Richard E. McClead

Severity of Neonatal Retinopathy of Prematurity Is Predictive of Neurodevelopmental Functional Outcome at Age 5.5 Years

Objective. The purpose of this study was to assess the relation between neonatal retinopathy of prematurity (ROP) in very low birth weight infants and neurodevelopmental function at age 5.5 years. Methods. Longitudinal follow-up of children occurred in 2 cohorts of the Multicenter Cryotherapy for Retinopathy of Prematurity Study. The extended natural history cohort followed 1199 survivors of <1251 g birth weight from 5 centers. The threshold randomized cohort (ThRz) followed 255 infants <1251 g from 23 centers who developed threshold ROP and who consented to cryotherapy to not more than 1 eye. At 5.5 years both cohorts had ophthalmic and acuity testing and neurodevelopmental functional status determined with the Functional Independence Measure for Children (WeeFIM). Results. Evaluations were completed on 88.7% of the extended natural history cohort; 87% had globally normal functional skills (WeeFIM: >95). As ROP severity increased, rates of severe disability increased from 3.7% among those with no ROP, to 19.7% of those with threshold ROP. Multiple logistic regression analysis demonstrated that better functional status was associated with favorable visual acuity, favorable 2-year neurological score, absence of threshold ROP, having private health insurance, and black race. Evaluations were completed on 87.4% of the ThRz children. In each functional domain, the 134 children with favorable acuity in their better eye had fewer disabilities than did the 82 children with unfavorable acuity: self-care disability 25.4% versus 76.8%, continency disability 4.5% versus 50.0%, motor disability 5.2% versus 42.7%, and communicative-social cognitive disability 22.4% versus 65.9%, respectively. Conclusion. Severity of neonatal ROP seems to be a marker for functional disability at age 5.5 years among very low birth weight survivors. High rates of functional limitations in multiple domains occur in children who had threshold ROP, particularly if they have unfavorable visual acuity.

Pediatric severe sepsis in U.S. children's hospitals.

Objectives: To compare the prevalence, resource utilization, and mortality for pediatric severe sepsis identified using two established identification strategies. Design: Observational cohort study from 2004 to 2012. Setting: Forty-four pediatric hospitals contributing data to the Pediatric Health Information Systems database. Patients: Children 18 years old or younger. Measurements and Main Results: We identified patients with severe sepsis or septic shock by using two International Classification of Diseases, 9th edition, Clinical Modification–based coding strategies: 1) combinations of International Classification of Diseases, 9th edition, Clinical Modification codes for infection plus organ dysfunction (combination code cohort); 2) International Classification of Diseases, 9th edition, Clinical Modification codes for severe sepsis and septic shock (sepsis code cohort). Outcomes included prevalence of severe sepsis, as well as hospital and ICU length of stay, and mortality. Outcomes were compared between the two cohorts examining aggregate differences over the study period and trends over time. The combination code cohort identified 176,124 hospitalizations (3.1% of all hospitalizations), whereas the sepsis code cohort identified 25,236 hospitalizations (0.45%), a seven-fold difference. Between 2004 and 2012, the prevalence of sepsis increased from 3.7% to 4.4% using the combination code cohort and from 0.4% to 0.7% using the sepsis code cohort (p < 0.001 for trend in each cohort). Length of stay (hospital and ICU) and costs decreased in both cohorts over the study period (p < 0.001). Overall, hospital mortality was higher in the sepsis code cohort than the combination code cohort (21.2% [95% CI, 20.7–21.8] vs 8.2% [95% CI, 8.0–8.3]). Over the 9-year study period, there was an absolute reduction in mortality of 10.9% (p < 0.001) in the sepsis code cohort and 3.8% (p < 0.001) in the combination code cohort. Conclusions: Prevalence of pediatric severe sepsis increased in the studied U.S. children’s hospitals over the past 9 years, whereas resource utilization and mortality decreased. Epidemiologic estimates of pediatric severe sepsis varied up to seven-fold depending on the strategy used for case ascertainment.

