A CLINICAL STUDY OF PULMONARY EMBOLISM* AN ANALYSIS OF 146 FATAL CASES

HUGH ROBERTSON, M.s., M.D.

Corinna Borden Keen Fellow in Surgery, Jefferson Medical College

PHILADELPHIA,

F ATAL puImonary embohsm, Iike the termina1 convuIsions of uremia, is the tragic fina expIosion of a disease

process that has been smouIdering under- ground for a proIonged period. The popping eyes, the suffocation, the sudden death are a11 caused by the impaction of the emboIus in the puImonary artery and the formation of fresh thrombus about it. The formation of the cIot, its sIipping, its nonchaIant ascent through the femora1 and iIiac veins to the vena cava are a11 so devoid of symp- toms that no warning is given unIess attention is paid to the patient’s minor compIaints Such is the picture of puI- monary emboIism as it unfoIds when a Iarge number of these catastrophes is care- fuIIy analyzed and the pertinent detaiIs compared.

This paper wiI1 attempt to fit together the saIient points of 146 fata puImonary emboIisms. The records were taken from the Robert Packer HospitaI, Sayre, Penn- syIvania, the Jefferson HospitaI and the PhiIadeIphia Genera1 HospitaI, PhiIadeI- phia, PennsyIvania, and from question- naires sent to friends in wideIy distributed areas of the United States; it therefore represents an exceIIent cross section of the emboIism probIem in this country. An attempt was made to eIicit the foIIowing information :

I. The physica and nervous make-up of these unfortunate patients.

2. The earIy symptoms of the disorder.

PENNSYLVANIA

3. The story of the “crash.” 4. The rBIes pIayed by factors, such as

infection, operative or obstetric procedures, anesthesia, systemic disease, etc.

THE PATIENTS

It is surprising how painstakingIy the head, neck, chest, abdomen, peIvis, and extremities are described in cases of this type, and how often the patient is for- gotten. The patient may have been a gangIing negro Iaborer, a stodgy Lithu- anian scrub-woman or an excitabIe IittIe Jewish shopkeeper, but usuaIIy no record was made of such facts. The height and weight of the patient were in many in- stances added to the records by the pathoIogist. With the death of the patient and a Iapse of severa years, any facts not recorded on the history sheet are Iost forever.

Eighty-two of the patients were men and sixty-four were women. Sex apparentIy had no bearing on the disorder. In hospitaIs where there are active gynecoIogic and obstetrica services, the proportions of men to women were reversed.

The average age of the entire group was 44 years. One patient was I)$ another 89, and most of the group had passed their fortieth birthday.

Inasmuch as the height and weight of many patients were not recorded, it is impossibIe to give accurate averages, but so many of the group were described as

* Clinical Research Project sponsored by Corinna Borden Keen Research FelIowship, Jefferson Medical College.

3

4 American journal of Surgery Robertson-PuImonary EmboIism JULY, 1938

“obese ” that it can be definiteIy stated Sixty-five per cent of the group had sub- that puImonary emboIism is more prevaIent norma bIood pressure at some time during among the overweight than among the their convaIescence, whiIe 5 per cent Iean. were def?niteIy hypertensive. Hypotension

No race or group appeared to be immune was not of itseIf a necessary factor.

L

CHART I.

- 146 FATAL PULMONARY EMBOLISMS =

--TUE PATIENTS-

from the disorder, but the bIack man is apparentIy sIightIy Iess susceptibIe to emboIism than the white man. The Jew seems to be Iess frequentIy affected than other groups.

The nervous make-up of the patient was onIy rareIy mentioned in case reports, but in the group seen and examined personaIIy by the writer, an impressive number ex- hibited a stodgy and morose personaIity.

EARLY SYMPTOMS AND SIGNS

In spite of the fact that the chart may show convaIescence to be progressing spIendidIy, the patient does not fee1 at a11 spIendid. He is uneasy, but cannot teI1 why. He often has a sense of impending disaster and speaks to his reIatives or friends about it. These facts, however, are rareIy ex- pressed in writing on the chart; they are usuaIIy ferreted out of the famiIy or the attending nurses after the death of the patient.

UnexpIained moderate fever occurred during the convaIescence of twenty-seven patients (I 8 per cent).

OnIy eight of the 104 patients who were apparentIy free of frank infection showed pain or tenderness prior to the onset of chest symptoms. Three of these patients hd a pain in the operative site; five had pain in the femora1 region. However, the attend- ing nurses, when questioned cIoseIy, stated that many of the unfortunate individuaIs compIained of minor aches, pains, or “uneasy feeIings” of which neither the

= 146 FATAL PULMONARY EMBOLISMS =

EARLY SIGNS Sr SYMPTOMS

UnexpIained moderate fever : 18% FrankIy infected wounds : 16% Unexplained pain in operative site : 2% Unexplained pain in leg : 3%

\Definite phIebitis : 4% Symptoms and signs so mild that they

were not recorded : 45%

LATE SIGNS & SYMPTOMS

Gasped, fainted, became paIIid Died within one hour Chest pain, cyanosis, hemoptysis Lived severa hours or days

t 39%

61%

NEW SERIES VOL. XLI, No. I Robertson-PuImonary EmboIism American ~~~~~~~ of surgery 5

patient nor the nurse spoke to the attending physicians.

It wiII be seen, therefore, that the pro- droma1 symptoms of this disorder are insignificant and can onIy be discovered by patience and perseverence on the part of the attendant. It often happens that minor symptoms may have major significance.

THE CRASH

In marked contrast to the peacefu1 prodromata is the crashing cIimax of the disease. The patient prepares to Ieave the hospita1, but drops gasping to the Aoor. Most often the patient “faints.” Some have severe “chiIIs.” One patient in this series, who had been in the psychopathic ward and was not confined to bed at aI1, dropped dead of massive emboIism whiIe waIking in the hospita1 grounds.

The symptoms of the cIosing chapter depend upon the size, and hence upon the site of Iodgement, of the emboIus. If the emboIus is a massive one and compIeteIy bIocks the main branch of the puImonary artery, the bIood suppIy to both Iungs is shut off. The patient gasps, becomes paIIid, and dies aImost instantIy. Fifty-seven patients in this group (39 per cent) died in. this fashion. If the main branch is onIy partiaIIy bIocked, on the other hand, the patient becomes cyanotic instead of pallid, and faints; occasionaIIy a severe chiI1, accompanied by sharp chest pain and dyspnea, is the first symptom. The partia1 bIock graduaIIy becomes a compIete one because of the accumuIation of newIy formed thrombus about the emboIus. Such patients Iive for severa hours or days, and may even be rescued by the TrendeIenburg operation or may occasionaIIy recover with medica treatment. In this series, eighty- nine (61 per cent), died in this manner.

