Cardiovascular response to dopamine in hypotensive preterm neonates with severe hyaline membrane disease

The effect of low dose (2, 4, and 8 g/kg per min) dopamine infusion on blood pressure, heart rate and renal function was studied in 18 hypotensive, preterm infants with severe hyaline membrane disease (HMD). Significant dose-related effects found during dopamine infusion were systolic and diastolic blood pressure elevation and diuretic effect, while heart rate increase occurred only with 8 g/kg per min of the drug. This indicates, that in the preterm neonate, dopamine at low doses has a pronounced effect on the alpha-and dopamine-receptors, while its beta-receptor stimulating activity is minimal. We demonstrated a significantly decreased metabolic clearance rate of dopamine in preterm infants. Thus, beside the differences in the vascular receptors' maturation, the decreased metabolic clearance rate should also be taken into account when explaining the cardiovascular and renal effects of low dose dopamine infusion in these babies. Dopamine was found to be useful in normalizing low arterial blood pressure, in improving impaired peripheral circulation, and in producing a marked diuresis in hypotensive preterm neonates with severe hyaline membrane disease.Abbreviations CVP central venous pressure - HMD hyaline membrane disease - tcpO₂ transcutaneous oxygen tension - TPVR total peripheral vascular resistance     

Remifentanil for INSURE in preterm infants: a pilot study for evaluation of efficacy and safety aspects

Aim:  To evaluate intubating conditions, extubation times and outcome in preterm infants receiving remifentanil as induction agent for the INSURE procedure.
Methods:  In twenty-one preterm infants of 29 to 32 weeks gestation and signs of respiratory distress, we utilized remifentanil as induction agent for the INSURE procedure. Following intubation and surfactant application, the infants were mechanically ventilated until respiratory drive was judged to be satisfactory for continuing CPAP therapy. Intubating conditions were classified by our own scoring system by rating limb movements, coughing and breathing. Heart rate, blood pressure and oxygen saturation were recorded during the entire INSURE procedure.
Results:  Remifentanil provided excellent or good intubating conditions in all patients. We observed no serious side effects after remifentanil infusion, in particular, no thorax rigidity, clinically significant bradycardia or arterial hypotension. Average extubation time after surfactant administration was 16.9 min (1–45 min); none of the infants had to be reintubated. Following extubation, the infants required only 3.3 days (1–8 days) of CPAP therapy. None exhibited serious complications of prematurity like periventricular leucomalacia, intraventricular haemorrhage >I°, necrotizing enterocolitis or retinopathy.
Conclusion:  In this pilot study, INSURE with remifentanil was associated with good intubating conditions and early extubation resulting in an excellent neonatal outcome.     

Effect of morphine on respiratory drive in trigger ventilated pre-term infants

The response to morphine (100 microgram (microg)/kg bolus, 10 microg/kg/h infusion) of 14 babies (median birth weight/gestation 1. 37 kg/30 weeks) trigger ventilated for hyaline membrane disease was compared to a group of 26 babies (median birth weight/gestation 1.1 kg/28 weeks) also trigger ventilated for hyaline membrane disease but not treated with morphine. The effect of morphine on triggered breath rate was very variable with no significant difference between the groups seen until 12 h after starting the infusion (mean [95% CI] difference=-17 [-33, -2] breaths/min). In those babies (n=11) who had plasma morphine levels measured there was no significant reduction in triggered rate over time despite significantly increasing plasma morphine levels. Babies who produced morphine-6-glucuronide at 12 h showed a significantly greater reduction in triggered breath rate than those who did not (median change -22 breaths/min compared to -4 breaths/min).     

