fatal pulmonary embolismjnm.snmjournals.org/content/10/1/28.full.pdf · 2006-12-19 · fatal...

FATAL PULMONARY EMBOLISM

Norman D. Poe, Earl K. Dore, Leonard A. Swanson and George V. Taplin

Laboratory of Nuclear Medicine and Radiation Biology, UCLA, Los Angeles, California

Massive pulmonary embolism is a dramatic, oftenfatal, event. If death is not immediate, embolectomyusing cardiopulmonary bypass is feasible, and a number of reports have appeared in recent years attesting to its value (1-3). However, emergency embolectomy is not practical on a wide scale.

In over 300 cases of pulmonary embolism withpositive lung-scan findings, we have observed thatmajor or fatal embolization rarely is the first evidence of a thromboembolic process. Most patientshave symptoms or signs of small emboli antedatingthe catastrophic episode by 5-7 days or more. Lungscanning is an effective and widely applicable testfor identifying occlusion of lobar, segmental andsome subsegmentai pulmonary arteries (6,7), whileadequate anticoagulation is known to definitely reduce the incidence and mortality from recurrentemboli (8). Detection of these minor or "signal"

emboli by lung-perfusion scanning followed by intensive anticoagulation is a potentially effective meansof preventing massive embolization.

This paper describes the clinical course andautopsy findings in seven patients with massive pulmonary embolism and suggests that lung scanningmay play an important role in reducing the incidenceof fatal attacks.

METHODS

In noncritically ill patients 180-350 ^Ci of 131I-

labeled macroaggregated human serum albuminwere injected intravenously in an antecubital veinwith the patient in the upright position. The posteriorscan was begun immediately, followed by anteriorand/or lateral views as indicated for better localization of ischemie areas. Critically ill patients werebrought to the Radioisotope Department in theirhospital beds, and the isotope was administered inthe recumbent or semirecumbent position. Usuallyonly an anterior scan could be obtained in thesepatients. Scans were performed on scanners (PickerNuclear) with 3 X 2 or 5 X 2-in. Nal(Tl) crystalsat speeds of 60-200 cm/min.

CASE REPORTS

Case 1. A 30-year-old male had a history of pneumonia and hemoptysis in 1962. On July 1, 1966, hedeveloped chest pain, cough, and fever and wastreated for pneumonia. An x-ray on July 5 showedresidual inflammatory disease at the left base. Eightdays later he experienced dyspnea, hemoptysis andsyncope without fever or pain. A chest film showedno change except possibly slight cardiac enlargement.On July 14 the dyspnea increased. He became cy-anotic and had an accentuated pulmonic secondsound. The right knee was tender from an injury 5days earlier. The serum glutamic oxaloacetic trans-aminase (SCOT) was 67 units (normal <40),and the lactic dehydrogenase (LDH) was 580 units(normal <550). The EKG showed anterior wallischemia with incomplete right bundle branch block.The chest film demonstrated a prominent pulmonaryartery with oligemia of the right lung and hyperemiaof the left upper lobe. The lung scan indicatedmarked ischemia of both bases and the right upperlobe with relatively increased perfusion of the leftupper lobe. Ten thousand units of heparin wereimmediately given subcutaneously followed by 7,500units intravenously every 6 hr. However, two clotting times in the next 24 hr were only 10 and 18min (hospital normal <15 min). Because the patient did not improve clinically, a vena cavai plicationwas performed the following day. The patient's con

dition deteriorated during the operation, and emergency embolectomy using cardiopulmonary bypasswas attempted. No occlusion could be found in themain pulmonary artery, and even with back flushingfrom the left atrium very little embolie material couldbe removed. The pulmonary arterial pressure remained elevated, and the patient expired in surgery.At autopsy the artery to the left lower lobe was corn-

Received Feb. 2, 1968; revision accepted April 4, 1968.For reprints contact: Norman D. Poe, Laboratory of Nu

clear Medicine, 900 Veteran Ave., Los Angeles, Calif.90024.

