Continued challenges in pediatric anesthesia during COVID-19 in 2022: An international survey from the pediatric anesthesia COVID-19 collaborative.

INTRODUCTION: This international survey explored the ongoing impact of COVID-19 on pediatric anesthesiology. It assessed COVID-19's impact on the practice of pediatric anesthesiology, staffing, job satisfaction, and retention at the beginning of 2022 and addressed what should be done to ameliorate COVID-19's impact and what initiatives hospitals had implemented. METHODS: This survey focused on five major domains: equipment/medication, vaccination/testing, staffing, burnout, and economic repercussions. Pilot testing for questionnaire clarity was conducted by members of the Pediatric Anesthesia COVID-19 Collaborative. The survey was administered by e-mail to a representative of the 72 collaborative centers. Respondents were instructed to answer based on their institution's practice from February through April of 2022. Descriptive statistics with 95% confidence intervals are reported. RESULTS: Seventy of seventy-two institutions participated in this survey (97% response rate). Fifty-nine (84%) were from the United States, and 11 (16%) included other countries. The majority experienced equipment (68%) and medication (60%) shortages. Many institutions reported staffing shortages in nursing (37%), perioperative staff (27%), and attending anesthesiologists (11%). Sixty-two institutions (89%) indicated burnout was a frequent topic of conversation among pediatric anesthesiologists. Forty-three institutions (61%) reported anesthesiologists leaving current practice and 37 (53%) early retirement. Twenty-eight institutions (40%) canceled elective cases. The major suggestions for improving job retention included improving financial compensation (76%), decreasing clinical time (67%), and increasing flexibility in scheduled clinical time (66%). Only a minority of institutions had implemented the following initiatives: improving financial compensation (19%), increased access to mental health/counseling services (30%), and assistance with child or elder care (7%). At the time of the survey, 34% of institutions had not made any changes. CONCLUSION: Our study found that COVID-19 has continued to impact pediatric anesthesiology. There are major discrepancies between what anesthesiologists believe are important for job satisfaction and faculty retention compared to implemented initiatives. Data from this survey provide insight for institutions and departments for addressing these challenges.

Patient and Process Outcomes among Pediatric Patients Undergoing Appendectomy during the COVID-19 Pandemic: An International Retrospective Cohort Study.

BACKGROUND: COVID-19 forced healthcare systems to make unprecedented changes in clinical care processes. The authors hypothesized that the COVID-19 pandemic adversely impacted timely access to care, perioperative processes, and clinical outcomes for pediatric patients undergoing primary appendectomy. METHODS: A retrospective, international, multicenter study was conducted using matched cohorts within participating centers of the international PEdiatric Anesthesia COVID-19 Collaborative (PEACOC). Patients younger than 18 yr old were matched using age, American Society of Anesthesiologists Physical Status, and sex. The primary outcome was the difference in hospital length of stay of patients undergoing primary appendectomy during a 2-month period early in the COVID-19 pandemic (April to May 2020) compared with prepandemic (April to May 2019). Secondary outcomes included time to appendectomy and the incidence of complicated appendicitis. RESULTS: A total of 3,351 cases from 28 institutions were available with 1,684 cases in the prepandemic cohort matched to 1,618 in the pandemic cohort. Hospital length of stay was statistically significantly different between the two groups: 29 h (interquartile range: 18 to 79) in the pandemic cohort versus 28 h (interquartile range: 18 to 67) in the prepandemic cohort (adjusted coefficient, 1 [95% CI, 0.39 to 1.61]; P < 0.001), but this difference was small. Eight centers demonstrated a statistically significantly longer hospital length of stay in the pandemic period than in the prepandemic period, while 13 were shorter and 7 did not observe a statistically significant difference. During the pandemic period, there was a greater occurrence of complicated appendicitis, prepandemic 313 (18.6%) versus pandemic 389 (24.1%), an absolute difference of 5.5% (adjusted odds ratio, 1.32 [95% CI, 1.1 to 1.59]; P = 0.003). Preoperative SARS-CoV-2 testing was associated with significantly longer time-to-appendectomy, 720 min (interquartile range: 430 to 1,112) with testing versus 414 min (interquartile range: 231 to 770) without testing, adjusted coefficient, 306 min (95% CI, 241 to 371; P < 0.001), and longer hospital length of stay, 31 h (interquartile range: 20 to 83) with testing versus 24 h (interquartile range: 14 to 68) without testing, adjusted coefficient, 7.0 (95% CI, 2.7 to 11.3; P = 0.002). CONCLUSIONS: For children undergoing appendectomy, the COVID-19 pandemic did not significantly impact hospital length of stay.

