Kidney function in cyclosporine-treated paediatric pulmonary transplant recipients.

BACKGROUND: Lung or heart-lung transplantation is a useful therapy in life-threatening pulmonary disorders during childhood. Cyclosporine A is a major immunosuppressive treatment but has a number of adverse effects including nephrotoxicity. There have been no reports on the long-term evolution of renal function in a large series of paediatric pulmonary transplantation recipients. METHODS: We examined 19 patients followed up for at least 3 years after pulmonary transplantation. The mean time of follow-up was 5.36 years. Kidney function was evaluated by calculation of glomerular filtration rate (GFR) according the Schwartz formula. RESULTS: The GFR was normal before transplantation in all patients. The short-term evolution of GFR was marked by a significant drop during the first and until the 6th month. Then, regardless of the level reached at the end of the 6th month, the GFR remained stable in all patients except one until the end of follow-up. At the end of follow-up, 31% had normal GFR, 57% had mild chronic renal failure, and 5% had advanced renal failure. Hypertension was frequent and associated with renal failure. CONCLUSIONS: Paediatric pulmonary recipients showed evidence of long-term cyclosporine A-associated nephrotoxicity. Most of this toxicity occurred during the first 6 months.

Evaluating the prognosis of multiple, severely traumatized children in the intensive care unit.

OBJECTIVE: To assess the Pediatric Risk of Mortality (PRISM) score and to identify other prognosis factors in severe, multiple trauma in children. DESIGN: Retrospective study over a 9-year period. SETTING: A Pediatric Intensive Care Unit (PICU) in a University Hospital. PATIENTS AND PARTICIPANTS: One hundred and thirty-three traumatized children, 8.6 years (8 months-16 years), were reviewed. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Pediatric Trauma Score (PTS), Injury Severity Score (ISS), New ISS (NISS), Glasgow Coma Scale (GCS) score, and PRISM were calculated. The areas under the Receiver Operating Characteristic (ROC Az) curves, were compared. Univariate and multivariate analyses were performed. The mortality rate was 25.6%. PRISM performed well for discrimination between survivors and non-survivors. Az PRISM 0.9387 (0.029) was not different from Az GCS score 0.9451 (0.027) (P=0.568), but was significantly different from Az ISS 0.756 (0.052) (P<0.001), Az NISS 0.7606 (0.051) (P<0.001), and Az PTS 0.8244 (0.047) (P=0.016). Death was significantly associated with head trauma (P=0.014), PRISM >35, PTS <5, GCS <7, and ISS or NISS >32 (P<0.00001). PRISM >35 (P=0.001) and GCS <7 (P=0.003) were independent risk factors of death. CONCLUSIONS: PRISM is a reliable tool for evaluating the prognosis of multiple, severely traumatized children. Its relative simplicity and the fact that it is extremely widespread as a general prognosis score in PICUs represent other arguments for its use. Due to the leading influence of head trauma on mortality, GCS, a score even simpler than PRISM, showed identical accuracy regarding survival prediction.

Successful treatment of fungal right atrial thrombosis complicating central venous catheterization in a critically ill child.

A 9-year-old boy was admitted to our pediatric intensive care unit after multiple trauma. On the 17th day post trauma, he developed catheter-related sepsis with candidemia. After removal of the catheter and 6 days of unsuccessful intravenous antifungal therapy, conventional and transesophageal two-dimensional echocardiography was performed revealing a large right atrial thrombus. Surgical thrombectomy under cardiopulmonary bypass was performed and the patient recovered within a few days. Fungal right atrial thrombus is a rare, life-threatening complication of central venous catheterization. Two-dimensional echocardiography is a simple and effective diagnostic technique that should be performed when candidemia is detected. The proper therapeutic response depends on the findings of this examination. For a symptomatic patient with a large, mobile thrombus, we strongly recommend thrombectomy. Surgery not only allows removal of the mass and thus elimination of the mechanical complication but is also a key to management of infection.

Double-lung transplantation in children: a report of 20 cases. The Joint Marseille-Montréal Lung Transplant Program.