28 JOURNAL OF NUCLEAR MEDICINE

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FIG. l. Anterior (above) and posterior (not shown) scans dem- autopsy occlusive stricture was found in artery to left lower lobe,onstrate marked ischemia in regions of right upper and middle All major arteries on right were filled with adherent and nonad-lobes with lesser ischemia of both lower lobes. Part of perfusion herent emboli (shaded area). Partial occlusion of right lower lobedefect in left lower lobe results from cardiac displacement. At artery become complete during interval between scan and death.

pletely occluded by a fibrous ring (Fig. 1). Thebranches of the right main pulmonary artery werealmost completely occluded by emboli of varyingage, and many well organized emboli were seen inthe smaller arteries of the right lung. The source ofthe emboli was not determined.

Case 2. A 200-lb 23-year-old female developedthrombophlebitis in both legs on Nov. 29, 1964, 6days postpartum. Her usual cigarette cough was accentuated from a recent "cold" but there was no

chest pain and the lungs were clear. On Dec. 1, subcutaneous administration of 5,000 units of heparinfour times a day was begun. This was increased to7,500 units on Dec. 3 and to 10,000 units on Dec.8 because of inadequate prolongation of clottingtimes. On Dec. 9 left chest pain, increased coughand tachycardia developed. There was a questionableleft parasternal rub, and the pulmonic second soundwas accented. The electrocardiogram was consistentwith acute cor pulmonale. Her condition improved

the following day but on Dec. 11 she felt faint andnauseated and had more chest pain. The SCOT andLDH were 12 and 400 units, respectively. A lungscan was consistent with multiple emboli to bothlungs. She expired suddenly 3 hr later while beingevaluated for possible embolectomy. At autopsy alarge antemortem embolus was found at the bifurcation of the main pulmonary artery. Nearly all thelarge- and medium-sized pulmonary arteries contained both adherent and nonadherent emboli. Onlysmall areas of the right middle and upper lobe andthe left apex contained crÃ©pitantlung. A 9-cm organized clot was present in the left iliac vein.

Case 3. A 48-year-old male developed suddenonset of severe crushing chest pain, diaphoresis andhemoptysis on Aug. 2, 1965. He had a past historyof pulmonary embolism and had been treated 1month earlier for a pneumonitis although a diagnosisof embolism had also been entertained. A lung scanshowed marked ischemia of the right lung and the

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FIG. 2. Single anterior scan indicates that perfusion is limited At autopsy all major vessels except those to right upper lobe posalmost totally to left upper lobe. Embolectomy was performed fol- teriorly and to left upper lobe were occluded with fresh and or-lowing scan, and large embolus was removed from right main ganizing emboli (shaded areas). Resolving infarcts were present inpulmonary artery. No other significant emboli could be removed. ischemie regions (lined areas).

Volume 10, Number 1 29



POE, DORE, SWANSON AND TAPLIN

10-19-65 10-19-65 10-27-65

FIG. 3. A single anterior scan shows ischemia in regions ofleft apex, right middle lobe and right lower lobe laterally 8 daysbefore death. At autopsy occlusive, well-organized emboli (shaded

areas) were found in arteries to these regions. Infarcts were alsopresent (lined areas). Immediate cause of death was recent, massivesaddle embolus (dotted area).

left base. Embolectomy was immediately performedwith total cardiopulmonary bypass, and a large em-bolus was removed from the right main pulmonaryartery. However, the patient could not maintain anormal blood pressure, and he expired. At autopsyonly the vessels to the right upper lobe posteriorlyand a few segments of the left upper lobe werepatent (Fig. 2). The others were occluded by freshand organizing emboli some of which were adherent.Areas of resolving infarction were also found. Theetiology of the emboli was not ascertained.