Prevalence of COVID-19 and Risk Factors for Infection Among Pediatric Anesthesia Patients: A Report From the PEACOC Research Network.

BACKGROUND: The Pediatric Anesthesia COVID-19 Collaborative (PEACOC) is a research network to advance the care of children during the pandemic. Here we calculate the prevalence of coronavirus disease 2019 (COVID-19) among children undergoing anesthesia, look at prevalence in the population data from the Centers for Disease Control and Prevention (CDC), and assess independent risk factors for infection. METHODS: This was a multicenter, retrospective, observational study. Children aged 28 days to 18 years scheduled for anesthesia services at 12 centers requiring universal COVID-19 testing from March 29, 2020 to June 30, 2020 were included. COVID-19 positivity rates among those tested were plotted and trends were assessed using the Cochran Armitage test of trend. Independent risk factors were explored using multivariable logistic regression. RESULTS: Data were collected and analyzed on 33,320 anesthesia encounters including 265 children with COVID-19. Over the study period, the rates of infections in the pediatric anesthesia population did not demonstrate a significant trend. In the general population, there was a significant downward trend in infection rates ( P < .001). In exploratory analysis, multivariable risk factors for a COVID-19 positive test were Black/African American race, Hispanic ethnicity, American Society of Anesthesiologists (ASA) physical status III or above, overweight and obese body mass index (BMI), orthopedic cases, abdominal cases, emergency cases, absence of injury and trauma, and West region (all P < .05). CONCLUSIONS: Rates of COVID-19 in pediatric anesthesia patients were consistently lower than in the general population. Independent risk factors of a positive test for children were identified. This is the first time universal testing for a single infectious disease was undertaken on a wide scale. As such, the association of infection with surgical case type or emergency case status is unprecedented.

Spring-mediated cranioplasty versus endoscopic strip craniectomy for sagittal craniosynostosis.

OBJECTIVE: Endoscopic strip craniectomy (ESC) and spring-mediated cranioplasty (SMC) are two minimally invasive techniques for treating sagittal craniosynostosis in early infancy. Data comparing the perioperative outcomes of these two techniques are sparse. Here, the authors hypothesized that outcomes would be similar between patients undergoing SMC and those undergoing ESC and conducted a study using the multicenter Pediatric Craniofacial Surgery Perioperative Registry (PCSPR). METHODS: The PCSPR was queried for infants under the age of 6 months who had undergone SMC or ESC for sagittal synostosis. SMC patients were propensity score matched 1:2 with ESC patients on age and weight. Primary outcomes were transfusion-free hospital course, intensive care unit (ICU) admission, ICU length of stay (LOS), and hospital length of stay (HLOS). The authors also obtained data points regarding spring removal. Comparisons of outcomes between matched groups were performed with multivariable regression models. RESULTS: The query returned data from 676 infants who had undergone procedures from June 2012 through September 2019, comprising 580 ESC infants from 32 centers and 96 SMC infants from 5 centers. Ninety-six SMC patients were matched to 192 ESC patients. There was no difference in transfusion-free hospital course between the two groups (adjusted odds ratio [aOR] 0.78, 95% CI 0.45-1.35). SMC patients were more likely to be admitted to the ICU (aOR 7.50, 95% CI 3.75-14.99) and had longer ICU LOSs (incident rate ratio [IRR] 1.42, 95% CI 1.37-1.48) and HLOSs (IRR 1.28, 95% CI 1.17-1.39). CONCLUSIONS: In this multicenter study of ESC and SMC, the authors found similar transfusion-free hospital courses; however, SMC infants had longer ICU LOSs and HLOSs. A trial comparing longer-term outcomes in SMC versus ESC would further define the roles of these two approaches in the management of sagittal craniosynostosis.

A survey of the global impact of COVID-19 on the practice of pediatric anesthesia: A study from the pediatric anesthesia COVID-19 Collaborative Group.

