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Acute Pancreatitis
Acute Pancreatitis A. H. AARON, M.D., F.A.C.P.* ELMER MILCH, M.D., F.A.C.S.**
ACUTE primary pancreatitis (acute secondary pancreatitis, pancreatic apoplexy, acute pancreatic necrosis, gangrenous and suppurative pancreatitis) is one of the few abdominal catastrophes in which the result of treatment by conservative medical means is more effective than surgical intervention. In acute abdominal conditions the physician and the surgeon attempt to be as accurate as possible in their diagnosis. If an acute perforated peptic ulcer is suspected, and on opening the abdomen we find an acute cholecystitis with calculi, the patient has lost nothing, as both usually require surgical treatment. However, if a diagnosis of primary acute pancreatitis is volunteered and the patient is treated by conservative methods, should a surgically amenable lesion be present and not recognized the delay results in increasing mortality and morbidity. There is a tremendous responsibility in the correct diagnosis of this lesion, and it must be emphasized. It is important to realize that acute primary pancreatitis may be, and frequently is, a postoperative complication following operations on the biliary and upper gastrointestinal tract. Elsewhere in this volume Dr. E. N. Collins discusses the etiology of acute pancreatitis, and Drs. H. M. Pollard and R. J. Bolt present the laboratory procedures with normal values and diagnostic interpretation.
PATHOLOGY
Grossly the organ is enlarged, edematous, and on cutting shows areas of necrosis and hemorrhage, dotted with yellowish white opaque patches of fat necrosis. Similar evidences of fat necrosis may be found on the peritoneum and other organs. In accordance with the severity of the reaction a slough or an abscess may be present. It is believed that the * Clinical Professor of Medicine, University of Buffalo School of Medicine; Attending Physician at the Buffalo General Hospital, Buffalo, New York. Diplomate, American Board of Internal Medicine.
** Assistant Clinical Professor of Surgery at the University of Buffalo; Attending Surgeon at the Buffalo General Hospital. Dip/ornate, American Board of Surgery. 451
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milder clinical attacks are those associated with transient pancreatic edema. The edematous type may subside producing very little damage. The more severe forms may result in permanent changes. Fat necrosis is due to the action of the pancreatic lipase. It is believed that the hemorrhagic phenomena, as well as necrosis, are caused by vascular lesions resulting from the action of the free trypsin on the blood vessels. Peritonitis involving first the adjacent tissues and then ultimately the greater portion of the abdomen with ileus and widely distributed fat necrosis may occur. Hemorrhage into the abdomen or adjacent tissues may take place. It is important to bear in mind that the severity of the clinical picture may be dependent upon the degree of the pathologic changes present. DIAGNOSIS
Clinical Picture
Primary acute pancreatitis more frequently occurs in obese, middleaged males who have overindulged in food or alcohol. Severe pain in the left epigastric area, radiating to the left back, retrosternal or interscapular areas, left chest or left flank, is present. At times there is reference of the pain to either side of the neck, but usually the left, this being dependent upon the involvement of the diaphragm. If this is secondary pancreatitis in a patient who has had attacks of biliary colic, he will tell the attending physician that this attack is entirely different from his previous attacks, which were usually confined to the right upper quadrant. This one is more severe and overwhelming. It is this pain picture and distribution that should arouse at once in the physician's mind the possibility of acute pancreatitis. Nausea and vomiting occur in approximately 80 per cent of cases. Jaundice is present in about one-fourth, and is due either to obstruction of the common duct by a gallstone, pressure on the duct by the swollen head of the pancreas, or an associated hepatitis. Hematemesis, as a complicating symptom confusing the clinical picture, occurred in ten of 307 patients reported by Paxton and Paine 1 and melena occurred in four cases reported by O'Brien and Thayer.2 Physical Signs
The patient may be in shock. There frequently is limitation of the respiratory movements due to an alteration in the position of the diaphragm or involvement of the peritoneal covering of the diaphragm. The temperature and pulse vary with the pathology, the length of time that has elapsed since the onset of the attack, and the presence of complications. Cyanosis has not been present in our cases. On examination the abdomen may be distended, with tenderness in
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the left upper quadrant and frequently in the left costovertebral angle. Peristalsis is absent due to a paralytic ileus. There may be dullness in the flanks due to the presence of hemorrhagic or reactive fluid. Rebound tenderness is present. Early flatness on percussion at the base of the left lung, not altered by deep breathing, is evidence of atelectasis due to the rising diaphragm or the accumulation of fluid in the left pleural cavity. This sign may occur in any patient who has diaphragmatic peritonitis, regardless of the etiology. It occurs earlier and more frequently, however, in lesions of the upper abdomen such as acute pancreatitis or perforated peptic ulcer. In our experience it has been more common on the right side with peptic ulcer and on the left with acute pancreatitis. Cutaneous Signs
Sigmund and Shelley 3 in an excellent review summarize these various manifestations in patients with acute hemorrhagic pancreatitis, and emphasize the importance of the escape of trypsin. They report a case of their own in which they describe the development of livedo reticularis. All of the::le phenomena are limited to seepage of hemoglobin-colored fluid from the abdominal cavity through the peritoneal openings and fascial planes. A small amount of fluid may be readily withdrawn with a 5 cc. syringe and a 21 gauge needle to confirm this finding. This fluid may be hemorrhagic and contain enzymatic substances. These late signs usually appearing on the second to fourth days are edema, induration, and an ecchymotic discoloration of the skin in the region of the left flank, or possibly both flanks and sometimes about the umbilicus. This is a combination of the Cullen sign of discoloration about the umbilicus due to the presence of blood in the peritoneal cavity, and that described by Grey-Turner due to the extravasation of blood into the left flank. It is not necessarily associated with necrosis of the local tissue due to the presence of pancreatic ferments. That these signs may occur as a result of retroperitoneal extravasation has been demonstrated by Fallis. 4 The clinician should bear in mind that the above mentioned signs occur late, and he must not wait for their appearance to make a diagnosis of pancreatitis. They are confirmatory signs. Laboratory Findings
