Treatment algorithm
Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
ibuprofen or indomethacin
Cyclooxygenase inhibitors (e.g., nonsteroidal anti-inflammatory drugs) inhibit prostaglandins, and have been shown to be effective in ductal closure in preterm infants.[8] Treatment is given in the first few days of life after a patent ductus arteriosus (PDA) has become clinically evident or has been diagnosed by echo.
Indomethacin was previously the standard of care; however, ibuprofen is now largely considered the pharmacotherapy of choice due to its similar efficacy but significantly better safety profile.[58][59][60][61]
One Cochrane review comparing both oral and intravenous ibuprofen with indomethacin found a decreased risk of necrotizing enterocolitis and transient kidney injury in patients treated with ibuprofen, with similar effectiveness between interventions.[58]
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Both ibuprofen and indomethacin have been shown to reduce the risk of severe intraventricular hemorrhage, although indomethacin appears to be more effective, hence why it is used in preference to ibuprofen as a prophylactic treatment in very low birth weight babies.[55] Studies suggest that high-dose ibuprofen may increase the likelihood of PDA closure compared to standard-dose ibuprofen.[55][58][62][63] High-dose ibuprofen may therefore be considered the preferred dosage; however, significant caution should be exercised in preterm infants younger than 26 weeks due to a lack of data in this age group.[59] Studies have reported that oral ibuprofen is as effective as intravenous ibuprofen, with no significant difference in morbidity demonstrated.[58][64][65]
Treatment with indomethacin has shown to be successful in closing symptomatic PDAs compared with placebo.[8][66] While some centers practice a prolonged course of indomethacin (>4 and usually 7 doses), no significant difference has been shown in successful PDA closure, need for retreatment, need for surgical ligation, or such outcomes as mortality and the incidence of comorbidities such as chronic lung disease or necrotizing enterocolitis with this longer regimen.[67]
Infants being treated with ibuprofen and indomethacin must have electrolytes, creatinine, urine output and platelets followed regularly during administration. Feeds are withheld. B-type natriuretic peptide-guided treatment has been shown to reduce the number of primary indomethacin doses in infants with PDA.[68] Complications with indomethacin can include necrotizing enterocolitis, bleeding, or renal dysfunction.[56][57]
If the first course of ibuprofen or indomethacin is unsuccessful, a second course is usually given prior to consideration of procedural closure.[59]
Primary options
ibuprofen lysine: standard-dose regimen: 10 mg/kg intravenously as a loading dose, followed by 5 mg/kg every 24 hours for 2 doses; high-dose regimen: 15-20 mg/kg intravenously as a loading dose, followed by 7.5 to 10 mg/kg every 24 hours for 2 doses
Secondary options
indomethacin: infants <48 hours of age: 0.2 mg/kg intravenously as a loading dose, followed by 0.1 mg/kg every 12-24 hours for 2 doses; infants 2-7 days of age: 0.2 mg/kg intravenously every 12-24 hours for 3 doses; infants >7 days of age: 0.2 mg/kg intravenously as a loading dose, followed by 0.25 mg/kg every 12-24 hours for 2 doses
OR
ibuprofen: standard-dose regimen: 10 mg/kg orally as a loading dose, followed by 5 mg/kg every 24 hours for 2 doses; high-dose regimen: 15-20 mg/kg orally as a loading dose, followed by 7.5 to 10 mg/kg every 24 hours for 2 doses
surgical ligation
Surgical ligation is usually considered after medical therapy has failed to result in ductal closure or is contraindicated.[59] It can be performed on premature infants as small as 600 g. Surgical ligation of the duct generally has very high success rates with low associated morbidity.[75][77] Complications are rare and include recanalization of the duct, pneumothorax, effusion, hemorrhage, and wound infection.[76] While one study did show a relatively high late mortality in preterm infants, this was felt to be related to the high risk inherent in this population, rather than to the surgery itself.[77] There has been some inquiry into the favorability of surgical ligation as first-line management in this population.[78][79] However, there are currently limited data to allow for adequate comparison of the two treatment approaches.[78]
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One review suggested that there may be little benefit to prophylactic surgical ligation compared with no therapy or medical therapy, with no significant decrease in mortality or bronchopulmonary dysplasia.[80] Another review refuted earlier postulations that primary surgical ligation may decrease the incidence of necrotizing enterocolitis.[81]
Videothorascopic surgical ligation is being used with increasing frequency in selected cases with good results.[82]
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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer
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