Willa H Drummond

Nitric oxide inhalation in infants with respiratory distress syndrome

OBJECTIVE This study was designed to test the hypothesis that nitric oxide inhalation increases systemic arterial blood oxygen tension of prematurely delivered infants with respiratory distress syndrome. METHODS Nitric oxide was administered to 23 preterm infants with a diagnosis of respiratory distress syndrome. The infants were randomly assigned to receive either 5 or 20 ppm of nitric oxide and were studied between 24 and 168 hours after delivery. The treatment period for each infant lasted 15 minutes and was preceded by and followed by a 15-minute control period. We evaluated all outcome variables by using two-way repeated measures analysis of variance; p values less than 0.01 were considered significant. RESULTS Nitric oxide inhalation caused significant increases in the following: arterial blood oxygen tension, directly measured arterial oxyhemoglobin saturation, and transcutaneously measured arterial oxyhemoglobin saturation. No differences between the effects of the two nitric oxide concentrations were detected, nor were residual effects detected 15 minutes after either dose of nitric oxide was discontinued. CONCLUSIONS Inhalation of both 5 and 20 ppm nitric oxide causes concentration-independent increases in the blood oxygen tensions of preterm infants with respiratory distress syndrome. We speculate that nitric oxide inhalation may be a useful adjunctive therapy for these patients.

The Clinical Profile of the Newborn with Persistent Pulmonary Hypertension Observations in 19 Affected Neonates

In 19 neonates with severe cyanosis, normal chest x-rays, anatomically normal hearts, and a high incidence of perinatal complications, the clinical course was characterized by variable sustained cyanosis. Cardiac catheteriza tion data showed high systemic or suprasystemic pulmonary artery pressure with right to left intracardiac shunting via the foramen ovale and ductus arteriosus. Arterial oxygen tension at an inspired oxygen concentration above 65 per cent was helpful in distinguishing these patients from those with congenital heart disease, and for predicting prognosis.

Hemodynamic Effects of Pulmonary Arterial Infusion of Vasodilators in Newborn Lambs

Summary: Pulmonary arterial infusion of prostaglandin E1 (mean dose, 1 μg/kg/min) in term neonatal lambs ventilated with room air resulted in a slight fall hi pulmonary arterial pressure (P ≤0.05). Infusion during ventilation with low oxygen mixtures resulted in a parallel fall in pulmonary and arterial pressures and resistances. Intrapulmonary infusion of acetylcholine (mean dose, 3.9 μg/kg/min) in lambs during ventilation with room air caused a slight fall in mean systemic arterial pressure and systemic vascular resistance. When repeated with low oxygen ventilation, infusion of acetylcholine caused a parallel fall in both pulmonary and systemic arterial pressures and resistances. Infusion of tolazoline at a mean dose of 0.21 mg/kg/min did not change pulmonary or systemic arterial pressures or resistances when the lambs were ventilated with room air or with hypoxic gas mixtures although individual animals experienced marked falls in systemic arterial pressure.Pulmonary arterial infusion of each of the three vasodilators during hypoxic ventilation resulted hi potentially adverse hemodynamic effects. This occurred despite prior ductal ligation, implying that doses effective for pulmonary vasodilatation may exceed doses without systemic effects particularly hi the acute hypoxic state.Speculation: Vasodilators specific for pulmonary vascular smooth muscle have not been developed. Nonspecific vasodilators cause relaxation of pulmonary and systemic-vascular smooth muscle which is most marked during hypoxemia. Increased pulmonary blood flow will result from vasodilatation only if the ratio of pulmonary to systemic vascular resistance decreases or if cardiac output rises. Parallel changes in pulmonary and systemic resistance with vasodilators during hypoxic pulmonary hypertension with right to left shunting may prevent clinically useful improvement in oxygenation.