The Serum Amylase Test. The serum amylase test, the importance of which has been emphasized by Elman,5 should be performed routinely in all abdominal conditions soon after the patient's admission to the hospital. Elman stressed this finding as a useful baseline. He advises repeating the test ::leveral times within the first 48 hours if one suspects acute pancreatitis. These determinations serve as a valuable indicator of the presence of pancreatitis. Acute pancreatitis is an occasional complication following upper
A. H. Aaron, Elmer Milch abdominal operations, such as biliary tract or gastric resections, and can be recognized only by serial amylase determinations in these circumstances. The method of doing the amylase test should be that one which the individual hospital and laboratory has consistently carried out. Unfortunately, an increased serum amylase may occur in patients with acute abdominal conditions other than pancreatitis, but seldom reaches the high figures, eight to ten times the normal, seen in acute primary pancreatitis. Smogyi 6 has reported on the estimation of serum amylase in peritoneal fluid, and Keith, Zollinger and McCleery,7 substantiated by Meyers and his associates 8 state: "The peritoneal fluid amylase was consistently higher than the blood amylase, and the elevation persisted for two to four days longer than blood amylase findings. This may be an additional amylase determination of diagnostic import." While peritoneal fluid amylase determinations may be of some additional value in diagnosis, we must emphasize the importance of frequent, daily blood estimations beginning early in the attack of the disease because of the tendency of the figure to fall as time goes on. Serum amylase values may be increased by the injection of an opiate such as morphine or codeine. In a recent editorial, Elman 9 calls attention to this observation by Lagerlof,lo Gross and his co-authors,l1 and Wapshaw. 12 He also suggests there may be an elevation of the enzyme due to anuria or temporary renal failure. In our experience the greatest single error in amylase determinations had been that which occurs in the laboratory, and I should like to impress the value of repetition of the test. Amylase determination is the single most valuable laboratory aid at the present time. Elman has suggested that any patient who has had biliary tract disease or suspected pancreatitis should be so informed, or be given a small card indicating that he has such a disease and emphasizing his proneness to an attack of acute pancreatitis. If he is not in contact with his personal physician during an attack, amylase tests should be done. Blood Lipase; Hemoglobin Concentration. Increases in lipase values in the urine and blood occur, but have not been as thoroughly studied and correlated with the disease as has the blood amylase test. Cattell and Warren13 call attention to the importance of the recognition of hemoglobin concentration and its early occurrence, as well as its value as an indicator for the maintenance of electrolyte and blood volume. Antithrombin Titer. This has not been as thoroughly studied and correlated as has the amylase test. Serum Calcium. In 1942 Edmondson and Fields 14 noted the appearance of tetany during the course of acute pancreatitis. This observation led to the finding of low serum calcium levels in the disease. These authors
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suggested the finding to be due to the action of lipase-splitting neutral fat, which precipitate calcium as soaps in and about the pancreas. This factor, plus the fixation of calcium in the tissues, results in a withdrawal of calcium from the blood with a fall in the serum calcium. Glucose. The estimation of blood glucose, alone, is of no great diagnostic value. There is a moderate increase in blood sugar of a transitory nature in a small number of the cases. Roentgenologic Findings. Every patient with an acute abdominal disorder is entitled to a flat film. It is of great value in acute pancreatitis in a negative fashion. Poppe}15 called attention to the following conditions which may be demonstrated in the x-ray film: (1) local ileus in the duodenum or ileum; (2) calcification of the pancreas; (3) biliary calculi; (4) fluid in the left pleural cavity; (5) fluid in the abdomen; (6) absence or presence of air beneath the diaphragm. Differential Diagnosis Biliary Tract Disease with Calculi. This is the most common lesion to be differentiated from acute pancreatitis. It occurs more frequently in women, and during pregnancy. There is a history of colic requiring morphine, with intermittent periods of freedom from attacks. Vague digestive upsets may be ascribed to pregnancy. There may have been chills, fever, jaundice, and a white stool. Upon examination tenderness to deep pressure and hammer percussion is found over the liver and gallbladder area, as well as muscle spasm. The clinical picture is not as severe as that of acute pancreatitis unless a gangrenous or acute suppurating cholecystitis is present. Then the differential diagnosis may be difficult because there frequently is an associated pancreatitis with these lesions and the serum amylase test may be elevated. A previous roentgenogram may have demonstrated a nonfunctioning gallbladder or one containing calculi. It is important to ask the patient about these factors. Pain may be referred to the right shoulder and retrosternal area. The previous history provides the most important information for eliminating biliary tract disease. Jaundice is much more frequent in biliary tract disease. Perforated Gastric or Duodenal Ulcer. Again, the previous history of pain, food and alkali reli(ilf over a period of time, usually in a younger person, is of great importance. There is more diffuse abdominal tenderness and muscle rigidity present in this entity. Of great diagnostic help is the history of previous roentgenologic study demonstrating the presence of a peptic ulcer. A flat film revealing the presence of air in the subdiaphragmatic spaces is most important. A penetrating or perforating peptic ulcer into the pancreas may invoke an acute pancreatitis with alterations in the serum amylase.
