High-dose versus low-dose tranexamic acid for paediatric craniosynostosis surgery: a double-blind randomised controlled non-inferiority trial.

BACKGROUND: Tranexamic acid (TXA) reduces blood loss and transfusion in paediatric craniosynostosis surgery. The hypothesis is that low-dose TXA, determined by pharmacokinetic modelling, is non-inferior to high-dose TXA in decreasing blood loss and transfusion in children. METHODS: Children undergoing craniosynostosis surgery were enrolled in a two-centre, prospective, double-blind, randomised, non-inferiority controlled trial to receive high TXA (50 mg kg-1 followed by 5 mg kg-1 h-1) or low TXA (10 mg kg-1 followed by 5 mg kg-1 h-1). Primary outcome was blood loss. Low dose was determined to be non-inferior to high dose if the 95% confidence interval (CI) for the mean difference in blood loss was above the non-inferiority margin of -20 ml kg-1. Secondary outcomes were transfusion, TXA plasma concentrations, and biological markers of fibrinolysis and inflammation. RESULTS: Sixty-eight children were included. Values were non-inferior regarding blood loss (39.4 [4.4] vs 40.3 [6.2] ml kg-1 [difference=0.9; 95% CI: -14.2, 15.9]) and blood transfusion (21.3 [1.6] vs 23.6 [1.5] ml kg-1 [difference=2.3; 95% CI: -2.1, 6.7]) between high-dose (n=32) and low-dose (n=34) groups, respectively. The TXA plasma concentrations during surgery averaged 50.2 (8.0) and 29.6 (7.6) µg ml-1. There was no difference in fibrinolytic and inflammatory biological marker concentrations. No adverse events were observed. CONCLUSIONS: Tranexamic acid 10 mg kg-1 followed by 5 mg kg-1 h-1 is not less effective than a higher dose of 50 mg kg-1 and 5 mg kg-1 h-1 in reducing blood loss and transfusion in paediatric craniosynostosis surgery. CLINICAL TRIAL REGISTRATION: NCT02188576.

Italian COnsensus in Neuroradiological Anesthesia (ICONA).

Anesthetic management of patients undergoing endovascular procedures for treating intracranial aneurysms or cerebrovascular malformations must consider a number of specific challenges, in addition to those associated with anesthesia for other specialties. In addition to maintenance of physiological stability, manipulation of systemic and cerebral hemodynamic parameters may be required to treat any sudden unexpected catastrophic neurological events. A multidisciplinary group including neuro- and pediatric anesthesiologists, interventional neuroradiologists, neurosurgeons, and a clinical methodologist contributed to this document. This consensus working group from 21 Italian institutions identified open questions regarding the best practices for management of anesthesia during endovascular neuroradiological procedures for intracranial aneurysms and cerebrovascular malformations, and addressed these by formulating practical consensus statements. At the first meeting in November 2015, nine key areas were identified regarding choice of anesthetic, patient monitoring, hemodynamic targets, postoperative care, and the management of neuromuscular blockade, anticoagulant and/or antiplatelet therapy, and special considerations for pediatric patients. Nine subgroups were established and a medical librarian performed literature searches in the Cochrane and MEDLINE/PubMed databases for each group. Groups drafted literature summaries and provisional responses in the form of candidate consensus statements based on evidence, when possible, and clinical experience, when this was lacking. Final wording was agreed at a meeting in April 2016 and where possible evidence was graded using United States Preventive Services Task Force criteria. Consensus (defined as >90% agreement) was based on evidence, clinical experience, clinician preference, feasibility in the Italian healthcare system, and cost/benefit considerations.

Incidence of pain after craniotomy in children.

BACKGROUND: There is very few information regarding pain after craniotomy in children. OBJECTIVES: This multicentre observational study assessed the incidence of pain after major craniotomy in children. METHODS: After IRB approval, 213 infants and children who were <10 years old and undergoing major craniotomy were consecutively enrolled in nine Italian hospitals. Pain intensity, analgesic therapy, and adverse effects were evaluated on the first 2 days after surgery. Moderate to severe pain was defined as a median FLACC or NRS score ≥ 4 points. Severe pain was defined as a median FLACC or NRS score ≥ 7 points. RESULTS: Data of 206 children were included in the analysis. The overall postoperative median FLACC/NRS scores were 1 (IQR 0 to 2). Twenty-one children (16%) presented moderate to severe pain in the recovery room and 14 (6%) during the first and second day after surgery. Twenty-six children (19%) had severe pain in the recovery room and 4 (2%) during the first and second day after surgery. Rectal codeine was the most common weak opiod used. Remifentanil and morphine were the strong opioids widely used in PICU and in general wards, respectively. Longer procedures were associated with moderate to severe pain (OR 1.30; CI 1.07-1.57) or severe pain (OR 1.41; 1.09-1.84; P < 0.05). There were no significant associations between complications, pain intensity, and analgesic therapy. CONCLUSION: Children receiving multimodal analgesia experience little or no pain after major craniotomy. Longer surgical procedures correlate with an increased risk of having postoperative pain.

