Analgesic Effects of a Novel Combination of Regional Anesthesia After Pediatric Cardiac Surgery: A Retrospective Cohort Study.

OBJECTIVE: The objective of this study was to determine whether the use of regional anesthesia in children undergoing congenital heart surgery was associated with differences in outcomes when compared to surgeon-delivered local anesthetic wound infiltration. DESIGN: A retrospective cohort study. SETTING: At a single pediatric tertiary care center. PARTICIPANTS: Pediatric patients who underwent primary repair of septal defects between January 1, 2018, and March 31, 2022. INTERVENTIONS: The patients were grouped by whether they received surgeon-delivered local anesthetic wound infiltration or bilateral pectointercostal fascial blocks (PIFBs) and a unilateral rectus sheath block (RSB) on the side ipsilateral to the chest tube. MEASUREMENTS AND MAIN RESULTS: Using overlap propensity score-weighted models, the authors examined postoperative opioid requirements (morphine milliequivalents per kilogram), pain scores, length of stay, and time under general anesthesia (GA). Eighty-nine patients were eligible for inclusion and underwent analysis. In the first 12 hours postoperatively, the block group used fewer morphine equivalents per kilogram versus the infiltration group, 0.27 ± 0.2 v 0.64 ± 0.42, with a weighted estimated decrease of 0.39 morphine equivalents per kilogram (95% CI -0.52 to -0.25; p < 0.001), and had lower pain scores, 3.2 v 1.6, with a weighted estimated decrease of 1.7 (95% CI -2.3 to -1.1; p < 0.001). The length of stay and time under GA also were shorter in the block group with weighted estimated decreases of 22 hours (95% CI -33 to -11; p = 0.001) and 18 minutes (95% CI -34 to -2; p = 0.03), respectively. CONCLUSIONS: Bilateral PIFBs and a unilateral RSB on the side ipsilateral to the chest tube is a novel analgesic technique for sternotomy in pediatric patients. In this retrospective study, these interventions were associated with decreases in postoperative opioid use, pain scores, and hospital length of stay without prolonging time under GA.

Development of a physiologically based pharmacokinetic model of diisononyl phthalate (DiNP) in pregnant rat and human.

A physiologically based pharmacokinetic (PBPK) model for di-isononyl phthalate (DiNP) was developed by adapting the existing models for di(2-ethylhexyl) phthalate (DEHP) and di-butylphthalate (DBP). Both pregnant rat and human time-course plasma and urine data were used to address the hydrolysis of DiNP in intestinal tract, plasma, and liver as well as hepatic oxidative metabolism and conjugation of the monoester and primary oxidative metabolites. Data in both rats and humans were available to inform the uptake and disposition of mono-isononyl phthalate (MiNP) as well as the three primary oxidative metabolites including hydroxy (7-OH)-, oxo (7-OXO)-, and carboxy (7-COX)-monoisononyl phthalate in plasma and urine. The DiNP model was reliable over a wide range of exposure levels in the pregnant rat as well as the two low exposure levels in humans including capturing the nonlinear behavior in the pregnant rat after repeated 750 mg/kg/day dosing. The presented DiNP PBPK model in pregnant rat and human, based upon an extensive kinetic dataset in both species, may provide a basis for assessing human equivalent exposures based upon either rodent or in vitro points of departure.

The effect of intraoperative methadone during pediatric cardiac surgery on postoperative opioid requirements.

