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Biliary Drainage by Duodenal Intubation*
BILIARY DRAINAGE BY DUODENAL INTUBATION* WILLlAM DALE BEAMER. M.D.t
and present experience with upper intestinal intubation renders it desirable to revaluate our ability to make adequate examinations of the biliary tract by collection of bile from the duodenum. Certainly the procedure as commonly practiced by those not thoroughly indoctrinated in the use of the duodenal tube often leads to inconclusive results, when but little basic knowledge is necessary for correct interpretation of the findings. It is my purpose here to review the principles and to recognize those factors which produce unsatisfactory results. PAST
HISTORY OF DUODENAL I NTU BATION
The use of a mechanical device to empty the gastro-intestinal tract was initiated by Kussmaul, who first practiced gastric lavage in 1867. 1 The first serious attempt to enter the duodenum came twenty-eight years later when Hemmeter2 used a combination of two tubes. On the distal end of one tube was a balloon grooved on its upper surface when inflated in the stomach. The groove was designed to act as a guide for the entrance of the second tube into the pyloric canal. Obviously such an arrangement, although ingenious, could not be practical because of the difficulty and often impossibility of placing the distal end of the groove opposite the pylorus. Kuhn 3 in 1898 attempted to improve upon this by inserting a wire spiral in an ordinary stomach tube, and by patient and painstaking manipulation to insert it into the duodenum. Thus matters stood until 1909 when Einhorn 4 developed a small bore, soft rubber tube which ended in a perforated metal capsule. The tube was found to be generapy useful for aspirating either gastric or duodenal contents .. From the Department of Physiology and the Gastro-enterological Section of the Department of Medicine, Jefferson Medical College, Philadelphia. t Ross V. Patterson Fellow in Physiology and Gastro-enterology, Jefferson Medical College. 1659
1660
WILLIAM DALE BEAMER
or for tubal feedings into either the stomach or duodenum. Rehfuss in his recent book6 describes the development of his tip in 1912. Gross,o Palefski,1 Levin,u Lyon8 and others devised modified tips also, but such improvements did little to revive the lagging interest in biliary drainage. The necessary stimulus was provIded by LyonlU in 1919, who made successful clinical application of the idea after having read a footnote in a paper by Meltzerl l two and a half years previously, suggesting that 25 cc. of 25 per cent magnesium sulfate would relax the sphincter of Oddi as well as the duodenal wall and permit the bile to flow. Although based upon a "law of reciprocal innervation," for which eVidence is lacking (cf. Ivy's review 12 ), there is little doubt of normal relationship between relaxation of the sphincter of Oddi and increased gallbladder pressure not necessarily dependent on nerve pathways. However, this does not minimize the great step forward. Since that time there has been no especial improvement either in the technic of duodenal intubation or in methods of obtaining a dependable flow of bile. The studies have mainly been confined to learning which substances are most potent in their cholagogue effect. TECHNIC OF PASSING THE TUBE
Confidence on the part of the operator is a definite prerequisite for successful passage of the tube. The patient must be put completely at ease. Time spent in first explaining and reassuring him may spell the difference between successful drainage of the gallbladder and failure. If there is likelihood of nausea, the throat may be painted with 1 per cent nupercaine solution, but in so doing the patient must be forewarned of the drying and numbing effect since its unexpected. occurrence may make him more apprehensive. As the tube is swallowed, gagging may occur in spite of carefully repeated instructions. Without raising the voice, the operator directs the patient to cease swallowing and take several deep breaths of air through his wide-open mouth. The head must never be thrown back, but must be maintained in a normal position at all times. If,in spite of all precautions, revulsion occurs after two or three attempts, the patient should be sent home with instructions to take a sedative before retiring. The next morning the procedure may be repeated, and it is probable that with time to review his part and
BILIARY DRAINAGE BY DUODENAL INTUBATION
1661
