Cell Saver Blood Reinfusion Up to 24 Hours Post Collection in Pediatric Cardiac Surgical Patients Does Not Increase Incidence of Hospital-Acquired Infections or Mortality.

Cell saver blood reinfusion, a blood conservation technique recently available for pediatric use, is typically limited to 6 hours post processing to guard against bacterial contamination. We hypothesize that reinfusion of cell saver blood up to 24 hours post collection in children after cardiac surgery will not increase the incidence of hospital-acquired infections (HAI). The primary aim is to compare incidence of HAI between children receiving cell saver blood ≤6 hours vs. >6 to ≤24 hours from its collection. The secondary aim is to compare mortality and clinical outcomes. Retrospective chart review of children ≤18 years undergoing cardiac surgery with cardiopulmonary bypass (CPB) from 2013 to 2018 when cell saver collection and bedside temperature controlled storage became standard of care. Patients on extracorporeal membrane oxygenation (ECMO) within 48 hours postoperatively and those who did not receive cell saver were excluded. The primary outcome was HAI incidence postoperative days 0-6. Demographic data included diagnosis, surgical severity score, and clinical outcomes. 466 patients, 45% female. No significant between-group differences identified. There was no significant difference in HAI (control 8.5% vs. treatment 8.0%, p = .80) and death (control 7.9% vs. treatment 4.9%, p = .20). Noninferiority testing indicated the treatment group was not statistically inferior to the control group (p = .0028). Kaplan-Meier curve depicted similar status between-group rates of no infection or death; 92% treatment vs. 91% control. Total volume allogeneic red blood cell transfusion (allogeneic blood transfusion [ABT]) up to 24 hours postoperatively was significantly less in the treatment group, p < .0001. Incidence of HAI or mortality was not increased in patients receiving cell saver blood reinfusion >6 to ≤24 hours post collection. Treatment subjects received significantly less volume of ABT. Considering the risks of ABT, these findings support cell saver blood reinfusion up to 24 hours post collection.

Elevated free hemoglobin and decreased haptoglobin levels are associated with adverse clinical outcomes, unfavorable physiologic measures, and altered inflammatory markers in pediatric cardiac surgery patients.

BACKGROUND: There are data suggesting that free hemoglobin (Hb), heme, and iron contribute to infection, thrombosis, multiorgan failure, and death in critically ill patients. These outcomes may be mitigated by haptoglobin. STUDY DESIGN AND METHODS: 164 consecutively treated children undergoing surgery for congenital heart disease were evaluated for associations between free Hb and haptoglobin and clinical outcomes, physiologic metrics, and biomarkers of inflammation RESULTS: Higher perioperative free Hb levels (and lower haptoglobin levels) were associated with mortality, nosocomial infection, thrombosis, hours of intubation and inotropes, increased interleukin-6, peak serum lactate levels, and lower nadir mean arterial pressures. The median free Hb in patients without infection (30 mg/dL; 29 interquartile range [IQR], 24-52 mg/dL) was lower than in those who became infected (39 mg/dL; IQR, 33-88 mg/ 31 dL; p = 0.0046). The median mechanical ventilation requirements were 19 (IQR, 7-72) hours in patients with higher levels of haptoglobin versus 48 (IQR, 18-144) hours in patients with lower levels (p = 0.0047). Transfusion dose, bypass duration, and complexity of surgery were all significantly correlated with Hb levels and haptoglobin levels. Multivariate analyses demonstrated that these variables were independently and significantly associated with outcomes. CONCLUSIONS: Elevated pre- and postoperative levels of free Hb and decreased levels of haptoglobin were associated with adverse clinical outcomes, inflammation, and unfavorable physiologic metrics. Transfusion, RACHS score, and duration of bypass were associated with increased free Hb and decreased haptoglobin. Further investigation of the role of hemolysis and haptoglobin as potential mediators or markers of outcomes is warranted.

Cuffed endotracheal tubes in neonates and infants undergoing cardiac surgery are not associated with airway complications.

