Joseph R. Custer

Respiratory syncytial virus morbidity and mortality estimates in congenital heart disease patients: a recent experience.

ObjectiveTo determine recent morbidity and mortality rates from respiratory syncytial virus infection in a pediatric congenital heart disease population. DesignRetrospective cohort study design. SettingThe C. S. Mott Childrens Hospital, University of Michigan Medical Center. PatientsA total of 740 pediatric patients hospitalized at the University of Michigan Medical Center for symptomatic respiratory syncytial virus infection, of whom, 79 patients had clinically important congenital heart disease. InterventionsNone. Measurements and Main ResultsWe retrospectively examined the charts of 740 patients hospitalized at our childrens hospital from July 1, 1983 to June 30, 1990 with symptomatic respiratory syncytial virus infection to assess morbidity and mortality outcomes. Seventy-nine patients had congenital heart disease and 40 of these patients had pulmonary hypertension. For the entire cohort and a subset of patients with community-acquired infection, those patients with congenital heart disease had longer durations of hospitalization and greater need for, and days of, both intensive care and mechanical ventilation than patients without congenital heart disease. Mortality risk for respiratory syncytial virus community-acquired infection was not different for congenital heart disease vs. noncongenital heart disease patients (0.0% vs. 0.2%; p = 1.00). When examining only patients with congenital heart disease, those patients with pulmonary hypertension had increased hospital days and greater intensive care and mechanical ventilation durations compared with patients without this diagnosis. The overall mortality rate was low and was equally low for congenital heart disease groups with or without pulmonary hypertension (2.5 vs. 2.6). For community-acquired illness, no mortality was found in either congenital heart disease group. When the cohort of congenital heart disease patients was divided into pre- and postribavirin administration eras, no differences in mean hospital duration, ICU days, and mechanical ventilation days were noted. Of the 79 congenital heart disease patients, only two died during their hospitalization in which respiratory syncytial virus infection occurred. Both patients had nosocomial-acquired respiratory syncytial virus and both were from the postribavirin administration cohort. One of these two patients had received antiviral therapy. Neither death was secondary to respiratory syncytial virus respiratory failure (based on pathologic examination). ConclusionsWe conclude that respiratory syncytial virus mortality risk in pediatric patients with congenital heart disease is less than the risk reported a decade ago. Respiratory syncytial virus infection in congenital heart disease patients with pulmonary hypertension is associated with increased morbidity but not increased mortality rates. The markedly decreased respiratory syncytial virus mortality risk in patients with congenital heart disease currently experienced is likely secondary to improvements in intensive care management and advances in the surgical correction in this population rather than antiviral therapy.

Amino acid loss and nitrogen balance in critically ill children with acute renal failure: a prospective comparison between classic hemofiltration and hemofiltration with dialysis.

Hypothesis: Amino acid (AA) loss is not equivalent on continuous venovenous hemofiltration (CVVH) compared with continuous venovenous hemodiafiltration (CVVHD). Amino acid supplementation may be necessary to adjust for a greater clearance on CVVH to maintain nitrogen balance similar to that of CVVHD. Objective: To compare AA losses and nitrogen balance between CVVH and CVVHD in children with acute renal failure. Setting: Pediatric patients in the pediatric intensive care unit of a tertiary referral center. Design: Prospective randomized crossover study in consecutive children who required hemofiltration. Patients: A total of 12 plasma clearance studies for AA and urea, consisting of 24‐hr collections of ultrafiltrate and urine for nitrogen balance, was performed on six patients during CVVH and CVVHD. Patients received total parenteral nutrition (TPN) with caloric intake 20% to 30% above their resting energy expenditure measured by indirect calorimetry and 1.5 g/kg/day protein of TPN. Study conditions were comprised of 2 L/hr/1.73 m2 of dialysate or prefiltered replacement fluid and hemofilter flow rates of 4 mL/kg/min were maintained for all patients. Methods and Main Results: Amino acid clearances were greater on CVVH than CVVHD, except for glutamic acid, where clearance was 6.73 ± 2.31 (SEM) mL/min/1.73 m2 on CVVH and 7.59 ± 2.79 mL/min/1.73 m2 for CVVHD (NS). The clearance difference between the two modalities was 30%. Urea clearance was equivalent (30.1 ± 1.74 mL/min/1.73 m2 and 29.0 ± .97 mL/min/1.73 m2) for CVVH and CVVHD, respectively. Amino acid loss on CVVH and CVVHD was similar (12.50 ± 1.29 g/day/1.73 m2 vs. 11.61 ± 1.86 g/day/1.73 m2, respectively), representing 12% and 11%, respectively, of the daily protein intake. The catabolic state, as measured by urea nitrogen appearance, was high for all patients during the 48‐hr study period with a mean of 291 mg/kg/day during CVVH, and 245 mg/kg/day for CVVHD. Nitrogen balance varied from a negative 12.95 g/day/1.73 m2 to a positive 4.93 g/day/1.73 m2 on CVVH and a negative 7.69 g/day/1.73 m2 to a positive 5.50 g/day/1.73 m2 on CVVHD. Conclusions: Clearance of AA is greater on CVVH than on CVVHD, but no significant difference in AA loss was present between the two therapies. Nitrogen balance often is not met on either therapy when a standard 1.5 g/kg/day protein and a resting energy expenditure of 120% to 130% of calories is delivered by TPN.