with inhibitions lowered by the sedative he may be able to carry out the intubation without difficulty. When the tube reaches the lower pole of the stomach, usually at the 56-cm. mark, 8 ounces of warm water or saline are introduced through a funnel, and withdrawn immediately by gravity siphonage. Difficulty of entrance and evacuation of the solution may indicate that cardiospasm has prevented the tip of the tube from entering the stomach. This may be overcome by a few minutes' distraction, such as reading a newspaper or walking about. It is inadvisable to attempt complete recovery of the solution or to lavage further, since time spent here is unnecessary and is tiring to the patient. The tube may be clamped off or left open. The patient lies on his right side with his shoulder low and hips elevated so that the heavy tip will gravitate to the pylorus. He is then instructed to swallow easily at intervals so that at least twenty minutes are consumed in permitting the tube to advance 20 cm. At the same time, for psychic stimulation of peristaltic activity, he may imagine he is digesting some favorite food. Aaron 13 suggests pressure or percussion over the fifth dorsal vertebra, and tapotement (a tapping motion of the fingers on the epigastrium by rapid supination of the hands when the hypothenar eminences rest upon the abdomen), or the application of Crede's method of placental delivery to the stomach. Any of these methods may be useful in causing a stubborn pyloric sphincter to open. The patient should not be hurt or unduly excited, since any unexpected action may cause the stomach to relax. 6 A temporary change of position, even walking about, may permit the tip to enter the duodenum. The correct position of the tip in the duodenum is best determined by fluoroscopy, but when this is not available a flow of viscid yellow bile is good evidence. A flow of turbid bile or of the neutral or alkaline contents means that the tip is in the duodenum but that it may still be in the cap, proximal to the ampulla of Vater, or may even have reached the jejunum. Auscultation upon injecting air is helpful but not too exact. There is no sure way of checking the position except by roentgen examination. The mere presence of bile should not be misleading. It is easily regur~itated into the stomach, but here the bile salts are precipitated and a sediment appears in place of the viscid material previously mentioned.
1662
WILLlAM DALE BEAMER
Care must still be exercised to prevent regurgitation of the tip into the stomach, which may occur from restlessness of the patient or, more frequently, with nausea due to retrograde movements of the duodenum which push the tip in a proximal rather than a distal directionY The patient should not talk during the entire procedure because of the nauseating effect of the tube in the throat. A difference of opinion exists, however, and some may encourage the patient to talk to increase his confidence. Nevertheless, at this point particularly he should be oblivious to his surroundings and may sleep, read or listen to the radio. It is advisable not to keep the patient intubated longer than necessary. OBTAINING THE SPECIMENS
The physiology of the mechanism for emptying the gallbladder has been studied extensively but still is imperfectly understood. That the closing and opening of the sphincter of Oddi (the existence of which is now generally agreed upon) is important, is seen in all experimental studies on the pressures exerted by the secreting liver, gallbladder and the various ducts.16. 17 Direct relaxation of the sphincter of Oddi seems of value, and nitroglycerin18 • 20. 26 has frequently been suggested for this purpose. In my experience, however, this drug is inconsistent in reducing the spasm of the sphincter and too often permits the tip of the tube to fall back into the stomach; therefore I have discontinued its use. Pavatrine (B-diethylaminoethyl fluorene-9-carboxylate hydrochloride) in doses of 360 mg. has yielded fairly good results. It is believed to relax the duodenum and sphincter of Oddi. When introduced through the tube into the duodenum there is usually a quiescent period of fifteen to twenty-five minutes, after which the "B" bile makes an abrupt appearance. The color changes in the bile are gradual, the most intense golden brown occurring about twenty-five minutes after the first flow. When the administration of the drug is successful the resultant formation of a fluorescent turbid yellow solution in the alkaline duodenum is apt to be confusing in the first collections of bile. When pavatrine has not induced a flow of bile I have found that a magnesium sulfate-peptone solution seldom is effective either.