STUDY OBJECTIVE: To determine the incidence of postoperative airway complications in infants <5kg in weight undergoing cardiac surgery intubated with Microcuff (Kimberley-Clark, Roswell, GA) endotracheal tubes (ETTs). DESIGN: Retrospective review of infants weighing <5.0 kg with congenital heart disease (CHD) presenting for cardiac surgery. SETTING: Single-center, tertiary pediatric cardiac critical care unit at a university hospital. PATIENTS: A total of 208 infants weighing <5 kg underwent cardiac surgery for CHD from 2008 to 2013. INTERVENTION: Intubation with Microcuff (Kimberley-Clark) ETTs. STUDY DESIGN: Retrospective review of infants weighing <5.0 kg with CHD presenting for cardiac surgery to a single-center tertiary care university hospital. MEASUREMENTS: Perioperative data were collected. Primary outcome was development of tracheal stenosis and/or reintubation for stridor. Stridor was defined as mild (≤2 doses of racemic epinephrine), moderate (>2 doses of racemic epinephrine), or severe (requiring reintubation). Secondary outcomes were variables possibly contributing to postextubation stridor. Infants with a tracheostomy, airway anomalies, and death prior to initial extubation were excluded. Logistic regression analysis was performed to evaluate the association between clinical risk factors and the incidence of postextubation stridor. RESULTS: A total of 208 infants weighing <5 kg underwent cardiac surgery for CHD from 2008 to 2013; 12 subjects were excluded for death prior to initial extubation. No infant developed tracheal stenosis. The incidence of any stridor was 20.9% (95% confidence interval, 15.8%-27.1%) with severe stridor in 2 cases (1%). Age at surgery, weight, duration of intubation, dexamethasone use, and ETT size were not significantly associated with postextubation stridor. Presence of a comorbidity was significantly associated with stridor (P=.01). CONCLUSIONS: Microcuff ETTs in infants <5.0 kg in weight undergoing cardiac surgery are associated with a low incidence of severe postextubation stridor. Because cuffed ETTs allow for improved control of ventilation/oxygenation and decreased risk of aspiration, they should be considered for use in this high-risk population. Larger studies are needed to confirm these results.

Neurodevelopmental outcomes after neonatal cardiac surgery: Role of cortical isoelectric activity.

OBJECTIVES: Neonates with congenital heart disease are at risk for impaired neurodevelopment after cardiac surgery. We hypothesized that intraoperative EEG activity may provide insight into future neurodevelopmental outcomes. METHODS: Neonates requiring surgery had continuous intraoperative EEG and hemodynamic monitoring. The level of EEG suppression was classified as either: slow and continuous; moderate burst suppression; severe burst suppression; or isoelectric (no brain activity for >3 minutes). Follow-up neurodevelopmental outcomes were assessed using the Vineland Adaptive Behavior Scale II (Vineland-II). RESULTS: Twenty-one neonates requiring cardiac surgery developed a slow and continuous EEG pattern after general anesthesia. Ten neonates (48%) maintained continuous brain electrical activity with moderate burst suppression as the maximum level of EEG suppression. Eleven neonates (52%) developed severe burst suppression that progressed into an isoelectric state during the deep hypothermic period required for circulatory arrest. However, the duration of this state was significantly longer than circulatory arrest times (111.1 ± 50 vs 22.3 ± 17 minutes; P < .001). At a mean follow-up at 5.6 ± 1.0 years, compared with neonates with continuous brain electrical activity, neonates who developed an isoelectric state had lower Vineland-II scores in communication. There was an inverse relationship between composite Vineland-II scores and duration of isoelectric activity (R = -0.75, P = .01). Of neonates who experienced an isoelectric state, durations of >90 minutes were associated with the lowest Vineland-II scores (125.0 ± 2.6 vs 81.1 ± 12.7; P < .01). CONCLUSIONS: The duration of cortical isoelectric states seems related to neurodevelopmental outcomes. Strategies using continuous EEG monitoring to minimize isoelectric states may be useful during complex congenital heart surgery.

Pharmacokinetics of ε-Aminocaproic Acid in Neonates Undergoing Cardiac Surgery with Cardiopulmonary Bypass.

BACKGROUND: Antifibrinolytic medications such as ε-aminocaproic acid (EACA) are used in pediatric heart surgery to decrease surgical bleeding and transfusion. Dosing schemes for neonates are often based on adult regimens, or are simply empiric, in part due to the lack of neonatal pharmacokinetic information. The authors sought to determine the pharmacokinetics of EACA in neonates undergoing cardiac surgery and to devise a dosing regimen for this population. METHODS: Ten neonates undergoing cardiac surgery with cardiopulmonary bypass were given EACA according to standard practice, and blood was drawn at 10 time points to determine drug concentrations. Time-concentration profiles were analyzed using nonlinear mixed effects models. Parameter estimates (standardized to a 70-kg person) were used to develop a dosing regimen intended to maintain a target concentration shown to inhibit fibrinolysis in neonatal plasma (50 mg/l). RESULTS: Pharmacokinetics were described using a two-compartment model plus an additional compartment for the cardiopulmonary bypass pump. First-order elimination was described with a clearance of 5.07 l/h × (WT/70). Simulation showed a dosing regimen with a loading dose of 40 mg/kg and an infusion of 30 mg · kg · h, with a pump prime concentration of 100 mg/l maintained plasma concentrations above 50 mg/l in 90% of neonates during cardiopulmonary bypass surgery. CONCLUSIONS: EACA clearance, expressed using allometry, is reduced in neonates compared with older children and adults. Loading dose and infusion dose are approximately half those required in children and adults.

Longer RBC storage duration is associated with increased postoperative infections in pediatric cardiac surgery.

