Reduction in Clinical Variance Using Targeted Design Changes in Computerized Provider Order Entry (CPOE) Order Sets: Impact on Hospitalized Children with Acute Asthma Exacerbation.

OBJECTIVES: Unwarranted variance in healthcare has been associated with prolonged length of stay, diminished health and increased cost. Practice variance in the management of asthma can be significant and few investigators have evaluated strategies to reduce this variance. We hypothesized that selective redesign of order sets using different ways to frame the order and physician decision-making in a computerized provider order entry system could increase adherence to evidence-based care and reduce population-specific variance. PATIENTS AND METHODS: The study focused on the use of an evidence-based asthma exacerbation order set in the electronic health record (EHR) before and after order set redesign. In the Baseline period, the EHR was queried for frequency of use of an asthma exacerbation order set and its individual orders. Important individual orders with suboptimal use were targeted for redesign. Data from a Post-Intervention period were then analyzed. RESULTS: In the Baseline period there were 245 patient visits in which the acute asthma exacerbation order set was selected. The utilization frequency of most orders in the order set during this period exceeded 90%. Three care items were targeted for intervention due to suboptimal utilization: admission weight, activity center use and peak flow measurements. In the Post-Intervention period there were 213 patient visits. Order set redesign using different default order content resulted in significant improvement in the utilization of orders for all 3 items: admission weight (79.2% to 94.8% utilization, p<0.001), activity center (84.1% to 95.3% utilization, p<0.001) and peak flow (18.8% to 55.9% utilization, p<0.001). Utilization of peak flow orders for children ≥8 years of age increased from 42.7% to 94.1% (p<0.001). CONCLUSIONS: Details of order set design greatly influence clinician prescribing behavior. Queries of the EHR reveal variance associated with ordering frequencies. Targeting and changing order set design elements in a CPOE system results in improved selection of evidence-based care.

Extracellular heat shock protein 60 (Hsp60) levels in children with septic shock.

OBJECTIVE AND DESIGN: Recent data suggest that extracellular Hsp60 modulates the host innate immune response. We analyzed plasma Hsp60 levels in children admitted to a level III tertiary care PICU with septic shock. MATERIALS AND SUBJECTS: Blood samples were obtained from children meeting criteria for septic shock (n = 63), critically ill children without septic shock (n = 10), and healthy controls (n = 24). TREATMENT: Not applicable. METHODS: Hsp60 levels were measured in the plasma using a commercially available ELISA. Differences between groups were analyzed with a Kruskal-Wallis one way ANOVA due to the non-parametric nature of the data. A p value < or = 0.05 was considered significant. RESULTS: Extracellular Hsp60 levels were significantly higher in children with septic shock (median, 16.7 ng/mL) compared to both critically ill children without septic shock (median, 0 ng/mL) and healthy controls (median, 0 ng/mL, p <0.001). CONCLUSIONS: Extracellular Hsp60 levels are significantly elevated in children with septic shock compared with both healthy controls and critically ill children without sepsis. Extracellular Hsp60 may play a role in the pathogenesis of sepsis in children.

Recombinant tissue plasminogen activator in the treatment of central venous catheter occlusion in children.

Tissue plasminogen activator was used to treat 228 children with 320 central venous catheter (CVC) occlusion events. Patency was restored in 91% of CVCs after 1 to 3 treatments, with no adverse events. Tissue plasminogen activator is effective in restoring patency to occluded CVCs and is a viable alternative to CVC removal or urokinase treatment.

Intracatheter nitroglycerin infusion fails to prevent catheter-related venous thrombosis: a randomized, controlled trial.

OBJECTIVE: Catheter-related thrombosis is a common problem in the pediatric intensive care unit. Strategies that reduce the incidence of thrombosis may have significant clinical advantage. Nitroglycerin (NTG) infusions release nitric oxide (NO). NO is responsible for much of the vasodilating and antithrombotic properties of the vasculature. We hypothesized that an intracatheter NTG infusion would reduce the incidence of catheter-related thrombosis. DESIGN: Prospective, randomized, controlled trial. SETTING: Pediatric intensive care unit. PATIENTS AND PARTICIPANTS: Children of 6 years or less with femoral venous catheters who were not on antithrombotic therapy. INTERVENTIONS: Subjects were randomly assigned to NTG or control groups. NTG group patients received NTG at 0.1 mcg x kg x min in 5 % dextrose; control group patients received only 5 % dextrose. Infusions were delivered continuously through the catheter until the catheter was removed. Demographic data, physical and laboratory findings, catheter insertion attempts and infusate composition were recorded. Clinical evidence of vascular thrombosis or catheter malfunction was noted. Ultrasound examinations were performed within 2 days of catheter insertion and within 2 days after removal. MEASUREMENTS AND RESULTS: Forty-four patients (age 12.0 +/- 2.6 months) completed the study, 21 in the NTG group and 23 in the control group. Duration of catheter placement was 7.5 +/- 0.7 days. Twelve of 44 patients (27 %) had thrombi: 7/21 in the NTG group; 5/23 in the control group (p = NS). There were no significant differences between children with and without thrombi in age, gender, number of insertion attempts, duration of catheter placement, clinical signs of thrombosis or infections. CONCLUSIONS: Catheter-related thrombosis is common after placement of femoral venous catheters in children. Low dose intracatheter NTG infusion does not protect against catheter-related venous thrombosis in children.