BACKGROUND: Pediatric anesthesiology has been greatly impacted by COVID-19 in the delivery of care to patients and to the individual providers. With this study, we sought to survey pediatric centers and highlight the variations in care related to perioperative medicine during the COVID-19 pandemic, including the availability of protective equipment, the practice of pediatric anesthesia, and economic impact. AIM: The aim of the survey was to determine how COVID-19 directly impacted pediatric anesthesia practices during the study period. METHODS: A survey concerning four major domains (testing, safety, clinical management/policy, economics) was developed. It was pilot tested for clarity and content by members of the Pediatric Anesthesia COVID-19 Collaborative. The survey was administered by email to all Pediatric Anesthesia COVID-19 Collaborative members on September 1, 2020. Respondents had six weeks to complete the survey and were instructed to answer the questions based on their institution's practice during September 1 - October 13, 2020. RESULTS: Sixty-three institutions (100% response rate) participated in the COVID-19 Pediatric Anesthesia Survey. Forty-one hospitals (65%) were from the United States, and 35% included other countries. N95 masks were available to anesthesia teams at 91% of institutions (n = 57) (95% CI: 80%-96%). COVID-19 testing criteria of anesthesia staff and guidelines to return to work varied by institution. Structured simulation training aimed at improving COVID-19 safety and patient care occurred at 62% of institutions (n = 39). Pediatric anesthesiologists were economically affected by a reduction in their employer benefits and restriction of travel due to employer imposed quarantine regulations. CONCLUSION: Our data indicate that the COVID-19 pandemic has impacted the testing, safety, clinical management, and economics of pediatric anesthesia practice. Further investigation into the long-term consequences for the specialty is indicated.

Minimally Invasive Endoscopic Surgery for Infantile Craniosynostosis: A Longitudinal Cohort Study.

OBJECTIVE: To evaluate patient outcomes of minimally invasive endoscopic strip craniectomy (ESC) for craniosynostosis. STUDY DESIGN: This is a retrospective cohort analysis (2004-2018) of 500 consecutive infants with craniosynostosis treated by ESC with orthotic therapy at a single center. Operative outcomes included transfusions, complications, and reoperations as well as head circumference change based on World Health Organization percentiles. Multivariable logistic regression was used to identify risk factors associated with blood transfusion. Paired t tests were used for within-patient comparisons and Fisher exact test to compare syndromic and nonsyndromic subgroups. RESULTS: ESC was associated with low rates of blood transfusion (6.6%), complications (1.4%), and reoperations (3.0%). Risk factors for transfusion included syndromic craniosynostosis (P = .01) and multiple fused sutures (P = .02). Median surgical time was 47 minutes, and hospital length of stay 1 day. Transfusion and reoperation rates were higher among syndromic patients (both P < .001). Head circumference normalized by 12 months of age relative to World Health Organization criteria in infants with sagittal, coronal, and multisuture craniosynostosis (all P < .001). CONCLUSIONS: ESC is a safe, effective, and durable correction of infantile craniosynostosis. ESC can achieve head growth normalization with low risks of blood transfusion, complications, or reoperation. Early identification of craniosynostosis in the newborn period and prompt referral by pediatricians allows families the option of ESC vs larger and riskier open reconstruction procedures.

Population Pharmacokinetics of Intraperitoneal Bupivacaine Using Manual Bolus Atomization Versus Micropump Nebulization and Morphine Requirements in Young Children.