FACTORS IN EMBOLISM

Trauma was present in every instance, whether accidenta1, operative, puerpera1, septic, or psychic. In the so-caIIed “ medica ” putmonary emboIisms, over- work, starvation, proIonged iIIness and

worry furnished the duI1 and protracted torture which is more upsetting than actua1 physica injury.

Type of operation and postoperative treatment apparentIy had IittIe to do with the incidence of puImonary emboIism in this group. The fact that some of the oper- ative procedures were proIonged and diffl- cuIt is countered by the fact that other patients simiIarIy treated did not deveIop emboIism. The author beIieves that the reputation acquired by certain operative procedures, such as prostatectomy, of readiIy giving rise to emboIism is due to the type of patient rather than to the operation itself. In other words, the oId man with a Iarge prostate may deveIop puImonary emboIism just as truIy after having fractured his cIavicIe or whiIe Iaid up with rheumatism. Ovarian cystec- tomy aIso has a reputation as a preIude to embolism, but the usua1 type of patient with this pathoIogy is often an extremeIy frayed-out oId Iady who might as easily deveIop emboIism after having sIipped upon the ice and fractured her hip.

In the present series, 128 patients (87 per cent), had been III in bed for a week before emboIism deveIoped, but in tweIve instances death struck in Iess than a week. Three patients died within two days after operation. Two instances were found in which the patients had not been confined continuousIy in bed.

The type of anesthesia used in the oper- ative group varied according to the prev- aIence of the anesthesia in use in the hospita1 in which the patient was treated. AbdominaI operations furnished more puI- monary emboIi than chest surgery, but more abdomina1 then chest surgery is done in the hospitaIs used in this study.

Frank infection played a rBIe in onIy twenty-two cases (15.7 per cent), and mostIy in the younger patients. TypicaI of these infective cases were fata emboIisms in chiIdren with peritonitis. Infection cer- tainIy is a definite factor in phIebitis, but phIebitis with perivascuIar infiItration and induration is quite a different pathoIogic

6 American Journal of Surgery Robertson-PuImonary EmboIism JULY, 1938

picture from the “ siIent ” thrombosis portant in the TrendeIenburg operation giving rise to emboIi_sm. OnIy six (4 per because it furnishes a passageway for the cent) of the entire group had cIinica1 introduction of the sound carrying the

FIG. I. The puImonary artery. MouIage cast made from &a1 sections of a normal cadaver. At this angle the right branch does not show its true size, which is about one-third Iarger in diameter than the Ieft branch. Notice how quickIy the main branches break up into very much smaIIer

FIG. 2. Showing the posterior curve of the Ieft branch of the pulmonary artery. The cast in this view (from the Ieft) shows the true position of the pulmonary artery in the erect human body.

twigs.

phlebitis; typica of these patients were those with diabetic gangrene, two of whom deveIoped massive puImonary emboIism after amputation.

rubber tube which acts as retractor and tourniquet.

ANATOMY OF THE PULMONARY ARTERY

The puImonary artery is a much Iarger vesse1 and Iies much nearer the sternum than one wouId suppose. It is equa1 in diameter to the aorta. The conus arteriosus Iies immediateIy beneath the sternum at the third rib; the puImonary vaIve is mid- way between the second and third ribs. The puImonary artery Iies upon the aorta in its first portion, but graduaIIy roIIs off it to the left, so that at its bifurcation the right branch can pass through the aortic arch. On either side of the conus arteriosus Iie the right and Ieft atria, the right being the more prominent anteriorIy. The peri- cardium is firmIy attached to the puI- monary artery at its bifurcation and to the aorta where that vesse1 arches posteriorIy. Behind these two great vesseIs Iies the transverse sinus of the pericardium, im-

From wax casts, made from norma cadavers, the posterior sweep of the Ieft branch of the puImonary artery and the transverse course of the right branch through the aortic arch and behind the superior vena cava may be easily seen. The right branch, carrying bIood to the three Iobes of the right Iung, is about one- third Iarger in diameter than the Ieft branch. As soon as the main branches reach their respective Iungs, they immediateIy spread out in a11 directions; the diameter of the vesseIs rapidIy diminishes as the periphery is reached. There is quite free anastomosis between the fine termina1 twigs of each IobuIe but none between adjacent IobuIes.

The puImonary artery is suppIied with sympathetic and parasympathetic fibers from the cardiac pIexus.

PHYSIOLOGY OF THROMBOSIS AND EMBOLISM

The formation of cIots both in and out- side the bIood vesseIs has been repeatedIy

NE w SERSBS VOL. XLI, No. I Robertson-Pulmonary Embohm American ~~~~~~~ or surgery

FIG. 3. The great vessels of the chest shown in their reIation to the trachea and the right atrium. The nail was driven through the second left interspace close to the sternum; its head indicates the reIation of the vesseIs to the anterior chest wall.

FIG. 4. The relations of the structures passing beneath the arch of the aorta. Notice the areolar space which permits expansion of the vessels without impingement of neighboring structures.

FIG. 5. CephaIic view, showing the reIations of the right branch to the arch of the aorta and the bifurcation of the trachea. The mode1 was turned sIightIy to the Ieft so as to show the bifurcation of the trachea. This alters the true anteroposterior appearance.

FIG. 6. The right branch of the pulmonary artery shown in reIation to the aorta and the bifurcation of the trachea.

8 American Journal of Surgery Robertson-PuImonary EmboIism JULY. 1938

observed. (It is very diff&uIt to produce 3. Increase in Iipoid content. aseptic thrombosis in animaIs.) The jeIIing 4. Increased CO2 combining power of normal bIood in a test tube is quite a (acidosis).

-wE BACTEPI~L SECRET\• NS ARE E~IOLOG~C FACTORS.

THE BACTERrA THEMSELVES MAY OR MAY No’l- 6E FOUND.

CHART II.

different process from the formation of the firm, sticky cIot that cIoses a Iacerated or infected vesse1 where endotheIium and ceI1 secretions play their parts.

