Peritoneal adhesions

PERITONEAL

ADHESIONS*

STUDIES ON THEIR PREVENTION WITH SODIUM RICINOLEATE S. F. SEELEY, M.D.,

MAJOR,

M.C.

Office of Surgeon GeneraI, United States Army WASHINGTON,

T

HE

formation of intra-abdomina1 adhesions, an essentia1 process in the heahng of al1 structures covered by peritoneum, has engaged surgeons since the advent of abdominal surgery. OnIy when this formation has been excessive, wherein remnants of adult fibrous tissue remain in abnorma1 regions, can the formation of adhesions be considered unfavorabIe. Cases in which these remnants disturb the functiona1 efficiency of abdomina1 viscera are rather numerous and their prevention constitutes an important probIem in surgery. HertzIer’ emphasizes that “ heaIing by first intention. is exactIy paraIIe1 with the formation of adhesions. The formation of permanent adhesions is a condition not to be prevented but to be controIIed, one to be made to take pIace onIy where we need even under aseptic them.” UnfortunateIy, conditions, trauma of tissues remote from the site of operative apposition resuIts in the formation of adhesions which bind structures to the abdomina1 waI1 or to each other, causing interference with normal function. It is the prevention of these adhesions that has Ied surgeons to attempt to assist norma heaIing aIong controIIed lines. Many of these measures have been contrary to essentia1 principIes of heaIing. Others have been designed either to avoid the necessity of heaIing by care in preventing trauma, or to enhance heaIing by stimulation of the norma mechanism. The Iatter methods have been the most successful. To prevent adhesions is to prevent heaIing. To contro1 the extent of adhesions is the goal of every surgeon. Thus the problem has been approached with the thought abnorma1 apposition of of preventing *This

D.C.

structures. Definite principIes have been foIIowed to attain this goal, some have proved to be harmfu1, some have been harmIess, and a few have been beneficia1. As HertzIer’ states, “The idea of preventing adhesions has led to the introduction of anything that couId be bent, poured or powdered with the usua1 resuIt of making matters worse.” I have been abIe to compiIe the following methods employed to prevent adhesions : I. Avoidance of trauma to the peritoneum bv (1) CarefuI handIing of tissues (2) Use of rubber sheets, etc., to protect the peritoneum during operation (3) Use of rubber covered clamps to compress tissues Avoidance of necrosis of tissues (4) by tight Iigatures of foreign (5) Minima1 introduction materiaIs II. Operative covering of denuded areas bY

(1) OmentaI

grafts or interposition of intact omentum (3) PeritoneaI transplants (4) Eversion of peritonea1 margins into wounds in closure. (5) Inversion of peritoneum to cover stumps of ligated vesseIs, amputated viscera, Iines of anastomoses, etc. Mechanical separation of denuded areas by (I) Inflation of viscera: (A) Boric acid soIution in the bIadder

(2) Apposition

III.

article was submitted for pubhcation by the author previous to his undertaking Executive Offxcer of the Procurement and Assignment Service. 579

his present duties as

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SeeIey-PeritoneaI

(B) Enemas or gases in the Iarge bowe1 (2) Interposition of (A) Foreign soIid or semisoIid materiaIs: I, Cloth of catgut, fish bladder and calf 2, ox peritoperitoneum; neum (Cargile membrane) ; 3. oiIed siIk; 4, siIver foi1; 3, tin foi1; 6, goIdbeater skin; 7, IanoIin-boric acid paste; 8, agar-geIatin paste; 9, acacia mucilage; 10, acacia-gelatin paste; I I, CoIIodion; 12, aristol powder; 13, iodoform powder 03) Viscid foreign Iubricants : I, Vitreous of calf eye; 2, mucin; 3, olive oi1; 4, Iiquid petroIatum; 5, vaseIine oil (parafin); 6, yeIIow vaseIine; 7, human01 ; 8, omenta1 oil of ox; 9, camphorated 0iI; 10, IanoIin; 1 I, LanoIin and parafhn foreign IubriK> Nonviscid cants: I, SaIine solutions; 2. saline-adrenaIin soIutions; 3, gIucose soIutions; 4, magnesium suIfate soIution; 3, defibrinated bIood Gases: I, Air; 2, oxygen CD) Anticoagulants (to prevent co(3) aguIation of pIastic exudate) (A) Hirudin (B) Citrate soIutions (C) Ammonium oxoIate soIution Digestants (to remove pIastic (4) exudate) (A) Pus obtained by steriIe turpentine abscess of thigh (B) Pepsin-preg1 iodine soIution (C) Peptone gi ;f,,dp$n a am movement of (5) Postoperative structures (A) EarIy movement of patient in bed