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Vascular Accidents in the Abdomen. Vascular accidents in the abdomen occur and mimic acute pancreatitis. This is to be suspected when one has a patient with perivascular disease, or a cardiac lesion as a source of emboli, with evidences of embolic phenomena elsewhere. Hematemesis and melena are important clinical evidences. Amylase is not usually elevated, and if it is the levels are not so high. Coronary Insufficiency or Occlusion. In 1943 Gottesman, Casten and Beller16 found that patients with acute pancreatitis had changes in their electrocardiograms of a type that may occur in myocardial infarction. This points to the necessity for careful clinical investigation of a patient giving a history of previous distress on exertion, or anginal attacks with characteristic pain distribution. The electrocardiographic findings in pancreatic disease have no special significance, as shown by GubnerY They may be related to shock, alteration in coronary flow and serum electrolytic changes, or viscerocardiac reflexes which are present in other acute abdominal conditions. Bauerlein and Stobbe 18 call attention to the fact that their many electrocardiograms on persons suffering from shock and alterations in potassium blood content show no changes from normal. They recently reported a case of acute pancreatitis in which severe electrocardiographic findings were present in life, but with no change in the coronary vessels evident at autopsy. Intestinal Obstruction. Intestinal obstruction is distinguished by the absence of an etiologic factor in a well taken history, the presence of a scar on the abdomen indicating a previous surgical procedure, late colic of the intestinal type, the presence of visible peristalsis, and adequate roentgenographic studies demonstrating evidences of' intestinal obstruction. Raffensperger19 has reported moderately increased serum amylase in intestinal obstruction. Clinical Summary
The finding in a male who has overindulged in alcohol or food of acute pain in the left upper quadrant boring through to the back, evidences of shock, a serum amylase that is ten to twenty times normal, fluid at the left base, roentgenologic evidences of duodenal ileus and the presence of abdominal fluid warrants the diagnosis of acute pancreatitis. Cutaneous signs occur late, from the third day on, and should not be waited for to make the diagnosis. Warning!
Beware of the possible presence of a surgical condition which requires immediate intervention. Pain may confuse the picture, since a person with an acute abdominal attack may have received an opiate, which elevates the amylase figure, before he is examined.
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Surgeon::; and physicians are in general agreement that if the diagnosis of acute primary pancreatitis can be made, with the elimination of etiologic factor::; such as ruptured peptic ulcer or biliary tract disease, the patient should be treated medically rather than by immediate surgical intervention. ORDERS FOR TREATMENT OF ACUTE PANCREATITIS
Routine Orders Chemistries
Treatment of Shock; Fluid and Electrolyte Balance
1. 2. 3. 1. 2. 3. 4.
5. 6.
7.
Pain Sedation
8.
Rela.ration of Sphincter of Oddi
10.
Abdominal Disient'ion and Vomiting Reduction of Pancreatic Secretions A ntiobiotics
11. 12. 13. 14.
Steroids
n.
Daily urinalysis Complete blood count Hematocrit Fasting blood glucose Blood urea Serum Cl-, K+, Na+, C02, A/G ratio Serum calcium immediately after the third day a. If deficit, calcium gluconate 10 cc. of 10% solution intravenously Type and cross match 1500 cc. blood immediately a. Give 500 cc. whole blood as soon as possible b. Additional given if shock persists 100 cc. serum albumin slowly intravenously-repeat in 4 hours if shock continues 2000 cc. 10% Travcrt's solution in N/2 NaCl with 0.3% KCl a. 1 ampule ascorbin added to clysis b. 20 units regular insulin into each bottle intravenously 20 units regular insulin for each 100 grams of glucose Demerol 50 mg. every 3 to 4 hours or p.r.n., or morphine sulfate 8 mg. (Ys grain) if Dernerol fails Luminal sodium 120 mg. (2 grains) or Doriden 500 rng. a. Demerol 50 mg. every 4 hours or p.r.n. b. Atropine 0.6 mg. (1/100 grain) c. Choice of papaverine 120 mg. (2 grains) intravcnously or nitroglycerin 0.6 mg. (I /100 grain) Nothing by mouth Insert nasogastric tube and connect to suction Chart intake and output Atropine given as above or Banthine 50 to 100 mg. every 6 hours orally or intravenously
15. a. b. 16. a. b. c.
Forticillin 400,000 units intrarnuscularly every 8 hOur8 Dihydrostreptomycin 0.5 gram every 8 hours Hydrocortisone 100 mg. Corticotropin 40 units per cc. HP Acthar Gel 20 units per cc. intramuscularly
Pain
Every effort should be made to relieve pain as quickly as possible, because severe pain is frequently accompanied by vasoconstriction which may reduce pancreatic blood supply sufficiently to convert simple edema to necrosis. Demerol in 50 mg. doses is valuable. Its use intravenously may be necessary. Morphine has been avoided because it induces spasms of the sphincter of Oddi. Nevertheless, we have found morphine to be the best drug in many instances, and have u::;ed it. Comfort has also em-
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phasized its value. It may be that the diminution of secretion by the use of the atropine-Banthine type of drug may lessen the importance of the spasm of the sphincter of Oddi under these circumstances. Relaxation of the sphincter of Oddi is desirable because of associated pain and further reflux of bile into the pancreatic duct. The most effective antispasmodic agents for this purpose are papaverine 120 mg. (2 grains) given intravenously, nitroglycerin 0.4 to 1.3 mg. (1/150 to 1/50 grain) given sublingually, amylnitrate pearls, or atropine 1.3 mg. (1/50 grain) given intramuscularly.
