Cerebral blood flow velocity changes in preterm infants after a single dose of indomethacin: duration of its effect

Indomethacin decreases cerebral blood flow velocity and blood flow in the preterm infant. The duration of this negative effect has not been established. Cerebral blood flow velocity was evaluated in 24 preterm infants with symptomatic patent ductus arteriosus before and during the first 12 hours after a single intravenous dose of indomethacin, 0.1 mg/kg. Cerebral blood flow velocity was estimated by serial Doppler investigations of the anterior cerebral arteries. Indomethacin administration led to an instantaneous decrease of peak systolic flow velocity, temporal mean flow velocity, and end-diastolic flow velocity of the anterior cerebral arteries in all infants, which was maximal between 2 and 40 minutes after indomethacin administration and was followed by a more sustained recovery of all velocities to baseline values. Temporal mean flow velocity was not different from pre-indomethacin values at 3 hours after the administration. It is concluded that indomethacin can impact the cerebral circulation of the preterm infant for at least 2 hours. This may have consequences in preterm infants with unstable hemodynamics and pulmonary function.     

Aortic flow velocity curves in the diagnosis and the followup of symptomatic patent ductus arteriosus in preterm infants during therapeutic interventions

In preterm infants, persistent ductus arteriosus (PDA) fails to close soon after birth and becomes symptomatic (sPDA) in about 40% of the infants, causing cardio-respiratory deterioration by a left-to-right shunt across the PDA. Aortic run-off of blood, predominantly occurring during ventricular diastole, causes an abnormal diastolic retrograde aortic blood flow. This aortic reverse flow can be assessed semi-quantitatively in a noninvasive way, using continuous-wave Doppler-ultrasonography. An increased ratio (R/F ratio) of the abnormal retrograde aortic blood flow (R) related to the normal forward flow (F) in the aorta indicates presence of sPDA in preterm infants. The R/F ratio was assessed in 30 premature infants, including 13 cases without sPDA, and 17 infants with sPDA--in 12 of them before and after surgical ligation of PDA, in five concomitantly to pharmacological closure of PDA by the application of indomethacin. The R/F ratio was low in all infants without sPDA and in infants following surgical ligation of PDA. On the other hand, a high R/F ratio was found in all patients with sPDA before specific treatment. During indomethacin-induced closure of PDA the R/F ratio decreased continuously, whereas it remained high in infants with sPDA not responding to indomethacin treatment.     

Effects of prophylactic indomethacin on renal and intestinal blood flows in premature infants

Background: Prophylactic indomethacin reduces severe intraventricular hemorrhage and symptomatic patent ductus arteriosus in premature infants. The purpose of this study was to investigate the effects of prophylactic low‐dose indomethacin on renal and intestinal blood flow. Methods: Subjects were 19 extremely low‐birthweight infants admitted to our hospital and enrolled in a multicenter randomized control trial to study the efficacy and complications of prophylactic low‐dose indomethacin in the reduction of severe intraventricular hemorrhage and patent ductus arteriosus (indomethacin and placebo groups, ten and nine infants, respectively). We measured blood flow velocity in the right renal artery (right RA) and superior mesenteric artery (SMA) with pulsed Doppler ultrasound before and after the administration of the first dose of 0.1 mg/kg indomethacin or placebo. Results: End‐diastolic blood flow velocity (EDV) in the right RA and SMA increased significantly after the administration of indomethacin (P = 0.0414 and 0.0284, respectively), although the time‐averaged mean blood flow velocity (TAV) did not change significantly in either artery. In the placebo group, the pre‐ and postadministration values for TAV and EDV in the right RA and SMA did not differ. Neither group showed a significant change in the relative vascular resistance (mean blood pressure/TAV) in the right RA or SMA. EDV in the left pulmonary artery was significantly reduced only after the administration of indomethacin (P = 0.0284). Conclusions: Prophylactic low‐dose indomethacin increases the diastolic blood flow in the RA and SMA via a reduction in the ductal shunt volume, with no change in the regional vascular resistance.     

