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 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 7  |  Issue : 3  |  Page : 121-124

Oral paracetamol versus intravenous paracetamol in the closure of patent ductus arteriosus: A proportion meta-analysis


1 Department of Pediatric Cardiology, National Heart Foundation Hospital, Dhaka, Bangladesh
2 Department of Neonatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

Date of Web Publication2-Aug-2018

Correspondence Address:
Dr. Mohammad Kamrul Hassan Shabuj
Department of Neonatology, Bangabandhu Sheikh Mujib Medical University, Dhaka
Bangladesh
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcn.JCN_119_17

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  Abstract 


Background: Patent ductus arteriosus (PDA) is a common cause of neonatal morbidity. We aimed to do this meta-analysis to compare the efficacy of oral paracetamol/acetaminophen and intravenous (IV) paracetamol for the closure of hemodynamically significant PDA (hsPDA) in preterm infants. Methodology: Medline, Embase, and Google Scholar databases were searched for citations. We included 14 studies with significant PDA and used either oral or IV paracetamol for PDA treatment. Pooled proportion of PDA closured was analyzed. Results: We included 14 studies with 454 premature infants having PDA. Pooled proportion of PDA closure with oral paracetamol was 77.79% (95% confidential interval [CI] 72.92—82.15) in fixed effect and 75.77% (95% 65.48—84.74) in random effect model. In case of IV paracetamol group, pooled portion of PDA closure was 81.52% (95% 74.00—87.64) and 81.52 (95% CI 74.62—87.55) in fixed and random model, respectively. The difference of proportion in the fixed effect model was 3.75% (95% CI, −5.08—11.64) (P = 0.37), and in the random effect model, it was 5.75 (95% CI, 3.14—13.74) (P = 0.181). Conclusion: Our study concluded that pooled proportion of PDA closure is comparable with oral versus IV route of paracetamol use.

Keywords: Paracetamol, patent ductus arteriosus, proportion meta-analysis


How to cite this article:
Hossain J, Shabuj MK. Oral paracetamol versus intravenous paracetamol in the closure of patent ductus arteriosus: A proportion meta-analysis. J Clin Neonatol 2018;7:121-4

How to cite this URL:
Hossain J, Shabuj MK. Oral paracetamol versus intravenous paracetamol in the closure of patent ductus arteriosus: A proportion meta-analysis. J Clin Neonatol [serial online] 2018 [cited 2018 Aug 15];7:121-4. Available from: http://www.jcnonweb.com/text.asp?2018/7/3/121/238392




  Introduction Top


Ductus arteriosus (DA) is the shunt that makes communication between pulmonary artery to aorta and it is one of the basic shunts necessary in the prenatal life to maintain fetal circulation.[1],[2] After birth due to transition of circulation, it will be closed. At 24—72 h, it is functionally closes in the term and healthy newborns.[3],[4] Ductus closure happens after birth due to increased postnatal levels of PaO2, increased in pulmonary flow, and decline of prostaglandin E2 (PGE2)[5],[6] and due to reduction PGE2 vasodilation effect on DA.[7],[8],[9] It may be remained open for some unwanted effect of transition. It is reported that patent DA (PDA) is common among preterm infants, 30% in very low birth weight infants (<1500 g)[10] and 50% in extremely low birth weight ones (<1000 g).[11] Failure to closure ductus in the preterm infants for long period of time leads to severe respiratory distress, requires prolonged ventilatory support, and increases change of pulmonary hemorrhage, bronchopulmonary dysplasia, necrotizing enterocolitis, renal functional impairment, intraventricular hemorrhage, periventricular leukomalacia, cerebral palsy, and death.[12] These aforementioned complications indicated the urgency of PDA treatment. There are several modalities of treatment of PDA. Paracetamol is one of the treatment options. Several case series and meta-analysis[13],[14],[15] showed that paracetamol has similar effect as ibuprofen. However, our main concern is different route of administration of paracetamol. We did this meta-analysis to see the efficacy of oral use of paracetamol versus intravenous (IV) paracetamol.