In spite of the muItipIicity of theories concerning coaguIation in vitro, a11 of which presuppose phenomena which expIain but cannot as yet be proved, onIy three factors are invoIved in the process: the bIood cells, the Auid in which the ceIIs are suspended, and the endothehum in contact with the bIood stream. In the norma state, the bIood cells are borne freeIy, in a compIex suspending medium aIong an endothelium surface. CoaguIation within a vessel (thrombosis) may be experimentaIIy pro- duced by aItering the norma status of any one of the three factors, the ceIIs, the Auid, or the endothelium. Trauma, either physica or psychic, affects a11 three of these factors, but not equaIIy in different animaIs. These changes are apparently provoked by fright, Ioss of body fluid, and the absorption of cataboIic tissue products.

Chemical Changes in the Plasma: I. Decrease in aIbumin content. 2. Increase in gIobuIin content.

5. Increase in calcium content. 6. Increase in fibrinogen content. Changes in Cell Constituents: I. Increase of pIateIets. 2. Increase of Ieucocytes. 3. Decrease of red ceIIs. Cbanges in Blood Phenomena: I. Marked acceIeration of sedimentation

rate of red ceIIs. 2. Increased aggIutination and clumping

of pIateIets. 3. InstabiIity of electric charge of eIec-

troIytic eIements of blood coIIoids. 4. Increased bIood viscosity. 5. Shortening of bleeding and coagu-

Iation time. Changes in the bIood structure, in the

reticula-endotheIia1 system, or in the bIood- vessel waIIs, have a definite deterrent or acceIerative influence upon intravascuIar cIotting. That an increase in the coag- uIabiIity of bIood plasma may occur in previousIy heaIthy persons, causing wide- spread thrombotic Iesions with none of the usua1 provocative factors, such as disease, trauma or operation, was announced by Brown and Nygaard’ in 1935. This con-

NEW SEFUES VOL. XLI, No. I Robertson-PuImonary EmboIism American ~~~~~~~ of surgery g

dition is undoubtedIy reIated to the so- Gibbon,’ and others, who found that com- caIIed “effort thrombosis” of Loehr,2 pIete obstruction caused death, but that described in 1929. Rosenow’s theory that partia1 obstruction caused few symptoms.

CHART III.

a11 thrombosis and emboIism resuIt from bacteria1 infection has as yet not been accepted, but recentIy Genou4 (Ig35), has described a form of aseptic thrombosis which begins with bacteremia and ends with an aseptic cIot.

WhiIe it is heId by some pathoIogists that the symptoms of puImonary emboIism are often due to progressive thrombosis in the puImonary artery and that fata symp- toms arise when and if occIusion becomes absoIute, this does not appear IikeIy for these reasons :

I. PracticaIIy a11 puImonary emboIi ex- hibit a coiIed appearance which couId onIy be produced by churning about in the heart and being thrown forcibIy into the puI- monary artery.

2. At Sayre, in 193 I, RonaId HamiIton and the author produced artificia1 emboIi in dogs by injecting a mixture of ferric chIoride and bismuth into the femora1 vein, thereby producing a11 cIassic symptoms of massive puImonary emboIism, incIuding the eIectrocardiographic findings described by PauI D. White.5

3. The effect of obstructing the puI- monary artery by graduated externa1 compression has been repeatedIy studied by Ha11 and Ettinger,‘j ChurchiII and

It wouId be diffIcuIt to expIain the pro- gressiveIy severe symptoms of the patient with an incompIete bIock of the puImonary artery on the basis of puImonary throm- bosis aIone. Moreover, in nearIy every case of fata puImonary emboIism, the source of the emboIus can be found if enough patience is exerted in the search. PuI- monary thrombosis without emboIism is possible, but uncommon.

One of the popuIar misconceptions of puImonary emboIism is that the emboIus originates in a phIebitic area. This is not aIways true. PhIebitis may exist without thrombosis, and when the two coexist, the cIot is usuaIIy so adherent to the inflamed vesse1 waI1 that it cannot be jarred Ioose. In onIy a smaI1 proportion of cases does thrombophlebitis resuIt in puImonary em- boIism; the adhesiveness of the cIot is the determining factor. Once the Iarge cIot begins to craw1 instead of becoming canal- ized, the fate of the patient is seaIed. The resuIting emboIus has not occurred because the intern had the patient waIk too soon or because the nurse permitted the patient to go to the bathroom.

It is definiteIy estabIished that veins are contractiIe by sympathetic stimuIation just as are the arteries. Gotz,8 in 1864,

IO American Journal of Surgery Robertson-PuImonary EmboIism JULY, 1938

found that he couId cause the abdominal veins of the frog to diIate markedIy by tapping the intestines with the handIe of a scaIpe1. More recentIy, BayIissg was abIe to cause simiIar venous diIatation in animaIs by destroying their sympathetic suppIy. The Iate beIoved John B. Deaver recognized this fact and spoke repeatedIy of the gentIeness with which one shouId work in the vicinity of the Iarge abdominal pIexuses which he termed “the abdomina1 brain.”

Just as IocaI trauma to the sympathetic fibers can cause IocaI venous diIatation, so aIso can the depressor fibers of the para- sympathetic cause venous diIatation if the Aoor of the fourth be depressed. Such parasympathetic stimuIation may aIso be achieved with acetyIchoIine, or the vaso- motor center .may be stimuIated with epinephrine. CeII chemistry is, therefore, a definite factor in vascular tone, and there is a definite reIation between ceI1 chemistry, metabolism and the endocrine system. RecentIy the maIe sex hormone (andro- sterone) has been prepared syntheticaIIy from stero1, a component of many foods, as has aIso the femaIe hormone(progesterone). WohIbachlO decIares that vitamin ~1 is directIy concerned in the physioIogy of the nervous system and that vitamin c deficiency affects mesenchyma1 tissues, particuIarIy the formation and maintenance of interceIIuIar materiaIs. The menopausa1 vasodiIatation is another exampIe of endo- crine contro1 of vascuIar tone. Marine’l proved the iodine-thyroid reIationship many years ago. Camp and Higgins12 demonstrated that potassium is capabIe of exerting a11 the effects of epinephrine. Iron metabolism is definiteIy influenced by the spleen, according to Wright,13 and the spIeen is in turn inffuenced by the auto- nomic system. CaIcium metaboIism is controIIed by the parathyroids.

This series of delicate controIs and baI- antes can be compared to a carefuIIy baI- anced Ay-whee1 of a turbine. The spokes of the whee1 are the endocrine gIands, the rim is the autonomic system binding together the spokes; the hub is ceI1 metab-

oIism. The power to turn the wheel is furnished by assimiIabIe food and water, acted upon by enzymes, under the contro1 of hormones and vitamins. Let us imagine two such wheeIs, one niceIy balanced, the other out of baIance, and subject them to equa1 strain by rotation at a high speed. One wiI1 spin harmIessIy, the other wiI1 crack and ffy apart when its Iimit of toIer- ante is reached.

