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Journal of Orthopaedic Surgery and... Jan 2023The quality of reduction is an important factor affecting clinical outcomes for displaced femoral neck fractures (FNFs). However, concerns remain about the invasiveness... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The quality of reduction is an important factor affecting clinical outcomes for displaced femoral neck fractures (FNFs). However, concerns remain about the invasiveness of open reduction and internal fixation (ORIF) as compared to that of closed reduction and internal fixation (CRIF), and the choice between ORIF and CRIF as an optimal treatment strategy for displaced pediatric FNF remains controversial.
MATERIALS AND METHODS
MEDLINE, Embase, and the Cochrane Library were systematically searched for studies published up to December 22, 2022, that compared ORIF and CRIF techniques for treating FNF in children. Pooled analysis identified differences in surgical outcomes between ORIF and CRIF, especially regarding postoperative complications, such as osteonecrosis of the femoral head (ONFH), nonunion, coxa vara deformity, leg-length discrepancy LLD, and premature physeal closure (PPC).
RESULTS
We included 15 studies with 635 pediatric FNF cases in our review. Of these, 324 and 311 were treated with ORIF and CRIF, respectively. The pooled analysis revealed that no significant differences existed between each reduction technique for ONFH (odds ratio [OR] = 0.89; 95% confidence interval [CI] 0.51-1.56; P = 0.69), nonunion (OR = 0.51; 95% CI 0.18-1.47; P = 0.21), coxa vara deformity (OR = 0.58; 95% CI 0.20-1.72; P = 0.33), LLD (OR = 0.57; 95% CI 0.18-1.82; P = 0.35), and PPC (OR = 0.72; 95% CI 0.11-4.92; P = 0.74).
CONCLUSIONS
Despite concerns about the invasiveness of ORIF, no differences in complications exist between ORIF and CRIF after FNF in children. Therefore, we believe that ORIF should be performed in FNF when the fracture is irreducible by closed manner.
Topics: Humans; Child; Coxa Vara; Fracture Fixation, Internal; Femoral Neck Fractures; Open Fracture Reduction; Plastic Surgery Procedures; Retrospective Studies; Treatment Outcome
PubMed: 36650541
DOI: 10.1186/s13018-023-03525-x -
World Journal of Orthopedics Aug 2017To better understand how pediatric floating knee injuries are managed after the wide spread use of new orthopaedic technology.
AIM
To better understand how pediatric floating knee injuries are managed after the wide spread use of new orthopaedic technology.
METHODS
We searched EMBASE, COCHRANE and MEDLINE computerized literature databases from the earliest date available in the databases to February 2017 using the following search term including variants and pleural counterparts: Pediatric floating knee. All studies were thoroughly reviewed by multiple authors. Reference lists from all articles were scrutinized to identify any additional studies of interest. A final database of individual patients was assembled from the literature. Univariate and multivariate statistical tests were applied to the assembled database to assess differences in outcomes.
RESULTS
The English language literature contains series with a total of 97 pediatric patients who sustained floating knee injuries. Patients averaged 9.3 years of age and were mostly male (73). Approximately 25% of the fractures were open injuries, more tibia (27) than femur (10). Over 75% of the fractures of both the tibia and the femur involved the diaphysis. More than half (52) of the patients were treated non-operatively for both fractures. As a sequela of the injury 32 (33%) patients were left with a limb length discrepancy, 24 (25%) patients had lengthening of the injured limb at follow up, while 8 (8%) had shortening of the affected limb. Infection developed in 9 patients and 3 had premature physeal closure. Younger patients were more likely to be treated non-operatively ( < 0.001) and patients treated with operative intervention had statistically significant shorter hospital length of stays ( = 0.001).
CONCLUSION
Given the predominance of non-operative management in published studies, the available literature is not clinically relevant since the popularization of internal fixation for pediatric long-bone fractures.
PubMed: 28875130
DOI: 10.5312/wjo.v8.i8.638 -
The Cochrane Database of Systematic... Jan 2008Patent ductus arteriosus (PDA) is associated with increased mortality and morbidity in preterm infants. Prophylactic indomethacin results in favorable intermediate... (Review)
Review
BACKGROUND
Patent ductus arteriosus (PDA) is associated with increased mortality and morbidity in preterm infants. Prophylactic indomethacin results in favorable intermediate outcomes such as reduction of significant PDA, need for surgical ligation, severe intraventricular hemorrhage and serious pulmonary hemorrhage without modifying long-term neurosensory outcomes. Little is known about the effectiveness and safety of prophylactic surgical closure of the PDA in extremely low birth weight (ELBW) infants.
