Lorenzo Mirabile

Efficacy and safety of ketamine in refractory status epilepticus in children

Objective: To evaluate the efficacy and safety of ketamine (KE) in the management of refractory convulsive status epilepticus (RSE) in children. Methods: In November 2009, we started using KE for treating all children consecutively referred for RSE. Clinical and treatment data were analyzed. Results: Between November 2009 and June 2011, 9 children with RSE received IV KE. In 8 patients, SE had persisted for more than 24 hours (super-refractory RSE), with a median of 6 days (mean 8.5 ± 7.5; range 2–26 days). Prior to KE administration, conventional anesthetics were used, including midazolam, thiopental, and propofol in 9, 5, and 4 patients each. Median dose of KE in continuous IV infusion was 40 gamma(μg)/kg/min (mean 36.5 ± 18.6 gamma[μg]/kg/min; range 10–60 gamma[μg]/kg/min). Midazolam was administered add-on to prevent emergence reactions. The use of KE was associated with resolution of RSE in 6 children. None of the patients experienced serious adverse events. Among the 3 individuals who did not respond to KE, 2 were cured by surgical removal of epileptogenic focal cortical dysplasia. Conclusion: In this small, open-label, unblinded series with no concurrent control group, KE appears effective and safe in treating RSE in children. Larger, randomized studies are needed to confirm data emerging from this preliminary observation. Classification of evidence: This study provides Class IV evidence that IV KE can be effective in treating children with RSE (no statistical analysis was done).

Tracheobronchial obstruction: follow-up study of 100 children treated with airway stenting

OBJECTIVE We described a cohort of 100 children with a wide variety of airway obstruction who underwent stent positioning in the last 7 years. The study examined the outcomes of this treatment in the largest series of paediatric patients reported in the literature with special concern over safety and clinical effectiveness. METHODS We performed a retrospective analysis of 100 consecutive paediatric patients who underwent stent insertions between January 2005 and May 2012. Statistical analysis was performed and exact likelihood was used. RESULTS A total of 235 stents were placed for severe airway obstruction. One hundred and twelve silicone stents (cylinder, hourglass or Y-shaped), 120 metallic stents (covered Nitinol stents, expandable coronary and vascular stents) and 3 biodegradable polydioxanone (PDS) stents were used. Eighty patients presented clinical improvement after stent insertion, 17 were weaned off mechanical ventilation and 3 showed no significant clinical improvement [95% confidence interval (CI) 0.1-8.0%]. Complications were different according to stent type. In our cohort, no fatal stent-related complications have been observed. At follow-up (median 41.4 months, range 1.1-145.4) complete resolution was registered for 60 patients (66%; 95% CI 55-76%), 17 are still under treatment, 9 were lost to follow-up, 8 underwent surgery and 6 died of causes not stent related. CONCLUSION Airway stenting represents a conservative treatment before more invasive surgical procedures and can be very effective when performed in selected children and in specialized centres by physicians experienced in rigid and flexible bronchoscopy.

Neonatal liver abscesses due to Candida infection effectively treated with caspofungin

Candidiasis is relatively frequent in neonatal and pediatric intensive care units (ICUs), particularly in preterm infants less than 28 weeks of gestational age. Neonatal candidiasis shows high mortality and is often associated to poor neurodevelopmental prognosis in survivor patients. Amphotericin B and fluconazole are the first choice drugs for the treatment of neonatal candidiasis. Caspofungin is an alternative antifungal agent, which is recommended for invasive candidiasis in adults, but has been poorly experienced in neonates and infants as far as now. We report the first two infants with Candida liver abscesses treated with caspofungin. In the first infant bloodstream and liver lesions were cleared by combination therapy with fluconazole, liposomal amphotericin and caspofungin, while in the second one by caspofungin alone.

Efficacy of ketamine in refractory convulsive status epilepticus in children: a protocol for a sequential design, multicentre, randomised, controlled, open-label, non-profit trial (KETASER01).