Use of extracorporeal life support as a bridge to pediatric cardiac transplantation

BACKGROUND Extracorporeal life support (ECLS) has been used for post-cardiotomy rescue, but its use as a bridge to heart transplantation (OHT) in patients with post-surgical or end-stage ventricular failure remains controversial. METHODS Records were reviewed for patients receiving ECLS for ventricular failure from January 1991 to August 2001. Patients listed for OHT were analyzed separately. Listing for OHT requirements were improbable myocardial recovery, absence of contraindications (central nervous system damage, high pulmonary resistance, ongoing infection, etc.), and parental consent. Outcome variables included patient demographics, diagnosis, days from ECLS initiation to United Network for Organ Sharing (UNOS) listing (latency), list time, renal function, and survival to discharge. RESULTS Of 145 patients with ventricular failure who received ECLS, 21 pediatric patients were UNOS listed. Of 124 non-listed patients, 57 (46%) survived to discharge. All but 3 survivors were separated from ECLS in </=7 days. Twelve underwent OHT and 10 survived to discharge (list time, 6 days; median ECLS time, 14 days). Five had ECLS discontinued without undergoing OHT (1 later underwent OHT, 2 survived to discharge). Five experienced complications while receiving ECLS and died without undergoing OHT. Six of 9 patients who required dialysis for renal failure died. Of 11 infants listed, 4 were weaned from ECLS without undergoing OHT (2 survived to discharge), 5 had OHT (ECLS support, 4 days; 4 survived to discharge) and 2 died (ECLS support, 16 and 47 days). CONCLUSIONS (1) Extracorporeal life support can be used as a bridge to OHT (even among the infant population) for at least 2 weeks with acceptable survival and hospital discharge rates, and (2) renal insufficiency with the concomitant requirement for dialysis decreases the likelihood of survival before and after OHT.

Extracorporeal life support outcome for 128 pediatric patients with respiratory failure.