Systemic and pulmonary vascular effects of selective dopamine receptor blockade and stimulation in lambs

ABSTRACT: Vascular dopamine (DA1) receptors may modulate circulatory hemodynamics in lambs. We evaluated resting dopaminergic tone in lambs by pharmacologically manipulating peripheral DA1 receptors with i.v. SCH 23390, (a highly selective, competitive DA1 receptor antagonist) and i.v. fenoldopam, (a highly selective DA1 receptor agonist) in unanesthetized lambs, instrumented for circulatory studies, while measuring the systemic and pulmonary vascular changes that the manipulations induced. We examined both the independent effects of DA1 receptor stimulation and blockade as well as the effects of the agonist and the antagonist infused together (competitive interaction). SCH 23390, infused at 2.5 μg/kg·min−1, caused significant increases in left atrial, systemic, and pulmonary artery pressure, as well as an increase in systemic vascular resistance and a decrease in heart rate. Fenoldopam, infused at the dose of 60 μg/kg·min−1 caused significant decreases in mean systemic artery pressure and systemic vascular resistance while increasing cardiac index and mean pulmonary artery pressure. SCH 23390 blunted the fenoldopam-induced effects. Our data suggest that dopaminergic influence may be active in the maintenance of resting hemodynamics of the lamb.

Electronic prescribing in pediatrics

This policy statement identifies the potential value of electronic prescribing (e-prescribing) systems in improving quality and reducing harm in pediatric health care. On the basis of limited but positive pediatric data and on the basis of federal statutes that provide incentives for the use of e-prescribing systems, the American Academy of Pediatrics recommends the adoption of e-prescribing systems with pediatric functionality. The American Academy of Pediatrics also recommends a set of functions that technology vendors should provide when e-prescribing systems are used in environments in which children receive care.

Chloralose Alters Both Basal Hemodynamics and Cardiovascular Responses to Alveolar Hypoxia in Chronically Instrumented, Spontaneously Breathing Lambs'

ABSTRACT: We studied the effects of chloralose anesthesia on the basal hemodynamic state and on the cardiovascular response to alveolar hypoxia in chronically instrumented, spontaneously breathing lambs, compared with responses to the saline vehicle. Chloralose significantly increased heart rate (23%), mean systemic arterial pressure (11%), systemic vascular resistance (21%), mean pulmonary arterial pressure (23%), and pulmonary vascular resistance (46%) (n=30, p<0.05, ANOVA). These changes were unrelated to baseline tone of the circulation, cardiac output, mean left atrial pressure, or physiologically important changes in arterial blood gas tensions. In addition, chloralose-treated lambs had increased heart rate, systemic vascular resistance, and pulmonary vascular resistance compared to controls during alveolar hypoxia (13- 15% F1O2). Importantly, chloralose-treated lambs did not increase their cardiac output during alveolar hypoxia as did control lambs. During hypoxia, systemic vascular resistance remained elevated in chloralose-treated lambs, but declined in control lambs. Chloralose has been recommended as an ideal anesthetic agent for cardiovascular experimentation. Our data suggest that chloralose-induced alterations in basal hemodynamics and in cardiovascular responses to alveolar hypoxia represent an uncontrolled variable in acute experimental studies. Complex cardiovascular alterations caused by anesthesia should be considered in experimental design

Pulmonary and systemic vascular effects of SKF-82526-J, a new specific peripheral dopamine receptor agonist, in unanesthetized neonatal lambs.

We examined the circulatory effects of SKF-82526-J, a new specific dopamine receptor agonist, using chronically instrumented neonatal lambs. Serial infusion of doses ranging from 1.4 to 337 micrograms/kg/min did not change cardiac output, heart rate, left atrial pressure, systemic arterial pressure (SAP) or vascular resistance (SVR). Pulmonary pressure (PAP) increased from 22.6 +/- 1.1 to 35.8 +/- 4.0 mm Hg at 337 micrograms/kg/min (p less than 0.005) and pulmonary resistance (PVR) changed from 0.099 +/- 0.01 to 0.15 +/- 0.03 mm Hg/ml/kg/min (p less than 0.025). After 3-12 min of recovery, SAP increased in all lambs (range 6-57 mm Hg), while PAP fell, without change in cardiac output. Thus, the ratio of PVR/SVR returned more quickly to baseline (4 min) than either PVR or SVR alone. We conclude, based on physiologic evidence, that the newborn lamb pulmonary circulation has no vasodilating dopamine receptors.