Case 4. A 27-year-old motorcyclist was immobilizedon Sept. 8, 1965, for multiple fractures of the rightleg. On Sept. 27 he complained of substernal chestpain. His pulse was 140 and his respiration rate 28.The pain persisted during the following week, andhis temperature rose to 100.4Â°F. His white count

was 5,200, his SGOT 104 and his LDH 670 units.Incomplete right bundle branch block developed onOct. 4. The following day he became hypotensiveand had a respiratory rate of 44. Decreased breathsounds and a pleural friction rub were present inthe left lung. There was evidence of thrombophlebitisin the fractured leg. Atelectasis in the right midlungfield and possible pneumonitis in the right upperlobe and at the right base were found on chest x-ray.The lung scan disclosed complete ischemia of theleft lung and right lower lung. Intravenous heparinwas begun, and an emergency embolectomy with totalcardiopulmonary bypass was performed later thatday. The main pulmonary artery was clear but some"old clots" were milked from the right and left main

branches. The emboli were of varying ages, somecontaining lines of Zahn and proliferating endothelialcells. A vena cavai ligation was then performed.Hypoxia was encountered during the bypass proce

dure, and the patient never regained consciousness.He expired 4 days later. A massive firm adherentembolus was found distally in the left pulmonaryartery at autopsy.

Case 5. A 60-year-old man had a hemicolectomyfor diverticulitis on Sept. 26, 1965. Low-grade feverdeveloped in the postoperative period, but no sourceof infection could be discovered on re-explorationon Oct. 10. His temperature subsequently rose to102Â°F.A single anterior lung scan made on Oct. 19

originally was interpreted as normal but in retrospectdemonstrated several oligemic regions. An LDH onOct. 21 was 710 units, but the patient was not puton anticoagulants. Evidence of thrombophlebitis ofthe left leg was found on Oct. 25. He suddenly became acutely dyspneic and cyanotic on Oct. 27 anddied. The autopsy disclosed a massive saddle em-bolus. In addition, well-organized emboli which appeared to have been in position for a matter ofweeks were found in the branches of the arteries tothe left upper and right lower lobes correspondingto the poorly perfused areas seen on the earlier scan(Fig. 3). Thrombi were present in the left femoraland iliac veins.

Case 6. A 41-year-old white male with a historyof recurrent thrombophlebitis and intermittent chestpain and diaphoresis since 1963 entered the hospitalon Aug. 10, 1966, complaining of shortness of breathand pressure in the chest. The lungs and extremitieswere negative on admission but calf tenderness developed 6 days later. Anticoagulation with heparinand warfarin was begun. A scan on Aug. 14 wasconsistent with bilateral embolism and this was confirmed by angiography. In addition, both the electrocardiogram and the vectorcardiogram indicatedseptal infarction. He was discharged as improved on





Sept. 13 on warfarin with a prothrombin time twicenormal. On Oct. 3 he became dyspneic and collapsed. The prothrombin time on 2 mg of warfarindaily was 13.5 sec (11 sec control). Five thousandunits of IV heparin were given followed by 5,000units every 4 hr subcutaneously. The white countwas 9,900. On Oct. 4, 50,000 units of IV heparinin 1,000 cc 5% dextrose in water was administeredat 10 drops/min. Random clotting times were 13,34 and 23 min. On Oct. 5, a total of 36,000 units ofheparin was given, and the clotting times were 28, 42and l3l/2 min. A repeat scan the next day indicated

new emboli and a vena cavai plication was performed. The patient's condition deteriorated during

the procedure and an embolectomy on cardiopul-monary bypass followed. With the aid of lung compression "several large emboli" were removed but the

patient could not tolerate removal from bypass. Anangiogram demonstrated persistent vascular occlusions but further attempts to remove the emboli wereonly partially successful, and the patient expired.The autopsy disclosed recent and organized embolidistal to the main pulmonary artery occluding thevessels to the left upper lobe and lingula, the rightlower and middle lobes, and the branches to the rightupper lobe. A thrombus was found in the left iliacvein. In addition, the heart showed severe coronaryartery disease and a healed septal infarction.

