Ronald A. Bronicki

Dexamethasone reduces the inflammatory response to cardiopulmonary bypass in children

BACKGROUND A randomized, prospective, double-blind study of 29 children was performed to evaluate the hypothesis that dexamethasone administration prior to cardiopulmonary bypass would decrease the inflammatory mediator release and improve the postoperative clinical course. METHODS Fifteen children received dexamethasone (1 mg/kg intravenously) and 14 (controls) received saline solution 1 hour prior to CPB. Serial blood analyses for interleukin-6, tumor necrosis factor-alpha, complement component C3a, and absolute neutrophil count were performed. Postoperative variables evaluated included temperature, supplemental fluids, alveolar-arterial oxygen gradient, and days of mechanical ventilation. RESULTS Dexamethasone caused an eightfold decrease in interleukin-6 levels and a greater than threefold decrease in tumor necrosis factor-alpha levels after CPB (p < 0.05). Complement component C3a and absolute neutrophil count were not affected by dexamethasone. The mean rectal temperature for the first 24 hours postoperatively was significantly lower in the group given dexamethasone than in the controls (37.2 degrees +/- 0.4 degrees C versus 37.7 degrees +/- 4 degrees C; p = 0.007). Dexamethasone-treated patients required less supplemental fluid during the first 48 hours (22 +/- 28 mL/kg versus 47 +/- 34 mL/kg; p = 0.04). Compared with controls, dexamethasone-treated children had significantly lower alveolar-arterial oxygen gradients during the first 24 hours (144 +/- 108 mm Hg versus 214 +/- 118 mm Hg; p = 0.02) and required less mechanical ventilation (median duration, 3 days versus 5 days; p = 0.02). CONCLUSIONS Dexamethasone administration prior to CPB in children leads to a reduction in the postbypass inflammatory response as assessed by cytokine levels and clinical course.

Management of the postoperative pediatric cardiac surgical patient.

Objective:To review the salient aspects and latest advances in the management of the postoperative pediatric cardiac patient. Data Source:A Medline-based literature source. Conclusion:The practice of pediatric cardiac intensive care has evolved considerably over the last several years. These efforts are the result of a collaborative effort from all subspecialties involved in the care of pediatric patients with congenital heart disease. Discoveries and innovations that are representative of this effort include the extension of cerebral oximetry from the operating room into the critical care setting; mechanical circulatory devices designed for pediatric patients; and surgery in very low birth weight neonates. Advances such as these impact postoperative management and make the field of pediatric cardiac intensive care an exciting, demanding, and evolving discipline, necessitating the ongoing commitment of various disciplines to pursue a greater understanding of disease processes and how to best go about treating them.

Review of Inhaled Nitric Oxide in the Pediatric Cardiac Surgery Setting

Surgical intervention for congenital heart disease (CHD) can be complicated by pulmonary hypertension (PH), which increases morbidity, mortality, and medical burden. Consequently, postoperative management of PH is an important clinical consideration to improve outcomes. Inhaled nitric oxide (iNO) is a widely accepted standard of care for PH and has been studied in the context of cardiac surgery for CHD. However, large randomized, double-blind, placebo-controlled, multicenter clinical trials in pediatric patients are limited. This review will provide an overview of the clinical studies in this setting and will discuss general treatment considerations to facilitate a better understanding of the clinical use of iNO for PH after pediatric cardiac surgery.

The impact of mechanical ventilation time before initiation of extracorporeal life support on survival in pediatric respiratory failure: a review of the Extracorporeal Life Support Registry.

