Successful Pulmonary Embolectomy ofa Saddle Pulmonary Thromboembolismin a Preterm NeonateKaarthigeyan Kalaniti, MBBS, MDa, Mauro Lo Rito, MDb, Edward J. Hickey, MDb,c, V. Ben Sivarajan, MD, MSc,d,e

abstractSymptomatic pulmonary thromboembolism (PTE) is rare in neonates, and thediagnosis is often made only postmortem. The true incidence is probablyunderestimated because of its varying presentations, ranging from mildrespiratory distress to acute right-heart failure and cardiovascular collapse.We report a sudden cardiorespiratory collapse on day 10 of life in a pretermneonate who was subsequently diagnosed as having a saddle pulmonaryembolus. The patient underwent an emergency surgical embolectomy asa salvage procedure. Considering the potentially lethal complications of PTE,neonatologists and pediatricians should maintain a high degree of suspicion ininfants with sudden inexplicable deterioration in cardiorespiratory status.Surgical removal of the thrombus is an invasive procedure and potentiallycarries a high mortality rate. Two term neonatal survivors of surgicalintervention have been reported in the medical literature so far. However, webelieve that this is the first documented preterm neonatal survivor aftersurgical intervention for a massive saddle PTE.

Pulmonary thromboembolism (PTE) isa rare disorder in newborn infants,usually related to indwelling centrallines.1 Although rare, the diagnosis ofpulmonary embolism should besuspected in an infant withunexplained hypoxemia or rightventricular failure, especially in infantswith a prolonged need for a centralline. Few cases of spontaneousneonatal PTE have been described inthe literature.2–4 Only 3 publishedreports have documented successfulpulmonary embolectomy inneonates.3–5 We believe this is the firstdocumented report of successfulpulmonary embolectomy for saddlePTE in a preterm neonate.

CASE REPORT

A premature male weighing 2065 gwas born by vaginal delivery at33 weeks of gestational age after anuneventful pregnancy in a remote rural

hospital. No significant pregnancycomplications were noted in theantenatal period. The baby had Apgarscores of 7 and 8 at 1 and 5 minutes,respectively. Mild respiratory distressnecessitated continuous positiveairway pressure for a few hours afterbirth. There was no history of umbilicalcatheterization. He was transferredwithin the first few days of life to thepostnatal ward focusing on feeding andgrowth. On day 10 of life, he hadsudden apneic spells with lethargy,acute cyanosis, poor perfusion, andpoor respiratory effort. The heart ratewas 60 to 70 beats/minute withoxygen saturation (SpO2) 60% to 65%(both pre- and postductal). Bag-maskventilation with 100% fraction ofinspired oxygen (FIO2) wascommenced, and normal saline boluseswere given in an attempt to improvethe poor perfusion. There was noimprovement in oxygenation; hencethe baby was intubated and

Divisions of aNeonatology, Department of Paediatrics;bCardiovascular Surgery, Department of Surgery; dCardiacCritical Care, Department of Critical Care Medicine;eCardiology, Department of Paediatrics; cThe Hospital forSick Children, Faculty of Medicine, University of Toronto,Toronto, Ontario, Canada

Dr Kalaniti reviewed the medical literature anddrafted the manuscript; Drs Lo Rito, Hickey, andSivarajan reviewed the manuscript; Dr Sivarajanrevised the manuscript; Dr Kalaniti finalized themanuscript; Drs Lo Rito and Hickey approved thefinal manuscript; and Dr Sivarajan approved themanuscript as submitted.

www.pediatrics.org/cgi/doi/10.1542/peds.2014-3242

DOI: 10.1542/peds.2014-3242

Accepted for publication Jan 26, 2015

Address correspondence to Dr V. Ben Sivarajan,Critical Care Medicine, The Hospital for SickChildren, 555 University Ave, Toronto, ON M5G 1X8,Canada. E-mail: ben.sivarajan@sickkids.ca

PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online,1098-4275).

