Dincer Yildizdas

Hyperferritinemia in the critically ill child with secondary hemophagocytic lymphohistiocytosis/sepsis/multiple organ dysfunction syndrome/macrophage activation syndrome: what is the treatment?

IntroductionHyperferritinemia is associated with increased mortality in pediatric sepsis, multiple organ dysfunction syndrome (MODS), and critical illness. The International Histiocyte Society has recommended that children with hyperferritinemia and secondary hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS) should be treated with the same immunosuppressant/cytotoxic therapies used to treat primary HLH. We hypothesized that patients with hyperferritinemia associated secondary HLH/sepsis/MODS/MAS can be successfully treated with a less immunosuppressant approach than is recommended for primary HLH.MethodsWe conducted a multi-center cohort study of children in Turkish Pediatric Intensive Care units with hyperferritinemia associated secondary HLH/sepsis/MODS/MAS treated with less immunosuppression (plasma exchange and intravenous immunoglobulin or methyl prednisolone) or with the primary HLH protocol (plasma exchange and dexamethasone or cyclosporine A and/or etoposide). The primary outcome assessed was hospital survival.ResultsTwenty-three children with hyperferritinemia and secondary HLH/sepsis/MODS/MAS were enrolled (median ferritin = 6341 μg/dL, median number of organ failures = 5). Univariate and multivariate analyses demonstrated that use of plasma exchange and methyl prednisolone or intravenous immunoglobulin (n = 17, survival 100%) was associated with improved survival compared to plasma exchange and dexamethasone and/or cyclosporine and/or etoposide (n = 6, survival 50%) (P = 0.002).ConclusionsChildren with hyperferritinemia and secondary HLH/sepsis/MODS/MAS can be successfully treated with plasma exchange, intravenous immunoglobulin, and methylprednisone. Randomized trials are required to evaluate if the HLH-94 protocol is helpful or harmful compared to this less immune suppressive and cytotoxic approach in this specific population.

Pseudomonas aeruginosa infections due to electronic faucets in a neonatal intensive care unit.

Aim:  To evaluate the role of electronic faucets in a newborn intensive care unit during a Pseudomonas aeruginosa outbreak.

Growth hormone and insulin‐like growth factor 1 levels and their relation to survival in children with bacterial sepsis and septic shock

Objectives:  Despite improved supportive care, the mortality of sepsis and septic shock is still high. Multiple changes in the neuroendocrine systems, at least in part, are responsible for the high morbidity and mortality. A reduced circulating level of insulin‐like growth factor and an elevated level of growth hormone are the reported characteristic findings early in the course of sepsis and septic shock in adults. The aim of this study was to evaluate the changes of growth hormone/insulin‐like growth factor 1 axis in sepsis and septic shock and investigate the relationship between these hormones and survival.

The use of surfactant in children with acute respiratory distress syndrome: efficacy in terms of oxygenation, ventilation and mortality

PURPOSE The aim of this prospectively designed study was to investigate the efficacy of surfactant (S) for acute respiratory distress syndrome (ARDS) in children. MATERIALS AND METHODS Children with ARDS were included in this study. Surfactant (Survanta, Abbott, USA) was given intratracheally at a dose of 150 mg/kg every 12 h for a total of two doses. During the study period none of the patients received permissive hypercapnia, high frequency ventilation, nitric oxide or ECMO. Peak inspiratory pressure (PIP), positive end expiratory pressure (PEEP), ventilation rate, mean airway pressure, tidal volume (TV), Murray index, PaO2/FiO2, ventilation index (VI), oxygen index (OI) and arterial oxygen tension difference (A-aDO2) were measured before and 48 h after surfactant treatment. Duration of mechanical ventilation therapy, duration in paediatric intensive care unit (PICU) and mortality rate were recorded. RESULTS Among the 36 children who met the inclusion criteria, 12 were treated with surfactant. The mean age was 72.5+/-56.2 months; 47% of children were male. Infants were ventilated by pressure-controlled ventilators whereas for older children volume-controlled ventilators were used. Sepsis (42%) was the main predisposing factor followed by pneumonia (25%) and malignancy (17%). The baseline characteristics including age, predisposing factors, gender, PIP, PEEP, A-aDO2, PaO2/FiO2, OI, TV, VI and Murray index were similar in the surfactant and non-surfactant (NS) group (p>0.05). There were significant improvements in PIP, PEEP, A-aDO2, PaO2/FiO2, OI, TV, VI and Murray index in the surfactant group after surfactant treatment compared with NS group (p<0.05). Duration of PICU stay and ventilator treatment was longer in NS group (14+/-3.7, 1.8+/-3.2 days vs. 9.2+/-3.1, 8.6+/-1.9 days), (p<0.05). Mortality rate was 42% in surfactant compared with 63% in the NS group, (p>0.05). Children in the surfactant group lived significantly longer (p<0.05). CONCLUSIONS Modified natural surfactant is an effective treatment option in children with ARDS for improving gas exchange, decreasing the use of ventilatory support and increasing survival time.