BILIARY DRAINAGE BY DUODENAL INTUBATION
1663
In dogs the response to pavatrine is not the same as in the human subject. In ten experiments16 a flow of bile was noted in only two, amounting to no more than 15 cc. in either case, and the bile was not concentrated. So far the substance found most effective in emptying the gallbladder is a mixture of cream and egg yolk, the stimulating effect depending on the fat content. 21 This does not excite the duodenum as much as olive oip2 but has the disadvantage in common with all other media of mixing with the samples of bile. In order to avoid contamination, I have allowed the tube to progress to the third portion of the duodenum or into the jejunum, introduced the stimulant followed by a little air, and then have withdrawn the tube until the tip reached the middle of the descending portion of the duodenum. The substances apparently act as well from the jejunum as from above, but it is not always possible to encourage the longer journey of the tube. The next most effective substance is a solution of 5 or 10 per cent peptone. I have used Bacto-protone (a mixture of proteoses) in the same strength and prefer it, as with this preparation there is usually sharper delineation and more rapid collection of the gallbladder bile than with peptone. In controlled experiments on dogs having duodenal cannulas, a flow of concentrated gallbladder bile occurred within five minutes after instilling 25 cc. of 5 per cent Bacto-protone into either the duodenum or jejunum. T!\,enty-four experiments were performed with only one failureY Two dogs were used in four additional experiments. One had a bisected loop of jejunum and an intact nervous system except for the divided myenteric plexus; the other had an intestinal anastomosis just above an ileal fistula, and was vagotomized and splanchnicectomized. The proteose solution was perfused through the loop and fistula. The latter animal gave no response to the stimulus while the former yielded a flow of bile similar in all respects to that of normal dogs. This could suggest that the stimulus is carried by way of extrinsic reflex pathways, but it may indicate simply that the ileum is incapable of cooperation. It is said that cholecystokinin is generated in the duodenum. In the Curtis Clinic, we use a solution consisting of 20 cc. of 7 per cent peptone and 10 cc. of 50 per cent magnesium sulfate
1664
WILLIAM DALE BEAMER
with successful drainages in about 70 per cent of all cases. The magnesium suIfate tends to relax the sphincter of Oddi (but may fail if used alone 15. 21) and the peptone is presumed to cause the gallbladder to contract. The completeness of evacuation is always questionable unless a dye-filled gallbladder is visualized by roentgen examination before and afterward. I am quite sure that it rarely empties completely. SOME FACTORS INVOLVED IN EMPTYING
It appears important that the intubation should be begun early in the morning, since there is a psychophysical disturbance with increased duodenal irritability in most individuals whose breakfast is delayed. To effect a satisfactory drainage it is also important that the gallbladder be well filled, as it normally is after a twelve-hour fast. A full gallbladder exerts an increased pressure to insure a flow of bile. One should not be misled into wrong diagnosis on the basis of absence of gallbladder bile when the organ has not had a sufficient length of time in which to store up bile. The pressure of the bile in a well-filled gallbladder may influence its tone. A high tonus may be just as important in maintaining a sufficient pressure within the gallbladder as active contraction of the musculature during the emptying process. At any rate, Bainbridge and Dale 23 found that distention augmented tonus rhythm without causing contraction in anesthetized dogs, and Ivy12 has never seen a good contraction in dogs in the digestive state with a partially emptied or contracted gallbladder. In addition, Deissler and Higgins 27 found that a certain optimum pressure was necessary in guinea pigs' gallbladders to produce normal tonus rhythm and that higher pressures would overcome the resistance of the sphincter of Oddi with leakage of the fluid. Although the gallbladder is rather well supplied with fine nerve fibers and ganglia, present-day evidence suggests that these may exert a regulatory influence on tonus rather than initiate gallbladder contraction. That such tonus changes may be carried by nerve pathways would seem to be true from the experience of Boyden and Parmacek,24 who frequently obtained a slight flow of bile on mere perception of fried bacon, or the observation of Levene25 of a sudden increase in the size of the gallbladder during nausea.
BILIARY DRAINAGE BY DUODENAL INTUBATION
1665
We note that upon stimulation we do not always obtain a response in increased bile flow even when the gallbladder is fairly well filled. We may deduce that such a failure may be due to a low intraluminal pressure 12 , 27 which makes a stimulus ineffectual when it would be adequate if the tone level were higher. Of course it may be due to abnormal spasticity of the sphincter of Oddi. Because of this we should not be hasty in drawing the conclusion that there is obstruction due to other causes when we do not obtain a flow of bile. EXAMINING THE BILE
Students always ask, "What should we look for?" The normal calor sequence of the biliary drainage is prima facie evidence of a normally functioning biliary tract. The consensus among gas.troenterologists is that the dark "B" bile comes only from the gallbladder. One may obtain a concentrated bile upon occasion in a cholecystectomized patient, but this would argue for a compensatory condition which is desirable. When "B" bile is present in only small amounts and with a relatively low concentration, it may be assumed that the gallbladder is functioning poorly. Complete absence of "B" bile is indicative of a blocked or nonfunctiorting gallbladder. Absence of "A," "B" and "C" fractions must be due to complete closure of the common bile duct. Except in the last case, no one attempt is sufficiently conclusive for diagnosis. The degree of clarity or turbidity of the fraction is somewhat indicative of the state of the organs. Microscopic examination only elaborates the picture of the color sequence. It reflects the condition of the part from which the bile originated. The examiner looks first for those particles usually present in disease of that part of the gall tract. The key to the anatomical structure from which the bile was obtained is in the type of desquamated epithelial cell which he views under the microscope; for example, the tall columnar cells which line the gallbladder serve as a check on the accuracy of recognizing "B" bile as coming from that structure. He further looks for pus, blood and crystals, especially cholesterol anq calcium bilirubinate. In studying the pus cells, he notes whether they are bile-stained and whether they are degenerate, as these are clues to the extent of disease and the degree of stasis. He also examines the contents for parasites and bacteria,
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WILLIAM DALE BEAMER
making cultures in any uncertain case. In this latter connection, I might add that after careful mouth cleansing and with sterile apparatus the chances of obtaining an accurate culture are fairly good. When the same growth is found in two or three subsequent drainages and associated with other indications of infection, the evidence must not be ignored. If roentgen study, such as the cholecystogram, is possible in conjunction with the drainage, four especially valuable details can be elicited in addition to what can be learned without it. 1. 2. 3. 4.