MoraIe is the sum of a person’s physica condition pIus his personaIity. It is the smooth hum of his fly-whee1 or its discord- ant vibration. It is the most apparent index of a patient’s progress towards recovery. AI1 known factors favoring throm- bosis are furthered when a patient becomes depressed. When a patient’s disposition and moraIe go into a sIump, something is wrong, even though his chart is “normaI.”

THE DIAGNOSIS OF THROMBOSIS

Except in rare instances (4 per cent in this series of 146 fata puImonary emboIisms), thrombosis occurs without phIebitis; the usua1 symptoms of redness, edema and tenderness that characterize phIebitis are therefore of IittIe vaIue in diagnosing thrombosis, aIthough Owarel* has found a characteristic tenderness in the soIe of the foot accompanying thrombosis of the foot or leg. When thrombosis deveIops in the Iarge veins of the abdomen or the smaI1 veins of the uterus or prostate, there are few or no symptoms of the thrombosis per se, but transient miId genera1 symptoms of thrombosis (or of the pathoIogic compIex giving rise to the thrombosis), do occur. This author, aI- though he repeatedIy missed such symp- toms at the time, has discovered Iater to his consternation that they had actuaIIy been present. From persona1 observation, it has become evident that restIessness, vague maIaise, indefinite discomfort in the Iegs or abdomen, and a psychic sIump have preceded emboIism by severa hours or days. Such symptoms in the convaIescence of an obese or eIderIy patient must be regarded seriousIy, and shouId never be

NEW SERIES VOL. XLI, No. I Robertson-PuImonary EmboIism American ~~~~~~~ of surgery I I

dismissed with the prescription of five gr. of 2. Platelet Count (Rees-Ecker Metbod). aspirin or a sedative.

At first thought it wouId appear that be- Method: Moisten a red ceI1 pipette with

cause of the very definite changes which diIuting fluid. Make a freeIy bIeeding

occur in the bIood after operation, earIy puncture wound; avoid squeezing the

thrombosis couId be discovered with the aid tissues. Draw the bIood to the 0.5

of the laboratory. The contrary, however, is mark. FiII to the IOI mark with

unfortunateIy true, for the simpIer Iabora- diIuting A uid. Count as you wouId the

tory tests have IittIe practica1 significance red ceIIs.

and the more significant tests are so com- Dilutingfluid:

pIicated that the ordinary hospita1 Iabora- Sodium citrate.. . . . . . .3.8 gm.

tory wouId be physicaIIy and financiaIIy FormaIin. . . . . . .0.2 C.C.

unabIe to do repeated determinations on a11 Brilliant cresyI bIue . . . . o. I cc. DistiIIed water, to make. . 100.0 C.C.

convaIescent patients. It is evident that the thrombophiIe must be picked out Significance: PIateIets appear among

cIinicaIIy, checked with Iaboratory aid, and the red ceIIs as sharpIy outIined

treated expectantIy. round, ova1 or eIongated gIobuIes of

Of the muItitude of tests designed to aid unstained hyaIine. Norma1 count:

in the diagnosis of thrombosis onIy three 250,000 to 350,000. PIateIets are

are practica1 enough for use in the average increased after operation in propor-

hospita1. These wiI1 be discussed brieff y : tion to the severity of the operation. If the pIateIet count faIIs beIow

I. Blood Coagulation Time (Lee-White norma Iimits and continues Iow, a Method). thrombus may be deveIoping in some

Method: Use a cIean 5 C.C. syringe; rinse, part of the circuIation.

HI, and empty with norma saIine Comment: PIateIet counts are notabIy

solution so that the barre1 is sur- unreIiabIe due to technica diffrcuIties.

rounded with the isotonic soIution. Done by the same person, however, a

QuickIy withdraw 5 C.C. of bIood series of counts may be vaIuabIe in

from a vein and empty I C.C. into each showing a trend in the number of

of three smaI1 (8 mm.), tubes which circuIating pIateIets; individua1

have been cIeaned with bichromate counts mean IittIe.

cIeaning soIution and rinsed in dis- tiIIed water. Rotate the tubes end- 3. Sedimentation Rate of Erytbrocytes.

wise each 30 seconds unti1 the bIood Method: The bIood sampIe shouId be coIumn retains its shape on inversion. taken without the aid of a tourniquet Record this time in minutes. if possibIe; since venous hyperemia is

Significance: Norma1 bIood cIots in from beIieved to change the isoeIectric 5 to 8 minutes. After operation cIot- point of the bIood coIIoids. The needIe ting time is shortened unti1 the fourth is removed from the syringe and the day. Shortening beyond the four-day bIood is expeIIed into a test tube, the period or at any time during convaIes- waIIs of which have been moistened cence is suggestive of thrombosis. with a saturated soIution of sodium

Comment: This is the simpIest and most citrate. The bIood is mixed thor-

practica1 of the tests. Time required: oughIy with the sodium citrate by ten minutes. When carefuIIy done, inverting the tube severa times with- the resuIts paraIIe1 those of the more out shaking. The bIood is then drawn compIicated but possibIy more ac- into a sedimentation tube to a mark curate “pIasma cIotting index” of and the dispIacement of the pIasma Quick.s6 coIumn read in one hour.

I2 American Journal of Surgery Robertson-Pulmonary EmboIism JULY, 1938

SignQicance: The normal settIing of the red ceIIs is 15 mm. in one hour. The rate is increased during the first few days after operation (young patients: &IO days; aduIts: 3-4 days; oId patients : 10-20 days). AcceIerated sedimentation at other times during convaIescence shouId be regarded with apprehension.

Comment: Time required: one hour. An increased settIing of the red ceIIs is the most constant finding in thrombo- sis; a sedimentation reading shouId be promptIy made and repeated daiIy whenever thrombosis is suspected.

THE TREATMENT OF THROMBOSIS

Once massive thrombosis has set in IittIe can be done, for emboIism in minor or major form then becomes a certainty. The question of increasing or decreasing the patient’s activity is a toss-up and the entire outIook is a gIoomy one. If, however, the thrombophiIe can be recognized earIy, certain vaIuabIe procedures may be insti- tuted which wiI1 make further thrombosis unIikeIy and permit the minor thrombosis to subside.

After KugeImass15 suggestion, a Ioiv-fat, low-protein diet is given to decrease the cIotting factors of the bIood. The intra- venous injection of I0 c.c. of I0 per cent sodium thiosuIphate soIution each day for three days, foIIowed by other series of injections at three-day intervaIs, wiI1 decrease the prothrombin and have IittIe influence on the fibrinogen (Bancroft and StanIey-Brown16).