Effects of indomethacin and ibuprofen on mesenteric and renal blood flow in preterm infants with patent ductus arteriosus

OBJECTIVE: To evaluate the effect of intravenous ibuprofen and indomethacin for treatment of patent ductus arteriosus (PDA) on mesenteric and renal blood flow velocity in preterm infants. STUDY DESIGN: Seventeen mechanically ventilated preterm infants (<33 weeks' gestation) with PDA received either 0.2 mg/kg indomethacin (n = 8) or 10 mg/kg ibuprofen (n = 9), infused over 15 minutes. Mesenteric and renal blood flow velocity were measured by using Doppler ultrasonography. RESULTS: Indomethacin caused a significant reduction in mesenteric and renal blood flow velocity 30 minutes after drug administration; mesenteric and renal blood flow velocity did not return to the pretreatment values by 120 minutes. Ibuprofen did not alter blood flow 30 minutes after treatment, and blood flow increased 120 minutes after treatment. Mesenteric and renal blood flow velocity changes were significantly different between the 2 treatment groups. CONCLUSIONS: Compared with indomethacin, ibuprofen did not significantly reduce mesenteric and renal blood flow velocity.     

Patent ductus arteriosus and cystic periventricular leucomalacia in preterm infants

AIM: To test the association between early disturbances in hemodynamics induced by left-to-right shunting through the duct and cystic periventricular leucomalacia. PATIENTS: Forty-six preterm infants (27-32 wk) admitted to the neonatal intensive care unit with risk criteria. METHODS: Patent ductus arteriosus was evaluated on days 1 and 4, and was significant (sPDA) in cases of absent or reversed end diastolic flow in the subductal aorta. Resistance index was measured in the anterior cerebral artery and in the subductal aorta. MAIN OUTCOME: Diagnosis of cystic periventricular leucomalacia between day 10 and day 50. RESULTS: The 12 infants who developed cystic periventricular leucomalacia were compared with those who did not. On day 1, sPDA was more frequent (64% vs 26%; p = 0.03) in the cystic periventricular leucomalacia group, left ventricular output was higher (median = 341 vs 279 ml kg-1.min-1; p = 0.005), and rescue surfactant was more frequently used (83% vs 47%; p = 0.03). This latter association was confirmed by multivariate analysis. Resistance index in the anterior cerebral artery was increased in cases of significant patent ductus arteriosus (p < 0.01) and was correlated with resistance index in the subductal aorta. CONCLUSION: On day 1 in this selected population, sPDA has an effect on blood flow velocity waveform in cerebral arteries and is associated with an increase in the emergence of cystic periventricular leucomalacia. This association could be casual rather than causal.     

Range-gated pulsed Doppler ultrasonographic evaluation of carotid arterial blood flow in small preterm infants with patent ductus arteriosus

Range-gated pulsed Doppler (RGPD) ultrasonography was utilized to study the effect of a patent ductus arteriosus (PDA) on carotid arterial blood flow in small preterm infants. Carotid arterial flow velocity studies were performed on 23 preterm infants, sampling right and left carotid arteries. Studies on seven infants after PDA ligation and on seven who developed no evidence of PDA were used as controls. A strong relationship was demonstrated between diastolic reversal in the carotid arteries and PDA. The results of this study indicate that the RGPD flow velocity curve from the carotid artery is more sensitive than M-mode echocardiography or clinical examination in detecting PDA, and that PDA in small preterm infants is associated with a distinct abnormality in the carotid arterial flow pattern.     