Does the gallbladder fill well, and is it of normal shape? Are there any calculi present? Is the duodenal tube in the optimal position for drainage? Does the emptying of the gallbladder as seen on the x-ray plates agree with the volumes and color sequence of the bile fractions obtained?
It is understandable that one may wish to perform a duodenalbiliary drainage when there are no radiographic facilities available. But it is not so justifiable, in my opinion, to make roentgen studies of the gall tract without a concomitant duodenal intubation, provided the latter is not specifically contraindicated by (1) acute infections of undetermined origin, (2) calculi liable to produce impaction, or (3) acute coronary or serious cardiovascular conditions. CONCLUSIONS
Recent years have seen a shift away from biliary drainage as a therapeutic measure; it has come to be regarded only as a diagnostic medium. It is apparent, however, that there are toxic substances which may be removed only by periodic flushing of the biliary tract, and that the duodenal tube is an important adjuvant. In no other way are we as well able to follow the progress of our therapy. The benefit which patients with gall tract disease experience from periodic drainages cannot be fully ascribed t'o psychic reasons. BIBLIOGRAPHY 1. Clendening, L. and Hashinger, E.: Methods of Treatment. St. Louis, C. V. 2.
Mosby Co., 1941. Hemmeter, J. c.: Johns Hopkins Hosp. Bull., April, 1895; New York Med. Rec., Sept. 13, 1921.
BILIARY DRAINAGE BY DUODENAL INTUBATION
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3. Kuhn, F.: Arch. f. Verdaungs Kranklieiten, 1898; Lyon: Non-Surgical Drainage of Gall Tract. Philadelphia, Lea & Febiger, 1923. 4. Einhorn, M.: New York Med. Rec., Oct. 9, 1909. 5. Gross, M.: New York Med. J., Aug. 22, 1914. 6. Rehfuss, M. E.: Indigestion. Philadelphia, W. B. Saunders Co., 1943. 7. Palefski, I. 0.: Interstate Med. J., Aug. 22, 1914. 8. Lyon, B. B. V.: J.A.M.A., 74:276, 1920. 9. Levin, A. J.: J.A.M.A., 76:1007, 1921. 10. Lyon, B. B. V.: J.A.M.A., 73:980, 1919. 11. Meltzer, S. J.: Am. J. Med. Se., ])3:469, 1917. 12. Ivy, A. C.: Physiol. Rev., 14:1, 1934. 13. Aaron, C. D.: Diseases of the Digestive Organs: Diagnosis and Treatment. Philadelphia, Lea & Febiger, 1927. 14. Ingelfinger, F. J. and Moss, R. E.: Am. J. Physiol., 136:561, 1942. 15. Bergh, G. S. and Layne, J. A.: Am. J. Digest. Dis., 9:162, 1942. 16. Unpublished experiments. 17. Kozoll, D. D. and Necheles, H.: Surg., Gynec. & Obst., 74:27, 1942. 18. Leuth, H. C.: Am. J. Physiol., 99:237, 1931. 19. Unpublished experiments. 20. Best, R. R. and Hicken, H. F.: Am. J. Surg., 39:533, 1938. 21. Kozoll, D. D. and Necheles, H.: Surg., Gynec. & Obst., 74:692, 1942. 22. Elton, N. W.: Rev. Gastroenterol., 7:65, 1940. 23. Bainbridge, F. A. and Dale, H. H.: J. Physiol., 33:138, 1905-06. 24. Boyden, E. A. and Parmacek, L.: Proc. Soc. Exper. BioI. & Med., 25:462, 1928. 25. Levene, G.: Am. J. Rocnt. & Rad. Ther., 26:97, 1931. 26. Waiters, W., McGowan, J. M., Butsch, W. L. and Knepper, P. A.: J.A.M.A., 109:1591, 1937. 27. Deissler, K. and Higgins, G.: Am. J. Physiol., 112:430, 1935.