BACKGROUND: Intraperitoneal (IP) administration of local anesthetics is used in adults and children for postoperative analgesia after laparoscopic surgery. Population pharmacokinetics (PK) of IP bupivacaine has not been determined in children. Objectives of this study were (1) to develop a population PK model to compare IP bupivacaine administered via manual bolus atomization and micropump nebulization and (2) to assess postoperative morphine requirements after intraoperative administration. We hypothesized similar PK profiles and morphine requirements for both delivery methods. METHODS: This was a prospective, sequential, observational study. After institutional review board (IRB) approval and written informed parental consent, 67 children 6 months to 6 years of age undergoing robot-assisted laparoscopic urological surgery received IP bupivacaine at the beginning of surgery. Children received a total dose of 1.25 mg/kg bupivacaine, either diluted in 30-mL normal saline via manual bolus atomization over 30 seconds or undiluted bupivacaine 0.5% via micropump nebulization into carbon dioxide (CO2) insufflation tubing over 10-17.4 minutes. Venous blood samples were obtained at 4 time points between 1 and 120 minutes intraoperatively. Samples were analyzed by liquid chromatography with mass spectrometry. PK parameters were calculated using noncompartmental and compartmental analyses. Nonlinear regression modeling was used to estimate PK parameters (primary outcomes) and Mann-Whitney U test for morphine requirements (secondary outcomes). RESULTS: Patient characteristics between the 2 delivery methods were comparable. No clinical signs of neurotoxicity or cardiotoxicity were observed. The range of peak plasma concentrations was 0.39-2.44 µg/mL for the manual bolus atomization versus 0.25-1.07 µg/mL for the micropump nebulization. IP bupivacaine PK was described by a 1-compartment model for both delivery methods. Bupivacaine administration by micropump nebulization resulted in a significantly lower Highest Plasma Drug Concentration (Cmax) and shorter time to reach Cmax (Tmax) (P < .001) compared to manual bolus atomization. Lower plasma concentrations with less interpatient variability were observed and predicted by the PK model for the micropump nebulization (P < .001). Adjusting for age, weight, and sex as covariates, Cmax and area under the curve (AUC) were significantly lower with micropump nebulization (P < .001). Regardless of the delivery method, morphine requirements were low at all time points. There were no differences in cumulative postoperative intravenous/oral morphine requirements between manual bolus atomization and micropump nebulization (0.14 vs 0.17 mg/kg; P = .85) measured up to 24 hours postoperatively. CONCLUSIONS: IP bupivacaine administration by micropump nebulization demonstrated lower plasma concentrations, less interpatient variability, low risk of toxicity, and similar clinical efficacy compared to manual bolus atomization. This is the first population PK study of IP bupivacaine in children, motivating future randomized controlled trials to determine efficacy.

Endoscopic Versus Open Repair for Craniosynostosis in Infants Using Propensity Score Matching to Compare Outcomes: A Multicenter Study from the Pediatric Craniofacial Collaborative Group.

BACKGROUND: The North American Pediatric Craniofacial Collaborative Group (PCCG) established the Pediatric Craniofacial Surgery Perioperative Registry to evaluate outcomes in infants and children undergoing craniosynostosis repair. The goal of this multicenter study was to utilize this registry to assess differences in blood utilization, intensive care unit (ICU) utilization, duration of hospitalization, and perioperative complications between endoscopic-assisted (ESC) and open repair in infants with craniosynostosis. We hypothesized that advantages of ESC from single-center studies would be validated based on combined data from a large multicenter registry. METHODS: Thirty-one institutions contributed data from June 2012 to September 2015. We analyzed 1382 infants younger than 12 months undergoing open (anterior and/or posterior cranial vault reconstruction, modified-Pi procedure, or strip craniectomy) or endoscopic craniectomy. The primary outcomes included transfusion data, ICU utilization, hospital length of stay, and perioperative complications; secondary outcomes included anesthesia and surgical duration. Comparison of unmatched groups (ESC: N = 311, open repair: N = 1071) and propensity score 2:1 matched groups (ESC: N = 311, open repair: N = 622) were performed by conditional logistic regression analysis. RESULTS: Imbalances in baseline age and weight are inherent due to surgical selection criteria for ESC. Quality of propensity score matching in balancing age and weight between ESC and open groups was assessed by quintiles of the propensity scores. Analysis of matched groups confirmed significantly reduced utilization of blood (26% vs 81%, P < .001) and coagulation (3% vs 16%, P < .001) products in the ESC group compared to the open group. Median blood donor exposure (0 vs 1), anesthesia (168 vs 248 minutes) and surgical duration (70 vs 130 minutes), days in ICU (0 vs 2), and hospital length of stay (2 vs 4) were all significantly lower in the ESC group (all P < .001). Median volume of red blood cell administered was significantly lower in ESC (19.6 vs 26.9 mL/kg, P = .035), with a difference of approximately 7 mL/kg less for the ESC (95% confidence interval for the difference, 3-12 mL/kg), whereas the median volume of coagulation products was not significantly different between the 2 groups (21.2 vs 24.6 mL/kg, P = .73). Incidence of complications including hypotension requiring treatment with vasoactive agents (3% vs 4%), venous air embolism (1%), and hypothermia, defined as <35°C (22% vs 26%), was similar between the 2 groups, whereas postoperative intubation was significantly higher in the open group (2% vs 10%, P < .001). CONCLUSIONS: This multicenter study of ESC versus open craniosynostosis repair represents the largest comparison to date. It demonstrates striking advantages of ESC for young infants that may result in improved clinical outcomes, as well as increased safety.