Respiratory Failure in Infants Weighing 1000 g or Less at Birth

Yu, V. Y. H., and Hollingsworth, E. (1979). Aust. Paediatr. J. , 15, 152–159. Respiratory failure in Infants weighing 1000 g or less at birth. The prognosis for infants weighing <1000 g has improved coincident with the improved ventilatory support in their neonatal management. There are many problems leading to respiratory failure which are particularly significant and peculiar to these infants. Of the 55 infants weighing <1000 g admitted in 1977 and 1978, 58% had hyaline membrane disease and 69% had preterm recurrent apnoea. Fifty-one infants required assisted ventilation, or whom 28 were ventilated from birth. Though these infants could be ventilated successfully with low peak airway and positive end-expiratory pressures, 52% of the ventilated infants required it for more than seven days, despite the use of intermittent mandatory ventilation and continuous positive airway pressure during weaning. The neonatal survival rate for assisted ventilation in infants weighing <1000 g was 57%. Seventeen of the ventilated infants developed pulmonary interstitial emphysema, a condition which was associated with an increased incidence of pneumothorax (four infants) and bronchopulmonary dysplasia (ten infants). Infants recovering from bronchopulmonary dysplasia required up to 76 days of assisted ventilation and 84 days of oxygen therapy. No major handicaps were detected on follow-up except for one infant with retrolental fibroplasia. Optimal management of respiratory failure in infants weighing <1000 g can now result in increased survival with morbidity approaching those of larger preterm infants. As our knowledge, skills, techniques and equipment continue to improve, so will survival and morbidity rates.     

Remifentanil analgosedation in preterm newborns during mechanical ventilation

Aim:  To assess efficacy of remifentanil in preterm newborns during mechanical ventilation.
Methods:  Remifentanil was administered by continuous intravenous infusion to provide analgesia and sedation in 48 preterm infants who developed respiratory distress and required mechanical ventilation. We examined the doses needed to provide adequate analgesia, extubation time after the discontinuation of opioid infusion, the presence of side effects and safety of the use.
Results:  Remifentanil provided adequate analgesia, with a significant reduction of NIPS and COMFORT score since 1 h after starting the infusion of remifentanil. The drug was initially administered at a dose of 0.075 μg/kg/min, but in 73% of newborns the latter had to be increased; at a dose of 0.094 ± 0.03 (mean ± standard deviation) μg/kg/min, 97% of the newborns received adequate analgesia and sedation. The time elapsed between the discontinuation of remifentanil infusion and extubation was 36 ± 12 min. Treatment was started between the 1st and the 17th day of life. The mean duration of therapy was 5.9 ± 5.7 days. No side effects on the respiratory or cardiovascular system were observed.
Conclusion:  Remifentanil is a manageable and effective opioid in the newborn undergoing mechanical ventilation, though randomized controlled trials and information about long-term outcomes are necessary.     

Effects of midazolam and morphine on cerebral oxygenation and hemodynamics in ventilated premature infants

BACKGROUND: Midazolam sedation and morphine analgesia are commonly used in ventilated premature infants. OBJECTIVES: To evaluate the effects of midazolam versus morphine infusion on cerebral oxygenation and hemodynamics in ventilated premature infants. METHODS: 11 patients (GA 26.6-33.0 weeks, BW 780-2,335 g) were sedated with midazolam (loading dose 0.2 mg/kg, maintenance 0.2 mg/kg/h) and 10 patients (GA 26.4-33.3 weeks, BW 842-1,955 g) were sedated with morphine (loading dose 0.05 mg/kg, maintenance 0.01 mg/kg/h). Changes in oxyhemoglobin (Delta cO2Hb) and deoxyhemoglobin (Delta cHHb) were assessed using near infrared spectrophotometry. Changes in cHbD (= Delta cO(2)Hb - Delta cHHb) reflect changes in cerebral blood oxygenation and changes in concentration of total hemoglobin (Delta ctHb = Delta cO2Hb + Delta cHHb) represent changes in cerebral blood volume (DeltaCBV). Changes in cerebral blood flow velocity (DeltaCBFV) were intermittently measured using Doppler ultrasound. Heart rate (HR), mean arterial blood pressure (MABP), arterial oxygen saturation (saO2) and transcutaneous measured pO2 (tcpO2) and pCO2 (tcpCO2) were continuously registered. Statistical analyses were carried out using linear mixed models to account for the longitudinal character study design. RESULTS: Within 15 min after the loading dose of midazolam, a decrease in saO2, tcpO2 and cHbD was observed in 5/11 infants. In addition, a fall in MABP and CBFV was observed 15 min after midazolam administration. Immediately after morphine infusion a decrease in saO2, tcpO2 and cHbD was observed in 6/10 infants. Furthermore, morphine infusion resulted in a persistent increase in CBV. CONCLUSIONS: Administration of midazolam and morphine in ventilated premature infants causes significant changes in cerebral oxygenation and hemodynamics, which might be harmful.     