A multicenter cohort study of treatments and hospital outcomes in neonatal abstinence syndrome.

OBJECTIVES: To compare pharmacologic treatment strategies for neonatal abstinence syndrome (NAS) with respect to total duration of opioid treatment and length of inpatient hospital stay. METHODS: We conducted a cohort analysis of late preterm and term neonates who received inpatient pharmacologic treatment of NAS at one of 20 hospitals throughout 6 Ohio regions from January 2012 through July 2013. Physicians managed NAS using 1 of 6 regionally based strategies. RESULTS: Among 547 pharmacologically treated infants, we documented 417 infants managed using an established NAS weaning protocol and 130 patients managed without protocol-driven weaning. Regardless of the treatment opioid chosen, when we accounted for hospital variation, infants receiving protocol-based weans experienced a significantly shorter duration of opioid treatment (17.7 vs 32.1 days, P < .0001) and shorter hospital stay (22.7 vs 32.1 days, P = .004). Among infants receiving protocol-based weaning, there was no difference in the duration of opioid treatment or length of stay when we compared those treated with morphine with those treated with methadone. Additionally, infants treated with phenobarbital were treated with the drug for a longer duration among those following a morphine-based compared with methadone-based weaning protocol. (P ≤ .002). CONCLUSIONS: Use of a stringent protocol to treat NAS, regardless of the initial opioid chosen, reduces the duration of opioid exposure and length of hospital stay. Because the major driver of cost is length of hospitalization, the implications for a reduction in cost of care for NAS management could be substantial.

Dopamine pharmacokinetics in critically ill newborn infants.

SummaryDopamine is frequently used in critically ill newborn infants for treatment of shock and cardiac failure, but its pharmacokinetics has not been evaluated using a specific analytical method. Steady-state arterial plasma concentrations of dopamine were measured in 11 seriously ill infants receiving dopamine infusion, 5–20 μg · kg−1 · min−1, for presumed or proven sepsis and hypotensive shock.Steady-state concentrations of dopamine ranged from 0.013–0.3 μg/ml. Total body clearance averaged 115 ml · kg−1 · min−1. The apparent volume of distribution and elimination half life averaged 1.8 1 · kg−1 and 6.9 min, respectively.No relationship was observed between dopamine pharmacokinetics and gestational age, postnatal age or birthweight. Substantial interindividual variation was seen in dopamine pharmacokinetics in seriously ill infants, and plasma concentrations could not be predicted accurately from its infusion rate.Marked variation in clearance explains in part, the wide dose requirements of dopamine needed to elicit clinical response in critically ill newborn infants.

Implementation of a Neonatal Abstinence Syndrome Weaning Protocol: A Multicenter Cohort Study.

OBJECTIVES: To evaluate the generalizability of stringent protocol-driven weaning in improving total duration of opioid treatment and length of inpatient hospital stay after treatment of neonatal abstinence syndrome (NAS). METHODS: We conducted a retrospective cohort analysis of 981 infants who completed pharmacologic treatment of NAS with methadone or morphine from January 2012 through August 2014. Before July 2013, 3 of 6 neonatology provider groups (representing Ohio’s 6 children’s hospitals) directed NAS nursery care by using group-specific treatment protocols containing explicit weaning guidelines. In July 2013, a standardized weaning protocol was adopted by all 6 groups. Statistical analysis was performed to identify effects of adoption of the multicenter weaning protocol on total duration of opioid treatment and length of hospital stay at the protocol-adopting sites and at the sites with preexisting protocol-driven weaning. RESULTS: After adoption of the multicenter protocol, infants treated by the 3 groups previously without stringent weaning guidelines experienced shorter duration of opioid treatment (23.0 vs 34.0 days, P < .001) and length of inpatient hospital stay (23.7 vs 31.6 days, P < .001). Protocol-adopting sites also experienced a lower rate of adjunctive drug therapy (5% vs 21%, P = .004). Outcomes were sustained by the 3 groups who initially had specific weaning guidelines after multicenter adoption (duration of treatment = 17.0 days and length of hospital stay = 23.3 days). CONCLUSIONS: Adoption of a stringent weaning protocol resulted in improved NAS outcomes, demonstrating generalizability of the protocol-driven weaning approach. Opportunity remains for additional protocol refinement.

