Case ReportARDS and Massive Pulmonary Embolism: The CombinedUse of Extracorporeal Membrane Oxygenation(ECMO) with Thrombolytics

Brett Dickens, Casey Bryant , John Gaillard, and Nathaniel Westphal

Departments of Emergency Medicine and Anesthesiology, Wake Forest School of Medicine, Winston-Salem, NC, USA

Correspondence should be addressed to Casey Bryant; casbryan@wakehealth.edu

Received 12 July 2019; Revised 30 January 2020; Accepted 14 February 2020; Published 28 April 2020

Academic Editor: Kenneth S. Waxman

Copyright © 2020 Brett Dickens et al.-is is an open access article distributed under the Creative Commons Attribution License,which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Pancreatitis causes a systemic inflammatory response that can lead to acute respiratory distress syndrome (ARDS). We present acase of severe ARDS complicated by a pulmonary embolism (PE) in a 39-year-old female that developed rapidly progressivepancreatitis secondary to hypertriglyceridemia.

1. Introduction

Venovenous (VV) extracorporeal membrane oxygenation(ECMO) is a treatment option for management of severeARDS. -is report details a case of ARDS secondary tohypertriglyceridemia-induced pancreatitis complicated byobstructive shock secondary to a massive pulmonaryembolism.

Our review of the literature regarding thrombolytic usewhile on ECMO revealed only three case studies and a singlecase series. Two of the three case reports were in neonates:myocardial infarction [1] and intracardiac thrombus [2].-ethird case was from our facility and discussed catheter di-rected thrombolysis for a massive PE post-cardiac arrestwhile on venoarterial (VA) and later VV ECMO [3]. Finally,the case series consisted of 13 cases of massive PE at a singlecenter where all patients were placed on VA ECMO. Eightpatients received systemic thrombolytics, three receivedcatheter-directed thrombolysis, and four underwent surgicalembolectomy [4]. None of these cases discussed the use ofthrombolytics on ECMO with acute pancreatitis.

2. Case Presentation

A 39-year-old female with history of Tourette syndrome,hypothyroidism, non-insulin-dependent diabetes mellitus

(Hb A1c 6.3), obesity (BMI 38.7 kg/m2), and hyperlipidemiapresented to a community emergency department forevaluation of abrupt onset abdominal pain, nausea, andvomiting. Her lipase level was 7,465 IU/L, and the computedtomography (CT) findings of her abdomen and pelvis wereconsistent with uncomplicated pancreatitis. Further workuprevealed triglycerides of 7,121mg/dL with no known historyof hypertriglyceridemia in the past. She did not take anyculprit medications for hypertriglyceridemia.

She was admitted to the community hospital for fluidresuscitation and was started on an insulin infusion. Onhospital day 2, she became oliguric and developed dyspneawith bilateral infiltrates on chest x-ray concerning for ARDS.She was intubated later that day for hypoxic respiratoryfailure. Although an echocardiogramwas not obtained at theoutside hospital, her x-ray findings were not thought to bepulmonary edema due to heart failure by the clinicianscaring for her at the time. On hospital day 3, the patient wastransferred to our academic medical center for the man-agement of ARDS requiring mechanical ventilation, pan-creatitis, and worsening renal function. At the time ofadmission to our hospital, the triglyceride level had im-proved to 996mg/dL, and the lipase level had improved to923 IU/L on the insulin infusion. Although other modalitiesof treatment such as plasmapheresis have been shown to beefficacious in lowering triglycerides, this patient was

HindawiCase Reports in Critical CareVolume 2020, Article ID 1032629, 5 pageshttps://doi.org/10.1155/2020/1032629

continued on insulin infusion and IV fluid repletion giventhe significant decrease in triglyceride levels [5].

