Pitfalls of adverse event reporting in paediatric cardiac intensive care.

AIMS: To evaluate the pitfalls of incident reporting in a complex medical environment. METHODS: Retrospective review of 211 incident reports in a paediatric cardiac intensive care unit (CICU). Two adverse event reporting databases were compared: database A (DA), the hospital's official reporting system, is non-anonymous and reports are predominantly made by nurses; database B (DB) is anonymous and reports are submitted by a CICU consultant who collects data from daily ward rounds. Both databases classify adverse events into incident type (drug errors, ventilation, cannulae/indwelling lines, chest drains, blood transfusion, equipment, operational) and severity (0 = no, 1 = minor, 2 = major, 3 = life threatening consequences). RESULTS: Between 1 April 1998 and 31 July 2001 there were 211 adverse events involving 178 patients (11.87%), among 1500 patients admitted to CICU. A total of 112 incidents were reported in DA, 143 in DB, and 44 in both. In isolation, both databases gave an unrepresentative picture of the true frequency and severity of adverse events. Under-reporting was especially notable for less severe events (grade 0, or near misses) CONCLUSION: Incident reporting in the medical field is highly variable, and is heavily influenced by profession of the reporters as well as anonymity. When adverse event reporting is based predominantly on the observations of a single professional group, the data are grossly inaccurate.

Predicting outcome in ex-premature infants supported with extracorporeal membrane oxygenation for acute hypoxic respiratory failure.

OBJECTIVE: To identify predictors of outcome in ex-premature infants supported with extracorporeal membrane oxygenation (ECMO) for acute hypoxic respiratory failure. METHODS: Retrospective review of ex-premature infants with acquired acute hypoxic respiratory failure requiring ECMO support in the United Kingdom from 1992 to 2001. Review of follow up questionnaires completed by general practitioners and local paediatricians. RESULTS: Sixty four ex-premature infants (5-10 each year) received ECMO support, despite increased use of advanced conventional treatments over the decade. The most common infective agent was respiratory syncytial virus (85% of cases). Median birth gestation was 29 weeks and median corrected age at the time of ECMO support was 42 weeks. Median ECMO support duration was relatively long, at 229 hours. Survival to hospital discharge and to 6 months was 80%, remaining similar throughout the period of review. At follow up, 60% had long term neurodisability and 79% had chronic pulmonary problems. Of pre-ECMO factors, baseline oxygen dependence, younger age, and inpatient status were associated with non-survival (p < or = 0.05). Of ECMO related factors, patient complications were independently associated with adverse neurodevelopmental outcome and death (p < 0.01). CONCLUSIONS: Survival rates for ex-premature infants after ECMO support are favourable, but patients suffer a high burden of morbidity during intensive care and over the long term. At the time of ECMO referral, baseline oxygen dependence is the most important predictor of death, but no combination of the factors considered was associated with a mortality that would preclude ECMO support.

Cardiac ECMO for biventricular hearts after paediatric open heart surgery.

OBJECTIVE: To delineate predictors of hospital survival in a large series of children with biventricular physiology supported with extracorporeal membrane oxygenation (ECMO) after open heart surgery. RESULTS: 81 children were placed on ECMO after open heart surgery. 58% (47 of 81) were transferred directly from cardiopulmonary bypass to ECMO. Hospital survival was 49% (40 of 81) but there were seven late deaths among these survivors (18%). Factors that improved the odds of survival were initiation of ECMO in theatre (64% survival (30 of 47)) rather than the cardiac intensive care unit (29% survival (10 of 34)) and initiation of ECMO for reactive pulmonary hypertension. Important adverse factors for hospital survival were serious mechanical ECMO circuit problems, renal support, residual lesions, and duration of ECMO. CONCLUSIONS: Hospital survival of children with biventricular physiology who require cardiac ECMO is similar to that found in series that include univentricular hearts, suggesting that successful cardiac ECMO is critically dependent on the identification of hearts with reversible ventricular dysfunction. In our experience of postoperative cardiac ECMO, the higher survival of patients cannulated in the operating room than in the cardiac intensive care unit is due to early effective support preventing prolonged hypoperfusion and the avoidance of a catastrophic cardiac arrest.