In the last 3 1/2 years, we have performed 20 double-lung transplantations in children between 7 and 16 years old (mean age, 13 years). One patient had primitive bronchiolitis obliterans and the other 19, cystic fibrosis. Eight patients were operated on in an emergency situation, 7 of them requiring ventilator support before transplantation. The procedures were en bloc double-lung transplantation in the first 11 patients with separate bronchial anastomoses in 10, and sequential bilateral lung transplantation in the later 9 patients. There were no operative deaths. Two patients died in the hospital on postoperative days 37 and 73, and there were four late deaths, which were due to infection, rejection, and bronchiolitis obliterans. The acceptable incidence of airway complications, the improvement in lung function of survivors, and the acceptable midterm survival make double-lung transplantation an acceptable alternative to heart-lung transplantation in children. However, in very small children, heart-lung transplantation may be preferable because of the size of the airway anastomoses at risk.

Double-lung transplantation in mechanically ventilated patients with cystic fibrosis.

Many lung transplant programs consider ventilator dependence as a contraindication for transplantation. Among 54 patients in whom bilateral lung transplantations for cystic fibrosis were performed by the Joint Marseille-Montreal Lung Transplant Program, 10 were ventilator dependent. Three of them died in the early postoperative period (30%): 2 as a result of cerebral anoxia and sepsis, 1 of Pseudomonas cepacia pneumonia. Two patients died at 15 and 19 months after transplantation of obliterative bronchiolitis and secondary bacterial pneumonitis. Another 2 patients in whom obliterative bronchiolitis developed underwent retransplantation with a heart-lung block; 1 of those was operated on at 12 months and is well at 29 months after his initial transplantation; the second was operated on at 34 months and died of primary graft failure. Three other patients are alive and well at 3, 11, and 14 months after transplantation. Actuarial survival at 1 year was 70%. The postoperative course and the infectious and rejection complications were no different from those in patients who underwent transplantation while spontaneously breathing. Obliterative bronchiolitis developed in 66% of patients at risk (2 of 6 patients surviving more than 6 months). We conclude that transplantation in mechanically ventilated patients with cystic fibrosis is not associated with an increase in morbidity or mortality after bilateral lung transplantation. Long-term survival, as in patients who undergo transplantation while spontaneously breathing, is limited by the development of obliterative bronchiolitis.

Bilateral single-lung transplantation in children.

BACKGROUND: This study examined our experience with bilateral single-lung transplantation in pediatric patients. METHODS: Between 1988 and 1995, we have performed 32 double-lung transplantations in children. The first 10 were performed en bloc, the following 22 by bilateral single-lung transplantation. Indications for bilateral single-lung transplantation were cystic fibrosis in 16 patients, primitive obliterative bronchiolitis in 1, pulmonary artery hypertension in 1, and retransplantation in 4. Patients' ages ranged from 7 to 16 years (mean, 12 years). Four patients underwent a parenchymal reduction (lobectomy or bilobectomy). Bilateral single-lung transplantation was performed with a "clam-shell" incision, normothermic cardiopulmonary bypass, and a beating heart. RESULTS: There was one postoperative death (heart failure in a retransplantation patient). Bleeding was moderate, and 4 patients had a bloodless procedure. Bronchial healing was satisfactory, with 3 patients receiving temporary left main bronchus stenting. There were two hospital deaths (recurrent cytomegalovirus infection in a retransplantation patient and multiorgan failure at 2 months) and seven late deaths, caused by infection (mostly cytomegalovirus), obliterative bronchiolitis, or both. Actuarial survival was 75% at 1 year, 56% at 2 years, and 36% at 3 years. CONCLUSIONS: We conclude that bilateral single-lung transplantation appears to be an acceptable technique, even in small children. Bronchial healing is satisfactory, and no revascularization procedure appears necessary. Midterm and long-term results are comparable with those of heart-lung transplants, and in view of the current problems with organ donation, we think it is an adequate strategy in pediatric lung parenchymal disease.

Lung infections in pediatric lung transplantation: experience in 49 cases.

