Susan M. Goobie

Efficacy of Tranexamic Acid in Pediatric Craniosynostosis Surgery: A Double-blind, Placebo-controlled Trial

Background:Extensive blood loss is common in pediatric craniosynostosis reconstruction surgery. Tranexamic acid (TXA) is increasingly used to reduce perioperative blood loss in various settings, but data on its efficacy are limited in children. The purpose of this randomized, double-blind, placebo-controlled, parallel trial was to evaluate the efficacy of TXA in pediatric craniosynostosis correction surgery. The primary and secondary outcome variables were reduction in perioperative blood loss and reduction in blood transfusion, respectively. Methods:Forty-three children, ages 2 months to 6 yr, received either placebo or TXA in a loading dose of 50 mg·kg−1, followed by an infusion of 5 mg·kg−1·h−1 during surgery. TXA plasma concentrations were measured. Results:The TXA group had significantly lower perioperative mean blood loss (65 vs. 119 ml·kg−1, P < 0.001) and lower perioperative mean blood transfusion (33 vs. 56 ml· kg−1, P = 0.006) compared to the placebo group. The mean difference between the TXA and placebo groups for total blood loss was 54 ml·kg−1 (95% CI for the difference, 23–84 ml·kg−1) and for packed erythrocytes transfused was 23 ml·kg−1 (95% CI for the difference, 7–39 ml·kg−1). TXA administration also significantly diminished (by two thirds) the perioperative exposure of patients to transfused blood (median, 1 unit vs. 3 units; P < 0.001). TXA plasma concentrations were maintained above the in vitro thresholds reported for inhibition of fibrinolysis (10 &mgr;g·ml−1) and plasmin-induced platelet activation (16 &mgr;g·ml−1) throughout the infusion. Conclusions:TXA is effective in reducing perioperative blood loss and transfusion requirement in children undergoing craniosynostosis reconstruction surgery.

Improvements in patient blood management for pediatric craniosynostosis surgery using a ROTEM®-assisted strategy – feasibility and costs

Moderate to severe intraoperative bleeding and the presence of acquired coagulopathy remain serious problems in the management of major pediatric craniosynostosis surgery. After implementation of a ROTEM®‐assisted patient blood management (PBM) strategy, using primarily purified coagulation factor concentrates, feasibility and costs of this new regimen were analyzed.

The efficacy of antifibrinolytic drugs in children undergoing noncardiac surgery: a systematic review of the literature.

Children undergoing major surgery are frequently exposed to a high risk of blood loss often requiring transfusion. Although the risks associated with blood product transfusion have considerably decreased over the last decade, transfusion is still associated with significant morbidity and mortality. Thus, rigorous efforts should be made to decrease surgical bleeding and the need for blood product transfusion. Antifibrinolytic drugs have been shown to be effective when used in both adult and pediatric surgical patients. While there are data in adults to support safety, data remain limited for pediatric patients. Since the restriction of aprotinin use in 2008, the most commonly used antifibrinolytic drugs have been the lysine analogs, tranexamic acid (TXA), and &egr;-aminocaproic acid, which inhibit the conversion of plasminogen to plasmin and decrease the degree of fibrinolysis. We performed a systematic review of the literature pertaining to the efficacy of antifibrinolytic drugs in children undergoing noncardiac surgery. During spine surgery, both TXA and &egr;-aminocaproic acid decrease blood loss and transfusion requirements; however, this information comes from small, mainly retrospective trials. Two prospective, randomized, controlled trials have tested the efficacy of TXA in children undergoing craniofacial surgery and have reported that TXA decreases transfusion requirements. Two pharmacokinetic trials were also recently published and are summarized in this review. No data have been published regarding the efficacy of TXA administration in the pediatric trauma population. Further data are still needed in this field of study, and we discuss some perspectives for future research.

Hemostatic Changes in Pediatric Neurosurgical Patients as Evaluated by Thrombelastograph

Thromboembolic events are a known complication in neurosurgical patients. There is evidence to suggest that a hypercoagulable state may develop perioperatively. Thrombelastograph® (TEG®) coagulation analysis is a reliable method of evaluating hypercoagulability. We evaluated coagulation by using TEG® data in pediatric neurosurgical patients undergoing craniotomy to determine whether a hypercoagulable state develops intraoperatively or postoperatively. Thirty children undergoing craniotomy for removal of a tumor or seizure focus were studied. Blood was analyzed with TEG® data by using native and celite techniques, at three time points for each patient: preoperatively after induction of anesthesia; intraoperatively during closure of the dura; and on the first postoperative day. Compared with preoperative indices, closing and postoperative celite TEG® values were indicative of hypercoagulability with shortened coagulation time values (P < 0.001), prolonged &agr; angle divergence values (P < 0.001), and above-normal TEG® coagulation indices (P ≤ 0.002). Reaction time values were shortened, and maximal amplitude of clot strength values were prolonged but did not reach statistical significance. Hypercoagulation develops early after resection of brain tissue in pediatric neurosurgical patients as assessed by using TEG® data. Further studies are needed to determine the clinical significance of this hypercoagulable state.