and present experience with upper intestinal intubation renders it desirable to revaluate our ability to make adequate examinations of the biliary tract by collection of bile from the duodenum. Certainly the procedure as commonly practiced by those not thoroughly indoctrinated in the use of the duodenal tube often leads to inconclusive results, when but little basic knowledge is necessary for correct interpretation of the findings. It is my purpose here to review the principles and to recognize those factors which produce unsatisfactory results. PAST
HISTORY OF DUODENAL I NTU BATION
The use of a mechanical device to empty the gastro-intestinal tract was initiated by Kussmaul, who first practiced gastric lavage in 1867. 1 The first serious attempt to enter the duodenum came twenty-eight years later when Hemmeter2 used a combination of two tubes. On the distal end of one tube was a balloon grooved on its upper surface when inflated in the stomach. The groove was designed to act as a guide for the entrance of the second tube into the pyloric canal. Obviously such an arrangement, although ingenious, could not be practical because of the difficulty and often impossibility of placing the distal end of the groove opposite the pylorus. Kuhn 3 in 1898 attempted to improve upon this by inserting a wire spiral in an ordinary stomach tube, and by patient and painstaking manipulation to insert it into the duodenum. Thus matters stood until 1909 when Einhorn 4 developed a small bore, soft rubber tube which ended in a perforated metal capsule. The tube was found to be generapy useful for aspirating either gastric or duodenal contents .. From the Department of Physiology and the Gastro-enterological Section of the Department of Medicine, Jefferson Medical College, Philadelphia. t Ross V. Patterson Fellow in Physiology and Gastro-enterology, Jefferson Medical College. 1659
1660
WILLIAM DALE BEAMER
or for tubal feedings into either the stomach or duodenum. Rehfuss in his recent book6 describes the development of his tip in 1912. Gross,o Palefski,1 Levin,u Lyon8 and others devised modified tips also, but such improvements did little to revive the lagging interest in biliary drainage. The necessary stimulus was provIded by LyonlU in 1919, who made successful clinical application of the idea after having read a footnote in a paper by Meltzerl l two and a half years previously, suggesting that 25 cc. of 25 per cent magnesium sulfate would relax the sphincter of Oddi as well as the duodenal wall and permit the bile to flow. Although based upon a "law of reciprocal innervation," for which eVidence is lacking (cf. Ivy's review 12 ), there is little doubt of normal relationship between relaxation of the sphincter of Oddi and increased gallbladder pressure not necessarily dependent on nerve pathways. However, this does not minimize the great step forward. Since that time there has been no especial improvement either in the technic of duodenal intubation or in methods of obtaining a dependable flow of bile. The studies have mainly been confined to learning which substances are most potent in their cholagogue effect. TECHNIC OF PASSING THE TUBE
Confidence on the part of the operator is a definite prerequisite for successful passage of the tube. The patient must be put completely at ease. Time spent in first explaining and reassuring him may spell the difference between successful drainage of the gallbladder and failure. If there is likelihood of nausea, the throat may be painted with 1 per cent nupercaine solution, but in so doing the patient must be forewarned of the drying and numbing effect since its unexpected. occurrence may make him more apprehensive. As the tube is swallowed, gagging may occur in spite of carefully repeated instructions. Without raising the voice, the operator directs the patient to cease swallowing and take several deep breaths of air through his wide-open mouth. The head must never be thrown back, but must be maintained in a normal position at all times. If,in spite of all precautions, revulsion occurs after two or three attempts, the patient should be sent home with instructions to take a sedative before retiring. The next morning the procedure may be repeated, and it is probable that with time to review his part and
BILIARY DRAINAGE BY DUODENAL INTUBATION
1661
with inhibitions lowered by the sedative he may be able to carry out the intubation without difficulty. When the tube reaches the lower pole of the stomach, usually at the 56-cm. mark, 8 ounces of warm water or saline are introduced through a funnel, and withdrawn immediately by gravity siphonage. Difficulty of entrance and evacuation of the solution may indicate that cardiospasm has prevented the tip of the tube from entering the stomach. This may be overcome by a few minutes' distraction, such as reading a newspaper or walking about. It is inadvisable to attempt complete recovery of the solution or to lavage further, since time spent here is unnecessary and is tiring to the patient. The tube may be clamped off or left open. The patient lies on his right side with his shoulder low and hips elevated so that the heavy tip will gravitate to the pylorus. He is then instructed to swallow easily at intervals so that at least twenty minutes are consumed in permitting the tube to advance 20 cm. At the same time, for psychic stimulation of peristaltic activity, he may imagine he is digesting some favorite food. Aaron 13 suggests pressure or percussion over the fifth dorsal vertebra, and tapotement (a tapping motion of the fingers on the epigastrium by rapid supination of the hands when the hypothenar eminences rest upon the abdomen), or the application of Crede's method of placental delivery to the stomach. Any of these methods may be useful in causing a stubborn pyloric sphincter to open. The patient should not be hurt or unduly excited, since any unexpected action may cause the stomach to relax. 6 A temporary change of position, even walking about, may permit the tip to enter the duodenum. The correct position of the tip in the duodenum is best determined by fluoroscopy, but when this is not available a flow of viscid yellow bile is good evidence. A flow of turbid bile or of the neutral or alkaline contents means that the tip is in the duodenum but that it may still be in the cap, proximal to the ampulla of Vater, or may even have reached the jejunum. Auscultation upon injecting air is helpful but not too exact. There is no sure way of checking the position except by roentgen examination. The mere presence of bile should not be misleading. It is easily regur~itated into the stomach, but here the bile salts are precipitated and a sediment appears in place of the viscid material previously mentioned.