OBJECTIVES
To identify and summarize evidence from randomized controlled trials investigating the effectiveness and safety of prophylactic surgical ligation of the PDA on mortality and morbidities of preterm infants less than 1000 g at birth as compared to no prophylaxis or prophylactic cyclooxygenase inhibitors.
SEARCH STRATEGY
The standard search strategy for the Cochrane Neonatal Review Group was performed by two review authors. Searches were made of MEDLINE (1966 to December 2006), EMBASE (1980 to December 2006), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2006), and abstracts of annual meetings of the Society for Pediatric Research (1995 - 2006). Contacts were made with the authors of published articles.
SELECTION CRITERIA
Randomized or quazi-randomized controlled trials that enrolled infants less than 28 weeks gestation or less than 1000 g at birth who are on assisted ventilation and/or supplemental oxygen without clinical signs of hemodynamic significance of the ductus arteriosus were considered. Trials addressing prophylactic surgical ligation of the patent ducts arteriosus (i.e. procedure done during the first 72 hours of life) versus no intervention or cyclooxygenase inhibitor prophylaxis were included. The primary outcome was bronchopulmonary dysplasia (BPD). Other important short and long-term neonatal outcomes were also considered.
DATA COLLECTION AND ANALYSIS
Standard methods of the Cochrane Collaboration and its Neonatal Review Group were used to assess the methodologic quality of the trials. Retrieved articles were assessed for eligibility and data was abstracted independently by two reviewer authors. Where data were incomplete, the primary investigators were contacted for further information and clarifications. For dichotomous outcomes, relative risk (RR) and its associated confidence interval were calculated. For continuous outcomes, treatment effect was expressed as mean difference and its calculated standard deviation. When appropriate, meta-analysis of pooled data was performed assuming a fixed effect model
MAIN RESULTS
Only one eligible study that enrolled 84 ELBW infants was identified. The prophylactic group had ductal ligation performed within 24 hours of life following a pre-specified protocol, while the control group received standard care without indomethacin. Prophylactic surgical ligation of the PDA resulted in a statistically significant reduction of severe stage II or III necrotizing enterocolitis (NEC), [RR 0.25, 95% CI (0.08,0.83), p value 0.02, NNT 5]. The study found no statistically significant difference in mortality, severe grade III and IV intraventricular hemorrhage (IVH), BPD, and retinopathy of prematurity (ROP). Of note, the study was unblinded and underpowered to detect clinically important differences in the above mentioned outcomes.
AUTHORS' CONCLUSIONS
Prophylactic surgical ligation of the PDA did not decrease mortality or BPD in ELBW infants. A significant reduction of stage II or III NEC was noted. Based on the current evidence, the high rate of spontaneous closure, availability of effective safe medical therapies, and the potential short and long-term complications of surgical ligation, the use such prophylactic surgical therapy is not indicated in the management of the preterm infants.
Topics: Ductus Arteriosus, Patent; Humans; Infant, Extremely Low Birth Weight; Infant, Newborn; Infant, Premature; Ligation
PubMed: 18254095
DOI: 10.1002/14651858.CD006181.pub2 -
The Cochrane Database of Systematic... Sep 2018Indomethacin is used as standard therapy to close a patent ductus arteriosus (PDA) but is associated with reduced blood flow to several organs. Ibuprofen, another... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Indomethacin is used as standard therapy to close a patent ductus arteriosus (PDA) but is associated with reduced blood flow to several organs. Ibuprofen, another cyclo-oxygenase inhibitor, may be as effective as indomethacin with fewer adverse effects.
OBJECTIVES
To determine the effectiveness and safety of ibuprofen compared with indomethacin, other cyclo-oxygenase inhibitor(s), placebo, or no intervention for closing a patent ductus arteriosus in preterm, low-birth-weight, or preterm and low-birth-weight infants.
SEARCH METHODS
We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2017, Issue 10), MEDLINE via PubMed (1966 to 30 November 2017), Embase (1980 to 30 November 2017), and CINAHL (1982 to 30 November 2017). We searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials.
SELECTION CRITERIA
Randomised or quasi-randomised controlled trials of ibuprofen for the treatment of a PDA in preterm, low birth weight, or both preterm and low-birth-weight newborn infants.
DATA COLLECTION AND ANALYSIS
Data collection and analysis conformed to the methods of the Cochrane Neonatal Review Group. We used the GRADE approach to assess the quality of evidence.