Case 7. A 48-year-old white female had a chole-cystectomy in Aug. 1966. On Sept. 21 she hadsudden onset of right flank pain aggravated by respiration. There was no cough or hemoptysis. Hertemperature was 100Â°F. Decreased breath sounds

and dullness were found at the right base but evidence of peripheral phlebitis was lacking. The white

count was 10,800 with 84% polymorphs. The urinal-ysis showed 4â€”6WBCs/high-power field. The chestx-ray was compatible with pneumonitis or infarctionat the right base, and this area was ischemie on thelung scan. Antibiotics were begun the following day,but on Sept. 23 her temperature rose to 101.8Â°F,

the pain worsened and the right lower lobe infiltrateincreased in size. The white count was 11,800. Adiagnosis of viral pneumonitis was favored over embolism, and no anticoagulation was given. Subsequently, her fever subsided and the white countdropped to 5,700 but the pleuritic pain increased asdid the amount of right pleural fluid. On Oct. 14 thepatient felt well and was afebrile, but she suddenlydeveloped acute respiratory distress, cyanosis andshock and expired without chest pain. At autopsyan antemortem saddle embolus was found whichalmost totally occluded both branches of the mainpulmonary artery. A small infarcÃ¬was found in theright lower lobe. The source of the emboli could notbe determined.

COMMENTS

The pertinent findings of the seven patients arelisted in Table 1. Although one patient had severecoronary artery disease, the primary cause of deathdetermined by autopsy was pulmonary embolism.Had embolization not intervened, all of the patientspresumably would have survived.

Pulmonary symptoms developed a minimum of8 days before death in all patients. Based on therecorded history and physical findings, pulmonaryembolism should have been a major considerationin the differential diagnosis in these patients. However, in two the diagnosis was not strongly consid-

Cose SexAge1

Mole302

Female233

Male484

Male275

Male606

Male417

Female 48TABLE

1.Clinical

diagnosisPneumonitisPostparlum

thrombophlebitisPneumonitisLeg

fracturePostoperative

infectionThrombophlebitis,

pulmonaryemboliPneumonitisSUMMARY

OFInterval

betweeninitialsymptoms

anddeath15

days13

days1

month8

days17

days2

months23

daysCASE

REPORTDATAInterval

betweenpositivescans and

surgery ordeath24

hr3

hr1

hr6

hr8

hr2

months23

daysAutopsy

findingsFresh

and organizing emboli in largeand small pulmonaryarteries.Saddle

embolus. Adherent and non-

adherent emboli in large andmedium sizedvessels.Fresh

and organizing emboli Insegmental vessels. Resolvinginfarcts.Fresh

and resolving emboli in largearteries.Massive

saddle embolus with wellorganized segmentaiemboli.Recent

and organized emboli inlobar and segmentalvessels.Massive

saddle embolus with oldpulmonary infarction.




POE, DORE, SWANSON AND TAPLIN

ered until the patients developed thrombophlebitisor failed to respond to therapy for thrombophlebitis.Three were treated for some form of pneumonitis.Of the remaining two, the signs and symptoms in onewere attributed to a postoperative infection whilethe other had no diagnosis made until he developedmajor embolization. Four of the patients received noanticoagulation or only terminal heparinization. Theothers were receiving anticoagulants, but full therapeutic levels were not maintained.

The lung scans in all the patients were abnormalalthough one, based on a single anterior scan, wasinterpreted as normal initially. At autopsy, all thepatients had gross evidence of emboli, some of whichwere adherent. Since fixation to the intima requires aminimum of 4-5 days (9), lung scans would havebeen positive well in advance of massive embolization. In the three who did have scans performed 8days or more antemortem, one patient was correctlydiagnosed and treated for pulmonary embolism; inthe second, the ischemie area at the lung base wasattributed to pneumonitis rather than infarction; andin the third the scan was incorrectly interpreted asnormal.

In all seven autopsies, the sites of vascular occlusion correlated well with the ischemie areas seen onthe scans (Figs. 1-3). However, in three cases massive saddle embolization intervened between thetime of the scan and the patient's death (Cases 2, 5

and 7 ) and in another a partial lobular arterial occlusion became complete (Case 1).

In the past decade there has been a sharp rise inthe recognition of pulmonary-embolic disease bothclinically and pathologically. However, because ofthe great frequency with which the diagnosis still isnot made, no reliable morbidity or mortality statistics are available. In the last 4 years, we have scannedover 700 patients with suspected pulmonary embolism. Most were referred from medical serviceswith just a few from the surgical, orthopedic andobstetrical services. Of this number the seven fatalcases reported here represent the total known deathsin which pulmonary embolism was the primary andnot a contributory or incidental finding. None of thepatients had congestive heart failure or known malignant disease. Six were young, and all were potentially salvageable.