Heparin (anti-prothrombin), obtained from the Iiver and other organs, was first suggested as an anti-coagulant by HoweII33 in 1925. It is water-soIubIe, non-toxic, thermostabIe, and gives no protein reac- tions when injected into the bIood stream. When added to a soIution of thrombin, ac- cording to Wright, l3 or incubated with it for many hours, heparin does not interfere with the coaguIating effect of thrombin on fibrinogen; it is therefore not a direct antithrombin. Howe11 suggests that he-

parin combines or reacts with prothrombin to prevent its transformation to thrombin. Heparin and cephaIin (thrombokinase, tissue-extract), neutraIize one another, so that a heparin-cephaIin baIance apparentIy governs thrombin formation. RecentIy Best, CharIes, and Cowan34 have reported beneficia1 cIinica1 resuIts in thrombosis through the use of heparin prepared by themseIves at the University of Toronto. It is therefore possibIe, with cIinica1 evi- dence of thrombosis, to cut down new intra- vascuIar cIotting (at Ieast temporariIy), by the injection of a harmIess substance.

The use of the more active anti-co- aguIants in post-operative thrombosis is fraught with danger, for their effect is transitory and Iysis of the thrombus might cause the cIot to Iose its grip on the vesse1 waI1 with disastrous resuIts.

The patient must be encouraged to become interested in games or in Iight reading, his fluid intake must be increased, he shouId be out of bed if possibIe, and his minor compIaints ought to be carefuIIy re- corded and sympatheticaIIy treated. More important, further eIective surgery shouId be postponed or avoided.

THE RELATION OF SYMPTOMS

TO THE EXTENT

OF BLOCKAGE

The size of emboIic objects that can reach the puImonary artery is sometimes startIing. The Iargest emboIus seen by the author was equa1 in diameter to the thumb and more than twice as Iong; it measured I I .3 by 2.0 ems. It was firm, brittIe, brick- red in coIor and mottIed with purpIe; it cIearIy consisted of a vein cast foIded upon itseIf three times and was buried in a ge1 of recent currant-jeIIy cIot. In contrast to such an emboIus is the soft, fragiIe type that plugs the smaIIer branches or even the whoIe artery and must be removed piece- mea1; this type is the resuIt of muItipIe smaI1 emboIi pIus active puImonary throm- bosis. MicroscopicaIIy the emboIus is seen to consist of Iamina of fibrin buried in vascuIar dkbris.

NEW SERIES VOL. XLI, No. I Robertson-PuImonary EmboIism American ~~~~~~~ of surgery I 3

The emboIus may cause one or a11 four of A block of either branch prevents bIood the foIIowing types of puImonary artery from reaching the entire Iung suppIied by bIockage : that branch. BIood flow to the opposite

FIG. 7. Massive block of the main stem. Second- ary thrombosis has filled the entire arterial tree. Emdedde’d in the dkbris is a co&d cast of the femora1 vein.

I. BIock of the main item. 2. BIock of the right branch. 3. BIock of the Ieft branch. 4. Lobar bIock. Massive bIock of the main stem causes

immediate death. This is the embolie syncopale of Rochet. l7 No bIood can get to the Iungs, and cerebra1 anemia and death promptIy ensue. If the bIock be onIy partia1, the set of symptoms so abIy described by White5 as car pulmonale appears. There is coIlapse, syncope, and paIIor. The tremendous diIatation of the right heart causes marked precordia1 puIsa- tion. The reffux into the vena cava causes distention and puIsation of the juguIas veins. There is a gaIIop rhythm, with definite eIectrocardiographic signs (upright T wave with reIativeIy normaI P and QRS

waves in Iead IV), of a diIated, Iaboring right heart. X-ray shows the greatIy diIated right heart and aIso diIation of the puImonary artery.

FIG. 8. Complete block of the right branch with thrombosis of a11 terminal twigs.

Iung is greatIy increased, so much so, that symptoms of congestion often deveIop. As contrasted with massive bIock, intense cyanosis and dyspnea are seen instead of paIIor and syncope. Rochet describes this type of emboIism as embolie aspbyxique. Severe chest pain ushers in the symptoms. The right heart is moderateIy diIated and there is a partia1 reffux into the vena cava which may or may not cause distention and puIsation of the juguIar veins. If fresh thrombosis deveIops about the impacted emboIism, the entire puImonary tree may become bIocked, so that death becomes inevitabIe. There is no doubt but that incompIete branch bIocks have been foI- lowed by dissoIution of the emboIus and recovery.

Lobar bIock undoubtedIy accounts for many “post-operative pneumonias.” FoI- Iowing a sudden onset of chest pain, dyspnea, and cyanosis, the patient coughs up rusty sputum. There is very IittIe back pressure into the right heart; the pathoIogy as we11 as the symptoms are respiratory

14 American Journal of Surgery Robertson-PuImonary EmboIism JULY, 1938

rather than circuIatory. The adjacent DIFFERENTIAL DIAGNOSIS

Iobes become congested. The bIoodIess Iobe Atelectasis (from aspiration) gives rise may become airIess and coIIapse. There is to symptoms very similar to the minor

CHART IV.

6. 7 E!LECTWARDIC&APH 6 X-RAY I

CHART v.

no crisis such as in a Iobar pneumonia; instead, the patient runs a proIonged course

forms of puImonary emboIism, but at-

and usuaIIy gets weI1. When such symp- eIectasis appears earIier after anesthesia than emboIism or infarction. Because the

toms foIIow a known thrombophIebitis or an unexpIained sIight fever, the diagnosis

Iesion of ateIectasis is usuaIIy centraIIy Iocated and in line with a main bronchus

shouId be apparent. it does not cause so much pIeuritic pain as

NEW SERIESVOL. XLI,No. I Robertson-PuImonary EmboIism American ~~~~~~~ of surgery I 3

infarction, whiIe irritation within the bronchus gives rise to more severe cough

Coronary occlusion causes termina1 symp- toms easiIy confused with those of puI-

and fever than does infarction. UsuaIIy monary embolism. The same etioIogic

-DZACtNO~lS’n

1. sE!VER??, C’HES’f P&N 2. C!~NOt!& 3. DYZ!PN 4. C!ONdES ION Or’ I;s4

OR PULM.EDT!MA

CHART VI.

g+gg CHART VII.

the ateIectatic area can be demonstrated by x-ray and confirmed by bronchoscopy.