1662
WILLlAM DALE BEAMER
Care must still be exercised to prevent regurgitation of the tip into the stomach, which may occur from restlessness of the patient or, more frequently, with nausea due to retrograde movements of the duodenum which push the tip in a proximal rather than a distal directionY The patient should not talk during the entire procedure because of the nauseating effect of the tube in the throat. A difference of opinion exists, however, and some may encourage the patient to talk to increase his confidence. Nevertheless, at this point particularly he should be oblivious to his surroundings and may sleep, read or listen to the radio. It is advisable not to keep the patient intubated longer than necessary. OBTAINING THE SPECIMENS
The physiology of the mechanism for emptying the gallbladder has been studied extensively but still is imperfectly understood. That the closing and opening of the sphincter of Oddi (the existence of which is now generally agreed upon) is important, is seen in all experimental studies on the pressures exerted by the secreting liver, gallbladder and the various ducts.16. 17 Direct relaxation of the sphincter of Oddi seems of value, and nitroglycerin18 • 20. 26 has frequently been suggested for this purpose. In my experience, however, this drug is inconsistent in reducing the spasm of the sphincter and too often permits the tip of the tube to fall back into the stomach; therefore I have discontinued its use. Pavatrine (B-diethylaminoethyl fluorene-9-carboxylate hydrochloride) in doses of 360 mg. has yielded fairly good results. It is believed to relax the duodenum and sphincter of Oddi. When introduced through the tube into the duodenum there is usually a quiescent period of fifteen to twenty-five minutes, after which the "B" bile makes an abrupt appearance. The color changes in the bile are gradual, the most intense golden brown occurring about twenty-five minutes after the first flow. When the administration of the drug is successful the resultant formation of a fluorescent turbid yellow solution in the alkaline duodenum is apt to be confusing in the first collections of bile. When pavatrine has not induced a flow of bile I have found that a magnesium sulfate-peptone solution seldom is effective either.
