Study | Intervention | Outcome | ||||||
---|---|---|---|---|---|---|---|---|
Time, h* | Strength | Dose | Time to first effect† | Treatment duration | Adjunctive therapy | Outcome | Adverse events | |
Intervention: topical nitroglycerin ointment | ||||||||
Denkler and Cohen43 | 6 | 2% | 14 mm/kg‡ | Minutes | 1 dose | None reported | CR | No |
Wong et al.40 | 2 | 2% | 4 mm/kg | 15 min | 1 dose | None reported | CR | No |
< 24 | 2% | 4 mm/kg | 8 h | 12 h | None reported | CR | ↓BP | |
1 | 2% | 4 mm/kg | 15 min | 1 dose | None reported | CR | No | |
0.5 | 2% | 4 mm/kg | 8 h | 24 h | None reported | CR | ↓BP, ↑HR | |
Baserga et al.25 | 1 | 2% | 4 mm/kg | 30 min | 1 dose | None reported | CR | No |
1.5 | 2% | 4 mm/kg | 45 min | 1 dose | None reported | CR | No | |
1 | 2% | 4 mm/kg | 30 min | 1 dose | None reported | CR | ↓BP | |
Vasquez et al.30 | 7 | 2% | < 4 mm/kg | 8 h | 27 d | None reported | CR | No |
Mousavi et al.38 | NS | 2% | 4 mm/kg | NR | NS | None reported | Death | No |
Akingbola et al.34 | < 24 | 2% | 4 mm/kg | 24 h | 21 d | tPA, heparin | Loss of tip of left great toe | Swelling bulla |
Mosalli et al.35 | NS | 2% | < 4 mm/kg | 8 h | 21 d | None reported | CR | No |
Samiee-Zafarghandy et al.22 | 144 | 2% | 4 mm/kg | 24 h | 14 d | None reported | Lost second and third toes | No |
Dilli et al.33 | NS | 2% | 4 mm/kg | 3 d | 15 d | tPA, heparin, intravenous nitroglycerin | CR | No |
Parra et al.29 | NS | NS | NS | NS | NS | Heparin | CR | No |
Vivar del Hoyo et al.24 | First hours after ischemia | 2% | 4 mm/kg | NS | 5–18 d | None reported | CR | No |
Han et al.37 | 48 | 2% | 4 mm/kg | 23 d§ | 36 d | 100% humidity | CR | No |
Isik et al.36 | NS | NS | NS | Weeks | NS | Heparin | Reduced movement and reflexes, muscle atrophy | No |
Kuttysankaran et al.32 | NS | NS | NS | 2 d | 4 d | None reported | CR | No |
Weeraskera et al.27 | NS | NS | 4 mm/kg | 18 h | 14 d | Heparin, milrinone | CR | No |
Intervention: glyceryl trinitrate patch | ||||||||
O’Reilly et al.28 | 2.5 | 0.2 mg | NS | NS | 1 h | None reported | CR | No |
Varughese and Koh41 | 4 | 0.4 mg | NS | 7 h | 30 h | None reported | CR | ↓BP |
Intervention: glyceryl trinitrate patch | ||||||||
Maffei et al.23 | 0.5 | 1-cm2 patch containing glyceryl trinitrate 5 mg per 7 cm2 | 1 h | 7 d | None reported | CR | No | |
1 | 3 h | 4 d | None reported | CR | No | |||
Teo and Shah31 | 12 h after heparin initiation | NS | NS | 5 d | 7 d | Heparin, enoxaparin | CR | No |
Yong et al.42 | NS | NS | NS | NS | NS | tPA, heparin | 4 NR | No |
1 CR | ||||||||
Mintoft et al.26 | Immediately | 9-cm2 patches containing 18.7 mg GTN | NS | 2 d¶ | CR | Methemoglobinemia | ||
5 d¶ | Loss of tips of toes | Methemoglobinemia | ||||||
Intervention: topical nitroglycerin ointment and glyceryl trinitrate patch | ||||||||
Ancora et al.39 | At 8 h of life 120 | NS | NS | NS | 5 d | Antibiotic cream | Partial loss of distal finger and toe | No |
11 d | ||||||||
Intervention: topical nitroglycerin spray | ||||||||
Kamar et al.44 | NS | NS | NS | NS | 7 d | None reported | Partial loss of distal finger and toe | No |
Note: BP = blood pressure, CR = complete resolution, HR = heart rate, NR = no response, NS = not stated, tPA = tissue plasminogen activator.
↵* Start time of intervention after the tissue injury.
↵† Time between the start of treatment with the nitroglycerin product and the first signs of improved perfusion recorded by the responsible care provider.
↵‡ We calculated this dose by converting 1 inch of ointment (specified by Denkler and Cohen43) to millimetres and dividing by the infant’s weight of 1.8 kg.
↵§ Improvement observed 23 d after admission to the neonatal intensive care unit.
↵¶ Treatment discontinued because of methemoglobinemia.