case report topical nitroglycerine for neonatal arterial … · 2020. 1. 27. · artery...

Hindawi Publishing CorporationCase Reports in PediatricsVolume 2013 Article ID 608516 7 pageshttpdxdoiorg1011552013608516

Case ReportTopical Nitroglycerine for Neonatal Arterial AssociatedPeripheral Ischemia following Cannulation A Case Report andComprehensive Literature Review

Rafat Mosalli12 Mohamed Elbaz2 and Bosco Paes3

1 Department of Pediatrics Umm Al Qura University PO Box 7607 Mecca 21955 Saudi Arabia2Department of Pediatrics International Medical Center Hael Street PO Box 2172 Jeddah 21451 Saudi Arabia3 Department of Pediatrics (Neonatal Division) McMaster University HSC-3A 1280 Main Street West HamiltonON Canada L8S 4K1

Correspondence should be addressed to Bosco Paes paesmcmasterca

Received 30 July 2013 Accepted 8 September 2013

Academic Editors R Lauterbach J Muraskas and K Sarafidis

Copyright copy 2013 Rafat Mosalli et al This is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited

Arterial cannulation in neonates is usually performed for frequent blood pressure monitoring and blood samplingThe procedurewhile easily executed by skilled neonatal staff can be associated with serious complications such as vasospasm thrombosisembolism hematoma infection peripheral nerve damage ischemia and tissue necrosis Several treatment options are availableto reverse vascular induced ischemia and tissue damage Applied interventions depend on the extent of tissue involvement andwhether the condition is progressive and deemed life threatening Standard noninvasive measures include immediate catheterremoval limb elevation and warming the contralateral extremity Topical vasodilators anticoagulation thrombolysis and surgeryare considered secondary therapeutic strategies A comprehensive literature search indicates that topical nitroglycerin has beenutilized for the treatment of tissue ischemia in three preterms with umbilical arterial catheters and four with peripheral arteriallines We report the first successful use of nitroglycerine ointment in a critically ill preterm infant with ischemic hand changes afterbrachial artery cannulation

1 Introduction

Arterial catheter insertion in the premature infant is usuallyundertaken to facilitate easy blood sampling for requireddiagnostic investigations and to monitor blood pressure andhemodynamic stability in a quiescent state This is normallyaccomplished through the insertion of indwelling umbilicalarterial catheters soon after birth or if unsuccessful thealternative placement of peripheral arterial lines in commonsites such as the radial ulnar dorsalis pedis or posteriortibial arteries Prior to initiation of the procedure circulatorysufficiency evidence of adequate collateral blood flow atthe selected site absence of bleeding diatheses local skininfection and limb malformation are basic prerequisites [1]Pretermneonates have a small arterial diameter relative to thecatheter size and they are therefore more susceptible to com-plications such as iatrogenic trauma vasopasm thrombosis

and thromboembolism with subsequent tissue ischemia andnecrosis of the involved anatomical region

The usual treatment of ischemic injuries includes imme-diate removal of the catheter elevation of the affected limband application of warm compresses to the opposite limb(reflex vasodilation) but these maneuvers afford variablesuccess Anticoagulants such as unfractionated [2 3] or lowmolecular weight heparin [2 4 5] and thrombolysis withtissue plasminogen activator [6ndash9] are primarily employedwhen complete thrombotic occlusion of the vessel occurswith rapidly progressive ischemia and the risks associatedwith surgery are considered substantial or even detrimental[2] Streptokinase and urokinase [10] have been utilized incase reports but overall none of the drug strategies have beenevaluated through robust controlled clinical trials

A comprehensive literature search was conducted ofexisting scientific databases and 7 case reports of peripheral

2 Case Reports in Pediatrics

ischemia due to arterial cannulation in the neonatewere iden-tified with complete recovery attributed to the applicationof topical nitroglycerine We describe the first case whichinvolved catheter insertion into the brachial artery

2 Case Report

A Saudi Arabian girl weighing 520 g was born at 25 weeksgestational age to a 35-year-old gravida 4 para 3 motherThere was no family or medical history of a thrombophilicdisorder The infant was a vaginal delivery with Apgar scoresof 3 at 1 minute and 8 at 5 minutes The birth weight wasappropriate for gestational age with no dysmorphic featuresThe infant was immediately intubated received surfactantand was mechanically ventilated The initial chest X-ray wascompatible with respiratory distress syndrome Shortly afterbirth the baby developed hypotension Umbilical venousand arterial lines were inserted and a dopamine drip wasstarted at 10mcgkgminute with subsequent stability Apartial sepsis workup was performed and the baby wasstarted on ampicillin and gentamicin Hyperglycemia on day2 was managed with an insulin infusion Cerebral ultrasoundon day 3 of life was normalThe umbilical venous and arteriallines were removed on day 7 of life