  Methodology Top


Data search and data extraction

Medline, Embase, and Google Scholar databases were searched for citation. Data forms were used to collect required information. Two reviewers extracted the articles that included hemodynamically significant PDA (hsPDA) in preterm infants and used paracetamol as an intervention. hsPDA was defined as the presence of at least one of the following criteria: internal ductal diameter 1.4 mm/kg body weight, left atrium -to-aortic root ratio >1.4, and unrestrictive pulsatile transductal flow. For proportional meta-analysis, we included those articles that included only paracetamol or paracetamol with placebo and paracetamol versus ibuprofen. We used the medical subject heading term and title as a searching procedure of the articles. Two reviewers independently extracted data, if there was any disagreement solved by consensus.

Quality assessment of the studies

The quality of the trials, assessed by the Cochrane-Recommended Grading Recommendation Assessment and Evaluation, was low-grade quality as majority of the articles were case series.

Statistical analysis

The extracted data were analyzed by the weighted proportion ratio by Mantel-Haenszel fixed and random effect model. Revman, version 5.3, Copenhagen, Denmark and Medcal software, were used for data analysis. The pooled data were presented by the forest plot and heterogeneity was analyzed by Q and I2 statistics, and publication bias was assessed by funnel plot.


  Results Top


We included 14 studies with 454 premature infants having PDA. Of those studies, five studies were controlled trails [Figure 1]. The study characteristics were described in terms of gestational age, route of administration, duration of treatment, and events of closure of PDA [Table 1]. Pooled proportion of PDA closure with oral paracetamol was 77.79% (95% confidential interval [CI] 72.92—82.15) in fixed effect and 75.77% (95% 65.48—84.74) in random effect model [Figure 2] and publication bias was shown by funnel plot and there was good symmetry of the plot [Figure 3]. In case of IV paracetamol group, pooled portion of PDA closure was 81.52% (95% 74.00—87.64) and 81.52 (95% CI 74.62—87.55) in fixed and random model, respectively [Figure 4], and publication bias also assessed by the funnel plot [Figure 5]. The difference of proportion was in the fixed effect model was 3.75% (95% CI, −5.08—11.64) (P = 0.37), and in the random effect model, it was 5.75 (95% CI, 3.14—13.74) (P = 0.181). Hence, both in the fixed and random effect model, oral and IV paracetamol was comparable.
Figure 1: Study inclusion procedure

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Table 1: Characteristics of the included studies

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Figure 2: Pooled proportion of PDA closure with oral Paracetamol

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Figure 3: Pooled proportion of PDA closure by IV Paracetamol

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Figure 4: Funnel plot for publication bias analysis in oral Paracetamol group

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Figure 5: Funnel plot for publication bias analysis in IV Paracetamol group

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  Discussion Top


In this meta-analysis, we compared the efficacy of oral paracetamol with the efficacy of IV paracetamol in terms of closure of hsPDA in premature infants in 14 studies. We had analyzed the proportion of PDA closure in ten case series and four controlled trials. Our study finding was comparable with the several studies in terms of proportion of PDA closure, but all those studies also did the invention comparison meta-analysis with ibuprofen versus paracetamol with 2 RCTs.[13],[14] Das et al.[13] The meta-analysis of the five randomized controlled trials (RCTs) done by Huang et al.[15] showed that proportion PDA closure was comparable with our study. However, this study also compared paracetamol with ibuprofen. No study was found that compared oral paracetamol versus IV paracetamol. The strength of our study was (i) More studies were included (ii) Publication bias was analyzed and showed funnel plot symmetry. Our study had several limitations: (i) no subgroup analysis was done for different dose schedule, for duration of treatment, (ii) not all the included studies were RCT, and (iii) we did not show the adverse effect comparison.


  Conclusion Top


Events of closure of hsPDA in premature infants with oral and IV paracetamol were comparable in pooled proportion, and any route of administration can be used.[29]

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Ohlsson A, Shah PS. Paracetamol (acetaminophen) for patent ductus arteriosus in preterm or low-birth-weight infants. Cochrane Database Syst Rev 2015;3:CD010061.  Back to cited text no. 14
    
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