Aileen B. Sedman

Angiotensin-converting enzyme inhibitor fetopathy.

Angiotensin-converting enzyme (ACE) inhibitors are widely used for controlling hypertension. Their use in women who are pregnant is not without risk to the fetus. We describe three infants exposed in utero to ACE inhibitors who had adverse outcomes. These cases, combined with other reports in the literature, suggest strongly that these drugs are fetotoxic. ACE inhibitor fetopathy is characterized by fetal hypotension, anuria-oligohydramnios, growth restriction, pulmonary hypoplasia, renal tubular dysplasia, and hypocalvaria. Although the true frequency of adverse fetal effects has yet to be determined, because of the debilitating and lethal nature of the fetal damage when it occurs, it is our recommendation that ACE inhibitors not be used in pregnancy, particularly in the second and third trimesters.

Invited Review Recognition and management of angiotensin converting enzyme inhibitor fetopathy

Angiotensin converting enzyme (ACE) inhibitors are extensively used for the treatment of hypertension, to decrease proteinuria, and to mitigate hyperfiltration. These drugs now have been shown to be fetotoxic causing profound fetal hypotension, renal tubular dysplasia, anuria-oligohydramnios, growth restriction, hypocalvaria, and death when used in the second and third trimesters of pregnancy. We recommend that ACE inhibitors not be used in pregnancy. However, if a child is born with ACE inhibitor fetopathy, aggressive therapy with dialysis to remove the inhibitor may mitigate the profound hypotensive effects. Therapy will depend on the specific ACE inhibitor, and care recommendations cannot be generalized for the entire class of drugs as their protein binding and volume of distribution differ substantially.

Tissue and cellular basis for impaired bone formation in aluminum-related osteomalacia in the pig.

Bone formation is impaired in aluminum-associated bone disease. Reductions in the number of osteoblasts or in the function of individual osteoblasts could account for this finding. Thus, quantitative bone histology and measurements of bone formation were done at three skeletal sites in piglets given aluminum (Al) parenterally, 1.5 mg/kg per d, for 8 wk (Al, n = 4) and in control animals (C, n = 4). Bone Al was 241 +/- 40 mg/kg per dry weight in Al and 1.6 +/- 0.9 in C, P less than 0.001. All Al-treated animals developed osteomalacia with increases in osteoid seam width, osteoid volume, and mineralization lag time at each skeletal site, P less than 0.05 vs. C for all values. Mineralized bone formation at the tissue level was lower in Al than in C, P less than 0.05 for each skeletal site, due to reductions in active bone forming surface. Bone formation at the cellular level was similar in each group, however, and total osteoid production by osteoblasts did not differ in C and Al. Aluminum impairs the formation of mineralized bone in vivo by decreasing the number of active osteoblasts, and this change can be distinguished from the effect of aluminum to inhibit, either directly or indirectly, the calcification of osteoid.

Relevance of the agency for healthcare research and quality patient safety indicators for children's hospitals

Objectives. Patient safety indicators (PSIs) were developed by the Agency for Healthcare Research and Quality. Our objectives were (1) to apply these algorithms to the National Association of Childrens Hospitals and Related Institutions (NACHRI) Aggregate Case Mix Comparative Database for 1999–2002, (2) to establish mean rates for each of the PSI events in childrens hospitals, (3) to investigate the inadequacies of PSIs in relation to pediatric diagnoses, and (4) to express the data in such a way that childrens hospitals could use the PSIs determined to be appropriate for pediatric use for comparison with their own data. In addition, we wanted to use the data to set priorities for ongoing clinical investigations and to propose interventions if the indicators demonstrated preventable errors. Methods. The Agency for Healthcare Research and Quality PSI algorithms (version 2.1, revision 1) were applied to childrens hospital administrative data (1.92 million discharges) from the NACHRI Aggregate Case Mix Comparative Database for 1999–2002. Rates were measured for the following events: complications of anesthesia, death in low-mortality diagnosis-related groups (DRGs), decubitus ulcer, failure to rescue (ie, death resulting from a complication, rather than the primary diagnosis), foreign body left in during a procedure, iatrogenic pneumothorax, infection attributable to medical care (ie, infections related to surgery or device placement), postoperative hemorrhage or hematoma, postoperative pulmonary embolism or venous thrombosis, postoperative wound dehiscence, and accidental puncture/laceration. Results. Across the 4 years of data, the mean risk-adjusted rates of PSI events ranged from 0.01% (0.1 event per 1000 discharges) for a foreign body left in during a procedure to 14.0% (140 events per 1000 discharges) for failure to rescue. Review of International Classification of Diseases, Ninth Revision, Clinical Modification codes associated with each PSI category showed that the failure to rescue and death in low-mortality DRG indicators involved very complex cases and did not predict preventable events in the majority of cases. The PSI for infection attributable to medical care appeared to be accurate the majority of the time. Incident risk-adjusted rates of infections attributable to medical care averaged 0.35% (3.5 events per 1000 discharges) and varied up to fivefold from the lowest rate to the highest rate. The highest rates were up to 1.8 times the average. Conclusions. PSIs derived from administrative data are indicators of patient safety concerns and can be relevant as screening tools for childrens hospitals; however, cases identified by these indicators do not always represent preventable events. Some, such as a foreign body left in during a procedure, iatrogenic pneumothorax, infection attributable to medical care, decubitus ulcer, and venous thrombosis, seem to be appropriate for pediatric care and may be directly amenable to system changes. Evidence-based practices regarding those particular indicators that have been reported in the adult literature need to be investigated in the pediatric population. In their present form, 2 of the indicators, namely, failure to rescue and death in low-mortality DRGs, are inaccurate for the pediatric population, do not represent preventable errors in the majority of pediatric cases, and should not be used to estimate quality of care or preventable deaths in childrens hospitals. The PSIs can assist institutions in prioritizing chart review-based investigations; if clusters of validated events emerge in reviews, then improvement activities can be initiated. Large aggregate databases, such as the NACHRI Case Mix Database, can help establish mean rates of potential pediatric events, giving childrens hospitals a context within which to examine their own data.

