Morphine increases synchronous ventilation in preterm infants

Objectives: To examine the short-term cardiorespiratory effects of intravenous morphine infusion in ventilated preterm infants.
Methodology A randomized double-blind placebo-controlled trial in a neonatal intensive care unit. Twenty-six preterm infants (29-36 weeks gestation) with hyaline membrane disease requiring ventilatory assistance on the first day after birth were included in the study. A loading dose of morphine 100 μg/kg over 30 min followed by a continuous intravenous infusion at 10 μg/kg per hour was given. Primary measures were heart rate, blood pressure, respiratory rate and interaction of spontaneous respiration with mechanical ventilation. Secondary measures were durations of oxygen therapy, ventilator therapy and hospitalization as well as incidence of bronchopuimonary dysplasia, periventricular haemorrhage and pneumothorax.
Results Morphine-treated infants spent a significantly greater percentage of total ventilated time breathing in synchrony with their ventilators (median [IQ]= 72[58-87] vs 31 [17-51]%; P = 0.0008). Heart rate and respiratory rate, but not blood pressure, were reduced in morphine-treated infants. Duration of oxygen therapy was reduced (median [IQ]= 4.5[3-7] vs 8[4.75-12.5] days; P = 0.046).
Conclusions Intravenous morphine infusion increases synchronicity of spontaneous and ventilator-delivered breaths in preterm infants. Morphine reduces heart rate and respiratory rate without reducing blood pressure, and may help to reduce duration of oxygen therapy in preterm infants with hyaline membrane disease.     

Spontaneous DNA synthesis of blood lymphoid cells in premature newborn infants,in older premature infants and in full-term newborn infants

In adults, blood cells which synthesize DNA spontaneously are large, pale lymphoid phagocytes. In fetal blood, transitional cells label spontaneously in addition to the lymphoid phagocytes (Prindull et al., 1975a, b). In the present study, we have measured quantitatively by scintillation counting, spontaneous thymidine incorporation of blood cells from different groups of infants.When compared with the conditions in the normal adult, spontaneous DNA synthesis of peripheral blood lymphoid cells is increased by a factor of 16.4 in premature newborn infants (P<0.002), by a factor of 8.7 in full-term newborn infants (P<0.01), and in older premature infants studied at the time of their calculated birth dates by a factor of 4.3 (P<0.001).Spontaneously labelling blood cells most likely are, at least in part, hematopoietic stem cells from the bone marrow.With technical assistance of Brigitte Prindull.     

Olfactory reflexes in newborn infants

Olfactory reflexes were tested, using pippermint odor in 110 newborn infants, in the first two days of life. Responses were normal in all the children excepting those with birth asphyxia in whom abnormal responses or no responses were obtained.     

Irregular breathing in young lambs and newborn infants during heat stress

Ten healthy unanaesthetized full-term lambs, aged 4-12 days, were studied during moderate radiant heat stress, and 21 full-term newborn infants were studied during moderate convective heat stress. The rate of breathing and the breathing pattern were recorded, using strain gauges made of mercury-filled rubber tubing placed around the thorax and abdomen. In both the lambs and the infants the respiratory rate increased during heat stress. When this increase began, both the lambs and infants had short periods of very rapid breathing followed by short apnoeas. The concentrations of carbon dioxide and water in a flow-through system collecting expired air increased during the short periods of rapid breathing and then decreased again during the subsequent short apnoeic period.     

Early postnatal hypoglycaemia in newborn infants of diabetic mothers

This study found that early postnatal hypoglycaemia was mainly induced by foetal hyperinsulinaemia, in close relation to maternal hyperglycaemia. even in well-controlled pregnancies of 59 mothers with insulin-treated diabetes mellitus, 29 with insulin-dependent diabetes mellitus and 30 with gestational diabetes mellitus. Ten of the newborn children (17%) had a blood glucose concentration below 1.0mmol 1^-1 at 2h postnatally. Cord insulin-like growth factor-1 or glucagon concentrations were not related to the early decline of blood glucose.     