PURPOSE The aim of this study was to describe a single-center experience with pediatric extracorporeal life support (ECLS) and to determine variables predictive of outcome in pediatric patients, both before the institution of ECLS and while on support. METHODS From October 1985 to September 1998 the authors supported 128 children with severe acute hypoxemic respiratory failure(n = 121, Pao2/FIo2 ratio = 58+/-29) or acute hypercarbic respiratory failure (n = 7, Paco2 = 128+/-37), despite maximal conventional ventilation. Mode of access included venoarterial bypass (VA, n = 64), venovenous bypass (VV, n = 53), and VV to VA bypass (n = 11). The techniques used included lung rest, pulmonary physiotherapy, diuresis to dry weight using hemofiltration if needed, minimal anticoagulation, and optimal systemic oxygen delivery. RESULTS The median age was 1.4 years (range, 2 weeks to 17 years). The mean duration of ECLS was 288+/-240 hours (range, 4 to 1148 hours or 0.2 to 47.8 days). Lung compliance increased from 0.32+/-0.02 mL/cm H2O/kg to 0.59+/-0.03 mL/cm H2O/kg in survivors, but only increased from 0.34+/-0.02 mL/cm H2O/kg to 0.35+/-0.02 mL/cm H2O/kg in nonsurvivors (P<.002 comparing change between survivors and nonsurvivors). Mean body weight decreased from 9%+/-2% over dry weight to 4%+/-2% in survivors, whereas in nonsurvivors the mean body weight increased from 25%+/-5% over dry weight to 35%+/-7% (P<.001). Outcome results by diagnosis were pneumonia, 73%; acute respiratory distress syndrome, 67%; and airway support, 60%, with overall lung recovery occurring in 77%, and hospital survival in 71%. Multivariate logistic regression modelling of patients with hypoxemic respiratory failure found the only pre-ECLS variable significantly associated with outcome to be pH (P<.05). Variables during the course of ECLS significantly associated with decreased survival were the presence of creatinine greater than 3.0 (P<.01), the need for inotropes (P<.04), failure to return the patient to dry weight (P<.04), and lung compliance that did not improve significantly. (P<.01). CONCLUSIONS ECLS provides life support in severe respiratory failure in children, allowing time for injured lungs to recover. Pre-ECLS predictors, such as pH and variables during ECLS, such as presence of renal failure, improvement in compliance, return to dry weight, and the need for inotropes on ECLS, may be useful for predicting outcome.

The impact of soluble tumor necrosis factor receptor etanercept on the treatment of idiopathic pneumonia syndrome after allogeneic hematopoietic stem cell transplantation

Idiopathic pneumonia syndrome (IPS) refers to a diffuse, noninfectious, acute lung injury after hematopoietic stem cell transplantation. Historically, IPS is associated with respiratory failure and mortality rates exceeding 50%. Preclinical studies have implicated tumor necrosis factor-alpha as an important effector molecule in the development of disease. We studied the tumor necrosis factor-alpha inhibitor, etanercept, combined with corticosteroids in treating 15 patients (median age, 18 years; range, 1-60 years) with IPS. Eight of 15 patients required mechanical ventilation at therapy onset. Etanercept was administered subcutaneously at a dose of 0.4 mg/kg (maximum 25 mg) twice weekly, for a maximum of 8 doses. Therapy was well tolerated with no infectious pulmonary complications noted. Ten of 15 patients had a complete response, defined as the ability to discontinue supplemental oxygen support during study therapy. The median time to complete response was 7 days (range, 3-18 days), with a day 28 survival of 73%. IPS onset was associated with elevations of several inflammatory proteins in the bronchoalveolar lavage fluid and plasma, and response to therapy correlated with reductions in pulmonary and systemic inflammation. The combination of etanercept and corticosteroids is safe and is associated with high response rates and improved survival in patients with IPS.

Venovenous versus venoarterial extracorporeal life support for pediatric respiratory failure : Are there differences in survival and acute complications?