Perioperative Outcomes and Management in Pediatric Complex Cranial Vault Reconstruction: A Multicenter Study from the Pediatric Craniofacial Collaborative Group.

BACKGROUND: The Pediatric Craniofacial Collaborative Group established the Pediatric Craniofacial Surgery Perioperative Registry to elucidate practices and outcomes in children with craniosynostosis undergoing complex cranial vault reconstruction and inform quality improvement efforts. The aim of this study is to determine perioperative management, outcomes, and complications in children undergoing complex cranial vault reconstruction across North America and to delineate salient features of current practices. METHODS: Thirty-one institutions contributed data from June 2012 to September 2015. Data extracted included demographics, perioperative management, length of stay, laboratory results, and blood management techniques employed. Complications and outlier events were described. Outcomes analyzed included total blood donor exposures, intraoperative and perioperative transfusion volumes, and length of stay outcomes. RESULTS: One thousand two hundred twenty-three cases were analyzed: 935 children aged less than or equal to 24 months and 288 children aged more than 24 months. Ninety-five percent of children aged less than or equal to 24 months and 79% of children aged more than 24 months received at least one transfusion. There were no deaths. Notable complications included cardiac arrest, postoperative seizures, unplanned postoperative mechanical ventilation, large-volume transfusion, and unplanned second surgeries. Utilization of blood conservation techniques was highly variable. CONCLUSIONS: The authors present a comprehensive description of perioperative management, outcomes, and complications from a large group of North American children undergoing complex cranial vault reconstruction. Transfusion remains the rule for the vast majority of patients. The occurrence of numerous significant complications together with large variability in perioperative management and outcomes suggest targets for improvement.

Multivariable predictors of substantial blood loss in children undergoing craniosynostosis repair: implications for risk stratification.

BACKGROUND: Operative treatment of craniosynostosis is associated with substantial blood loss, often requiring transfusion of packed red blood cells (PRBC) and coagulation products. AIMS: The aim of this prospective study was to analyze thromboelastographic (TEG) parameters and platelet fibrinogen product to determine predictors of substantial blood loss, and the need for PRBC transfusion and coagulation products. METHODS: With IRB approval, we enrolled 120 children undergoing craniosynostosis repair with a standardized anesthetic, fluid management, and TEG measurements at predefined times. Outcomes of interest were intraoperative blood loss, and need for PRBC transfusion and coagulation products. Multivariable logistic regression and receiver operating characteristic (ROC) curve analysis was applied to determine independent predictors of substantial blood loss and need for coagulation products. RESULTS: One hundred and eighteen children were included in the analysis. Forty-four required PRBC transfusion (median 26 ml·kg(-1) ; IQR: 22-42) with median blood loss of 56 ml·kg(-1) (IQR: 43-83). Factors associated with the PRBC transfusion included type of surgery, duration of surgery, and three TEG parameters, α-angle, MA, and K-time (all P < 0.001). A predictive algorithm was developed by subgroup analysis of cranial vault reconstruction (CVR) patients for substantial intraoperative blood loss (defined as ≥60 ml·kg(-1) ) and need for coagulation products with ROC-derived cut-off values: platelet fibrinogen product, <343; α-angle, <62°; MA, <55 mm; K-time, >2.1 min. The best prognostic combination included at least two of these four predictors (sensitivity 89%, specificity 90%). Multivariable regression identified MA as the only independent predictor of coagulation product administration (P < 0.001) and ROC analysis identified MA <46 mm as the optimal cut-off (sensitivity 86%, specificity 94%). CONCLUSIONS: Risk for substantial intraoperative blood loss can be assessed using TEG parameters and platelet fibrinogen product, whereas the need for coagulation products is strongly related to low MA. Patients susceptible to substantial blood loss can be risk stratified based on their TEG/platelet fibrinogen product profile.