血N端脑钠肽前体在早产儿症状性动脉导管未闭诊治中的应用价值

目的探讨血浆N端脑钠肽前体(NT-pro BNP)在早产儿症状性动脉导管未闭(s PDA)诊治中的临床应用价值。方法选取2013年10月—2014年9月入住新生儿重症监护病房、胎龄28~32周、出生体质量??1 500 g的早产儿107例,分别于生后第4、7天检测NT-pro BNP,采血后30 min内行超声心动图检查。根据生后第4天超声心动图检查结果分PDA组(39例)与对照组(68例);PDA组根据有无超声血流动力学显著改变及临床表现分为症状性PDA(s PDA组,20例)和无症状性PDA(as PDA组,19例);s PDA组再根据是否服用布洛芬分为治疗组(13例)与非治疗组(7例)。结果生后第4天,s PDA组患儿血浆NT-pro BNP水平高于as PDA组,as PDA组高于对照组,差异均有统计学意义(P??0.05);生后第7天,s PDA组患儿血浆NT-pro BNP水平高于as PDA组和对照组,差异有统计学意义(P??0.05),as PDA组与对照组的差异则无统计学意义(P??0.05)。治疗组生后第7天血浆NT-pro BNP水平较第4天显著下降,差异有统计学意义(P??0.05);非治疗组生后第7天与第4天血浆NT-pro BNP水平的差异无统计学意义(P??0.05)。PDA患儿生后第4天血浆NT-pro BNP水平与动脉导管(DA)直径、左心房/主动脉根部内径比值(LA/AO)及DA直径与左肺动脉内径比值(TDD/LPA)呈正相关(r=0.498~0.670,P均??0.05)。生后第4天血浆NT-pro BNP水平预测s PDA的ROC曲线下面积(AUC)为0.969(95%CI:0.938~1.000),NT-pro BNP水平在13 964 pg/m L时,诊断s PDA的灵敏度为95%,特异度为95.4%。结论 s PDA早产儿血浆NT-pro BNP水平明显增高,治疗后下降。第4天血浆NT-pro BNP是预测s PDA的敏感指标,动态监测血浆NT-pro BNP水平变化对指导早产儿PDA治疗策略的选择有重要临床价值。     

氨基末端脑钠肽前体预测早产儿症状性动脉导管未闭的价值

目的 探讨氨基末端脑钠肽前体(NT-proBNP)预测早产儿症状性动脉导管未闭(sPDA)的价值。方法 选择2014年6月至2015年4月出生、胎龄≤32周、48 h内超声心动图确定存在动脉导管的早产儿为研究对象,监测其临床表现,于生后3 d及5 d检测血清NT-proBNP水平并行超声心动图检查,根据患儿临床表现、超声心动图结果分为sPDA组及非症状性动脉导管未闭(asPDA)组,分析血清NT-proBNP水平与超声指标的关系,比较两组间相同日龄血清NT-proBNP水平,ROC曲线确定血清NT-proBNP水平预测sPDA的敏感性、特异性。结果 共69例早产儿纳入研究,其中sPDA组13例,asPDA组56例。血清NT-proBNP水平与动脉导管管径、左房内径与主动脉根部内径比值(LA/AO)呈正相关关系(分别r=0.856、0.713,均 PPCI:0.892~1.000,PCI:0.848~1.000,P结论 NT-proBNP可能是动脉导管分流量的量化指标;生后3 d 及5 d血清NT-proBNP水平的检测均有助于早期预测sPDA。     

Introduction of plasma indomethacin level monitoring and evaluation of an effective threshold level in very low birth weight infants with symptomatic patent ductus arteriosus