Spontaneous pneumothorax shouId not be confused with emboIism because of the definite character of the breath sounds and the shifting of the mediastinum which ac- company pneumothorax. A bed-side x-ray of the chest shouId settIe a11 doubt.

factors are apparentIy invoIved; in fact, according to Matas’* and DeTakatslg there are times when the two Iesions occur simuItaneousIy. HamiIton31 suggests that a carefu1 review of the patient’s history may bring to Iight past events that would clarify the cIinica1 picture, such as angina1 attacks, dyspnea, exhaustion, or long-

16 A m&can Journal of Surgery Robertson-Pulmonary EmboIism JULY, 1938

standing auricuIar fibriIIation. Lead IV of ticuIar interest about this record are that the eIectrocardiographic tracing (with the it differs from the Iead IV tracing of the T’ right hand ejectrode appIied to the pre- or T3 types of coronary thrombosis ”

I -DIAGNOSlS- - L, 1 *PLEURldY * I

CHART VIII.

cordium between the sternum and the nippIe-Iine) “ wiI1 record an upright T-wave

FIG. Q. TypicaI pulmonary infarct.

with reIativeIy normaI P and QRS waves in acute COT pulmonale. The points of par-

(PauI D. Whites). Except in contempIation of the TrendeIenburg operation it is not necessary to differentiate the two disorders, and the treatment of one wouId in nowise detract from the proper treatment of the other.

THE SYMPTOMS OF PULMONARY

INFARCTION

From cIinica1 records, one wouId assume that puImonary infarction is a rare occur- rence; from autopsy records, however, puImonary infarction becomes a common occurrence. From clinica records, post- operative pleurisy appears to be rather frequent; in autopsy records, postoperative pIeurisy is rareIy found. There can be but one expIanation: the clinica diagnosis is missed.

The puImonary infarct is aIways of the hemorrhagic variety. With the bIockage of a termina1 twig of the puImonary artery, a cone-shaped area of Iung becomes avascu- Iar. There is quite free anastomosis between the termina1 twigs of the pulmonary artery; the anastomosing branches at once fiI1 the deprived area. But there is a Iimit to

NEW SERIES VOL. XLI, No. I Robertson-PuImonary EmboIism American ~~~~~~~ ,,fsurgery I 7

the amount of bIood the anastomosing branch can carry and the vaIient effort soon faiIs. CoaguIation and thrombosis foIIow.

Infarction has not the dramatic crash of the massive emboIus. The symptoms await the deveIopment of an irritative pIeurisy. MiIder forms of bIand infarction cause IittIe more distress than a “catch in the side” and possibIy a dry cough. Septic or maIig- nant infarcts, even though minute in size, cause progressive and even disastrous resuIts.

Upon examining the records of a very Iarge group of puImonary infarctions at the PhiIadeIphia Genera1 HospitaI, it was found that the average age of the patient was decidedIy Iower than in any of the emboiism groups. Also, it was evident that infection pIayed a very prominent rBIe. One striking feature was the Iarge number of bIand and steriIe infarctions that occurred in infectious diseases (here Genou’s4 theory of aseptic thrombosis is briIIiantIy ap- pIicabIe) ; yet onIy one in five of the in- farctions was diagnosed prior to necropsy. Because many bIand infarctions hea promptIy with few symptoms, one is Ied to beIieve that a great number of infarctions are constantIy occurring in the surgica1 and medica wards without being recognized. So frequentIy has the recorded cause of death after operation been upset by the pathoIo- gist in this Iarge series of emboIism and infarction, that one shouId eye with suspi- cion any cIinica1 diagnosis of puImonary edema, puImonary coIIapse, or myocarditis with faiIure of the right heart, unIess that diagnosis has been checked at autopsy. This is one more argument for routine outopsies.

TREATMENT

Oxygen shouId be administered as soon as any cyanosis is apparent and continued unti1 a11 hope has been abandoned, but since bIood can carry onIy a given amount of oxygen it is futiIe to attempt to push the oxygen indiscriminateIy when Iarge por- tions of the Iung are bIoodIess.

Papaverine, first suggested by PaIzO in Ig 14 as a vasodiIator, is at present the most advocated drug in the medica treatment of these catastrophes. It does not keep we11 in soIution, but the crystaIs dissoIve rapidIy in a 1.0 C.C. ampuIe of physioIogic saIt soIution. The usua1 dose is 30.0 mg. ($5 gr.). When papaverine is sIowIy in- jected intravenousIy it shortIy causes generaIized vasodilation, incIuding in its action a rather pronounced vasodiIation of the puImonary artery, permitting the emboIus to be partiaIIy disIodged and aIIowing a coIumn of bIood to be squeezed past the obstruction. A synthetic drug (eupaverine) has recentIy been made avaiI- abIe; it has the same pharmaceutica1 properties as papaverine, but is Iess toxic. SpasmaIgin is a proprietary preparation combining papaverine hydrochloride 2 I .o

mg. (s gr.), pantopon (an opium deriva- tive) 12.0 mg. (56 gr.), and atrina1 (a beIIadonna derivative) 1.0 mg. (x0 gr.) in a I. I C.C. ampuIe. However, it has the disadvantage of subcutaneous or intra- muscuIar use? whereas papaverine or eu- paverine may be injected intravenousIy. CoIIins32 reports the successfu1 use of spasmaIgin in nine of ten puimonary emboIisms. AIthough it is diffxcuIt to evaIuate resuIts when a proportion of pa- tients with puImonary emboIism recover without any treatment whatever, De Takatslg beIieves that Iives may be saved through the use of papaverine.

When the juguIar veins stand out promi- nentIy and puIsate, venous section wiI1 reIieve the right heart of some of its burden. It is a principIe of physics that after a certain pressure is reached, no more fluid can be pushed through an aperature even though dangerous additiona pressure is appIied. ChurchiII 21 has found the right heart and the puImonary artery nearIy coIIapsed proxima1 to a compIete puImonary bIock due to the pIaying out of the right ventricIe. In such cases it is possibIe that intravenous A uids, especiaIIy gIucose, might be of assistance if any bIood at a11 can be squeezed past the emboIus.

18 A m&can Journd of Surgery Robertson-Pulmonary EmboIism JULY, 1938

DigitaIis in fuI1, but not toxic, doses may heIp the Iaboring right heart.

Morphine, used unsparingIy, wiI1 combat excitement. Its effect upon the respiration shouId not prevent its use, for the diffIcuIty is with the circuIation, not with respiration. If respiration faiIs, the respirator might be of assistance, but bIoodIess Iungs can do IittIe even though respiration be continued.