Cardiovascular effects of an intravenous bolus of morphine in the ventilated preterm infant

AIM: To examine the cardiovascular effects of an intravenous bolus of morphine, 100 microg/kg, in 17 ventilated preterm infants. METHODS: Heart rate and blood pressure were monitored. Right ventricular output, superior vena caval flow, and the width of the ductus arteriosus were measured by Doppler echocardiography 10 and 60 minutes after the morphine injection, and the values compared with baseline values by the paired t test. RESULTS: There was a small but significant fall in heart rate (2.1% at 10 minutes, 4.3% at 60 minutes) consistent with a sedative effect. There was no effect on systolic, diastolic, or mean blood pressure. There was no significant effect on systemic blood flow as measured by either right ventricular output or superior vena caval flow. Ductal width was significantly reduced by a mean of 16% at 60 minutes, suggesting that normal duct closure was not inhibited. CONCLUSION: No cardiovascular effects of an intravenous bolus of morphine could be detected.     

INTRAVENOUS INFUSION OF GLUCOSE AND SODIUM BICARBONATE IN HYALINE MEMBRANE DISEASE

A controlled trial of the effect of intravenous infusion of glucose and sodium bicarbonate was performed in 48 low weight newborn infants with hyaline membrane disease. The experimental design included diagnosis by clinical and radiological criteria and random assignment to the treatment and control series. In treated infants the mortality rate was lower, early death occurred less frequently and the neonatal survival curve was improved when compared with controls. Only the difference in survival curves of treated and control patients was statistically significant. Systolic blood pressure was found to be a factor of considerable prognostic significance. We conclude that intravenous infusions of glucose and sodium bicarbonate should be part of the routine therapy of infants with hyaline membrane disease.     

晚期早产儿呼吸系统疾病患病临床特点

目的：探讨晚期早产儿呼吸系统疾病患病的临床特点。方法：选取2009年1月至2010年12月在我院产科出生的新生儿,其中晚期早产儿 (胎龄34~36+6周)630例,足月儿4401例,早期早产儿（胎龄≤33+6周）328例。其中患呼吸系统疾病者包括晚期早产儿84例,足月儿135例,早期早产儿182例。比较3组新生儿呼吸系统疾病发病情况、临床特点及危重程度。结果：（1）晚期早产儿组呼吸系统疾病发生率、病死率及危重症比例均高于足月儿组,而低于早期早产儿组(P<0.01)。（2）晚期早产儿组呼吸困难起病时间早于足月儿组,晚于早期早产儿组（P<0.01）;呼吸增快百分比较其他两组高,而三凹征百分比较低(P<0.05); 晚期早产儿组需氧疗及机械通气的比例均明显高于足月儿组,而低于早期早产儿组(P<0.05)。（3）多元线性回归分析发现血氧分压降低、红细胞压积减低、血pH值减低、呼吸减慢、动脉血氧饱和度减低、动脉收缩压减低、5 min Apgar评分减低、胎龄较小、血尿素氮增高、心率增快、呼吸增快是新生儿呼吸系统疾病危重症的影响因素。结论：晚期早产儿比足月儿更容易出现呼吸系统疾病,危重程度较重,需加强呼吸支持。晚期早产儿呼吸困难多表现为呼吸增快,起病时间早于足月儿而晚于早期早产儿。对于晚期早产儿,如发现呼吸困难、心率、血压异常及多系统受累表现,常提示其病情危重,应积极治疗。     

Use of [13C]bicarbonate for metabolic studies in preterm infants: intragastric versus intravenous administration