MAIN RESULTS
We included 39 studies enrolling 2843 infants.Ibuprofen (IV) versus placebo: IV Ibuprofen (3 doses) reduced the failure to close a PDA compared with placebo (typical relative risk (RR); 0.62 (95% CI 0.44 to 0.86); typical risk difference (RD); -0.18 (95% CI -0.30 to -0.06); NNTB 6 (95% CI 3 to 17); I = 65% for RR and I = 0% for RD; 2 studies, 206 infants; moderate-quality the evidence). One study reported decreased failure to close a PDA after single or three doses of oral ibuprofen compared with placebo (64 infants; RR 0.26, 95% CI 0.11 to 0.62; RD -0.44, 95% CI -0.65 to -0.23; NNTB 2, 95% CI 2 to 4; I test not applicable).Ibuprofen (IV or oral) compared with indomethacin (IV or oral): Twenty-four studies (1590 infants) comparing ibuprofen (IV or oral) with indomethacin (IV or oral) found no significant differences in failure rates for PDA closure (typical RR 1.07, 95% CI 0.92 to 1.24; typical RD 0.02, 95% CI -0.02 to 0.06; I = 0% for both RR and RD; moderate-quality evidence). A reduction in NEC (necrotising enterocolitis) was noted in the ibuprofen (IV or oral) group (18 studies, 1292 infants; typical RR 0.68, 95% CI 0.49 to 0.94; typical RD -0.04, 95% CI -0.07 to -0.01; NNTB 25, 95% CI 14 to 100; I = 0% for both RR and RD; moderate-quality evidence). There was a statistically significant reduction in the proportion of infants with oliguria in the ibuprofen group (6 studies, 576 infants; typical RR 0.28, 95% CI 0.14 to 0.54; typical RD -0.09, 95% CI -0.14 to -0.05; NNTB 11, 95% CI 7 to 20; I = 24% for RR and I = 69% for RD; moderate-quality evidence). The serum/plasma creatinine levels 72 hours after initiation of treatment were statistically significantly lower in the ibuprofen group (11 studies, 918 infants; MD -8.12 µmol/L, 95% CI -10.81 to -5.43). For this comparison, there was high between-study heterogeneity (I = 83%) and low-quality evidence.Ibuprofen (oral) compared with indomethacin (IV or oral): Eight studies (272 infants) reported on failure rates for PDA closure in a subgroup of the above studies comparing oral ibuprofen with indomethacin (IV or oral). There was no significant difference between the groups (typical RR 0.96, 95% CI 0.73 to 1.27; typical RD -0.01, 95% CI -0.12 to 0.09; I = 0% for both RR and RD). The risk of NEC was reduced with oral ibuprofen compared with indomethacin (IV or oral) (7 studies, 249 infants; typical RR 0.41, 95% CI 0.23 to 0.73; typical RD -0.13, 95% CI -0.22 to -0.05; NNTB 8, 95% CI 5 to 20; I = 0% for both RR and RD). There was low-quality evidence for these two outcomes. There was a decreased risk of failure to close a PDA with oral ibuprofen compared with IV ibuprofen (5 studies, 406 infants; typical RR 0.38, 95% CI 0.26 to 0.56; typical RD -0.22, 95% CI -0.31 to -0.14; NNTB 5, 95% CI 3 to 7; moderate-quality evidence). There was a decreased risk of failure to close a PDA with high-dose versus standard-dose of IV ibuprofen (3 studies 190 infants; typical RR 0.37, 95% CI 0.22 to 0.61; typical RD - 0.26, 95% CI -0.38 to -0.15; NNTB 4, 95% CI 3 to 7); I = 4% for RR and 0% for RD); moderate-quality evidence).Early versus expectant administration of IV ibuprofen, echocardiographically-guided IV ibuprofen treatment versus standard IV ibuprofen treatment, continuous infusion of ibuprofen versus intermittent boluses of ibuprofen, and rectal ibuprofen versus oral ibuprofen were studied in too few trials to allow for precise estimates of any clinical outcomes.
AUTHORS' CONCLUSIONS
Ibuprofen is as effective as indomethacin in closing a PDA. Ibuprofen reduces the risk of NEC and transient renal insufficiency. Therefore, of these two drugs, ibuprofen appears to be the drug of choice. The effectiveness of ibuprofen versus paracetamol is assessed in a separate review. Oro-gastric administration of ibuprofen appears as effective as IV administration. To make further recommendations, studies are needed to assess the effectiveness of high-dose versus standard-dose ibuprofen, early versus expectant administration of ibuprofen, echocardiographically-guided versus standard IV ibuprofen, and continuous infusion versus intermittent boluses of ibuprofen. Studies are lacking evaluating the effect of ibuprofen on longer-term outcomes in infants with PDA.
Topics: Administration, Oral; Cyclooxygenase Inhibitors; Ductus Arteriosus, Patent; Enterocolitis, Necrotizing; Humans; Ibuprofen; Indomethacin; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Injections, Intravenous; Randomized Controlled Trials as Topic; Treatment Failure
PubMed: 30264852
DOI: 10.1002/14651858.CD003481.pub7 -
JPMA. the Journal of the Pakistan... Oct 2022The management of patent ductus arteriosus (PDA) in preterm neonates remains controversial. A retrospective review was conducted to determine the outcomes in preterm...