OBJECTIVES: Infants and children undergoing open heart surgery routinely require multiple RBC transfusions. Children receiving greater numbers of RBC transfusions have increased postoperative complications and mortality. Longer RBC storage age is also associated with increased morbidity and mortality in critically ill children. Whether the association of increased transfusions and worse outcomes can be ameliorated by use of fresh RBCs in pediatric cardiac surgery for congenital heart disease is unknown. INTERVENTIONS: One hundred and twenty-eight consecutively transfused children undergoing repair or palliation of congenital heart disease with cardiopulmonary bypass who were participating in a randomized trial of washed versus standard RBC transfusions were evaluated for an association of RBC storage age and clinical outcomes. To avoid confounding with dose of transfusions and timing of infection versus timing of transfusion, a subgroup analysis of patients only transfused 1-2 units on the day of surgery was performed. MEASUREMENTS AND MAIN RESULTS: Mortality was low (4.9%) with no association between RBC storage duration and survival. The postoperative infection rate was significantly higher in children receiving the oldest blood (25-38 d) compared with those receiving the freshest RBCs (7-15 d) (34% vs 7%; p = 0.004). Subgroup analysis of subjects receiving only 1-2 RBC transfusions on the day of surgery (n = 74) also demonstrates a greater prevalence of infections in subjects receiving the oldest RBC units (0/33 [0%] with 7- to 15-day storage; 1/21 [5%] with 16- to 24-day storage; and 4/20 [20%] with 25- to 38-day storage; p = 0.01). In multivariate analysis, RBC storage age and corticosteroid administration were the only predictors of postoperative infection. Washing the oldest RBCs (> 27 d) was associated with a higher infection rate and increased morbidity compared with unwashed RBCs. DISCUSSION: Longer RBC storage duration was associated with increased postoperative nosocomial infections. This association may be secondary in part, to the large doses of stored RBCs transfused, from single-donor units. Washing the oldest RBCs was associated with increased morbidity, possibly from increased destruction of older, more fragile erythrocytes incurred by washing procedures. Additional studies examining the effect of RBC storage age on postoperative infection rate in pediatric cardiac surgery are warranted.

Washing red blood cells and platelets transfused in cardiac surgery reduces postoperative inflammation and number of transfusions: results of a prospective, randomized, controlled clinical trial.

OBJECTIVES: Children undergoing cardiac surgery with cardiopulmonary bypass are susceptible to additional inflammatory and immunogenic insults from blood transfusions. We hypothesize that washing red blood cells and platelets transfused to these patients will reduce postoperative transfusion-related immune modulation and inflammation. DESIGN: Prospective, randomized, controlled clinical trial. SETTING: University hospital pediatric cardiac intensive care unit. PATIENTS: Children from birth to 17 yrs undergoing cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: Children were randomized to an unwashed or washed red blood cells and platelet transfusion protocol for their surgery and postoperative care. All blood was leuko-reduced, irradiated, and ABO identical. Plasma was obtained for laboratory analysis preoperatively, immediately, and 6 and 12 hrs after cardiopulmonary bypass. Primary outcome was the 12-hr postcardiopulmonary bypass interleukin-6-to-interleukin-10 ratio. Secondary measures were interleukin levels, C-reactive protein, and clinical outcomes. MEASUREMENTS AND MAIN RESULTS: One hundred sixty-two subjects were studied, 81 per group. Thirty-four subjects (17 per group) did not receive any blood transfusions. Storage duration of blood products was similar between groups. Among transfused subjects, the 12-hr interleukin ratio was significantly lower in the washed group (3.8 vs. 4.8; p = .04) secondary to lower interleukin-6 levels (after cardiopulmonary bypass: 65 vs.100 pg/mL, p = .06; 6 hrs: 89 vs.152 pg/mL, p = .02; 12 hrs: 84 vs.122 pg/mL, p = .09). Postoperative C-reactive protein was lower in subjects receiving washed blood (38 vs. 43 mg/L; p = .03). There was a numerical, but not statistically significant, decrease in total blood product transfusions (203 vs. 260) and mortality (2 vs. 6 deaths) in the washed group compared to the unwashed group. CONCLUSIONS: Washed blood transfusions in cardiac surgery reduced inflammatory biomarkers, number of transfusions, donor exposures, and were associated with a nonsignificant trend toward reduced mortality. A larger study powered to test for clinical outcomes is needed to determine whether these laboratory findings are clinically significant.

State-dependent laryngomalacia in sleeping children.

Laryngomalacia is a common congenital laryngeal abnormality. Despite its being widely discussed in the literature, the pathophysiology is not clearly understood. Both anatomic and neuromuscular theories have been suggested to explain laryngomalacia. We report 4 cases of laryngomalacia in which the presenting signs occurred during sleep. Awake flexible nasopharyngolaryngoscopy failed to demonstrate supraglottic structure collapse. Only while the patients were breathing spontaneously under general anesthesia was laryngomalacia noted. A proposed algorithm for diagnosis and treatment is included. These 4 cases of state-dependent laryngomalacia support a neuromuscular cause for laryngomalacia.