The metabolic fate of substrates in humans can be examined by the use of stable isotopes, one of which, [13C]bicarbonate, may serve to estimate CO2 production rate. In view of minimizing the burden of metabolic studies for preterm infants, the authors determined whether intragastric and intravenous infusions of [13C]bicarbonate would achieve the same 13CO2 enrichment in expired air during steady state. A second aim of this study was to determine the minimum time required to reach steady state during intragastric infusion. Ten preterm infants received a primed continuous [13C]bicarbonate infusion intragastrically, followed by an intravenous infusion the next day. Breath samples were obtained every 30 min by the direct sampling method. 13CO2 isotopic enrichment, expressed as atom percent excess, was measured by isotopic ratio mass spectrometry. Two-tailed t tests were used to detect statistically significant differences between the infusion routes. The isotopic enrichment at plateau did not differ between intragastric and intravenous infusion. A steady state of 13CO2 enrichment was achieved after 60 min of intravenous infusion and after 120 min of intragastric infusion. In conclusion, intragastric infusion of [13C]bicarbonate may serve to estimate the whole-body CO2 production rate in preterm infants. To reach 13CO2 steady state, a minimum of 120 min of bicarbonate administration is required.     

Effect of single loading dose of intravenous caffeine infusion on superior mesenteric artery blood flow velocities in preterm infants

Aim:   To evaluate the effects of a single loading dose of caffeine base (10 mg/kg) on superior mesenteric artery (SMA) blood flow velocities (BFV).
Methods:   Eighteen preterm infants of gestational age ≤32 weeks gestation were investigated prospectively. SMA BFV before infusion, 1 h, 2 h and 6 h after a single loading dose of caffeine were measured using Doppler ultrasonography.
Results:   The peak systolic velocity in SMA decreased by 18% from baseline at 1 h after caffeine infusion and improved towards the baseline by 6 h after the infusion. The reduction in velocity after caffeine infusion was not statistically significant. No significant changes were observed in heart rate, blood pressure and incidence of necrotising enterocolitis.
Conclusion:   A single 10 mg/kg intravenous loading dose of caffeine does not cause a significant reduction in SMA BFV and therefore does not place the preterm intestine at increased risk of ischemic injury.     

Risk factors for sensorineural hearing loss in extremely premature infants

Objective: To identify potentially preventable risk factors for sensorineural hearing loss (SNHL) in extremely premature infants.
Methodology A case control study of survivors with gestational age (GA) <28 weeks or birthweight (BW) <1000 g using data collected prospectively in our Neonatal Intensive Care Unit database. Each subject with bilateral SNHL >40dB was matched according to GA, BW and sex with two controls who had neither sensorineural nor conductive hearing loss.
Results Infants with SNHL had increased mean (±s.d.) days ventilated (53 ± 21 vs 37±23 days, P = 0.006) and in oxygen (107±44 vs 69±28 days, P = 0.02) compared with controls. The risk for SNHL was increased for infants who spent >90 days in oxygen (OR 4.0 [95% Cl 1.1-15.6]), had maximum FiO₂ >0.90 (5.6 [1.2-26.9]), minimum plasma Na <125mmol/L (5.6 [1.1-27.8] or maximum pH >7.60 (5.6 [1.1-89.0]). Neither maximum serum bilirubin nor exposure to ototoxic drugs was associated with SNHL.
Conclusions: Avoidance of severe hyponatraemia and extreme alkalosis, as well as use of surfactant to minimize the severity of hyaline membrane disease, may result in a decreased incidence of SNHL in extremely premature infants.     

肺表面活性物质预防早产儿呼吸窘迫综合征疗效观察

目的 探讨肺表面活性物质(PS)预防早产儿呼吸窘迫综合征(RDS)的疗效。方法2001年3月～2002年6月我院产科出生早产儿22例；胎龄29～32周；体重1050～1720g。将其分为预防组10例，治疗组12例。预防组于生后30min内即从气管插管内滴入PS(Curosurf，120mg)，用药后应用鼻塞持续气道正压(CPAP)辅助呼吸；治疗组于确诊RDS后应用PS，方法同预防组。结果预防组CPAP辅助呼吸时间、鼻管法氧疗时间明显缩短；PaO2、PaCO2、pH与治疗组比较有显著差异；预防组均存活，不用机械通气，无肺出血、支气管肺发育不良等并发症。结论应用PS预防早产儿RDS，可减轻病情，避免机械通气、缩短氧疗时间，减少早期及后期并发症。     

