Christian Stocker

Mechanisms of a reduced cardiac output and the effects of milrinone and levosimendan in a model of infant cardiopulmonary bypass

Objectives: A low cardiac output state is an important cause of morbidity after pediatric cardiopulmonary bypass. The objectives of our study were to define the early precipitants of the reduced cardiac output and to investigate the effects on these of milrinone and levosimendan in a model of pediatric cardiopulmonary bypass. Design: Experimental study. Setting: Research laboratory at a university‐affiliated, tertiary pediatric center. Subjects: Eighteen piglets. Interventions: Piglets, instrumented with systemic, pulmonary arterial, and coronary sinus catheters, pulmonary and circumflex arterial flow probes, and a left ventricular conductance‐micromanometer‐tipped catheter, underwent cardiopulmonary bypass with aortic cross‐clamp and cardioplegic arrest. At 120 mins, they were assigned to control, milrinone, or levosimendan groups and studied for a further 120 mins. Measurements and Main Results: In controls, between 120 and 240 mins, cardiac output decreased by 15%. Systemic vascular resistance was unchanged, but pulmonary vascular resistance increased by 19%. Systemic arterial elastance increased by 17%, indicating increased afterload. End‐systolic elastance was unchanged, and coronary sinus oxygen tension decreased by 4.0 ± 1.7 mm Hg. In animals receiving milrinone cardiac output was preserved, and in animals receiving levosimendan cardiac output increased by 14%. Both drugs prevented an increase in arterial elastance and pulmonary vascular resistance after cardiopulmonary bypass. Systemic vascular resistance decreased by 31% after levosimendan, and end‐systolic elastance increased by 48%, indicating improved contractility. Both agents prevented a decrease in coronary sinus oxygen tension. Conclusions: Increased afterload, which is not matched by an equivalent elevation in contractility, contributes to the reduced cardiac output early after pediatric cardiopulmonary bypass in this model. This increase is prevented by milrinone and levosimendan. Both agents exert additional beneficial effects on pulmonary vascular resistance and myocardial oxygen balance, although levosimendan has greater inotropic properties.

Recent developments in the perioperative management of the paediatric cardiac patient.

Purpose of review Survival of infants born with complex cardiac anomalies has dramatically improved, and the growing population of patients with congenital heart disease reaching adulthood has resulted in an increased incidence of long-term complications related to the perioperative period. This review focuses on recent advances in strategies to prevent, detect, treat, or predict early and late complications arising from open heart surgery for congenital heart disease. Recent findings Aprotinine and recombinant factor VIIa may effectively reduce the risk of excessive perioperative bleeding, and the use of steroids, complement component C4A, heparin-coated circuits, and modified ultrafiltration may play a role in the control of the postoperative inflammatory response. Milrinone is becoming increasingly popular in the prevention and treatment of the reduced postoperative cardiac output, and extracorporeal life support has become a well established and successful form of support for postoperative myocardial dysfunction, even in the functionally univentricular heart. In recent years interest increased in optimizing myocardial protection using contents-differentiated and temperature-differentiated blood cardioplegia and in optimizing cerebral protection using a higher haematocrit during bypass and by using selective regional perfusion in favour of circulatory arrest. Summary Hearts can be mended, but salvation of hearts and brains needs further rigorous attention.

The influence of bypass temperature on the systemic inflammatory response and organ injury after pediatric open surgery: A randomized trial

OBJECTIVE Systemic cooling for cardiopulmonary bypass is widely used to attenuate the systemic inflammatory response syndrome and organ injury in children after open surgery. We compared the effects of moderate (24 °C) and mild (34 °C) hypothermia during bypass on markers of the systemic inflammatory response syndrome and organ injury, and on clinical outcome after corrective surgery for congenital heart disease. METHODS Sixty-six children (mean age, 6.8 ± 5.7 months; mean weight, 6.2 ± 2.3 kg) were randomized to 24 °C or 34 °C bypass temperature during cardiac surgery. Perfusion strategies were otherwise strictly identical. Clinical data and blood samples were collected before bypass, 5 minutes after aortic crossclamp release, and 4, 24, and 48 hours after bypass. Patients were followed up until discharge from the hospital. RESULTS In the 54 children with outcome data, bypass temperature did not influence the duration of mechanical ventilation between the 24 °C group and the 34 °C group (median [interquartile range] 22 [13-40] hours vs 14 [8-40] hours, P = .14), intensive care unit stay (43 [24-49] hours vs 29 [23-47] hours, P = .79), blood loss (29 [20-38] mL/kg vs 23 [13-38] mL/kg, P = .36), or incidence of postoperative infection (9% vs 11%, P = 1.0). There was no evidence of an influence of bypass temperature on the markers of acute inflammation, innate immune response, organ injury, coagulation, or hemodynamics. CONCLUSIONS There is no evidence that the systemic inflammatory response syndrome and organ injury after pediatric open surgery are influenced by bypass temperature. The routine use of hypothermic bypass may not be warranted in the pediatric population.