A quality improvement project to reduce length of stay for neonatal abstinence syndrome.

BACKGROUND AND OBJECTIVE: Neonatal abstinence syndrome (NAS), a self-limiting condition, is associated with clinical symptoms that may require pharmacological intervention. Optimal treatment of NAS remains undetermined, but the hospital length of stay (LOS) for patients with NAS is partially dependent upon a standard treatment protocol used. Prolonged LOS for patients with NAS can lead to adverse patient harm, impaired maternal–infant attachment, and significant health care costs. Therefore, we conducted a quality improvement study to reduce the LOS for infants with NAS. METHODS: In 2009, a multidisciplinary NAS Taskforce was created to implement a standardized treatment protocol, discuss the strengths and weaknesses of the current medical and nursing management, and improve communication among staff. Infants with NAS that required pharmacological intervention were followed throughout their hospitalization. Readmission within 30 days of hospital discharge was tracked as a balancing measure. RESULTS: Ninety-two infants were eligible for the project including 23 infants from a baseline period (January 2007–August 2009). Reliable monitoring of symptoms and the administration of a standardized morphine protocol effectively reduced LOS from 36 days to 18 days by June 2012. This improvement was sustained through December 2012. No patients were readmitted for NAS treatment. CONCLUSIONS: The most effective interventions that impacted LOS for infants with NAS were the development of a staff NAS education program and the implementation of a standard treatment protocol. The formation of the NAS Taskforce was also essential because it facilitated communication and the dissemination of vital treatment information among all clinical staff.

An Intervention to Decrease Narcotic-Related Adverse Drug Events in Children's Hospitals

OBJECTIVES. Narcotic-related adverse drug events are the most common adverse drug events in hospitalized children. Despite multiple published studies describing interventions that decrease adverse drug events from narcotics, large-scale collaborative quality improvement efforts to address narcotic-related adverse drug events in pediatrics have not been described. The purpose of this study was to evaluate collaborative-wide narcotic-related adverse drug event rates after a collection of expert panel–defined best practices was implemented. METHODS. All 42 childrens hospitals in the Child Health Corporation of America were invited to participate in the Institute for Healthcare Improvement–style quality improvement collaborative aimed at reducing narcotic-related adverse drug events. A collection of interventions known or suspected to reduce narcotic-related adverse drug events was recommended by an expert panel, with each site implementing ≥1 of these best practices on the basis of local need. Narcotic-related adverse drug event rates were compared between the baseline (December 1, 2004, to March 31, 2005) and postimplementation periods (January 1, 2006, to March 31, 2006) after an a priori–defined intervention ramp-up time (April 1, 2005, and December 31, 2005). Secondary outcome measures included constipation rates and narcotic-related automated drug-dispensing-device override percentages. RESULTS. Median narcotic-related adverse drug event rates decreased 67% between the baseline and postimplementation time frames across the 14-site collaborative. Constipation rates decreased 68.9%, and automated drug-dispensing-device overrides decreased from 10.18% to 5.91% of all narcotic doses administered. CONCLUSIONS. Implementation of ≥1 expert panel–recommended interventions at each participating site resulted in a significant decrease in narcotic-related adverse drug events, constipation, and automated drug-dispensing-device overrides in a 12-month, 14-site childrens hospital quality collaborative.

