Erythromycin treatment for gastrointestinal dysmotility in preterm infants

To report our clinical experience on the use of oral erythromycin for the treatment of severe gastrointestinal dysmotility in preterm infants.

Methodology:

A case series study of seven preterm infants (six were very low birthweight) with severe intestinal dysmotility in a tertiary neonatal centre.

Results:

All responded favourably without adverse effects and tolerated full enteral feeding within 1–2 weeks of the commencement of the drug.

Conclusions:

As prolonged total parenteral nutrition carries significant risk of complications, this therapy could be considered in selected preterm infants who fail to establish enteral feeding after an extended period, and in whom an anatomically obstructive lesion of the gastrointestinal tract has been excluded. Meanwhile, we would caution against the widespread implementation of this therapeutic approach until formal evaluation by randomized controlled trials have established the exact role of erythromycin, or its analogues, in the treatment of intestinal dysmotility in preterm infants.     

口服红霉素治疗早产儿喂养不耐受的多中心临床对照研究

目的探讨口服不同剂量红霉素对早产儿喂养不耐受的治疗效果及可能存在的不良反应。方法选取2008年1月至2010年3月在广东省16家三级甲等医院新生儿科住院并诊断为喂养不耐受的早产儿,随机分为3组:大剂量组(第8～10日龄起口服红霉素12.5mg/kg,每8h给药,疗程7～10天),小剂量组(口服红霉素5mg/kg,给药方法同上),对照组(完全不用胃肠动力调节药物)。记录临床资料,比较各组患儿的喂养相关指标及宫外生长迟缓(EUGR)发生率等,并评估药物不良反应。结果纳入研究的患儿共122例,其中大剂量组37例,小剂量组47例,对照组38例。入组后两治疗组患儿体重增长速度、体重开始增长日龄、肠内热卡达到基础热卡日龄、达到全肠道喂养日龄及体重EUGR发生率等方面均较对照组明显改善(P<0.05),但按胎龄32周再分亚组后比较,以体重为指标EUGR发生率差异无统计学意义(P>0.05)。所有治疗组患儿随访6个月均未见明显红霉素不良反应。结论本研究中选取的两种剂量红霉素口服对早产儿(包括胎龄<32周者)喂养不耐受均有治疗作用,所采用的红霉素治疗方案未见明显不良反应。     

Efficacy of oral erythromycin for treatment of feeding intolerance in preterm infants

OBJECTIVE: To determine the efficacy and safety of oral erythromycin (EM) for feeding intolerance in preterm infants < 35 weeks gestation. STUDY DESIGN: In this randomized, double-blinded, placebo-controlled trial, preterm infants with feeding intolerance were randomly allocated to a treatment group given EM ethyl succinate 10 mg/kg every 6 hours for 2 days, followed by 4 mg/kg every 6 hours for another 5 days, or to a control group given placebo. The primary outcome was time to full feeding (150 mL/kg/day) after the start of treatment. RESULTS: Each group comprised 23 preterm infants, almost all of whom were < 32 weeks gestation. Baseline characteristics were similar between the 2 groups. Times to full feeding were significantly shorter and the number of withheld feeds were significantly less in the EM group than the control group; the respective medians (interquartile ranges) were 7 days (6 to 9 days) versus 13 days (9 to 15 days) (P < .001) and 1 episode (0 to 2 episodes) versus 9 episodes (2 to 13 episodes) (P < .001). No significant differences in episodes of sepsis, necrotizing enterocolitis, and cholestasis were observed. CONCLUSIONS: Oral EM was effective and safe for treatment of feeding intolerance in preterm infants.     

Randomised controlled trial of cisapride in preterm infants

AIM: To determine the effect of cisapride on gastrointestinal motility in preterm infants. METHODS: Cisapride (0.2 mg/kg, 8 hourly ) or placebo was given first for seven days in a double blind randomised crossover study of 10 preterm infants. Gastrointestinal motility was assessed on day 3 of each treatment. The half gastric emptying time (GET1/2) was determined by using ultrasonography to measure the decrease in the gastric antral cross sectional area after a feed. The whole gastrointestinal transit time (WGTT) was assessed by timing the transit of carmine red through the gut. Treatments were compared using the Wilcoxon matched pairs signed ranks test. RESULTS: Median (range) birthweight was 1200 (620, 1450) g and postconceptional age 33 (29, 34) weeks at recruitment. GET1/2 was significantly longer during cisapride treatment than during placebo; the median of the differences (95% confidence interval) was 19.2 (11, 30 minutes, p=0.008). WGTT was also longer during cisapride treatment, but the difference was not significant; the median of the differences was 11(-18, 52 hours, p=0.1). CONCLUSIONS: Cisapride delays gastric emptying and may delay WGTT in preterm infants. Its use to promote gastrointestinal motility in this group cannot be recommended.     