-e patient arrived to our medical intensive care unit(MICU) overnight with severe ARDS (P/F of 90) secondaryto pancreatitis (Figure 1). Vital signs included: bloodpressure 122/63mmHg, heart rate 150 beats per minute,respiratory rate 23 per minute, temperature 103.4°F (39.7°C),and pulse oximetry 95%. Ventilator settings were: assistcontrol with set volume target 350 cc (∼6 cc/kg, IBW 59 kg),rate 26, FiO2 100%, PEEP 16 cmH2O, PIP 38 cmH2O, Pplat34. Arterial blood gas (ABG) on arrival was pH 7.16/pCO246/pO2 91. -e base deficit was 12. Lactic acid was3.32mmol/L. -e patient’s ECG at the time of arrivalrevealed sinus tachycardia with HR in the 150 s, incompleteright bundle branch block (RBBB), and S1Q3T3morphology(Figure 2). No prior ECG was available for comparison.

Over the next few hours, she became increasingly hy-potensive with anuria. Her extremities were noted to be cooland dusky. Her peripheral pulses were only able to be ob-tained by the Doppler signal. Vasopressin and norepi-nephrine were used to maintain a mean arterial pressure of65mmHg.-e patient was continued on an insulin drip, anda 10% dextrose/normal saline drip for treatment of thehypertriglyceridemia. She was also started on empiric broad-spectrum antibiotics because of concern for septic shock.

Given the patient’s hemodynamic instability on pre-sentation, transthoracic echocardiogram was obtained thatrevealed a severely dilated right ventricle (RV) with mod-erately reduced function (Figure 3). In the parasternal shortaxis view, there was septal flattening in both systole anddiastole consistent with elevated RV pressure and volumeoverload. -e left ventricle (LV) was hyperdynamic with anejection fraction of >70%. She was initiated on a heparininfusion at that time due to suspicion for pulmonaryembolism.

Her hypoxia continued to worsen after arrival withoxygen saturations decreasing to 84–86%. -e patient wassedated to a Richmond Agitation Sedation Score (RASS) of5, paralyzed using cisatracurium and inhaled epoprostenolwas initiated. Despite these treatments, her conditioncontinued to worsen (norepinephrine up to 22mcg/min andvasopressin 0.04U/min) with ongoing hypoxia, so the de-cision was made to cannulate her for VV ECMO approxi-mately 12 hours after admission to our hospital. Proning isperformed at our center, but was not pursued due to thepatient’s worsening hemodynamics. Cannulation was per-formed with a 31 French Avalon bicaval cannula (Maquet,Rastatt, Germany) via the right internal jugular vein. -epatient remained anuric for the next 24 hours with a risingBUN and Cr (initial BUN 12, Cr 1.44 increased to BUN 16,and Cr 2.16). -erefore, continuous renal replacementtherapy (CRRT) was initiated for acute renal failure, whichwas believed to be due to acute tubular necrosis from shockand hypoxia.

At the time of cannulation, her condition was felt to bemultifactorial with severe ARDS and distributive shock dueto both sepsis and systemic inflammation from over-whelming pancreatitis. -e right ventricular dilation anddysfunction was believed to be due to acidemia, high

ventilator settings, and hypoxia. Obstructive shock due toacute PE was also high on the differential.

After cannulation for VV ECMO, the patient remainedhypoxic and hemodynamically unstable. Bedside point ofcare ultrasound (POCUS) was performed that revealedcontinued RV dilation and decreased function that had notimproved with the addition of epinephrine for inotropicsupport (5 mcg/min), correction of acidosis and hypoxia,and minimization of ventilator support (pressure controlventilation 20 with PEEP 10, rate 10, and FiO2 40%). Bi-lateral lower extremity venous duplex ultrasounds revealed athrombus in the right femoral vein. Due to high suspicionfor PE contributing to the refractory shock and hypoxemicstate, 50mg of alteplase (tPA) (10mg bolus, 40mg infusiongiven over 2 hours) was administered systemically. Ap-proximately 1 hour after completing the infusion of tPA, thepatient’s hemodynamics had improved to the point wherevasopressors were weaned off and inotropic support hadbeen titrated down to epinephrine 2mcg/min. -is con-cluded the events of hospital day 1 at our facility and day 3 ofher total hospitalization.