The effect of induction of anesthesia and intubation on end-expiratory lung level and regional ventilation distribution in cardiac children.

Background:  During the induction of anesthesia, changes in functional residual capacity and ventilation distribution (VD) occur. Although these physiological changes are well investigated in adults, little data are available in infants and children.

Measurement of ventilation and cardiac related impedance changes with electrical impedance tomography

IntroductionElectrical impedance tomography (EIT) has been shown to be able to distinguish both ventilation and perfusion. With adequate filtering the regional distributions of both ventilation and perfusion and their relationships could be analysed. Several methods of separation have been suggested previously, including breath holding, electrocardiograph (ECG) gating and frequency filtering. Many of these methods require interventions inappropriate in a clinical setting. This study therefore aims to extend a previously reported frequency filtering technique to a spontaneously breathing cohort and assess the regional distributions of ventilation and perfusion and their relationship.MethodsTen healthy adults were measured during a breath hold and while spontaneously breathing in supine, prone, left and right lateral positions. EIT data were analysed with and without filtering at the respiratory and heart rate. Profiles of ventilation, perfusion and ventilation/perfusion related impedance change were generated and regions of ventilation and pulmonary perfusion were identified and compared.ResultsAnalysis of the filtration technique demonstrated its ability to separate the ventilation and cardiac related impedance signals without negative impact. It was, therefore, deemed suitable for use in this spontaneously breathing cohort.Regional distributions of ventilation, perfusion and the combined ΔZV/ΔZQ were calculated along the gravity axis and anatomically in each position. Along the gravity axis, gravity dependence was seen only in the lateral positions in ventilation distribution, with the dependent lung being better ventilated regardless of position. This gravity dependence was not seen in perfusion.When looking anatomically, differences were only apparent in the lateral positions. The lateral position ventilation distributions showed a difference in the left lung, with the right lung maintaining a similar distribution in both lateral positions. This is likely caused by more pronounced anatomical changes in the left lung when changing positions.ConclusionsThe modified filtration technique was demonstrated to be effective in separating the ventilation and perfusion signals in spontaneously breathing subjects. Gravity dependence was seen only in ventilation distribution in the left lung in lateral positions, suggesting gravity based shifts in anatomical structures. Gravity dependence was not seen in any perfusion distributions.

Urotensin II is raised in children with congenital heart disease

Urotensin II (U-II) is a vasoactive peptide that has been highly conserved throughout evolution. U-II has been described as the most potent vasoconstrictor yet identified.1 The identification in humans of immune reactive U-II in plasma, the U-II receptor, and U-II expression in the myocardium, arterial system, and kidney and the elevation of U-II in important disease states such as hypertension and congestive heart failure suggest that U-II may be an important mediator in the regulation of cardiovascular function.1–4 U-II has never been investigated in children with congenital heart disease (CHD) and in those undergoing cardiac surgery requiring cardiopulmonary bypass (CPB). The objective of this study was twofold. Firstly, we compared plasma U-II in children with CHD with concentrations in healthy children; and secondly, we examined the 24 hour profile of U-II in children undergoing open heart surgery. Forty children undergoing surgery for CHD were recruited, of whom 20 had low or normal preoperative pulmonary blood flow (LNF group; undergoing valve repairs, relief of outflow tract obstruction, tetralogy of Fallot repair, Fontan operations, and arterial switch operation) and 20 had high preoperative pulmonary blood flow (HF group; undergoing closure of septal defects). In the HF patients, preoperative angiotensin converting enzyme inhibitors were being taken by five children, diuretics by seven, and digoxin by one child. Seventeen of the children with CHD underwent modified ultrafiltration (MUF) after CPB, according to institutional protocols. Twenty children without cardiopulmonary or renal disease who were undergoing day case surgical procedures were also recruited for the study (controls). In controls, a single blood sample was taken after induction of anaesthesia. In …

Anticoagulation strategies and difficulties in neonatal and paediatric extracorporeal membrane oxygenation (ECMO).