足月新生儿急性呼吸窘迫综合征临床特征及预后

为探讨足月新生儿急性呼吸窘迫综合征( ARDS)的临床特征,提高对该病的认识,以便及早采取有效的治疗,参照 1994年美国和欧洲 ARDS评审会议制订的 ARDS诊断标准,对 1999年 1月～ 2002年 3月 NICU住院的有青紫、呼吸困难、需机械通气治疗的 87例足月新生儿进行回顾性调查分析.结果显示符合足月新生儿 ARDS诊断者共 10例,发病率 11.5%,死亡率 20.0%.其临床特征为①急性起病,原发病后( 11.4± 13.8) h出现症状;②进行性呼吸困难,严重低氧血症;③ PaO2/FiO2<200 mmHg;④急性期胸部 X线表现双肺弥漫性浸润影或"白肺";⑤需用呼吸机进行机械通气治疗 >48 h;⑥不能用其他呼吸系统疾病或心脏疾病解释.表明足月新生儿 ARDS临床上并不少见,严密临床观察及动态胸部 X线检查、血气分析可明确诊断,及早机械通气治疗,从而改善预后.     

The efficacy of oral theophylline in ventilated premature infants

40 ventilated premature infants, with gestational ages of 24-34 weeks and a mean birthweight of 1422 g, were entered into a randomised controlled trial. 20 of the infants received orally 5 mg/ml anhydrous theophylline dissolved in 20% pure alcohol, with a loading dose of 5 mg/kg and then 1.25 mg/kg every 6 h. Plasma samples were assayed via an emit enzyme immunoassay, demonstrating satisfactory serum levels in all infants at 54 h after the loading dose. Possible side-effects were seen only in two infants, in one a tachycardia (220 beats/min) and the other became agitated during treatment.     

Clinical prediction of post-extubation radiological changes of the chest in newborn infants

Objective: Whether a chest radiograph should be performed routinely in all infants after extubation, or selectively only in those with clinical deterioration, is a controversy in neonatal unit practice. This study tested the hypothesis that most cases of post-extubation radiological deterioration in the lungs could be detected by clinical assessment. Methods: A chest radiograph was performed at 8 h post-extubation in 100 episodes of extubation in 85 newborn infants ventilated for a variety of lung diseases. Each infant was assessed at the same time by a neonatologist blinded to the radiological findings, to determine whether a chest radiograph would have been requested based on clinical judgement. The infants were continuously monitored for their respiratory and oxygenation status before and after extubation. Results: Compared to the pre-extubation chest radiographs, 23 of the 100 post-extubation chest radiographs showed either deterioration of the pre-existing lung pathologies or appearance of significant new pathologies. The clinicians' assessment failed to detect most of the deterioration, with a sensitivity of only 21.7%. Systematic analysis of the infants' clinical parameters showed that the development of significant intercostal/subcostal retraction, and an increase in inspired oxygen concentration by ≥ 7% after extubation, were the best predictors of post-extubation radiological deterioration (sensitivity 82.6%, specificity 62.3%, positive predictive value 39.6%, and negative predictive value 92.3%). Serial blood gas in contrast had little predictive value. Conclusion: We conclude that most cases of radiological deterioration of the lungs after extubation are clinically predictable, provided the correct clinical criteria are used.     