Randomised controlled trial of albumin infusion in ill preterm infants

We assessed the effect of albumin infusion on weight loss and ventilation requirement in sick premature infants. Thirty infants, median gestational age 29 weeks, were entered into a randomised controlled trial, at a median of 2 days of age. The infants, all with an albumin level <-30 g/l, received either 5 ml/kg of 20% albumin or 5 ml/kg of their maintenance fluids (placebo), both given as part of the total daily fluid requirement. The response to the infusion was assessed by comparing two periods; 12 h immediately prior to the infusion and 12–24hh after the infusion. Albumin infusion was associated with a significant increase in albumin level and a significant reduction in weight, but in the placebo group there was a significant increase in weight. There were, however, no significant changes in the peak inspiratory pressure in response to either infusion. There was only a modest reduction (<15%) in the inspired oxygen concentration, which occurred in both groups, but reached statistical significance only following the albumin infusion. We conclude that our results suggest that albumin infusion in hypoalbuminaemic sick preterm infants is unlikely to alter their respiratory status.     

Randomised controlled trial of oral vitamin A supplementation in preterm infants to prevent chronic lung disease

BACKGROUND: Intramuscular supplementation with vitamin A in large doses may reduce the incidence of chronic lung disease. AIM: To investigate whether oral supplementation with vitamin A would reduce the incidence of chronic lung disease in a group of extremely low birthweight infants. METHODS: Infants with birth weight < 1000 g were randomised at birth to receive oral vitamin A supplementation (5000 IU/day) or placebo for 28 days. The primary outcome was oxygen dependency at 28 days of age or death. RESULTS: A total of 154 infants were randomised; 77 received vitamin A (median birth weight (interquartile range) 806 (710-890) g), and 77 received placebo (median birth weight (interquartile range) 782 (662-880) g). Plasma vitamin A concentrations in the supplemented group were significantly higher at 24 hours of age but did not differ significantly at birth, 12 hours of age, 7 days, or 28 days of life. There were no significant differences in the proportion of infants who survived, required oxygen at 28 days, required oxygen at 36 weeks postmenstrual age, survived without chronic lung disease at 36 weeks, survived without significant retinopathy, or who survived without significant intraventricular haemorrhage. CONCLUSIONS: Oral supplementation with 5000 IU vitamin A in extremely low birthweight infants does not significantly alter the incidence of chronic lung disease. However, this dose may have been inadequate to achieve optimal serum retinol concentrations.     

Randomised controlled trial of allopurinol prophylaxis in very preterm infants.

Allopurinol, an inhibitor of xanthine oxidase (an enzyme capable of generating superoxide radicals following hypoxiaischaemia), was investigated in preterm infants to determine its ability to prevent the complications of neonatal intensive care which may be associated with oxidative injury. Four hundred infants of between 24 and 32 weeks'' gestation were randomly allocated to receive enteral allopurinol (20 mg/ml) or an equivalent dose of placebo for seven daily doses. At admission, plasma hypoxanthine concentrations were significantly higher in infants who subsequently developed periventricular leucomalacia (PVL), bronchopulmonary dysplasia (BPD), or retinopathy of prematurity (ROP), but there was no difference in the primary endpoint (PVL) between the treated and control groups. The failure of allopurinol prophylaxis in this group of infants is probably related to the complex nature of the pathological processes and to the timing of treatment. If oxidant injury is an important mechanism of cellular injury in these preterm infants, an alternative biochemical modulator would be required, or a combination of agents might be effective.     

Randomised controlled trial of a synthetic triglyceride milk formula for preterm infants

AIMS—To test whether use of infant formula containing synthetic structured triglycerides results in: (i) increased palmitate absorption; (ii) increased total fat absorption; (iii) reduction in calcium soap formation in the gut; and hence (iv) increased calcium absorption.
METHODS—A randomised study was made of 24 infants comparing three formulas, one containing the synthetic fat Betapol with 74% of palmitate in the 2-position, which was substantially higher than in the two comparison diets (8.4% and 28%). The hypothesised outcomes were tested using balance studies, detailed chemical analysis of stool specimens and dual calcium isotope tracers (⁴⁴calcium orally and ⁴⁶calcium intravenously).
RESULTS—Three of the four hypotheses were confirmed: use of a formula rich in 2-position palmitate (i) improved palmitate (16:0) and also (18:0) absorption; (ii) reduced the formation of insoluble calcium soaps in the stool; and (iii) improved calcium absorption, determined by the dual tracer technique from 42 (SE 3)% to 57 (7)%.
CONCLUSION—Synthetic triglycerides that mimic the stereoisometric structure of those in breast milk may have a valuable role in the design of formulas used for preterm infants in neonatal intensive care units.

