Allan Goldman

Early postoperative monocyte deactivation predicts systemic inflammation and prolonged stay in pediatric cardiac intensive care

ObjectiveSepsis and systemic inflammatory response syndrome (SIRS) are major causes of morbidity and mortality after cardiopulmonary bypass. Attempts to suppress proinflammatory mediators have failed to improve outcomes in sepsis or in patients undergoing cardiopulmonary bypass. Recent work in adult patients has suggested that the balance between pro- and anti-inflammatory mediators is more important than the level of proinflammatory response alone. This balance may be reflected by the expression of monocyte human lymphocyte antigen (HLA)-DR, with low concentrations indicating an excess of anti-inflammatory stimuli and relative immunodeficiency. We investigated the relationship between monocyte HLA-DR expression and the subsequent development of sepsis/SIRS in children undergoing cardiopulmonary bypass. DesignA prospective, observational, clinical study. SettingA tertiary pediatric cardiac center. PatientsEighty-two infants and children undergoing elective cardiac surgery between March and December 1999. Measurements and Main ResultsMonocyte HLA-DR expression was assessed before and after surgery and was found to be related to the length of hospital stay and the development of complications including sepsis/SIRS. The inflammatory insult of cardiopulmonary bypass decreased monocyte HLA-DR expression in all children. Lowest concentrations were seen within 72 hrs of surgery and were significantly lower in cases that subsequently required prolonged intensive care support (p < .0001, Mann-Whitney). HLA-DR expression on <60% of circulating monocytes was associated with a greatly increased risk of later (minimum 4 days) development of sepsis/SIRS (odds ratio, 12.9; 95% confidence interval, 3.4–47.5). Low HLA-DR was an independent predictor for the development of sepsis/SIRS after correction for age, bypass time, complexity of surgery, Paediatric Index of Mortality, and surgeon on multiple logistic regression analysis. ConclusionsPatients with decreased HLA-DR in the early postoperative period represent a subpopulation at greatly increased risk of later sepsis/SIRS. Such patients may benefit from strategies aimed to reduce this risk.

The waiting game: bridging to paediatric heart transplantation

BACKGROUND Although mechanical circulatory support might not increase the number of adults surviving to transplantation, because of the shortage of donor organs, the situation might be different for children. Our aim was to assess the effect of mechanical assist devices to bridge children with end-stage cardiomyopathy to heart transplantation. METHODS A 5-year retrospective review was undertaken with data from the UK paediatric transplant programme and from bridging to transplant done at two paediatric transplant centres in the UK. FINDINGS Between Jan 1, 1998 and Dec 31, 2002, 22 children with end-stage cardiomyopathy, median age 5.7 years (range 1.2-17), were supported by a mechanical assist device as a bridge to first heart transplantation, with a 77% survival rate to hospital discharge. Nine were supported by a paracorporeal ventricular assist device, six received transplantation, five survived to discharge (55%), with one late death. 13 were supported by extra-corporeal membrane oxygenation, and 12 were transplanted and survived to discharge (92%) with one late death. With urgent listing, the median waiting time for a heart was 7.5 days (range 1.5-22 days). The correlation between the proportion of patients bridged to transplantation and the proportion of patients dying while on the transplant waiting list was r=-0.93, p=0.02. INTERPRETATION Our findings lend support to the hypothesis that a national mechanical assist programme to bridge children to transplantation can minimise the number dying while on the heart transplant waiting list. In the context of urgent listing and a short waiting time, extra-corporeal membrane oxygenation seems to provide the safest form of support.