Surgical treatment of craniosynostosis in infants: open vs closed repair.

PURPOSE OF REVIEW: Correction of craniosynostosis may require extensive surgical interventions with related intra and postoperative complications especially hemorrhage. To reduce the intervention's impact and associated complications, less invasive surgical alternatives have evolved. The present review comprehensively summarizes surgical techniques, perioperative anesthesia management, success rates, complications, the results of outcome evaluations, and predictors of intra and postoperative complications. RECENT FINDINGS: Recent evaluations suggest that less invasive methods represent valuable techniques with comparable cosmetic and volumetric results but reduced overall impact and complications. Furthermore, risk stratification based on predictors might optimize safety and guide decision-making concerning the required level of postoperative clinical care. SUMMARY: Neuroendoscopic techniques, designed to minimize surgical incision, dissection, and blood loss, are becoming efficacious and valuable alternative therapeutic options reducing the need for fluid replacement and invasive hemodynamic monitoring. Since hemorrhage represents the most important complication in open craniosynostosis repair, prevention strategies such as the use of tranexamic acid should be considered. Sufficient correction of entailed coagulopathies is crucial.

Predictors of clinically significant postoperative events after open craniosynostosis surgery.

BACKGROUND: Craniosynostosis surgery is associated with clinically significant postoperative events requiring intensive care unit (ICU) admission. The authors investigate specific variables, which might influence the risk for these events, and thereby make recommendations regarding the need for postoperative ICU admission. METHODS: A retrospective review of 225 children undergoing open craniosynostosis repair at a single center during a 10-yr period is reported. The primary outcome measure was the incidence of predefined clinically relevant postoperative cardiorespiratory and hematological events requiring ICU admission. RESULTS: The incidences of postoperative cardiorespiratory and hematological events requiring ICU care were 14.7% (95% CI, 10.5 to 20.1%) and 29.7% (95% CI, 24.0 to 36.3%), respectively. Independent predictors of cardiorespiratory events were body weight less than 10 kg, American Society of Anesthesiologists physical status 3 or 4, intraoperative transfusion of greater than 60 ml/kg packed erythrocytes, and the occurrence of an intraoperative complication. The independent predictors of hematological events were body weight less than 10 kg, American Society of Anesthesiologists physical status 3 or 4, intraoperative transfusion of greater than 60 ml/kg packed erythrocytes, transfusion of hemostatic products (fresh-frozen plasma, platelets, and/or cryoprecipitate), and tranexamic acid not administered. CONCLUSIONS: Children undergoing craniosynostosis surgery are at increased risk for clinically significant postoperative events requiring ICU admission if they are less than 10 kg body weight, American Society of Anesthesiologists physical status 3 or 4, require intraoperative transfusion of greater than 60 ml/kg of packed erythrocytes, receive hemostatic blood products, or if they develop a significant intraoperative complication. Tranexamic acid administration was associated with fewer postoperative events. A predictive clinical algorithm for pediatric patients having major craniosynostosis surgery was developed and validated to risk stratify these patients.

Endoscopic pediatric neurosurgery: implications for anesthesia.

Endoscopic surgery is increasingly utilized in neurosurgery for all pediatric age groups. Endoscopic intraventricular neurosurgery represents a unique approach to intracranial pathology but may cause a unique set of limitations and potential complications. Important endoscopic neurosurgical techniques and their indications, perioperative anesthesia management, complications, and success rates are reviewed with special emphasis on endoscopic third ventriculostomy and endoscopic-assisted strip craniectomy in early infancy. Despite encouraging short- and long-term results of early pediatric endoscopic neurosurgery, multicenter randomized studies will be needed to further determine safety and the effect on cognitive development and quality of life.

Population pharmacokinetics of tranexamic acid in paediatric patients undergoing craniosynostosis surgery.