-e insulin infusion was discontinued on hospital day 5once triglycerides dropped below 500mg/dL and gemfi-brozil was started. By day 5, the patient developed throm-bocytopenia, which was concerning for heparin inducedthrombocytopenia (HIT). Other considerations for thethrombocytopenia include CRRT, vancomycin-inducedthrombocytopenia, and the use of epoprostenol. Argatrobanwas used for anticoagulation for 6 days until the HIT an-tibody screen and serotonin release assay were negative.

-e patient continued to require VV ECMO for hypoxicrespiratory failure despite improvement in the infiltrates onher chest x-rays. A CTangiogram of the chest was performedon hospital day 10 to evaluate the lung vasculature forsuspicion of recurrent or persistent PE. Multiple pulmonaryemboli were identified involving the distal right main pul-monary artery and multiple lobar pulmonary arteries(Figure 4). A CT of the abdomen/pelvis performed at thesame time revealed extensive peripancreatic fluid collectionsand a thrombus in the portal vein extending into the splenicvein and superior mesenteric vein (SMV).

Due to the extensive venous thromboemboli and in-ability to wean from ECMO, interventional cardiology was

Figure 1: Chest x-ray.

2 Case Reports in Critical Care

consulted and performed catheter directed thrombolysis(CDT) via an EndoWave Infusion Catheter System (EKOS)on hospital day 11. -e patient’s hypoxia improved to thepoint where she was able to be decannulated from ECMO onhospital day 12. CRRT was continued until hospital day 13,at which time she was transitioned to intermittent hemo-dialysis. On hospital day 14, she was extubated. A repeatechocardiogram that day revealed an ejection fraction of55–60% with normal size and function of the right ventricle.On hospital day 18, she transferred out of the intensive careunit.

Due to extensive diffuse venous thromboemboli, hy-percoagulability studies were sent including antithrombinIII, protein C and S, antinuclear antibody screen, cardiolipinIgA/IgM/IgG, plasminogen activity, and thrombophilia

genotype panel (including factor V Leiden). -e patient washeterozygous for factor II 20210 mutation. Hematology wasconsulted and reported this mutation alone does not typi-cally require anticoagulation, because the mutation does notoften lead to VTE. In this case, the mutation was thought tobe contributory to the patient’s significant thromboembolilikely induced by the severe systemic inflammatory responsecaused by pancreatitis. Hematology recommended indefi-nite anticoagulation.

-e patient’s course was also unfortunately complicatedby limb ischemia, believed to be due to microthrombi fromher hypercoagulable state and her concomitant vasopressor

25mm/s 10mmV 10Hz 8.0 SP2 12SL 239 CID: 3 EID: 31 EDT: 20:58 10-SEP-2018 Order: 489806058 Account: 30093509370

Figure 2: Electrocardiogram.

Figure 3: Echocardiogram.

Figure 4: Computed tomography.

Case Reports in Critical Care 3

requirement. Ultimately, she required bilateral below kneeamputations for dry gangrene. Expectant management waspursued for the gangrenous distal fingertip injuries. Shecompleted a stay in acute rehabilitation, and approximately 3months after discharge from rehab the patient returned forcarpal tunnel release surgery, eschar removal of the left indexfinger, and amputation through the right ring finger at theDIP joint. She was also scheduled to follow-up regardingbilateral lower extremity prosthesis placement and fitting.Approximately 7 months after the date of admission to ourhospital, the patient reached out to team members throughsocial media and indicated that she was doing well andprogressing in her rehabilitation. She has since been lost toany further follow-up.

3. Discussion

Our team acknowledges that VA ECMO is the extracor-poreal treatment of choice when pulmonary embolism is thecause of cardiogenic shock [6]. Our patient was placed onVV ECMO as the initial hypothesis was that her cor pul-monale was due to her critical illness and high ventilatorsettings. When her RV function did not improve afteroptimizing these conditions, the search for alternative ex-planations of her illness continued. She was ultimately giventhrombolytics due to a high clinical suspicion for PE.Transitioning to VAV support was also discussed, but thiswas decided against due to the peripheral limb ischemia thatshe was already demonstrating. -is case highlights thecomplex and high stakes nature of caring for critically illpatients as well as the importance of assessing treatments forresponse and continuing the pursuit of alternative expla-nations when patients do not respond as expected tointerventions.