Near-fatal grape aspiration with complicating acute lung injury successfully treated with extracorporeal membrane oxygenation.

OBJECTIVE: In this report of a near-fatal case of grape aspiration successfully treated with extracorporeal membrane oxygenation (ECMO), we highlight the danger of feeding seedless grapes to young children and demonstrate that ECMO can provide cardiopulmonary support for cases of acquired large-airway disruption and can facilitate therapeutic intervention. DESIGN: Case report. SETTING: A tertiary pediatric intensive care unit and ECMO center. PATIENT: A healthy 14-month-old boy aspirated a seedless grape while playing at home and suffered a cardiopulmonary arrest of 15 mins in duration. He responded to advanced life support with return of cardiac output but developed intractable cardiopulmonary failure secondary to aspirated grape particles and postobstructive pulmonary edema. INTERVENTIONS: The patient was emergently transferred to the regional ECMO center and placed on venoarterial ECMO. Bronchoscopies were performed in the stable environment provided by ECMO, aspirated particles were removed from the large airways, and lung recovery was facilitated. MEASUREMENTS AND MAIN RESULTS: End-organ perfusion was restored via ECMO during a period of severe intractable cardiopulmonary failure. Pulmonary recovery occurred during a 6-day ECMO run and was facilitated by therapeutic bronchoscopy. The patient was reviewed 1 yr later and has made a full neurodevelopmental recovery, despite a 15-min out-of-hospital cardiac arrest. CONCLUSIONS: Aspiration of a seedless grape is a life-threatening event in a small child. This danger is not fully appreciated by parents in the UK. ECMO may be life saving in cases of acquired large-airway disruption resulting in severe cardiopulmonary failure, including foreign body aspiration, as long as end-organ perfusion is maintained.

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.

Sulindac sulfide, but not sulindac sulfone, inhibits colorectal cancer growth.

Sulindac sulfide, a metabolite of the nonsteroidal antiinflammatory drug (NSAID) sulindac sulfoxide, is effective at reducing tumor burden in both familial adenomatous polyposis patients and in animals with colorectal cancer. Another sulindac sulfoxide metabolite, sulindac sulfone, has been reported to have antitumor properties without inhibiting cyclooxygenase activity. Here we report the effect of sulindac sulfone treatment on the growth of colorectal carcinoma cells. We observed that sulindac sulfide or sulfone treatment of HCA-7 cells led to inhibition of prostaglandin E2 production. Both sulindac sulfide and sulfone inhibited HCA-7 and HCT-116 cell growth in vitro. Sulindac sulfone had no effect on the growth of either HCA-7 or HCT-116 xenografts, whereas the sulfide derivative inhibited HCA-7 growth in vivo. Both sulindac sulfide and sulfone inhibited colon carcinoma cell growth and prostaglandin production in vitro, but sulindac sulfone had no effect on the growth of colon cancer cell xenografts in nude mice.

Meloxicam inhibits the growth of colorectal cancer cells.

Cyclooxygenase-2 has been reported to play an important role in colorectal carcinogenesis. The effects of meloxicam (a COX-2 inhibitor) on the growth of two colon cancer cell lines that express COX-2 (HCA-7 and Moser-S) and a COX-2 negative cell line (HCT-116) were evaluated. The growth rate of these cells was measured following treatment with meloxicam. HCA-7 and Moser-S colony size were significantly reduced following treatment with meloxicam; however, there was no significant change in HCT-116 colony size with treatment. In vivo studies were performed to evaluate the effect of meloxicam on the growth of HCA-7 cells when xenografted into nude mice. We observed a 51% reduction in tumor size after 4 weeks of treatment. Analysis of COX-1 and COX-2 protein levels in HCA-7 tumor lysates revealed a slight decrease in COX-2 expression levels in tumors taken from mice treated with meloxicam and no detectable COX-1 expression. Here we report that meloxicam significantly inhibited HCA-7 colony and tumor growth but had no effect on the growth of the COX-2 negative HCT-116 cells.