When a11 eIse faiIs and the patient is comatose, an operative remova of the bIock shouId certainIy be attempted. The TrendeIenburg operation is a formidabIe task with tremendous odds against its success, but the patient and his famiIy expect courage in the surgeon at just such a crisis. It is the patient’s Iast chance.

PuImonary infarction offers a much rosier picture so far as treatment is con- cerned. Many infarctions hea entireIy with no treatment whatever, but in the others inteIIigent treatment must wait upon recognition. Strapping of the chest reIieves much of the pain and codeine reIieves the cough. AmytaI or one of the barbiturates insures rest. Heat has proven very soothing and can do no harm.

PREVENTION OF INFARCTION AND EMBOLISM

EvaIuation of prophyIactic measures directed against a disorder which ffuctuates in prevaIence as does pulmonary emboIism, is fraught with per& Von Beckz2 of KarIs- ruhe reported that during the years from IgIg to 1928, 27,730 operations were performed with onIy three fatal puImonary embolisms (0.01 per cent, or one embolic death in each 9,243 operations). The gen- era1 prevaIence of fata puImonary em- boIism in Europe and America in 2,Ig6,834 operations from 1913 to 1931 was 0.27 per cent23 (one emboIic death in each 500 operations). Von Beck used no routine prophyIaxis; if his patients had worn a red sock on one foot and a green one on the other, a wrong concIusion to a fortunate experience might have been reached. Says Matas 93 “It is obvious that any pro- phyIactic measures instituted in a routine fashion during a reIativeIy immune period

wouId be credited to whatever preventive treatments have been instituted, when in reaIity they pIayed no part in the immunity.”

Most measures advocated for the preven- tion of postoperative puImonary emboIism have for their basis a stimuIation of vascuIar flow by physiotherapy. Some of the suggested measures are bizarre: roIIers are instaIIed on the bed, and the patient is instructed to rub his feet and Iegs against them; rhythmicaIIy contracting air cushions are strapped to the patient’s Iegs; Ievers are constructed to raise and Iower the patient’s limbs. More practica1 and just as effective are Eugene PooI’s~~ exercises, suggested in 1913, which prevent stagnation in the Iarge veins and do much to encourage the con- vaIescent patient by giving him something that he himseIf can do to aid his recovery. Raising the foot of the bed for periods of an hour severa times daiIy aIso prevents pooIing of bIood in Iarge vesseIs, but most patients compIain of headache if the feet are eIevated for too Iong periods at a time.

The practice of keeping each patient in bed for a specified period after operation has become a custom as compIicated as the correct use of tabIe siIver. No puImonary emboIism has ever resuIted from getting a patient out of bed “too soon” aIthough interns and nurses have been repeatedIy made scapegoats in the scrambIe of at- tendants to escape responsibiIity after an emboIic death. The oId Iady with a frac- tured hip is not kept in bed for proIonged periods; why shouId the oId Iady with gaII- bIadder disease?

WeIch,26 in I 878, demonstrated concIu- siveIy that stagnation of the bIood stream was not of itseIf the cause of thrombosis; physiotherapy, therefore, shouId be aided and abetted by psychotherapy and voca- tiona1 therapy. CuIts exist because the doctor has been negIigent of the patient’s personaIity in his zea1 to cure organic disease. Nothing shouId be permitted to disturb or irritate the sick man. Deaths shouId never be permitted to occur in the wards. The noisy or very III patient should

NEW SERIES VOL. XLI, No. I Robertson-PuImonary EmboIism American JW~~I of surgery 19

be removed to a quiet room. Kindness, prostatic disease or the patient with chronic consideration and encouragement do much osteomyeIitis has been assigned the gloom- to hasten convaIescence. This is not new, iest and most disma1 corner avaiIabIe.

AFTEFZ EU$ENE U POOL , _JOUR. AM.MED. A%N., 60: \202,lPl3

FLEXION

KNEE EXTENDED

I ’ FLEYIOI; 6L FLE6”F’ON ROTATION OF

F \N~EQS WRISTS

I SIDE TO SIDE

CHART IX.

for in the thirteenth century Henri de MondeviIIe advised his students to “en- courage the patient with music of the sweet-stringed psaItery and with forged messages describing the death and con- fusion of his enemies, or his eIevation to a bishopric if he be a churchman.”

That the patient is fussy and diff%uIt to manage shouId not inffuence the courtesy of the attendants. The patient did not come to the hospita1 for pIeasant companion- ship; he Ieft his home, his business and his associates to submit to unpIeasant pro- cedures upon the advice of his physician. Once the physician accepts the care of a patient’s body he must aIso accept the patient’s disposition and personaIity, pIeas- ant or unpIeasant.

The patient must not be permitted to Iie in bed and worry. He must be encouraged to move about in bed and become inter- ested in things as soon as comfort permits. ChiIdren’s wards have been made bright and attractive, but the oId man with

KugeImann,16 MiIIs,26 and CIark2’ have a11 shown that a Iow-fat, Iow-protein diet is Ieast conducive to thrombotic changes; this type of diet shouId be instituted upon any sign of thrombosis or infarction or to suspected thrombophiles, rather than given routineIy to al1 patients after operation. BuI12* warns against fluid Ioss during or after operation; the Auid intake shouId be increased upon the appearance of any symptoms of discomfort however mild.

The routine administration of medicina1 substances to a11 patients after operation has been found futiIe by nearIy a11 investi- gators. TroeI12g and Boshamer30 have de- pIored the routine use of thyroid extract after operation. CertainIy thyroid extract shouId be given the hypothyroid patient as soon as he is admitted to the hospita1 and continued as soon after operation as possi- bIe. More basa1 metaboIic readings shouId be made on eIective surgica1 patients. The same principIes shouId appIy in the use of anticoaguIants such as hirudin, sodium

20 American Journal of Surgery Robertson-Pulmonary Embolism JULY, ,938

thiosulphate, sodium citrate, peptone, etc. evidence is accumulating which points to

It is not sound therapeutics to compel 500 some factor which upsets the sympathetic- patients to live on milk and cream because parasympathetic balance of the vascular

CHART x.

one of them is apt to develop a peptic ulcer; we must find some means of picking out the thrombophilic patient, and then treat him.

Accidents do not just happen; they are made. No short-cut or rule-of-thumb method of preventing infarction or em- bolism can avail. Each patient must be evaluated and treated individually. No elective operative procedure should be attempted unless the patient has been in the hospital for a sufficient length of time for careful study by the surgeon.