OBJECTIVES: Pulmonary infections, and particularly cytomegalovirus (CMV) infections, are a major cause of morbidity after lung transplantation. We report here our results in 49 pediatric lung transplantations. METHODS: Between may 1988 and 1997, we have done 49 lung transplantations in 42 children (en bloc double lung transplantation (DLT):10, HLTx:7, sequential bilateral sequential-lung transplantation (BSLT):31, single-lung transplantation (SLT): 1). In seven, it was a retransplantation. Among these, 34 were cystic fibrosis (CF) patients, all with multiresistant organisms (Pseudomonas aeruginosa, Burkholderia cepacia, Achromobacter xylososydans, Staphylococcus aureus). All patients were treated with multiantibiotic prophylaxy adapted to the preoperative cultures. Donor-recipient CMV matching was possible in only 31 cases. CMV prophylaxy and immunosuppression protocols have evolved with time, with a current protocol of IV Gancyclovir prophylaxy for 3 months and triple drug immunosuppression without post-operative rabbit anti-thymocyte globulin (RATG) induction. There was no perioperative mortality in the primary transplantations and three early deaths in the whole group (6.1%). RESULTS: Only five patients had no pulmonary infection. The patients presented 3.2 infection episodes per year, 75% localized on the lungs, 41% during the first 3 months. Among the 13 deaths in the 1st year, 10 were directly related to infection, 60% due to CMV. After the 1st year, in all patients dying of pulmonary dysfunction or obliterative bronchiolitis (OB), bacterial infections were associated. There was no serious fungal infection. Actuarial survival at 3 months, 1, 3, 5 years were 85, 65.7, 47.5 and 28.5%, respectively. There was a significant difference in 3 year survival between patients receiving CMV negative organs (40%) and CMV positive organs (17%). CONCLUSION: In our experience, as in other's, pulmonary infection risk is important in lung transplantation. Bacterial infections were mainly an aggravating factor of secondary pulmonary dysfunction or OB, and were not the primary cause of death. CMV infections have been very severe and lead us, despite the scarcity of donors, to avoid positive donors in negative recipients, this leads to disastrous mid-term results in our experience, despite prophylaxis.

[Study of tracheobronchial healing after lung and heart-lung transplantation. Apropos of 64 anastomoses]. / Etude de la cicatrisation trachéo-bronchique après transplantations pulmonaires et cardio-pulmonaires. A propos de soixante-quatre anastomoses.

The authors report an analysis concerning the healing of tracheo-bronchial anastomoses after lung- and heart-lung transplantation. The present study includes 64 anastomoses selected from a total of 80 cases. Sixteen had to be excluded because of early post-operative death; none of these deaths was related to an air-way complication. Bronchial healing was assessed by bronchoscopic follow-up; the appearance of the suture-line was classified according to Couraud's grades. The initial reference was the examination at 2 weeks, which was compared to subsequent follow-up. At the initial assessment, 42 anastomoses were grade I, 4 were grade II, and 18 were grade III. The subsequent anatomic result was satisfactory for 52 sutures (81%). The complications were malacia in 2 cases, stenoses treated with a stenting device in 4 cases, dehiscence in 6 cases. The duration of ischemia and post-operative mechanical respiratory support, as well as the proximal or distal site of the anastomosis appeared to be of significant prognostic value.

[Recent developments in the treatment of pediatric acute respiratory distress syndrome]. / Les développements récents dans le traitement du syndrome de détresse respiratoire aigu en pédiatrie.

Acute respiratory distress syndrome (ARDS) is a severe condition with a high mortality rate, despite conventional treatment using mechanical ventilation. Better understanding of the pathophysiology and awareness of important iatrogenic lung injury secondary to mechanical ventilation has led to new therapeutic principles. Mechanical ventilation strategy during ARDS is characterized by positive end-expiratory pressure, increase in the inspiratory time, high inspiratory oxygen concentration and, more recently, use of permissive hypercapnia. High frequency ventilation allows optimal lung recruitment under small tidal volume. The effectiveness of extracorporeal oxygenation techniques is demonstrated, but because of their cost and morbidity these therapies are rational only in patients who seem likely to die. Partial liquid ventilation and inhaled nitric oxide have great potential but require further studies. Intratracheal exogenous surfactant might be beneficial but controlled trials are needed to confirm the usefulness of this expensive therapy. Finally, a number of adjuncts to mechanical ventilation are currently available to minimize iatrogenic lung injury and improve the outcome. The role of these new treatments must be defined with randomized and controlled clinical trials using homogenous inclusion criteria.

[Value of surfactant in the treatment of acute respiratory distress syndrome in a child]. / Intérêt du surfactant exogène dans le traitement du syndrome de détresse respiratoire aiguë de l'enfant.

BACKGROUND: Adult respiratory distress syndrome has a high mortality rate, despite treatment including mechanical ventilation with positive end-expiratory pressure, increase of the inspiratory time and high inspiratory oxygen concentration. Exogenous surfactant, a well established treatment in premature newborns with neonatal respiratory distress syndrome has only been occasionally evaluated in adult respiratory distress syndrome. CASE REPORT: A 3 year-old child suffered from adult respiratory distress secondary to respiratory syncytial virus infection. Both mechanical ventilation and inhaled nitric oxide failed to improve the respiratory distress. Two doses of intratracheal surfactant application immediately improved pulmonary functions, transiently after the first instillation on day 13 and definitely after the second one, on day 16. CONCLUSION: Exogenous surfactant appeared to be useful for the survival of our patient but prospective evaluation of this treatment in adult respiratory distress syndrome is needed.