Objectives: To examine the Extracorporeal Life Support Organization (ELSO) registry database of infants and children with acute respiratory failure to compare outcome and complications of venovenous (VV) vs. venoarterial (VA) Extracorporeal Life Support (ECLS). Design: Retrospective cohort study. Setting: ELSO registry for pediatric pulmonary support. Patients: All nonneonatal pediatric pulmonary support ECLS cases treated at U.S. centers and reported to the ELSO registry as of July 1997. Patients were excluded if they had one or more of the following diagnoses: hematologic‐oncologic, cardiac, abdominal surgical, burn, metabolic, airway, or immunodeficiency disorder. Interventions: Venoarterial or venovenous extracorporeal life support for severe pulmonary failure. Measurements and Main Results: From 1986 to June of 1997, 763 pediatric patients met the inclusion criteria. Overall, 595 were initially managed with VA bypass, and 168 with VV bypass. The VA group was younger (mean ± SD, 26.1 ± 42.2 months for VA vs. 63.5 ± 68.7 months for VV) and smaller (11.8 ± 15.1 kg vs. 22.9 ± 23.8 kg) (p < .001). There were no differences between groups in number of days on mechanical ventilation before ECLS, number of hours on ECLS, or number of hours on mechanical ventilation post‐ECLS in survivors. Mean pH and PaCO2 values, positive end‐expiratory pressure, and mean airway pressure just before placing the patient on ECLS were also similar. VA‐treated patients had higher FIO2 requirements (p = .034), lower PaO2 (p = .047), and lower PaO2/FIO2 ratio (p = .014) just before cannulation. There was a trend of higher peak inspiratory pressure in VA‐treated patients (p = .053). Overall, survival rate was not different for the two groups (55.8% for VA vs. 60.1% for VV; p = .33). Central nervous system complications were not different between the two groups. Examination of the same variables was then conducted after dividing the patients into four subgroups. There were no significant differences in survival or complications during bypass between VV and VA modes of ECLS in any subgroup. Stepwise logistic regression modeling was performed to control for variables associated with the outcome survival for VV and VA‐treated groups, and variables measured before bypass were identified as being associated with improved survival. There was a trend of improved survival in the VV‐treated patients (p = .12). Conclusions: Overall survival of pediatric patients with acute respiratory failure supported by VA or VV ECLS was comparable. A randomized clinical trial may be useful in clarifying these observations.

Continuous venovenous hemodiafiltration in infants and children

Continuous venovenous hemodiafiltration (CVVHD) is not commonly used in pediatric intensive care units due to the lack of suitable equipment needed for this technique of renal replacement therapy (RRT). We have used an adapted hemodialysis machine that includes a blood pump controller, an air leak detector, and a venous pressure monitor over the past year in the pediatric intensive care unit. Blood lines available for hemodialysis were used for CVVHD, limiting the extracorporeal circuit volume to 38 mL, which allows for CVVHD capability in an infant as small as 4.5 kg without a blood-primed circuit. We have compared this experience to previous continuous arteriovenous hemodiafiltration (CAVHD) at our institution. The two groups (CVVHD and CAVHD) were similar in age, weight, blood pressure, and indication for RRT. There was significantly less number of hemofilters used, an improved number of hours per hemofilter, and a significantly less change of RRT modality due to ineffective dialysis (CVVHD 0% v CAVHD 32%) when using CVVHD. Furthermore, an average of 48% less heparin was used in the CVVHD population. We conclude that CVVHD can be safely and effectively carried out in infants and small children with less heparinization, no need for arterial access, and less risk of ineffective RRT.

Continuous Quality Improvement: Reducing Unplanned Extubations in a Pediatric Intensive Care Unit

Objective. Unplanned extubation (UEX) is a potentially serious complication of mechanical ventilation. Limited information is available regarding factors that contribute to UEXs and subsequent reintubation of children. We monitored UEXs in our pediatric intensive care unit (PICU) for a 5-year period to assess the incidence and patient conditions associated with UEX and to evaluate whether targeted interventions were associated with a reduced rate of UEXs. Methods. Over a 5-year period, demographic and clinical information was collected prospectively on all patients who required an artificial airway while admitted to the PICU. Additional information was collected for patients who experienced an UEX. Educational sessions and care management protocols were developed, implemented, and modified according to issues identified via the monitoring program. Results. From a total of 2192 patients who required 13 630 airway days (AWD), 141 (6%) patients experienced 164 UEXs. The overall rate of UEX for the study period was 1.2 UEXs per 100 AWD, and this rate decreased from 1.5 in the first year to 0.8 in the last year. UEXs were more common in children who were younger than 5 years (1.6 vs 0.6 UEX per 100 AWD) compared with older children. The UEX children experienced significantly longer length of mechanical ventilation (6 vs 3 days) and longer length of PICU stay (8 vs 4 days) compared with non-UEX children. Forty-six percent of the UEXs occurred in patients who were weaning from mechanical ventilation, and 22% of those patients required reintubation. Conclusions. We conclude that UEX in pediatric patients is associated with longer length of mechanical ventilation and length of stay in the PICU. A continuous quality improvement monitoring and educational program that identified high-risk patients for UEX (younger patients) and patients who were at low risk for subsequent reintubation (weaning patients) contributed to a reduction of these potentially adverse events.

