Liposomal amphotericin B in critically ill paediatric patients.

WHAT IS KNOWN AND OBJECTIVE: Literature provides much evidence regarding liposomal amphotericin B treatment for fungal infections in neonates and infants. Relevant data regarding critically ill paediatric patients of older age are scarce. We aimed to present our experience regarding liposomal amphotericin B use in critically ill paediatric patients from a tertiary-care paediatric hospital in Athens, Greece. METHODS: We prospectively identified all paediatric patients who received treatment with liposomal amphotericin B in the intensive care unit of a tertiary-care paediatric hospital during a 3-year period (2005-2008). Data were retrieved from the evaluation of the available medical records. RESULTS AND DISCUSSION: Twenty-three (nine females, mean age: 26·4 months, range: 5-39 months) critically ill paediatric patients were included; 12 had malignancy. In 16 of the 23 included children, liposomal amphotericin B was administered for the treatment of confirmed fungal infections (all but one were invasive), whereas in seven patients, it was used as pre-emptive treatment. One patient received voriconazole concomitantly. Eleven of the 16 children with documented infections were cured; five improved. Six of the seven children who received pre-emptive treatment also showed clinical improvement. Nine deaths were noted, all attributed to underlying diseases. Two cases of hepatotoxicity and one case of nephrotoxicity (all leading to drug-discontinuation) occurred. Seven and five cases of mild reversible hypokalaemia and hyponatraemia, respectively, were also noted. WHAT IS NEW AND CONCLUSION: According to the findings of our small case series, liposomal amphotericin B may provide a useful treatment option for fungal infections of vulnerable critically ill paediatric patients with considerable comorbidity.

A review of paediatric admissions to a general intensive therapy unit over a 13-year period.

Paediatric admissions to a general ITU are briefly reviewed. Although it may not be an ideal arrangement it is suggested that children can be safely cared for in such a unit. The problems created by the child with acute upper airway obstruction are discussed to demonstrate the way in which the unit is organized to receive acutely ill children.

Correlation between serum IL-6 and CRP levels and severity of head injury in children.

OBJECTIVE: To examine interleukin-6 (IL-6) and C-reactive protein (CRP) release in children with head injury (HI) and investigate if there is a correlation between the levels of these two proteins and the severity of HI. DESIGN: Prospective clinical investigation. SETTING: Eight-bed paediatric intensive care unit in a university hospital. PATIENTS: Forty-five children were followed up for 4 days after HI and their serum IL-6 and CRP levels were measured. MEASUREMENTS AND RESULTS: Peak serum IL-6 levels occurred 4 h postinjury, decreasing over time. CRP was normal 4 h after injury, then increased reaching peak levels in 48 h. Children with admission Glasgow Coma Scale (GCS) scores of 8 or less had higher IL-6 levels compared to children with GCS scores higher than 8, 4 and 12 h post-injury (p<0.01 and p<0.05, respectively). IL-6 was higher in children with admission PRISM scores of 10 or more than in those with PRISM scores lower than 10 at 4 and 12 h (p<0.05). CRP levels were higher in patients with GCS scores of 8 or less compared to patients with GCS scores higher than 8 at 24, 48 and 72 h (p<0.05, p<0.02 and p<0.02, respectively) . Patients with PRISM scores of 10 or more had higher CRP levels compared to those with PRISM scores lower than 10 at 24, 48 and 72 h (p<0.05). Peak CRP levels correlated well with peak IL-6 levels (r = 0.49, p<0.001). No correlation between IL-6 or CRP levels and mortality or clinical outcome was found. CONCLUSIONS: Serum IL-6 and CRP levels are elevated in children with HI and there is a relation between the severity of HI and the levels of these proteins. There was no correlation between IL-6, CRP and outcomes of the patients.

Air leaks from the respiratory tract in mechanically ventilated children with severe respiratory disease.