Copyright © 2015 by the American Academy ofPediatrics

FINANCIAL DISCLOSURE: The authors have indicatedthey have no financial relationships relevant to thisarticle to disclose.

FUNDING: No external funding.

POTENTIAL CONFLICT OF INTEREST: The authors haveindicated they have no potential conflicts of interestto disclose.

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mechanically ventilated. His heartrate improved, 4-limb bloodpressures showed no gradient, andcardiac examination revealed normalheart sounds with a flow murmur atthe upper sternal border. There wasno hepatomegaly. Broad-spectrumantibiotics were commenced afterdrawing appropriate cultures.Differential diagnoses of septic,cardiac, or metabolic causes wereentertained at this point.Postintubation, the SpO2 slightlyimproved to 80% to 85% in 100%FIO2. Arterial blood gas revealedsevere hypoxemia (arterial partialpressure of oxygen [PaO2] 26 mmHg)with mild mixed respiratory andmetabolic acidosis. Chest radiographwas unremarkable. A referral wasmade to our tertiary care center forconsultation, acute management, andtransportation of this sick neonate.

Upon the transport team’s arrival,repeat arterial blood gas showedpersistent hypoxemia (PaO2 24 mmHg) with SpO2 80% to 85% in 60% to80% FIO2. Recommendations weremade to commence prostaglandin E1(PGE1) infusion and then, based onthe response, to wean ventilation andFIO2 to 21%. With this strategy, the

patient’s hemodynamics and gasexchange were stabilized (achievingoxygen saturations between 88% and95%) before 700-km air transport toour tertiary center. Based on theclinical presentation, congenital heartdisease with ductal-dependentpulmonary blood flow was suspected,resulting in direct transport to thecardiac critical care unit.

Urgent bedside transthoracic two-dimensional echocardiographyrevealed a structurally normal heartwith a patent ductus arteriosusshunting left to right. A largeechogenic mass (Fig 1) was seen inthe main pulmonary artery occluding∼50% of the lumen and extendinginto the right and left pulmonaryartery with almost completeocclusion on the right. The rightventricle was dilated, with theintraventricular septum bowing intothe left ventricle. There was a patentforamen ovale with right-to-leftshunting. Pertinent findings on initiallaboratory investigations showedthrombocytopenia (platelets 54000/mL),but normal coagulation studies(prothrombin time, internationalnormalized ratio, and activatedpartial thromboplastin time). D-dimer

test was positive (2.32 µg/mL). Therewas no known family history ofthrombophilia. An urgent contrastedcomputerized tomography scandemonstrated a large filling defectconsistent with a large saddle PTE inthe distal main and both branches ofthe pulmonary arteries (Fig 2). Anultrasound Doppler screen for anyother sites of venous obstruction didnot reveal any evidence of thrombosis.Baseline cranial ultrasound andneuroimaging showed a smallintraparenchymal hemorrhage in theleft parietal lobe.

The risks of thrombolysis andsurgical embolectomy were initiallybelieved to be significant in light ofthe patient’s gestational age andweight. As a result, anticoagulationtherapy with unfractionated heparininfusion was initiated. PGE1 infusionwas continued. Three hours after theinitiation of heparin infusion, thepatient had hemodynamic instabilitywith profound desaturations, loss ofend-tidal carbon dioxide readings,bradycardia, and hypotension. He wasresuscitated with normal salineboluses and low-dose epinephrineand started with dopamine andepinephrine infusions for inotropicsupport. The neonate was thenurgently taken to the operating roomfor surgical embolectomy.

A median sternotomy approach wasperformed, and cardiopulmonarybypass was established throughcannulation of the ascending aortaand right atrial appendage. Theductus arteriosus was ligated, anda transverse arteriotomy of theproximal main pulmonary arteryrevealed an organized thrombus,which was retrieved as a single piece.The saddle thrombus formed a cast ofthe bifurcating pulmonary vessels(Fig 3). The distal pulmonary arteriesappeared completely patent withoutresidual thrombus. The patient wasseparated uneventfully fromcardiopulmonary bypass. Theintraoperative echocardiogramdemonstrated good biventricular

FIGURE 1Short-axis view from transthoracic two-dimensional echocardiogram showing the thromboembolusin the main pulmonary artery. Av, aortic valve; LA, left atrium; MPA, main pulmonary artery; PTE,pulmonary thromboembolus; Pv, pulmonary valve; RV, right ventricular.

