The efficacy of heparin in maintaining peripheral infusions in neonates

Abstract The study set out to determine the survival times of peripheral total parenteral nutrition (TPN) infusion sites in neonates using a prospective, single blind, randomised trial design. The effects of various concentrations of co-administered heparin was measured using survival analysis, and of other continuous variables using multivariate analysis, against a non-heparinized control group. The study was conducted in special care baby unit located within a specialist maternity hospital in London, United Kingdom. Heparin at 0.1, 0.25, 0.5 and 1 IU/ml was added to TPN infusions delivered through peripheral veins and the survival times of the infusions determined. For infusion sites receiving heparinized fluids, the relative risk of failure decreased and the median survival time increased as the heparin concentration increased, with a maximal effect at a heparin concentration of 0.5 IU/ml (P<0.001). Multivariate analysis using the Cox proportional hazard model confirmed the efficacy of heparin and high-lighted a history of infusion therapy and the co-administration of gentamicin (from a range of drugs analysed) as being risk factors associated with infusion site failure.Conclusion Intravenous infusion survival time can be prolonged using heparin additive at an optimal concentration of 0.5 IU/ml. This should also be of additional interest to paediatricians as heparin is an ubiquitous drug on neonatal units and its clinical use needs to be rationalised.     

Lower insulin secretory response to glucose induced by artificial nutrition in children: prolonged and total parenteral nutrition

Long-term parenteral nutrition (TPN) in children is associated with sustained hyperinsulinemia due to a high nutriment infusion flow 12 h/24 h, with plausible lipotoxicity secondary to repeated lipid infusions and with changes in incretin hormone release. The aim of this study was to test whether long-term TPN can lead to an alteration in beta-cell function. Thirteen children (age 9.5 +/- 3.9 y) on total TPN without obvious alternation in glucose tolerance were included. beta-Cell function was quantified with an intravenous glucose tolerance test (IVGTT) and a graded glucose infusion. First phase insulin release (FPIR) was low in five patients. The same demonstrated a lower insulin release under graded glucose infusion, although plasma glucose reached values as high as 15 mM. These data emphasize that metabolic conditions induced by TPN can lead to lower insulin secretory response to glucose. Patients who remain dependent on TPN are at risk of developing glucose tolerance disorders.     

Latamoxef and the newborn.

Thirty one preterm neonates who had clinical, radiological, or bacteriological evidence of infection and who would normally have received gentamicin and penicillin were treated with latamoxef (Moxalactam) 100 mg/kg/day. All were examined prospectively for clinical improvement and possible side effects. Biochemical and haematological values were monitored and pharmacokinetic variables determined. Thirty babies improved during treatment; latamoxef was effective in eradicating the infecting organisms in 7 of 9, including three babies infected with Lancefield group B streptococci. High serum concentrations of latamoxef were achieved after either intravenous or intramuscular administration and accumulation did not occur. Treatment had no effect on renal or hepatic function nor did it result in increased serum values of non-protein bound bilirubin. Clotting studies, where performed, were normal and no babies had bloody stools. Two disulfiram-like reactions were recorded. Latamoxef proved a safe and efficacious alternative to gentamicin with penicillin in the initial treatment of neonates with clinical evidence of infection.     

Parenteral nutrition-induced hepatobiliary dysfunction in infants and prepubertal rabbits

We analyzed clinical, biochemical, and histo- logic parameters of ten infants with parenteral nutrition-induced hepatobiliary dysfunction. The data were compared with the results of a rabbit model. All infants were born prematurely with low birth weight. Their clinical diagnoses were necrotizing enterocolitis (6), gastroschisis (1), intrauterine volvulus (1), and lung hypoplasia (2). All required total (TPN) or partial parenteral nutrition for at least 8 weeks. All had repeated episodes of infections or sepsis. A rise in bilirubin and aminotransferase levels occurred after a minimum of 5 weeks; peak bilirubin levels ranged from 4 to 14 mg% and aminotransferases from 40 to 140 IU/l. One child later developed gallstones. Liver biopsies after 1 to 24 months showed fibrosis, bile-duct proliferation, cholestasis, and hydropic degeneration. All of the above-mentioned clinical factors have been accused of causing the observed biochemical and histologic changes. In our rabbit model we were able to produce almost identical symptoms by TPN alone: gallbladder distension, sludge, and stones developed after 1–4 weeks of TPN as well as uncharacteristic changes in aminotransferases and bilirubin after 4 weeks. Liver histology revealed severe hydropic degeneration of zone 3 as early as 1 week after beginning TPN. A rise of fibrosis and bile-duct proliferation after 1 to 4 weeks of infusion was statistically significant. Cholestasis, as was observed in the infants, could not be detected. In our model, all alterations observed could be attributed exclusively to TPN. We therefore assume that TPN was the true cause of the dysfunction. In a second experimental series infusions were reduced to 80% PN and free access to lab chow. These animals produced normal feces, indicating physiologic enteral stimulation. They developed the same degenerative and proliferative histologic changes, whereas gallbladder distension, sludge, and stones were not noted. We conclude that: (1) The TPN solution itself is responsible for the histologic changes in the liver, which is supported by the fact that hydropic degeneration of zone 3 is typical of a direct toxic effect; and (2) Complete enteral starvation with an absence of enteral stimulation causes disease of the lower biliary tract. Accepted: 23 February 1999     