Pediatric peripherally inserted central catheters: complication rates related to catheter tip location.

OBJECTIVE: To compare complication rates between central venous catheter tip location and noncentral tip location after peripherally inserted central catheter (PICC) placement in children. METHODS: Between 1994 and 1998, data from all children who underwent PICC placement were analyzed. Patient demographics, catheter characteristics, catheter duration, infusate composition, and catheter complications were entered prospectively into a computerized database. Catheter tip locations were determined by fluoroscopy and were defined as central if they resided in the superior vena cava, right atrium, or high inferior vena cava at or above the level of the diaphragm, and as noncentral if located elsewhere. Differences in complication rates between the central and noncentral groups were analyzed. RESULTS: Data from a total of 1266 PICCs were analyzed from 1053 patients with a mean age of 6.49 +/-.2 years (range: 0-45.0 years). Of the 1266 PICCs, 1096 (87%) were central in tip location, and 170 (13%) were noncentral in tip location. The central group had 42 complications of 1096 catheters (3.8%), while the noncentral group had 49 complications of 170 catheters (28.8%). Controlling for patient age, catheter size, gender, and catheter duration with a logistic regression model, there remained a statistically significant increased likelihood of complication in the noncentral group versus the central group (adjusted odds ratio: 8.28; 95% confidence interval: 5.11-13.43). CONCLUSIONS: Centrally placed catheter tips are associated with fewer complications than are noncentrally placed catheter tips. Clinicians should ensure that catheter tips reside centrally after PICC placement in infants and children.

Postoperative management of children after single-stage laryngotracheal reconstruction.

OBJECTIVE: To report the safety and efficacy of a postoperative approach that avoids pharmacologic and physical restraints and allows liberal physical activity after single-stage laryngotracheal reconstruction in children. DESIGN: Retrospective study. SETTING: Tertiary care pediatric intensive care unit. PATIENTS: One hundred thirty-three children who underwent single-stage laryngotracheal reconstruction, including laryngotracheoplasty, tracheal resection, and cricotracheal resection. INTERVENTIONS: Five-year period of data collection regarding postoperative care and complications. MEASUREMENTS AND MAIN RESULTS: The medical records of all patients (age range, 2-336 months; mean age +/- SEM, 66 +/- 5 months) who underwent single-stage laryngotracheoplasty, tracheal resection, or cricotracheal resection between 1993 and 1998 were reviewed. Tracheally intubated, awake, and unrestrained patients (group 1, n = 54; mean age, 113 +/- 8 months) were compared with tracheally intubated, sedated, and restrained patients (group 2, n = 79; mean age, 33 +/- 3 months). Pediatric intensive care unit length of stay was less in group 1 in comparison with group 2 patients (11.2 +/- 0.5 days vs. 13.7 +/- 0.6 days; p = .007). Hospital length of stay was less in group 1 than group 2 patients (16.7 +/- 1.0 days vs. 21.1 +/- 1.1 days; p = .01). Adverse events were fewer in group 1 compared with group 2 patients: atelectasis, 44% vs. 73% (p < .001); postextubation stridor, 22% vs. 53% (p < .001); and withdrawal syndromes, 0% vs. 43% (p < .001). The occurrence of pneumonia, airleak syndromes, unplanned extubation, and aspiration events was not different between groups. CONCLUSIONS: For developmentally appropriate children, postoperative management after single-stage laryngotracheal reconstruction does not require the use of physical and pharmacologic restraints. Older children who are not sedated or restrained and who are allowed liberal physical activity have shorter pediatric intensive care unit and hospital lengths of stay, and a decreased incidence of postoperative adverse events. Centers performing single-stage laryngotracheal reconstruction should consider a postoperative management strategy that avoids sedatives, muscle relaxants, and physical restraints, and allows liberal bedside physical activity in developmentally appropriate children.