Our objectives were to evaluate the frequency of air leaks (AL) from the respiratory tract (pneumothorax, pneumomediastinum, pneumoperitoneum, subcutaneous emphysema) in critically ill children on mechanical ventilation (MV) for severe respiratory diseases, and to examine whether AL could be correlated with specific clinical events or ventilator settings. The study constitutes a retrospective cohort of 80 consecutive critically ill children receiving MV for severe respiratory diseases between 1986 and 1993. Patients (mean age 2.9 +/- 0.6 years, 49 males and 31 females), were admitted to the Pediatric Intensive Care Unit (PICU) with acute respiratory syndrome (ARDS) (27%), asthma (15%), bronchiolitis (10%), pneumonia (21%), pulmonary congenital diseases (9%), or foreign body aspiration (18%). Patients were divided into two groups; those with AL (n=22) and those without air-leaks (non-AL) (n = 58). Air leaks developed in 22 of 80 patients or in 27.5%. Survival was significantly lower in the AL group, compared to the non-AL group (41% vs. 76%, P < 0.01). The odds ratio that a patient with multiple organ system failure (MOSF) or infection would develop AL was 2.96 and 2.19, respectively. Candida and Pseudomonas species were recovered with significantly higher frequency in the AL group compared with the non-AL group (P < 0.025). There was a strong positive correlation between the incidence of AL and high ventilatory pressures (PIP 36 vs. 29.7 cm H(2)O, P < 0.001), or large tidal volumes (V(T) 12 vs. 9 mL/kg, P < 0.05), suggesting that large volumes might elicit injury to the pulmonary epithelium. Multiple logistic regression analysis showed that only V(T) was independently associated with the development of AL in children with primary severe respiratory disease (r(2) = -0.38, P = 0.01). In conclusion, MV will produce AL, particularly when high peak airway pressures (barotrauma) or large tidal volumes (volotrauma) are delivered by the ventilator. Sepsis, MOSF, and lung superinfection with Pseudomonas or Candida species may be also important factors in the development of AL in critically ill children.

Efficacy of phototherapy and/or exchange transfusions in neonatal jaundice.

In a review of treatment of neonatal jaundice, the authors studied the impact of phototherapy on outcome. From comparing exchange transfusion treatment over a 39-month period prior to the availability of phototherapy to a 39-month period incorporating phototherapy in the treatment regimen, the authors conclude that phototherapy (1) acts slowly but constantly to reduce bilirubin levels and (2) is effective even in severe hemolytic jaundice, but its effectiveness is inversely related to the degree of hemolysis. While phototherapy can never totally replace exchange transfusion, it can certainly reduce the number of transfusions needed.

Subclinical VZV reactivation in immunocompetent children hospitalized in the ICU associated with prolonged fever duration.

A prospective observational study was conducted to examine whether asymptomatic VZV reactivation occurs in immunocompetent children hospitalized in an ICU and its impact on clinical outcome. A secondary aim was to test the hypothesis that vaccinated children have a lower risk of reactivation than naturally infected children. Forty immunocompetent paediatric ICU patients and healthy controls were enrolled. Patients were prospectively followed for 28 days. Clinical data were collected and varicella exposure was recorded. Admission serum levels of TNF-a, cortisol and VZV-IgG were measured. Blood and saliva samples were collected for VZV-DNA detection via real-time PCR. As a comparison, the detection of HSV-DNA was also examined. Healthy children matched for age and varicella exposure type (infection or vaccination) were also included. VZV reactivation was observed in 17% (7/39) of children. Children with VZV reactivation had extended duration of fever (OR = 1.17; 95% CI, 1.02-1.34). None of the varicella-vaccinated children or healthy controls had detectable VZV-DNA in any blood or saliva samples examined. HSV-DNA was detected in saliva from 33% of ICU children and 2.6% of healthy controls. Among children with viral reactivation, typing revealed wild-type VZV and HSV-1. In conclusion, VZV reactivation occurs in immunocompetent children under severe stress and is associated with prolonged duration of fever.

Ciprofloxacin in critically ill children.

Data regarding the use of fluoroquinolones in critically ill children are scarce. We present our experience regarding the use of ciprofloxacin in this specific patient population. We prospectively identified all paediatric patients who received ciprofloxacin treatment in the intensive care unit of the tertiary care P. & A. Kyriakou Children's Hospital during a three year period (2005 to 2008). Eighteen paediatric patients (mean age 23 months, 12 females) who received intravenous ciprofloxacin were identified. Various underlying diseases, including malignancy and immunodeficiency, were observed. None of the evaluated patients had cystic fibrosis. Fourteen patients had bacteraemia (mainly caused from Gram-negative pathogens), one had Stenotrophomonas maltophilia pneumonia, while no pathogen was identified in three patients. The latter patients received ciprofloxacin due to the severity of their clinical manifestations. All patients with microbiologically documented infections recovered. Three deaths attributed to the underlying diseases were noted. Within a 10-day follow-up, two cases of diarrhoea, one case of vomiting and one case of reversible supraventricular tachycardia were noted. No case of QT prolongation was noted. The short-term follow-up hampered any assessment of joint and cartilage toxicity, potentially associated with ciprofloxacin treatment. Our study suggests that ciprofloxacin may be a useful option for critically ill children without cystic fibrosis. Even though firm conclusions regarding the safety profile of ciprofloxacin in critically ill children could not be drawn, our study provides useful information regarding short-term adverse events associated with ciprofloxacin.

Hepatotoxicity due to Atractylis gummifera-L.

The authors describe an intoxication by Atractylis gummifera in a 7-year old boy who drunk an extract made from the plant's root as traditional medicine. He was admitted to the Hospital 2 days after ingestion, in coma stage II, with epigastric pain, vomiting and general anxiety. Laboratory findings showed severe hepatocellular damage and acute renal failure. In spite of all treatment and therapeutic efforts, the boy died 8 days after admission. A postmortem histopathological study of the liver confirmed the panlobular hepatic necrosis and allowed the differential diagnosis of the intoxication from Reye syndrome.