BILIARY DRAINAGE BY DUODENAL INTUBATION
1663
In dogs the response to pavatrine is not the same as in the human subject. In ten experiments16 a flow of bile was noted in only two, amounting to no more than 15 cc. in either case, and the bile was not concentrated. So far the substance found most effective in emptying the gallbladder is a mixture of cream and egg yolk, the stimulating effect depending on the fat content. 21 This does not excite the duodenum as much as olive oip2 but has the disadvantage in common with all other media of mixing with the samples of bile. In order to avoid contamination, I have allowed the tube to progress to the third portion of the duodenum or into the jejunum, introduced the stimulant followed by a little air, and then have withdrawn the tube until the tip reached the middle of the descending portion of the duodenum. The substances apparently act as well from the jejunum as from above, but it is not always possible to encourage the longer journey of the tube. The next most effective substance is a solution of 5 or 10 per cent peptone. I have used Bacto-protone (a mixture of proteoses) in the same strength and prefer it, as with this preparation there is usually sharper delineation and more rapid collection of the gallbladder bile than with peptone. In controlled experiments on dogs having duodenal cannulas, a flow of concentrated gallbladder bile occurred within five minutes after instilling 25 cc. of 5 per cent Bacto-protone into either the duodenum or jejunum. T!\,enty-four experiments were performed with only one failureY Two dogs were used in four additional experiments. One had a bisected loop of jejunum and an intact nervous system except for the divided myenteric plexus; the other had an intestinal anastomosis just above an ileal fistula, and was vagotomized and splanchnicectomized. The proteose solution was perfused through the loop and fistula. The latter animal gave no response to the stimulus while the former yielded a flow of bile similar in all respects to that of normal dogs. This could suggest that the stimulus is carried by way of extrinsic reflex pathways, but it may indicate simply that the ileum is incapable of cooperation. It is said that cholecystokinin is generated in the duodenum. In the Curtis Clinic, we use a solution consisting of 20 cc. of 7 per cent peptone and 10 cc. of 50 per cent magnesium sulfate
1664
WILLIAM DALE BEAMER
with successful drainages in about 70 per cent of all cases. The magnesium suIfate tends to relax the sphincter of Oddi (but may fail if used alone 15. 21) and the peptone is presumed to cause the gallbladder to contract. The completeness of evacuation is always questionable unless a dye-filled gallbladder is visualized by roentgen examination before and afterward. I am quite sure that it rarely empties completely. SOME FACTORS INVOLVED IN EMPTYING
It appears important that the intubation should be begun early in the morning, since there is a psychophysical disturbance with increased duodenal irritability in most individuals whose breakfast is delayed. To effect a satisfactory drainage it is also important that the gallbladder be well filled, as it normally is after a twelve-hour fast. A full gallbladder exerts an increased pressure to insure a flow of bile. One should not be misled into wrong diagnosis on the basis of absence of gallbladder bile when the organ has not had a sufficient length of time in which to store up bile. The pressure of the bile in a well-filled gallbladder may influence its tone. A high tonus may be just as important in maintaining a sufficient pressure within the gallbladder as active contraction of the musculature during the emptying process. At any rate, Bainbridge and Dale 23 found that distention augmented tonus rhythm without causing contraction in anesthetized dogs, and Ivy12 has never seen a good contraction in dogs in the digestive state with a partially emptied or contracted gallbladder. In addition, Deissler and Higgins 27 found that a certain optimum pressure was necessary in guinea pigs' gallbladders to produce normal tonus rhythm and that higher pressures would overcome the resistance of the sphincter of Oddi with leakage of the fluid. Although the gallbladder is rather well supplied with fine nerve fibers and ganglia, present-day evidence suggests that these may exert a regulatory influence on tonus rather than initiate gallbladder contraction. That such tonus changes may be carried by nerve pathways would seem to be true from the experience of Boyden and Parmacek,24 who frequently obtained a slight flow of bile on mere perception of fried bacon, or the observation of Levene25 of a sudden increase in the size of the gallbladder during nausea.
BILIARY DRAINAGE BY DUODENAL INTUBATION
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We note that upon stimulation we do not always obtain a response in increased bile flow even when the gallbladder is fairly well filled. We may deduce that such a failure may be due to a low intraluminal pressure 12 , 27 which makes a stimulus ineffectual when it would be adequate if the tone level were higher. Of course it may be due to abnormal spasticity of the sphincter of Oddi. Because of this we should not be hasty in drawing the conclusion that there is obstruction due to other causes when we do not obtain a flow of bile. EXAMINING THE BILE
Students always ask, "What should we look for?" The normal calor sequence of the biliary drainage is prima facie evidence of a normally functioning biliary tract. The consensus among gas.troenterologists is that the dark "B" bile comes only from the gallbladder. One may obtain a concentrated bile upon occasion in a cholecystectomized patient, but this would argue for a compensatory condition which is desirable. When "B" bile is present in only small amounts and with a relatively low concentration, it may be assumed that the gallbladder is functioning poorly. Complete absence of "B" bile is indicative of a blocked or nonfunctiorting gallbladder. Absence of "A," "B" and "C" fractions must be due to complete closure of the common bile duct. Except in the last case, no one attempt is sufficiently conclusive for diagnosis. The degree of clarity or turbidity of the fraction is somewhat indicative of the state of the organs. Microscopic examination only elaborates the picture of the color sequence. It reflects the condition of the part from which the bile originated. The examiner looks first for those particles usually present in disease of that part of the gall tract. The key to the anatomical structure from which the bile was obtained is in the type of desquamated epithelial cell which he views under the microscope; for example, the tall columnar cells which line the gallbladder serve as a check on the accuracy of recognizing "B" bile as coming from that structure. He further looks for pus, blood and crystals, especially cholesterol anq calcium bilirubinate. In studying the pus cells, he notes whether they are bile-stained and whether they are degenerate, as these are clues to the extent of disease and the degree of stasis. He also examines the contents for parasites and bacteria,
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making cultures in any uncertain case. In this latter connection, I might add that after careful mouth cleansing and with sterile apparatus the chances of obtaining an accurate culture are fairly good. When the same growth is found in two or three subsequent drainages and associated with other indications of infection, the evidence must not be ignored. If roentgen study, such as the cholecystogram, is possible in conjunction with the drainage, four especially valuable details can be elicited in addition to what can be learned without it. 1. 2. 3. 4.