Soluble nitric oxide donor and surfactant improve oxygenation and pulmonary hypertension in porcine lung injury.

Acute lung injury (ALI) is associated with diminished surfactant activity and pulmonary hypertension. NONOates are soluble NO donors which release NO in solution. Intratracheal NONOates reduce pulmonary hypertension and improve oxygenation in ALI. We hypothesized that the pharmacologic properties of NO donors would be unaltered after surfactant admixture in vitro and that aerosolized NONOate activity would be enhanced by surfactant pretreatment in vivo. NO donors were added to saline or surfactant and analyzed for nitrite/nitrate production and aortic ring vasodilation. Surfactant did not alter nitrate/nitrite production or aortic ring vasodilation. A porcine model of ALI with pulmonary hypertension was produced using intravenous oleic acid. Animals were assigned to Surfactant-Saline, Surfactant-NONOate, Saline-Saline, or Saline-NONOate groups. Saline or surfactant was instilled into the trachea, followed by gas exchange, pulmonary function, and hemodynamic measurements. NONOate or saline was then aerosolized, and additional data were collected. Oxygenation was improved in the Surfactant-NONOate group, while pulmonary hypertension was selectively reduced in both NONOate groups. Aerosolized NONOate following surfactant pretreatment improves oxygenation and reduces pulmonary hypertension in ALI.

Aerosolized soluble nitric oxide donor improves oxygenation and pulmonary hypertension in acute lung injury.

Acute respiratory distress syndrome (ARDS) is a major cause of morbidity and mortality in critically ill patients. The associated ventilation/perfusion mismatch and pulmonary hypertension are amenable to treatment with inhaled nitric oxide (NO) gas. Compounds formed by reacting NO with various nucleophiles (NONOates) release NO spontaneously and induce vasodilation. Intratracheally administered NONOates result in selective reduction in pulmonary hypertension. We hypothesized that a nebulized NONOate would improve oxygenation and reduce pulmonary vascular resistance in oleic acid-induced acute lung injury and pulmonary hypertension. Pigs underwent catheterization of the pulmonary artery, left atrium, and right atrium, and a flow probe was positioned around the pulmonary artery. Acute lung injury and pulmonary hypertension were induced with intravenous oleic acid. Animals were randomly assigned to receive either nebulized saline or the NONOate 2-(dimethylamino)ethylputreanine/NO (DMAEP/NO). Hemodynamic, gas exchange, pulmonary function, methemoglobin, and nitrite/nitrate measurements were obtained for 60 min. Animals in the DMAEP/NO group had improvement in PaO2 as compared with control animals (from 139 +/- 19 mm Hg to 180 +/- 19 mm Hg in the DMAEP/NO group [n = 6]; and from 144 +/- 6 mm Hg to 150 +/- 9 mm Hg in the saline group [n = 6], p < 0.05). After aerosol treatment, animals in the DMAEP/NO group had a greater reduction in pulmonary vascular resistance index (PVRI) than did control animals (from 81 +/- 17 dyne. s/cm5/kg to 34 +/- 8 dyne. s/cm5/kg; and from 104 +/- 16 dyne. s/cm5/kg to 64 +/- 11 dyne. sec/cm5/ kg in the saline group at 60 min, p < 0.05). There were no differences between the groups in systemic vascular resistance index (SVRI), cardiac index (CI), methemoglobin, nitrite/nitrate, or lung pathology scores. We conclude that DMAEP/NO improves oxygenation and has selective pulmonary vasodilating properties without causing significant systemic toxicity in this porcine model of acute lung injury.

Analysis of TEST (TES and Tris) yolk buffer effects on human sperm.