Treatment of Henoch-Schönlein Purpura Glomerulonephritis in Children with High-Dose Corticosteroids plus Oral Cyclophosphamide

Background: Henoch-Schönlein Purpura (HSP) is a common childhood vasculitis with manifestations in numerous organ systems, including glomerulonephritis. Patients with more severe HSP-associated glomerulonephritis may develop chronic renal failure. Currently, no widely accepted treatment protocols exist for patients with significant renal involvement. Methods: We retrospectively reviewed the clinical courses of 12 children (mean age 9 years) with HSP glomerulonephritis treated with high-dose corticosteroids plus oral cyclophosphamide. All patients had nephrotic-range proteinuria, and all had significant histopathologic changes on biopsy, including crescentic nephritis in 10 patients. Treatment consisted of either intravenous pulse methylprednisolone or oral prednisone followed by oral cyclophosphamide (2 mg/kg/day) for 12 weeks, along with either daily or alternate-day oral prednisone. Prednisone was tapered following completion of cyclophsophamide. Results: Serum albumin rose significantly after treatment from 2.8 ± (SD) 0.5 to 3.7 ± 0.4 g/dl (p < 0.001), and there was a concurrent reduction in proteinuria, as reflected by decreasing serial protein-to-creatinine ratios: from 6.3 ± 4.4 to 0.8 ± 0.8 (p = 0.002). Renal function remained normal in all patients. Hypertension developed during treatment in 10 patients, all but 1 of whom were normotensive at last follow-up, 35 ± 17 months following biopsy. Conclusions: We conclude that treatment of children with HSP nephritis with high-dose corticosteroids plus oral cyclophosphamide is safe and, as in nephrotic syndrome, appears to significantly reduce proteinuria which is a known risk factor for the development of renal insufficiency in HSP. Further studies with larger numbers of patients should be conducted to confirm this finding.

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.

Evaluation of the agency for healthcare research and quality pediatric quality indicators.

OBJECTIVES. Pediatric quality indicators were developed in 2006 by the Agency for Healthcare Research and Quality to identify potentially preventable complications in hospitalized children. Our objectives for this study were to (1) apply these algorithms to an aggregate childrens hospitals discharge abstract database, (2) establish rates for each of the pediatric quality indicator events in the childrens hospitals, (3) use direct chart review to investigate the accuracy of the pediatric quality indicators, (4) calculate the number of complications that were already present on admission and, therefore, not attributable to the specific hospitalization, and (5) evaluate preventability and calculate positive predictive value for each of the indicators. In addition, we wanted to use the data to set priorities for ongoing clinical investigation. METHODS. The Agency for Healthcare Research and Quality pediatric quality indicator algorithms were applied to 76 childrens hospitals discharge abstract data (1794675 discharges) from 2003 to 2005. Rates were calculated for 11 of the pediatric quality indicators from all 3 years of discharge data: accidental puncture or laceration, decubitus ulcer, foreign body left in during a procedure, iatrogenic pneumothorax in neonates at risk, iatrogenic pneumothorax in nonneonates, postoperative hemorrhage or hematoma, postoperative respiratory failure, postoperative sepsis, postoperative wound dehiscence, selected infections caused by medical care, and transfusion reaction. Subsequently, clinicians from 28 childrens hospitals reviewed 1703 charts in which complications had been identified. They answered questions as to correctness of secondary diagnoses that were associated with the indicator, whether a complication was already present on admission, and whether that complication was preventable, nonpreventable, or uncertain. RESULTS. Across 3 years of data the rates of pediatric quality indicators ranged from a low of 0.01/1000 discharges for transfusion reaction to a high of 35/1000 for postoperative respiratory failure, with a median value of 1.85/1000 for the 11 pediatric quality indicators. Indicators were often already present on admission and ranged from 43% for infection caused by medical care to 0% for iatrogenic pneumothorax in neonates, with a median value of 16.9%. Positive predictive value for the subset of pediatric quality indicators occurring after admission was highest for decubitus ulcer (51%) and infection caused by medical care (40%). Because of the very large numbers of cases identified and its low preventability, the indicator postoperative respiratory failure is particularly problematic. The initial definition includes all children on ventilators postoperatively for >4 days with few exclusions. Being on a ventilator for 4 days would be a normal occurrence for many children with extensive surgery; therefore, the majority of the time does not indicate a complication and makes the indicator inappropriate. CONCLUSIONS. A subset of pediatric quality indicators derived from administrative data are reasonable screening tools to help hospitals prioritize chart review and subsequent improvement projects. However, in their present form, true preventability of these complications is relatively low; therefore, the indicators are not useful for public hospital comparison. Identifying which complications are present on admission versus those that occur within the hospitalization will be essential, along with adequate risk adjustment, for any valid comparison between institutions. Infection caused by medical care and decubitus ulcers are clinically important indicators once the present-on-admission status is determined. These complications cause significant morbidity in hospitalized children, and research has shown a high level of preventability. The pediatric quality indicator software can help childrens hospitals objectively review their cases and target improvement activities appropriately. The postoperative-respiratory-failure indicator does not represent a complication in the majority of cases and, therefore, should not be included for hospital screening or public comparison. Chart review should become part of the development process for quality indicators to avoid inappropriate conclusions that misdirect quality-improvement resources.