Objective: To evaluate the relationship between duration of mechanical ventilation before the initiation of extracorporeal life support and the survival rate in children with respiratory failure. Extracorporeal life support has been used as a rescue therapy for >30 yrs in children with severe respiratory failure. Previous studies suggest patients who received >7–10 days of mechanical ventilation were not acceptable extracorporeal life support candidates as a result of irreversible lung damage. Design: A retrospective review encompassing the past 10 yrs of the International Extracorporeal Life Support Organization Registry (January 1, 1999, to December 31, 2008). Setting: Extracorporeal Life Support Organization Registry database. Patients: A total of 1325 children (≥ 30 days and ⩽ 18 yrs) met inclusion criteria. Interventions: None. Measurements and Main Results: The following pre-extracorporeal life support variables were identified as independently and significantly related to the chance of survival: 1) >14 days of ventilation vs. 0–7 days was adverse (odds ratio, 0.32; p < .001); 2) the presence of a cardiac arrest was adverse (odds ratio, 0.56; p = .001); 3) pH per 0.1-unit increase was protective (odds ratio, 1.15; p < .001); 4) oxygenation index, per 10-unit increase was adverse (odds ratio, 0.95; p = .002); and 5) any diagnosis other than sepsis was related to a more favorable outcome. Patients requiring >7–10 or >10–14 days of pre-extracorporeal life support ventilation did not have a statistically significant decrease in survival as compared with patients who received 0–7 days. Conclusions: There was a clear relationship between the number of mechanical ventilation days before the initiation of extracorporeal life support and survival. However; there was no statistically significant decrease in survival until >14 days of pre-extracorporeal life support ventilation was reached regardless of underlying diagnosis. We found no evidence to suggest that prolonged mechanical ventilation should be considered as a contraindication to extracorporeal life support in children with respiratory failure before 14 days.

Vancomycin-associated acute kidney injury in pediatric cardiac intensive care patients.

OBJECTIVE Acute kidney injury (AKI) is a significant source of morbidity among critically ill pediatric patients, including those that have undergone cardiac surgery. Vancomycin may contribute to AKI in pediatric patients admitted to a cardiac intensive care unit. DESIGN AND SETTING Patients admitted to the cardiac intensive care unit at Texas Childrens Hospital and received vancomycin over a 4-year period were included in a case-control study. Patients were excluded if they underwent renal replacement therapy during vancomycin therapy. Patient demographic and disease state variables, vancomycin therapy variables, and use of other nephrotoxic medications were collected. The overall incidence of AKI was calculated based on doubling of serum creatinine during or within 72 hours of vancomycin therapy (vancomycin-associated AKI [vAKI]). Patients who developed vAKI were matched with three patients who did not develop vAKI, and conditional logistic regression was used to determine independent risk factors for vAKI. RESULTS A total of 418 patients met study criteria (males 57.8%) and infants (31 days to 2 years) were the most populous age group (48.6%). Vancomycin-associated AKI occurred in 30 patients (7.2%), which resulted in a total of 120 patients (30 cases; 90 controls). No significant differences were noted in vancomycin dosing between groups. Vancomycin-associated AKI patients were less likely to have undergone cardiac surgery (P < .05), more likely to have undergone extracorporeal membrane oxygenation (P < .05), and had greater exposure to nephrotoxic medications (P < .05). A conditional logistic regression model identified extracorporeal membrane oxygenation as associated with vAKI (odds ratio 14.4, 95% confidence interval 1.02-203, P = .048) and patients with prior cardiovascular surgery (odds ratio 0.10, 95% confidence interval 0.02-0.51, P < .01) or an elevated baseline serum creatinine (odds ratio 0.009, 95% confidence interval 0.0002-0.29, P < .01) as less likely to develop vAKI. CONCLUSIONS Vancomycin-associated AKI occurs infrequently in the pediatric cardiac intensive care population and is strongly associated with patient critical illness.

Venous oximetry and the assessment of oxygen transport balance.

Objective: To review the principles of venous oximetry; the physiology of oxygen transport balance; clinical studies on venous oximetry; and the assignment of a classification of recommendation and level of evidence. Data Source: A MEDLINE-based literature source. Conclusion: One of the tenets of critical care medicine is to provide a timely and accurate assessment of tissue oxygenation. In conjunction with other monitoring modalities, the routine deployment of central venous catheters readily enables the clinician to complete this task.

An overview of mechanical circulatory support in children.

