Prospective, controlled study of an intervention to reduce errors in neonatal antibiotic orders.

OBJECTIVE: To evaluate the effectiveness of an interactive computerized order set with decision support (ICOS-DS) in preventing medication errors in neonatal late-onset sepsis (LOS). STUDY DESIGN: Prospective, controlled comparison of error rates in antibiotic orders for neonates admitted to the Medical University of South Carolina neonatal intensive care unit with suspected LOS (after postnatal day of life 3) prior to (n=153) and after (n=146) implementation of the ICOS-DS. Antibiotic orders were independently evaluated by two pharmacists for prescribing errors, potential errors and omissions. Prescribing errors included>10% overdoses or underdoses, inappropriate route, schedule or antibiotic, drug-drug or drug-disease interactions, and incorrect patient demographics. Potential errors included misspelled drugs, leading decimals, trailing zeroes, impractical doses and error-prone abbreviations. Multiple errors and omissions in an order were counted individually. RESULTS: Overall error rate per order decreased from 1.7 to 0.8 (P<0.001) and potential error rate from 1.0 to 0.06 (P<0.001). The reduction in omission error rate per order from 0.2 to 0.1 was not significant (P=0.17). The prescribing error rate per order increased from 0.4 to 0.7 (P=0.03) because of the use of incorrect patient weights (P<0.001). Renal dysfunction was significantly associated with an increased risk of prescribing errors (odds ratio=3.7, P=0.01) which was not significantly different for handwritten versus ICOS-DS orders (P=0.15). CONCLUSIONS: The ICOS-DS significantly improved the quality of neonatal LOS antibiotic orders although the use of incorrect patient weights was increased. In both groups, orders for patients with renal dysfunction were at risk for prescribing errors. Further evaluation of interventions to promote medication safety for this population is needed.

International experience with trisomy 21 infants placed on extracorporeal membrane oxygenation.

OBJECTIVE: To characterize the international experience concerning neonates with trisomy 21 (T21) managed with extracorporeal membrane oxygenation (ECMO), and to compare and contrast this group of patients to the neonatal ECMO population as a whole. METHODS: Data from the Extracorporeal Life Support Organization for newborn infants placed on ECMO between January 1984 and June 1999 were analyzed. Infants with T21 were compared with the group of infants without T21. RESULTS: Fifteen thousand nine hundred forty-six infants, including 91 (n = 91) with the diagnosis of T21, were placed on ECMO for neonatal respiratory failure during the 14.5-year period. T21 infants were overrepresented in the ECMO population by several-fold when compared with the incidence of T21 in the general population. Eighty-seven of the 91 T21 infants were placed on ECMO after 1989. The distribution of primary diagnoses leading to ECMO differed between the groups (T21 vs non-T21): primary persistent pulmonary hypertension, 47.3% versus 13%; meconium aspiration syndrome, 23.1% versus 32.9%; sepsis, 7.7% versus 13.2%; congenital diaphragmatic hernia, 7.7% versus 19.9%; and respiratory distress syndrome, 3.3% versus 7.9%. Although survival to discontinuation of ECMO was similar in the 2 groups, likelihood of survival to discharge was decreased for T21 infants (65.9% vs 75.6%) because of increased post-ECMO mortality. CONCLUSIONS: Extracorporeal Life Support Organization registry data suggests that T21 infants are at a significantly higher risk of being placed on ECMO for neonatal respiratory failure than the general population, perhaps as a result of delayed extrauterine pulmonary vascular adaptation, as manifested in the high rate of primary persistent pulmonary hypertension as the primary diagnosis. There may have been a shift in attitude regarding the use of ECMO in the T21 patient after 1989. Although most T21 patients placed on ECMO will survive, the prognosis is more guarded in this population when compared with all infants so managed. The long-term neurodevelopmental outcome of this group of T21 ECMO survivors is currently unknown.

Early discharge with home antibiotic therapy in the treatment of neonatal infection.

OBJECTIVE: To determine the feasibility and cost of home antibiotic therapy for a select group of neonates. METHODS: A cohort of neonates at a university hospital who met criteria for home antibiotic therapy at discharge were prospectively followed (November 1995 to October 1997) for type and duration of antibiotic therapy as well as for hospital readmission. RESULTS: During the study period, 95 infants diagnosed with sepsis, presumed sepsis, pneumonia, or uncomplicated meningitis (having received > 10 days of in-hospital therapy) met prior, established, criteria for home antibiotic therapy. The mean +/- SD birth weight of the cohort was 3160 +/- 526 gm, with a mean gestational age of 38.4 +/- 2.1 weeks. A total of 59 infants (62%) received antimicrobial therapy for a clinical presentation consistent with sepsis or presumed sepsis, and 24 infants (25%) were treated for pneumonia. Ampicillin and gentamicin were prescribed for 56% of the cohort, and ceftriaxone was prescribed for 21% of the cohort. Four of those infants were switched from intravascular ampicillin/gentamicin therapy to intramuscular ceftriaxone after discharge due to loss of intravascular access. With a bilirubin level of > 8, four additional infants were changed from ceftriaxone back to ampicillin and gentamicin to complete coverage. The mean age at discharge was 5.2 days, with a mean hospitalization cost of $6121 for that period. There were no rehospitalizations or emergency department visits secondary to a worsening clinical course. CONCLUSION: In this cohort of neonates who met early discharge and defined home antibiotic therapy criteria, there were no serious complications or treatment failures reported; in addition, there were fewer costs compared with continued inpatient treatment.

