Complications of umbilical artery catheterization in a model of extreme prematurity.

OBJECTIVE: Umbilical artery catheter (UAC) use is common in the management of critically ill neonates; however, little information exists regarding the anatomic and vascular effects of UAC placement in premature newborns. STUDY DESIGN: Baboons were delivered at 125 days of gestation (term=185 days), treated with surfactant, had UACs placed and were ventilated for either 6 or 14 days. Animals were assigned to short-term (6 days, n=6) and long-term (14 days, n=30) UAC placement. At necropsy, aortas were removed with UACs still in place. Histological examination of upper, middle and lower aorta specimens stained with hematoxylin and eosin and immunolabeled to detect smooth muscle (alpha-actin) was carried out in a blinded manner. Controls were delivered at 125, 140 and 185 days and the aortas acquired immediately after birth. None of the non-catheterized control animals (125 days, n=4; 140 days, n=5; and 185 days, n=5) had aortic vessel thrombi or vascular wall abnormalities. RESULT: All 6 animals with short-term (6/6, 100%) and 18 animals with long-term (18/30, 60%) UAC placement displayed aortic thrombi and neointimal proliferation of the vascular wall. The majority (60%) of analyzed animals with UAC placement displaying neointimal hyperplasia were immunopositive for alpha-actin, indicating the presence of smooth muscle in these lesions. CONCLUSION: Our findings suggest that both short- and long-term UAC use is associated with aortic wall pathological abnormalities compared with control animals. This study emphasizes the judicious use and early removal of UACs if possible in order to potentially prevent significant hemostatic and aortic wall vascular complications.

Contrast sonography, video densitometry and intervillous blood flow: a pilot project.

PURPOSE: To examine the feasibility of constructing time-intensity (TI) curves from the intervillous space with an intravascular ultrasound contrast agent and computer assisted video densitometry. STUDY DESIGN: We sedated nine pregnant baboons, optimized the grey scale and color Doppler images of their placentas, and then fixed the transducers in place. For each injection of contrast, we recorded images on videotape without changing the ultrasound image processing functions. Video images were captured using a Macintosh personal computer equipped with a video-capture board using image analysis software (Image 1.4, W Rasband, NIH). For each injection, we sampled digitized images of a fixed region of interest at regular intervals. After computing the mean video density of each image, we used the sampling frequency to construct TI curves depicting any change over time as the contrast agents washed into and out of the intervillous space. RESULTS: Three of four agents tested produced changes in the video density of the placenta. TI curves were established using both grey scale and color Doppler signal augmentation. As expected, intra-arterial agents produced rapid accumulation and decay. Intravenous agents produced more protracted effects secondary to bolus dilution and transit through the right heart and pulmonary vascular bed. CONCLUSION: TI curves may be generated from the intervillous space with the use of a transpulmonary ultrasound contrast agent and video densitometry. If validated by further study, this may allow investigators to apply ultrasound and indicator-dilution theory to intervillous blood flow.

Randomized, multicenter trial of inhaled nitric oxide and high-frequency oscillatory ventilation in severe, persistent pulmonary hypertension of the newborn.