BACKGROUND: Tranexamic acid (TXA) effectively reduces blood loss and transfusion requirements during craniofacial surgery. The pharmacokinetics of TXA have not been fully characterized in paediatric patients and dosing regimens remain diverse in practice. A mixed-effects population analysis would characterize patient variability and guide dosing practices. OBJECTIVE: The objective of this study was to conduct a population pharmacokinetic analysis and develop a model to predict an effective TXA dosing regimen for children with craniosynostosis undergoing cranial remodelling procedures. METHODS: The treatment arm of a previously reported placebo-controlled efficacy trial was analysed. Twenty-three patients with a mean age 23 ± 19 months received a TXA loading dose of 50 mg/kg over 15 min at a constant rate, followed by a 5 mg/kg/h maintenance infusion during surgery. TXA plasma concentrations were measured and modelled with a non-linear mixed-effects strategy using Monolix 4.1 and NONMEM(®) 7.2. RESULTS: TXA pharmacokinetics were adequately described by a two-compartment open model with systemic clearance (CL) depending on bodyweight (WT) and age. The apparent volume of distribution of the central compartment (V1) was also dependent on bodyweight. Both the inter-compartmental clearance (Q) and the apparent volume of distribution of the peripheral compartment (V2) were independent of any covariate. The final model may be summarized as: CL (L/h) = [2.3 × (WT/12)(1.59) × AGE(-0.0934)] × e(η1), V1 (L) = [2.34 × (WT/12)(1.4)] × e(η2), Q (L/h) = 2.77 × e(η3) and V2 (L) = 1.53 × e(η4), where each η corresponds to the inter-patient variability for each parameter. No significant correlation was found between blood volume loss and steady-state TXA concentrations. Based on this model and simulations, lower loading doses than used in the clinical study should produce significantly lower peak concentrations while maintaining similar steady-state concentrations. CONCLUSIONS: A two-compartment model with covariates bodyweight and age adequately characterized the disposition of TXA. A loading dose of 10 mg/kg over 15 min followed by a 5 mg/kg/h maintenance infusion was simulated to produce steady-state TXA plasma concentrations above the 16 µg/mL threshold. This dosing scheme reduces the initial high peaks observed with the larger dose of 50 mg/kg over 15 min used in our previous clinical study.

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·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 µg·ml(-1)) and plasmin-induced platelet activation (16 µg·ml(-1)) throughout the infusion. CONCLUSIONS: TXA is effective in reducing perioperative blood loss and transfusion requirement in children undergoing craniosynostosis reconstruction surgery.

Robotic assisted laparoscopic ureteral reimplantation in children: case matched comparative study with open surgical approach.

PURPOSE: Surgical treatment may be required in some patients with vesicoureteral reflux. With the recent development of robotic assistance, laparoscopic treatment of vesicoureteral reflux has gained popularity. We sought to evaluate our initial experience with pediatric robotic assisted laparoscopic intravesical and extravesical ureteral reimplantation, and to compare outcomes with the open technique. MATERIALS AND METHODS: A retrospective chart review was performed on all patients who underwent robotic assisted laparoscopic ureteral reimplantation between 2007 and 2010. Comparisons were made with a case matched cohort of patients who underwent the open technique. The groups were compared using t tests for numerical variables and chi-square comparisons or Fisher's exact test for categorical variables. A Kaplan-Meier model was used to compare success rates. RESULTS: A total of 19 patients underwent intravesical and 20 underwent extravesical robotic assisted laparoscopic ureteral reimplantation during the study period. They were compared to 22 patients undergoing intravesical and 17 undergoing extravesical open ureteral reimplantation. Although the robotic assisted approach was associated with a longer operative time (p <0.001), children undergoing intravesical robotic assisted reimplantation had a shorter duration of urinary catheter drainage, fewer bladder spasms and a shorter hospital stay compared to those undergoing the intravesical open technique (p <0.01). There were no significant differences in these parameters when comparing extravesical robotic assisted reimplantation to the extravesical open technique. Overall success rates were similar among patients who underwent robotic assisted laparoscopic ureteral reimplantation and open reimplantation (p >0.5). CONCLUSIONS: Robotic assisted laparoscopic ureteral reimplantation offers similar success rates to the gold standard, open ureteral reimplantation. Future large scale studies will be required to define further the costs and benefits of robotic assisted laparoscopic ureteral reimplantation in the surgical treatment of vesicoureteral reflux.

Long-term experience and outcomes of robotic assisted laparoscopic pyeloplasty in children and young adults.