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function, and the main and branchedpulmonary arteries were patent withlaminar flow. Histopathology of theembolus showed layered thrombuswith no evidence of organization oractive infection.

Within 24 hours of embolectomy, thepatient was extubated and inotropicsupport was discontinued.Continuous heparin infusion therapywas transitioned to subcutaneous lowmolecular weight heparin (LMWH).A partial prothrombotic workup(protein C, protein S, antithrombin IIIlevel, fibrinogen, serum antinuclearantibodies, factor V Leiden mutation,

antiphospholipid antibody, andanticardiolipin antibody screens) ofthe patient and family members didnot reveal an inherited or acquiredcause of thrombophilia. A repeatcranial ultrasound before dischargeshowed no interval change. Theneonate was discharged on twicedaily subcutaneous LMWH for6 months with periodic monitoringof anti-Xa levels. He did not requirefurther hospitalizations afterdischarge. At his 3- and 6-monthfollow-ups at our center, he wasfound to be doing well withoutresidual or recurrent thrombus in the

pulmonary artery or other systemicvessels. In addition, the infant hadattained age-appropriateneurodevelopmental milestones.

DISCUSSION

In the entire pediatric population,neonates are at the greatest risk forvenous thromboembolism, witha second peak in incidence duringpuberty and adolescence.1,6 PTE isa rare event in the neonatal period;however, it is unclear how manyevents go unrecognized. Recognitionand definitive diagnosis are keys toprompt life-saving therapy.

Clinical signs of severe arterialhypoxemia unresponsive to standardventilatory maneuvers suggesta diagnosis of ductal dependency forpulmonary blood flow. The usualcause of this finding in a newborn iscongenital heart disease. In ourpatient, an unusual finding ofobstructive thrombus preventingpulmonary blood flow was confirmed.In either circumstance, earlyreestablishment of ductal patency isoften essential to survival. Clearly,early use of transthoracicechocardiography was important forearly definitive diagnosis anddirected management.

Making decisions regarding thedefinitive treatment strategy inclinically significant PTE can bechallenging. Appropriate evidence-based PTE treatment algorithms forneonates are lacking and oftenextrapolated from either adulttreatment guidelines or isolated casereports.1,7 Treatment options availablefor PTE in neonates includethrombolytic therapy with tissueplasminogen activator orembolectomy (either catheter-basedor open surgical).1,8 Catheter-basedtherapy in this situation wascontraindicated, as withdrawing thePTE proximally using a catheter-basedapproach imposed a significant risk ofuncontrolled systemic embolizationgiven the neonate’s right-to-left shuntat the patent foramen ovale.

FIGURE 2Computed tomography angiogram (coronal and axial view) demonstrating a large filling defect inthe distal main and both branch pulmonary arteries with nonvisualization of distal filling confirminga large saddle pulmonary thromboembolus (arrow). LPA, left pulmonary artery; RPA, right pulmo-nary artery.

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Treatment should focus onrecanalization of the occluded vesselas well as prevention of furtherthrombus growth and reoccurrence.Use of anticoagulants such asunfractionated heparin or LMWHprevents extension of the existing PTE.The major potential risk ofthrombolytic therapy, especially inpreterm neonates, is a massiveintracranial hemorrhage. Becausewithholding anticoagulation isa decision equally active to that ofcommencing treatment, the individualrisk-benefit ratio has to be carefullyconsidered. In our case, because thepatient was initially stable on PGE1therapy, the preference was tocontinue with unfractionated heparin,especially in light of the risks ofprematurity. This initial strategy wasinadequate, and because ofhemodynamic deterioration, surgicalpulmonary embolectomy wasundertaken as a salvage procedure.Pulmonary embolectomy should berestricted to those patients in whomthrombolytic therapy iscontraindicated, when delay intreatment is deemed unacceptable, or

if the patient’s condition deterioratesafter intensive medical orthrombolytic therapy.