The three patients with a working diagnosis ofpneumonitis deserve special attention. While it iswell recognized that many findings in bacterial pneumonitis mimic those of pulmonary infarction, severalfeatures are found in these patients which shouldincrease the suspicion of embolism or infarction.These include the development of "pneumonitis" in

relatively young people without obvious predisposing

conditions; a history of recurrent unexplained pneumonias; little or no elevation of the white blood cellcount; poor response to antibiotic therapy; or historyof pulmonary embolism, thrombophlebitis or hemoptysis. Although lung scans may not help in differentiating the etiology of the ischemia in areas ofinfiltrate seen on a chest film, the presence of otherischemie areas in roentgenographically normal lungis characteristic of embolism because it has beenfound that emboli to the lungs are usually multiple

While the increased use of lung scanning combinedwith early anticoagulation will not eliminate the mortality from pulmonary embolism, it offers a reasonable alternative to the two less practical proceduresof routine prophylactic anticoagulation and emergency embolectomy. Anticoagulation of high-riskgroups, such as elderly patients with hip fractures, hasreduced or eliminated fatal pulmonary embolism(8). However, in the absence of specific indicationsthere has been a general reluctance on the part ofphysicians to use anticoagulant prophylaxis to prevent pulmonary embolism. This stems not only fromconcern over possible hemorrhagic complicationsbut also from a lack of awareness of the efficacy ofthis approach as well as from difficulties in patientselection. The availability and use of cardiopulmo-nary bypass on an emergency basis has stimulatedinterest in embolectomy, but surgical treatment, oncemassive embolism has occurred, presents even moreproblems with potentially little chance of success.A survey of cardiovascular surgeons who have attempted this procedure elicited a mortality rate of57% in 137 patients (70). In defense of theseapparently poor results, it is assumed that the mortality would have been 100% without surgery. Manyquestions remain to be resolved in evaluating emergency embolectomy, but the basic problem is thatpatients, who because of mechanical obstructioncould survive only with removal of the embolus,rarely survive long enough to institute even partialcardiopulmonary bypass. In a study of 283 fatalcases of emboli proved at autopsy on the surgicalservice of the Massachusetts General Hospital, Donaldson estimated that only one out of five patientssurvived long enough to institute a surgical procedure(77). In those who survive massive embolism formore than several hours but remain in critical condition, the data are still too few to indicate that embolectomy is to be preferred over intensive medicalsupport.

The rationale behind prevention of fatal pulmonary embolization rests as much on adequate therapyas it does on the diagnosis of warning or "signal"

emboli. A review of the anticoagulant program inthe three patients in this series who received therapy





24 hr or more before death as well as others whodid not suffer fatal complications demonstrates agenerally ineffectual use of these agents. Heparinwas usually given by the deep subcutaneous routein doses rarely exceeding 30,000-40,000 units/day.Although the clotting times would sometimes be wellin the therapeutic range, adequate anticoagulationwas not maintained continuously. Therefore, theeffectiveness of treatment was reduced or lost. Intermittent intravenous heparin given in doses of 10,000or more units every 4 hr for at least the first 24-48hr following the first signs of embolism with clottingtimes maintained at least two times the standard normal at all times is now the recommended therapeuticprogram. A detailed review of the rationale of heparintherapy in thromboembolism has recently been published and need not be reviewed further here (12).

Expansion of nuclear-medicine programs in mostmajor hospitals and many smaller hospitals meansthat the scanning equipment necessary for detectionof pulmonary emboli is now available to a large segment of the medical community. As pulmonaryemboli are diagnosed with greater frequency, it becomes apparent that the disease does not carry therelatively high mortality that has been attributed toit in the past. Nevertheless, pulmonary embolism hasbeen found to be the most common fatal pulmonarydisease seen at autopsy and ranks among the topthree nonfatal pulmonary diseases (13). The diseaseis an important one which can now be recognizedand in many cases treated successfully.