Objective: The aim of this review is to highlight an emerging problem with anticoagulation-related complications in neonatal and paediatric ECMO, to explore for flaws in the currently recommended anticoagulation management responsible for these problems and to discuss possible strategies mitigating further escalation of the issue. Data Sources: Pertinent neonatal and paediatric literature on the topic of interest and international Extracorporeal Life Support Organisation (ELSO) registry data request. Conclusions: The international ELSO registry data reveals increasing rates of anticoagulation-related complications during neonatal and paediatric ECMO worldwide. The causes are multifactorial and the proposed solution to the problem is to match anticoagulation management to the pathophysiological complexity of haemostasis on ECMO.

Enteroviral myocarditis in neonates.

Enteroviruses are a leading cause of viral infections in children. While most enteroviral infections are mild and self‐limiting, severe disease such as a viral sepsis syndrome, myocarditis, hepatitis and meningoencephalitis may occur. We present two cases of neonatal enteroviral myocarditis. Cardiorespiratory failure occurred in both cases, and severe shock refractory to conventional treatment required support with extracorporeal membrane oxygenation (ECMO). One child with coxsackievirus B3 myocarditis failed to recover and died after 3 weeks on ECMO, while one child could be decannulated successfully after 9 days of ECMO and recovered completely subsequently. In conclusion, neonatal myocarditis has a very high mortality, and ECMO should be considered early in neonates with rapid clinical and echocardiographic deterioration despite adequate inotropic support.

Controversies of prophylactic hypothermia and the emerging use of brain tissue oxygen tension monitoring and decompressive craniectomy in traumatic brain-injured children

BACKGROUND Despite being the leading cause of death and disability in the paediatric population, traumatic brain injury (TBI) in this group is largely understudied. Clinical practice within the paediatric intensive care unit (PICU) has been based upon adult guidelines however children are significantly different in terms of mechanism, pathophysiology and consequence of injury. AIM To review TBI management in the PICU and gain insight into potential management strategies. METHOD To conduct this review, a literature search was conducted using MEDLINE, PUBMED and The Cochrane Library using the following key words; traumatic brain injury; paediatric; hypothermia. There were no date restrictions applied to ensure that past studies, whose principles remain current were not excluded. RESULTS Three areas were identified from the literature search and will be discussed against current acknowledged treatment strategies: Prophylactic hypothermia, brain tissue oxygen tension monitoring and decompressive craniectomy. CONCLUSION Previous literature has failed to fully address paediatric specific management protocols and we therefore have little evidence-based guidance. This review has shown that there is an emerging and ongoing trend towards paediatric specific TBI research in particular the area of moderate prophylactic hypothermia (MPH).

Ventilation and cardiac related impedance changes in children undergoing corrective open heart surgery

Electrical impedance tomography (EIT) can determine ventilation and perfusion relationship. Most of the data obtained so far originates from experimental settings and in healthy subjects. The aim of this study was to demonstrate that EIT measures the perioperative changes in pulmonary blood flow after repair of a ventricular septum defect in children with haemodynamic relevant septal defects undergoing open heart surgery. In a 19 bed intensive care unit in a tertiary childrens hospital ventilation and cardiac related impedance changes were measured using EIT before and after surgery in 18 spontaneously breathing patients. The EIT signals were either filtered for ventilation (ΔZV) or for cardiac (ΔZQ) related impedance changes. Impedance signals were then normalized (normΔZV, normΔZQ) for calculation of the global and regional impedance related ventilation perfusion relationship (normΔZV/normΔZQ). We observed a trend towards increased normΔZV in all lung regions, a significantly decreased normΔZQ in the global and anterior, but not the posterior lung region. The normΔZV/normΔZQ was significantly increased in the global and anterior lung region. Our study qualitatively validates our previously published modified EIT filtration technique in the clinical setting of young children with significant left-to-right shunt undergoing corrective open heart surgery, where perioperative assessment of the ventilation perfusion relation is of high clinical relevance.