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CASE REPORT
Year : 2021  |  Volume : 22  |  Issue : 3  |  Page : 257-259

Phenomenal role of nitroglycerin in the treatment of neonatal digital gangrene


1 Department of Neonatology, Ram Manohar Lohia Hospital, Delhi, India
2 FNB Reproductive Medicine, BACC Bengaluru, Karnataka, MD Obstetrics and Gynaecology, PGIMER, Chandigarh, India

Date of Submission10-Jul-2020
Date of Decision28-Jul-2020
Date of Acceptance25-Nov-2020
Date of Web Publication30-Jun-2021

Correspondence Address:
Garima Sachdeva
House No. 201, Top Floor, Dr. Mukherjee Nagar, Delhi - 110 009
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijpd.IJPD_117_20

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  Abstract 


Introduction: Placement of peripheral venous catheter is a common requirement for the neonates requiring intensive care unit admissions. This simple procedure can sometimes lead to catastrophic complications such as peripheral tissue ischemia/gangrene. This is particularly common in preterm neonates. Effective treatment is very important to prevent long-term sequelae or need for amputation. Nitroglycerin (NTG) is a potent smooth muscle relaxant and improves vascular flow. Case Report: Here, we report a case of neonatal digital gangrene which was successfully treated with topical NTG with no adverse outcome. Discussion: Topical NTG is a potential treatment option for neonatal peripheral gangrene.

Keywords: Blackish discoloration, gangrene, intensive care unit, ischemia, neonates, nitroglycerin


How to cite this article:
Choudhary R, Choudhary S, Sachdeva G, Maria A. Phenomenal role of nitroglycerin in the treatment of neonatal digital gangrene. Indian J Paediatr Dermatol 2021;22:257-9

How to cite this URL:
Choudhary R, Choudhary S, Sachdeva G, Maria A. Phenomenal role of nitroglycerin in the treatment of neonatal digital gangrene. Indian J Paediatr Dermatol [serial online] 2021 [cited 2021 Jul 24];22:257-9. Available from: https://www.ijpd.in/text.asp?2021/22/3/257/319938




  Introduction Top


A rare iatrogenic complication of intensive care unit stay for the newborns is peripheral tissue ischemia. Delay in treatment has the potential to cause complete necrosis/gangrene and eventually the loss of an affected limb. Some of the causes of this dreaded complication include extravasation of the intravenously given drugs, vasoactive drugs, or improperly placed catheters resulting in the peripheral vasospasm, or it can occur secondary to vascular injury provoking a thromboembolic event.[1]

Nitroglycerin (NTG) belongs to the class of nitric oxide donors. It activates the enzyme guanylate cyclase, which increases cyclic guanosine monophosphate (cGMP). cGMP acts on smooth muscles of the blood vessels and other tissues, resulting in vasodilatation of the arteries and veins, thus improving the blood flow in cases of vasospasm or tissue ischemia.[2]

There is limited evidence to support the use of topical NTG in the treatment of ischemic vascular injury in the neonates. Here, we present a case of a preterm neonate, who developed digital gangrene secondary to peripheral intravenous catheter placement. On treatment with topical NTG, complete resolution was seen within a week, with no adverse outcome.


  Case Report Top


A premature female infant was born at 26 + 3 weeks period of gestation to a multigravida following preterm premature rupture of membranes, 3 days before the delivery. As a routine protocol, the woman was given a course of antibiotics and steroid cover. There was no history of diabetes or fever or any unhealthy discharge in the mother. The patient went into preterm labor and delivered vaginally. The birth weight was 685 g and APGAR was 6/8/8. The baby was admitted to the neonatal intensive care unit and was put on continuous positive airway pressure (CPAP). Within 2 hours of life, the baby was intubated and was put on mechanical ventilation because of increasing FiO2 requirement on CPAP (FiO2 >40%). Surfactant was administered at 2 and 26 hours of life because of worsening distress. The baby was diagnosed with patent ductus arteriosus which required pharmacological closure with injection paracetamol. The sepsis screen was negative. The baby was extubated on day 3 of life and was on orogastric feeds. Cranial ultrasound was done which revealed Grade-4 intraventricular hemorrhage which resolved on conservative management. The baby developed anemia of prematurity (packed cell volume - 22 and hemoglobin - 6.8 g/dL) requiring multiple blood transfusions. Blackish discoloration developed on the toes of the left foot postinsertion of a peripheral intravenous line [Figure 1]. The coagulation profile and platelet count were within normal limits. Doppler ultrasound of the left leg was normal (normal flow in the anterior tibial artery, posterior tibial artery, and popliteal artery). A plastic surgeon was consulted because of digital gangrene. The intra-venous catheter was removed. Topical NTG ointment (2%) was applied three times a day over the affected digits. Perfusion of the toes improved gradually with improvement in the skin color [Figure 2]. There was a complete resolution of gangrene within 9–10 days of treatment [Figure 3]. The infant's blood pressure, heart rate, respiratory rate, and oxygen saturation were normal during the treatment. Methemoglobin levels were also measured twice, which were normal. No other adverse effects of NTG therapy were noted. The baby showed remarkable recovery and was discharged at day 70 of life, weighing 1.8 kg.
Figure 1: Digital gangrene following insertion of peripheral venous catheter

