Lee P. Ferguson

Relationship Between Arterial Partial Oxygen Pressure After Resuscitation From Cardiac Arrest and Mortality in Children

Background— Observational studies in adults have shown a worse outcome associated with hyperoxia after resuscitation from cardiac arrest. Extrapolating from adult data, current pediatric resuscitation guidelines recommend avoiding hyperoxia. We investigated the relationship between arterial partial oxygen pressure and survival in patients admitted to the pediatric intensive care unit (PICU) after cardiac arrest. Methods and Results— We conducted a retrospective cohort study using the Pediatric Intensive Care Audit Network (PICANet) database between 2003 and 2010 (n=122 521). Patients aged <16 years with documented cardiac arrest preceding PICU admission and arterial blood gas analysis taken within 1 hour of PICU admission were included. The primary outcome measure was death within the PICU. The relationship between postarrest oxygen status and outcome was modeled with logistic regression, with nonlinearities explored via multivariable fractional polynomials. Covariates included age, sex, ethnicity, congenital heart disease, out-of-hospital arrest, year, Pediatric Index of Mortality-2 (PIM2) mortality risk, and organ supportive therapies. Of 1875 patients, 735 (39%) died in PICU. Based on the first arterial gas, 207 patients (11%) had hyperoxia (PaO2 ≥300 mm Hg) and 448 (24%) had hypoxia (PaO2 <60 mm Hg). We found a significant nonlinear relationship between PaO2 and PICU mortality. After covariate adjustment, risk of death increased sharply with increasing hypoxia (odds ratio, 1.92; 95% confidence interval, 1.80–2.21 at PaO2 of 23 mm Hg). There was also an association with increasing hyperoxia, although not as dramatic as that for hypoxia (odds ratio, 1.25; 95% confidence interval, 1.17–1.37 at 600 mm Hg). We observed an increasing mortality risk with advancing age, which was more pronounced in the presence of congenital heart disease. Conclusions— Both severe hypoxia and, to a lesser extent, hyperoxia are associated with an increased risk of death after PICU admission after cardiac arrest.

Relationship between Arterial Partial Oxygen Pressure Following Resuscitation from Cardiac Arrest and Mortality in Children

Background— Observational studies in adults have shown a worse outcome associated with hyperoxia after resuscitation from cardiac arrest. Extrapolating from adult data, current pediatric resuscitation guidelines recommend avoiding hyperoxia. We investigated the relationship between arterial partial oxygen pressure and survival in patients admitted to the pediatric intensive care unit (PICU) after cardiac arrest. Methods and Results— We conducted a retrospective cohort study using the Pediatric Intensive Care Audit Network (PICANet) database between 2003 and 2010 (n=122 521). Patients aged <16 years with documented cardiac arrest preceding PICU admission and arterial blood gas analysis taken within 1 hour of PICU admission were included. The primary outcome measure was death within the PICU. The relationship between postarrest oxygen status and outcome was modeled with logistic regression, with nonlinearities explored via multivariable fractional polynomials. Covariates included age, sex, ethnicity, congenital heart disease, out-of-hospital arrest, year, Pediatric Index of Mortality-2 (PIM2) mortality risk, and organ supportive therapies. Of 1875 patients, 735 (39%) died in PICU. Based on the first arterial gas, 207 patients (11%) had hyperoxia (PaO2 ≥300 mm Hg) and 448 (24%) had hypoxia (PaO2 <60 mm Hg). We found a significant nonlinear relationship between PaO2 and PICU mortality. After covariate adjustment, risk of death increased sharply with increasing hypoxia (odds ratio, 1.92; 95% confidence interval, 1.80–2.21 at PaO2 of 23 mm Hg). There was also an association with increasing hyperoxia, although not as dramatic as that for hypoxia (odds ratio, 1.25; 95% confidence interval, 1.17–1.37 at 600 mm Hg). We observed an increasing mortality risk with advancing age, which was more pronounced in the presence of congenital heart disease. Conclusions— Both severe hypoxia and, to a lesser extent, hyperoxia are associated with an increased risk of death after PICU admission after cardiac arrest.