First results are described of individually tailored indomethacin dose rates employing on-line drug level monitoring for pharmacologically induced ductal constriction in very low birth weight infants with symptomatic patent ductus arteriosus (sPDA). In addition prolonged indomethacin therapy was introduced. From our data it appears that the effective threshold indomethacin level for the induction of ductus constriction has to be about 1000 ng/ml 10 h postdosing, while ductus closure can be maintained with a dose rate that exceeds a plasma level of 500 ng/ml for at least 1 week. These maintenance levels were also effective in completely suppressing the urinary metabolite excretion rates of PGI₂ and PGE₂, which are potential mediators of ductal relaxation. On-line indomethacin level monitoring appears to be practically essential for prolonged indomethacin therapy to overcome the marked variation of indomethacin disposition in preterm infants with sPDA.Abbreviations sPDA symptomatic patent ductus arteriosus - PDA-MUR patent ductus arteriosus murmur - PGE-M 7-hydroxy-5,11-diketotetranorprostane-1,16-dioic acid - IMV intermittent mandatory ventilation - R/F retrograde and forward flow ratio - HPLC high pressure liquid chromatography - GC-MS gas chromatography-mass spectrometry Dedicated to Prof. Dr. H. Bickel on the occasion of his 65th birthday     

Effect of indomethacin on superior mesenteric artery blood flow velocity in preterm infants

In 15 preterm infants with symptomatic patent ductus arteriosus, blood flow velocity changes in the superior mesenteric artery were investigated with Doppler ultrasound just before and during the first 12 hours after a single dose of indomethacin. Indomethacin administration led to an instantaneous decrease in all infants of temporal mean flow velocity in the superior mesenteric artery, which was maximal 10 minutes after administration of indomethacin, followed by a more sustained recovery, slightly greater than baseline values, 12 hours after indomethacin treatment. Simultaneously determined temporal mean flow velocity of the anterior cerebral artery, used as an indicator of changes in cerebral blood flow, had a similar pattern as in the mean flow velocity in the superior mesenteric artery (r = 0.49; p less than 0.001). Our data suggest that indomethacin lowered blood supply to the bowel, similar to its action on cerebral blood flow.     

The relationship between the continuous opening of arterial catheters and platelet parameters in preterm infants北大核心CSCD

Objective To analyze the correlation between the continuous opening of patent ductus arteriosus (PDA) in preterm infants and platelet parameters in the first 24 hours of life. Methods The preterm infants (gestational age <34 weeks) admitted to Neonatal Intensive Care Unit(NICU)of the Affiliated Xuzhou Hospital of Southeast University from November 2012 to July 2018 were enrolled. The following data were collected retrospectively: the platelet parameters in the first 24 hours of life, clinical factors possibly related to continuous opening of PDA, and echocardiography examination fin-dings on the 4 -7 day after birth. According to the diagnostic criteria of PDA, all preterm infants were divided into symptomatic PDA (sPDA) group, non - sPDA (nsPDA) group, and non - PDA (nPDA) group. SPSS 20.0 software was used for data analysis. Data were analyzed by Chi -square test,LSD or Tambane's T2 of One - Way analysis of variance, and binary Logistic regression analysis of the receiver operating characteristic (ROC) curve. Results Totally 760 preterm infants were chosen, and among them there were 67 cases (8. 8%) in sPDA group, 106 cases (14. 0%) in nsPDA group,and 587 cases (77. 2%) in nPDA group. There were significant differences in the terms of gestation age,birth weight,platelet counts (PLT),and plateletcrit (PCT) in the first 24 hours of life among 3 groups (all P < 0. 05). The smaller gestation age, the lower birth weight, the lower PLT and PCT in the first 24 hours of life,and the higher incidence of PDA in preterm infants. There were no significant differences in the platelet distribution width,mean platelet volume,and platelet large cell ratio in the first 24 hours of life among 3 groups (all P >0. 05). The low lower birth weight and PCT in the first 24 hours of life were independent risk factors for the occurrence of sPDA in preterm infants (P =0. 013,0. 000). The risk of occurrence of sPDA in preterm infants will be increased by 3.279 -fold (95% CI;2. 369 -4.479) if PCT in the first 24 hours of life is decreased by 0. 10%. The area under the ROC curves of PCT and PLT in the first 24 hours of life for prediction of sPDA in preterm infants was 0. 757 (95%C/:0.712 -0.814) and 0.718 (95%C/:0.671 -0.768),respectively. The best cutoff values of PCT and PLT were 0. 178% (sensitivity was 75. 7%, specificity was 71. 9%) and 207. 5 x 10 /L (sensitivity was 71. 4% specificity was 63. 2%). Conclusions The continuous opening of PDA in preterm infants may have correlation with the platelet. The low PCT, rather than PLT, in the first 24 hours of life was an independent risk factor and has medium predictive value for the occurrence of sPDA in preterm infants on the 4 - 7 day after birth. © 2019 Authors. All rights reserved.     