Does the gallbladder fill well, and is it of normal shape? Are there any calculi present? Is the duodenal tube in the optimal position for drainage? Does the emptying of the gallbladder as seen on the x-ray plates agree with the volumes and color sequence of the bile fractions obtained?
It is understandable that one may wish to perform a duodenalbiliary drainage when there are no radiographic facilities available. But it is not so justifiable, in my opinion, to make roentgen studies of the gall tract without a concomitant duodenal intubation, provided the latter is not specifically contraindicated by (1) acute infections of undetermined origin, (2) calculi liable to produce impaction, or (3) acute coronary or serious cardiovascular conditions. CONCLUSIONS
Recent years have seen a shift away from biliary drainage as a therapeutic measure; it has come to be regarded only as a diagnostic medium. It is apparent, however, that there are toxic substances which may be removed only by periodic flushing of the biliary tract, and that the duodenal tube is an important adjuvant. In no other way are we as well able to follow the progress of our therapy. The benefit which patients with gall tract disease experience from periodic drainages cannot be fully ascribed t'o psychic reasons. BIBLIOGRAPHY 1. Clendening, L. and Hashinger, E.: Methods of Treatment. St. Louis, C. V. 2.
Mosby Co., 1941. Hemmeter, J. c.: Johns Hopkins Hosp. Bull., April, 1895; New York Med. Rec., Sept. 13, 1921.
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3. Kuhn, F.: Arch. f. Verdaungs Kranklieiten, 1898; Lyon: Non-Surgical Drainage of Gall Tract. Philadelphia, Lea & Febiger, 1923. 4. Einhorn, M.: New York Med. Rec., Oct. 9, 1909. 5. Gross, M.: New York Med. J., Aug. 22, 1914. 6. Rehfuss, M. E.: Indigestion. Philadelphia, W. B. Saunders Co., 1943. 7. Palefski, I. 0.: Interstate Med. J., Aug. 22, 1914. 8. Lyon, B. B. V.: J.A.M.A., 74:276, 1920. 9. Levin, A. J.: J.A.M.A., 76:1007, 1921. 10. Lyon, B. B. V.: J.A.M.A., 73:980, 1919. 11. Meltzer, S. J.: Am. J. Med. Se., ])3:469, 1917. 12. Ivy, A. C.: Physiol. Rev., 14:1, 1934. 13. Aaron, C. D.: Diseases of the Digestive Organs: Diagnosis and Treatment. Philadelphia, Lea & Febiger, 1927. 14. Ingelfinger, F. J. and Moss, R. E.: Am. J. Physiol., 136:561, 1942. 15. Bergh, G. S. and Layne, J. A.: Am. J. Digest. Dis., 9:162, 1942. 16. Unpublished experiments. 17. Kozoll, D. D. and Necheles, H.: Surg., Gynec. & Obst., 74:27, 1942. 18. Leuth, H. C.: Am. J. Physiol., 99:237, 1931. 19. Unpublished experiments. 20. Best, R. R. and Hicken, H. F.: Am. J. Surg., 39:533, 1938. 21. Kozoll, D. D. and Necheles, H.: Surg., Gynec. & Obst., 74:692, 1942. 22. Elton, N. W.: Rev. Gastroenterol., 7:65, 1940. 23. Bainbridge, F. A. and Dale, H. H.: J. Physiol., 33:138, 1905-06. 24. Boyden, E. A. and Parmacek, L.: Proc. Soc. Exper. BioI. & Med., 25:462, 1928. 25. Levene, G.: Am. J. Rocnt. & Rad. Ther., 26:97, 1931. 26. Waiters, W., McGowan, J. M., Butsch, W. L. and Knepper, P. A.: J.A.M.A., 109:1591, 1937. 27. Deissler, K. and Higgins, G.: Am. J. Physiol., 112:430, 1935.