Adhesions

JUNR,

194.2

Massage of abdomen Posture to eIiminate apposition of operated structures StimuIation of peristaIsis by, I, IocaI heat to abdomen; 2, drugs EarIy movement and exercise of patient out of bed IV. StimuIation of the peritonea1 defense mechanism (I) Amniotic fluid concentrate (2) Sodium ricinoleate The above Iist serves to confirm the statement of HertzIer,l and is eIaborate testimony to the inadequacy of any singIe measure to prevent unfavorabIe adhesions. Before discussing the resuIts obtained by the above measures it is we11 to review briefly the processes encountered in the formation of adhesions, processes synonymous with norma healing. The majority of the foIIowing is taken from Hertz1er.l Primary healing (under favorabIe conditions, without sepsis, disturbance of coaguIation, or the presence of foreign bodies or of digestive juices) : Upon the coaptation of peritonea1 surfaces there is an aImost immediate outpouring of a cIear, structureIess exudate which covers the surface. Within ten minutes fibrin is formed within this exudate. This process is compIeted within one hour and the exudate contracts. In three or four days this fibrinous materia1 begins to be converted without repIacement into fibrous tissue, this process being completed within six to eight days. Meanwhile Iarge macrophage ceIIs of the reticuIo-endotheIia1 system settIe out from the peritonea1 fluid onto the heaIing area, each ceI1 becoming ffattened and serving as an isIand of new endotheIia1 covering. This process resuIts in peritoneahzation of the denuded surface in seven to ten days. According to HertzIerl the peritoneum is we11 heaIed in four to seven days. This union affords a protective Iayer over the muscular and mucosa1 Iayers which require much Ionger to hea1. Delayed or secondary healing (under unfavorabIe conditions, such as hemorrhage,

NEW SERIES VOL. LVI. No. 3

Seeley-PeritoneaI

interposition of foreign bodies or devitaIized tissues, infection, presence of digestive juices and delay or prevention of the coagulation of bIood serum) : Under these conditions coaptation is hindered or prevented by the presence of foreign bodies or devitalized tissue, the formation of fibrin is prevented by factors uhich prevent coagulation, or fibrin is destroyed by the action of digestive juices. Hence the processes of primary healing are delayed and another process intervenes to promote healing. This consists of the development of a granuIar fibrin, not a fibrillar fibrin as in primary heaIing. This granular fibrin forms a protective coating to limit the spread of infection. It is later absorbed, then fibrous healing takes place. In overwhelming infections or the sudden estrnvasation of intestina1 contents into the peritoneal cavity, even this granular fibrin cannot form and a less effective attempt is made in the nature of a granular exudate which may aggIutinate structures, but which is incapable of forming the temporary adhesions of granuIar exudate in delayed healing. Agglutinated surfaces offer Iittle resistance to spreading infection. Granular fibrin, if successfu1, resists spread. FibrilIar fibrin then takes over the function of heaIing. From the above it is evident that certain physiologica processes are essential to healing of the peritoneum. First, an esudate must be thrown out which is capable of coaguIating, thus forming granular of fibrillar fibrin. Second, removal of granular fibrin must be accompIished in order that fibrillar heahng may take place. Opie’ has found that lytic enzymes are elaborated by polymorphonuclear Ieucocytes which remove this materia1 by digestion. Others have shown that these cells and the monocytes of the reticulo-endothelial system remove foreign material. Third, monocytes must be present which adhere to the surface of the healing area, then flatten to form new endothelium. No doubt there are other important factors, such as elements of bIood serum and peri-

Adhesions

American

Journal

ol’Surgcry

581

toneal fluid, immune substances of which little is understood. It is assumed by Steinberg3 and others that the ability, of the peritoneum to combat infection is a IocaI process, not a genera1 body immune response. Jones and McClure4 summarize a discussion of attempts to prevent adhesions as foIIows : “Complete soIution of the problem lies in perfecting our imitations of those methods by which nature accomplishes the prevention and ablation of adhesions.” We know that nature’s methods include the outpouring of an exudate of blood serum, the coagulation of this serum with subsequent production of granular or fibrillar fibrin, the digestion of librin by Iytic enzymes from poIymorphonuclear leucocytes, the regeneration of endothelium by monocytes, and the elaboration of certain substances to combat bacteria and toxins. An analysis of the methods employed to prevent adhesions shows that attempts have been made to assist nature’s processes as follows: (I) The covering of denuded areas with insoluble or slowly soluble materials to confine the area of healing; (2) the hastening of coagulation of blood serum (aristol powder) or the substitution of a coagulum (acacia-gelatin, agar-gelatin, collodion, etc.); (3) the separation of structures by lubrication with substitutes for exudate fluid (saline, glucose, dextrose, liquid petrolatum, etc.) ; f-1) assisting or hastening of the digestion of iibrin (,peptone, papain, trypsin), and (sj the loosening of temporary adhesions by early movement of structures (early exercise, stimulation of peristalsis, etc.). While there have been both favorable and unfavorable reports on the employment of these measgeneral conclusions ures, the folIowing seem to voice the verdict of the recent literature: Foreign

Solid

or

Semisolid

Materials.