Old agent, new experience: colistin use in the paediatric Intensive Care Unit—a multicentre study

Nosocomial infections caused by multidrug-resistant (MDR) microorganisms are a common problem around the world, especially in Intensive Care Units. The aim of this study was to investigate the efficacy and safety of colistin therapy in paediatric patients with severe nosocomial infections caused by MDR Gram-negative bacteria. There were 87 episodes in 79 paediatric Intensive Care Unit patients in five different hospitals; each patient was treated intravenously with colistin and evaluated. Of the 79 patients, 54.4% were male and the median age was 30 months. The most commonly isolated microorganism was Acinetobacter baumannii, the most common isolation site was tracheal aspirate fluid and the most common type of infection was ventilator-associated pneumonia. The mean colistin dose in patients without renal failure was 5.4 ± 0.6 mg/kg/day, the mean therapy duration was 17.2 ± 8.4 days and the favourable outcome rate was 83.9%. Serious side effects were seen in four patient episodes (4.6%) during therapy; two patients suffered renal failure and the others had convulsive seizures. Other patients tolerated the drug well. The infection-related mortality rate was 11.5% and the probability of death within the first 9 days of treatment was 10 times higher than after the first 9 days. In conclusion, this study suggests that colistin is effective in the treatment of severe nosocomial infections caused by MDR Gram-negative bacteria and is generally well tolerated by patients, even after relatively long-term use.

Severe scorpion envenomation in children: Management in pediatric intensive care unit

Background: Scorpion envenomation is a common public health problem worldwide and children are at greater risk of developing severe cardiac, respiratory and neurological complications. The aim of this study was to evaluate the effects of antivenin and/or prazosin use on prognosis of scorpion-envenomed children admitted to pediatric intensive care unit (PICU). Methods: The standardized medical records of 45 children hospitalized with severe scorpion sting in PICU were retrospectively evaluated. General characteristics of the children, clinical and laboratory findings, treatment approaches and prognosis were evaluated. Results: The mean age of the patients were 6.1 ± 4.1 years ranging between 4 month and 15 years. Male to female ratio was 1.8. Thirty-three (71.1%) cases of scorpion stings came from rural areas. Twenty-six (57.8%) of the patients were stung by Androctonus crassicauda. The most common sting localization was the foot-leg (55.6%). The mean duration from the scorpion sting to hospital admission was 4.5 ± 2.6 hours. The most common findings at presentation were cold extremities (95.5%), excessive sweating (91.1%) and tachycardia (77.7%). The mean leukocyte count, and serum levels of glucose, lactate dehydrogenase, creatine phosphokinase and international normalized ratio were found above the normal ranges. Prazosin was used in all patients, dopamine in 11 (24.4%) and Na-nitroprusside in 4 (8.8%) patients. Two children died (4.4%) due to pulmonary oedema. These children, in poor clinical status at hospital admission, needed mechanical ventilation, and death occurred despite use of antivenin and prazosin in both of them. Conclusion: The current management of children with severe scorpion envenomation consists of administration of specific antivenom and close surveillance in a PICU, where vital signs and continuous monitoring enable early initiation of therapy for life-threatening complications. The aggressive medical management directed at the organ system specifically can be effective. Our data indicated that when admission to hospital is late, the beneficial effect of antivenom and/or prazosin is questionable in severe scorpion stings.

Pulmonary hypertension, heart failure and neutropenia due to diazoxide therapy

Primary persistent hyperinsulinaemic hypoglycaemia is characterised by clinical symptoms that occur when blood glucose levels drop below the normal range. Diazoxide treatment remains the mainstay of medical therapy. Tolerance of diazoxide is usually excellent, but several side effects of this drug have been described. We present a 4-month-old girl who developed pulmonary hypertension, heart failure and neutropenia during diazoxide therapy. Diazoxide toxicity was suspected and the drug was withdrawn on day 13. During the next 3 days, respiratory and haemodynamic status dramatically improved and she was weaned from mechanical ventilation. Control white blood cell count was 8800 cells/mm3 and a new echocardiography showed modreduction of pulmonary artificial pressure to 20 mmHg and resolution of atrial and ventricular enlargement. Paediatric physicians should be in mind of pulmonary hypertension, heart failure and neutropenia developing during diazoxide therapy.