Noninvasive ventilation and low-flow veno-venous extracorporeal carbon dioxide removal as a bridge to lung transplantation in a child with refractory hypercapnic respiratory failure due to bronchiolitis obliterans.

OBJECTIVE: To report the successful management of end-stage hypercapnic respiratory failure through the association of noninvasive mechanical ventilation and a novel automated device (Decapsmart) of low-flow veno-venous extracorporeal CO2 removal. DESIGN: Case report. SETTINGS: Pediatric intensive care unit at a tertiary care children's hospital. PATIENT: A pediatric patient affected by bronchiolitis obliterans with refractory hypercapnic respiratory failure. The patient received successful lung transplantation after respiratory support with noninvasive mechanical ventilation and a novel automated device of low-flow veno-venous extracorporeal CO2 removal. INTERVENTIONS: Treatment of end-stage hypercapnic respiratory failure with the association of noninvasive ventilation and low-flow veno-venous extracorporeal CO2 removal as a bridge to lung transplantation. MEASUREMENTS AND MAIN RESULTS: Respiratory support controlling hypercapnia, limiting volutrauma, barotraumas, and preventing the incidence of ventilator-associated pneumonia/lung colonization. CONCLUSION: Noninvasive mechanical ventilation and Decapsmart have proven efficacious in managing refractory hypercapnic respiratory failure in a pediatric patient awaiting lung transplantation.

Epilepsy associated with supratentorial brain tumors under 3 years of life.

OBJECTIVE: To investigate the clinical features and outcome of epilepsy in children under 3 years of age with supratentorial brain tumors. METHODS: Patients under 3 years with primary supratentorial hemispheric brain tumors were collected during a 10-year period through a database including demographic and clinical features, neuroimaging, tumor location, developmental outcome, pharmacological and surgical treatment, and tumor histology. Postoperative outcome was assessed according to Engel classification. RESULTS: Among 28 children evaluated, twenty (71.4%) suffered from epilepsy. Mean age at seizure onset was 18.7 months (range: 1-60). In fifteen (75%) children, epilepsy was an early manifestation or the presenting symptom of the tumor; seizures were focal in 8 (53.3%) and generalized in 7 (46.7%) individuals. Three (15%) children presented with an epileptic encephalopathy and continuous spike-waves during sleep. Of the five children with epilepsy onset after surgery, four had focal seizures. Post-surgical follow-up ranged from 4 to 10 years (mean: 7.6+/-3.74). The outcome of epilepsy was generally good, with most children (76.4%) being seizure free (Engel I) or showing >90% improvement in seizure frequency (Engel II) after surgery. However, in about 20% of the cases, epilepsy persisted despite surgery and different AEDs regimen. Best epilepsy outcome was observed in patients with low-grade tumors (p<0.01) and without neurological deficits after surgery (p<0.001). CONCLUSIONS: Epilepsy is a common and early symptom in infants with brain tumors. Its outcome is negatively influenced by high tumor malignancy and by the persistence of neurological deficits after surgery. Treatment of these patients needs a multidisciplinary approach.

Medulloblastoma variants: age-dependent occurrence and relation to Gorlin syndrome--a new clinical perspective.

PURPOSE: We aimed to test the hypothesis that medulloblastoma (MB) variants show a different age distribution and clinical behavior reflecting their specific biology, and that MB occurring at very young age is associated with cancer predisposition syndromes such as Gorlin syndrome (GS). EXPERIMENTAL DESIGN: We investigated the frequency, age distribution, location, response to treatment, outcome, and association with familial cancer predisposition syndromes in a series of 82 cases of MB in patients ages <14 years diagnosed at the Giannina Gaslini Children's Hospital, Genoa, between 1987 and 2004. RESULTS: Desmoplastic MB and MB with extensive nodularity (MBEN), were present in 22 of 82 cases (27%) and were more frequent in children ages