Pharmacokinetic-therapeutic studies of ceftriaxone in premature and mature newborn infants

Ceftriaxone a third generation Cephalosporine exhibits a high degree of antimicrobial activity against the most common pathogens causing life threatening infections in premature and newborn infants. Ceftriaxone was used therapeutically in 16 premature and newborn infants with proven or suspected bacterial infections. Pharmakokinetic investigations were performed during this therapeutic trial. 0.1 ml of blood was taken at 2, 6 and 10 hours after intravenous administration of 50 mg/kg BW Ceftriaxone administered as a single daily bolus injection. Again on day two and four 2 hours after readministration of the same dose, serum concentrations were determined by a biologic test method. With these five samples only, we were able to calculate all clinically relevant pharmakokinetic parameters. There was a high degree of agreement between the experimentally determined and the calculated parameters. Premature infants showed a lower Cmax (115 micrograms/ml) which corresponded to the higher volume of distribution of 44% in this age group. Newborn infants in contrast showed a Cmax of 129 micrograms/ml corresponding to a volume of distribution of 39%. The halflife of elimination was 10.4 and 9.6 hours resp. for premature and mature newborn infants. Cumulation of the drug was seen during the first two days of treatment. A steady state however ensued on day three in both age groups after which no further increase in maximum serum concentrations was seen. Our data suggest, that 50 mg/kg BW once daily given intravenously by bolus-injection or short infusion over 30 minutes constitutes sufficient therapy for serious bacterial infections in premature and newborn infants with susceptible organisms.(ABSTRACT TRUNCATED AT 250 WORDS)     

Postmortem angiocardiography in newborn infants with congenital malformation of the heart and great vessels

In congenital malformations of the heart and great vessels with a fatal outcome a postmortem angiocardiography may contribute to diagnosis. In this technique the heart is not dissected and the topographical relationships remain unchanged. A postmortem angiocardiography is of particular interest if no autopsy is to be performed. Some patho-anatomical details are demonstrated in three selected cases: newborn infants with 1. hypoplastic left heart syndrome, 2. truncus arteriosus communis with interruption of the aortic arch, and 3. aottic-left ventricular tunnel.     

新生儿侵袭性霉菌感染早期诊断和治疗研究近况

近年来由于新生儿NICU的发展、广谱抗生素及免疫抑制剂的广泛应用,加上新生儿处于免疫发育尚未成熟阶段,侵袭性霉菌感染日益引起重视。据Friedman等报道,侵袭性霉菌感染已成为极低出生体重儿院内感染的主要原因。霉菌是引起NICU院内感染的第三种常见病菌。侵袭性霉菌感染增加了新生儿、早产儿、极低出生体重儿的病死率和致残率,病死率约为20％～40％。我院NICU近十年来侵袭性霉菌感染的发病率为1．73％,病死率为37．5％。因此,早期诊断和早期治疗侵袭性霉菌感染能降低新生儿、早产儿的死亡率和改善预后。为进一步提高早期诊断和治疗,兹结合有关文献作一阐述。     

Diagnosis of 21-hydroxylase deficiency in newborn infants by GC-MS of urinary steroids

Abstract In a study using gas chromatography-mass spectrometry (GC-MS) on urine specimens from 16 normal infants and 16 infants with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (aged 1 day to 4 weeks), the major steroids recognized in all infants were: 16α-hydroxy-dehydroepiandrosterone, 16β-hydroxy-dehydroepiandrosterone, 16-oxo-androstenediol, androstenetriol, 15β, 17α-dihydroxy-pregnenolone and 16α-hydroxy-pregnenolone.
Pregnanetriol was detectable in three normal infants (aged 3, 6 and 15 days) but the levels seen in 15 CAH patients were in a higher range. Pregnanetriolone, 5β-17-hydroxy-pregnanolone and 15β, 17α-dihydroxy-pregnanolone were present in the urine of 15 CAH patients, but were not detectable in any of the normal infants. The older the patient, the higher the level was of each of these four steroids.
The results indicate that, even on day 1, patients with CAH due to 21-hydroxylase deficiency may be positively identified using GC-MS of urine specimens. This does not preclude the possibility that a minority of patients with CAH, most likely those with mild 21-hydroxylase deficiency, may not exhibit the characteristic GC-MS findings on day 1, as seen in one of the 18 CAH patients.     