     

红霉素对新生儿胃肠道功能紊乱的疗效观察

目的 评估口服红霉素对新生儿胃肠道功能紊乱的疗效.方法 采用随机、双盲、安慰剂对照试验,选择2009年1月至2011年12月于深圳市儿童医院新生儿重症监护室住院的90例患儿作为研究对象,随机分为小剂量红霉素组、大剂量红霉素组和对照组,每组30例,分别给予3 mg/(kg·次)、10 mg/(kg·次)红霉素或等量生理盐水口服或鼻饲,每8小时1次,疗程14 d.比较各组患儿达到半量、3/4量及全量肠内营养时间、肠外营养时间及住院时间.结果 与对照组[(8.1±0.4)d,(13.5±1.0)d,(15.7±1.2)d]比较,大剂量红霉素组[(3.0±0.5)d,(6.2±0.7)d,(8.2±1.0)d]和小剂量红霉素组[(6.2±0.5)d,(8.3±0.6)d,(10.6±1.1)d]患儿达到半量、3/4量及全量肠内营养的时间均明显提前(P＜0.05).肠外营养时间[(14.2±1.4)d vs (9.3±1.2)d vs (7.8±1.1)d]及住院时间[(13.0±1.4)d vs (8.1 ±0.8)d vs (6.8±0.7)d],对照组明显长于不同剂量红霉素组,3组间比较差异均有统计学意义(P＜0.05).治疗期间发生肝功能损害、脓毒症的患儿,不同剂最红霉素组两组相似,但是比对照组明显降低.未见口服红霉素治疗的相关不良反应(QT间期延长、心律失常).结论 口服红霉素可以作为肠内营养不足的新生儿胃肠道功能紊乱的治疗方法,并且口服大剂量红霉素较小剂量效果更好.     

Randomised controlled study of early use of inhaled corticosteroid in preterm infants with respiratory distress syndrome

AIM: To investigate the therapeutic efficacy of inhaled fluticasone propionate, started on day 1 of age, on ventilated preterm infants with respiratory distress syndrome. METHODS: Starting within 24 hours of age, ventilated preterm infants (gestation < 32 weeks, birthweight < 1.5 kg) with respiratory distress syndrome were given a 14 day course (two puffs, 12 hourly) of either fluticasone propionate (250 microg/puff) (group 1, n=27) or placebo (group 2, n=26) with a metered dose inhaler-spacer device. Response to treatment was assessed by the rate of successful extubation by days 7 and 14 of age, changes in respiratory system mechanics, death, occurrence of chronic lung disease, and other neonatal complications. RESULTS: More infants in the treatment group were successfully extubated by 14 days of age than those in the placebo group (17/27 vs 8/26; p = 0.038). The treated infants also showed a more significant improvement in respiratory system compliance during the first 14 days of life. The two groups, however, did not differ significantly in their need for systemic steroids after day 14 of age, death, or the occurrence of chronic lung disease. The treatment was not associated with any increase in neonatal complications, including those attributable to steroid induced side effects. CONCLUSION: These results provide preliminary evidence that early treatment with inhaled corticosteroids may be beneficial to ventilated preterm infants with respiratory distress. Further study of its use in a large scale randomised trial is warranted.     

Randomised trial of erythromycin on the development of chronic lung disease in preterm infants

AIMS—To determine if erythromycin given from birth reduces the inflammatory response and the incidence and severity of chronic lung disease.
METHODS—Seventy five infants less than 30 weeks of gestation and ventilated from birth for lung disease were randomly assigned to receive erythromycin intravenously for 7 days or to no treatment. Ureaplasma urealyticum was detected in tracheal secretions by culture and polymerase chain reaction. Differential cell counts were obtained from bronchoalveolar lavage fluid collected daily for 5 days and concentrations of the cytokines interluekins IL-1β and IL-8, and tumour necrosis factor α (TNF-α) were measured. Chronic lung disease (CLD) was defined as oxygen dependency at 36 weeks of gestation.
RESULTS—Nine infants (13%) were positive for U urealyticum. The inflammatory cytokines in the lungs increased over the first 5 days of life in all babies, but no association was found between their concentrations and the development of CLD. Those treated with erythromycin showed no significant differences from the non- treated group in the differential cell counts or concentrations of the cytokines. The two groups had a similar incidence of CLD. Babies infected with U urealyticum did not have a more pronounced cytokine response than those without infection. Chorioamnionitis was associated with significantly higher concentrations of IL-1β and IL-8 on admission: these babies had less severe acute lung disease and developed significantly less CLD.
CONCLUSIONS—U urealyticum in the trachea was not associated with an increased inflammatory response in preterm infants. Erythromycin did not reduce the incidence or severity of CLD.