Clinical redesign using all patient refined diagnosis related groups.

Objective. Clinical redesign of processes in hospitals that care for children has been limited by a paucity of severity-adjusted indicators that are sensitive enough to identify areas of concern. This is especially true of hospitals that analyze pediatric patient care using standard Centers for Medicare and Medicaid Services (CMS) diagnosis-related groups (DRGs). The objectives of this study were to determine whether 1) utilization of all-patient refined (APR)-DRG severity-adjusted indicators (length of stay, cost per case, readmission rate) from the National Association of Childrens Hospitals and Related Institutions (NACHRI) database could identify areas for improvement at University of Michigan Mott Childrens Hospital (UMMCH) and 2) hospital staff could use the information to implement successful clinical redesign. Methods. The APR-DRG Classification System (version 20) was used with the NACHRI Case Mix Comparative Database by severity level comparison from 1999 to 2002. Indicators include average length of stay (ALOS), case mix index, cost per case, and readmission rate for low acuity asthma (APR-DRG 141.1). UMMCH cases of 141.1 (n = 511) were compared with NACHRI 141.1 (n = 64 312). Although not part of the standard report, mortality rates were calculated by NACHRI for UMMCH and an aggregate of NACHRI member childrens hospitals. Results. Data from 1999 revealed that in noncomplicated asthma cases (level 1 severity), the UMMCH ALOS versus NACHRI ALOS was slightly longer (UMMCH 2.16 days vs NACHRI 2.14 days), and the cost per case was higher (UMMCH

Aluminum toxicity in childhood

2824 vs NACHRI

Hepatic Abnormalities Associated with Aluminum Loading in Piglets

2738), whereas levels 2, 3, and 4 cases (moderate, major, and extreme severity) indicated the ALOS and cost per case were lower than the national aggregate. This showed that the APR-DRG system was sensitive enough to distinguish variances of care within a diagnosis according to severity level. After analysis of internal data and meeting with clinicians to review the indicators, 3 separate clinical processes were targeted: 1) correct documentation of comorbidities and complications, 2) standardized preprinted orders were created with the involvement of the pediatric pulmonologists, and 3) standardized automatic education for parents was started on the first day of admission. Yearly data were reviewed and appropriate adjustments made in the education of both residents and staff. In 2002, the UMMCH ALOS dropped to 1.75 ± .08 days from 2.16 ± .09. In 2002, the NACHRI ALOS was 2.00 days ± 0.01 versus the UMMCH ALOS of 1.75 days ± 0.0845, indicating that the UMMCH ALOS dropped significantly lower than the NACHRI aggregate database over the 3-year period. Cost per case of UMMCH compared with NACHRI after the 3 years indicated that UMMCH increased 12%, whereas the NACHRI aggregate increased 18%. These data show that length of stay and cost per case relative to the national database improved after clinical redesign. Improvements have been sustained throughout the 3-year period. Readmission rates ranged from 2.97% to 0.80% and were less than the national cohort by the third year. There were no mortalities in the UMMCH inpatient asthma program. This demonstrates that clinicians believed that the data from the APR-DRG acuity-adjusted system was useful and that they were then able to apply classical clinical redesign strategies to improve cost-effectiveness and quality that was sustained over 3 years. Conclusions. Severity-adjusted indicators were useful for identifying areas appropriate for clinical redesign and contributed to the improvement in cost-effective patient care without a detriment in quality indicators. This method of using a large comparative database, having measures of severity, and using internal analysis is generalizable for pediatric hospitals and can contribute to ongoing attempts to improve cost-effectiveness and quality in medical care.