The Preventable Harm Index: An Effective Motivator to Facilitate the Drive to Zero

N early a decade ago, the Institute of Medicine’s (IOM) report on the state of American Healthcare focused attention on the need to develop systems and processes to improve patient safety in hospitals. Although initially debated, it is now generally accepted that preventable medical errors are common and preventable deaths occur. In response to the IOM report, healthcare providers have implemented strategies and tactics, some adopted from industry, that create an organized approach to identifying and minimizing error. An issue that has generated significant discussion since the IOM report is preventable harm. This concept assumes that complications are not inevitable and many untoward outcomes are preventable. Although debate continues about how to define preventable versus inevitable harm, few people, including patients and their families, would question the value of striving to reduce or eliminate preventable harm where it is identified. We will describe a motivational tool, the preventable harm index (PHI), that we developed in our hospital to facilitate our drive to reduce preventable harm. By using the science of improvement, multiple authors have demonstrated important progress on specific and system-wide quality outcomes. However, the drive to zero preventable harm will likely require novel interventions, especially those that change hospital staff behaviors. Leape and Berwick point out, ‘‘the combination of complexity, professional fragmentation, and tradition of individualism, enhanced by a well-entrenched hierarchical authoritarian structure and diffuse accountability, forms a daunting barrier to creating the habits and beliefs of common purpose, teamwork, and individual accountability for successful interdependence that a safe culture requires.’’ Changing that kind of culture requires two essential ingredients: clear metrics for monitoring and effective motivation. The Ascension Health System began the journey to eliminate preventable harm in 2002 and recently summarized its efforts. It has not yet eliminated preventable harm, but did report significant reductions in hospital mortality rate. An essential part of its 8-stage process of change was the need to ‘‘establish a sense of urgency.’’ This message of urgency motivated staff, from senior physicians to junior administrative

Stable isotope model for estimating colonic acetate production in premature infants

In premature infants, a nutritionally significant proportion of lactose is apparently fermented in the colon to acetate. To estimate the rate of entry of acetate into the peripheral circulation, a model that takes into account extraction of gut-derived acetate by splanchnic and hepatic tissues was developed. Using a [1-13C]acetate orogastric infusion technique, six studies were carried out on five premature infants during constant orogastric feeding. Ranges in gestational age, postnatal age, and breath H2 concentration (corrected for CO2 content) were 28-32 weeks, 16-29 days, and 45-252 microL/L, respectively. The estimated rate of entry of acetic acid (mean +/- SD) was 63.7 +/- 33.8 mumol.kg-1.min-1 (range, 22.9-123.2 mumol.kg-1.min-1), which corresponded to 64.3% +/- 38.6% (24%-136%) of the potential two carbon units from dietary lactose. Thus, a substantial fraction of dietary lactose in premature infants may be converted to acetic acid; this conversion could have a significant effect on protein as well as energy requirements.

Quality Improvement Initiative to Reduce the Necrotizing Enterocolitis Rate in Premature Infants

OBJECTIVE: To reduce the incidence of necrotizing enterocolitis (NEC) among very low birth weight (VLBW) infants admitted to 8 intensive care nurseries from a 2010 baseline of 8.0% to <4.0% by 2012 and sustain for 6 months using quality improvement (QI) methodology. METHODS: A multidisciplinary NEC QI team used the Vermont Oxford Network definition of NEC and the Institute for Healthcare Improvement model. The specific aims were evidenced based and included (1) standardized early human milk feedings, (2) conservative feeding guidelines during blood transfusions and indomethacin treatment, and (3) restriction of ranitidine use in VLBW infants. Inclusion criteria included VLBW infants admitted within the study period without NEC. Exclusion criteria included established NEC or spontaneous intestinal perforation unrelated to NEC. The incidence of NEC and NEC-related surgery were tracked using statistical process control methodology. RESULTS: The baseline NEC rate in 2010 was 8% (27 NEC cases in 335 VLBW infants). After initiation of early human-milk feeding and conservative feeds during blood transfusions guidelines in November 2011, only 3.1% (19 of 606 VLBW infants) had developed NEC through December 2013 (P = .001). Special cause variation was noted in June 2012 establishing a new centerline at 3.1%. NEC-related mortality decreased from a 2010 baseline mean of 2.7% to a new baseline mean of 0.9% from January 2011 to December 2013. CONCLUSIONS: Implementation of QI initiatives decreased the NEC rate from 8.0% to <4.0%. Early human milk feedings and conservative feeding during blood transfusion policies appear to have significant impact on NEC reduction.