Introduction Status epilepticus (SE) is a life-threatening neurological emergency. SE lasting longer than 120 min and not responding to first-line and second-line antiepileptic drugs is defined as ‘refractory’ (RCSE) and requires intensive care unit treatment. There is currently neither evidence nor consensus to guide either the optimal choice of therapy or treatment goals for RCSE, which is generally treated with coma induction using conventional anaesthetics (high dose midazolam, thiopental and/or propofol). Increasing evidence indicates that ketamine (KE), a strong N-methyl-d-aspartate glutamate receptor antagonist, may be effective in treating RCSE. We hypothesised that intravenous KE is more efficacious and safer than conventional anaesthetics in treating RCSE. Methods and analysis A multicentre, randomised, controlled, open-label, non-profit, sequentially designed study will be conducted to assess the efficacy of KE compared with conventional anaesthetics in the treatment of RCSE in children. 10 Italian centres/hospitals are involved in enrolling 57 patients aged 1 month to 18 years with RCSE. Primary outcome is the resolution of SE up to 24 hours after withdrawal of therapy and is updated for each patient treated according to the sequential method. Ethics and dissemination The study received ethical approval from the Tuscan Paediatric Ethics Committee (12/2015). The results of this study will be published in peer-reviewed journals and presented at international conferences. Trial registration number NCT02431663; Pre-results.

Residual tracheobronchial malacia after surgery for vascular compression in children: treatment with stenting†.

OBJECTIVES: Surgery for vascular anomalies can occasionally fail to relieve symptoms, especially when severe tracheobronchial malacia persists. We studied outcomes in children who underwent airway stenting for severe post-surgical airway malacia and tested known clinical and surgical prognostic factors. METHODS: Among 257 children evaluated for tracheobronchial vascular compression, we reviewed the clinical charts for the 59 patients (23%) who underwent surgery. After surgery, children in whom severe malacia and respiratory symptoms persisted underwent airway stenting. RESULTS: Among the 59 patients (boys: 58.1%, median age: 6.4 months, age range: 0.1–182.8 months), 79.7% had major comorbidities, 39% additional upper airway anomalies and 15.2% abnormal bronchial anatomy. Diagnostic imaging identified seven vascular anomalies: innominate artery compression 27.1%, left bronchial compression from the descending aorta and left pulmonary artery 20.3%, lesions associated with right aortic arch 22.0%, double aortic arch 13.6%, bovine arch type 10.2%, aberrant right subclavian artery 5.1% and pulmonary artery sling 1.7%. For severe residual malacia and severe persistent respiratory symptoms, 20 patients (33.9%) had silicone or metallic stents inserted. The most frequent indication for stenting was double aortic arch (P = 0.02 by chi-square test). A clinical prognostic factor for permanent stenting was left bronchial compression from the descending aorta and left pulmonary artery [odds ratio (OR): 14.667, 95% confidence interval (CI): 2.881–74.659], particularly if associated with congenital heart disease (OR: 30.00, 95% CI: 4.349– 206.927). All silicone stents but one were successfully removed; metallic uncovered stents were patent and completely re-epithelialized. CONCLUSIONS: When surgery leaves severe airway obstruction and respiratory symptoms unchanged, children with tracheobronchial malacia can safely undergo airway stenting.

Successful simultaneous correction of complex congenital tracheal stenosis and tetralogy of fallot.

Congenital tracheal stenosis is frequently associated with heart malformations. Simultaneous correction of both anomalies has been advocated by several authors. We describe our experience with a premature neonate with congenital tracheal stenosis and tetralogy of Fallot. The anomalies were corrected during the same surgical procedure with the aid of extracorporeal circulation. The implications of the operative and postoperative courses, concerning both the cardiac anomaly and the tracheal anomaly are discussed.

Quadri clinico-endoscopici

Per tracheomalacia (TM) o discinesia tracheale s’intende un indebolimento congenito o acquisito della parete tracheale che collabisce con gli atti del respiro. La trachea malacica presenta sia una debolezza intrinseca degli anelli cartilaginei che appaiono meno consistenti e plicabili, sia un ridotto tono muscolare della pars membranacea, che sono causa del suo collasso durante il ciclo respiratorio.