Atrial natriuretic peptide in the diagnosis of patent ductus arteriosus

The aim of this study was to measure plasma atrial natriuretic peptide in preterm infants with a patent ductus arteriosus before and after closure with indomethacin. Atrial natriuretic peptide was measured in 28 preterm infants with clinical and echocardiographic evidence of a patent ductus arteriosus and in eight preterm infants who did not develop clinical evidence of a patent ductus arteriosus. Plasma concentration of atrial natriuretic peptide was measured by radioimmunoassay. In 18 infants the patent ductus arteriosus closed after one course of indomethacin; atrial natriuretic peptide levels decreased from median 1240 pg/ml (range 201-5483 pg/ml) to 266 pg/ml (range 62-1108 pg/ml). In four infants the patent ductus arteriosus closed after two courses of indomethacin and two infants had surgical ligation after indomethacin treatment failed. The patent ductus arteriosus closed spontaneously in four infants (atrial natriuretic peptide median level 152 pg/ml, range 61-495 pg/ml). In the eight infants without patent ductus arteriosus, atrial natriuretic peptide level was median 224 pg/ml (range 38-876 pg/ml). Measurement of plasma atrial natriuretic peptide concentration has a role in predicting when indomethacin treatment is indicated.     

Pharmacokinetics of intra-arterial indomethacin treatment for patent ductus arteriosus

Summary We present pharmacokinetic data of prolonged, intra-arterial indomethacin treatment (i.e. induction plus maintenance dose) for symptomatic patent ductus arteriosus (sPDA) in 26 ventilated premature infants. sPDA was assessed by two-dimensional and pulsed Doppler echocardiography. Permanent ductal closure occurred in 20 (76%) infants. Plasma levels of indomethacin were 1.18±0.74; 1.8±1.0; 1.51±0.93 and 1.25±0.98 g/ml (mean±SD) at 12, 24, 48 and 72 h after initial dose administration. All except one patient who responded with ductal closure, showed plasma levels above 0.25 g/ml throughout the 3 day treatment period and no case of sPDA reopening was noted. Although target concentrations over time were not defined, the data indicate that the maintenance levels measured were within the therapeutic range. A negative correlation was found for plasma drug levels and postnatal age (r=0.52;P<0.01). Volume of drug distribution was 0.23±0.18l/kg, total clearance 0.1±0.11 ml/min and elimination constant 0.06±0.05h^–1 (mean±SD). The great variation in pharmacokinetic data reflects the heterogeneity of the population studied with respect to extracellular fluid space, cardiovascular status, serum protein and other parameters.     

Prolonged indomethacin treatment in preterm infants with symptomatic patent ductus arteriosus: efficacy,drug level monitoring,and patient selection

Indomethacin treatment for 1 week monitored by drug level determinations was evaluated in 32 preterm infants with symptomatic patent ductus arteriousus (sPDA). Inter- and intra-individual indomethacin dispositions varied considerably with the need for marked dosage adjustments to maintain the drug level within the proposed therapeutic range. The overall success rate of this prolonged treatment was 63%. There were no significant differences between the groups of responders (n=20), relapsers (n=5) and non-responders (n=7) with respect to postnatal age, sex, total indomethacin dose, and indomethacin serum concentrations. The responders, however, had significantly higher birth weights. Eighty-five percent of infants weighing more than 1000g (n=20) were treated successfully. Only four of these children experienced adverse reactions. The benefit-to-risk ratio was lowest in the group of infants weighing 1000 g or less (n=12) with a success rate of only 25% and, potentially, severe adverse reactions in ten infants. In conclusion, prolonged indomethacin treatment is an alternative to conventional short-term treatment and appears to be particularly efficacious and safe in infants weighing more than 1000 g. In infants weighing 1000 g or less and suffering from severe pulmonary diseases, this treatment cannot generally be recommended. The advantage of on-line drug level monitoring during indomethacin treatment deserves further investigation.     