Fig. 69. Anteroposterior and lateral roentgenograms of thoracic and lumbar vertebrae showing position of needles for block of splanchnic nerves. Injection of 10 cc. of an ammonium sulfate-benzyl alcohol solution through each needle gave 10 months' relief of abdominal pain due to pancreatitis. (From Journal-Lancet 72: 76--83 [Feb.)
1952.)
The relief of pain can be obtained in a few patients only by repeated blocking of the sympathetic ganglia with a one per cent solution of procaine or xylocaine (Fig. 69). Ganglia T 10 to Tu are blocked bilaterally every 12 to 24 hours until symptoms have subsided. However, the paravertebral block has not been especially helpful in our hands. The method described by Pender and Lundy 20 follows: "Needles 120 mm. in length are inserted just under the twelfth rib and passed in an anteromedial direction until the tips of the needles lie on the anterior surface of the body of the first lumbar vertebra or the twelfth thoracic vertebra. The injection of 10 to 20 cc. of 0.75 per cent solution of ammonium sulfate and 0.75 per cent solution of benzyl alcohol usually aggravates the pancreatic pain for about half an hour and then gives relief. The duration of the relief is unpredictable, ranging from a few days to many months."
The use of continuous or intermittent epidural procaine anesthesia to relieve the pain in severe cases of acute pancreatitis has been very encouraging21 (Fig. 70).
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Fig. 70. Continuous epidural analgesia. Note position of catheter in epidural space in relation to origin of nerve supply to pancreas. In placing the needle in the epidural space the procedure as described by Hingson and South worth is followed. A wheal is made in the skin over the chosen lumbar or thoracic interspace and the subcutaneous tissues down to the ligament are infiltrated with 1 per cent procaine solution. A special 16 gauge Huber pointed needle is inserted in a slightly upward direction until the point meets the ligament. A 2 cc. syringe, filled with 1 per cent procaine solution, is then attached to the needle and gentle pressure is made on the plunger with the thumb while the needle is slowly advanced. When the epidural space is entered there is a sudden give to the plunger. The syringe is disconnected from the needle and the needle is carefully observed for any flow of spinal fluid. It is then checked again by attaching an empty syringe to the needle and making sure that no spinal fluid can be withdrawn. A No. 372 F. ureteral catheter is then threaded through the needle and advanced to the desired level within the epidural space, and small amounts of solution are injected as the tip of the catheter is advanced so as to separate the epidural tissues and facilitate the passage of the catheter. A test dose of 5 cc. is given to be certain that the catheter is not in the subarachnoid space. Subsequently, 5 to 10 cc. of 1 per cent procaine is injected every 30 minutes as required. It is better, in our experience, to give frequent small doses than to depend upon larger amounts at longer intervals. In order to produce anesthesia of the nerves supplying the pancreas, the tip of the ureteral catheter should be placed at the level of the eighth thoracic spinal segment. To reach this level it should lie at a point between the spinous processes of the fifth and sixth thoracic vertebrae. (From Cattell, R. B. and Warren, K. W.: Surgery of the Pancreas.)
Shock Every effort should be made to overcome the shocklike picture by the administration of plasma or whole blood in the indicated amounts checked by proper laboratory procedures. The use of serum albumin has recently been reported by KenweII22 as a most important aid in the treatment of acute pancreatitis. It is suggested that its value is on the basis of an antitrypsinogen factor. Recent studies23 . 24 provide no evidence
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that the albumin inhibits trypsin. However, during the acute phasn of pancreatitis there is a definite whole blood volume deficit, plasma volume deficit and a definite depletion of red cell masl:l. With the above I:lhoclclike picture and a definite plasma volume deficit, serum albumin in amounts of 100 to 200 cc. intravenously in an adult of average size is a valuable adjunct in the immediate treatment of shock in acute pancreatitis. The frequent use of serum albumin il:l definitely indicated to dissipate the associated shock picture. 25 Fluid and Electrolyte Balanee
Nothing by mouth is permitted to these patients, hence it is paramount. that fluid and electrolyte balance be maintained to promote adequate renal function. Normal saline is given parenterally to offset sodium and chloride loss due to vomiting and intubation, plus adequate potassium to avoid hypopotassemia. Glucose solutions are contraindicated unless covered by adequate amounts of insulin. AbdOlninal Distention and VOlniting
This is best controlled by the insertion of an indwelling nasogastric or intestinal tube connected to a Wangensteen suction apparatul:l. Suppuration
The use of antibiotics in the prevention of suppuration is difficult to evaluate, but past experience justifies their prophylactic use. In our hands a combination of penicillin and streptomycin has been most effective, and the inevitable presence of peritonitis warrants their use in every case to avert bacterial growth in a rnactive fluid. Reduction of Pancreatic Secretions (HornlOnal and Nervous StiIllulation)
The hormonal stimulation of the pancreas is inhibited by restricting food and liquids by mouth. Pancreatic secretions are also subjected to nervous stimulation mediated via the vagus nerve. Such drugs as atropine 0.6 mg. (1/100 grain) or Banthine 50 to 100 mg. intramuscularly can depress the vagal activity and reduce secretion. Drugs such as prostigmine, which stimulate the vagus nerves and thus pancreatic secretion, are withheld. H ypocalceIllia