Mechanical cardiac support in children with congenital heart disease with intention to bridge to heart transplantation

OBJECTIVES A significant number of children affected by congenital heart disease (CHD) develop heart failure early or late after surgery, and heart transplantation (OHTx) remains the last treatment option. Due to shortage of donor organs in paediatric group, mechanical circulatory support (MCS) is now routinely applied as bridging strategy to increase survival on the waiting list for OTHx. We sought to assess the impact of MCS as intention to bridge to OHTx in patients with CHD less than 16 years of age. METHODS From 1998 to 2013, 106 patients received 113 episodes of MCS with paracorporeal devices as intention to bridge to OHTx. Twenty-nine had CHD, 15 (52%) with two-ventricle (Group A) and 14 (48%) with single-ventricle physiology (Group B). In Group A, 5 children had venoarterial extracorporeal membrane oxygenation (VA ECMO), 6 left ventricular assist device (LVAD), 2 biventricular assist device (BIVAD), 1 VA ECMO followed by BIVAD and 1 BIVAD followed by VA ECMO. In Group B, VA ECMO was used in 7 children, univentricular assist device (UVAD) changed to VA ECMO in 4, UVAD in 2 and surgical conversion to two-ventricles physiology with BIVAD support changed to VA ECMO in 1. RESULTS Twenty-one of 29 (72%) children survived to recovery/OHTx. Seven of 29 (59%) survived to discharge. In Group A, 11/15 (73%) survived to recovery/OHTx and 9/15 (60%) survived to discharge. Four of 15 (27%) died awaiting OHTx. One child had graft failure requiring VA ECMO and was bridged successfully to retransplantation. One child dying after OHTx had acute rejection, was supported with VA ECMO and then BIVAD but did not recover. One patient had an unsuccessful second run on BIVAD 1 year after recovery from VA ECMO. In Group B, 10/14 (71%) survived to recovery/OHTx and 8/14 (57%) survived to discharge. Four of 14 (29%) died awaiting OHTx. Of deaths after OHTx, 1 occurred intraoperatively and 1 was consequent to graft failure and had an unsuccessful second run with VA ECMO. CONCLUSIONS Children with CHD can be successfully bridged with MCS to heart transplantation. Single-ventricle circulation compared with biventricular physiology does not increase the risk of death before transplant or before hospital discharge.

The temporal relationship between glucose-corrected serum sodium and neurological status in severe diabetic ketoacidosis

Objective Cerebral oedema is a potentially devastating complication of diabetic ketoacidosis (DKA). The relationship between osmolar changes, acid–base changes and development of cerebral oedema during therapy is unclear. Design Retrospective cohort study on 53 children with severe DKA (mean pH at presentation 6.92±0.08). Cerebral oedema was diagnosed using neurological status, response to osmotherapy, and neuroimaging, and classified as: early (occurring ≤1 h after presentation, n=15), late (1–48 h, n=17) or absent (controls, n=21). The temporal profiles for various osmolar and acid–base profiles were examined using a random coefficients fractional polynomial mixed model, adjusted for known risk factors. Results The three groups could not be differentiated by demographic, osmolar or acid–base variables at presentation. All osmolar and acid–base variables showed non-linear temporal trajectories. Children who developed late onset oedema showed dramatically different temporal profiles for effective osmolality and glucose-corrected serum sodium (both p<0.001). Glucose-corrected sodium provided better qualitative discrimination, in that it typically fell in children who developed late oedema and rose in controls. The maximum between-group difference for both variables approximated the median time of clinical cerebral oedema onset. Blood glucose and acid–base temporal profiles did not differ between the groups. Late onset oedema patients received more fluid in the first 4 h, but this did not influence the osmolar or glucose-corrected sodium trajectories in a predictable fashion. Conclusions Glucose-corrected serum sodium may prove a useful early warning for the development of cerebral oedema in DKA.