BACKGROUND: Pain control in pediatric patients undergoing cardiac surgery presents a unique challenge. Postoperatively, many of these patients require long-term opioid infusions and sedation leading to need for prolonged weaning from opioids and longer hospital stays. We hypothesized that intravenous methadone as the sole opioid in children having cardiac surgery with cardiopulmonary bypass would improve perioperative pain control and decrease overall perioperative use of opioid analgesics and sedatives. METHODS: We instituted a practice change involving pediatric patients aged <18 years who underwent cardiac surgery with cardiopulmonary bypass over a 14-month period, comparing the patient population who had surgery prior to the institution of intraoperative methadone usage to patients who had surgery in the months following. We then separated patients into two groups: neonatal (aged < 30 days) and non-neonatal (aged > 30 days to 18 years). Our primary outcome was intraoperative and postoperative opioid requirements measured in morphine equivalents intraoperatively, during the first 24 hours postoperatively, and up to postoperative day 7. Secondary outcomes included extubation rates in the OR, pain and sedation scores, sedation requirements, and time to start of oxycodone. RESULTS: Patients in both groups had similar demographics. In neonatal patients, the postintervention group required significantly lower doses of intraoperative opioids. There was no statistically significant difference in postoperative opioid use. In non-neonatal patients, the postintervention group required significantly less intraoperative opioids. Postoperatively, those in the postintervention group required significantly less opioids in the first 24 hours. CONCLUSION: The use of intraoperative methadone appears to be a reasonable alternative to the use of fentanyl with potential other benefits both intra- and postoperatively of decreased total dose of opioids and other sedatives. Future studies will assess for any improvement in total postoperative opioid requirements during the total hospital stay, and potential use of methadone by the ICU team.

A Study of Practice Behavior for Endotracheal Intubation Site for Children With Congenital Heart Disease Undergoing Surgery: Impact of Endotracheal Intubation Site on Perioperative Outcomes-An Analysis of the Society of Thoracic Surgeons Congenital Cardiac Anesthesia Society Database.

BACKGROUND: In adults undergoing cardiopulmonary bypass surgery, oral intubation is typically preferred over nasal intubation due to reduced risk of sinusitis and infection. In children, nasal intubation is more common and sometimes preferred due to perceived benefits of less postoperative sedation and a lower risk for accidental extubation. This study sought to describe the practice of nasal intubation in the pediatric population undergoing cardiopulmonary bypass surgery and assess the risks/benefits of a nasal route against an oral one. METHODS: Patients <18 years of age in the Society of Thoracic Surgeons Congenital Heart Surgery Database between January 2010 and December 2015 were included. Patients with a preoperative endotracheal tube, tracheostomy, or known airway anomalies were excluded. Multivariable modeling was used to assess the association between route of tracheal intubation and a composite measure of infection risk (wound infection, mediastinitis, septicemia, pneumonia, and endocarditis). Covariates were included to adjust for important patient characteristics (eg, weight, age, comorbidities), case complexity, and center effects. Secondary outcomes included length of intubation, hospital length of stay, and airway complications including accidental extubations. We also performed a subanalysis in children <12 months of age in high-volume centers (>100 cases/y) examining how infection risk may change with age at the time of surgery. RESULTS: Nasal intubation was used in 41% of operations in neonates, 38% in infants, 15% in school-aged children, and 2% in adolescents. Nasal intubation appeared protective for accidental extubation only in neonates (P = .02). Multivariable analysis in infants and neonates showed that the nasal route of intubation was not associated with the infection composite (relative risk [RR], 0.84; 95% CI, 0.59-1.18) or a shorter length of stay (RR, 0.992; 95% CI, 0.947-1.039), but was associated with a shorter intubation length (RR, 0.929; 95% CI, 0.869-0.992). Restricting to high-volume centers showed a significant interaction between age and intubation route with a risk change for infection occurring between approximately 6-12 months of age (P = .003). CONCLUSIONS: While older children undergoing nasal intubation trend similar to the adult population with an increased risk of infection, nasal intubation in neonates and infants does not appear to carry a similar risk. Nasal intubation in neonates and infants may also be associated with a shorter intubation length but not a shorter length of stay. Prospective studies are required to better understand these complex associations.

Double-Blind, Randomized, Placebo-Controlled Trial Comparing the Effects of Antithrombin Versus Placebo on the Coagulation System in Infants with Low Antithrombin Undergoing Congenital Cardiac Surgery.