On day 14 the baby developed acute renal failuresecondary to sepsis with poor urine output hypotensionmetabolic acidosis hyperkalemia and a raised creatinineNumerous attempts were made to insert a peripheral arterialline for frequent blood sampling and blood pressuremonitor-ingwithout success Due to the severity of illness and need forarterial access a decision was made to insert a right brachialartery catheter but after 8 hours the middle ring and indexfingers of the right hand were noted to be cold and cyanosedand the arterial line was immediately removed (Figure 1)The hand was elevated and warm compresses were appliedto the contralateral limb Ischemic changes soon becameevident and 4 hours later progressed to involve the distalpart of the fingers which started showing signs of probableearly necrosis (Figure 2) The international normalized ratio(INR) and partial thromboplastin time were normal Acomplete prothrombotic screen was not performed becausethe event was not spontaneous there was no family historyof thrombophilia and there was a causal relationship of theischemia with the brachial cannulation procedure [11] ADoppler ultrasound indicated a sluggish flow through thebrachial artery without definite visualization of a thrombuswhich suggested that the underlying etiology was morelikely vasospasm rather than thrombosis Anticoagulationwas considered as one possible strategy to preserve perfusionand prevent digital loss but the risks of heparinization andpotential bleeding were considered significant A ribbon of2 nitroglycerin ointment (less than 4mmkg) was initiallysparingly applied to the fingers approximately 2 cm proximalto the line of pallor Slight improvement in color andperfusion was noted in the fingers over the next 8 hoursTopical nitroglycerinwas subsequently applied every 8 hours1 cm proximal to the ischemic site following the anatomiccourse of the brachial artery Methemoglobin levels were

Figure 1Digital involvement of the right hand 8 hours after brachialartery cannulation

Figure 2 Signs of early necrosis in the finger tips

monitored daily and stayed in the normal range (metHgblt 1)

There was a gradual improvement in color and capillaryrefill over the next several days By day 12 the area ofischemia was limited to the tips of the fingers and treatmentwas discontinued on day 21 (Figures 3 and 4) The nailbeds were intact with full restorative function of the fingers(Figure 5) The baby made an uneventful recovery from herrenal failure was extubated at 1 month of age and waseventually discharged home at 34 weeks corrected gestationalage weighing 185 kg

3 Discussion

Neonates have several risk factors that predispose them tothrombosis and catheter induced ischemia [11] A systematicreview of spontaneous neonatal arterial thromboembolismclassified these as congenital acquired inherited prothrom-botic abnormalities and maternal [12] factors The coagula-tion system in newborns matures slowly with mean plasma

Case Reports in Pediatrics 3

Figure 3 Resolving ischemia of the 2nd 3rd 4th and 5th fingers5 days after the ischemic event (dorsal and palmar aspects of thehand)

Figure 4 Residual ischemia at the tip of the middle finger after 10days

Figure 5 Complete resolution 7 weeks after the incident

concentrations of the vitamin-K dependent factors contactfactors and direct inhibitors of thrombin being approxi-mately 50 of adult values at birth [13ndash15] whereas 1205722-macroglobulin factors V VIII and XIII and vonWillebrandfactor are increased in the first few weeks of life [16 17]Healthy preterms gradually attain adult coagulant proteinlevels by 6 months of age but in the interim any illnessmay disrupt hemostasis leading to a fall in 1205722-macroglobulinwith subsequent thrombosis and ischemia [18]Moreover theplacement of catheters may cause additive vascular endothe-lial damage which incites a rapid inflammatory cascadethat enhances platelet adhesion and aggregation through therelease of adenosine diphosphate and thromboxane resultingin localized stasis reduction in blood flow and thrombosis[19] The affected area is soon compromised with absentpulses and becomes pale cool andmarkedly discolored [20]

There are recommended sites for central and peripheralarterial vascular access which are considered relatively safebecause of a collateral circulation (radial dorsalis pedis pos-terior tibial arteries and less commonly ulnar) [21 22] Therespective vessels are also easily identified with a fibreopticsource or the vessels are directly visible for catheterization(umbilical arteries) However these purported safe sites arenot without risk from ischemic changes and digital or limbnecrosis [23ndash26] Equally the placement and position ofumbilical arterial catheters may result in clinical vascularcompromise In a Cochrane meta-analysis of 5 randomisedor quasirandomised studies Barrington [27] reported thatischemic phenomena were significantly less common withhigh positioned catheters (tip in the descending aorta abovethe level of the diaphragm and below the subclavian arteryRR 053 95 CI 044ndash063) The author recommends thatthe practice of low placed umbilical catheters should beabandoned because of the inherent risks

Brachial artery cannulation or puncture for blood sam-pling should be avoided in infants because of the risk ofthrombosis and proximity to the median nerve unless theindication is urgent and access is no longer available throughthe usual sites [28] However Schindler et al in a retrospec-tive study described their safe experience with 112 brachialarterial lines in infants lt5 kg [29] Reported complicationswere few temporary occlusion (119899 = 1) local infection (119899 =1) and local hematoma (119899 = 5) There are several reports ofsignificant complicationswith brachial artery catheterizationGiaquinta et al described a 3-day-old infant who sustainedmajor ischemic changes following an attempt to cannu-late the brachial artery [30] Microvascular reconstructivesurgery was performed to salvage blood flow to the limbIn our case similar problems ensued and a trial of topicalnitroglycerin proved successful Coombs et al described aseries of eleven ill patients aged 1 day through 2 yearsfour of whom had a gestational age between 26 and 31weeks and a birth weight range of 980 to 2200 g [31] Theinfants had repeated radial and brachial artery puncturesin an attempt to establish vascular access which resulted invessel occlusion and severely compromised limb perfusionAll underwent arteriotomy embolectomy and reconstructivevascular surgery with good outcomesThe authors developedan algorithmic multidisciplinary approach to brachial artery


thrombosis which weighs the risk of benefit versus harmfor each instituted therapeutic intervention while mandatingsurgery for absolute indications