CONCLUSIONS

It is imperative for neonatologists andpediatricians to maintain a highdegree of suspicion for PTE in infantswith sudden deterioration ofoxygenation, acute respiratorydistress, or unexplainedhemodynamic instability. Thesefindings should allow considerationof a broad differential diagnosisincluding PTE. In our case, earlyinitiation of PGE1 allowed forstabilization and establishment of thedefinitive diagnosis byechocardiography. It is important toconsider all the therapeutic options,including stabilization of the PTEwith heparin infusion followed bydefinitive therapy. Surgicalmanipulation through embolectomycarries a risk of distal embolization ofthe thrombus to peripheralpulmonary arteries that may beinaccessible to the surgeon.4 Despitethese risks, it is important to be

aware of the value of surgicalembolectomy in the management ofacutely unstable patients or thosewith additional risk factors forstandard medical thrombolysis.

REFERENCES

1. Paes BA, Nagel K, Sunak I, Rashish G, ChanAK; Thrombosis and Hemostasis inNewborns (THiN) Group. Neonatal andinfant pulmonary thromboembolism:a literature review. Blood CoagulFibrinolysis. 2012;23(7):653–662

2. Sawyer T, Antle A, Studer M, Thompson M,Perry S, Mahnke CB. Neonatal pulmonaryartery thrombosis presenting as persistentpulmonary hypertension of the newborn.Pediatr Cardiol. 2009;30(4):520–522

3. Gamillscheg A, Nürnberg JH, Alexi-Meskishvili V, et al. Surgical emergencyembolectomy for the treatment offulminant pulmonary embolism ina preterm infant. J Pediatr Surg. 1997;32(10):1516–1518

4. De Blanche LE, Schmitz ML, Johnson CE,Best TH, Drummond-Webb JJ. Successfulsurgical management of a neonate witha saddle pulmonary embolus. Ann ThoracSurg. 2004;78(1):e1–e2

5. Lambert V, Durand P, Devictor D, PlanchéC, Serraf A. Unilateral right pulmonarythromboendarterectomy for chronicembolism: a successful procedure in aninfant. J Thorac Cardiovasc Surg. 1999;118(5):953–954, discussion 957

6. Biss TT, Brandão LR, Kahr WH, Chan AK,Williams S. Clinical features and outcomeof pulmonary embolism in children. Br JHaematol. 2008;142(5):808–818

7. Nowak-Göttl U, Janssen V, Manner D, KenetG. Venous thromboembolism in neonatesand children—update 2013. Thromb Res.2013;131(Suppl 1):S39–S41

8. Veldman A, Nold MF, Michel-Behnke I.Thrombosis in the critically ill neonate:incidence, diagnosis, and management. VascHealth Risk Manag. 2008;4(6):1337–1348

FIGURE 3Intraoperative image of the saddle thrombus that formed a cast of the bifurcating pulmonaryvessels.

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DOI: 10.1542/peds.2014-3242 originally published online April 20, 2015; 2015;135;e1317Pediatrics 

Kaarthigeyan Kalaniti, Mauro Lo Rito, Edward J. Hickey and V. Ben Sivarajanin a Preterm Neonate

Successful Pulmonary Embolectomy of a Saddle Pulmonary Thromboembolism

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DOI: 10.1542/peds.2014-3242 originally published online April 20, 2015; 2015;135;e1317Pediatrics 

Kaarthigeyan Kalaniti, Mauro Lo Rito, Edward J. Hickey and V. Ben Sivarajanin a Preterm Neonate

Successful Pulmonary Embolectomy of a Saddle Pulmonary Thromboembolism

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