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目的 探讨心功能改变对早产儿早期脑血流的影响.方法 2007年1-7月在暨南大学第二附属医院深圳市人民医院新生儿科住院的261例胎龄为29～36+6周的早产儿于生后不同日龄根据左心室射血分数(EF)各分为3组.应用经颅多普勒监测早产儿生后1、3、7 d的大脑中动脉血流速度指标及血管弹性指标.应用彩色多普勒超声心动图监测早产儿心功能指标及主动脉瓣口峰值流速.记录生后1 d早产儿胎龄及出生体重,并监测体温、血气、血糖、血压及红细胞比积.结果 生后1、3、7 d早产儿的脑血流速度均随EF增加而加快;EF与大脑中动脉收缩期峰值流速、舒张期末血流速度、平均血流速度均呈正相关(r分别为0.70、0.41、0.61,P均<0.01),而EF与血管阻力指数及弹性指数未见明显相关性.结论 早产儿早期脑血流速度受左室泵血功能的影响,而胎龄及出生体重是影响早产儿早期左室泵血功能的重要因素.     

The effect of phototherapy on cerebral blood flow velocity in preterm infants

Cerebral blood flow velocity was studied with two-dimensional/pulsed Doppler ultrasound before, during and after discontinuation of phototherapy in 22 preterm infants (gestational age ≤32 weeks), who were treated for a minimum of 12h with blue-light phototherapy for non-haemolytic hyperbilirubinaemia. Before the cerebral blood flow velocity measurements, patency of the ductus arteriosus was diagnosed by Doppler echocardiography. All infants had normal brain ultrasound scans. Mean cerebral blood flow velocity increased significantly after initiation of phototherapy in all infants. Only in “healthy” (non-ventilated) infants did cerebral blood flow velocity return to pre-phototherapy values (baseline) after discontinuation of phototherapy, whereas in “unhealthy” (ventilated) infants cerebral blood flow velocity did not return to baseline. In 10 infants the ductus arteriosus reopened during phototherapy. In those infants, mean cerebral blood flow velocity returned to pre-phototherapy values after 2h of phototherapy prior to its discontinuation.     

Symptomatic patent ductus arteriosus in very-low-birth-weight infants: 1987-1989.

Symptomatic patent ductus arteriosus (sPDA) may occur in up to 50% of very-low-birth-weight (VLBW, less than or equal to 1500 g) infants. We reported a 16% incidence in 1979-1980 in a totally inborn population, demonstrating the importance of early fluid management. Although survival of VLBW infants, especially those less than 1000 g, has increased, sPDA has not been carefully re-examined. Therefore, we sought to determine if the incidence, morbidity, treatment, or risk factors for sPDA had changed in this population. Between January 1, 1987 and December 31, 1989 all VLBW infants with sPDA surviving greater than 72 h (119/636) were identified and compared to matched controls (n = 70). Incidence and onset of sPDA were 19% and 10 +/- 6 days (+/- S.D.), respectively, the former increasing from 8% to 33% between 1251-1500 g and 500-750 g, respectively (P less than 0.001). Fluid and colloid administration were similar in sPDA and control infants. sPDA was associated with the occurrence of chronic lung disease (18% vs 7%, P = 0.005) and intracranial hemorrhage (53% vs 21%, P less than 0.001). Using stepwise logistic regression analysis we were unable to create a model that accurately predicted sPDA. Medical management and indomethacin were unsuccessful in 66% and 25%, respectively, of infants so treated; 43% required surgical ligation. Although survival of VLBW infants has increased, our incidence of sPDA remains low, with greater than 80% of infants demonstrating spontaneous closure when fluid and colloid administration are judiciously used.     