Nitroglycerine is a known smooth muscle relaxant whichis readily absorbed through intact skin Preterm infantshave an immature epidermal permeability barrier whichlikely enhances drug absorption and may produce systemiccomplications [32 33] Nitroglycerine forms free radicalnitric oxide which activates guanylate cyclase and increasescellular guanosine 31015840 51015840-cyclic monophosphateThis dephos-phorylates smooth muscle myosin which regulates the con-tractile state and results in vasodilation [34] The amountof absorbed nitroglycerine and systemic levels achieved islikely directly related to the quantity of ointment and size ofthe area of application [35] The usual starting dose of 2nitroglycerine ointment is 4mmkg (or 2mg measured as01mL in a syringe) which is equivalent to 02ndash05120583gkgminadministered intravenously [36] The vasodilation is evidentwithin 15ndash30 minutes and the hemodynamic effects may besustained for as long as 6 hrs Side effects can occur such ashypotension tachycardia flushing and methemoglobinemiadue to nitric oxide production Hypotension and tachycardiawere documented in a few reports [37ndash39] but resolved inthe majority of cases without treatment Prolonged use ofnitroglycerinemay cause methemoglobinemia andmonitor-ing of levels is important However this complication hasonly been noted in adults receiving high doses of intravenousnitroglycerin [40 41]

Topical nitroglycerin has been used in neonates forseveral indications A search of MEDLINE PubMed Web ofScience CINAHL Cochrane Databases DARE and OVIDwas performed using the followingmesh terms nitroglycerinOR topical nitroglycerin AND artery OR arterial catheterAND tissue ischemia OR necrosis AND infant-newborn ORneonate Retrieved citations were also scanned for addi-tional pertinent references The search yielded 14 articlessix of which were relevant Two articles reported 3 casesof ischemia one in association with a femoral artery can-nulation in a 31-week premature infant at 2 months of age[6] one with a left axillary artery injury during centralvenous catheter placement [42] and one case during radialartery sampling [42] In the latter two examples completerecovery occurred with treatment while in the formeraggressive management with tissue plasminogen activatorheparin and topical nitroglycerin resulted in a relatively goodoutcome with residual dry gangrene at the tip of the leftgreat toe Topical nitroglycerin has been employed to aidin the insertion of peripheral venous catheters in neonatesbut use was discontinued because of limited success andaccompanying concerns of hypotensionwhichmayhave beendose-related [35 43 44] Nitroglycerin ointment may alsobe beneficial in tissue ischemia following extravasation ofparenteral solutions [45] Currently there are 4 publishedstudies on the use of topical nitroglycerin in neonates forthe reversal of peripheral ischemia due to arterial cannula-tion These involve 7 preterm infants (gestational age range23ndash33 weeks) and the outcomes are uniformly positive(Table 1) [37ndash39 46] Our report in which repeated dosesof topical nitroglycerin relieved distal ischemia and resulted

in complete resolution and normal perfusion of the affectedhand adds to the existing case series However the underlyingpathophysiological mechanism suggests that recovery mayonly occur in cases associated with intense vasospasm of thetraumatized vessel and is perhaps less likely to resolve withtrue embolism or occlusive thrombosis without additionalanticoagulation and thrombolysis

In essence anticoagulation with unfractionated heparinshould be reserved for definite occlusive thrombi Lowmolecular weight heparin may also be used if no inva-sive procedures or thrombolytic therapy is planned [2 12]Thrombolytic therapy with tissue plasminogen activatorshould be instituted for thrombi unresponsive to unfraction-ated heparin in the presence of progressive tissue ischemiaAbsolute indications for surgery include total limb ischemiaevidence of compartment syndrome or pregangrenous tissueevolution and documented absence of arterial blood flow byDoppler ultrasound or angiography for gt24 hours [12 31]

The only other reported therapeutic option for neonatallimb ischemia associated with arterial vasopasm is sympa-thetic blockade The anesthetic procedure directly inducesvascular dilation through a mechanism that is not endothe-lium dependent [47] and is conjointly enacted through theinhibition of afferent impulses that reduces pain-relatedrelease of epinephrine and norepinephrine and decreasesperipheral vasoconstriction [48] De Carolis et al [49]describe a series of 12 cases in which peripheral nerve block-ade alone (119899 = 6) or combined with anticoagulation (119899 =4) was safely employed to treat limb ischemia Thrombosiswas reported occurring soon after birth (119899 = 2) or in asso-ciationwith umbilical arterial catheterization (119899 = 8) periph-eral arterial puncture (119899 = 1) or cannulation (119899 = 1) How-ever in the described cases complete recovery occurred in5 infants 5 required subsequent amputations of a limb ordigits and one died More recently Ponde et al [50] furtherdocumented residual ischemia of the finger tips following aninfraclavicular brachial plexus block in a 900 g female infantwho had an accidental peripheral arterial puncture Theauthors [49 50] recommend peripheral nerve blockade as aneffective procedure for arterial vasospasm but the outcomesindicate significant morbidity and stress the importance of amultidisciplinary approach to limb ischemia as advocated byCoombs et al [31]