Blood calcium studies should be carried out daily, and calcium gluconate administered upon the appearance of calcium deficit. Calcium gluconate intravenously, 1 gram daily, usually is adequate. Diabetes Mellitus
It is imperative that the blood and the urine be examined at frequent intervals since some of these patients develop diabetes and require insulin
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therapy. The insulin therapy must also be closely watched and insulin shock avoided, because hypoglycemic stimulation of the vagal mechanism of pancreatic secretions may prove deleterious. Permanent diabetes is a common after-effect of acute pancreatitis. Steroids
Elman has stated correctly that the use of cortisone is still quite experimental. He has seen it used most effectively in dosages of 200 mg. a day. A good lead might be an eosinophil count which, if high in the presence of severe symptoms, might suggest the absence of adrenocortical stimulation and therefore the administration of cortisone, or preferably hydrocortisone, parenterally. Cattell and Warren13 state that cortisone orally caused no appreciable change of water, potassium or sodium values in the pancreatic juice. There was a decrease in volume output for the first two days. Stephenson, Pfeffer and Saypo12 6 report a patient with acute hemorrhagic pancreatitis who was in a serious, almost moribund state but recovered following the use of cortisone. All of the factors associated with shock, which may produce a depletion of the cortical steroids, may be present and supplemental administration indicated. Duration of Therapy
The duration of medical therapy depends upon the progress of the patient. The clinical and physical findings are the best guides. The rapidity of recovery from the shocklike state, the return of the temperature to normal, a drop in the leukocyte count and the decrease of evidences of abdominal disease are the most important guides. A careful watch must be kept for complications such as hematoma, acute cyst formation, abscess formation or spreading peritonitis, any of which require surgical intervention. These complications are suggested by persistence of fever, particularly of an intermittent type, for more than a week and the presence of a mass which can be detected by palpation or x-ray study showing displacement of the stomach. Indications for Surgical Intervention in Acute Pancreatitis
Once the diagnosis of acute pancreatitis is firmly established, conservative treatment is the therapy of choice. However, if any doubt exists as to the exact diagnosis, immediate surgical intervention is indicated, since all other conditions simulating acute pancreatitis may be amenable to surgical therapy. If an operation is performed and acute pancreatitis is found, it is our opinion that the abdomen should be closed immediately unless definite disease is found in the biliary tract. Routine drainage of the nonpathologic gallbladder or common duct is of no avail if the acute pancreatitis
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is on a vascular basis rather than due to disease of the biliary tract~and this in our opinion is often the case. Once nonsurgical treatment is instituted, operation is performed only for the complications of the disease such as lesser sac abscess or cyst. Surgical procedures on the biliary tract are never indicated either in the acute or quiescent stage of pancreatitis unless definite biliary tract disease is demonstrated. When at all possible the operation, if indicated, should be performed when the acute phase of the pancreatitis has completely subsided. PROGNOSIS
Some years ago we reported a series of cases of acute pancreatitis in which patients subjected to immediate operation showed a mortality of 35 per cent, while in those in whom operation was delayed or omitted the mortality rate was 5 per cent. These figures do not reflect the present use of improved combative measures. Bockus27 in a recent communication reports a total mortality of 4.3 per cent. There was, however, a 37 per cent mortality in eight cases in which laparotomy was done during the acute phase. There were no deaths of patients who had an elective operation after the acute symptoms subsided, and one death among 82 patients treated medically during the acute phase of the disease. O'Brien and Thayer2 had an initial mortality of 8 per cent in 108 cases treated conservatively. A further follow-up revealed a total mortality of 13 per cent. Twenty-six of their patients had only one attack; 74 per cent had further attacks. REFERENCES Especially recommended are the excellent text by Warren and Cattell (ref. 13), the annual reviews of the pancreas by Elman appearing each year in Gastroenterology, the enlightening review of the subject by Machella in the Veterans Administration Technical Bulletin of March 2, 1953 (ref. 28), and the numerous outstanding contributions on fundamentals and clinical aspects by Mandred Comfort. 1. Paxton, J. R. and Payne, J. H.: Acute Pancreatitis: Statistical Review of 307 Established Cases of Acute Pancreatitis. Surg., Gynec. & Obst. 89: 69-75
(Jan) 1948.
2. O'Brien, J. J. and Thayer, T. R.: Pancreatitis. New England J. Med. 253 (9):
355 (Sept. 1) 1955. 3. Sigmund, W. J. and Shelley, W. B.: Cutaneous Manifestations of Acut(Pancreatitis. New England J. Med. 251 (21): 851 (Nov. 18) 1954. 4. Fallis, L. S.: Acute Pancreatitis. Proc. Royal Soc. Med. 46: 113, 1953. 5. Elman, R., Arneson, N. and Graham, E. A.: Value of Blood Amylase Estimations in Diagnosis of Pancreatic Disease: Clinical Study. Arch. Surg. 19: 943 (Pt. 1) 1929. 6. Smogyi, M.: Micromethods for Estimation of Diastase. J. BioI. Chem. 125: 399414 (Sept.) 1938. 7. Keith, L. M. Jr., Zollinger, R. M. and McCleery, R. J.: Peritoneal Fluid Amylase Determinations as Aid in Diagnosis of Acute Pancreatitis. Arch. Surg. 61: 930, 1950.