While acute pancreatitis is a common disease, there arefew documented cases of PE in this patient population.Vascular complications associated with pancreatitis arethought to be related to the release of proteolytic enzymesthat cause vessel erosion allowing for pseudocyst formationand endothelial disruption resulting in local vasculitis, ul-timately leading to an increased risk of thrombosis [7].-ereis an increased risk of hemorrhage associated with thesevascular complications, particularly when there is pseudo-cyst formation. Life threatening bleeding can occur.

-ere are few case reports of patients receivingthrombolysis during an episode of acute pancreatitis. Reviewof the literature revealed once such case which involved a 54-year-old man initially misdiagnosed with STEMI who re-ceived thrombolytics with no life-threatening complications[8]. -e second case discussed a 47-year-old man with acutealcoholic pancreatitis who received thrombolytics forSTEMI and subsequently died of retroperitoneal hemor-rhage from pseudocyst rupture [9]. Additionally, a singlecase was published that discussed the successful use ofthrombolysis in a patient with both a pulmonary embolismand acute pancreatitis [7].

-e standard dose of tPA for massive PE is 100mginfused over 2 hours. However, literature review did notreveal a standard dose for a patient on VV ECMO, and the

diagnosis in our patient had not been confirmed. Addi-tionally, there was concern for possible hemorrhagic con-version of pancreatitis or other complications given thepatient’s complexity. In this case, the reduced dose of 50mg(10mg bolus, 40mg infusion over 2 hours) proved effica-cious and improved hemodynamics immediately with noadverse effects. However, the patient did later require CDTvia EKOS catheter for further treatment of persistent pul-monary emboli that were prohibiting her from weaning offECMO support. -e increased volume of distributioncontributed by the ECMO circuit may have contributed tothe decreased overall efficacy of the initial dose ofthrombolytics.

Standard dosing for tPA was extrapolated for use inPE. Importantly, when tPA is given for ailments such asstroke, only a fraction of the total blood volume may enterthe circulation of the affected organ (15% of the totalcirculation in the case of the brain). -is is much differentthan the 100% of blood volume that cycles through thepulmonary vasculature. Recent studies have supported adecreased dose with improved safety profile, though thetopic of treating submassive PE with thrombolytics re-mains controversial. -e Moderate Pulmonary EmbolismTreated with -rombolysis (MOPETT) trial illustrated atrend towards safe and effective tPA administration atlower than normal dosing for submassive PE [10]. -ePulmonary Embolism -rombolysis (PEITHO) trialdemonstrated a trend towards reduced cardiac compli-cations (death or hemodynamic instability) at 7 days afteradministration of full dose tenecteplase for submassivePE. In that study of over 1,000 patients, death and car-diovascular collapse were decreased by nearly 56% byusing tenecteplase plus heparin compared to heparinalone; however, major bleeding and hemorrhagic strokeincreased by as much as 10-fold [11]. In an attempt tobypass such bleeding complications, catheter-directedtherapy was proposed as an alternative. -e SEATTLE IIstudy, published in 2015, showed that catheter-directedtherapy of thrombolytics for submassive PE could effec-tively reduce RV dilation, pulmonary hypertension, andanatomic thrombus burden while also possibly mini-mizing intracranial hemorrhage [12]. While catheter-di-rected thrombolysis has proven effective in submassivePE, it has never been compared in a head to head trialagainst systemic thrombolytics so the topic continues tobe debated. In summary, for submassive PE, the indica-tion, appropriate dose, and route of thrombolytic treat-ment all remain controversial.

4. Conclusion

-is case highlights the complexity in managing critically illpatients with multiple acute comorbidities including hy-percoagulability, ARDS, obstructive shock, and acute pan-creatitis each complicating the available treatment optionsand goals in therapy. Additionally, it highlights the im-portance of continued studies looking at thrombolytic ad-ministration in both ECMO patients as well as acutepancreatitis.

4 Case Reports in Critical Care

Conflicts of Interest

-e authors declare that they have no conflicts of interest.

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