Pharmacokinetics and protein binding of intravenous ibuprofen in the premature newborn infant

The elimination, disposition and protein binding of ibuprofen (IBU) in premature infants were studied for use in the prevention of intraventricular hemorrhage and closure of patent ductus arteriosus. The kinetic profile of i.v. IBU lysine (10 mg/kg bolus) given within the first 3 h after birth was studied in 21 premature neonates (mean birthweight = 944.7 g, range: 575–1450 g; gestational age: 26.8 weeks, range: 22–31 weeks). Blood samples (0.3 ml/sample) were obtained at time 0 and at 1, 3, 6, 12, 24, 48, and 72 h post-dose for IBU by high-performance liquid chromatography (HPLC). Kinetic analyses assumed applicability of one open-compartment model and calculations from the model-independent areas under the time concentration curve (AUC). Data (mean ± SEM) show that apparent volume of distribution (AVd) was 62.1 ± 3.9 ml/kg, plasma t _1/2 beta was 30.5 ± 4.2 h, elimination rate constant (k_el) was 0.032 ± 0.004 h^-1plasma clearance was 2.06 ± 0.33 ml/kg/h and plasma concentration (Cp) at 1 h was 180.6 ±11.1 mg/1. Gestational age and birthweight were not related to drug elimination. In 10 neonates, IBU maintenance dose of 5 mg/kg once daily on days 2 and 3 generated mean Cp of 116.6 ± 54.5 mg/1 and 113.6 ± 58.2mg/1, respectively. Protein binding by ultrafiltration and capillary electrophoresis showed that the percentage bound IBU was significantly lower in full term cord plasma (94.98 ± 0.39%, n = 26) compared to adult plasma protein (mean ± SE = 98.73 ± 0.31%, n = 8, p < 0.0001). Compared to data from adults and older children, IBU elimination is markedly prolonged in neonates and protein binding is slightly lower. Thus, investigational and clinical therapeutic regimens should be adjusted to account for decreased drug disposition to ensure safe and effective therapy.     

围产期窒息母儿血浆催乳素水平变化研究

为探讨窒息新生儿母、儿血浆催乳素( PRL)水平变化与相关性及其意义,采用放射免疫分析法对 25例围产期窒息儿及 20例正常对照组母血、脐血及新生儿血浆 PRL水平进行测定并进行动态观察.结果显示窒息组母血、脐血及新生儿血浆 PRL水平均显著高于正常对照组( P均 <0.01);重度窒息组母血、脐血及新生儿血浆 PRL水平均高于轻度窒息组,差异具有显著性( P<0.01, <0.001, <0.01),窒息儿母血、脐血及新生儿血浆 PRL水平具有显著的正相关关系( r=0.54,P<0.05).窒息新生儿复苏后血浆 PRL水平显著增高,生后第 2 d PRL水平逐渐下降,生后第 10 d血浆 PRL水平虽高于正常对照组,但差异无显著性( P>0.05).提示围产期窒息新生儿血浆、脐血、母血 PRL水平显著增高,其可能的机理是窒息时缺氧缺血导致脑组织释放兴奋性氨基酸增加,进而刺激垂体前叶释放 PRL,导致血浆及脐血 PRL水平增高.因此认为,血浆 PRL水平可作为判断新生儿窒息程度及由窒息缺氧所致新生儿脑损伤恢复状况的一项参考指标.     

Serum magnesium level and sleep behavior of newborn infants

Polygraphic studies were performed in 14 fullterm newborns. The sleep behavior of the infants was correlated to the serum Mg level. Correlations could be demonstrated between serum Mg and active sleep, as well as between serum Mg and quiet sleep. With increasing serum Mg quiet sleep increased, whereas active sleep decreased. After Mg injection quiet sleep increased and active sleep decreased even more. There were also corresponding correlations between serum Mg and rapid eye movements, submental muscle tone, and gross body movements.