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8. Meyers, S. G., Brown, J. R., Boone, R. and Henderson, H.: Clinical Manifestations of Pancreatitis. Gastroenterology 28 (5): 803 (May) 1955. 9. Elman, R.: Acute Pancreatitis and the Laboratory. Surg., Gynec. & Obst. 100 (2): 241 (Feb.) 1955. 10. Lagerlof, H.: Normal Esterases and Pancreatic Lipase in Blood; Study with New Chemical and Clinical Methods (Second Secretin Test). Acta med. Scandinav. 120: 407, 1945. 11. Gross, J. B., Comfort, M. W., Mathieson, D. W. and Power, M. D.: Elevated Values for Serum Amylase and Lipase Following Administration of Opiates. Preliminary Report. Proc., Staff Meet., Mayo Clin. 26: 81, 1951. 12. Wapshaw, H.: Lancet 1: 373,1953. 13. Cattell, R. B., and Warren, K. W.: Surgery of Pancreas. Philadelphia, W. B. Saunders Co., 1953. 14. Edmondson, H. A. and Fields, 1. A.: Relation of Calcium and Lipids to Acute Pancreatic Necrosis; Report of 15 Cases in One of Whieh Embolism Occurred. Arch. Int. Med. 67: 177-190 (Feb.) 1942. 15. Poppel, M. H.: Roentgen Manifestations of Pancreatic Disease. Springfield, Ill., C. C Thomas, 1951. 16. Gottesman, J., Casten, D. and Beller, A. J.: Changes in Electrocardiogram Induced by Acute Pancreatitis. J.A.M.A. 123: 892, 1943. 17. Gubner, R. S.: Electrocardiographic Changes in Abdominal Disease. J.A.M.A. 124: 122-123 (Jan. 8) 1944. 18. Bauerlein, T. C. and Stobbe, L. H. 0.: Acute Pancreatitis Simulating Myocardial Infarction with Characteristic Electrocardiographic Changes. Gastroenterology 27 (6): 861 (Dec.) 1954. 19. Raffensperger, E. C.: Elevated Serum Pancreatic Enzyme Values without Primary Intrinsic Pancreatic Disease. Ann. Int. Med. 35: 342, 1951. 20. Pender, J. W. and Lundy, J. S.: Diagnostic and Therapeutic Nerve Blocks. Journal-Lancet 72: 76 (Feb.) 1952. 21. Orr, R. B., and Warren K. W.: Continuous Epidural Analgesia in Acute Pancreatitis. Lahey Clin. Bull. 6: 204-210, 1950. 22. Kenwell, H. N. and Wels, P. B.: Acute Hemorrhagic Pancreatitis. Report of 11 Consecutive Cases Treated with Human Serum Albumin. Surg., Gynec. & Obst.96: 169, 1953. 23. Keith, L. M. Jr., and Watman, R. N.: Blood Volume Deficits in Pancreatitis. Surgical Forum, Clinical Congress of American College of Surgeons, 1954. Philadelphia, W. B. Saunders Co., p. 380. 24. Elliott, D. W.: Mechanism of Benefit Derived from Concentrated Human Serum Albumin in Experimental Acute Pancreatitis. Surgical Forum, Clinical Congress of American College of Surgeons, 1954. Philadelphia, W. B. Saunders Co., p. 384. 25. ElIiott, D. W., Zollinger, R. M., Moore, R. and Ellison, E. H.: The Use of Human Serum Albumin in the Management of Acute Pancreatitis. Gastroenterology 28 (4): 563 (April) 1955. 26. Stephenson, H. E., Pfeffer, R. B. and Saypol, G. M.: Acute Hemorrhagic Pancreatitis. Arch. Surg. 62: 307, 1952. 27. Bockus, H. L., KaIser, M. H., Roth, J. L. A. and Bogoch, A. L.: Clinical Features of Acute Inflammation of Pancreas. A.M.A. Arch. Int. Med. 96 (3): 308 (Sept.) 1955. 28. Machella, T. E.: Veterans Administration Technical Bulletin, TB 10-87, March 2, 1953. 40 W. North Street Buffalo 2, New York
ACUTE primary pancreatitis (acute secondary pancreatitis, pancreatic apoplexy, acute pancreatic necrosis, gangrenous and suppurative pancreatitis) is one of the few abdominal catastrophes in which the result of treatment by conservative medical means is more effective than surgical intervention. In acute abdominal conditions the physician and the surgeon attempt to be as accurate as possible in their diagnosis. If an acute perforated peptic ulcer is suspected, and on opening the abdomen we find an acute cholecystitis with calculi, the patient has lost nothing, as both usually require surgical treatment. However, if a diagnosis of primary acute pancreatitis is volunteered and the patient is treated by conservative methods, should a surgically amenable lesion be present and not recognized the delay results in increasing mortality and morbidity. There is a tremendous responsibility in the correct diagnosis of this lesion, and it must be emphasized. It is important to realize that acute primary pancreatitis may be, and frequently is, a postoperative complication following operations on the biliary and upper gastrointestinal tract. Elsewhere in this volume Dr. E. N. Collins discusses the etiology of acute pancreatitis, and Drs. H. M. Pollard and R. J. Bolt present the laboratory procedures with normal values and diagnostic interpretation.
PATHOLOGY
Grossly the organ is enlarged, edematous, and on cutting shows areas of necrosis and hemorrhage, dotted with yellowish white opaque patches of fat necrosis. Similar evidences of fat necrosis may be found on the peritoneum and other organs. In accordance with the severity of the reaction a slough or an abscess may be present. It is believed that the * Clinical Professor of Medicine, University of Buffalo School of Medicine; Attending Physician at the Buffalo General Hospital, Buffalo, New York. Diplomate, American Board of Internal Medicine.