[Central alveolar hypoventilation syndrome and cerebral venous thrombosis: fortuitous association?]. / Syndrome d'hypoventilation alvéolaire centrale et thrombose veineuse cérébrale: association fortuite?

UNLABELLED: Central hypoventilation syndrome is defined as the failure of automatic control of breathing. Secondary central hypoventilation syndrome should distinguish from congenital central hypoventilation syndrome by brainstem abnormalities, place of respiratory control. CASE REPORTS: We report two clinical cases characterized by late onset central hypoventilation syndrome (three years--six months, and five years old): in the first case the diagnosis was made after general anesthesia and the second one presented with acute nocturnal comatose state. Neuroradiologic investigations showed bilateral cerebral sinus veinous thrombosis without any brainstem lesions. Moreover these children had severe behavior disorders: psychomotor instability, alterations of social relations, language dysfunction, and neurocognitive deficit. This symptomatology seems independent from central hypoventilation syndrome and cerebral venous thrombosis. CONCLUSION: Late onset central hypoventilation syndrome may be associated with cerebral venous thrombosis. Ischemia of central chemoreceptors or integration of their informations could be one of mechanism.

[Oxcarbazepine and DRESS syndrome: a paediatric cause of acute liver failure]. / Oxcarbazépine et syndrome DRESS: un cas pédiatrique révélé par une hépatite fulminante.

Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome, also called hypersensitivity reaction, is a severe idiosyncratic reaction to drugs, especially to anti-epileptic drugs. Clinical features associate cutaneous eruption, fever, multiple peripheral ganglions, and potentially life-threatening damage of one or more organs. DRESS syndrome is well described in adults treated with aromatic anti-epileptic drugs, such as phenytoin, phenobarbital, and carbamazepine, but also with other drugs. The new anti-epileptic drugs, such as oxcarbazepine also induce various cutaneous eruptions, but with less report of DRESS syndrome. In children, DRESS syndrome is rare and probably underdiagnosed. We report on the case of a 11-year-old girl hospitalised with an acute severe hepatitis revealing an oxcarbazepine-induced DRESS syndrome.

[Digitalized angiography of the thorax in children]. / Angiographie numérisée du thorax de l'enfant.

Technical aspects and indications for the use of digital subtraction angiography of thorax in 109 children are discussed, and the interest of this exploratory method emphasized in chronic respiratory disease in children. Results obtained are compared with other investigations for screening of bronchopulmonary dysplasia. Although generally reliable for exploration of thoracic aorta anomalies (coarctation and abnormal vascular arch) it is considered to be incompletely effective for investigation of congenital heart disease.

[Tracheobronchial healing after lung and heart-lung transplantations. Apropos of 64 anastomoses]. / Etude de la cicatrisation trachéo-bronchique après transplantations pulmonaires et cardio-pulmonaires. A propos de 64 anastomoses.

The authors report an analysis concerning the healing of tracheo-bronchial anastomoses after lung- and heart-lung transplantation. The present study includes 64 anastomoses selected from a total of 80 cases. Sixteen had to be excluded because of early post-operative death; none of these deaths was related to an air-way complication. Bronchial healing was assessed by bronchoscopic follow-up; the appearance of the suture-line was classified according to Couraud's grades. The initial reference was the examination at 2 weeks, which was compared to subsequent follow-up. At the initial assessment, 42 anastomoses were grade 1, 4 were grade II, and 18 were grade III. The subsequent anatomic result was satisfactory for 52 sutures (81%). The complications were malacia in 2 cases, stenoses treated with a stenting device in 4 cases, dehiscence in 6 cases. The duration of ischemia and postoperative mechanical respiratory support, as well as the proximal or distal site of the anastomosis appeared to be of significant prognostic value.

[Tamponade due to pericardial perfusion. A peranesthetic complication in a child]. / Tamponnade par perfusion péricardique. Accident peranesthésique chez un enfant.

This report describes a case of fatal peroperative cardiac tamponade in a 5-year-old boy. It was the consequence of myocardial perforation by a polyethylene central venous catheter and intrapericardial infusion. In case of peroperative unexplained cardiovascular collapse, repeat check of the position of the central venous catheter is mandatory.