The management of patent ductus arteriosus (PDA) in preterm neonates remains controversial. A retrospective review was conducted to determine the outcomes in preterm neonates with PDA. Data of neonates admitted to the Aga Khan University Hospital from January 2012 to December 2016 were retrieved from patient records. Of the 208 neonates included in the study, 143 (68.7%) received no treatment, while 65 (31.2%) underwent pharmacotherapy and/or surgical ligation for PDA closure. PDA closure was spontaneous in 109 (52.4%) neonates. The mean ±SD gestational age (GA) of neonates with spontaneous ductal closure was greater as compared to those who required some form of treatment [33±3.3 vs 29.7±3.1weeks, p=0.001]. Apnoea (OR:4.47; 95% CI:1.21-16.44), sepsis (OR:3.81; 95% CI:1.33-10.87), pulmonary haemorrhage (OR:4.88; 95% CI:1.24-19.19), and lower APGAR (OR:0.69; 95% CI:0.54-0.90) were associated with higher odds of mortality in our cohort. Our findings demonstrate that PDA resolves spontaneously in most preterm neonates and provide evidence that conservative treatment is not associated with mortality.
Topics: Humans; Infant, Newborn; Ductus Arteriosus, Patent; Gestational Age; Infant, Premature; Retrospective Studies; Tertiary Care Centers; Treatment Outcome
PubMed: 36660997
DOI: 10.47391/JPMA.3416 -
The Cochrane Database of Systematic... Apr 2007Indomethacin is a prostaglandin inhibitor used to treat patent ductus arteriosus (PDA) in preterm infants. Although indomethacin produces ductal closure in the majority... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Indomethacin is a prostaglandin inhibitor used to treat patent ductus arteriosus (PDA) in preterm infants. Although indomethacin produces ductal closure in the majority of cases, it is ineffective in up to 40% of patients. Furthermore, the ductus will re-open in up to 35% of infants who initially respond to the drug. Prolonging the course of indomethacin has the potential to achieve higher rates of ductal closure.
OBJECTIVES
To determine the effect of a prolonged course of indomethacin (compared to a short course) on the rate of treatment failure without unwanted side-effects in preterm infants with PDA.
SEARCH STRATEGY
The search included review of personal files, abstracts of conferences, and the following electronic databases: MEDLINE (1966 to December 2006), EMBASE (1974 to December 2006), and Oxford Database of Perinatal Trials, Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2006). No language restrictions were applied.
SELECTION CRITERIA
Randomized or quasi-randomized controlled trials including preterm infants with PDA, diagnosed on clinical and/or echocardiographic examination that evaluated indomethacin treatment by any route given as a long course (four or more doses) vs. a short course (three or fewer doses) were included in the review. Trials needed to report on at least one of the following outcomes: failure of PDA to close, need for re-treatment, PDA re-opening, PDA ligation, mortality, duration of assisted ventilation, chronic lung disease (CLD), duration of supplemental oxygen dependence, intraventricular hemorrhage (IVH) (all and severe), diminished urine output, increased serum creatinine, necrotizing enterocolitis (NEC), bleeding diathesis, retinopathy of prematurity (ROP), and duration of hospital stay.
DATA COLLECTION AND ANALYSIS
The three review authors independently abstracted data from each study. Relative risk (RR) and Risk Difference (RD) with 95% confidence intervals (CI) using the fixed effect model for meta-analysis are reported. When a statistically significant RD was found, the number needed to treat (NNT) or number needed to harm (NNH) was also calculated with 95% CIs. The I squared statistic was used to test for heterogeneity of results among included trials.
MAIN RESULTS
Five trials met inclusion criteria and included 431 infants. Prolonged indomethacin treatment when compared to the short course did not result in a statistically significant difference in PDA closure, re-treatment, re-opening, or ligation rates. The prolonged course was associated with an increased risk of NEC [typical RR 1.87 (95% CI 1.07, 3.27); typical RD 0.08 (95% CI 0.01, 0.15); NNH 13 (7, 100)] and a decreased incidence of renal function impairment, as evidenced by a lower proportion of infants having diminished urine output [typical RR 0.27 (95% CI 0.13, 0.6); typical RD -0.19 (95% CI -0.28, -0.09); NNT 5 (4, 11)] and increased serum creatinine level [typical RR 0.51 (95% CI 0.33, 0.77); typical RD -0.14 (95% CI -0.23, -0.06); NNT 7 (4, 16)].