OBJECTIVES: To determine whether precardiopulmonary bypass (CPB) normalization of antithrombin levels in infants to 100% improves heparin sensitivity and anticoagulation during CPB and has beneficial effects into the postoperative period. DESIGN: Randomized, double-blinded, placebo-controlled prospective study. SETTING: Multicenter study performed in 2 academic hospitals. PARTICIPANTS: The study comprised 40 infants younger than 7 months with preoperative antithrombin levels <70% undergoing CPB surgery. INTERVENTIONS: Antithrombin levels were increased with exogenous antithrombin to 100% functional level intraoperatively before surgical incision. MEASUREMENTS AND MAIN RESULTS: Demographics, clinical variables, and blood samples were collected up to postoperative day 4. Higher first post-heparin activated clotting times (sec) were observed in the antithrombin group despite similar initial heparin dosing. There was an increase in heparin sensitivity in the antithrombin group. There was significantly lower 24-hour chest tube output (mL/kg) in the antithrombin group and lower overall blood product unit exposures in the antithrombin group as a whole. Functional antithrombin levels (%) were significantly higher in the treatment group versus placebo group until postoperative day 2. D-dimer was significantly lower in the antithrombin group than in the placebo group on postoperative day 4. CONCLUSION: Supplementation of antithrombin in infants with low antithrombin levels improves heparin sensitivity and anticoagulation during CPB without increased rates of bleeding or adverse events. Beneficial effects may be seen into the postoperative period, reflected by significantly less postoperative bleeding and exposure to blood products and reduced generation of D-dimers.

Disparities in the management of paediatric splenic injury.

BACKGROUND: The non-operative management of splenic injury in children is recommended widely, and is possible in over 95 per cent of episodes. Practice appears to vary between centres. METHODS: The Trauma Audit and Research Network (TARN) database was interrogated to determine the management of isolated paediatric splenic injuries in hospitals in England and Wales. Rates of non-operative management, duration of hospital stay, readmission and mortality were recorded. Management in paediatric surgical hospitals was compared with that in adult hospitals. RESULTS: Between January 2000 and December 2015 there were 574 episodes. Children treated in a paediatric surgical hospital had a 95·7 per cent rate of non-operative management, compared with 75·5 per cent in an adult hospital (P < 0·001). Splenectomy was done in 2·3 per cent of children in hospitals with a paediatric surgeon and in 17·2 per cent of those treated in an adult hospital (P < 0·001). There was a significant difference in the rate of non-operative management in children of all ages. There was some improvement in non-operative management in adult hospitals in the later part of the study, but significant ongoing differences remained. CONCLUSION: The management of children with isolated splenic injury is different depending on where they are treated. The rate of non-operative management is lower in hospitals without a paediatric surgeon present.

Excretion of Di-2-ethylhexyl phthalate (DEHP) metabolites in urine is related to body mass index because of higher energy intake in the overweight and obese.

A higher body mass index (BMI) has been positively associated with the rate of excretion of di-2-ethylhexyl phthalate (DEHP) metabolites in urine in data from the National Health and Nutrition Examination Survey (NHANES), suggesting an association between DEHP exposure and BMI. The association, however, may be due to the association between body mass maintenance and higher energy intake, with higher energy intake being accompanied by a higher intake of DEHP. To examine this hypothesis, we ran a Monte Carlo simulation with a DEHP physiologically-based pharmacokinetic (PBPK) model for adult humans. A realistic exposure sub-model was used, which included the relation of body weight to energy intake and of energy intake to DEHP intake. The model simulation output, when compared with urinary metabolite data from NHANES, supported good model validity. The distribution of BMI in the simulated population closely resembled that in the NHANES population. This indicated that the simulated subjects and DEHP exposure model were closely aligned with the NHANES population of interest. In the simulated population, the ordinary least squares regression coefficient for log(BMI) as a function of log(DEHP nmol/min) was 0.048 (SE 0.001), as compared with the reported value of 0.019 (SE 0.005). In other words, given our model structure, the higher energy intake in the overweight and obese, and the concomitant higher DEHP exposure, describes the reported relationship between BMI and DEHP.

Genetics and genetic testing for age-related macular degeneration.