Cholinesterase activity and protein concentration in the serum of premature and newborn infants

Cholinesterase activity and concentrations of total protein, albumin and globulins were measured in the serum of 94 carefully selected prematures and newborns during the first week of life. Cholinesterase activity was significantly lower in prematures than in newborns. There was a weak correlation between serum concentration of albumin and cholinesterase activity. Total protein, albumin and gamma-globulins were significantly lower in premature babies. With the exception of alpha-1-globulin, all proteins correlated positively with gestational age. There was no difference in total serum protein concentration between small for gestational age infants and appropriate for gestational age infants. Postnatally, serum protein and cholinesterase activity rose by 27 44% within 7 to 10 weeks in prematures of 30-33 weeks of gestational age. A single infusion of 0.5 g/kg b.w. albumin transiently increased the protein concentration of prematures 1.5 fold; 7 to 10 weeks later, protein concentrations of treated and untreated prematures were no longer different. In conclusion, cholinesterase activity and protein concentrations correlated with gestational age. In prematures with disturbed microcirculation, albumin infusions resulted in a transient increase of protein concentration.     

A Population-based Case-Control Teratological Study of Three Parenteral Penicillins G

The purpose of the study was to check the human teratogenic potential of three penicillins G: parenteral treatments with benzylpenicillin, benzylpenicillin-procaine, and benzylpenicillin + benzylpenicillin-procaine during pregnancy in the population-based dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980–1996. Of 38,151 pregnant women who had babies without any defects (population control group), 303 (0.8%) were treated with penicillin G. Of 22,865 pregnant women who had offspring with congenital abnormalities, 236 (1.O%) were treated with penicillin G (crude OR with 95% CI = 1.3, 1.1–1.5). Of 812 mothers who deliveried babies affected with Down syndrome (patient controls), 15 (1.8%) had penicillin G treatment, and this rate exceeded significantly the figure of both the case and population control groups. This finding needs further studies. The case-control pair analysis did not indicate a teratogenic risk of three parenteral penicillin G treatments during the second-third months of gestation, i.e., in the critical period for major congenital abnormalities. The lower use of penicillins G was explained mainly by recall bias in the population control group. Thus, parenteral penicillin G treatments during pregnancy do not present a detectable teratogenic risk to the fetus.     

Natural odour preferences of newborn infants change over time

At their first sucking contact, neonates prefer an unwashed breast to a washed one, but an amniotic fluid (AF)- treated breast over a "natural odour" breast. We examined the development of these neonatal olfactory preferences. On days 3–4 significantly more babies still selected their mother's unwashed breast ( n = 21) than the washed alternative ( n = 8). Preferences for natural breast odours were more pronounced for girls than boys. In a subsequent experiment comprising another 28 babies, the number of babies who selected a naturally scented ( n = 9) vs an AP-treated breast ( n = 19) on days 2–5 were not reliably different. However, babies who selected the natural breast had longer pre-test maternal contact and had spent more time breastfeeding. Ten babies who chose the AF breast in the latter experiment were tested in the same manner several days later; all preferred the naturally smelling breast. While preferences for AF fade after birth, responsiveness to natural breast odours may be enhanced by postnatal experience.     