AUTHORS' CONCLUSIONS
Implications for practiceProlonged indomethacin course does not appear to have a significant effect on improving important outcomes, such as PDA treatment failure, CLD, IVH, or mortality. The reduction of transient renal impairment does not outweigh the increased risk of NEC associated with the prolonged course. Based on these results, a prolonged course of indomethacin cannot be recommended for the routine treatment of PDA in preterm infants. Implications for researchThere is a paucity of data on optimal dosing and duration of indomethacin therapy for the treatment of PDA, in particular for extremely low birth weight infants (ELBW) premature infants. It is likely that a single standard indomethacin regime is not the ideal for every premature infant. Therefore, individual patient response should be considered and evaluated, in particular in ELBW infants. Future randomized clinical trials should include this high risk population and investigate the effect of tailoring dose and duration of therapy to individual response in terms of echocardiographic findings and/or prostaglandin levels, focusing on clinically significant outcomes, including long-term neurodevelopmental outcomes. In addition, factors that may influence treatment effect, such as birth weight, gestational age, age at the time of randomization, total fluid intake, feeding practice, and severity of PDA, need to be taken into account when designing such studies.
Topics: Ductus Arteriosus, Patent; Humans; Indomethacin; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Prostaglandin Antagonists; Randomized Controlled Trials as Topic
PubMed: 17443527
DOI: 10.1002/14651858.CD003480.pub3 -
The Cochrane Database of Systematic... Jan 2020In preterm newborns, the ductus arteriosus frequently fails to close and the infants require medical or surgical closure of the patent ductus arteriosus (PDA). A PDA can... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In preterm newborns, the ductus arteriosus frequently fails to close and the infants require medical or surgical closure of the patent ductus arteriosus (PDA). A PDA can be treated surgically; or medically with one of two prostaglandin inhibitors, indomethacin or ibuprofen. Case reports suggest that paracetamol may be an alternative for the closure of a PDA. An association between prenatal or postnatal exposure to paracetamol and later development of autism or autism spectrum disorder has been reported.
OBJECTIVES
To determine the effectiveness and safety of intravenous or oral paracetamol compared with placebo or no intervention, intravenous indomethacin, intravenous or oral ibuprofen, or with other cyclo-oxygenase inhibitors for treatment of an echocardiographically diagnosed PDA in preterm or low birth weight infants.
SEARCH METHODS
We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2017, Issue 10), MEDLINE via PubMed (1966 to 6 November 2017), Embase (1980 to 6 November 2017), and CINAHL (1982 to 6 November 2017). We searched clinical trial databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials (RCT) and quasi-randomised trials.
SELECTION CRITERIA
We included RCTs in which paracetamol was compared to no intervention, placebo or other agents used for closure of PDA irrespective of dose, duration and mode of administration in preterm (≤ 34 weeks' postmenstrual age) infants. We both reviewed the search results and made a final selection of potentially eligible articles by discussion. We included studies of both prophylactic and therapeutic use of paracetamol.
DATA COLLECTION AND ANALYSIS
We performed data collection and analyses in accordance with the methods of the Cochrane Neonatal Review Group. We used the GRADE approach to assess the quality of evidence for the following outcomes when data were available: failure of ductal closure after the first course of treatment; neurodevelopmental impairment; all-cause mortality during initial hospital stay (death); gastrointestinal bleed or stools positive for occult blood; and serum levels of creatinine after treatment (µmol/L).
MAIN RESULTS
We included eight studies that reported on 916 infants. One of these studies compared paracetamol to both ibuprofen and indomethacin. Five studies compared treatment of PDA with paracetamol versus ibuprofen and enrolled 559 infants. There was no significant difference between paracetamol and ibuprofen for failure of ductal closure after the first course of drug administration (typical risk ratio (RR) 0.95, 95% confidence interval (CI) 0.75 to 1.21; typical risk difference (RD) -0.02, 95% CI -0.09 to 0.09); I² = 0% for RR and RD; moderate quality of evidence. Four studies (n = 537) reported on gastrointestinal bleed which was lower in the paracetamol group versus the ibuprofen group (typical RR 0.28, 95% CI 0.12 to 0.69; typical RD -0.06, 95% CI -0.09 to -0.02); I² = 0% for RR and RD; number needed to treat for an additional beneficial outcome (NNTB) 17 (95% CI 11 to 50); moderate quality of evidence. The serum levels of creatinine were lower in the paracetamol group compared with the ibuprofen group in four studies (moderate quality of evidence), as were serum bilirubin levels following treatment in two studies (n = 290). Platelet counts and daily urine output were higher in the paracetamol group compared with the ibuprofen group. One study reported on long-term follow-up to 18 to 24 months of age following treatment with paracetamol versus ibuprofen. There were no significant differences in the neurological outcomes at 18 to 24 months (n = 61); (low quality of evidence). Two studies compared prophylactic administration of paracetamol for a PDA with placebo or no intervention in 80 infants. Paracetamol resulted in a lower rate of failure of ductal closure after 4 to 5 days of treatment compared to placebo or no intervention which was of borderline significance for typical RR 0.49 (95% CI 0.24 to 1.00; P = 0.05); but significant for typical RD -0.21 (95% CI -0.41 to -0.02); I² = 0 % for RR and RD; NNTB 5 (95% CI 2 to 50); (low quality of evidence). Two studies (n = 277) compared paracetamol with indomethacin. There was no significant difference in the failure to close a PDA (typical RR 0.96, 95% CI 0.55 to 1.65; I² = 11%; typical RD -0.01, 95% CI -0.09 to 0.08; I² = 17%) (low quality of evidence). Serum creatinine levels were significantly lower in the paracetamol group compared with the indomethacin group and platelet counts and daily urine output were significantly higher in the paracetamol group.
