteers. METHODS An in vitro whole blood endotoxin stimulation model using 1 μg/ml lipopolysaccharide (LPS) over a 24 h time period was used to investigate the effects of 2 mM glutamine on HSP70 and inflammatory mediator release in healthy children. RESULTS The addition of 2 mM glutamine to the incubation media significantly increased HSP70 release over time (p < 0.05). This was associated with an early pro-inflammatory effect on TNF-α release at 4 h (p < 0.005) which was not seen at 24 h. There was a non significant trend towards higher levels of IL-6 and IL-10 following the addition of 2 mM glutamine, which appears to differ from the response reported in adult and animal models. CONCLUSION Glutamine supplementation of incubation media promotes HSP70 and early TNF- α release in an in vitro model using blood samples from healthy children.

Glutamine depletion and heat shock protein 70 (HSP70) in children with meningococcal disease

BACKGROUND & AIMS Heat shock proteins are classified into six main families, of which HSP70 is the best studied. HSP70 is postulated to modulate the immune/inflammatory response in critical illness. Glutamine promotes HSP70 release, however, little is known about the relationship between glutamine and HSP70 in paediatric critical illness. We therefore aimed to describe plasma levels of HSP70, inflammatory mediators and glutamine in critically ill children. METHODS A clinical audit identified 143 children with severe meningococcal disease, 78 convalescent children, in addition to 35 healthy paediatric controls. Stored plasma was used to measure plasma concentrations of HSP70, inflammatory mediators and glutamine. RESULTS HSP70 was significantly increased on admission (n = 143, mean 26.7 ng/ml; ±SD 79.95) compared with convalescence (n = 78, mean 3.16 ng/ml; ±SD 5.67). Glutamine levels were low (n = 132, mean 0.31 mmol/l; ±SD 0.13), which continued in convalescence (n = 65, mean 0.40 mmol/l; ±SD 0.14). Enteral glutamine provided only 28% of the recommendations. Glutamine was inversely correlated with length-of-stay (n = 98, r = -0.520, p < 0.001), ventilation (n = 98, r = -0.513, p < 0.001), lactate (n = 98, r = -0.41, p < 0.001) and CRP (n = 98, r = -0.51, p < 0.001). HSP70 was correlated with length-of-stay (n = 99, r = 0.30, p < 0.001), ventilation (n = 99, r = 0.31, p < 0.001), lactate (n = 99, r = 0.26, p < 0.001) and CRP (n = 99, r = 0.29, p < 0.001) and inflammatory mediators. There was no relationship between glutamine and HSP70 or inflammatory mediators. CONCLUSIONS During acute illness HSP70/inflammatory mediators are significantly increased, and glutamine is significantly depleted. However, glutamine and HSP70 were not correlated. Enteral feeds only provided a small proportion of the ASPEN/ESPEN recommendations for glutamine.