Long-Term Prostaglandin E1 Infusion for Newborns with Critical Congenital Heart Disease

Prostaglandin E1 is crucial for keeping the patent ductus arteriosus in critical congenital heart disease for the survival and palliation of particularly prematurely born babies until a cardiosurgical intervention is available. In this study, the side effects of prostaglandin E1 in newborns with critical congenital heart disease and clinical outcomes were evaluated. Thirty-five newborns diagnosed with critical congenital heart disease were treated with prostaglandin E1 between January 2012 and September 2014 at our hospital. Patient charts were examined for prostaglandin E1 side effects (metabolic, gastric outlet obstruction, apnea), clinical status, and prognosis. Acquired data were analyzed in the SPSS 20.0 program. Patients with birth weight under 2500 g needed more days of prostaglandin E1 infusion than ones with birthweight over 2500 g (P = 0.016). The ratio of patients with birth weight under 2500 g who received prostaglandin E1 longer than 7 days was higher than the patients with birth weight over 2500 g (P = 0.02). Eighteen side effects were encountered in 11 of 35 patients (31 %). Of these side effects, 1 patient had 4, 4 patients had 2, and 6 patients had only 1 side effect. Discontinuation of the therapy was never needed. Prostaglandin E1 is an accepted therapy modality for survival and outcome in critical congenital heart disease in particularly low-birth-weight babies until a surgical intervention is available. Side effects are not less encountered but are almost always manageable, and discontinuation is not needed.     

A randomised controlled trial of early insulin therapy in very low birth weight infants, "NIRTURE" (neonatal insulin replacement therapy in Europe)

Background

Studies in adult intensive care have highlighted the importance of insulin and improved glucose control on survival, with 32% reduction in mortality, 22% reduction in intensive care stay and halving of the incidence of bacteraemia. Very low birth weight infants requiring intensive care also have relative insulin deficiency often leading to hyperglycaemia during the first week of life. The physiological influences on insulin secretion and sensitivity, and the potential importance of glucose control at this time are not well established. However there is increasing evidence that the early postnatal period is critical for pancreatic development. At this time a complex set of signals appears to influence pancreatic development and β cell survival. This has implications both in terms of acute glucose control but also relative insulin deficiency is likely to play a role in poor postnatal growth, which has been associated with later motor and cognitive impairment, and fewer β cells are linked to risk of type 2 diabetes later in life.

Methods

A multi-centre, randomised controlled trial of early insulin replacement in very low birth weight babies (VLBW, birth weight < 1500 g). 500 infants will be recruited from 10 centres in the UK and Europe. Babies will be randomised to receive a continuous insulin infusion (0.05 units/kg/h) or to receive standard neonatal care from the first day of life and for the next 7 days. If blood glucose (BG) levels fall infants will receive 20% dextrose titrated to maintain normoglycaemia (4–8 mmol/l). If BG is consistently above 10 mmol/l babies will receive standard treatment with additional insulin infusion. The primary end point will be mortality on or before expected date of delivery, secondary end points will be markers of morbidity and include episodes of sepsis, severity of retinopathy, chronic lung disease and growth.

Trial Registration

Current Controlled Trials ISRCTN78428828. EUDRACT Number 2004-002170-34     

Nephrocalcinosis in preterm babies

OBJECTIVES: To determine prospectively the incidence and cause of nephrocalcinosis in preterm infants. STUDY DESIGN: Inborn babies of gestation less than 32 weeks or birth weight less than 1500 g were eligible to be entered into a prospective observational study. Two renal ultrasound scans were performed, the first at 1 month postnatal age and the second at term or discharge. Data were collected on gestation, birth weight, sex, race, family history of renal calculi, oliguria on first day, respiratory support (ventilation, steroid, and oxygen dependency), and use of nephrotoxic drugs (gentamicin, vancomycin, and frusemide). Intake of fluid, calcium, and phosphate and plasma urea, creatinine, calcium, and phosphate were recorded for the first 6 weeks of life. Random urinary calcium/creatinine, oxalate/creatinine, and urate/creatinine ratios and tubular absorption of phosphate were measured once at term. RESULTS: A total of 101 preterm infants were studied. Twenty three (23%) had abnormal ultrasound scans. Sixteen (16%) had nephrocalcinosis. On univariate analysis, gestational age, male sex, duration of ventilation, oxygen dependency, duration and frequency of gentamicin treatment, toxic gentamicin/vancomycin levels, and postnatal dexamethasone were significantly associated with nephrocalcinosis. In addition, babies with nephrocalcinosis had a lower intake of fluid, calcium, and phosphate, longer duration of total parenteral nutrition, and higher urinary oxalate/creatinine and urate/creatinine ratios than infants who did not have the condition. There was also a significant association with plasma urea and creatinine but not with plasma calcium or phosphate or urinary calcium. Multivariate analysis showed that the strongest predictors of nephrocalcinosis were duration of ventilation, toxic gentamicin/vancomycin levels, low fluid intake, and male sex. CONCLUSION: 16% of babies born at less than 32 weeks gestation developed nephrocalcinosis. The multifactorial origin, in particular, the association with extreme prematurity and severity of respiratory disease, is confirmed. In addition, an association with male sex, frequency and duration of gentamicin use, and high urinary oxalate and urate excretion is shown.     