These have been condemned by Hertzler’ as follows : “ Every conceivable foreign body has been employed in the peritoneai cavity, despite the fact that foreign bodies are the most certain means of provoking

582

American Journal of Surgery

SeeIey-PeritoneaI

adhesions. For most of them it may be said that they brought about the very thing they were introduced to prevent. The universa1 ruIe is, that what the peritoneum cannot absorb, it waIIs off or dies in the attempt.” Foreign Lubricants, Viscid. Some of these substances have been found to be too irritating whiIe most of them have faiIed to produce the desired resuIts. Liquid petroIatum was found by Norris and Davison” to be encapsuIated in muItipIe tumor-like masses many months after its introduction intraperitoneaIIy. Uncertain resuIts have been reported after the use of olive oil, vaseIine and camphorated oil. Foreign Lubricants, Nonviscid. These substances have served to iIIustrate the diff&uIty of retaining an isotonic or hypertonic soIution intraperitoneaIIy for a time sufficient to prevent adhesions between structures. AdrenaIin was added to saIine soIutions by Marve16 in an attempt to deIay absorption. Hypertonic soIutions have been found to remain for variable influenced by periods of time, somewhat the baIance of fluid between the body tissues, the bIood stream and the peritonea1 cavity. Indications are that hypertonic soIution are rapidIy rendered isotonic by osmosis and that the retention of an isotonic soIution within the peritonea1 cavity demands an excess of fluid within the body tissues and the blood stream if absorption is to be deIayed. Anticoagulants. HertzIer’ states, “ If the bIood of an animal is made incoaguIabIe by artificial means, such as by the use of leech extract of peptone, it prevents the formation of primary fibrin bundIes, and the wounds wiI1 not heal.” Pope’ and WaIker and Ferguson8 found that sodium citrate solutions intraperitonealIy were very effective in preventing adhesions, whiIe Straus,g Sweet, Chaney and WiIIson’O found them to be of no vaIue. Since the coagulation of exudate is necessary to the production of fibrin it is diffIcuIt to expIain good results on the basis of the prevention of coaguIation.

Adhesions

JUNE, ,942

Digestants. Th e use of digestants has been based on the findings of 0pie2 that poIymorphonucIear Ieucocytes elaborate Iytic enzymes which digest fibrin. The use of papain soIutions has met with pronounced success in the hands of Kubota,” Ochsner and his associates,12 WaIton13 and Yardumian and Cooper.14 It is we11 known that the escape of digestive materia1 from the stomach, pancreas or intestine prevents heaIing and frequently resuIts in peritonitis and death from inability of the organism to waII off infection. Johnson15 and his associates emphasize that the digestive action of papain and pepsin is dangerous in cases IikeIy to develop postoperative infection, in that these materiaIs destroy a first Iine of defense. Under aseptic conditions, however, papain soIutions have been shown to prevent 90.89 per cent of the recurrence of adhesions in experiments conducted by Ochsner and Garside. l6 Peritoneal Stimulants. WhiIe amniotic fIuid concentrate and sodium ricinoIeate are listed under this heading, it is recognized that any substance which causes an irritation to the peritoneum must be cIassed as a stimuIant. Pfeiffer and Issaeff” demonstrated in 1894 that the intraperitoneal injection of normaI broth, peptone or urine so aItered the IocaI defense of the peritoneum of guinea pigs that they could subsequentIy withstand doses of choIera vibrio that would otherwise be fata1. Morton’% found that IocaI peritonea1 immunity to hemoIytic streptococci couId be produced in rabbits by the injection of dextrose broth, I per cent sodium chIoride soIution and varying concentrations of glucose in water or in sahne. Hermann,lg Bargen,20 Judd and WaIdron,2l and Dixon and Bargen22 have shown that IocaI peritonea1 immunity is stimuIated by the injection of kiIIed suspensions of Escherichia coli and hemoIytic streptococci, and in more than 1,300 cases so stimuIated forty-eight hours prior to eIective resection of the coIon, mortaIity from peritonitis has been reduced 66 per cent. It is probabIe that much of the beneficia1 effect attributed to many of the

NEW SERIES VOL. L.VI. No. 3

SeeIey-PeritoneaI

solutions introduced intraperitoneally has been due to this peritoneal stimmation by nonspecific substances. SeeIey, Higgins and ?vlann2” demonstrated that even steriIe distilled water provoked an influx of 19.0 per cent polymorphonucIear neutrophils after six hours. Amniotic fluid concentrate, antiperitonitis vaccine (Bargen22) and 2.0 per cent sodium ricinoleate resulted in an influx of 36 per cent, 31 per cent, and 72 per cent, respectively, after three hours. The normal peritoneal fluid of the white rat does not contain polymorphonuclear neutrophils. This response in the peritoneum may be referred to as stimulation. It is important that the degree of stimulation be beIow the level of detrimental irritation. I have found that 1.0 +r cent sodium ricinoleate is well tolerated intraperitoneaIIy by rabbits, but that 2.0 per cent will occasionally result in death. Corwin2? reports the same experience. In monkeys I have tested sodium ricinoleate intraperitoneally in concentrations varying from 0.23 to 4.0 per cent and found it to be we11 torerated. White rats tolerated 2.0 per cent sodium ricinoleate \ ery weIl. Johnson’” reports that 1.0 per cent sodium ricinoIeate causes destruction of peritoneal endothehum in dogs. That I .o per cent sodium ricinoleate is well tolerated intraperitoneally in the human is attested to by the experience of Wangensteen2” and GrlIette.26 Wangensteen”j uses I .o per cent sodium ricinoIeate to cIeanse all mucous surfaces in gastric and intestinal anastomoses and employs 90 cc. of I .o per cent sodium ricinoIeate in a 70 kilogram man for peritonitis. GiIIette26 has used 1.0 per cent sodium ricinoleate intraperitoneally in over 300 cases of peritonitis, instilling 50 cc. at twelve-hour intervals. Ile believes it to be of definite value. Conflicting reports have appeared in the literature on the vaIue of amniotic fIuid concentrate in the prevention of adhesions. Johnson,2B Warren,“” TrusIe$O and Kimpton”’ report excehent results in the pre\.ention of adhesions experimentally and clinically. Rea and Wangensteen”’ found