Segregation analysis in Shwachman-Diamond syndrome: evidence for recessive inheritance.

Shwachman-Diamond syndrome is a rare disorder of unknown cause. Reports have indicated the occurrence of affected siblings, but formal segregation analysis has not been performed. In families collected for genetic studies, the mean paternal age and mean difference in parental ages were found to be consistent with the general population. We determined estimates of segregation proportion in a cohort of 84 patients with complete sibship data under the assumption of complete ascertainment, using the Li and Mantel estimator, and of single ascertainment with the Davie modification. A third estimate was also computed with the expectation-maximization (EM) algorithm. All three estimates supported an autosomal recessive mode of inheritance, but complete ascertainment was found to be unlikely. Although there are no overt signs of disease in adult carriers (parents), the use of serum trypsinogen levels to indicate exocrine pancreatic dysfunction was evaluated as a potential measure for heterozygote expression. No consistent differences were found in levels between parents and a normal control population. Although genetic heterogeneity cannot be excluded, our results indicate that simulation and genetic analyses of Shwachman-Diamond syndrome should consider a recessive model of inheritance.

The use of a laryngeal mask airway for emergent airway management in a prone child.

A 5-yr-old girl with Arnold-Chiari Malformation, Type 1, was accidentally tracheally extubated while positioned prone in a Mayfield neurosurgical headrest during a decompressive craniectomy and cervical laminectomy. While preparations were being made to return the patient to the supine position for reintubation, we placed a laryngeal mask airway (LMA) without difficulty. The child was kept in the prone position with the LMA in place using positive-pressure ventilation for the remainder of the operation. This case report emphasizes the practical, emergent use of a LMA to secure the airway of a pediatric patient in the prone position after accidental extubation.

Endoscopic strip craniectomy in early infancy: the initial five years of anesthesia experience.

BACKGROUND:Minimally invasive endoscopic strip craniectomy (ESC) is a relatively new surgical technique for treating craniosynostosis in early infancy. In this study we reviewed our anesthesia experience with ESC. The hypothesis was that infants with low body weight and syndromes would have a higher risk of perioperative blood transfusion and that those with respiratory complications are more likely to be admitted to the intensive care unit (ICU). METHODS:We retrospectively reviewed patient charts and anesthesia records of the first 100 consecutive infants who underwent ESC between May 2004 and December 2008 and follow-up evaluations until December 2009. Outcomes included (a) perioperative blood transfusion, (b) venous air embolism (VAE), (c) ICU admission, and (d) reoperation with craniofacial reconstruction procedures. Multivariable logistic regression was used to determine significant factors of patient outcomes. RESULTS:Infants ranging from 4 to 34 weeks of age (weight: 3.2 to 10.1 kg), presented for 87 single and 13 multiple ESC. Four infants had a craniofacial syndrome. The mean surgical time was 48 minutes (range: 26 to 86 minutes). Ninety-two infants had a median estimated blood loss of 23 mL (interquartile ranges [IQR]: 15 to 30 mL). Eight infants who required blood transfusion received a median amount of 17.2 mL/kg (IQR: 10.1 to 21.2 mL/kg). Body weight ⩽5 kg (P = 0.04), sagittal ESC (P < 0.01), syndromic craniosynostosis (P < 0.01), and earlier date of surgery in the series (P < 0.01) were factors associated with blood transfusion. VAE was detected in 2 infants with no changes in clinical outcome. Eight infants were admitted to the ICU. Factors associated with ICU admission were blood transfusion (P < 0.001) and respiratory complications (P < 0.001). Eighty-two infants were discharged on postoperative day 1 (range: 1 to 3 days). Six infants underwent subsequent fronto-orbital advancement and 1 cranial vault reconstruction. Multiple-suture craniosynostosis (P < 0.01), associated syndromes (P = 0.03), and ICU admission after ESC (P = 0.04) were predictive of reoperation. CONCLUSIONS:Twenty percent of infants undergoing ESC had 1 or more of the following: need for blood transfusion, VAE, respiratory complications, and ICU admission. Multivariable analysis confirmed that patients with lower body weight, those with earlier date of surgery in the series, those undergoing sagittal ESC, and those with syndromic craniosynostosis had a higher rate of blood transfusion. ICU admissions often occurred in infants requiring transfusion and those with respiratory complications. Infants with multiple-suture craniosynostosis were more likely to require subsequent craniofacial reconstruction procedures.