Considerable advances have been made in our understanding of age-related macular degeneration (AMD) genetics over the past decade. The genetic associations discovered to date are estimated to account for approximately half of AMD heritability, and functional studies of these variants have revealed new insights into disease pathogenesis, leading to the development of potential novel therapies. There is furthermore growing interest in genetic testing for predicting an individual's risk of AMD and offering personalised preventive or therapeutic treatments. We review the progress made so far in AMD genetics and discuss the possible applications for genetic testing.

Prevalence of referable, sight-threatening retinopathy in type 1 diabetes and its relationship to diabetes duration and systemic risk factors.

PurposeThe purpose of the study was to provide contemporary estimates for diabetic retinopathy (DR) prevalence in a well-defined UK cohort of patients with type 1 diabetes (T1DM) and investigate potential risk factors for proliferative diabetic retinopathy (PDR) and diabetic maculopathy.Patients and MethodsFour hundred and sixty four T1DM patients in North Hampshire had T1DM duration, demographic and systemic risk factor data evaluated retrospectively alongside their DR status in 2010 using logistic regression analysis.ResultsOverall prevalence of any retinopathy, PDR, and maculopathy was 71.5%, 6.5%, and 10.8%, respectively. PDR and maculopathy prevalence were 0 and 0.7% for <10 years T1DM duration. PDR prevalence was 4%, 8%, and 16% for 10-19.9 years, 20-29.9, years and ≥30 years duration, respectively. Maculopathy prevalence was 15.6%, 18%, and 11% for 10-19.9 years, 20-29.9 years, and ≥30 years duration, respectively. In univariate analysis, PDR was associated with T1DM duration (odds ratio (OR) 1.07/year), age (OR 1.03/year), systolic blood pressure (OR 1.03/mmHg), and antihypertensive therapy (OR 10.63), while maculopathy was associated with duration (OR 1.03/year) and statin therapy (OR 2.83). In multivariate analysis, disease duration (OR 1.07/year) and antihypertensive therapy (OR 6.87) remained significantly associated with PDR, and maculopathy with statin therapy (OR 2.27).ConclusionThis study confirms T1DM duration is a strong risk factor for sight-threatening DR. Maculopathy and PDR prevalence within 10 years of T1DM diagnosis is very low. PDR prevalence at 10-20 years was 4% and then doubled for every 10-year interval thereafter up to 16% with ≥30 years duration. Antihypertensive therapy and statin therapy were strongly associated with PDR and maculopathy, respectively.

Natural history of nonimmune-mediated thrombocytopenia and acute kidney injury in pediatric open-heart surgery.

OBJECTIVE: Thrombocytopenia and acute kidney injury (AKI) are common following pediatric cardiac surgery with cardiopulmonary bypass (CPB). However, the relationship between postoperative nadir platelet counts and AKI has not been investigated in the pediatric population. Our objective was to investigate this relationship and examine independent predictors of AKI. DESIGN: After IRB approval, we performed a retrospective review of the institution's medical records and database. SETTING: This study was performed at a single institution over a 5-year period. PATIENTS: We included patients <21 years of age undergoing cardiac surgery with CPB. INTERVENTIONS: Demographics, laboratory, and surgical characteristics were captured, and clinical event rates were recorded. MEASUREMENTS: Descriptive statistics were used to evaluate platelet and creatinine distributions. T-tests and chi-squared tests were used to compare characteristics among Acute Kidney Injury Network groups. Multivariable logistic and ordinal logistic regression models were used to determine the association of our predictor of interest, postoperative nadir platelet count and AKI. RESULTS: Eight hundred and fourteen patients (23% infants and 23% neonates) were included in the analysis. Postoperative platelet counts decreased 48% from baseline reaching a mean nadir value of 150 × 109 ·l-1 on postoperative day 3. AKI occurred in 37% of patients including 13%, 17%, and 6% with Acute Kidney Injury Network stages 1, 2, and 3, respectively. The magnitude of nadir platelet counts correlated with the severity of AKI. Independent predictors of severity of AKI include nadir platelet counts, CPB time, Aristotle score, patient weight, intra-operative packed red blood cell transfusion, and having a heart transplant procedure. CONCLUSIONS: In pediatric open-heart surgery, thrombocytopenia and AKI occur commonly following CPB. Our findings show a strong association between nadir platelet counts and the severity of AKI.