Carotid artery pseudoaneurysm as a complication of ECMO.

Any pulsatile neck mass after extracorporeal membrane oxygenation (ECMO) must be viewed as a pseudoaneurysm of the carotid artery until proven otherwise. Prompt diagnosis is necessary utilizing ultrasound. Angiography may not be necessary. Carotid artery pseudoaneurysm requires urgent surgical intervention to prevent catastrophic hemorrhage. The utilization of cardiopulmonary bypass may facilitate safe repair.

Early response to inhaled nitric oxide and its relationship to outcome in children with severe hypoxemic respiratory failure.

OBJECTIVE: To examine whether the early response to inhaled nitric oxide (iNO) is a measure of reversibility of lung injury and patient outcome in children with acute hypoxemic respiratory failure (AHRF). DESIGN: Retrospective review study. SETTING: Pediatric ICUs. PATIENTS: Thirty infants and children, aged 1 month to 13 years (median, 7 months) with severe AHRF (mean alveolar arterial oxygen gradient of 568+/-9.3 mm Hg, PaO2/fraction of inspired oxygen of 56+/-2.3, oxygenation index [OI] of 41+/-3.8, and acute lung injury score of 2.8+/-0.1). Eighteen patients had ARDS. INTERVENTIONS: The magnitude of the early response to iNO was quantified as the percentage change in OI occurring within 60 min of initiating 20 ppm iNO therapy. This response was compared to patient outcome data. MEASUREMENTS AND RESULTS: There was a significant association between early response to iNO and patient outcome (Kendall tau B r=0.43, p < 0.02). All six patients who showed < 15% improvement in OI died; 4 of the 11 patients (36%) who had a 15 to 30% improvement in OI survived, while 8 of 13 (61%) who had a > 30% improvement in OI survived. Overall, 12 patients (40%) survived, 9 with ongoing conventional treatment including iNO, and 3 with extracorporeal support. CONCLUSIONS: In AHRF in children, greater early response to iNO appears to be associated with improved outcome. This may reflect reversibility of pulmonary pathophysiologic condition and serve as a bedside marker of disease stage.

Extracorporeal support for intractable cardiorespiratory failure due to meningococcal disease.

BACKGROUND: Meningococcal disease is still associated with considerable mortality, despite the use of early antibiotics and management in specialised intensive care units, due principally to early refractory myocardial depression and hypotension as well as severe acute respiratory distress syndrome. Extracorporeal membrane oxygenation (ECMO) is a complex technology that uses a modified "heart-lung" machine to provide temporary cardiac and respiratory support. We reviewed the UK and Australian experience of the use of ECMO in patients with refractory cardiorespiratory failure due to meningococcal disease. METHODS: The records from all 12 known patients supported with ECMO for meningococcal disease in the UK and Australia since 1989 were reviewed. FINDINGS: 12 patients (aged 4 months to 18 years, median 26 months) with meningococcal disease received ECMO over 8 years. In seven patients, ECMO was required early for cardiac support for intractable shock within 36 h of admission to intensive care. In the other five patients, ECMO was indicated for respiratory failure due to severe adult respiratory distress syndrome, which tended to occur later in the disease. The paediatric risk of mortality score ranged from 13 to 40 (median 29, median predicted risk of mortality 72%). Six of the 12 patients required cardiopulmonary resuscitation before ECMO and the other six were deteriorating despite maximal conventional therapy. Overall, eight of the 12 patients survived, with six leading functionally normal lives at a median of 1 year (range 4 months to 4 years) of follow-up. INTERPRETATION: ECMO might be considered to support patients with intractable cardiorespiratory failure due to meningococcal disease who are not responding to conventional treatment.

Pharmacological control of pulmonary blood flow with inhaled nitric oxide after the fenestrated Fontan operation.