Molecular and clinical characterization of de novo and familial cases with microduplication 3q29: guidelines for copy number variation case reporting

Microdeletions of 3q29 have previously been reported, but the postulated reciprocal microduplication has only recently been observed. Here, cases from four families, two ascertained in Toronto (Canada) and one each from Edinburgh (UK) and Leiden (Netherlands), carrying microduplications of 3q29 are presented. These families have been characterized by cytogenetic and molecular techniques, and all individuals have been further characterized with genome-wide, high density single nucleotide polymorphism (SNP) arrays run at a single centre (The Centre for Applied Genomics, Toronto). In addition to polymorphic copy-number variants (CNV), all carry duplications of 3q29 ranging in size from 1.9 to 2.4 Mb, encompassing multiple genes and defining a minimum region of overlap of about 1.6 Mb bounded by clusters of segmental duplications that is remarkably similar in location to previously reported 3q29 microdeletions. Consistent with other reports, the phenotype is variable, although developmental delay and significant ophthalmological findings were recurrent, suggesting that dosage sensitivity of genes located within 3q29 is important for eye and CNS development. We also consider CNVs found elsewhere in the genome for their contribution to the phenotype. We conclude by providing preliminary guidelines for management and anticipatory care of families with this microduplication, thereby establishing a standard for CNV reporting.

Post-Operative Outcomes in Children With and Without Congenital Heart Disease Undergoing Noncardiac Surgery

BACKGROUND Significant advances have been made in the diagnosis and treatment of children with congenital heart disease (CHD), allowing for longer life expectancies and an increasing number who will require noncardiac surgery. OBJECTIVES This study sought to compare the incidence of mortality and major adverse post-operative outcomes following noncardiac surgery in children with and without CHD. METHODS Data from the 2012 pediatric database of the American College of Surgeons National Surgical Quality Improvement Program were analyzed. After propensity score matching, and stratification by severity of CHD, mortality and adverse post-operative outcomes were compared between controls and children with CHD. RESULTS Among the 51,008 children included in the database, 4,520 children with CHD underwent noncardiac surgery. After propensity score matching, we included 2,805 children with minor CHD, 1,272 with major CHD, and 417 with severe CHD. Children in each subgroup were matched and compared with controls without CHD who underwent noncardiac surgery of comparable complexity. The incidence of overall mortality was significantly higher in children with moderate (3.9%) and severe (8.2%) CHD compared with their controls (respectively, 1.7% [p < 0.001] and 1.2% [p = 0.001]). Both 30-day and overall mortality were significantly increased in children with severe CHD (odds ratio [OR]: 8.43, 95% confidence interval [CI]: 2.52 to 28.21; p < 0.001; OR: 7.32, 95% CI: 2.83 to 18.90; p < 0.001) compared with their matched controls. Overall mortality was also significantly increased in children with major CHD compared with their controls (OR: 2.28; 95% CI: 1.37 to 3.79; p = 0.002), whereas no difference was observed between children with minor CHD and their matched controls. CONCLUSIONS Children with major and severe CHD, undergoing noncardiac surgery, have an increased risk of mortality compared with children without CHD. Further studies need to identify the optimal environment for surgical procedures, develop trained multidisciplinary teams to care for children with CHD, and define management strategies for improving outcomes in this high-risk population.

Intraoperative management of blood loss during craniosynostosis surgery.

Craniosynostosis represents a relatively common disorder, with an estimated prevalence of one in 2000 births. The cranial deformity is due to the premature fusion of the cranial sutures. The rapid growth of the brain during the first years of life results in compensatory skull deformation, which can lead to intracranial hypertension and subsequent neurobehavioral impairments. Primary operative repair during the first year of life is generally recommended (1), and most of these procedures are performed in children under 6 months when circulating blood volume is low. Therefore, relatively small blood losses can have a significant impact on hemodynamics and coagulation. The surgical correction of craniofacial malformations will often require blood transfusion during or after surgery. Due to legal and socioeconomic factors and ethical and religious practices, several strategies have has been proposed to reduce or avoid transfusions. The strategies and techniques listed in Table 1 can substantially reduce the need for blood transfusions during craniosynostosis surgery. These approaches can be easily performed in adults and older children. However, their application in infants with craniofacial deformity is certainly more difficult and should probably be used in specialized centers with skilled personnel (2). Autologous blood transfusion