The Effect of Alpha-Adrenergic Blockade on the Pulmonary Vascular Response to Dopamine in Neonatal Lambs

Summary: The effect of alpha-adrenergic blockade by phentolamine on the pulmonary vascular response to dopamine was studied in chronically prepared newborn lambs. Dopamine was administered at doses of 2.7 μg·kg-1·min-1, 27 μ·kg-1·min-1 and 270μg·kg-1·min-1 with and without alpha-adrenergic blockade. Dopamine infusion at 270 μ·kg-1·min-1 caused a rise in the mean pulmonary artery pressure from 22 ± 3.2 mmHg (mean ± S.E.) at baseline to 36 ± 4.1 mmHg (P < 0.001). This rise was unaffected by alpha-adrenergic blockade. Dopamine infusion alone did not change pulmonary blood flow, but, in the presence of alpha-adrenergic blockade, pulmonary blood flow rose from 190 ± 12 ml·min-1·kg-1 at baseline to 280 ± 13 ml·min-1·kg-1 at the maximum dopamine infusion rate (P < 0.001). Pulmonary vascular resistance was the same before and after alpha-adrenergic blockade and did not change from the baseline value during dopamine infusion.

45 FOLLOW UP EVALUATION OF NEONATES TREATED WITH DRUGS AND HYPERVENTILATION FOR SEVERE PERSISTENT PULMONARY HYPERTENSION (PPHN)

12 infants were treated for PPHN from 1978 to 1980; nine survived. We were able to evaluate 5 of 7 [xBW=2.1 kg, xGA=37 (32-40), x5m Apgar=7] infants now >6 months old, who are being followed by their referring pediatricians. Surviving infants suffered episodes of hypo and hyperoxia 5/5, hypotension 3/5, and hypo and hypercarbia 5/5. An electrocardiogram, vector-cardiogram, and echocardiogram, chest x-ray, arterial blood gas, ophthalmologic exam, computerized brain scan (CAT), Bayley Scale of Infant Development, and physical examination by a pediatric cardiologist were done on each patient. No child was completely normal. Abnormalities include evidence of residual or previously undiagnosed cardiopulmonary disease in 3/5, minor CAT scan abnormalities in 3/5, and severe abnormality in 1/5, developmental delay in two children, severe in one (DQ<50) and borderline (DQ=86) in another, and optic atrophy in one child. None had evidence of retrolental fibroplasia or bronchopulmonary dysplasia. We conclude that these salvaged babies constitute a very high risk population for ongoing difficulties, whose followup needs include expensive multidisciplinary testing and treatment. Organized followup for these children must be developed. PPHN should be an identified risk category for enrollment in state Crippled Childrens funding programs.

RESPONSE OF NEWBORN LAMB TO ISOPROTERONOL INFUSION

We studied 6 chronically instrumented newborn lambs during normoxia (N) and hypoxia (H) on alternating days during infusion of isoproteronol (I) from .062 to 2.5 mcg/kg/min while measuring PAP, LAP, SAP, pulmonary flow (QP) heart rate (HR) and blood gases. Pulmonary (PVR) and systemic vascular resistance (SVR) and PVR/SVR were calculated. Infusion during N resulted in decreased SAP, PVR, SVR and increased HR, QP, and PVR/SVR. During H+I compared to N base, SAP, and SVR decreased and PAP, PVR, HR, QP, and PVR/SVR increased. QP increased significantly during H alone, and did not increase further with I infusion. Changes from N base to H base were not increased further when H+I was compared to H base except for HR which rose from 271±8 to 320±19 ml/kg/min.No arrhythmias occurred with I, but one lamb required resuscitation when QP fell to zero and respiration ceased during H+I at 2.5 mcg/kg/min. A significant persistent metabolic acidosis occurred during both H and N and continued into the recovery periods. Neonates may not benefit from isoproteronol infusion under hypoxic conditions.