AUTHORS' CONCLUSIONS
Moderate-quality evidence according to GRADE suggests that paracetamol is as effective as ibuprofen; low-quality evidence suggests paracetamol to be more effective than placebo or no intervention; and low-quality evidence suggests paracetamol as effective as indomethacin in closing a PDA. There was no difference in neurodevelopmental outcome in children exposed to paracetamol compared to ibuprofen; however the quality of evidence is low and comes from only one study. In view of concerns raised regarding neurodevelopmental outcomes following prenatal and postnatal exposure to paracetamol, long-term follow-up to at least 18 to 24 months' postnatal age must be incorporated in any studies of paracetamol in the newborn population. At least 19 ongoing trials have been registered. Such trials are required before any recommendations for the possible routine use of paracetamol in the newborn population can be made.
Topics: Acetaminophen; Cyclooxygenase Inhibitors; Ductus Arteriosus, Patent; Humans; Ibuprofen; Indomethacin; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Odds Ratio; Randomized Controlled Trials as Topic
PubMed: 31985831
DOI: 10.1002/14651858.CD010061.pub4 -
The Cochrane Database of Systematic... Jan 2008Indomethacin is a prostaglandin inhibitor used for the prevention and the treatment of patent ductus arteriosus (PDA). Although a 3-dose schedule has been commonly used,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Indomethacin is a prostaglandin inhibitor used for the prevention and the treatment of patent ductus arteriosus (PDA). Although a 3-dose schedule has been commonly used, there is no consensus on optimal dosage and duration of indomethacin therapy for PDA closure. There are potential adverse effects of indomethacin use in premature infants such as a reduction in cerebral, mesenteric and renal blood flow and platelet dysfunction. Administering indomethacin continuously over 36-hours has been suggested as a safer and more effective option to prevent such adverse effects.
OBJECTIVES
To compare the efficacy and safety of continuous infusion versus bolus administration of indomethacin in closing a symptomatic PDA in preterm infants.
SEARCH STRATEGY
The standard search strategy of Cochrane Neonatal Review was used: MEDLINE and EMBASE (1966 - March 2007), Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2007), bibliographies of reviews and trials were examined for references to other trials, previous symposia proceedings published in Pediatric Research (Pediatric Academic Societies Annual Meeting Abstract Book, 1972 - 2006). No language restrictions were applied.
SELECTION CRITERIA
Randomized and quasi-randomized controlled trials comparing continuous indomethacin infusion to bolus doses for closure of a symptomatic PDA in preterm infants with a symptomatic PDA diagnosed clinically and/or by echocardiography.
DATA COLLECTION AND ANALYSIS
The methodological quality of each study was assessed. Authors were contacted regarding missing data as well as to inquire about the outcomes that were not reported. Meta-analysis was performed to calculate relative risk (RR), risk difference (RD) and 95% confidence intervals (CI).
MAIN RESULTS
Only two small trials comparing continuous versus bolus indomethacin were eligible. Analysis of these studies showed that, although the primary outcome of PDA closure on days two and five slightly favored bolus administration, there was no statistical difference between the two groups. The estimates for PDA closure were RR 1.57 (95% CI 0.54, 4.60), RD 0.10 (95% CI -0.13, 0.33) for day 2 and RR 2.77 (95% CI 0.33, 23.14), RD 0.15 (95% CI -0.13, 0.42) for day five. There was no statistical difference between the bolus and continuous groups for the secondary outcomes of reopening of PDA, neonatal mortality, intraventricular hemorrhage (IVH) and necrotizing enterocolitis (NEC). These analyses were based on a very small number of events reported by these trials. None of the trials reported on outcomes such as requirement for retreatment with indomethacin or surgical ligation, mortality, bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), neurodevelopmental outcome and isolated intestinal perforation. The review demonstrated that there was a decrease in cerebral blood flow velocity after bolus injections and that the difference between the bolus and continuous infusion groups remained significant for 12 - 24 hour. In one study (Christmann 2002), the decrease in blood flow was maximum at 10 minutes [MD -46.40 (95% CI -75.41, -17.39)], while the other study (Hammerman 1995) reported a maximum drop at 30 minutes [MD -55.60 (95% CI -62.92, -48.28)]. Similar decrease in blood flow to the renal and mesenteric circulations following bolus administration was reported in one study (Christmann 2002). In both of these circulations, the decrease was maximum 30 minutes after the bolus injection [typical estimates for renal and mesenteric circulations, respectively: MD -42.00 (95% CI -76.59, -7.41) and MD -26.50 (95% CI -45.34, -7.66)] and lasted about two hours. None of the trials detected predefined levels of decreased urine output and increased levels of BUN and creatinine.