Insulin infusions in infants of birthweight less than 1250 g and with glucose intolerance

Fifteen preterm babies (mean gestation: 26.7 weeks; mean birthweight 860 g) with significant glucose intolerance were treated with insulin infusions. During the insulin infusions there was a significant increase in both the mean energy intake (60.8 +/- 25.1 cal/kg per day to 79.9 +/- 24.5 cal/kg per day; P less than 0.001) and the mean amount of intravenous dextrose tolerated (7.0 +/- 2.7 mg/kg per min to 9.2 +/- 2.6 mg/kg per min; P less than 0.01). The infusions were initiated at a mean postnatal age of 5.3 days (range: 2-12 days) and were continued for 1.5-17.5 days. Of the 998 blood glucose estimations performed during the insulin infusions, 28 (2.8%) were less than 2 mmol/l and 216 (21.6%) greater than 8 mmol/l. We conclude that continuous insulin infusion is a safe and effective way of managing glucose intolerance in very low birthweight infants, provided adequate means for continuous monitoring of blood glucose are available.     

出生畸形低体重儿围手术期处理十年回顾

目的 通过对10年来外科畸形低体重儿的围手术期治疗进行回顾性分析,为进一步提高外科畸形低体重新生儿的治愈率提供资料.方法 1996年1月～2006年8月期间上海交通大学医学院附属新华医院和上海儿童医学中心小儿外科收治的外科畸形低体重儿共104例,男69例,女35例,平均出生体重(2244±261)g(1 040～2490g),平均胎龄36+1周.分为2000年前(A组)共34例,2001年后(B组)共70例.结果 外科畸形低体重儿占同期收治新生儿的9.5%,总治愈率为67.3%.41例患儿应用机械通气,平均机械通气时间为6.2 d,45例患儿应用全胃肠外营养(TPN),平均TPN应用时间9.5 d.A组的治愈率为58.8%,12例患儿应用机械通气,平均机械通气时间3.2 d;7例患儿应用TPN,平均应用TPN时间7.5 d.B组的治愈率为71.4%,29例患儿应用机械通气,平均机械通气时间8.4 d;38例患儿应用TPN,平均应用TPN时间19.4 d.比较两组的发病率、治愈率和围手术期的基本处理,两组在治愈率、机械通气和TPN的使用率、平均机械通气时间和TPN平均应用时间上差异存在统计学意义(P＜0.05).结论 在围手术期应用合理、规范、有效的呼吸管理和营养支持,可以提高低体重儿畸形的治愈率.     

Tumor response and toxicity with multiple infusions of high dose 131I-MIBG for refractory neuroblastoma

BACKGROUND: (131)I Metaiodobenzylguanidine ((131)I-MIBG) is an effective targeted radiotherapeutic for neuroblastoma with response rates greater than 30% in refractory disease. Toxicity is mainly limited to myelosuppression. The aim of this study was to determine the response rate and hematologic toxicity of multiple infusions of (131)I-MIBG. PROCEDURE: Patients received two to four infusions of (131)I-MIBG at activity levels of 3-19 mCi/kg per infusion. Criteria for subsequent infusions were neutrophil recovery without stem cell support and lack of disease progression after the first infusion. RESULTS: Sixty-two infusions were administered to 28 patients, with 24 patients receiving two infusions, two patients receiving three infusions, and two patients receiving four infusions. All patients were heavily pre-treated, including 16 with prior myeloablative therapy. Eleven patients (39%) had overall disease response to multiple therapies, including eight patients with measurable responses to each of two or three infusions, and three with a partial response (PR) after the first infusion and stable disease after the second. The main toxicity was myelosuppression, with 78% and 82% of patients requiring platelet transfusion support after the first and second infusion, respectively, while only 50% had grade 4 neutropenia, usually transient. Thirteen patients did not recover platelet transfusion independence after their final MIBG infusion; stem cell support was given in ten patients. CONCLUSIONS: Multiple therapies with (131)I-MIBG achieved increasing responses, but hematologic toxicity, especially to platelets, was dose limiting. More effective therapy might be given using consecutive doses in rapid succession with early stem cell support.     