4 Conclusion

Topical 2 nitroglycerin ointment at a dose of 4mmkg maybe a useful initial therapy for the reversal of tissue ischemia inpremature and term babies who do not respond to standardnoninvasive measures after peripheral arterial cannulationSeveral questions remain unanswered The optimum time tocommence treatment after the ischemic event the frequencyand safety of administration in newborns especially preterminfants and the use of nitroglycerin in combination withother therapies has not been established Therefore prospec-tive studies evaluating specific prescriptive regimens arenecessary before this therapeutic option is implemented inclinical practice for arterial vasospasm Anticoagulation and


Table1Literature

review

ofneon

ates

treated

with

nitro

glycerin

fora

rterialcatheter-related

ischemiaandtheiro

utcomes

AuthorYear[Re

ference]

Gestatio

nalage

wk(Birthwtg)

Catheter

type

Region

andclinicalfi

ndings

2nitro

glycerin

topicald

ose

Outcome

Won

getal1992[37]

25(700)

24(780)

(1)R

ight

radial

(2)R

ight

radial

(1)N

opu

lseright

hand

blanched

(2)n

opu

lsebluefi

ngersrig

hthand

rigid

Ribb

on4m

mkgin

both

cases

(1)Improvem

entw

ithin

15minfull

recovery

in3h

r(2)T

wodo

sesw

ithcompleter

ecovery

after

16hr

except

for2

smallbluea

reas

Varugh

esea

ndKo

h2001

[38]

33(1870)

UAC

Ischem

icchangeso

verright

hip

Normalfemoral+po

plitealpu

lses

04m

gover

2hrmdash

twice

Improvem

ento

ver7

hrwith

complete

resolutio

naft

er30

hr

Basergae

tal2002

[39]

(1)3

0(1620)

(2)2

5(not

stated)

(3)2

3(660)

(1)U

AC(2)U

AC(3)L

eftradial

(1)P

oorp

erfusio

nleftlegweakfemoral+

tibialpulses

(2)R

ight

legblanchedabsentfem

oralpu

lse

cyanotictoes

(3)P

aleleft

hand

andfin

gersabsentradial

pulse

(1)4

singlea

pplications

over

affectedparts-do

seno

tstated

(2)4

mmkgmdash

four

single

applications

over

affectedparts

(3)ribbo

nof

ointment-d

osen

otsta

ted-3sin

glea

pplications

toaffectedareas

(1)C

ompleter

ecoveryin

45min

(2)C

ompleter

ecoveryin

45min

(3)Improvem

entin30

min

with

full

recovery

Vasqueze

tal2003

[46]

26(896)

Leftperip

heral

arteria

lline

(locatio

nno

tsta

ted)

Palecyanoticlefthand

with

discoloration

from

mid-palm

tofin

gertips

Ribb

on4m

mkg

q8h

rfor

27days

Improvem

entin8h

rwith

gradual

recovery

over

18ndash27daysN

odeficitat

8mon

ths

UAC

umbilicalarteria

lcatheter


thrombolysis should be considered for progressive ischemiabut should never be a substitute for surgery The approachto an infant with limb ischemia is critical and needs to besystematic collaborative multidisciplinary and standardizedin order to affect the best short- and long-term outcomes Itis important to note that if topical nitroglycerin therapy isinstituted consultation should be concurrently sought fromhematology and surgery to facilitate timely intervention andavoidance of vascular compromise

Disclosure

Please note that since there are no identifying features ofthe case consent for photographs and publication was notsought and this complies with the ethical standards of thelocal institutional research ethics board

Conflict of Interests

Rafat Mosalli Mohamed Elbaz and Bosco Paes have nofinancial or other conflict of interests to disclose

References

[1] A N Massaro K Rais-Bahrami and M R Eichelberger Atlasof Procedures in Neonatology M G Macdoanld J RamasethuEds pp 186ndash198 Wolters Kluwer Lippincott Williams andWilkins Philadelphia Pa USA 4th edition 2007

[2] P Monagle A K Chan N A Goldenberg et al ldquoAntithrom-botic therapy in neonates and children antithrombotic therapyand prevention of thrombosis 9th ed American College ofChest Physicians evidence-based clinical practice guidelinesrdquoChest vol 141 no 2 pp e737Sndashe801S 2012

[3] F Newall L Johnston V Ignjatovic and P Monagle ldquoUnfrac-tionated heparin therapy in infants and childrenrdquoPediatrics vol123 no 3 pp e510ndashe518 2009

[4] L A Michaels M Gurian T Hegyi and R A DrachtmanldquoLow molecular weight heparin in the treatment of venous andarterial thromboses in the premature infantrdquo Pediatrics vol 114no 3 pp 703ndash707 2004

[5] J I Malowany P Monagle D C Knoppert et al ldquoEnoxaparinfor neonatal thrombosis a call for a higher dose for neonatesrdquoThrombosis Research vol 122 no 6 pp 826ndash830 2008

[6] O Akingbola D Singh R Steiner E Frieberg andM PetresculdquoHigh-dose tissue plasminogen activator topical nitroglycerinand heparin for severe ischemic injury in a neonaterdquo ClinicalPediatrics vol 51 no 11 pp 1095ndash1098 2012