THE STIGMA

It may be concluded that, whereas fatal pulmonary embolism follows an operative procedure upon one patient and does not occur following a similar procedure by the same attendants upon another patient, the raison d’e”tre Iies in the patient and not in the operative procedure. One patient is possessed of a stigma, not present in the other patient, which tips the coagulation balance towards thrombosis. The nature of this stigma has never been determined, but

system through perverted hormone action, resulting in sedimentation of blood com- ponents normally held in suspension.

It has been shown that embolism is more common in young patients with infected wounds and in older patients with cardio- renal-vascular disease. Twenty years ago Alexis Carrel said of thrombosis and embolism : “Perhaps the blood, too, be- comes old.” Many complicated and in- genious theories since then have failed to come so near the apparent truth. If it be true that disease hastens senility, then we have an interesting explanation of the rela- tion of infection in the younger patients and of cardiovascular disease in the older patients to thrombosis and embolism. It is possible that the “wearing out” of the endocrine and hematopoietic systems brings the blood components to that state, not yet clearly defined, where abnorma1 clotting and embolism are apt to occur.

Be the cause what it may, clinicians are now picking out an occasional throm- bophiIe before embolism occurs. AIthough

NEW SERIES VOL. XLI. No. I Robertson-PuImonary EmboIism American Journal of Surgery 2 I

as yet no definite assurance can be offered 15. that emboIism and thrombosis can be prevented even though the stigmatized patient is discovered, the probIem is being 16. attacked in a more rationa manner than formerIy and eventua1 success is assured. 17.

Said gIoomy Bonaparte to Desaix at Marengo; “The battIe is Iost.” Desaix I** Iooked at his watch, found the hour was four o’cIock and said: “Sire, the battle is 19. Iost; but there is yet time to win another.” The other battIe was won.

2.

21.

I. BROWN, G. E., and NYGAARD, K. K. Essential thrombophiha. Proc. Staff Meet., Mayo Clin., IO:

1, 1935. 2.

3.

4.

5.

6.

LOEHR, W. So-caIIed traumatic thrombosis of the axihary and subcIavian veins. Deutscb. Ztscb. f. Cbir., 224: 263, 1929.

ROSENOW, E. C. A bacterioIogic study of puI- monary embolism. J. Infect. Dis., 40: 389, 1927.

GENOU, 0. The action of staphyIococcic secretions on the hematoblasts and their raIe in the pro- duction of postoperative thrombi. Ann. Inst. Pasteur, 54: 428, 1935.

WHITE, P. D. Acute car puImonaIe. Ann. Int. Med., 9: 115, 1935.

HALL, G. E. and ETTINGER, G. H. Experimental study of pulmonary emboIism. Can. M. A. J.,

28: 357, 1933. 7. CHURCHILL. E. D.. and GIBBON. J. H. Channes in

the circuIation produced by gradua1 occIus;on of the puImonary artery. J. Clin. Investigation, I I : 543. 1932.

GOTZ. Quoted by BayIiss. The Vasomotor System, 8.

9.

IO.

1923, page 142. BAYLISS, SIR W. M. The Vasomotor System, 1923,

page 70. WOHLBACH, S. B. The pathoIogic changes resulting

from vitamin deficiency. J. A. M. A., 108: 7,

1937. I I.

12.

‘3. ’ 4.

MARINE, D. ReIation of iodine to the structure of human thyroids. Arch. Int. Med., 4: 440, 1909.

CAMP and HIGGINS. J. Pbarmacol. 57: 376, 1936. WRIGHT, S. AppIied PhysioIogy, Ed. 5, 1935. OWARE, A. CIinicaI etioIogy of postoperative

thrombosis. Acta. cbir. Scandinau, 65: I I, 1929.

REFERENCES

22.

23.

24.

25.

26.

27.

28.

29.

30.

31.

32.

33.

34.

35.

KUGELMASS, I. N. EvaIuation of blood-cIotting factors in surgica1 diseases with special reference to thrombosis and embolism. Ann. Surg., go: 161,

1929. BANCROFT, F. W., and STANLEY-BROWN, M. Post-

operative thrombophIebitis and embolism. Surg., Gynec. FY Obst., 54: 898, 1932.

ROCHET, P. Postoperative pulmonary emboIism. Lyon cbir., 27: 64, 1930.

MATAS, R. Postoperative thrombosis and emboIism before and after Lister. Univ. Toronto Med. Bull., VOI. IO, 1932.

DETAKATS, G. The use of papaverine in acute arteria1 occlusion. J. A. M. A., 106: 1003, 1936.

PAL, J. The effect of papaverine on blood-vesseIs. Deutscb. med. Wcbnscbr., 40: 164, 1914.

CHURCHILL, E. D. Mechanism of death in pul- monary emboIism. Surg., Gynec. & Obst., 59: 5 I 3,

1934. VON BECK. (Htibner and Freundenberg.) Cbirurg,

3: 324, 1934. MATAS, R. Postoperative thrombosis and embolism

before and after Lister. Univ. Toronto Med. Bull., VOI. IO, 1932.

POOL, E. H. Systematic exercises in postoperative treatment. J. A. M. A., 60: 1202, 1913.

WELCH, W. H. Papers and Addresses. Baltimore, 1920. John Hopkins Press.

MILLS, C. A. Relation of protein diet to thrombosis. Ann. Surg., 91: 489, 1930.

CLARK, J. G. EtioIogy of postoperative femora1 thrombosis. Univ. Pennsylvania Med. Bull., 15:

154, 1902. BULL, P. 6000 post-mortem examinations in re-

spect to embolism. Acta cbir. Scandinav., 54: 315, 1921.

TROELL, A. Is thyroid hormone effective against emboiism? Zentralbl. f. Cbir., 58 : 2 I 32, 193 I.

BOSHAMER, K. Investigation on the origin and prophyIaxis of thrombosis. Deutscb. Ztscbr. f. Cbir., 22 I : 93, 1929.

HAMILTON, R. L. CardiovascuIar emergencies. In press.

COLLINS, D. J. PuImonary embolism. Am. J. Surg., 33: 210, 1936.

HOWELL, W. H. Pasteur Lecture. Proc. Inst. Med. Chicago, 1925.

BEST, C. H., CHARLES, A., and COWAN, C. Heparin, its preparation and use. Proc. Am. Pbysiol. Sot.,

1937. BANCROFT, F. W., STANLEY-BROWN, M., and

QUICK, A. L. Postoperative thrombosis and emboIism. Am. J. Surg., 28: 648, 1935.