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Figure 2: Gradual improvement in skin color (day 2 of treatment with nitroglycerin)

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Figure 3: Complete resolution of gangrene (day 10 of treatment with nitroglycerin)

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  Discussion Top


Peripheral vascular gangrene is a rare complication seen in preterm neonates. Various etiologies described in the literature for this condition are maternal diabetes, uterine artery thromboses, birth trauma, prematurity, congenital syphilis, uterine artery cannulation, polycythemia, intravenous/intra-arterial cannulations, and sepsis.[3] In this case, maternal diabetes and infection were ruled out. A negative screen for sepsis, normal Doppler, and the absence of any evidence of hypercoagulable state ruled out other causes of gangrene. Moreover, the digital gangrene developed after the placement of an intravenous catheter, indicating it to be the cause of the gangrene. Vessels of a neonate (especially premature infants) are fragile and are very susceptible to vasospasm, rupture, and thromboses. This results in ischemia and necrosis of the adjacent tissues. Similar findings were noted in this patient.

There is limited evidence in the literature to support the role of NTG in the treatment of peripheral gangrene in neonates. The data are limited to a few case reports which described a successful outcome with NTG for its use for gangrene associated with vasoactive substances such as dopamine,[4] and umbilical artery catheterization.[5] This baby showed a remarkable response to NTG.

Studies related to dosage and adverse effects profile of NTG in neonates are very limited. There is a theoretical concern of variable absorption of the topically administered drug, due to impaired skin maturity in premature infants. This can result in sudden changes in the hemodynamic status resulting in serious side effects in premature neonates. However, none of the studies until now have noted serious adverse events with the use of topical NTG.[6] Minor side effects such as erythema, venous stasis, and oozing have been reported if NTG is applied at the site of cannula.[2] Ideally, monitoring of hemodynamic parameters such as blood pressure and heart rate should be done while using NTG in neonates.

Studies have described the role of other pharmacological agents such as tissue plasminogen activator and anticoagulants such as heparin in addition to topical NTG for treating severe gangrene. Limited benefit of other pharmacological agents such as anticoagulants, thrombolytic, and local infiltration of phentolamine and hyaluronidase has also been described.[4] Severe gangrene, late presentation, and refractory cases may require amputation of toes to prevent the spread of gangrene to the entire feet or lower limb.[7]


  Conclusion Top


Topical NTG is a potential treatment option for neonatal peripheral gangrene. Timely initiation of treatment can result in complete recovery, thus eliminating the need for surgical debridement or amputation. However, more studies are required to establish the effective dosage and safety of its administration to the neonates and infants.

Informed consent

Consent was obtained from the parents of the newborn for the publication of the case report and the images.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the parents have given their consent for images and other clinical information to be reported in the journal. The parents understand that names and initials will not be published, and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Acknowledgment

We are extremely thankful to the parents of the newborn for their immense co-operation and for allowing us to publish the case and the photograph.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Singh J, Rattan KN, Gathwala G, Kadian YS. Idiopathic unilateral lower limb gangrene in a neonate. Indian J Dermatol 2011;56:747-8.  Back to cited text no. 1
[PUBMED]  [Full text]  
2.
van Reempts P, Van Overmeire B. Topical use of nitroglycerin ointment in neonates. J Pediatr 1990;116:155.  Back to cited text no. 2
    
3.
Musa AA. A review of diagnosis and modes of presentation of tropical idiopathic lower limb gangrene. Afr Health Sci 2006;6:49-50.  Back to cited text no. 3
    
4.
Denkler KA, Cohen BE. Reversal of dopamine extravasation injury with topical nitroglycerin ointment. Plast Reconstr Surg 1989;84:811-3.  Back to cited text no. 4
    
5.
Varughese M, Koh TH. Successful use of topical nitroglycerine in ischaemia associated with umbilical arterial line in a neonate. J Perinatol 2001;21:556-8.  Back to cited text no. 5
    
6.
Baserga MC, Puri A, Sola A. The use of topical nitroglycerin ointment to treat peripheral tissue ischemia secondary to arterial line complications in neonates. J Perinatol 2002;22:416-9.  Back to cited text no. 6
    
7.
Akingbola O, Singh D, Steiner R, Frieberg E, Petrescu M. High-dose tissue plasminogen activator, topical nitroglycerin, and heparin for severe ischemic injury in a neonate. Clin Pediatr (Phila) 2012;51:1095-8.  Back to cited text no. 7
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]



 

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