** Assistant Clinical Professor of Surgery at the University of Buffalo; Attending Surgeon at the Buffalo General Hospital. Dip/ornate, American Board of Surgery. 451
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milder clinical attacks are those associated with transient pancreatic edema. The edematous type may subside producing very little damage. The more severe forms may result in permanent changes. Fat necrosis is due to the action of the pancreatic lipase. It is believed that the hemorrhagic phenomena, as well as necrosis, are caused by vascular lesions resulting from the action of the free trypsin on the blood vessels. Peritonitis involving first the adjacent tissues and then ultimately the greater portion of the abdomen with ileus and widely distributed fat necrosis may occur. Hemorrhage into the abdomen or adjacent tissues may take place. It is important to bear in mind that the severity of the clinical picture may be dependent upon the degree of the pathologic changes present. DIAGNOSIS
Clinical Picture
Primary acute pancreatitis more frequently occurs in obese, middleaged males who have overindulged in food or alcohol. Severe pain in the left epigastric area, radiating to the left back, retrosternal or interscapular areas, left chest or left flank, is present. At times there is reference of the pain to either side of the neck, but usually the left, this being dependent upon the involvement of the diaphragm. If this is secondary pancreatitis in a patient who has had attacks of biliary colic, he will tell the attending physician that this attack is entirely different from his previous attacks, which were usually confined to the right upper quadrant. This one is more severe and overwhelming. It is this pain picture and distribution that should arouse at once in the physician's mind the possibility of acute pancreatitis. Nausea and vomiting occur in approximately 80 per cent of cases. Jaundice is present in about one-fourth, and is due either to obstruction of the common duct by a gallstone, pressure on the duct by the swollen head of the pancreas, or an associated hepatitis. Hematemesis, as a complicating symptom confusing the clinical picture, occurred in ten of 307 patients reported by Paxton and Paine 1 and melena occurred in four cases reported by O'Brien and Thayer.2 Physical Signs
The patient may be in shock. There frequently is limitation of the respiratory movements due to an alteration in the position of the diaphragm or involvement of the peritoneal covering of the diaphragm. The temperature and pulse vary with the pathology, the length of time that has elapsed since the onset of the attack, and the presence of complications. Cyanosis has not been present in our cases. On examination the abdomen may be distended, with tenderness in
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the left upper quadrant and frequently in the left costovertebral angle. Peristalsis is absent due to a paralytic ileus. There may be dullness in the flanks due to the presence of hemorrhagic or reactive fluid. Rebound tenderness is present. Early flatness on percussion at the base of the left lung, not altered by deep breathing, is evidence of atelectasis due to the rising diaphragm or the accumulation of fluid in the left pleural cavity. This sign may occur in any patient who has diaphragmatic peritonitis, regardless of the etiology. It occurs earlier and more frequently, however, in lesions of the upper abdomen such as acute pancreatitis or perforated peptic ulcer. In our experience it has been more common on the right side with peptic ulcer and on the left with acute pancreatitis. Cutaneous Signs
Sigmund and Shelley 3 in an excellent review summarize these various manifestations in patients with acute hemorrhagic pancreatitis, and emphasize the importance of the escape of trypsin. They report a case of their own in which they describe the development of livedo reticularis. All of the::le phenomena are limited to seepage of hemoglobin-colored fluid from the abdominal cavity through the peritoneal openings and fascial planes. A small amount of fluid may be readily withdrawn with a 5 cc. syringe and a 21 gauge needle to confirm this finding. This fluid may be hemorrhagic and contain enzymatic substances. These late signs usually appearing on the second to fourth days are edema, induration, and an ecchymotic discoloration of the skin in the region of the left flank, or possibly both flanks and sometimes about the umbilicus. This is a combination of the Cullen sign of discoloration about the umbilicus due to the presence of blood in the peritoneal cavity, and that described by Grey-Turner due to the extravasation of blood into the left flank. It is not necessarily associated with necrosis of the local tissue due to the presence of pancreatic ferments. That these signs may occur as a result of retroperitoneal extravasation has been demonstrated by Fallis. 4 The clinician should bear in mind that the above mentioned signs occur late, and he must not wait for their appearance to make a diagnosis of pancreatitis. They are confirmatory signs. Laboratory Findings
The Serum Amylase Test. The serum amylase test, the importance of which has been emphasized by Elman,5 should be performed routinely in all abdominal conditions soon after the patient's admission to the hospital. Elman stressed this finding as a useful baseline. He advises repeating the test ::leveral times within the first 48 hours if one suspects acute pancreatitis. These determinations serve as a valuable indicator of the presence of pancreatitis. Acute pancreatitis is an occasional complication following upper
A. H. Aaron, Elmer Milch abdominal operations, such as biliary tract or gastric resections, and can be recognized only by serial amylase determinations in these circumstances. The method of doing the amylase test should be that one which the individual hospital and laboratory has consistently carried out. Unfortunately, an increased serum amylase may occur in patients with acute abdominal conditions other than pancreatitis, but seldom reaches the high figures, eight to ten times the normal, seen in acute primary pancreatitis. Smogyi 6 has reported on the estimation of serum amylase in peritoneal fluid, and Keith, Zollinger and McCleery,7 substantiated by Meyers and his associates 8 state: "The peritoneal fluid amylase was consistently higher than the blood amylase, and the elevation persisted for two to four days longer than blood amylase findings. This may be an additional amylase determination of diagnostic import." While peritoneal fluid amylase determinations may be of some additional value in diagnosis, we must emphasize the importance of frequent, daily blood estimations beginning early in the attack of the disease because of the tendency of the figure to fall as time goes on. Serum amylase values may be increased by the injection of an opiate such as morphine or codeine. In a recent editorial, Elman 9 calls attention to this observation by Lagerlof,lo Gross and his co-authors,l1 and Wapshaw. 