Changes in pulmonary arterial pressure in preterm infants with chronic lung disease

BACKGROUND: Pulmonary arterial pressure (PAP) is raised in preterm infants with respiratory distress syndrome who subsequently develop chronic lung disease. The natural history of pulmonary hypertension in infants with chronic lung disease is unknown. OBJECTIVES: To investigate changes in PAP, assessed non-invasively using Doppler echocardiography, in infants with chronic lung disease during the 1st year of life. METHODS: Serial examinations were performed in infants with chronic lung disease and healthy preterm infants. The Doppler derived acceleration time to right ventricular ejection time ratio (AT/RVET) was calculated from measurements made from the pulmonary artery velocity waveform. RESULTS: A total of 248 examinations were performed in 54 infants with chronic lung disease and 44 healthy preterm infants. The median AT/RVET was significantly lower in infants with chronic lung disease than in healthy preterm infants (0.31 v 0.37). AT/RVET significantly correlated with age corrected for prematurity in both infants with chronic lung disease (r = 0.67) and healthy infants (r = 0.55). There was no significant difference between the rate of change in AT/RVET between the two groups. In infants with chronic lung disease, multivariate analysis showed that AT/RVET was significantly independently associated with age and inversely with duration of supplemental oxygen treatment. Median AT/RVET was significantly lower in infants with chronic lung disease until 40-52 weeks of age corrected for prematurity. CONCLUSIONS: Although PAP falls with increasing age in both infants with chronic lung disease and healthy preterm infants, it remains persistently raised in infants with chronic lung disease until the end of the 1st year of life.     

Intestinal perforation associated with indomethacin treatment in premature infants

Within 9 months we observed intestinal perforations in three very low birth weight (VLBW) infants undergoing indomethacin treatment for symptomatic patent ductus arteriosus (sPDA). The three patients exhibited striking similarities in their clinical courses and predisposing factors. Although clinical and histological criteria did not differentiate the perforations from necrotising enterocolitis (NEC), a well-known entity in premature infants, these events were remarkable to us since we had observed no other cases of NEC in recent years. From animal experiments and pathophysiological data, a role for indomethacin in gastrointestinal ischaemic damage must be considered. This communication is not meant to discredit indomethacin treatment. However, awareness of potential complications and careful monitoring during treatment is warranted.Abbreviations NEC necrotising enterocolitis - VLBW very low birth weight - sPDA symptomatic patent ductus arteriosus - RDS respiratory distress syndrome     

Symptomatic patent ductus arteriosus following prophylactic indomethacin. A clinical and biochemical appraisal.

Seven of 36 premature infants with birth weight less than 1,250 g who had been randomly assigned to either high-frequency ventilatory ventilation or conventional mechanical ventilation developed symptomatic patent ductus arteriosus (PDA) after receiving prophylactic indomethacin, 0.2 mg/kg, i.v. 24 h after birth. Infants who developed symptomatic PDA were more likely to be white and male and have more severe pulmonary insufficiency than infants who did not develop symptomatic PDA. Serum indomethacin levels were similar in both groups of patients. There was no difference in the degree of suppression or subsequent recovery of endogenous eicosanoid biosynthesis between infants who did and did not develop symptomatic PDA. Compared to conventional mechanical ventilation, high-frequency oscillatory ventilation had no significant effect on endogenous eicosanoid biosynthesis. The susceptibility of white male infants to symptomatic PDA following prophylactic indomethacin may represent the influence of maturational factors on ductus patency. Cyclooxygenase products do not appear to be involved in mediating ductus patency when symptomatic PDA occurs immediately following administration of prophylactic indomethacin.