Impact of junctional ectopic tachycardia on postoperative morbidity following repair of congenital heart defects

OBJECTIVE To determine the incidence of postoperative junctional ectopic tachycardia (JET), we reviewed 343 consecutive patients undergoing surgery between 1997 and 1999. The impact of this arrhythmia on in-hospital morbidity and our protocol for treatment were assessed. METHODS We reviewed the postoperative course of patients undergoing surgery for ventricular septal defect (VSD; n=161), tetralogy of Fallot (TOF; n=114), atrioventricular septal defect (AVSD; n=58) and common arterial trunk (n=10). All patients with JET received treatment, in a stepwise manner, beginning with surface cooling, continuous intravenous amiodarone, and/or atrial pacing if the haemodynamics proved unstable. A linear regression model assessed the effect of these treatments upon hours of mechanical ventilation, and stay on the cardiac intensive care unit (CICU). RESULTS Overall mortality was 2.9% (n=10), with three of these patients having JET and TOF. JET occurred in 37 patients (10.8%), most frequently after TOF repair (21.9%), followed by AVSD (10.3%), VSD (3.7%), and with no occurrence after repair of common arterial trunk. Mean ventilation time increased from 83 to 187 h amongst patients without and with JET patients (P<0.0001). Accordingly, CICU stay increased from 107 to 210 h when JET occurred (P<0.0001). Surface cooling was associated with a prolongation of ventilation and CICU stay, by 74 and 81 h, respectively (P<0.02; P<0.02). Amiodarone prolonged ventilation and CICU stay, respectively, by 274 and 275 h (P<0.05; P<0.06). CONCLUSIONS Postoperative JET adds considerably to morbidity after congenital cardiac surgery, and is particularly frequent after TOF repair. Aggressive treatment with cooling and/or amiodarone is mandatory, but correlates with increased mechanical ventilation time and CICU stay. Better understanding of the mechanism underlying JET is required to achieve prevention, faster arrhythmic conversion, and reduction of associated in-hospital morbidity.

Inhaled nitric oxide therapy in neonates and children: reaching a European consensus

Inhaled nitric oxide (iNO) was first used in neonatal practice in 1992 and has subsequently been used extensively in the management of neonates and children with cardiorespiratory failure. This paper assesses evidence for the use of iNO in this population as presented to a consensus meeting jointly organised by the European Society of Paediatric and Neonatal Intensive Care, the European Society of Paediatric Research and the European Society of Neonatology. Consensus Guidelines on the Use of iNO in Neonates and Children were produced following discussion of the evidence at the consensus meeting.

Impact of Rapid Leukodepletion on the Outcome of Severe Clinical Pertussis in Young Infants

OBJECTIVES: Bordetella pertussis is a common, underrecognized, and vaccine-preventable cause of critical illness with a high mortality in infants worldwide. Patients with severe cases present with extreme leukocytosis and develop refractory hypoxemia and pulmonary hypertension that is unresponsive to maximal intensive care. This may reflect a hyperviscosity syndrome from the raised white blood cell (WBC) count. Case reports suggest improved outcomes with exchange transfusion to reduce the WBC count. Our objective was to quantify possible benefits of aggressive leukodepletion. METHODS: We, as a regional PICU and extracorporeal membrane oxygenation referral center, adopted a strategy of aggressive leukodepletion in January 2005. The impact of this strategy on crude and case mix–adjusted survival of all infants who were critically ill with B pertussis were compared with control subjects from January 2001 to December 2004 and Extracorporeal Life Support Organisation registry data. RESULTS: Nineteen infants (7 [37%] boys) received intensive care for B pertussis from 2001 to 2009. Admission WBC counts were equivalent in 2 time periods: 2001–2004 (mean: 52 000/μL) and 2005–2009 (mean: 75 000/μL). In 2001–2004, 5 (55%) of 9 patients survived the ICU. Between 2005 and 2009, 9 (90%) of 10 patients survived. When case-mix adjustment for age, WBC count, and extracorporeal membrane oxygenation referral were considered, the 2001–2004 predicted survival (4.4 [49%] of 9.0) was equivalent to the observed mortality (4.0 [44%] of 9.0). Between 2005 and 2009, observed mortality (1.0 [10%] of 10.0) was significantly better than predicted (4.7 [47%] of 10.0). CONCLUSIONS: Leukodepletion should be considered in critically ill infants with B pertussis and leukocytosis.