Adhesions

American Journd or Surgrr,v

7-873

that it prevented adhesions in 70 per cent of rabbits in which the intestine had been traumatized and painted with tincture of iodine. They found that I .o per cent sodium ricinoleate prevented adhesions in 85 per cent of rabbits in a similar series. Lacey”” reported amniotic fluid was harmless when injected intraperitoneally, that it seemed to stimulate the peritoneum to a more powerfuI defense action, but that it couId not be depended upon to prevent adhesions. Gepfert”’ reported that after trauma to the bowe1 and stomach of dogs, repeated operations to separate adhesions resulted in the formation of fewer and less dense adhesions when amniotic Buid was used. EVALUATION

OF

RICINOLEATE

THE

EFFECTS

OF

SODIUM

INTRAPERITONEr\LLY

Sodium ricinoIeate is a soap, the sodium salt of ricinoleic acid. Larson”” and his associates have demonstrated that it has strong bactericida1, bacteriostatic and detoxifying properties, and that it is well toIerated intraperitoneally in experimenta animals. SeeIey, Higgins and Mann2:’ compared the effect of 2.0 per cent sodium ricinoleate, antiperitonitis vaccine ( BargenzO) and concentrated amniotic fluid when injected intraperitoneally into white rats. The total number of cells present in the peritoneal fluid and the amount of peritoneal fluid was determined at intervals with the following resuIts: (Table I ). CorwinZ4 reported similar results in rabbits when he compared the effect of intraperitoneal injection of I.0 per cent sodium ricinoleate and antiperitonitis vaccine. Rea”” reported excehent results following the use of three or four ounces of I per cent sodium ricinoleate intraperitoneahy in cases of gross or suspected contamination. In these studies it wiII be noted that sodium ricinoIeate was highly effective in provoking an increase of neutrophils and monocytes and was especially effective in provoking an increase in the amount of peritonea1 fluid which persisted for seven days in rats and for five days in rabbits. In

584

SeeIey-PeritoneaI

American JournaIof Surgery

a. study to determine the mechanism of this increase in peritonea1 fluid, Rider 37 found that sodium ricinoIeate behaved in soIution more Iike a crystaIIoid than a colloid, that it was readiIy diaIyzed and that it was incapabIe of producing an increase in its own voIume on a pureIy osmotic basis. He concIuded that the increase of ffuid within the peritonea1 cavity after the introduction of sodium ricinoleate was not due to pureIy physical effects but to some effect on secretory mechanisms.

Adhesions

JUNE. ,942

foIIows: 0.25 per cent, 0.5 per cent, I.0 per cent, 2.0 per cent, 3.0 per cent and 4.0 per cent in distiIIed water, 2.0 per cent in normaI saIine and 2.0 per cent in concentrated amniotic fIuid. Forty-eight monkeys were divided into eight groups. IntraperitoneaI injections were given, each group receiving different concentrations of sodium ricinoleate as prepared above. In order to standardize the dose, it was decided to give 3 cc. of soIution for each kiIogram of body weight. On this

TABLE I INTERVAL

SoIution used

Antiperitonitis (Bergen)

Control

cont.

Monocytes Neutrophils Wt.-of fluid

vaccine

Sodium ricinoleate per cent

Monocytes Neutrophils Wt. of fluid

2.0

Monocytes Neutrophils Wt. of fluid

18.01 .08 223.

I

14.77 I .22 546.

18.01 .08 223.

259.

18.01 223.

9.43 I. 17

.08

I I. 25

ON

THE

RICItiOLEATE CAVITY

INJECTION

TOLERANCE

WITHIN OF THE

THE

OF

3

II.37 8.72

6

12

11.58 10.52 8.50 16i:96

357.

295.

9.10 ‘3.37 280.

10.67 10.15 9.83 7.30 238. 190.

8.17

15.60

24

48

13.77

12.43

3.65 ‘94.

11.56

26.78 8.71 354. 30.

72

‘$8 159. 24.51 2.31 213. 43.35

168

io.30 30.47 .47 .08 228 335 23.90 24.25 .72 20 246. 257. 65.29

24.65

8.75 9. II .SI 23.76 7.45 12.15 7. I2 21.53 2013. 581. 3373. 988. 1522. 1583. 3692. 3’77.