AUTHORS' CONCLUSIONS
Due to a paucity of events and lack of precision, the available data was found to be insufficient to draw conclusions regarding the efficacy of continuous indomethacin infusion versus bolus injections for the treatment of PDA. Although continuous indomethacin seems to cause less alterations in cerebral, renal and mesenteric circulations, the clinical meaning of this effect is unclear. Definitive recommendations about the preferred method of indomethacin administration i.e. continuous versus bolus infusions for the treatment of PDA in premature infants cannot be made based on the current findings of this review.
Topics: Blood Flow Velocity; Cerebrovascular Circulation; Ductus Arteriosus, Patent; Humans; Indomethacin; Infant, Newborn; Infant, Premature; Infusions, Intravenous; Injections, Intravenous; Prostaglandin Antagonists; Randomized Controlled Trials as Topic
PubMed: 18254092
DOI: 10.1002/14651858.CD006071.pub2 -
Frontiers in Pediatrics 2021There is an ongoing debate on the optimal management of patent ductus arteriosus (PDA) in preterm infants. Identifying subgroup of infants who would benefit from...
There is an ongoing debate on the optimal management of patent ductus arteriosus (PDA) in preterm infants. Identifying subgroup of infants who would benefit from pharmacological treatment might help. To investigate the modulating effect of the differences in methodological quality, the rate of open-label treatment, and patient characteristics on relevant outcome measures in randomized controlled trials (RCTs). Electronic database search between 1950 and May 2020. RCTs that assessed pharmacological treatment compared to placebo/no treatment. Data is extracted following the PRISMA guidelines. Outcome measures were failure to ductal closure, surgical ligation, incidence of necrotizing enterocolitis, bronchopulmonary dysplasia, sepsis, periventricular leukomalacia, intraventricular hemorrhage (IVH) grade ≥3, retinopathy of prematurity and mortality. Forty-seven studies were eligible. The incidence of IVH grade ≥3 was lower in the treated infants compared to the placebo/no treatment (RR 0.77, 95% CI 0.64-0.94) and in the subgroups of infants with either a gestational age <28 weeks (RR 0.77, 95% CI 0.61-0.98), a birth weight <1,000 g (RR 0.77, 95% CI 0.61-0.97), or if untargeted treatment with indomethacin was started <24 h after birth (RR 0.70, 95% CI 0.54-0.90). Statistical heterogeneity caused by missing data and variable definitions of outcome parameters. Although the quality of evidence is low, this meta-analysis suggests that pharmacological treatment of PDA reduces severe IVH in extremely preterm, extremely low birth weight infants or if treatment with indomethacin was started <24 h after birth. No other beneficial effects of pharmacological treatment were found.
PubMed: 33634058
DOI: 10.3389/fped.2021.626262 -
Ibuprofen for the prevention of patent ductus arteriosus in preterm and/or low birth weight infants.The Cochrane Database of Systematic... Jan 2020Patent ductus arteriosus (PDA) complicates the clinical course of preterm infants and increases the risk of adverse outcomes. Indomethacin has been the standard... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Patent ductus arteriosus (PDA) complicates the clinical course of preterm infants and increases the risk of adverse outcomes. Indomethacin has been the standard treatment to close a PDA but is associated with renal, gastrointestinal, and cerebral side effects. Ibuprofen has less effect on blood flow velocity to important organs.
OBJECTIVES
Primary objectives To determine the effectiveness and safety of ibuprofen compared to placebo/no intervention, or other cyclo-oxygenase inhibitor drugs in the prevention of PDA in preterm infants.
SEARCH METHODS
We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 10), MEDLINE via PubMed (1966 to 17 October 2018), Embase (1980 to 17 October 2018), and CINAHL; 1982 to 17 October 2018). We searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials.