A spontaneous breathing trial with pressure support overestimates readiness for extubation in children

Objective: To evaluate the performance of an extubation readiness test based on a spontaneous breathing trial using pressure support. Design: Retrospective chart review. Setting: Pediatric intensive care unit. Patients: All infants and children admitted to the pediatric intensive care unit requiring intubation from July 2007 to December 2008 were eligible for this study. Interventions: Routine use of an extubation readiness test using pressure support set according to endotracheal tube size to determine completion of weaning and readiness for extubation. Measurements and Main Results: A total of 755 extubation readiness tests were performed in 538 patients with a pass rate of 83%. Of 500 children who passed the extubation readiness test and were extubated without planned noninvasive ventilation use, the extubation failure rate was 11.2% (5.8% required reintubation). Extubation failure was defined as need for noninvasive ventilation or reintubation within 24 hrs of planned extubation. Logistic regression analysis revealed a significant association between duration of mechanical ventilation and extubation failure. Children ventilated for over 48 hrs had an 18.5% failure rate despite passing an extubation readiness test before extubation and the extubation readiness test was not a significant predictor of extubation success. Most extubation failures were the result of inadequate gas exchange attributable to lower respiratory tract dysfunction. Conclusions: A spontaneous breathing trial using pressure support set at higher levels for smaller endotracheal tubes overestimates readiness for extubation in children and contributes to a higher failed extubation rate. The objective data obtained during an extubation readiness test may help to identify patients who will benefit from extubation to noninvasive ventilation.

Outcome of mechanical cardiac support in children using more than one modality as a bridge to heart transplantation

OBJECTIVES Mechanical cardiac support (MCS) can successfully be applied as a bridging strategy for heart transplantation (OHTx) in children with life-threatening heart failure. Emergent use of MCS is often required before establishing the likelihood of OHTx. This can require bridge-to-bridge strategies to increase survival on the waiting list. We compared the outcome of children with heart failure who underwent single MCS with those who required multiple MCS as a bridge to OHTx. METHODS A retrospective study of patients aged less than 16 years was conducted. From March 1998 to October 2005, we used either a veno-arterial extracorporeal membrane oxygenator (VA-ECMO), or the Medos® para-corporeal ventricular assist device (VAD). From November 2005 onwards, the Berlin Heart EXCOR® (BHE) device was implanted in the majority of cases. Several combinations of bridge-to-bridge strategies have been used: VA-ECMO and then conversion to BHE; BHE and then conversion to VA-ECMO; left VAD and then upgraded to biventricular support (BIVAD); conversion from pulsatile to continuous-flow pumps. RESULTS A total of 92 patients received MCS with the intent to bridge to OHTx, including 21 (23%) supported with more than one modality. The mean age and weight at support was similar in both groups, but multimodality MCS was used more often in infancy (P = 0.008) and in children less than 10 kg in weight (P = 0.02). The mean duration of support was longer in the multiple MCS group: 40 ± 48 vs 84 ± 43 days (P = 0.0003). Usage of multimodality MCS in dilated cardiomyopathy (19%) and in other diagnoses (29%) was comparable. Incidence of major morbidity (haematological sequelae, cerebrovascular events and sepsis) was similar in both groups. Survival to OHTx/explantation of the device (recovery) and survival to discharge did not differ between single MCS and multiple MCS groups (78 vs 81% and 72 vs 76%, respectively). CONCLUSION Bridge to OHTx with multiple MCS does not seem to influence the outcome in our population. Infancy and body weight less than 10 kg do not tend to produce higher mortality in the multiple MCS group. However, children receiving more than one modality are supported for longer durations.

Comparison of paracorporeal and continuous flow ventricular assist devices in children: preliminary results