BACKGROUND: Although inhaled nitric oxide (iNO) causes selective pulmonary vasodilation and improves oxygenation in newborn infants with persistent pulmonary hypertension, its effects are variable. We hypothesized (1) that the response to iNO therapy is dependent on the primary disease associated with persistent pulmonary hypertension of the newborn (PPHN) and (2) that the combination of high-frequency oscillatory ventilation (HFOV) with iNO would be efficacious in patients for whom either therapy alone had failed. METHODS: To determine the relative roles of iNO and HFOV in the treatment of severe PPHN, we enrolled 205 neonates in a randomized, multicenter clinical trial. Patients were stratified by predominant disease category: respiratory distress syndrome (n = 70), meconium aspiration syndrome (n = 58), idiopathic PPHN or pulmonary hypoplasia (excluding congenital diaphragmatic hernia) ("other": n = 43), and congenital diaphragmatic hernia (n = 34); they were then randomly assigned to treatment with iNO and conventional ventilation or to HFOV without iNO. Treatment failure (partial pressure of arterial oxygen [PaO2] < 60 mm Hg) resulted in crossover to the alternative treatment; treatment failure after crossover led to combination treatment with HFOV plus iNO. Treatment response with the assigned therapy was defined as sustained PaO2 of 60 mm Hg or greater. RESULTS: Baseline oxygenation index and PaO2 were 48 +/- 2 and 41 +/- 1 mm Hg, respectively, during treatment with conventional ventilation. Ninety-eight patients were randomly assigned to initial treatment with HFOV, and 107 patients to iNO. Fifty-three patients (26%) recovered with the initially assigned therapy without crossover (30 with iNO [28%] and 23 with HFOV [23%]; p = 0.33). Within this group, survival was 100% and there were no differences in days of mechanical ventilation, air leak, or supplemental oxygen requirement at 28 days. Of patients whose initial treatment failed, crossover treatment with the alternate therapy was successful in 21% and 14% for iNO and HFOV, respectively (p = not significant). Of 125 patients in whom both treatment strategies failed, 32% responded to combination treatment with HFOV plus iNO. Overall, 123 patients (60%) responded to either treatment alone or combination therapy. By disease category, response rates for HFOV plus iNO in the group with respiratory syndrome and the group with meconium aspiration syndrome were better than for HFOV alone or iNO with conventional ventilation (p < 0.05). Marked differences in outcomes were noted among centers (percent death or treatment with extracorporeal membrane oxygenation = 29% to 75%). CONCLUSIONS: We conclude that treatment with HFOV plus iNO is often more successful than treatment with HFOV or iNO alone in severe PPHN. Differences in responses are partly related to the specific disease associated with PPHN.

Hormonal response of the premature primate to operative stress.

There are few data on the hormonal response to operation in the premature infant. Studies examining the response of newborn human infants have been performed on patients beyond the first few days of life, where some adaptation to postnatal life has occurred. This study evaluated the response of the newly born premature primate to surgical stress. Premature baboons (75% gestation) were intubated, mechanically ventilated and underwent thoracotomy at 2 hours of life with exposure of the ductus arteriosus (PDA). In group 1, formalin was infiltrated to keep the ductus patent. In group 2, the PDA was ligated. Controls had no operation. Blood was drawn at 0, 6, 24, 48, 72, and 96 hours of age. Echocardiograms were performed to confirm patency or closure of the ductus and to monitor cardiac function. Epinephrine, norepinephrine, renin, and cortisol levels were measured. Cortisol levels rose in all groups. Operation stimulated a marked increase in catecholamine and renin levels in both operative groups, which was more marked in the group with PDA ligation at 24 hours. These data reflect expected pathophysiology since early PDA ligation exerts additional hemodynamic demand on the heart. In conclusion, the premature primate is able to mount a significant and severity-dependent endocrine response to stress.

Cardiac performance in ECMO candidates: echocardiographic predictors for ECMO.

Twenty-one neonates with severe respiratory failure, who met criteria in this center for extracorporeal membrane oxygenation (ECMO), underwent echocardiographic examinations to assess the role of cardiac dysfunction in determining the need for ECMO. The echocardiographic indexes of function included peak aortic and pulmonary flow velocity, aortic and pulmonary acceleration, shortening fraction, velocity of circumferential fiber shortening, right ventricular output, and left ventricular output. Patients were offered a staged treatment protocol using high-frequency oscillatory ventilation (HFOV), followed by ECMO if failing HFOV rescue. Nine patients demonstrated progressive deterioration and required ECMO (group 1); 12 patients recovered without ECMO (group 2). There were no significant intergroup differences in AaDO2, age, weight, gestational age, inotropic support, mean airway pressure, systemic blood pressure, or arterial blood gas parameters. Group 1 had significantly lower pulmonary and aortic peak flow velocities, lower pulmonary acceleration, lower shortening fraction, and lower velocity of circumferential fiber shortening (P less than .05). We found that values for peak pulmonary velocity less than 0.70 m/s with pulmonary acceleration less than 14 m/s2 would predict the need for ECMO in 7 of 9 group 1 patients and recovery without ECMO in 11 of 12 group 2 patients (P less than .01, Fisher's Exact test). We conclude that on initial echocardiographic evaluation, cardiac performance was impaired in those patients who subsequently required ECMO compared with a group of patients with similar severity in gas exchange who recovered without ECMO. We speculate that echocardiographic assessment of cardiac performance in ECMO candidates may prove useful in prediction of the subsequent need for ECMO or expedient transfer to an ECMO center.