Comparative neonatal morbidity of abdominal and vaginal deliveries after uncomplicated pregnancies.

OBJECTIVE: To determine whether the risk of cesarean section following uncomplicated pregnancies has been reduced by current obstetric practices by comparing the neonatal risk of vaginal deliveries with the risk incurred following abdominal delivery in otherwise uncomplicated pregnancies. DESIGN: Observational, cohort study. A subpopulation of 11,702 women without complications of pregnancy was identified from a perinatal database, classified by subsequent mode of delivery, and compared for neonatal morbidity. This analysis was repeated after the cesarean section group was further narrowed to include only "repeated elective" deliveries. SETTING: Low-risk inborn setting. Tertiary care (level III nursery) referral center and a community (level II nursery) hospital. INTERVENTION: Cesarean section performed electively, for cephalopelvic disproportion, or for failure to progress. OUTCOME VARIABLES: Chosen prior to data analysis: neonatal mortality and morbidity. RESULTS: Groups differed with regard to ethnicity and sex. Infants who were delivered by cesarean section were more likely to have 1-minute Apgar scores less than 4, require intermediate or intensive nursery care at admission (6.3% vs 1.3% [P < .001]), and require greater respiratory support (mechanical ventilation, 1.6% vs 0.3%; oxygen therapy, 4.9% vs 1.4%; or room air, 93.5% vs 98.4% [P < .001]) than infants who were delivered vaginally. Similar results were found when patients who were delivered vaginally and by repeated elective cesarean section were compared. CONCLUSION: Although reports have recently emerged suggesting otherwise, abdominal delivery following an uncomplicated pregnancy remains a risk factor for adverse neonatal outcome despite current obstetric practices.

Supplemental oxygen and gastric pH in unfed preterm infants.

Hypoxia has been associated with decreased gastric acidity in infants and children. In neonates, an inverse relationship between gestational age and gastric acidity may confound this association. To assess the relationship between oxygen supplementation and gastric acidity in premature neonates, mean 24-hour continuous measurements of gastric pH, obtained by an indwelling flexible gastric pH probe, were compared in infants requiring and not requiring oxygen. Patients were < 36 weeks' gestational age and were unfed before and during the assessment period. The gestational age of infants who required oxygen was less than that of infants who did not (30.5 +/- 3.0 vs 32.9 +/- 1.5 weeks, respectively). Other comparison variables were not different. The mean pH for infants requiring oxygen (4.4 +/- 1.7) was significantly greater than that of those not needing oxygen (2.7 +/- 1.2). After controlling for population characteristics and gestational age, we found that infants requiring oxygen still had significantly reduced gastric acidity.

Randomized, controlled trial of nasopharyngeal continuous positive airway pressure in the extubation of very low birth weight infants.

We conducted a prospective, randomized controlled trial to determine whether extubation of very low birth weight infants was facilitated by the use of nasopharyngeal continuous positive airway pressure (CPAP). Eligible infants included patients weighing 600 to 1500 gm at birth who required tracheal intubation within 48 hours of birth and who met specific predetermined criteria for extubation by day 14 of life. We also sought to determine whether varying the duration of nasopharyngeal CPAP influenced the likelihood of successful extubation. Infants underwent random assignment to receive nasopharyngeal CPAP until resolution of lung disease (n = 40), 6 hours of nasopharyngeal CPAP (n = 42), or oxygen supplementation delivered by hood (n = 42). Extubation failure was predefined as a requirement for > or = 80% oxygen, pH < or = 7.20, severe apnea, or predefined clinical deterioration, and extubation success was predefined as the ability to remain free of a requirement for mechanical ventilation for 7 days and a 66% reduction in the need for supplemental oxygen. Each group was similar with regard to race, sex, and birth weight. Extubation was successful in 62%, 61%, and 60% of infants. After stratification by birth weight, there were no significant differences in the rates of successful extubation among the treatment groups. We conclude that nasopharyngeal CPAP does not improve the likelihood of successful extubation of very low birth weight infants who are ready for extubation within the first 2 weeks of life.

Hyaline membrane disease: the role of ethnicity and maternal risk characteristics.