PURPOSE: Laparoscopic pyeloplasty is one of the more common robotic assisted procedures performed in children. However, data regarding long-term experience and clinical outcomes for this procedure are limited. We evaluated the long-term outcomes in a large series of patients undergoing robotic assisted laparoscopic pyeloplasty at a teaching institution, and the effect of a collaborative program between the robotic surgeons, surgical nurses and anesthesiologists on overall operative time. MATERIALS AND METHODS: We retrospectively reviewed 155 patients who underwent robotic assisted laparoscopic pyeloplasty between 2002 and 2009. Operative data, including surgical approach, type of procedure, total and specific operative times and placement of ureteral stents, were determined. Postoperative outcome measurements, including duration of hospital stay, duration of Foley catheter drainage, radiological findings and any subsequent complications, were assessed. RESULTS: Mean operative time and length of hospitalization decreased significantly by the end of the study. At a mean followup of 31.7 months the primary success rate was 96% (hydronephrosis was improved in 85% of patients and stable in 11%). The complication rate was 11%, and recurrent obstruction requiring redo robotic assisted laparoscopic pyeloplasty or open pyeloplasty developed in 3% of patients. Success rate and complication rate were unchanged during the study period. CONCLUSIONS: This study confirms that even within the confines of a pediatric urology training program successful collaboration between robotic surgeons, surgical nurses and anesthesiologists can lead to shorter operative times and hospital stays. Long-term surgical success and complication rates were comparable to open surgery.

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.

Lumbar sympathetic blockade in children with complex regional pain syndromes: a double blind placebo-controlled crossover trial.

BACKGROUND: Sympathetic blockade is used in the management of complex regional pain syndromes in children, but there are no data on the efficacy or mechanism(s) by which it produces pain relief. The purpose of this study is to compare the efficacy of lidocaine administered by lumbar sympathetic to IV route. METHODS: Under general anesthesia, children with unilateral lower limb complex regional pain syndromes received catheters along the lumbar sympathetic chain. In a double-blind placebo-controlled crossover design, patients received IV lidocaine and lumbar sympathetic saline or lumbar sympathetic lidocaine and IV saline. Spontaneous and evoked pain ratings and sensory thresholds were assessed before and after these two lidocaine/saline doses and between routes of lumbar sympathetic blockade and IV. RESULTS: Twenty-three patients, ages 10-18 yr, were enrolled. There was evidence for reduction of mean pain intensity of allodynia to brush (mean -1.4, 95% confidence interval [CI] -2.5 to -0.3) and to pinprick temporal summation (mean -1.3, 95% CI -2.5 to -0.2) with lidocaine treatment via the lumbar sympathetic blockade compared to IV route. Lumbar sympathetic blockade also produced significant reduction in pain intensity compared to pretreatment values of allodynia to brush, pinprick and pinprick temporal summation and verbal pain scores. IV lidocaine did not produce significant changes in spontaneous and evoked pain intensity measurements compared to pretreatment values. There were no carryover effects as assessed by route-by-period interaction. CONCLUSIONS: Under the conditions of this study, the results provide some direct evidence that a component of pain may be mediated by abnormal sympathetic efferent activity.

Cutaneous sensory abnormalities in children and adolescents with complex regional pain syndromes.

Complex regional pain syndromes (CRPS) have been recognized with increasing frequency in children. These disorders appear to differ markedly from those observed in adults. The International Association for the Study of Pain diagnostic criteria for CRPS were developed based on adult studies; these criteria have not been validated for children. We performed standardized neurological examination and quantitative sensory testing (QST) in a group of pediatric patients to characterize features of sensory dysfunction. Forty-two patients, with unilateral lower extremity CRPS of a mean duration of the pain and symptoms of 12.6 months, who met IASP adult-based criteria for CRPS underwent standardized neurological examination and QST. QST parameters were compared to values previously derived from age- and sex-matched pediatric healthy controls. In most respects, QST parameters did not differ significantly between patients and the normal reference values except for cold and heat pain detection thresholds. Allodynia to cold and/or heat (P<0.001) occurred in 21 patients. Cold allodynia was the most common QST abnormality in our patients. Twenty-six patients showed a combination of mechanical dynamic and static allodynia and allodynia to punctate temporal summation. There was a significant correlation between mechanical dynamic allodynia and allodynia to punctate temporal summation (P<0.001). As with adult CRPS, the thermal and mechanical sensory abnormalities appear in different combinations in different patients with similar clinical presentations. In a majority of patients, the pathogenesis of pain is seemingly of central origin.