Objectives With the scarcity of organs, a durable, reliable ventricular assist device (VAD) is required. The Berlin Heart EXCOR ® (BH) remains the most established VAD in the paediatric population. Implantable continuous flow (CF) VADs have been introduced to the paediatric field with encouraging early results. In this study, we compared the results of a newly introduced CF VAD (HeartWare VAD [HVAD] ® ) to results in a matched group of BH recipients. Methods The study included patients aged <16 years who received mechanical left VAD (LVAD) support between December 2005 and January 2016. The preimplant characteristics and postimplant outcomes of patients who received the HVAD were compared with those of a matched group who received the BH. Patients with congenital heart disease were excluded. Results Thirty patients were included in the study: 13 had received the HVAD and were matched with 17 patients who had received the BH LVAD. The only difference in preimplant characteristics was the need for higher inotropic support in the BH group. There was no difference in the need for right ventricular (RV) support (58.8% for BH vs 53.8% for HVAD, P  = 1.00) or in the incidence of cerebrovascular accidents (12.5% vs 7.7%, respectively, P  = 1.00), though the BH group showed prolonged mechanical ventilation (31.3% vs 0%, P  = 0.047). There were no deaths while on VAD support in either group. Patients with the HVAD showed a bimodal distribution for the primary end point (transplant/explant): All HVAD recipients who also required early RV support reached this end point within 30 days of receiving the implant. Conclusions Our early experience with the CF intracorporeal LVAD system (HVAD) indicates outcomes comparable to those with the well-established pulsatile flow paracorporeal LVAD (BH). The theoretical durability of the CF device, which might also allow for the possibility of hospital discharge and better quality of life, is yet to be proven.

Life-Threatening Organ Failure After Lamotrigine Therapy

We describe an 11-year-old girl with a seizure disorder who developed fever, rash, rhabdomyolysis, and multiorgan failure 2 weeks after commencing a transition from sodium valproate to lamotrigine therapy. To our knowledge, this patient represents the most severe life-threatening hypersensitivity lamotrigine reaction described in the pediatric literature. We recommend caution when prescribing lamotrigine to children on concomitant sodium valproate, and immediate discontinuation of lamotrigine and the provision of aggressive supportive care in patients with features of lamotrigine hypersensitivity.

Atrial arrhythmia after transcatheter closure of secundum atrial septal defects in patients ≥40 years of age

Aim Data on arrhythmia outcome following device closure of atrial septal defect (ASD) are lacking. This study provides medium-term follow-up data on atrial arrhythmias in patients who were ≥40 years of age at the time of transcatheter ASD closure. Methods and results It is a retrospective review. Mean age of the 159 patients was 57 years. Median follow-up was 3.6 years (range 6 months-10.9 years). Patients were classified, according to arrhythmia status prior to ASD closure, into Group I, no history of atrial arrhythmia (n = 119, mean age 55.5 years); Group II, paroxysmal atrial arrhythmia (n = 18, mean age 55.7 years); and Group III, persistent atrial fibrillation (n = 22, mean age 65.7 years). Group III patients were significantly older, had larger left atrial size, and had higher mean pulmonary arterial pressure than Group I and II patients (P < 0.001). Prior to closure, radiofrequency ablation was carried out in 12/18 (66%) of Group II and 3/22 (14%) of Group III. After device closure, 7 patients (6%) of Group I developed new atrial fibrillation. Fifty per cent (9/18) of Group II but only 9% (2/22) of Group III were in sinus rhythm on follow-up. Conclusion Device closure alone in patients with persistent atrial arrhythmia is not likely to restore sinus rhythm in the medium term. New atrial arrhythmia occurred in 6% of patients who were in sinus rhythm prior to device closure. At least 50% of the patients with paroxysmal atrial arrhythmia continue to have significant atrial arrhythmia following device closure, and the role of ablation prior to closure in patients with a history of arrhythmia requires refinement.

The Use of Daptomycin to Treat Methicillin-Resistant Staphylococcus Epidermidis Bacteremia in a Critically Ill Child with Renal Failure

Daptomycin is excreted primarily unchanged by the kidney. Dosage regimens in children with renal failure remain to be determined. We report the case of an 8-year-old child with multiorgan failure undergoing continuous peritoneal dialysis, successfully treated with intravenous daptomycin for methicillin-resistant Staphylococcus epidermidis bacteremia. A dosage of 8 mg/kg every 48 hour was used. Plasma peak and trough concentrations of daptomycin were 68 mg/L and 14.6 mg/L, respectively, on day 6 of treatment. The dosage regimen achieved daptomycin exposure comparable to that reported in adults undergoing continuous ambulatory peritoneal dialysis and receiving recommended dosages.