[7] G Demirel S S Oguz I H Celik et al ldquoEvaluation andtreatment of neonatal thrombus formation in 17 patientsrdquoClinical and Applied ThrombosisHemostasis vol 17 no 6 ppE46ndashE51 2011

[8] B Anderson P Urs D Tudehope and C Ward ldquoThe use ofrecombinant tissue plasminogen activator in the managementof infective intracardiac thrombi in pre-term infants withthrombocytopaeniardquo Journal of Paediatrics and Child Healthvol 45 no 10 pp 598ndash601 2009

[9] A Grieg ldquoThrombolysis of a neonatal brachial artery thrombo-sis with tissue plasminogen activatorrdquo Journal of Perinatologyvol 18 no 6 pp 460ndash462 1998

[10] U Nowak-Gottl K Auberger S Halimeh et al ldquoThrombolysisin newborns and infantsrdquoThrombosis and Haemostasis vol 82supplement 1 pp 112ndash116 1999

[11] R Bhat and P Monagle ldquoThe preterm infant with thrombosisrdquoArchives of Disease in Childhood vol 97 no 6 pp F423ndashF4282012

[12] G Rashish B A Paes K Nagel A K Chan and S ThomasldquoSpontaneous neonatal arterial thromboembolism infants atrisk diagnosis treatment and outcomesrdquo Blood Coagulationand Fibrinolysis 2013

[13] M Andrew B Paes R Milner et al ldquoDevelopment of thehuman coagulation system in the healthy premature infantrdquoBlood vol 72 no 5 pp 1651ndash1657 1988

[14] P Reverdiau-Moalic B Delahousse G Body P Bardos J Leroyand Y Gruel ldquoEvolution of blood coagulation activators andinhibitors in the healthy human fetusrdquo Blood vol 88 no 3 pp900ndash906 1996

[15] M Salonvaara P Riikonen R Kekomaki et al ldquoEffects of gesta-tional age and prenatal and perinatal events on the coagulationstatus in premature infantsrdquo Archives of Disease in Childhoodvol 88 no 4 pp F319ndashF323 2003

[16] K B Thomas A H Sutor N Altinkaya A Grohmann AZehenter and J U Leititis ldquovon Willebrand factormdashcollagenbinding activity is increased in newborns and infantsrdquo ActaPaediatrica vol 84 no 6 pp 697ndash699 1995

[17] B Schmidt L Mitchell F A Ofosu and M Andrew ldquoAlpha-2-macroglobulin is an important progressive inhibitor of throm-bin in neonatal and infant plasmardquoThrombosis and Haemosta-sis vol 62 no 4 pp 1074ndash1077 1989

[18] J K Shah L G Mitchell B Paes F A Ofosu B Schmidt andM Andrew ldquoThrombin inhibition is impaired in plasma of sickneonatesrdquo Pediatric Research vol 31 no 4 part 1 pp 391ndash3951992

[19] D C Stump and K G Mann ldquoMechanisms of thrombusformation and lysisrdquo Annals of Emergency Medicine vol 17 no11 pp 1138ndash1147 1988

[20] B D Braly ldquoNeonatal arterial thrombosis and embolismrdquoSurgery vol 58 no 5 pp 869ndash873 1965

[21] S N Randel B H Tsang J T Wung J M Driscoll Jr and LS James ldquoExperience with percutaneous indwelling peripheralarterial catheterization in neonatesrdquo American Journal of Dis-eases of Children vol 141 no 8 pp 848ndash851 1987

[22] S A Aldridge and J M Gupta ldquoPeripheral artery cannulationin newbornsrdquo Journal of the Singapore Paediatric Society vol 34no 1-2 pp 11ndash14 1992

[23] G W Cartwright and R L Schreiner ldquoMajor complicationsecondary to percutaneous radial artery catheterization in theneonaterdquo Pediatrics vol 65 no 1 pp 139ndash141 1980

[24] W W Hack A Vos and A Okken ldquoIncidence of forearm andhand ischaemia related to radial artery cannulation in newborninfantsrdquo Intensive Care Medicine vol 16 no 1 pp 50ndash53 1990

[25] C Breschan R Kraschl R Jost P Marhofer and R LikarldquoAxillary brachial plexus block for treatment of severe forearmischemia after arterial cannulation in an extremely low birth-weight infantrdquoPaediatric Anaesthesia vol 14 no 8 pp 681ndash6842004

[26] R C Spahr H M MacDonald and I R Holzman ldquoCatheter-ization of the posterior tibial artery in the neonaterdquo AmericanJournal of Diseases of Children vol 133 no 9 pp 945ndash946 1979

[27] K J Barrington ldquoUmbilical artery catheters in the newborneffects of position of the catheter tiprdquo Cochrane Database ofSystematic Reviews no 2 Article ID CD000505 2000


[28] DMWalton andB L ShortAtlas of Procedures inNeonatologyM G Macdonald J Ramasethu Eds p 89 Wolters KluwerLippincott Williams and Wilkins Philadelphia Pa USA 4thedition 2007

[29] E Schindler B Kowald H Suess B Niehaus-Borquez BTausch and A Brecher ldquoCatheterization of the radial orbrachial artery in neonates and infantsrdquo Paediatric Anaesthesiavol 15 no 8 pp 677ndash682 2005