OBJECTIVE: Our objective was to explore the association between maternal ethnicity and maternal antepartum complications of pregnancy, maternal sociodemographic factors, and newborn characteristics with the incidence of hyaline membrane disease. STUDY DESIGN: By using a retrospective cohort analysis the incidence of hyaline membrane disease was determined for 2295 preterm infants. The study population consisted of all live, inborn infants delivered vaginally from 1982 to 1987. Statistical differences were assessed by use of chi 2 and Student's t tests. A logistic regression procedure determined the relationship of ethnicity and hyaline membrane disease after the study was controlled for all other significant population differences. RESULTS: The differences between black and white populations in marital status, were statistically significant years of education, prolonged rupture of membranes, anemia, and chronic hypertension were statistically significant. Infants of black mothers were diagnosed with hyaline membrane disease less often than infants of white mothers (overall and at each gestational age interval). After the study was controlled for population differences, infants of black mothers were still found to experience hyaline membrane disease less often. CONCLUSION: These data suggest that hyaline membrane disease occurs less frequently, is less severe, and is accompanied by fewer related complications in black preterm infants.

Clinical diagnosis and management of respiratory distress in preterm neonates: effect of participation in a controlled trial.

The ability to generalize the results of a clinical trial depends on the ability to compare a population of patients with the population described in the trial, emphasizing the importance of objective diagnostic criteria in study design and clinical medicine. However, clinical decisions are often based on subjective interpretations of data. There is concern that bias that an experimental therapy is beneficial might lead to alterations in clinical diagnosis and management. To evaluate this concern, the authors reviewed a preexisting database comprising information obtained by trained personnel by chart review to investigate prospectively the frequency of the diagnosis of hyaline membrane disease and the use of mechanical ventilation before and during participation in a clinical trial of surfactant therapy during which such therapy was available exclusively through clinical trials. Major eligibility criteria for a randomized trial at the Medical University of South Carolina included mechanical ventilation and the diagnosis of hyaline membrane disease. Both the diagnosis of hyaline membrane disease and the use of mechanical ventilation increased between pre-surfactant and randomized trial periods (hyaline: 47.2% to 55.9%, P less than .05; ventilation: 55.6% to 66.3%, P less than .01). The possibility that enthusiasm for surfactant influenced clinical diagnosis and management of respiratory distress during this period cannot be dismissed.

Protein content and myosin light chain phosphorylation in uterine arteries during pregnancy.

During pregnancy, the ovine uterine artery changes from a low- to a high-stress artery. We investigated the hypotheses that the increased stress reflects alterations in vessel wall cellularity, smooth muscle cell contractile protein contents, or activation properties. Uterine artery diameter increased during pregnancy, whereas the fractional cellular composition and thickness of the muscularis were unchanged. Results of morphometry suggest that vessel growth is associated with cell elongation. Uterine arteries from pregnant ewes had greater protein contents than those from nonpregnant ewes (104 vs. 69 mg/g, respectively); there were corresponding increases in the absolute cellular contents of actin and myosin. While the fraction of light chain phosphorylated in response to phenylephrine was unaltered, the total amount of myosin light chain phosphorylated per gram wet weight increased significantly during pregnancy. In addition, the distribution of myosin heavy chain isoforms was also altered during pregnancy. The increased stress observed in the uterine artery during ovine pregnancy reflects, in part, increases in cellular contractile protein concentrations associated with hypertrophy.

Alterations in vascular smooth muscle contractility during ovine pregnancy.

During pregnancy, sheep develop attenuated systemic and uterine vascular responsiveness to alpha-adrenergic stimulation. To determine whether this reflects altered vascular smooth muscle function, we studied the responsiveness of smooth muscle isolated from systemic and uterine arteries to KCl and phenylephrine. Uterine, renal, and carotid arteries were collected from nonpregnant, pregnant (131 +/- 2 days, +/- SD), and late postpartum (144 +/- 4 days) ewes; endothelium was removed and open rings were hung for measurement of isometric force. There were no differences in concentration-response relationships nor maximal stresses generated to phenylephrine between nonpregnant, pregnant, and late postpartum states for carotid or renal arteries. However, the 50% maximal concentration for phenylephrine of uterine arteries in the nonpregnant state (2.8 +/- 0.9 x 10(-6) M) was greater than the pregnant state (0.76 +/- 0.05 x 10(-6) M). Moreover, uterine arteries from pregnant sheep generated significantly more stress than those from nonpregnant sheep (2.2 +/- 0.23 vs. 0.73 +/- 0.23 x 10(6) dyn/cm2, P less than 0.01). The attenuated systemic and uterine vascular responses associated with pregnancy do not result from diminished adrenergic sensitivity or contractile capability of arterial smooth muscle. In contrast, there is increased stress-generating capacity of uterine arterial smooth muscle during pregnancy, which is reversed during the postpartum period.