Tracheal surgery in children: outcome of a 12-year survey

OBJECTIVES Despite the fact that team management has improved the results in recent years, perioperative deaths and complications remain high in paediatric tracheal surgery. We reviewed our institutional experience by comparing our results with those in the literature. METHODS Between 2005 and 2017, 30 children underwent surgery for tracheal disease. Fifteen were boys and fifteen were girls (50% vs 50%). The median age at operation was 7 months (15 days-9.6 years), and the median weight was 5.2 kg (2.8-34 kg). Congenital tracheal stenosis was diagnosed in 25 children (83.3%), and 5 (16.7%) had acquired lesions. The mean internal diameter in congenital tracheal stenosis was 1.5 mm, with complete tracheal rings present in all patients. Associated malformations were bronchopulmonary in 11 cases (36.7%) and cardiovascular in 16 (53.3%). RESULTS No in-hospital deaths occurred in our data set. Overall mortality was 4 of 30 cases (13.3%). Twenty-four endoscopic reinterventions were required in 19 children (63%) and consisted of stent positioning in 13 (43.3%), balloon dilatation in 5 (16.7%), granulation removal in 4 (13.3%) and tracheostomy in 2 (6.7%). Of the survivors (26 of 30, 86.7%), 11 children (42.3%) did not require further examination on adequate tracheal diameter for age and absence of symptoms after a median follow-up period of 3.5 years. CONCLUSIONS The result of paediatric tracheal surgery depends on several factors. The number of cases treated at a particular centre is an important one, but our experience, although limited, can be compared with that at centres with a higher volume of cases. We emphasize the need for applying a multidisciplinary approach to master the surgical command of different reconstructive tracheal procedures, to manage associated defects, particularly cardiovascular defects, and to manage complications under endoscopic guidance. These can be considered the mainstays of building a successful tracheal programme.

Outcome of long-term complications after permanent metallic left bronchial stenting in children

OBJECTIVES We describe the way we treated 7 children with critical long-term complications after metallic balloon-expandable stenting in the left mainstem bronchus. METHODS Endoscopic follow-up included a first bronchoscopy 3 weeks after stenting, then monthly for 3 months, every 4-6 months up to 1 year and at scheduled times to calibrate stent diameter up to final calibration. When major complications occurred, patients underwent chest computed tomographic angiography. RESULTS In 1 of the 7 children (median age 2.8 years), metallic left bronchial stenting served as a bridge to surgery. After a median 4-year follow-up, all 7 children experienced recurrent stent ovalizations with stent breakage in 3 and erosion in 1. In 4 children, computed tomographic angiography showed abundant peribronchial fibrous tissue, in 2 left mediastinal rotation and in 1 displacement along the left bronchus after pulmonary re-expansion as the cause of stent-related complication. Of the 7 children, 6 underwent surgery (5 posterior aortopexy and 1 section of the ligamentum arteriosus) and 3 required nitinol stents placement within the metallic ones. One patient completed the follow-up, and 1 patient was lost to follow-up. All 5 remaining children still have permanent bronchial stents in place, patent and re-epithelialized after a median 10.5-year follow-up. There were no deaths. CONCLUSIONS Satisfactory anatomical relationships when children have stents placed in the left mainstem bronchus alone do not guarantee the final success. Several mechanisms intervene to cause critical stent-related complications in children during growth. Permanent metallic stents should be used carefully, and only in selected patients.

Airway stenting in a child with spondyloepiphyseal dysplasia congenita: 13-Year survival

We describe the case of a boy with spondyloepiphyseal dysplasia congenita. At birth, he experienced severe respiratory distress necessitating tracheotomy. Endoscopy done because mechanical ventilation failed to resolve desaturations disclosed severe tracheo-bronchomalacia. A Polyflex silicone stent was placed in the trachea (replaced by Y-Dumon stent) and 2 Palmaz metallic stents in the mainstem bronchi (overlapped with 2 Jomed stents 5 years later). Airway stenting guaranteed a suitable respiratory status and allowed a child who was expected to die at birth, to reach 13.5 years old in good conditions.