[30] A GiaquintaM Veroux C Virgilio et al ldquoBrachial thrombosisin a premature neonate A case reportrdquo Annali Italiani diChirurgia vol 83 no 2 pp 149ndash151 2012

[31] C J Coombs P W Richardson G J Dowling B R Johnstoneand P Monagle ldquoBrachial artery thrombosis in infants analgorithm for limb salvagerdquo Plastic and Reconstructive Surgeryvol 117 no 5 pp 1481ndash1488 2006

[32] N Rutter ldquoPercutaneous drug absorption in the newbornhazards and usesrdquo Clinics in Perinatology vol 14 no 4 pp 911ndash930 1987

[33] N Linder N Davidovitch B Reichman et al ldquoTopicaliodine-containing antiseptics and subclinical hypothyroidismin preterm infantsrdquo Journal of Pediatrics vol 131 no 3 pp 434ndash439 1997

[34] J Schrefer andDNissenMosbyrsquos GenRx 2001 A ComprehensiveReference for Generic and Brand Prescription Drugs pp 1791ndash1795 Mosby-Year Book St Louis Mo USA 2001

[35] P Guran G Beal N Brion and C Advenier ldquoTopical nitro-glycerin as an aid to insertion of peripheral venous catheters inneonatesrdquo Journal of Pediatrics vol 115 no 6 p 1025 1989

[36] M G Bogaert ldquoClinical pharmacokinetics of glyceryl trinitratefollowing the use of systemic and topical preparationsrdquo ClinicalPharmacokinetics vol 12 no 1 pp 1ndash11 1987

[37] A F Wong L M McCulloch and A Sola ldquoTreatment ofperipheral tissue ischemia with topical nitroglycerin ointmentin neonatesrdquo Journal of Pediatrics vol 121 no 6 pp 980ndash9831992

[38] M Varughese and T H Koh ldquoSuccessful use of topical nitro-glycerine in ischaemia associated with umbilical arterial line ina neonaterdquo Journal of Perinatology vol 21 no 8 pp 556ndash5582001

[39] M C Baserga A Puri A Sola et al ldquoThe use of topicalnitroglycerin ointment to treat peripheral tissue ischemia sec-ondary to arterial line complications in neonatesrdquo Journal ofPerinatology vol 22 no 5 pp 416ndash419 2002

[40] R M Bojar H Rastegar D D Payne et al ldquoMethemoglobine-mia from intravenous nitroglycerin a word of cautionrdquo Annalsof Thoracic Surgery vol 43 no 3 pp 332ndash334 1987

[41] G R Gibson J B Hunter D S Raabe Jr D L ManjoneyandF P Ittleman ldquoMethemoglobinemia produced by high-doseintravenous nitroglycerinrdquo Annals of Internal Medicine vol 96no 5 pp 615ndash616 1982

[42] G Maffei M Rinaldi and G Rinaldi ldquoResolution of peripheraltissue ischemia secondary to arterial vasospasm followingtreatment with a topical nitroglycerin device in two newbornscase reportsrdquo Journal of Perinatal Medicine vol 34 no 3 p 2522006

[43] P van Reempts and B vanOvermeire ldquoTopical use of nitroglyc-erin ointment in neonatesrdquo Journal of Pediatrics vol 116 no 1p 155 1990

[44] E C Maynard and W Oh ldquoTopical nitroglycerin ointment asan aid to insertion of peripheral venous catheters in neonatesrdquoJournal of Pediatrics vol 114 no 3 pp 474ndash476 1989

[45] K A Denkler and B E Cohen ldquoReversal of dopamine extrava-sation injury with topical nitroglycerin ointmentrdquo Plastic andReconstructive Surgery vol 84 no 5 pp 811ndash813 1989

[46] P Vasquez A Burd R Mehta M Hiatt and T HegyildquoResolution of peripheral artery catheter-induced ischemicinjury following prolonged treatment with topical nitroglycerinointment in a newborn a case reportrdquo Journal of Perinatologyvol 23 no 4 pp 348ndash350 2003

[47] K Johansson M Eriksson I Wahlqvist B von zur Muhlenand L Lind ldquoEffects of blockade of 120572- and 120573-adrenoceptors andneuropeptideY(1) receptors as well as brachial plexus blockadeon endothelium-dependent vasodilation in the human fore-armrdquo Clinical and Experimental Pharmacology and Physiologyvol 29 no 7 pp 603ndash607 2002

[48] C Traynor J L Paterson I D Ward M Morgan and G MHall ldquoEffects of extradural analgesia and vagal blockade on themetabolic and endocrine response to upper abdominal surgeryrdquoBritish Journal of Anaesthesia vol 54 no 3 pp 319ndash323 1982

[49] M P de Carolis I Bersani F Piersigilli et al ldquoPeripheralnerve blockade and neonatal limb ischemia our experience andliterature reviewrdquo Clinical and Applied ThrombosisHemostasisIn press

[50] V C Ponde D M Shah and S Mane ldquoRole of ultrasound-guided continuous brachial plexus block in the management ofneonatal ischemia in upper limbrdquo Saudi Journal of Anaesthesiavol 6 no 4 pp 423ndash425 2012

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ischemia due to arterial cannulation in the neonatewere iden-tified with complete recovery attributed to the applicationof topical nitroglycerine We describe the first case whichinvolved catheter insertion into the brachial artery