Congenital myotonic dystrophy: respiratory function at birth determines survival.

The clinical features of 14 neonates with congenital myotonic dystrophy were retrospectively reviewed. These babies represent all the new cases of congenital myotonic dystrophy seen in this department since 1982. Twelve babies were referred because of either difficulties in diagnosis or difficulties in the management of their respiratory problems. Of the 14 babies, 13 had birth asphyxia, 11 were premature, and four had intrauterine growth retardation. Ten babies required artificial ventilation from birth. Abnormalities on chest radiography included thin ribs (n =9) and raised right hemidiaphragms (n = 5). Recurrent episodes of collapse and consolidation of the lungs secondary to poor swallowing occurred in all ventilated babies. All babies ventilated for longer than four weeks died of respiratory complications before the age of 15 months. One baby was successfully extubated after diaphragmatic plication, but he died a few months later. Duration of ventilation was the best guide to prognosis.     

Evolution of neonatal intensive care in a district general hospital.

Before 1975 in Blackburn in the Premature Baby Unit monitoring facilities were limited. Ambient oxygen monitoring, blood gas analysis, and ventilation were not being performed. Gradually, special care was introduced and from 1978-80 all babies requiring intensive care and long term ventilatory care were transferred to the Regional Neonatal Intensive Care Unit. Not all babies with incipient or established respiratory failure, however, could be accepted, and those declined had unfavourable outcomes. In 1981 local intensive and ventilatory care was begun, and since then the survival of all babies has improved considerably. Our early neonatal mortality and neonatal mortality have fallen below the regional levels. In a district general hospital it is possible to achieve survival figures comparable with those of a regional centre.     

Long-term home parenteral nutrition in pediatrics: ten years of experience in 102 patients

One hundred two pediatric patients received all or part of their nutritional needs parenterally at home during the past decade. All received total parenteral nutrition (TPN) at night during an 8- to 12-h infusion. Patients with short bowel syndrome (33%), inflammatory bowel disease (23%), chronic intractable diarrhea (15%), chronic idiopathic intestinal pseudo-obstruction syndrome (10%), and malignancy (10%) made up the largest groups. The mean duration of parenteral support was 735 days (range, 90-3650 days); the mean number of catheters per patient was 2.1 (range, 1-8). Twenty-one patients continue to receive full or partial home TPN: four for more than 10 years and seven for more than 5 years. Fifty-one no longer require it and have had healing of mucosa or bowel adaptation. Complications related to administration of fluid and electrolytes were quite rare. Biotin deficiency was recognized once. Thirty-one have died, but only 13 deaths were related to TPN. Sepsis in nine and liver failure in two were the most common causes of death in the TPN-related group. Three of 21 still on home TPN have graduated either from high school or college. All but one of the school age children attend regular school; one attends a school for the medically disabled, another attends a school for the mentally gifted.     