BACKGROUND: A transient increase in pulmonary vascular resistance can result in hemodynamic compromise after a Fontan operation. An interatrial fenestration is designed to maintain cardiac output in these circumstances but may result in severe hypoxemia and a vicious circle due to hypoxemia induced pulmonary vasoconstriction. Our aim was to determine whether inhaled nitric oxide (iNO), a selective pulmonary vasodilator, could be used to reduce pulmonary vascular resistance in desaturated patients (SaO2 < or = 85%) after a fenestrated Fontan operation. METHODS AND RESULTS: Responses to iNO (20 ppm for 15 min) were assessed in 10 consecutive children with SaO2 < or = 85% and compared with 5 with SaO2 > 85% after a fenestrated Fontan operation. Exposure to iNO resulted in a significant increase in SaO2 (from 64 +/- 5% to 82 +/- 2%, P < .01) and reduction in transpulmonary gradient (TPG) (from 12.2 +/- 1 [SEM] to 9.6 +/- 1.1, P < .01) in patients with baseline SaO2 < or = 85%. Baseline saturation was a predictor of response to iNO, with a greater response in those with lower saturations (r = -.86, P < .01). In contrast, no significant effects were noted in PaO2 or TPG (from 122 +/- 46 mm Hg and 8 +/- 1.8 to 123 +/- 43 mm Hg and 7 +/- 1.2, respectively) in patients with baseline SaO2 > 85%. CONCLUSIONS: iNO improved both oxygenation and TPG in desaturated patients after the fenestrated Fontan operation, possibly by counteracting hypoxemia-induced pulmonary vasoconstriction. A trial of iNO should be considered in clinically unstable desaturated patients after the fenestrated Fontan operation.

Four patterns of response to inhaled nitric oxide for persistent pulmonary hypertension of the newborn.

OBJECTIVE: To determine the clinical role of inhaled nitric oxide (iNO) in the treatment of persistent pulmonary hypertension of the newborn (PPHN). STUDY DESIGN: Prospective open observational clinical study. SETTING: A regional cardiac and pediatric intensive care unit. METHODS: Twenty-five consecutive near-term neonates (> 35 weeks gestation) with severe PPHN (oxygenation index [OI] > 25) were given a trial of iNO of 20 ppm for 20 minutes. Neonates who showed a greater than 20% improvement in PaO2 as well as a decrease in the OI to below 40 were defined as responders and continued on this therapy. RESULTS: Four patterns of response emerged to the iNO therapy: Pattern 1 neonates (n = 2) did not respond to the initial trial of iNO-one survived. Pattern 2 neonates (n = 9) responded to the initial trial of iNO, but failed to sustain this response over 36 hours, as defined by a rise in the OI to > 40. Six survived, five with extracorporeal membrane oxygenation. Pattern 3 neonates (n = 11) responded to the initial trial of iNO, sustained this response, and were successfully weaned from iNO within 5 days--all survived to discharge. Pattern 4 neonates (n = 3) responded to the initial trial of iNO, but developed a sustained dependence on iNO for 3 to 6 weeks. All three died and lung histology revealed severe pulmonary hypoplasia and dysplasia. These neonates (pattern 4) not only required iNO for a longer period of time than did the sustained responders (pattern 3), but they required significantly higher doses of iNO during their first 5 days of iNO therapy. CONCLUSIONS: Early responses to iNO may not be sustained. Neonates with pulmonary hypoplasia and dysplasia may have a decreased sensitivity and differing time course of response to iNO when compared with patients who have PPHN in fully developed lungs.

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.

Extracorporeal membrane oxygenation as a bridge to definitive tracheal surgery in children.

Extracorporeal membrane oxygenation was used as a bridge for three infants with complicated long segment congenital tracheal stenosis to tracheal homograft transplantation with cadaveric tracheal homograft and for one child, with an extensive traumatic tracheal laceration caused by aspiration of a sharp foreign body, to definitive tracheal repair. In all four cases mechanical ventilation was impossible and death almost certain without extracorporeal membrane oxygenation.

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.