2 Case Report

A Saudi Arabian girl weighing 520 g was born at 25 weeksgestational age to a 35-year-old gravida 4 para 3 motherThere was no family or medical history of a thrombophilicdisorder The infant was a vaginal delivery with Apgar scoresof 3 at 1 minute and 8 at 5 minutes The birth weight wasappropriate for gestational age with no dysmorphic featuresThe infant was immediately intubated received surfactantand was mechanically ventilated The initial chest X-ray wascompatible with respiratory distress syndrome Shortly afterbirth the baby developed hypotension Umbilical venousand arterial lines were inserted and a dopamine drip wasstarted at 10mcgkgminute with subsequent stability Apartial sepsis workup was performed and the baby wasstarted on ampicillin and gentamicin Hyperglycemia on day2 was managed with an insulin infusion Cerebral ultrasoundon day 3 of life was normalThe umbilical venous and arteriallines were removed on day 7 of life

On day 14 the baby developed acute renal failuresecondary to sepsis with poor urine output hypotensionmetabolic acidosis hyperkalemia and a raised creatinineNumerous attempts were made to insert a peripheral arterialline for frequent blood sampling and blood pressuremonitor-ingwithout success Due to the severity of illness and need forarterial access a decision was made to insert a right brachialartery catheter but after 8 hours the middle ring and indexfingers of the right hand were noted to be cold and cyanosedand the arterial line was immediately removed (Figure 1)The hand was elevated and warm compresses were appliedto the contralateral limb Ischemic changes soon becameevident and 4 hours later progressed to involve the distalpart of the fingers which started showing signs of probableearly necrosis (Figure 2) The international normalized ratio(INR) and partial thromboplastin time were normal Acomplete prothrombotic screen was not performed becausethe event was not spontaneous there was no family historyof thrombophilia and there was a causal relationship of theischemia with the brachial cannulation procedure [11] ADoppler ultrasound indicated a sluggish flow through thebrachial artery without definite visualization of a thrombuswhich suggested that the underlying etiology was morelikely vasospasm rather than thrombosis Anticoagulationwas considered as one possible strategy to preserve perfusionand prevent digital loss but the risks of heparinization andpotential bleeding were considered significant A ribbon of2 nitroglycerin ointment (less than 4mmkg) was initiallysparingly applied to the fingers approximately 2 cm proximalto the line of pallor Slight improvement in color andperfusion was noted in the fingers over the next 8 hoursTopical nitroglycerinwas subsequently applied every 8 hours1 cm proximal to the ischemic site following the anatomiccourse of the brachial artery Methemoglobin levels were

Figure 1Digital involvement of the right hand 8 hours after brachialartery cannulation

Figure 2 Signs of early necrosis in the finger tips

monitored daily and stayed in the normal range (metHgblt 1)

There was a gradual improvement in color and capillaryrefill over the next several days By day 12 the area ofischemia was limited to the tips of the fingers and treatmentwas discontinued on day 21 (Figures 3 and 4) The nailbeds were intact with full restorative function of the fingers(Figure 5) The baby made an uneventful recovery from herrenal failure was extubated at 1 month of age and waseventually discharged home at 34 weeks corrected gestationalage weighing 185 kg

3 Discussion

Neonates have several risk factors that predispose them tothrombosis and catheter induced ischemia [11] A systematicreview of spontaneous neonatal arterial thromboembolismclassified these as congenital acquired inherited prothrom-botic abnormalities and maternal [12] factors The coagula-tion system in newborns matures slowly with mean plasma















4 Conclusion



Table1Literature

review

ofneon

ates

treated

with

nitro

glycerin

fora


ischemiaandtheiro

utcomes

AuthorYear[Re

ference]

Gestatio

nalage

wk(Birthwtg)

Catheter

type

Region

andclinicalfi

ndings

2nitro

glycerin

topicald

ose

Outcome

Won

getal1992[37]

25(700)

24(780)

(1)R

ight

radial

(2)R

ight

radial

(1)N

opu

lseright

hand

blanched

(2)n

opu

lsebluefi

ngersrig

hthand

rigid

Ribb

on4m

mkgin

both

cases

(1)Improvem

entw

ithin

15minfull

recovery

in3h

r(2)T

wodo

sesw

ithcompleter

ecovery

after

16hr

except

for2

smallbluea

reas

Varugh

esea

ndKo

h2001

[38]

33(1870)

UAC

Ischem

icchangeso

verright

hip

Normalfemoral+po

plitealpu

lses

04m

gover

2hrmdash

twice

Improvem

ento

ver7

hrwith

complete

resolutio

naft

er30

hr

Basergae

tal2002

[39]

(1)3

0(1620)

(2)2

5(not

stated)

(3)2

3(660)

(1)U

AC(2)U

AC(3)L

eftradial

(1)P

oorp

erfusio


tibialpulses

(2)R

ight


oralpu

lse

cyanotictoes

(3)P

aleleft

hand

andfin

gersabsentradial

pulse

(1)4

singlea

pplications

over

affectedparts-do

seno

tstated

(2)4

mmkgmdash

four

single

applications

over

affectedparts

(3)ribbo

nof

ointment-d

osen

otsta

ted-3sin

glea

pplications

toaffectedareas

(1)C

ompleter

ecoveryin

45min

(2)C

ompleter

ecoveryin

45min

(3)Improvem

entin30

min

with

full

recovery

Vasqueze

tal2003

[46]