Further properties of sodium ricinoIeate have been evaluated by the folIowing experimenLs: STUDIES

AFTER

CelIs in miIIions; fluid in milligrams

-

Amniotic fluid (amfetin)

IN HOURS

SODIUM

PERITONEAL

MONKEY

In order to determine the effect of various concentrations of sodium ricinoIeate within the peritoneal cavity of the monkey, the folIowing experiments were conducted. Monkeys (Pitbeous mindanensis mindame&s) were procured from pIantations in the southern PhiIippines. They were housed in Iarge pens with shelters and observed for three months for any evidence of mortality from disease. AI1 were heaIthy and none died during the period of observation except from fighting. A standard soIution (40 per cent) of sodium ricinoleate was used for stock. A series of eight diIutions were prepared as

basis, an adult human weighing 70 kg. wouId receive a dose of 2 I o cc. Intraperitoneal injection was made by suspending the animals by their hind Iimbs, thus aIIowing the viscera to faII toward the diaphragm. The soIution was introduced midway between the umbihcus and symphisis pubis. Before this method was used fauIty injections frequentIy resuIted because of movement of the animals. FoIIowing injection, animaIs of each group were kiIIed at intervals from twentyfour hours to twenty-one days. Death was produced by exsanguination foIlowing administration of a light chIoroform anesthesia. A compIete necropsy was carried out in each case, and particuIar attention was given to the degree of inflammation present and to the amount of fibrinous exudate or adhesions existing within the Portions of the Iiver, peritonea1 cavity. kidney, spIeen, smaI1 intestine and anterior

Nt w SERIES Var., LVI,

No. 3

SeeIey-PeritoneaJ

abdomina1 wall were fixed in formalin, sectioned and stained for histoIogic examination. Five contro1 animaIs were kilIed in a similar way and simiIar tissue specimens were removed for comparative study.

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Amerwnn Journal 01 Surgrry

585

saline than in the series injected with 2.0 per cent in distiIled water. The degree of inffammation in the series injected with 2.0 per cent in concentrated amniotic fluid was approximately the same as in the series

TABLE II 7.u.II ImmoP5PmIlw,

Th e general resuJts of these experiments are condensed into the accompanying table. CTabIe II.) The degree of inflammation and the density of adhesions correspond to the condition found at necropsy. Iqflammatory Reaction to Sodium Ricinoleate. The degree of inflammation and

the length of time that inflammation persisted was directly proportional to the concentration of sodium ricinoleate in distilled water. No evidence of inflammation was apparent after forty-eight hours when 0.23 per cent solution was employed; but it was apparent at the seventy-two hour examination when 2.0 per cent and 3.0 per cent solutions had been used. There was delinitely more inflammatory reaction in the series injected with a.0 per cent in normal

injected with 2.0 per cent in distilled water. In none of the animals was the solution fatal, except in the cases in which injection was made into the wall of the bowel. These faulty injections occurred in early experiments. To determine if necrosis of the bowel wall occurred when sodium ricinoleate solution was introduced into the peritoneal cavity with the certainty that the solution wasYintroduced into the peritoneal cavity and with the certainty that the solution was not injected into the bowel, a series of cases was studied in which the solutions were introduced through an incision made under aseptic technic. No deaths occurred in this group and at necropsy the bowel was found to be intact. This series is not included in the

386

American Journal of Surgery

Seeley-PeritoneaI

resu1t.s recorded in TabIe I, because of inffammation of adhesions which might resuIt from operative trauma. Production of Adhesions by Sodium Ricin-

FIG. I. Appearance of the normal cecum of the ad& rabbit.

oleate. In a11 cases after the injection of sodium ricinoIeate definite fibrinous exudate was found early, but the persistency of this exudate in the form of organized adhesions after the seventh day was very infrequent. Adhesions were not found in any of the animals Iater than seven days after being injected with concentrations of sodium ricinoleate of 2.0 per cent or Iess in distiIIed water. Very smaI1 strands were found in two cases in which the 3.0 per cent were used. and 4.0 per cent concentrations In onIy one case were adhesions encountered in which 2.0 per cent soIution in norma saIine was empIoyed. Adhesions were found in the animal kiIIed after seven days and in the one kiIIed after twenty-one days foIIowing the injection of 2.0 per cent sodium ricinoleate in concentrated amniotic fIuid. The foregoing experiments indicate that sodium ricinoIeate in concentrations from 0.23 to 4.0 per cent in distiIIed water, 2.0 per cent in norma saIine and 2.0 per cent in concentrated amniotic ffuid produces a definite inflammatory reaction in the peritonea cavity which is nonfata1. In a11 experiments a fibrinous exudate was formed foIIowing injection which infrequentIy resuIted in the formation of organized adhesions. WhiIe the series is smaI1 in which sodium ricinoIeate in concentrated amniotic

Adhesions

JUNE,,942

Auid was injected, adhesions were found more often in this series than in those in which distilIed water or normaI saIine was used as a diIuent.

of the cecum of the aduIt rabbit soon after trauma.