Use of extracorporeal life support in patients with congenital heart disease

ObjectivesTo review a large experience with extracorporeal life support in patients with congenital heart disease. To determine the major causes of mortality and morbidity in order to improve the results of using this technology in this patient population. DesignRetrospective chart review. PatientsTwenty-five patients between the ages of 1 day and 8 yrs. These patients had congenital heart disease and were clinically felt to be at high risk for death caused by cardiac failure or by respiratory failure complicated by congenital heart disease. InterventionsAll patients in this report were placed on extracorporeal life support to allow recovery of myocardial or pulmonary function. Measurements and Main ResultsOf these 25 patients, 52% were weaned from bypass support and 40% survived to discharge. Patients who were not weaned from extracorporeal life support characteristically suffered from irreversible neurologic injury, multiple organ failure, or bleeding complications. Only one patient died of irreversible cardiac failure. ConclusionsExtracorporeal life support can be useful in supporting patients with congenital heart disease with life-threatening cardiac or pulmonary failure. Improvements in limiting neurologic and bleeding complications may lead to improvements in the use of extracorporeal life support for this indication. However, prospective, randomized studies are needed to appreciate the role of extracorporeal life support in these patients.

Extracorporeal life support for pediatric respiratory failure : predictors of survival from 220 patients

The purpose of this report was to examine the Extracorporeal Life Support Organization registry database for predictors of outcome for severe pediatric respiratory failure managed with extracorporeal life support. Design:Retrospective cohort study. Setting:Extracorporeal Life Support Organization data registry. Patients:All nonneonatal pediatric patients who were treated in the United States with extracorporeal life support for severe pediatric respiratory failure reported to the Extracorporeal Life Support Organization registry as of August 1991. Patients with congenital heart disease and congenital gastrointestinal malformations were excluded from study. Interventions:Venoarterial or venovenous extracorporeal life support for severe life-threatening pulmonary failure. Measurements and Main Results:As of August 1991, 220 pediatric patients meeting study entry criteria were reported to the Registry having received extracorporeal life support for severe pulmonary failure, since 1982. Forty-six percent (102 of 220 patients) were successfully managed with this technology and survived to hospital discharge. The mean patient age was 36.8 ± 51.6 months. Fifty-one percent of the patients were male. The mean duration of mechanical ventilation before extracorporeal life support was 6.3 ± 5.9 days. Mean blood gas and ventilatory measurements obtained before extracorporeal life support were as follows: Paco2 52 ± 23 torr (6.9 ± 3.0 kPa); Pao2 59 ± 32 torr (7.8 ± 4.3 kPa); estimated alveolar-arterial oxygen gradient 561 ± 63.4 torr (74.8 ± 8.5 kPa); peak airway pressure 49.5 ± 13.1 cm H2O; mean airway pressure 24.3 ± 8.2 cm H2O; positive end-expiratory pressure 11.8 ± 6.3 cm H2O; ventilator rate 58 ± 64.4 breaths/min; and FIO2 0.98 ± 0.07. The mean duration of extracorporeal life support for all patients was 247 ± 164 hrs. For the 102 survivors, the mean time for decannulation from extracorporeal life support to extubation from mechanical ventilation was 6.5 ± 7.6 days. Step-wise multivariate logistic regression modeling found the following variables to be associated with patient survival: a) patient age, b) days of mechanical ventilation before extracorporeal life support, c) peak inspiratory pressure, d) alveolar-arterial oxygen gradient, and e) extracorporeal life support administered since December 31, 1988 (all p < .05). Conclusions:Extracorporeal life support may represent an effective rescue therapy for some selected pediatric patients with severe respiratory failure for whom conventional mechanical ventilation support has failed to improve. Predictors of survival for this life-support therapy exist that may be helpful for individual patient prognostication and future prospective study. (Crit Care Med 1993; 21:1604–1611)