极早产儿俯卧位机械通气对呼吸功能的影响

目的 探讨极早产儿俯卧位机械通气对呼吸功能的影响。方法 83例经口气管插管机械通气极早产儿随机分为仰卧位组和俯卧位组,4例退出研究,79例完成治疗和观察（仰卧位组37例,俯卧位组42例）,以容量辅助/控制模式机械通气。俯卧位组患儿每仰卧位通气4 h行俯卧位通气2 h。分组干预之前以及分组干预后仰卧位组每6 h、俯卧位组每于转换为俯卧位后的1 h,分别记录呼吸机参数、动脉血气分析和生命体征。结果 俯卧位组FiO₂、气道峰压,平均气道压、机械通气时间低于仰卧位组,差异有统计学意义（P < 0.05）;两组潮气量、呼气末正压的差异无统计学意义（P > 0.05）;俯卧位组的PO₂/FiO₂比值高于仰卧位组,而氧合指数、呼吸频率较低,差异均有统计学意义（P < 0.05）。两组PaO₂、pH、BE、心率和有创动脉血压平均压的差异无统计学意义（P > 0.05）。结论 俯卧位与仰卧位交替通气能改善机械通气极早产儿的氧合功能,降低吸入氧体积分数,缩短机械通气时间。     

Plasminogen did not affect lung function in surfactant-treated preterm lambs

Preterm infants with respiratory distress syndrome develop fibrin-rich hyaline membranes within the alveoli and have depressed fibrinolytic activity, which is thought to be due to a relative deficiency of plasminogen. Local fibrin deposition inhibits surfactant function and amplifies inflammation. We hypothesized that plasminogen administration to surfactant-treated preterm lambs would prevent fibrin-rich hyaline membrane formation, resulting in the amelioration of lung pathology and improved lung function. We randomly treated preterm lambs (gestational age 127-129 days) with either 16 mg of lysine-plasminogen (n = 10) or saline (n = 10), and ventilated them for 5 h. There were no significant differences in physiologic measurements of lung function (ventilation efficiency index, oxygenation index, dynamic compliance, quasi-static pressure volume curve), measures of lung injury (alveolar wash protein content and (125)I-albumin recovery) or surfactant pool size. The degree and extent of bronchiolar erosion and hyaline membrane formation were similar in the two groups. Plasminogen administration did not improve lung function or prevent hyaline membrane formation in surfactant-treated lambs.     

Cardiovascular effects of intravenous midazolam after open heart surgery

Midazolam is the sedating agent of choice in many paediatric intensive care units, and is usually administered as a continuous intravenous infusion with or without a preceding bolus dose. Ten haemodynamically stable children, ventilated in the early postoperative period after cardiac surgery and receiving intravenous morphine infusions, were given an intravenous bolus followed by a continuous infusion of midazolam. Haemodynamic data were recorded before the bolus, and 15 minutes and one hour later. A bolus of midazolam lowered the cardiac output by 24.1%. Arterial blood pressure, oxygen consumption, and mixed venous oxygen content fell significantly. There was a tendency for all variables subsequently to recover towards baseline values, within one hour, during a continuous infusion. An intravenous bolus of midazolam causes a transient but unwanted fall in cardiac output. It is suggested that in children who are receiving intravenous opiates, its use in the early postoperative period be limited to a continuous infusion.     

Randomised controlled trial of low dose fentanyl infusion in preterm infants with hyaline membrane disease

AIM: To evaluate the effects of low dose fentanyl infusion analgesia on behavioural and neuroendocrine stress response and short term outcome in premature infants ventilated for hyaline membrane disease. METHODS: Twenty seven ventilated preterm infants were randomly assigned to receive a mean fentanyl infusion of 1.1 (0.08 SE) micrograms/kg/h for 75 (5) hours, and 28 untreated infants were considered a control group. A behavioural sedation score was used to assess the infants' behaviour. Urinary metanephrine and the normetanephrine:creatinine molar ratio were determined at 0, 24, 48 and 72 hours. Outcome data and ventilatory indexes were recorded for each infant. RESULTS: The fentanyl group showed significantly lower behavioural stress scores and O2 desaturations than controls and lower urinary concentrations of metanephrine and normetanephrine at 24, 48, 72 hours. The two groups showed no significant difference in ventilatory variables or short term outcome. CONCLUSIONS: A short course of low dose fentanyl infusion reduces behavioural sedation scores, O2 desaturations and neuroendocrine stress response in preterm ventilated infants.     