FIG. 2. Appearance

STUDIES

ON THE PERSISTENCE

AFTER

TRAUMA OF

THE

TO

THE

OF ADHESIONS CECUM

RABBIT

Fifty adult rabbits were divided into five Under steriIe precautions and groups. nembutal anesthesia, the abdomen was opened by an incision in the midline above the umbiIicus. The entire cecum was traumatized by roughIy puIIing each segment through the fingers hoIding dry gauze. The abdomen was cIosed in two layers, chromic catgut being used in the peritoneum and muscIes and Iinen in the skin, and a colIodion dressing was appIied. An additiona dressing of three-inch stockinette was appIied to the entire trunk, holes being cut for the legs. Ten control animaIs were untreated. Before cIosing the abdomen in the remaining animaIs, four groups of ten animaIs each received 20 cc. intraperitoneaIJy, respectiveIy, of 6.0 per cent gum acacia soIution, 12.0 per cent gum soIution, concentrated amniotic acacia fluid (Amfetin-LiIIy) and I .o per cent sodium ricinoIeate (Soricin-MerreII). The animaIs were kiIIed and examined in each group after seven days. CuItures of the peritoneum were taken at the time of operation and at the time of examination. These were incubated on bIood-agar media. AI1 cuItures were negative except that in

NEW

SERIES VOL. L.VI,

No.

SeeIey-PeritoneaI

3

one anima1 the culture was positive at operation but negative at examination. This method of producing adhesions was

Frc. 3. Adhesions of the omentum and cecum to the Iine of incision and adjoining parietal wal1 srvcn days after trauma. (ControI animal.)

considered to be very drastic. After traumatizing the cecum there were generaIized petechia1 hemorrhages and numerous subserous hemorrhages. (Figs. I and 2.) Adhesions resuIting in contro1 animaIs were dense and diffIcuIt to separate. (Figs. 2 and 3,) Adhesions were more apt to occur between the cecum and the parieta1 waI1, due to the position of the animals and to the compression of the abdomen by the stockinette dressing. Upon examination it was found that a11 adhesions existed in one or more of four sites; omentum to cecum or parieta1 waI1, cecum to parieta1 waI1, cecum to folds of cecum or cecum to other structures such as mesentery, Ioop of smaI1 bowe1 or the tip of the uterus or ovary. The results are condensed in TabIe III: TABLE

III

T-

Adhesions.

Per Cent

Solution Used

IntcrVRI

1

&urn. ,men-

:ecum

-( P

t”Ill

Elsewhere

50 4” 10

80 60 40

1”

-

Adhesions

American

.Jmrn.ll ofSur~~rry

7-8- i

Gum acacia solution was used because it was hoped that some lubricating effect might be obtained if the solution remained

FIG. 4. Adhesions of the cecum to the line of incision and adjoining parietal waII and adhcsion between large howe and cecum wvrn da! s after trauma. (Control nnima1.)

within the peritoneaI cavity. It has been found that gum acacia given intravenousIy persists within the circulatory system for many months. It was hoped that if acacia soIution would remain on the circuIatory side of the peritonea1 cavity it would as well remain without the circulatory system if pIaced intraperitoneaIIy. However, chemica1 tests of the peritoneal fluid after twenty-four hours failed to demonstrate the presence of acacia. Tests of blood serum were negative at the same interval. I am unable to say how this material \vas eriminated. However, since AuspitzZs has demonstrated ground rice grains in the Iung and spIeen after intraperitoneal injection, it is not strange that acacia \~as removed. The number of adhesions found after the use of amniotic ffuid concentrate was aImost as great as in the control group. AIthough this solution has been found to be stimuIating to the peritoneum, it wiI1 be noted in the experiments of SeeIey, Higgins and Mann23 that this stimuIation did not resuIt in an appreciable increase of peritonea1 fluid. Warren29 states that amniotic fluid acts probabIy by reducing the oozing from injured surfaces. In the use of sodium ricinoleate there is a definite increase of peritoneal fluid. When we consider the scarcity of peritoneal adhesions in

588

American Journd of Surgery

SeeIey-PentoneaI

tubercuIous peritonitis with effusion it may be considered that exudation is of vaIue in preventing adhesions. Further, in case of infection within the peritonea1 cavity, absorption into the circuIation is to be avoided. Sodium ricinoIeate wouId not onIy tend to prevent absorption away from the peritonea1 space, but to reverse this process by causing exudation of fluid and ceIIs which are mixed with sodium ricinoIeate known to be bactericida1, bacteriostatic and detoxifying. The effects of sodium ricinoIeate intraperitoneaIIy may be summarized as foIIows : It causes an oytpouring of exudate into the peritonea1 cavity which is rich in neutrophiIs and monocytes, and from which is deposited dense fibrin. This furnishes fluid for Iubrication, fibrin for heaIing, neutrophiIs for phagocytosis and Iysis of fibrin and monocytes for regeneration of endotheIium, thus imitating nature in the processes of primary heaIing. In case of infection, the presence of sodium ricinoIeate further assists because of its bactericida1, bacteriostatic and detoxifying properties. SIowing or reversa1 of absorption from the peritonea1 cavity is of additiona1 vaIue. COMMENT