OBJECTIVE: To assess different parameters of TEST (TES and Tris) yolk buffer (TYB) treatment of human sperm that may contribute to the biologic effects of TYB on sperm function. DESIGN: The influence of TYB treatment on occurrence of acrosome reactions was studied, as was the influence of the concentration of acrosome-reacted sperm reacted by TYB or Biggers-Whitten-Whittingham medium (BWW) incubation on penetration levels in the sperm penetration assay (SPA). The necessity for the TYB to achieve enhanced SPA performance as well as the effect of heat shock on sperm also were studied. SETTING: Andrology laboratory of a university hospital. PATIENTS: Sperm donors. MAIN OUTCOME MEASURES: Sperm penetration levels in the SPA and acrosomal loss as evaluated by a fluorescent lectin staining technique. RESULTS: Sperm incubated in TYB for 42 to 46 hours at 4 degrees C demonstrated a higher rate of acrosomal loss than did sperm capacitated in BWW media for 20 to 22 hours. The difference was not significant. When insemination concentrations were normalized to identical concentrations of acrosome-reacted sperm, TYB treated specimens demonstrated much higher penetration levels compared with BWW specimens. Samples incubated in BWW versus TYB for 42 to 46 hours at 4 degrees C before heat shock had identical penetration levels. Samples washed with 37 degrees C BWW (positive heat shock) had significantly higher penetration levels than did samples washed with 4 degrees C BWW (negative heat shock). CONCLUSION: Although TYB treatment does increase the occurrence of acrosome reactions, this alone does not account for the dramatic increase in penetration levels in SPA seen with these samples. TEST yolk buffer is not required for enhancement of penetration, and the heat shock step of the procedure seems to be most important for enhancement of sperm fusion ability in the SPA.

Time required for oral ranitidine to decrease gastric fluid acidity.

This study documented gastric fluid acidity in ambulatory surgical patients 30-120 min after they had taken a 300-mg tablet of ranitidine, as changes specific to this relatively brief dose-to-sampling interval previously had not been delineated. At 20-120 min before outpatient surgery, ranitidine was given with 15 mL of water to 112 ASA physical status I-III adults without increased risk factors for aspiration of acidic gastric contents. After induction of general endotracheal anesthesia, the gastric fluid was aspirated. Volume and pH were compared with a reference group (pH = 1.6 +/- 1; n = 161) that did not receive an H2-antagonist or water. Of 40 patients sampled at 30-60 min after dosing, 26 had pH greater than or equal to 2.5; mean pH was 3.9 +/- 2 (P less than 0.05 vs reference by Wilcoxon signed rank and chi 2 tests). Beyond 90 min, 28 of 28 patients had a pH greater than or equal to 2.5, with a mean of 6.3 +/- 1. No significant differences were noted with respect to mean gastric volume. We conclude that in patients without additional risk factors, oral ranitidine consistently prevents acid production when it is administered more than 90 min before induction of anesthesia.

A comparison of progesterone and R5020 binding in endometrium, ovary, pituitary, and hypothalamus.

A cytoplasmic receptor is necessary for target tissues to respond to steroid hormones. Since the hypothalamic-pituitary unit is responsive to progestins, it might be expected to have a progesterone receptor. The clinical evaluation of receptors located in the central nervous system is not possible, so the clinical investigator must extrapolate from accessible tissues. To determine whether such extrapolation is valid, binding affinities and specificity of progesterone receptor sites in the cytoplasm of bovine uterus, ovary, hypothalamus, and pituitary were measured. In each particular tissue the receptors showed similar binding characteristics with progesterone and R5020. It is concluded that in a given species the receptor for progesterone is similar in all target tissues and probably results from the expression of the same gene.

Evidence for a human ovarian progesterone receptor.

The aromatization of androgens to estrogens in the ovary and the roles of estrogens in promoting follicular growth have been described by a number of investigators. Furthermore, specific receptors for estrogens have been defined in granulosa cells as well as other target tissues. In other estrogen-responsive tissues, there is also a progesterone receptor, which mediates estrogen antagonism at the molecular level. We have previously described an ovarian progesterone receptor in an animal model. We now describe a heat-labile ovarian cytoplasmic protein that specifically binds progestins with a very high affinity. The equilibrium dissociation constant for progesterone (Kd) = 4.8 X 10(-9)M and it is present in the ovary in a concentration of 3.3 X 10(-13) moles/mg of protein. Since the characteristics of this protein are compatible with an ovarian progesterone receptor, there is the implication that the ovary is a target organ for progesterone. Thus, progesterone may have a role in the modulation of ovarian physiology.

The antigonadotropic activity of Lithospermum ruderale I. The lack of steroid-like activity at the receptor level.

Previous work has demonstrated that extracts from the plant Lithospermum ruderale have antigonadotropic activity. The possibility of steroidal substances being responsible for this activity was examined at the receptor level. It was found that only at very high concentrations of crude lithosperm extract (LS) was progesterone, testosterone, or estradiol displaced from their respective uterine receptors. Because such high doses of LS may be toxic and because they are not required for in vivo or in vitro bioactivity, it is concluded that the antigonadotropic components of Lithospermum ruderale probably do not as a steroid.