Use of therapeutic plasma exchange in children with thrombocytopenia-associated multiple organ failure in the Turkish thrombocytopenia-associated multiple organ failure network.

Objective: Thrombocytopenia-associated multiple organ failure can lead to high mortality in critically ill children, possibly related to consequences of thrombotic microangiopathy. Plasma exchange therapy may improve thrombotic microangiopathy. The purpose of this observational cohort study is to describe whether there is an association between use of plasma exchange therapy and outcome in the Turkish thrombocytopenia-associated multiple organ failure network. Setting-Interventions: We performed a retrospective cohort analysis in patients with thrombocytopenia-associated multiple organ failure at three different PICUs comparing those who received plasma exchange (+) plus standard therapies with those who did not receive plasma exchange (–) and only received standard therapies. Results: Among 42 of the enrolled patients with thrombocytopenia-associated multiple organ failure, all had a primary or secondary sepsis diagnosis. Fifteen received plasma exchange therapy (PE [+] group) and 27 received standard medical treatment without plasma exchange (PE [–] group). The mean age was 17.69 months (8.24–54.22) in the PE (+) group and 13.46 months (6.47–20.55) in the PE (–) group. Age (p = 0.232), gender (p = 0.206), thrombocyte count (p = 0.09), Organ Failure Index score (p = 0.111), and pediatric logistic organ dysfunction score (p = 0.177) at admission were not statistically different between groups. The overall 28-day mortality was higher in the PE (–) group (70.37%) compared with the PE (+) group (26.67%) (univariate p = 0.006; multivariate controlling for pediatric logistic organ dysfunction, Organ Failure Index, Pediatric Risk of Mortality scores, and neurological failure p = 0.048). Length of stay was increased in the PE (+) group (p = 0.004). Conclusions: The positive association found between use of plasma exchange therapy and improved survival supports the potential of this therapy in Turkish children with thrombocytopenia-associated multiple organ failure. The positive, although less so, associated treatment effect observed after controlling for illness severity provides further rationale for performing a randomized controlled trial in the pediatric Turkish thrombocytopenia-associated multiple organ failure network. Sample size calculations call for a 100-patient trial with a pre hoc interim analysis after enrollment of 50 patients with thrombocytopenia-associated multiple organ failure.

Cerebral salt wasting in tuberculous meningitis: treatment with fludrocortisone.

Abstract Three cases of cerebral salt wasting complicating tuberculous meningitis are described. Diagnosis was based on hyponatraemia associated with high urinary sodium excretion and inappropriately high urine output in the presence of dehydration. Treatment with fludrocortisone resulted in sodium and fluid homeostasis.

Melatonin status in pediatric intensive care patients with sepsis.

Objective: Considering the potential immunomodulatory role of melatonin and its direct antioxidant activity, disturbances of the melatonin secretion pattern in the septic conditions could be particularly unfavorable. The aim of this study was to evaluate the nocturnal melatonin concentration and total 24-hr excretion of 6-sulfatoxymelatoninsulfate, melatonins major urinary metabolite, in children with sepsis in the pediatric intensive care unit. Design: Prospective observational pilot study. Setting: A pediatric intensive care unit. Patients: Twenty septic and 20 nonseptic children admitted between February 2008 and January 2010. Interventions: None. Measurement and Main Results: Blood and urine samples were obtained from each patient on days 1, 2, 3, 5, and 10. There were no significant differences between the groups concerning age and gender. The median nocturnal melatonin concentrations were not significantly different between septic and nonseptic patients during the study period (p > .05). A subgroup analysis in septic patients showed that the nocturnal melatonin concentrations in nonsurvivors were significantly higher than in survivors, whereas total 6-sulfatoxymelatoninsulfate excretions in nonsurvivors were significantly lower than in survivors (p = .001 and p = .015, respectively). Furthermore, nocturnal melatonin concentrations of septic patients in septic shock state were statistically significantly higher than those of septic patients without septic shock state (p = .002). The 24-hr 6-sulfatoxymelatoninsulfate excretions in septic patients with liver dysfunction were found significantly lower than those in septic patients without liver dysfunction (p = .015). The presence of sedation and mechanical ventilation had no effect on the nocturnal melatonin concentrations in septic patients (p = .953 and p = .922, respectively). Conclusion: The present study shows that, in contradiction to results in adult patients, the nocturnal melatonin concentrations are not decreased in septic pediatric intensive care unit patients despite severe disease. Further investigations are needed to identify whether treatment with melatonin may have beneficial effects in pediatric intensive care unit patients with sepsis/septic shock.