26(896)

Leftperip

heral

arteria

lline

(locatio

nno

tsta

ted)


with

discoloration

from

mid-palm

tofin

gertips

Ribb

on4m

mkg

q8h

rfor

27days

Improvem

entin8h

rwith

gradual

recovery

over

18ndash27daysN

odeficitat

8mon

ths

UAC

umbilicalarteria

lcatheter



Disclosure




References

























































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of






























4 Conclusion



Table1Literature

review

ofneon

ates

treated

with

nitro

glycerin

fora


ischemiaandtheiro

utcomes

AuthorYear[Re

ference]

Gestatio

nalage

wk(Birthwtg)

Catheter

type

Region

andclinicalfi

ndings

2nitro

glycerin

topicald

ose

Outcome

Won

getal1992[37]

25(700)

24(780)

(1)R

ight

radial

(2)R

ight

radial

(1)N

opu

lseright

hand

blanched

(2)n

opu

lsebluefi

ngersrig

hthand

rigid

Ribb

on4m

mkgin

both

cases

(1)Improvem

entw

ithin

15minfull

recovery

in3h

r(2)T

wodo

sesw

ithcompleter

ecovery

after

16hr

except

for2

smallbluea

reas

Varugh

esea

ndKo

h2001

[38]

33(1870)

UAC

Ischem

icchangeso

verright

hip

Normalfemoral+po

plitealpu

lses

04m

gover

2hrmdash

twice

Improvem

ento

ver7

hrwith

complete

resolutio

naft

er30

hr

Basergae

tal2002

[39]

(1)3

0(1620)

(2)2

5(not

stated)

(3)2

3(660)

(1)U

AC(2)U

AC(3)L

eftradial

(1)P

oorp

erfusio


tibialpulses

(2)R

ight


oralpu

lse

cyanotictoes

(3)P

aleleft

hand

andfin

gersabsentradial

pulse

(1)4

singlea

pplications

over

affectedparts-do

seno

tstated

(2)4

mmkgmdash

four

single

applications

over

affectedparts

(3)ribbo

nof

ointment-d

osen

otsta

ted-3sin

glea

pplications

toaffectedareas

(1)C

ompleter

ecoveryin

45min

(2)C

ompleter

ecoveryin

45min

(3)Improvem

entin30

min

with

full

recovery

Vasqueze

tal2003

[46]

26(896)

Leftperip

heral

arteria

lline

(locatio

nno

tsta

ted)


with

discoloration

from

mid-palm

tofin

gertips

Ribb

on4m

mkg

q8h

rfor

27days

Improvem

entin8h

rwith

gradual

recovery

over

18ndash27daysN

odeficitat

8mon

ths

UAC

umbilicalarteria

lcatheter



Disclosure




References

























































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















Table1Literature

review

ofneon

ates

treated

with

nitro

glycerin

fora


ischemiaandtheiro

utcomes

AuthorYear[Re

ference]

Gestatio

nalage

wk(Birthwtg)

Catheter

type

Region

andclinicalfi

ndings

2nitro

glycerin

topicald

ose

Outcome

Won

getal1992[37]

25(700)

24(780)

(1)R

ight

radial

(2)R

ight

radial

(1)N

opu

lseright

hand

blanched

(2)n

opu

lsebluefi

ngersrig

hthand

rigid

Ribb

on4m

mkgin

both

cases

(1)Improvem

entw

ithin

15minfull

recovery

in3h

r(2)T

wodo

sesw

ithcompleter

ecovery

after

16hr

except

for2

smallbluea

reas

Varugh

esea

ndKo

h2001

[38]

33(1870)

UAC

Ischem

icchangeso

verright

hip

Normalfemoral+po

plitealpu

lses

04m

gover

2hrmdash

twice

Improvem

ento

ver7

hrwith

complete

resolutio

naft

er30

hr

Basergae

tal2002

[39]

(1)3

0(1620)

(2)2

5(not

stated)

(3)2

3(660)

(1)U

AC(2)U

AC(3)L

eftradial

(1)P

oorp

erfusio


tibialpulses

(2)R

ight


oralpu

lse

cyanotictoes

(3)P

aleleft

hand

andfin

gersabsentradial

pulse

(1)4

singlea

pplications

over

affectedparts-do

seno

tstated

(2)4

mmkgmdash

four

single

applications

over

affectedparts

(3)ribbo

nof

ointment-d

osen

otsta

ted-3sin

glea

pplications

toaffectedareas

(1)C

ompleter

ecoveryin

45min

(2)C

ompleter

ecoveryin

45min

(3)Improvem

entin30

min

with

full

recovery

Vasqueze

tal2003

[46]

26(896)

Leftperip

heral

arteria

lline

(locatio

nno

tsta

ted)


with

discoloration

from

mid-palm

tofin

gertips

Ribb

on4m

mkg

q8h

rfor

27days

Improvem

entin8h

rwith

gradual

recovery

over

18ndash27daysN

odeficitat

8mon

ths

UAC

umbilicalarteria

lcatheter



Disclosure




References

























































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of


















Disclosure




References

























































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of













































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















case report topical nitroglycerine for neonatal arterial … · 2020. 1. 27. · artery...

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