Interleukin-10 and its role in clinical immunoparalysis following pediatric cardiac surgery

Objective:A systemic insult is associated with subsequent hyporesponsiveness to endotoxin (as measured by ex vivo tumor necrosis factor [TNF]-&agr; production) and an increased risk of late nosocomial infection in some patients. When combined with low monocyte surface major histocompatibility complex class II expression, this state of altered host defense is now commonly referred to as immunoparalysis. This study was undertaken to delineate the relationship between observed levels of the anti-inflammatory cytokine interleukin-10, common genetic polymorphisms that influence these levels, and the occurrence and severity of endotoxin hyporesponsiveness in children following elective cardiac surgery requiring cardiopulmonary bypass. Design:A prospective observational clinical study. Setting:A tertiary pediatric cardiac center. Patients:Thirty-six infants and children <2 yrs of age undergoing elective cardiac surgery requiring cardiopulmonary bypass. Interventions:None. Measurements and main results:We investigated the production of TNF-&agr;, interleukin-6, interleukin-8, interleukin-1 receptor antagonist, and interleukin-10 in whole blood in response to lipopolysaccharide (Neisseria meningitides 10 ng/mL) in samples drawn before, during, and up to 48 hrs after surgery. Patients were genotyped for the −1082, −819, and −592 interleukin-10 promoter polymorphisms. Whole blood cytokine response to lipopolysaccharide was reduced postoperatively to ≤50% of preoperative levels for all cytokines measured. Stimulated cytokine production was lowest in cases with the highest postoperative plasma interleukin-10 levels, which were in turn associated with the GCC haplotype. Those patients in whom the whole blood response to endotoxin was maintained (TNF-&agr; >100 pg/mL) over the first 48 hrs were more likely to have an uncomplicated short stay (odds ratio 4.7, 95% confidence interval 1–22). Conclusions:Immediately following cardiac surgery, many children become relatively refractory to lipopolysaccharide stimulation. This immunoparalysis appears to be related in part to high circulating levels of interleukin-10 and places these patients at increased risk of postoperative complications. Interleukin-10 genotype may be a risk factor for immunoparalysis.

Recombinant factor VII for severe bleeding during extracorporeal membrane oxygenation following open heart surgery.

Objectives: Severe bleeding is a recognized complication during mechanical cardiopulmonary support with extracorporeal membrane oxygenation. We present the use of recombinant activated factor VII (rFVIIa) for severe, refractory bleeding during extracorporeal membrane oxygenation support after open-heart surgery for congenital heart disease. Design: Retrospective review of all patients receiving rFVIIa on extracorporeal membrane oxygenation. Setting: A pediatric extracorporeal membrane oxygenation center located within the cardiac intensive care unit of a tertiary care children’s hospital. Patients: Four patients treated with rFVIIa for refractory bleeding on extracorporeal membrane oxygenation. Interventions: The patients received rFVIIa for severe, refractory blood loss despite applying clotting products and aprotinin infusion and excluding surgical reasons. Measurements and Main Results: rFVIIa was given 4–7 hrs after commencing extracorporeal membrane oxygenation; a second identical dose was administered 4 hrs later. Bleeding decreased significantly in all patients within 30 mins after the first dose of rFVIIa; no side effects were observed. Conclusions: rFVIIa is effective to achieve control of refractory hemorrhage in patients on extracorporeal membrane oxygenation. Now a randomized controlled trial to evaluate risks and benefits of rFVIIa on patients undergoing extracorporeal membrane oxygenation is required.