     

Randomised controlled trial of cisapride in feed intolerance in preterm infants

AIM—To assess the efficacy of cisapride in reducing the time required to establish enteral feeds in preterm infants.
METHODS—A randomised, double blind, placebo controlled trial was conducted of 34 infants of ⩽ 32 weeks of gestation, assigned to receive either cisapride 0.2 mg/kg/dose four times daily (n=18) or placebo (n=16).
RESULTS—The time taken by the babies to tolerate full enteral feeds was not significantly different between the groups (median 9.5days vs 10 days). There was a significantly lower incidence of large gastric residuals and regurgitation in the treated group compared with the placebo group. The number of episodes of large gastric residuals per infant was also significantly less. No adverse effects were noted.
CONCLUSION—The routine use of cisapride in preterm infants cannot be recommended to decrease the time to establish enteral feeds. Its use may be justified for clincally significant gastric stasis or regurgitation.

     

建立喂养不耐受早产儿的肠道喂养:小剂量红霉素随机对照研究

目的 探讨静脉应用小剂量红霉素防治早产儿喂养不耐受的效果并评估其临床应用的相关不良反应.方法 将60例胎龄>32周的早产儿随机分为低剂量红霉素组[5 mg/(kg·d),连用7 d]和对照组.记录并比较两组早产儿喂养不耐受发生率及达到全肠道喂养的时间.监测红霉素潜在的不良反应.结果 60例早产儿中25例出现喂养不耐受,发生率为41.67%(25/60).红霉素组及对照组喂养不耐受的发生率差别无统计学意义(x2=0.231,P=0.631).红霉素组取得完全肠内营养及恢复出生体质量的时间早于对照组,两组差异有统计学意义(P均<0.05).对照组的血清胆汁酸水平高于红霉素组,差异有统计学意义(t=3.202,P=0.003).两组早产儿其他肝功能生化指标差异均无统计学意义(P>0.05).结论 小剂最静脉红霉素对于胎龄>32周的早产儿,不能降低喂养不耐受的发生率,但可以缩短达到全肠道喂养及恢复出生体质量的时间,并能减少长期静脉营养相关的胆汁淤积改变,未发生肝功能损伤等不良反应.     

The effect of low-dose erythromycin on whole gastrointestinal transit time of preterm infants

The aim of the study was to determine the effect of a low oral dose of erythromycin on whole gastrointestinal transit time [WGTT]. Erythromycin [EM] [1.5 mg/kg, 6 hourly] or placebo was given first over 7 days in a double blind randomized crossover study of 21 preterm infants with feed intolerance. Median [range] birth weight was 1420 [690, 2200] g and postconceptual age 32. 5 [20, 36.4] weeks. WGTT was assessed on day 3 of each treatment, by timing the transit of carmine red through the gut. Treatments were compared using Student's paired t test. RESULTS: WGTT was significantly shorter following EM treatment as compared to placebo: mean [SD] 10.16 [4.6] h vs. 15. 9 [7.2] h, p<0.01. CONCLUSION: Oral low-dose EM significantly shortens WGTT of feed-intolerant preterm infants.     

Establishing enteral feeding in preterm infants with feeding intolerance: a randomized controlled study of low-dose erythromycin

OBJECTIVE: A prospective, double-blind, randomized, controlled trial was conducted to evaluate the effect of low-dose erythromycin on the time taken to attain full enteral feedings in preterm infants with very low birth weight and feeding intolerance. METHODS: Two groups of preterm infants (birth weight 相似文献   

Randomised controlled trial of eutectic mixture of local anaesthetics cream for venepuncture in healthy preterm infants