SELECTION CRITERIA
Randomised and quasi-randomised controlled trials comparing ibuprofen with placebo/no intervention or other cyclo-oxygenase inhibitor drugs to prevent PDA in preterm or low birth weight infants.
DATA COLLECTION AND ANALYSIS
We extracted outcomes data including presence of PDA on day three or four of life (after 72 hours of treatment), need for surgical ligation or rescue treatment with cyclo-oxygenase inhibitors, mortality, cerebral, renal, pulmonary, and gastrointestinal complications. We performed meta-analyses and reported treatment estimates as typical mean difference (MD), risk ratio (RR), risk difference (RD) and, if statistically significant, number needed to treat to benefit (NNTB) or to harm (NNTH), along with their 95% confidence intervals (CI). We assessed between-study heterogeneity by the I-squared test (I²). We used the GRADE approach to assess the quality of evidence.
MAIN RESULTS
In this updated analysis, we included nine trials (N = 1070 infants) comparing prophylactic ibuprofen (IV or oral) with placebo/no intervention or indomethacin. Ibuprofen (IV or oral) probably decreases the risk of PDA on day 3 or 4 (typical RR 0.39, 95% CI 0.31 to 0.48; typical RD -0.26, 95% CI -0.31 to -0.21; NNTB 4, 95% CI 3 to 5; 9 trials; N = 1029) (moderate-quality evidence). In the control group, the spontaneous closure rate was 58% by day 3 to 4 of age. In addition, ibuprofen probably decreases the need for rescue treatment with cyclo-oxygenase inhibitors (typical RR 0.17, 95% CI 0.11 to 0.26; typical RD -0.27, 95% CI -0.32 to -0.22; NNTB 4; 95% CI 3 to 5),and the need for surgical ductal ligation (typical RR 0.46, 95% CI 0.22 to 0.96; typical RD -0.03, 95% CI -0.05 to -0.00; NNTB 33, 95% CI 20 to infinity; 7 trials; N = 925) (moderate-quality evidence). There was a possible decrease in the risk of grade 3 or 4 intraventricular haemorrhage (IVH) in infants receiving prophylactic ibuprofen (typical RR 0.67, 95% CI 0.45 to 1.00; I² = 34%; typical RD -0.04, 95% CI -0.08 to- 0.00; I² = 60%; 7 trials; N = 925) (moderate-quality evidence). High quality evidence showed increased risk for oliguria (typical RR 1.45, 95% CI 1.04 to 2.02; typical RD 0.06, 95% CI 0.01 to 0.11; NNTH 17, 95% CI 9 to 100; 4 trials; N = 747). Low quality results from four studies (N = 202) showed that administering oral ibuprofen may decrease the risk of PDA (typical RR 0.47, 95% CI 0.30 to 0.74) and may increase risk of gastrointestinal bleeding (NNTH 7, 95% CI 4 to 25). No evidence of a difference was identified for mortality, any intraventricular haemorrhage (IVH), or chronic lung disease.
AUTHORS' CONCLUSIONS
This review shows that prophylactic use of ibuprofen, compared to placebo or no intervention, probably decreases the incidence of patent ductus arteriosus, the need for rescue treatment with cyclo-oxygenase inhibitors, and for surgical ductal closure. Adverse effects associated with ibuprofen (IV or oral) included increased risks for oliguria, increase in serum creatinine levels, and increased risk of gastrointestinal haemorrhage. There was a reduced risk for intraventricular haemorrhage (grade III - IV) but no evidence of a difference in mortality, chronic lung disease, necrotising enterocolitis, or time to reach full feeds. In the control group, the patent ductus arteriosus had closed spontaneously by day 3 or 4 in 58% of neonates. Prophylactic treatment exposes a large proportion of infants unnecessarily to a drug that has important side effects without conferring any important short-term benefits. Current evidence does not support the use of ibuprofen for prevention of patent ductus arteriosus. Until long-term follow-up results of the trials included in this review have been published, no further trials of prophylactic ibuprofen are recommended. A new approach to patent ductus arteriosus management is an early targeted treatment based on echocardiographic criteria within the first 72 hours of life, that have a high sensitivity for diagnosing a patent ductus arteriosus that is unlikely to close spontaneously. Such trials are currently ongoing in many parts of the world. Results of such trials will be included in updates of our "Ibuprofen for treatment of PDA" review.
Topics: Cerebral Hemorrhage; Cyclooxygenase Inhibitors; Drug-Related Side Effects and Adverse Reactions; Ductus Arteriosus, Patent; Enterocolitis, Necrotizing; Enzyme Inhibitors; Gastrointestinal Hemorrhage; Humans; Ibuprofen; Indomethacin; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Randomized Controlled Trials as Topic
PubMed: 31985838
DOI: 10.1002/14651858.CD004213.pub5