Upper Extremity Peripheral Intravenous Line Infiltration With Concomitant Loss of Pulses Treated With Lipoaspiration: A Case Report.

Peripheral intravenous cannulation in children is associated with occasional morbidity. We present a case where a large volume of blood, administered through a small peripheral cannula in the antecubital fossa, was found to have extravasated into the soft tissues, causing catastrophic vascular compromise. The expedient removal of the extravasate using a lipoaspiration cannula restored perfusion immediately to the affected limb and negated the need for surgical fasciotomies.

Cardiopulmonary Bypass Strategy for a Cyanotic Child With Hemoglobin SC Disease.

Hemoglobin SC (HbSC) disease is a hemoglobinopathy that may produce sickling under conditions of hypoxemia, dehydration, and acidosis. We present a case of HbSC disease and tricuspid atresia, type IB. We describe management by cardiopulmonary bypass CPB using exchange transfusion at initiation of bypass and fractionation of collected blood, allowing platelet and plasma apheresis, as an option for patients unable to undergo this procedure off pump.

Recurrence rate after Delorme's procedure with simultaneous placement of a Thiersch suture.

Introduction Rectal prolapse is a debilitating condition usually affecting elderly women. The management is generally surgical but the optimal operation remains unclear. The recurrence rate after Delorme's procedure has been found to be similar to that for an abdominal approach. Thiersch sutures have been associated with high rates of complications and recurrence. The aim of this study was to compare the outcomes of Delorme's procedure with those of a combined Delorme-Thiersch procedure. Methods A retrospective case note review was performed of all patients who underwent Delorme's procedure for rectal prolapse between 2008 and 2014 in a single centre. Results Sixty-seven patients (63 women) underwent Delorme's procedure during the study period. The majority (85%) of patients were over 75 years old. Twelve patients had a Thiersch suture placed at the time of the procedure. The median length of stay was 3 days (range: 0-19 days). Postoperative bleeding requiring either transfusion or readmission occurred in five patients (7.5%) and two patients (3.0%) were readmitted with pain. There was no difference in the rate of complications regardless of whether a Thiersch suture had been placed. Recurrence occurred in 8.3% of those who had a Thiersch suture compared with 21.8% of those who did not (p=0.26). There was no difference in the median time to recurrence between the groups. Conclusions There was no increase in complications after placement of a Thiersch suture with Delorme's procedure. The rate of recurrence could potentially be decreased with this combined technique. Additional studies are required to investigate this further.

Reduction in blood transfusion in a cohort of infants having cardiac surgery with cardiopulmonary bypass after instituting a goal-directed transfusion policy.

BACKGROUND: Current trends in pediatric cardiac surgery and anesthesiology include goal-directed allogeneic blood transfusion, but few studies address the transfusion of platelets and cryoprecipitate. We report a quality improvement initiative to reduce the transfusion of platelets and cryoprecipitate in infants having cardiac surgery with cardiopulmonary bypass (CPB). METHODS: Data from 50 consecutive patients weighing four to ten kilograms having cardiac surgery with CPB were prospectively collected after the institution of a policy to obtain each patient's platelet and fibrinogen levels during the rewarming phase of CPB. Data from 48 consecutive patients weighing four to ten kilograms having cardiac surgery with CPB prior to the implementation of the policy change were retrospectively collected. Demographics, laboratory values and blood product transfusion data were compared between the groups, using the Chi-square/Fisher's exact test or the T-Test/Wilcoxon Rank-Sum test, as appropriate. RESULTS: The results showed more total blood product exposures in the control group during the time from bypass through the first twenty-four post-operative hours (median of 2 units versus 1 unit in study group, p=0.012). During the time period from CPB separation through the first post-operative day, 67% of patients in the control group received cryoprecipitate compared to 32% in the study group (p=0.0006). There was no difference in platelet exposures between the groups. CONCLUSION: Checking laboratory results during the rewarming phase of CPB reduced cryoprecipitate transfusion by 50%. This reproducible strategy avoids empiric and potentially unnecessary transfusion in this vulnerable population.