Paraquat poisoning in a family.

A familial occurrence of acute paraquat (PQ) poisoning is reported. The mother administered a PQ solution to their 3 children aged 8 y, 6 y and 15 mo and then ingested an unknown amount of the herbicide herself. In the absence of history or diagnostic signs, the poisoning was initially misdiagnosed as gastroenteritis. Thirty h after the ingestions, serum PQ concentrations of the children were 60, <6 and 25 ng/ml respectively. Hemoperfusion was performed on all patients, and 2 of the children also received plasmapheresis and erythropheresis. The 3 children recovered fully but the mother died. According to these patients' data, the extracorporeal techniques had little effect on PQ removal, and the decreases in serum PQ were related to its urinary excretion.

Concentration of antibacterial agents in rat bone. A comparative study of gentamicin, ampicillin and cephaloridine.

The concentrations of Gentamicin, Ampicillin and Cephaloridine in thigh rat bone were studied. Measurements were done after a 24 h administration for 3 different times. Measurable quantities in the bone for the three antibiotics were detected. The best levels in relation with the M.I.C. of 4 microorganisms occurred in Cephaloridine (and in measurements of serum and bone (microgram/g). The concentration in the serum does not represent concentration in the bone. The most convenient parity was for Cephaloridine. The elimination of the drug in the bone was impressive after 2h. The slower fall occurred in Cephaloridine. Ampicillin had the same level in 4 and 6h. Gentamicin and Cephaloridine had failed to present measurable quantities in some of the animals of the last measurement.

Vitamin E serum levels in newborn infants undergoing phototherapy.

The serum vitamin E levels of 11 full-term and 10 premature infants, jaundiced and subjected to phototherapy, were measured and compared wth 9 premature and 10 full-term jaundiced control infants. No differences were observed before or after phototherapy or 1 week after stopping it. The same negative results were noted in the two groups of infants regarding the values of microhematocrit, Hb and reticulocytes.

The content of trace elements (Cu, Zn, Fe, Mg) in fingernails of children.

The concentrations of Cu, Zn, Fe and Mg in fingernails of 212 normal children, 109 males and 103 females, 6--11 years old, were determined by atomic absorption spectroscopy. A wide scatter of results in all trace element determinations in fingernails was found. Nevertheless, it was noted that the petrographical composition of the region influences the trace element concentration in fingernails. An age variation was observed for Cu and Fe. Nail concentrations of the same trace elements were significantly higher in male than in female children.

Vincristine overdose: experience with 3 patients.

Vincristine overdose (7.5 mg/m2) was accidentally administered to 3 children with acute lymphoblastic leukemia. Treatment included double-volume exchange transfusion, phenobarbital administered prophylactically, and folinic acid rescue 18 mg every 3 hours for 16 doses. Vincristine levels were also assayed and showed a dramatic decline in postexchange levels in the 2 patients who survived and an almost unchanged value in the patient who succumbed. Early signs of toxicity in the 2 survivors were peripheral neuropathy (day 4), bone marrow toxicity (day 5), gastrointestinal toxicity (days 6 and 7), and hypertension (days 7 and 8). Marrow aplasia lasted for 4 and 10 days, peripheral neuropathy for 15 and 42 days, gastrointestinal toxicity for 3 and 5 days, and hypertension for 5 and 14 days. The 2 children were discharged on days 13 and 16 and cytostatic therapy was restarted on days 18 and 25. Both are alive without evidence of leukemia. The third patient developed liver and marrow toxicity on day 3 and died on day 9. Postmortem examination showed leukemia infiltration of the liver and spleen.

Clinical and pharmacokinetic study of a single daily dose of amikacin in paediatric patients with severe gram-negative infections.

The efficacy and safety of a single 20 mg/kg daily dose of amikacin was studied in an open, uncontrolled trial in 56 infants and children. Most of the patients suffered from severe Gram-negative infection which had failed to respond to previous antibacterial therapy. Amikacin was given in combination with a beta-lactam antibiotic in 43 cases, with other antibiotics in five cases and monotherapy in eight cases. Pseudomonas aeruginosa was the most frequently isolated organism (27 cases). Clinical results were satisfactory in 98% of the infections treated. Two patients died, one from the infection and the other 8 weeks after therapy from unrelated causes. Amikacin serum concentrations were high during the first hour after iv infusion, low after 8 h and undetectable at 24 h. Nephrotoxicity and ototoxicity was not detected in any patient. Amikacin when used as a single daily dose in combination with a beta-lactam antibiotic was effective and safe in treating infants and children with severe Gram-negative infection.