Objective: For children with severe heart failure in whom medical management has failed, mechanical circulatory support in the form of either extracorporeal membrane oxygenation or ventricular assist device represents life-sustaining therapy. This review provides an overview of these two modalities, including a discussion of indications, contraindications, timing, and device selection, as part of the Pediatric Cardiac Intensive Care Society/Extracorporeal Life Support Organization Joint Statement on Mechanical Circulatory Support. Data Sources, Study Selection, Data Extraction: PubMed was searched using the following terms: ECMO, extracorporeal membrane oxygenation, ventricular assist device, VAD, and pediatric. Case reports, single-center series, multicenter studies, and registry reports were reviewed. Conclusions: The two technologies have unique advantages and disadvantages and may be considered complementary devices, although they are frequently used in sequence. Either modality may be used as bridge-to-transplant or bridge-to-recovery, and the choice of device and device timing is influenced by the acuity of illness, comorbidities, potential for recovery, and anticipated duration of support.

Current challenges in cardiac intensive care: optimal strategies for mechanical ventilation and timing of extubation.

The Congenital Heart Institute of Florida (CHIF), Divisions of Critical Care and Thoracic and Cardiovascular Surgery, All Children’s Hospital and Children’s Hospital of Tampa, University of South Florida College of Medicine, Florida Pediatric Associates and Cardiac Surgical Associates (CSA), Saint Petersburg and Tampa, Florida, United States of America; Children’s Hospital Boston, Harvard Medical School, Boston, Massachusetts, United States of America; Children’s Hospital of Orange County, Orange, California, David Geffen School of Medicine at the University of California, Los Angeles, United States of America; The Children’s Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America; Children’s Hospital of Wisconsin, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America

Cardiopulmonary Bypass-Induced Inflammatory Response: Pathophysiology and Treatment.

Objectives: The objectives of this review are to discuss the pathophysiology of the pro-inflammatory response to the cardiopulmonary bypass circuit, the impact of ischemia reperfusion injury on post-operative organ function, the compensatory anti-inflammatory response and the evidence for immune-modulatory strategies and their impact on outcomes. Data Source: MEDLINE, PubMed. Conclusion: Innovations such as the development of more biocompatible surfaces and miniaturized circuits, as well as the increasing expertise of surgeons, anesthesiologists and perfusionists has transformed cardiac surgery and the use of cardiopulmonary bypass into a relatively routine procedure with favorable outcomes. Despite these refinements, the attendant inflammatory response to bypass, ischemia reperfusion injury and the compensatory anti-inflammatory response contribute to post-operative morbidity and mortality. Additional studies are needed to further delineate the impact of immunomodulatory strategies on outcomes.

The Effects of Multiple Doses of Glucocorticoids on the Inflammatory Response to Cardiopulmonary Bypass in Children

Background: We previously demonstrated that a dose of glucocorticoids (GCs) administered prior to cardiopulmonary bypass (CPB) is effective at suppressing the inflammatory response to CPB and leads to an improved postoperative course. We evaluated whether an additional dose of GC administered eight hours prior to CPB would lead to further clinical benefit. Methods: We conducted a prospective study in which patients were randomized to receive placebo or GC eight hours prior to CPB, in addition to a dose of GC administered following induction of anesthesia. We measured serum inflammatory mediator levels and postoperative clinical parameters. Results: Thirty-one patients were included in the study. Eighteen patients received two doses of GC and 13 patients received a single does of GC. Complement C3a levels were significantly lower at 24 hours following surgery in those patients who received two doses of GC (3136 ± 1650 vs 1779 ± 1616 ng/mL, P = .04). There was no significant difference in tumor necrosis factor (TNF)-α or interleukin (IL)-6 levels at any time between groups. There was no significant difference in core body temperature or renal function (based on serum creatinine levels) between groups. There was no significant difference between groups in duration of mechanical ventilation (2.4 ± 1.5 vs 3.6 ± 3.7 days, two vs one dose, respectively, P = .33) or length of stay in the intensive care unit ([ICU]; 3.4 ± 1.4 vs 4.9 ± 3.6 days, 2 vs 1 dose, respectively, P = .15). Conclusion: While those patients who received two doses of GC prior to surgery had significantly less complement activation postoperatively, clinical outcomes did not differ between groups. We conclude that the practice of administering an additional dose of GC prior to CPB is not supported. However, a large randomized study is needed to conclusively discount the potential benefit of this strategy.