SUMMARY

In 700 patients with suspected pulmonary embolism, massive embolism was the primary cause ofdeath in seven. Of these seven, all had signs orsymptoms of emboli preceding the fatal episode by1 week or longer. At autopsy adherent emboli inmajor vessels or branches were present in six andcorrelated well with the areas of ischemia in thescan. Because lung scanning can detect ischemia produced by occlusion of vessels greater than a fewmillimeters in diameter and because adherence ofthe emboli to the intima indicates presence within thevessel for at least 4-5 days, the nonlethal embolieepisodes could have been detected in time to instituteprophylactic anticoagulation.

Lung scanning, by early confirmation of develop

ing pulmonary embolie disease, combined with adequate anticoagulation should materially reduce themortality from this disorder.

ACKNOWLEDGMENT

E. R. Jennings, Director of Laboratories at the MemorialHospital of Long Beach, granted permission to reproducethe autopsy diagrams. Radioisotopes were generously supplied by E. R. Squibb and Sons and Abbott Laboratories.The work was supported in part by Contract AT (04-1)GEN-12 between the U.S. Atomic Energy Commission andthe University of California at Los Angeles and a PickerFoundation Research Grant to the Memorial Hospital ofLong Beach, California.

REFERENCES

1. SAUTTER, R. D.: Massive pulmonary thromboembolism, experience with twelve pulmonary embolectomies.J. Am. Med. Assoc. 194:336, 1965.

2. BEALL, A. C., JR. AND COOLEY, D. A.: Currentstatus of embolectomy for acute massive pulmonary embolism. Am. J. Cordial. 16:828, 1965.

3. MILLIGAN, R. S., OLSEN, P. A., TOÃ“LE, G. J. ANDWOOD,N. E.: Surgical treatment of massive pulmonary embolism. Calli. Med. 104:204, 1966.

4. MARABU . S. A., WINEGARNER, F. G., MOORE, F. T.,OLIN, D. B. AND MOLNAR,W.: Pulmonary embolism andthe indications for embolectomy. Arch. Surg. 94:258, 1966.

5. PANETH, M.: Pulmonary embolectomy. 1. Thor. Cardiovascular Surg. 53:77, 1967.

6. MOSER, K. M., TISI, G. M., RHODES, P. G., LANDIS,G. A. ANDMÃ•ALE,A., JR.: Correlation of lung photoscanswith pulmonary angiography in pulmonary embolism. Am.J. Cardiol. 18:810, 1966.

7. POE, N. D., SWANSON,L. A., DORE, E. K., TAPLIN,G. V.: The course of pulmonary embolism. Am. Heart J.73:582, 1967.

8. THOMAS, D. P.: Treatment of pulmonary emboliedisease. New Engl. J. Med. 273:885, 1965.

9. FREIMAN, D. G.: Pathologic observations on experimental and human thromboembolism. In Pulmonary Embolie Disease, ed. by A. A. Sasahara and M. Stein, GruÃ±e& Stratton, New York, 1965, p. 81.

10. CROSS, F. S. AND MOWLEM, A.: A survey of thecurrent status of pulmonary embolectomy for massive pulmonary embolism. Circulation (Supplement) 35:1-86, 1967.

//. DONALDSON,G. A., WILLIAMS,C., SCANNELL,J. G.ANDSHAW, R. S.: A reappraisal of the application of theTrendelenburg operation to massive fatal embolism. NewEngl. J. Med. 268:171, 1963.

12. GUREWICH, V., THOMAS, D. P. AND STUART, R. K.:Some guidelines for heparin therapy of venous thromboem-bolic disease. /. Am. Med. Assoc. 199:116, 1967.

13. DEXTER, L. : Thromboemboli as a cause of corpulmonale. Bull. N.Y. Acad. Med. 41:981, 1965.




1969;10:28-33.J Nucl Med. Norman D. Poe, Earl K. Dore, Leonard A. Swanson and George V. Taplin Fatal Pulmonary Embolism

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