AIM—To assess the safety and efficacy of EMLA cream (eutectic mixture of local anaesthetics) used to induce surface anaesthesia for venepuncture in healthy preterm infants.METHODS—Nineteen infants, median gestational age 31 weeks (range 26-33 weeks) were assessed in a randomised, double blind, placebo controlled, cross-over trial. Changes in physiological variables (heart rate, blood pressure, oxygen saturation) and behavioural responses (neonatal facial coding system score, crying time) before and after venepuncture with EMLA cream were compared with those obtained with a placebo cream to assess efficacy. Toxicity was assessed by comparing methaemoglobin concentrations at 1 hour and 8 hours after application.RESULTS—There was no significant difference in efficacy between EMLA and placebo creams in physiological and behavioural responses. There was no significant difference in methaemoglobin concentrations one hour after the cream had been applied. At eight hours, however, concentrations were significantly higher after EMLA than placebo (p=0.016). There was no evidence of clinical toxicity.CONCLUSION—This study does not support the routine use of EMLA for venepuncture in healthy preterm infants.     

静脉应用小剂量红霉素防治早产儿喂养不耐受的Meta分析

摘要 目的 对静脉应用小剂量红霉素防治早产儿喂养不耐受的疗效和安全性的相关文献进行Meta分析,为早产儿喂养不耐受的治疗提供参考依据。方法 索Cochrane图书馆、PubMed、EMBASE、在研试验数据库、中国生物医学文献数据库、中国期刊全文数据库、万方数据库和维普中文科技期刊数据库等。检索红霉素防治早产儿喂养不耐受的RCT文献。按Cochrane系统评价方法进行文献质量评价,采用RevMan 5.0.17软件进行Meta分析。结果 共纳入18篇RCT文献,文献质量评价A级1篇,B级3篇,C级14篇。共纳入1 200例早产儿。Meta分析结果显示：①达到全肠内喂养时间：红霉素预防组加权均数差值（WMD）=-4.18（95%CI：-6.29 ~-2.08）,红霉素治疗组WMD=-4.69（95%CI：-6.38～-3.00）,两组均可较早实现全肠内喂养;胎龄≤32周亚组WMD＝-5.15（95%CI：-12.60～2.30）,与对照组差异无统计学意义。剔除低质量文献行敏感度分析,WMD=-5.48（95%CI：-11.66～0.69）,红霉素治疗组与对照组差异无统计学意义。②红霉素预防组住院时间（WMD=-1.10,95%CI：-3.65～1.37）和NEC发生率（OR=1.01,95%CI：0.24～4.22）与对照组差异无统计学意义;红霉素治疗组日均体重增加（WMD= 4.29,95%CI：-2.06～10.64）和NEC发生率 （OR=0.68,95%CI：0.18～2.56）与对照组差异无统计学意义;红霉素治疗组恢复至出生体重时间（WMD=-2.45,95%CI：-2.87～-2.04）、症状消失间（WMD＝-1.22,95%CI：-1.33～-1.11）及住院时间（WMD=-9.70,95%CI：-11.92～-7.49）与对照组差异有统计学意义。结论 对于喂养不耐受高危儿及胎龄≤32周的喂养不耐受早产儿,静脉应用小剂量红霉素的证据尚不足;对于胎龄>32周的喂养不耐受早产儿,今后研究应确定是否存在一个最佳剂量以缩短静脉营养时间及住院时间,在改善喂养不耐受的症状中红霉素可能起一定的作用。     

Randomised controlled trial of the effect of cisapride on the pyloric muscle in preterm infants

In this study we determined the effects of cisapride on the pyloric muscle in preterm infants. To perform a randomised, double blind, placebo controlled study, two groups each of 16 preterm newborns were given either cisapride (0.2 mg/kg every 8 h) or a placebo for at least 7 days. Infants were studied first on the day when treatment with cisapride or placebo was to be initiated (time 0), and then after 3 (time 1) and 7 days (time 2). In each group, the following parameters were studied by ultrasonography: cross-sectional diameter of the entire pylorus, muscle thickness, and length of the pyloric canal. Also, the mean daily total gastric aspirate volume was studied for the entire week of the study. At time 0, we observed no significant differences between the two groups with respect to diameter, muscle thickness and length of the pyloric muscle. At time 1 and time 2, both diameter and muscle thickness were significantly greater in the cisapride group than in the placebo group. Furthermore, the length of the pyloric canal was significantly greater in the cisapride group than in placebo group at time 2, though not so at time 1. For the entire week of the study, we found a significantly larger mean daily total gastric aspirate volume in the group of infants treated with cisapride compared to the placebo treated group. CONCLUSION: Cisapride significantly affects all of the main measurements of the pyloric muscle and causes a significantly larger amount of daily total gastric aspirate volume. Its use to promote feeding intolerance in preterm newborns cannot be recommended.