It shouId be emphasized that sodium ricinoIeate soIutions must be freshIy prepared in Pyrex glassware. I have found oId stock soIutions toxic, therefore, fresh stock shouId be used. Further, in an evaIuation of adhesions in experimenta work it is urged that very young animaIs and pregnant animaIs be avoided. I have noted that there is more peritoneal ffuid in such animaIs, and adhesions are more diffIcuIt or impossibIe to produce even under contro1 conditions. It is, therefore, obvious that an evaIuation of substances designed to avoid unfavorabIe adhesions shouId be carried out in aduIt, nonpregnant animaIs. It shouId be further emphasized that any agent designed to prevent or reduce the number of adhesions must be introduced very earIy. HertzIerl states that coaptation

Adhesions

JUNE,19‘12

of surfaces takes pIace within ten minutes and that for this reason the postoperative posture, movement of the patient or stimuIation of peristaIsis is unsuccessfu1 on this account. CONCLUSIONS

Healing of the peritoneum is exactIy paraIIe1 with the formation of adhesions. Any measure designed to prevent unfavorabIe adhesions must imitate nature’s methods of heaIing, not inhibit such processes. The most certain method of avoiding unfavorabIe adhesions is the Iimitation only of trauma to the area in which heaIing is desired. When there is trauma eIsewhere, or when foreign bodies, infection, digestive juices or factors which aIter coaguIation are present, heaIing occurs at unfavorable sites, and nature’s processes shouId be stimuIated. In the studies reported in this paper stimulation of the peritoneum by sodium ricinoIeate has been shown to imitate nature’s processes of heaIing by the production of an abundant exudate which is rich in neutrophiIic poIymorphonucIear Ieucocytes from which abundant and monocytes, fibrin is desposited. The presence of this abundant exudate acts as a Iubricant to prevent the formation of unfavorable adhesions. In addition, sodium ricinoIeate possesses bactericida1, bacteriostatic and detoxifying properties and by sIowing or reversing absorption from the peritonea1 cavity assists in combating infection. Sodium ricinoIeate has been demonstrated to be we11 toIerated intraperitoneaIIy in Iaboratory animaIs and in the human. It has been demonstrated that it is capabIe of preventing the majority of unfavorabIe adhesions after drastic trauma to the viscera and peritoneum of animals. REFERENCES I. HERTZLER, A. E. The Peritoneum. Vol. 2. St. Louis,

1919. Mosby Co. SurgicaI PathoIogy of the Peritoneum. PhiIadeIphia, 1935. Lippincott Co. 2. OPIE, E. L. Inffammation. Harvey Lectures. PhiladeIphia, 1910. Lippincott Co. 3. STEINBERG, B. A rapid method of protecting the peritoneum (by intraperitoneal injection of coIon baciIIi). Arch. &rg., 24: 308-317, 1932.

NI w Scn~~s Vol.. LVI. No. 3

Seeley-PeritoneaI

4. JONES, D. F. and MCCLURE, W. L. Practice of Surgery. Edited by Dean Lewis. Hagerstown, Md., !V. F. Prior Co. 5. NORRIS, J. C. and DAVISON, T. C. PeritoneaI reaction to Iiquid petrolatum, J. A. M. A., 103: 1846-1847, 1934. 6. RIARVEL, E. Prevention of peritonea1 adhesions by adrenal salt solution, with especia1 reference to the peIvis. J. A. M. A., 49: 986990, 1907. ;. POPE, S. The use of citrate solutions in the prevcntion of peritoneal adhesions. Ann. Surg., 59: IOIro6, 1914. Port:, S. The prevention of peritoneal adhesions by the use of citrate solutions. Ann. Surp., 63: zo$-20;. 1916. 8. \I’,\LKER, W. Il., JR. and FERGUSOK, L. hl. Pcritoneal adhesions: their prevention with tit rate solutions. .4nn. Sure., 63: 198-204, 1916. 0. STRAI:S, D. C. Concerning the vaIue of sodium citrate soIution in the prevention of peritonea1 adhesions. Surfi., Gvnec. w Obst., 22: 602-609, r91h. 10. SLEET, J. E., CHANEY, R. H. and WILLSOIC, [I. L. The prevention of postoperative adhesions in the prritoneaI cavity. Ann. Surg., 61: 297-305, 10 I 5. I I. K~wOTA, T. Experimental studies on the prcvention of peritoneal adhesions. Japan R4ed. \$‘orLd, 2: 220-229, 1922. II. C~HSNER, A. and MASOP\‘, F. Prevention of pcritoneal adhesions by the use of vegetabIe ferments. Proc. Sor. Exp. Bio/. c~ Med., 25: 524, 1928. O(:IISUER, A. and GARSIDE, E. PeritoneaI adhesions. Surg., C,vnec. ts* Obst., 54: 338-361, 1932. O(:t1svEa, A. and STERCK, A. Prevention of peritoncal adhrsions by papain; clinica study. Ann. Surg., ro4: ‘3&i-747, 1936. I 3. \VALTON, J. P. Trypsin preparations suitable for prevention of abdomina1 adhesions. J. Pbarmacol. e’+ Tberap. f:z.p., 40: 403-41 I, 1930. 14. ~.ARISIIMIAN, K. and COOPER, D. H. Pepsin in prrvention of abdominal adhesions. Arch. Surg., 29: 264-276, 1934. I j. JoHvsoN, L. f f. et al. Amniotic fluid concentrate as activator of peritoneal immunity. Surp., gnec. @+ f)hst., 62: 171-181, 1936. IO. Oct;sixra, A. and GARSIDE, E. PeritoneaI adhesions. Surg., Ct%ec. f’* Obst., $4: 338-361, 1932. 17. PFEIFFER, R. and ISSAEFF. Quoted in MedicaI Research CounciI. A system of bacterioIogy. Vol. 6, Immunity, ~931. IH. hiowox, Fi. W. Non-specific peritoneal immunization. Surp., G,?-net. e’+ Obst., 52: Iog3-~og8, 193’. 10. I IF.RMAYU, S. F. Experimental peritonitis and peritoneal immunity. Arch. Surg., 18: 22-23, 1929. 21). &R~.EN, J. A. PeritoneaI reactions to vaccine. hoc. Staf Meel., Mayo Clin., 8: 581-582, 1933. 2 I. Jl-DD, E. S. and WALDRON, G. W. The prevention of surgical CompIications. Wisconsin M. J., 34: 8793, 1935. 22. Dtxou, C. F. and BART,EN, J. A. Vaccination preceding colonic operations as protection against peritonitis. New lb& M. J., 35: 1-4, 1935. 23. SEELEY, S. I;., HIGGINS, G. M. and MANN, 1;.C. Studies on peritonitis: the cytoIogic response of the peritoneal fluid to certain substances. Proc. Staff. Meet., ,Mayo C/in., IO: 793-796. 1935.