NITRIC-OXIDE IS SUPERIOR TO PROSTACYCLIN FOR PULMONARY-HYPERTENSION AFTER CARDIAC OPERATIONS

BACKGROUND Severe pulmonary hypertension is still a cause of morbidity and mortality in children after cardiac operations. The objective of this study was to compare the vasodilator properties of inhaled nitric oxide, a novel pulmonary vasodilator, and intravenous prostacyclin in the treatment of severe postoperative pulmonary hypertension. METHODS Thirteen children (aged 3 days to 12 months) with severe pulmonary hypertension after cardiac operations were given inhaled nitric oxide (20 ppm x 10 minutes) and intravenous prostacyclin (20 ng.kg-1.min-1 x 10 minutes) in a prospective, randomized cross-over study. RESULTS Both nitric oxide and prostacyclin resulted in a reduction in pulmonary arterial pressure, although the mean pulmonary arterial pressure was significantly lower during nitric oxide therapy (28.5 +/- 2.9 mm Hg) than during prostacyclin therapy (35.4 +/- 2.1 mm Hg; p < 0.05). The mean pulmonary to systemic arterial pressure ratio was also significantly lower during nitric oxide than prostacylin administration (0.46 +/- 0.04 versus 0.68 +/- 0.05; p < 0.01), due mainly to only prostacyclin lowering systemic blood pressure. CONCLUSIONS Inhaled nitric oxide was a more effective and selective pulmonary vasodilator than prostacyclin and should be considered as the preferred treatment for severe postoperative pulmonary hypertension.

Nitric oxide might reduce the need for extracorporeal support in children with critical postoperative pulmonary hypertension.

BACKGROUND Postoperative pulmonary hypertension is a life-threatening, yet reversible complication of congenital heart operations. Although inhaled nitric oxide (iNO), a selective pulmonary vasodilator, has been shown extensively to improve short-term oxygenation and hemodynamic indices in these patients, its influence on patient outcome has not been evaluated. The purpose of this study was to assess retrospectively whether patients who fulfilled our criteria for extracorporeal life support (ECLS) for critical postoperative pulmonary hypertension still required ECLS after the administration of iNO therapy. METHODS Since January 1992, 10 patients (age 3 days to 10 months) fulfilled the criteria at our institution for ECLS for postoperative pulmonary hypertension. Of these, 5 could not be separated from cardiopulmonary bypass because of pulmonary hypertension, and 5 had critical pulmonary hypertension (pulmonary arterial pressure approaching systemic arterial pressure) causing severe cardiopulmonary compromise. RESULTS Six of the 10 ECLS candidates had a sustained response to iNO and survived to discharge from the hospital, without the need for rescue ECLS. Three patients still required ECLS after 30 minutes, 4 hours, and 8 hours of beginning iNO because of failing cardiac output, and 2 survived. The remaining patient died after 5 days of iNO therapy, but was no longer a candidate for ECLS because of sepsis and multiorgan system failure. CONCLUSIONS Children with critical pulmonary hypertension unresponsive to maximal conventional treatment may be managed successfully with iNO without the need for rescue ECLS. A trial of iNO should therefore be given before the use of ECLS in these patients.

Patient handovers within the hospital: translating knowledge from motor racing to healthcare

Introduction This paper expands the analogy between motor racing team pit stops and patient handovers. Previous studies demonstrated how the handover of patients following surgery could be improved by learning from a motor racing team. This has been extended to include contributions from several motor racing teams, and by examining transfers at several different interfaces at a non-specialist UK teaching hospital. Methods Letters of invitation were sent to the technical managers of nine Formula 1 motor racing teams. Semistructured interviews were carried out at a UK teaching hospital with 10 clinical staff involved in the handover of patients from surgery to recovery and intensive care. Results Three themes emerged from the motor racing responses; (1) proactive learning with briefings and checklists to prevent errors; (2) active management using technology to transfer information, and (3) post hoc learning from the storage and analysis of electronic data records. The eight healthcare themes were: historical working practice; problems during transfer; poor awareness of handover protocols; poor team coordination; time pressure; lack of consistency in handover practice; poor communication of important information; and awareness that handover was a potential threat to patient safety. Conclusions The lessons from motor racing can be applied to healthcare for proactive planning, active management and post hoc learning. Other high-risk industries see standardisation of working practices, interpersonal communication, consistency and continuous development as fundamental for success. The application of these concepts would result in improvements in the quality and safety of the patient handover process.