大剂量甲氨蝶呤目标浓度个体化调整研究

目的 探讨大剂量甲氨蝶呤(MTX)24 h输注治疗儿童急性淋巴细胞白血病目标浓度个体化调整的方法.方法 本研究涉及24例患儿105个疗程,检测MTX开始输注后第1和第6小时的血药浓度,根据已建立的大剂量MTX群体药物动力学模型,推算出该疗程稳态血药浓度(CSS)的预测值.根据CSS预测值,于MTX开始输注后第8小时调整MTX输注速度和剂量.MTX输注后第23小时再检测血药浓度(CSS实测值).结果 为达目标浓度,17例(71%)患儿进行了剂量调整.45个疗程(43%)调整了剂量,42个疗程增加了剂量,3个疗程减少了剂量.早期阶段(诱导缓解和巩固治疗方案后的大剂量MTX的疗程)29个疗程中有16个疗程增加了剂量,1个疗程减少了剂量;维持阶段76个疗程中有26个疗程增加了剂量,2个疗程减少了剂量.最终有95个(90%)疗程的CSS实测值达目标范围,8个疗程小于目标范围,2个疗程大于目标范围.如果不调整剂量,仅有74个(70%)疗程的CSS(不调整)在目标范围.调整MTX剂量,与不调整相比,可以明显增加CSS实测值达目标范围的疗程数(χ2=13.366,P=0.000).在剂量不调整的60个疗程中,CSS实测值和CSS预测值有较好的直线相关性(r=0.487,P=0.000);CSS实测值与MTX输注后第6小时的血药浓度也有一定的直线相关性(r=0.389,P=0.002).105个疗程MTX的总清除率(CL)实测值是(7.01±2.06)L/(m2·h).在所有疗程间CL相差最大达4.4倍,同一患儿不同疗程间CL相差最大达2.9倍.CL与患儿的年龄、体重和总胆红素呈直线负相关,与血磷呈直线正相关;化疗早期阶段疗程的CL有高于维持阶段疗程的倾向(P均＜0.05).结论 105个疗程大剂量MTX化疗,疗程间CL差异最大达4.4倍,需要目标浓度个体化调整.通过检测MTX输注后第1和第6小时的血药浓度,调整MTX输注速度和剂量,最终90%疗程的CSS实测值达目标范围.早期阶段大剂量MTX化疗更需要目标浓度个体化调整.     

Asymmetry of fetal cerebral hemispheres: in utero ultrasound study

AIMS: To assess survival and neurodevelopmental outcome following prolonged ventilation beyond 27 or 49 days of postnatal life in neonates treated with antenatal steroids and surfactant. METHODS: The medical records of 84 babies born in 1994-1996 requiring ventilation after 27 postnatal days at Liverpool Women's Hospital were reviewed to determine the duration of mechanical ventilation, survival, and neurodevelopmental outcome at 3 years of age. RESULTS: Fifty six babies were mechanically ventilated after 27 postnatal days but for less than 50 days; 48 (86%) survived to 3 years. Twenty six (54%) of the survivors had normal neurodevelopment at 3 years and seven (15%) had only mild disability. Twenty eight babies were ventilated after 49 postnatal days; 14 survived to 3 years. Five of these survivors were neurodevelopmentally normal at 3 years and two had mild disability. CONCLUSIONS: Survival decreases with more prolonged ventilation. When antenatal steroids and postnatal surfactant are used, there appears to be improved survival and neurodevelopmental outcome in preterm babies who require prolonged ventilation.     

Consensus on Timing of Intervention for Common Congenital Heart Diseases: Part II - Cyanotic Heart Defects

The purpose of this review/editorial is to discuss how and when to treat the most common cyanotic congenital heart defects (CHDs); the discussion of acyanotic heart defects was presented in a previous editorial. By and large, the indications and timing of intervention are decided by the severity of the lesion. While some patients with acyanotic CHD may not require surgical or transcatheter intervention because of spontaneous resolution of the defect or mildness of the defect, the majority of cyanotic CHD will require intervention, mostly surgical. Total surgical correction is the treatment of choice for tetralogy of Fallot patients although some patients may need to be palliated initially by performing a modified Blalock-Taussig shunt. For transposition of the great arteries, arterial switch (Jatene) procedure is the treatment of choice, although Rastelli procedure is required for patients who have associated ventricular septal defect (VSD) and pulmonary stenosis (PS). Some of these babies may require Prostaglandin E₁ infusion and/or balloon atrial septostomy prior to corrective surgery. In tricuspid atresia patients, most babies require palliation at presentation either with a modified Blalock-Taussig shunt or pulmonary artery banding followed later by staged Fontan (bidirectional Glenn followed later by extracardiac conduit Fontan conversion usually with fenestration). Truncus arteriosus babies are treated by closure of VSD along with right ventricle to pulmonary artery conduit; palliative banding of the pulmonary artery is no longer recommended. Total anomalous pulmonary venous connection babies require anastomosis of the common pulmonary vein with the left atrium at presentation. Other defects should also be addressed by staged correction or complete repair depending upon the anatomy/physiology. Feasibility, safety and effectiveness of treatment of cyanotic CHD with currently available medical, transcatheter and surgical methods are well established and should be performed at an appropriate age in order to prevent damage to cardiovascular structures.     

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).