[Severe lactic acidosis and thiamine deficiency during parenteral nutrition in a child]. / Acidose lactique sévère et déficit en thiamine au cours d'une nutrition parentérale chez un enfant.

We report the case of a leukemic child treated with chemotherapy and parenteral nutrition for three weeks, who developed a severe lactic acidosis. Clinical features included both digestive and neurological disorders associated with a moderate cardiovascular collapse. After elimination of a toxic, a neoplastic or a septic cause, a thiamin (or vitamin B1) deficiency was suspected because of the lack of vitamin supply to parenteral nutrition. Intravenous administration of thiamin rapidly controlled lactic and clinical features. The diagnosis was confirmed by a low plasmatic concentration of thiamin. Thiamin deficiency must be suspected in case of severe lactic acidosis during parenteral nutrition and systematically prevented by supply of vitamins.

[Lung transplantation and respiratory function tests. Functional outcome in the presence and absence of chronic rejection]. / Transplantations pulmonaires et EFR. Evolution fonctionnelle en présence ou en l'absence de rejet chronique.

Between may 1988 and march 1993, twenty five double lung transplants were performed and five heart/lung transplants. Lung function tests (EFR) were performed on these patients for a period of 19.2 +/- 3.4 months. The aim of this study was two-fold. First, to report our overall results and to estimate the role of the single breath nitrogen washout test (N2 slope) in the early detection of chronic rejection (RC). Secondly, to assess the diagnostic value of EFR in the discrimination of acute rejection (RA) and of cytomegalovirus pneumonitis (PCMV). There were 41 episodes of RA and 21 episodes of PCMV and they were analysed as a function of the presence or absence of RC. In the absence of RC, RA produced no change in EFR and PCMV was accompanied by a pure restrictive ventilatory defect. On the otherhand, RA and PCMV lead to a worsening of obstruction and an hypoxaemia which characterises RC. The diagnosis of RC was made, on average, 14.4 +/- 2.9 months after surgery. However, from the sixth month the nitrogen slope was significantly increased and other parameters of EFR (particular maximal flows at low lung volume) remained normal. Thus, our results suggest that the N2 slope, measured in the absence of any evidence of acute rejection, constitutes an early test for chronic rejection. When its pathological rise is compared to the results of histology (presence or absence of RC), it shows a sensitivity of 0.94 and a specificity of 0.93.

Fatal case of Reye's syndrome associated with H3N2 influenza virus infection and salicylate intake in a 12-year-old patient.

We describe a fatal case of Reye's syndrome in a 12-year-old male patient during an influenza A (H3N2) infection for which he received salicylates. In the current situation of the novel A/H1N1 virus pandemic, we believe that it is of high importance to emphasize the risks associated with salicylate intake to avoid the reappearance of Reye's syndrome.

[Respiratory complications of accidental drownings in children]. / Complications respiratoires des noyades accidentelles chez l'enfant.

Accidental drownings are severe and sometimes mortal events in children. Our study aims to better clarify the epidemiology and the respiratory complications of these accidents in our hospital. We led a retrospective study over 10 years concerning the children hospitalized for accidental drowning in our hospital centre. Age at the moment of the accident, sex, history of accident, hospitable care, thoracic imaging and neurological outcome of the children were studied. In total, 83 children were hospitalized (5 years on average, 70% being boys). The drowning especially took place in fresh water (71%), particularly in swimming pools (51.8%). Stages III and IV of drowning concerned 40.9% of the population. The coverage was the following one: admittance in ICU 57.8%, mechanical ventilation 34.9%, oxygen therapy 16.9%, antibiotics 87.9%. A normal chest x-ray was present in 45.7% of the cases. Drowning in fresh water, especially in contaminated fresh water (canal, WC, etc.), induced atelectasis (10.8%), whereas drowning in sea water induced diffuse infiltrates (8.4%). Aspiration pneumonia (33.7%) was present in both cases and a pulmonary oedema (6%) was only noticed during stage IV drowning. The secondary infections were rare (1 case was suspected and another probable). A child presented a secondary acute respiratory distress syndrome (1.2 %). Finally, 7 deaths (8.4%) and 1 case with severe neurological sequelae (1.2%) were noted. Accidental drowning causes important consequences in children. The long-term respiratory outcomes have not been properly studied. Prevention of such accidents is based on parental vigilance during their child's bathe.