Neonatal respiratory mechanics and development of bronchial hyperresponsiveness in preterm infants

BACKGROUND: In preterm ventilated infants, irreversible damage to the airway mucosa in the neonatal period might be related to the development of bronchial hyperresponsiveness (BHR) in subsequent years. AIMS: To evaluate whether neonatal indicators of long-term respiratory morbidity, respiratory system compliance (Crs) and resistance (Rrs), were causally related to bronchial responsiveness at the age of 2 and whether these relationships were affected by other factors. STUDY DESIGN: Mean neonatal Crs and Rrs of the first 3 days of life were assessed using the single breath occlusion technique. Bronchial challenge tests were performed at 2 years of age. When wheezing occurred during chest auscultation or oxygen saturation decreased below 90%, the provocative concentration of methacholine was recorded. SUBJECTS: Forty-five preterm infants of <37 weeks gestation, being mechanically ventilated within 24 h after birth. RESULTS: Decreased neonatal Crs was related to BHR (beta per ml/kPa, 0.061; 95% confidence interval, 0.019 to 0.103; p=0.006). Correction was required for radiological gradation of respiratory distress syndrome, the maximal peak inspiratory pressure required during mechanical ventilation and postnatal corticosteroid therapy. Neonatal Rrs, gestational age and birth weight were not related to subsequent BHR development. CONCLUSION: In ventilated preterm infants, decreased neonatal Crs was related to the development of BHR at the age of 2.     

Efficacy of phototherapy for hyperbilirubinaemia in infants with the respiratory distress syndrome

Objectives: To evaluate the efficacy of phototherapy for hyperbilirubinaemia in preterm infants with and without the respiratory distress syndrome (RDS).
Methodology: Prospective cohort study of preterm infants cared for at Kandang Kerbau Hospital, Singapore: 170 with RDS and 477 without RDS, sepsis or other complications (control group) presenting with non-haemolytic hyperbilirubinaemia at about the same time were exposed to daylight phototherapy when bilirubin concentrations exceeded 255 μmol/L or 222 μmol/L if <48h of age. Bilirubin values were monitored 6-hourly during exposure, and daily for at least 2 days postphototherapy.
Results The infants were comparable in birthweight, gestational age, postnatal age, haemoglobin, haematocrit and bilirubin values, at start. The response to phototherapy of the infants with RDS was comparable to that of the well preterm infants; the duration of exposure was 50.1 ± 1.6 (mean ± s.e.m.) versus 50.1 ± 1.4 h, 24-hour decline rate 25.71 ± 1.29% versus 26.32 ± 0.65, and overall decline rate 0.96± 0.03%/h versus 0.95±0.02%/h.
Conclusion The presence of RDS did not affect the efficacy of phototherapy for neonatal hyperbilirubinaemia in preterm infants.     

Parenteral nutrition effect on serum insulin in the preterm infant

Blood glucose and serum insulin levels were measured in two groups of preterm infants that had been matched for gestational age. Both groups were fed parenterally during the first 72 hours of life and were mechanically ventilated because of respiratory distress syndrome. Group A infants (n = 11) received 10% glucose (infusion rate 5 mg/kg/min) and group B infants (n = 12) received amino acid solution (1.2 g/kg/d) in addition to 10% glucose at the same rate as those in group A. Infants in both groups received 90 mL/kg of fluid per day. There was no difference in blood glucose or serum insulin levels between the two groups 24 hours after beginning the infusion; however, at 48 hours there was a significantly (P less than .01) higher insulin level in infants receiving amino acid and glucose infusion compared with those receiving only glucose. Blood glucose level remained stable in both groups. We conclude that, in the stable preterm infant, the higher insulin level associated with continuous amino acid infusion does not result in hypoglycemia.