Adhesions 24. CORWIN, W. C. The peritoneal cytolic response: an experimenta study. Am. J. Med. SC., 103: 251, ‘937. 25. WANGENSTEEN, 0. H. Personal communication, April, 1937. 26. GILLETTE. N. W. The avoidance and treatment of peritonitis. J. Med. Prac., 89-92, 1936. 27. WANGENSTEEN, 0. H. High gastric resection in cancer of the stomach with relation of personal experiences. Journal-Lancet, $7: 1-4, 193-. 28. JOHKSON, H. L. Observations on the prcvcntion of post-operative peritonitis and adhesions. Surg., Gynec. e* Obst., 45: 612-619, 192~. JOHYSOU, H. L.. Amniotic fluid concentratr in the prevention of adhesions. Nezo England .Af. J., I~J: 661-664, 1928. JOHNSON, H. L. Amfetin: its influence upon defcnsc and repair in serous cavities. .24ed. Arts., 30: 4oo-413, 1933. 29. M~ARREN, S. The effects of amniotic Ruid on scrous surfaces. Arch. Patbol., 6: 860-866, Ic)zH. 3”. TR~SLER, H. hl. Peritonitis: An experimental studv of healing in the peritoneum and the thrrapeutic effect of amniotic fluid conccntratc. Proc. S/aff. Meet., Mayo C/in., 4: 356, 1029. TR~SLER, I-1. RI. Experimental study of healing in the peritoneum and the therapeutic effect ol amniotic fluid concentrate. Arch. Surg., 22: 083~ 992, 193’. 3 I. I
32. REA, C. E. and WAN~ENSTEEN, 0. 1 I. Comparativr eflicacy of substances employed in the prcvrntion of peritonea1 adhesions. I’roc. Sot. Erper. Rio/. I? Med., 31: 1060-ro63, 1934. 33. LACI:Y, J. T. The prevention of peritoneal adhesions by amniotic fluid. Ann. SurR.. 92: ~81~ 203, 1930. I.ACEY, J. T. Amniotic fluid: clinical stud> lusing amniotic fluid in experimental studies on postoperative conditions) Ann. Sure., tar : j2c) $35, ‘035. 34. GEI~FERT, J. R. Intraperitoneal use of amniotic fIuid (amfetin) to promote smoother post-oprrative convalescence. Am. J. Surfi., 32: 40 44, 1036. 35. I.ARSOU, W. P. and ~IAL~ERSOIV, II. 0. The cffcct of concentration upon the neutralization of toxin f,~- sodium ricinoleate. Proc. SW. E.q)er. Hiol. F Med., 22: sso, 1925. LARSON, \v. P., F~ALVERSOPi, 11. o., EVANS, R. 1). and GREEN, R. G. The effect of surface tension

upon bacteria1 toxins. (:olloid depressants S,vmpos. hlonograph, 3: 1~2-157, I92j. LARSON, W. P. and NELSON, E. The effect of the surface tension on thr medium upon f,actcriaI growth. Proc. Sot. Esper. Riol. ti-’ Med. 21: 27% 279, 1924. 36. REA, CHARI.ES E. Personal communication. October I j, 1940. 37. RIDER, T. H.,,Unpublished data. 38. Ar’s~r-rz, H. Uber die behedeutung dcr Iymphrocgc fur die resorption kIeiner fiussigkeitswengen aus dcr bauchhuhle. Centralbl. J. Plysiol., IO: 2 19, 1Xg6.