12 He also suggests there may be an elevation of the enzyme due to anuria or temporary renal failure. In our experience the greatest single error in amylase determinations had been that which occurs in the laboratory, and I should like to impress the value of repetition of the test. Amylase determination is the single most valuable laboratory aid at the present time. Elman has suggested that any patient who has had biliary tract disease or suspected pancreatitis should be so informed, or be given a small card indicating that he has such a disease and emphasizing his proneness to an attack of acute pancreatitis. If he is not in contact with his personal physician during an attack, amylase tests should be done. Blood Lipase; Hemoglobin Concentration. Increases in lipase values in the urine and blood occur, but have not been as thoroughly studied and correlated with the disease as has the blood amylase test. Cattell and Warren13 call attention to the importance of the recognition of hemoglobin concentration and its early occurrence, as well as its value as an indicator for the maintenance of electrolyte and blood volume. Antithrombin Titer. This has not been as thoroughly studied and correlated as has the amylase test. Serum Calcium. In 1942 Edmondson and Fields 14 noted the appearance of tetany during the course of acute pancreatitis. This observation led to the finding of low serum calcium levels in the disease. These authors
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suggested the finding to be due to the action of lipase-splitting neutral fat, which precipitate calcium as soaps in and about the pancreas. This factor, plus the fixation of calcium in the tissues, results in a withdrawal of calcium from the blood with a fall in the serum calcium. Glucose. The estimation of blood glucose, alone, is of no great diagnostic value. There is a moderate increase in blood sugar of a transitory nature in a small number of the cases. Roentgenologic Findings. Every patient with an acute abdominal disorder is entitled to a flat film. It is of great value in acute pancreatitis in a negative fashion. Poppe}15 called attention to the following conditions which may be demonstrated in the x-ray film: (1) local ileus in the duodenum or ileum; (2) calcification of the pancreas; (3) biliary calculi; (4) fluid in the left pleural cavity; (5) fluid in the abdomen; (6) absence or presence of air beneath the diaphragm. Differential Diagnosis Biliary Tract Disease with Calculi. This is the most common lesion to be differentiated from acute pancreatitis. It occurs more frequently in women, and during pregnancy. There is a history of colic requiring morphine, with intermittent periods of freedom from attacks. Vague digestive upsets may be ascribed to pregnancy. There may have been chills, fever, jaundice, and a white stool. Upon examination tenderness to deep pressure and hammer percussion is found over the liver and gallbladder area, as well as muscle spasm. The clinical picture is not as severe as that of acute pancreatitis unless a gangrenous or acute suppurating cholecystitis is present. Then the differential diagnosis may be difficult because there frequently is an associated pancreatitis with these lesions and the serum amylase test may be elevated. A previous roentgenogram may have demonstrated a nonfunctioning gallbladder or one containing calculi. It is important to ask the patient about these factors. Pain may be referred to the right shoulder and retrosternal area. The previous history provides the most important information for eliminating biliary tract disease. Jaundice is much more frequent in biliary tract disease. Perforated Gastric or Duodenal Ulcer. Again, the previous history of pain, food and alkali reli(ilf over a period of time, usually in a younger person, is of great importance. There is more diffuse abdominal tenderness and muscle rigidity present in this entity. Of great diagnostic help is the history of previous roentgenologic study demonstrating the presence of a peptic ulcer. A flat film revealing the presence of air in the subdiaphragmatic spaces is most important. A penetrating or perforating peptic ulcer into the pancreas may invoke an acute pancreatitis with alterations in the serum amylase.
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Vascular Accidents in the Abdomen. Vascular accidents in the abdomen occur and mimic acute pancreatitis. This is to be suspected when one has a patient with perivascular disease, or a cardiac lesion as a source of emboli, with evidences of embolic phenomena elsewhere. Hematemesis and melena are important clinical evidences. Amylase is not usually elevated, and if it is the levels are not so high. Coronary Insufficiency or Occlusion. In 1943 Gottesman, Casten and Beller16 found that patients with acute pancreatitis had changes in their electrocardiograms of a type that may occur in myocardial infarction. This points to the necessity for careful clinical investigation of a patient giving a history of previous distress on exertion, or anginal attacks with characteristic pain distribution. The electrocardiographic findings in pancreatic disease have no special significance, as shown by GubnerY They may be related to shock, alteration in coronary flow and serum electrolytic changes, or viscerocardiac reflexes which are present in other acute abdominal conditions. Bauerlein and Stobbe 18 call attention to the fact that their many electrocardiograms on persons suffering from shock and alterations in potassium blood content show no changes from normal. They recently reported a case of acute pancreatitis in which severe electrocardiographic findings were present in life, but with no change in the coronary vessels evident at autopsy. Intestinal Obstruction. Intestinal obstruction is distinguished by the absence of an etiologic factor in a well taken history, the presence of a scar on the abdomen indicating a previous surgical procedure, late colic of the intestinal type, the presence of visible peristalsis, and adequate roentgenographic studies demonstrating evidences of' intestinal obstruction. Raffensperger19 has reported moderately increased serum amylase in intestinal obstruction. Clinical Summary
The finding in a male who has overindulged in alcohol or food of acute pain in the left upper quadrant boring through to the back, evidences of shock, a serum amylase that is ten to twenty times normal, fluid at the left base, roentgenologic evidences of duodenal ileus and the presence of abdominal fluid warrants the diagnosis of acute pancreatitis. Cutaneous signs occur late, from the third day on, and should not be waited for to make the diagnosis. Warning!
Beware of the possible presence of a surgical condition which requires immediate intervention. Pain may confuse the picture, since a person with an acute abdominal attack may have received an opiate, which elevates the amylase figure, before he is examined.
Acute Pancreatitis
457 TREATMENT
Surgeon::; and physicians are in general agreement that if the diagnosis of acute primary pancreatitis can be made, with the elimination of etiologic factor::; such as ruptured peptic ulcer or biliary tract disease, the patient should be treated medically rather than by immediate surgical intervention. ORDERS FOR TREATMENT OF ACUTE PANCREATITIS
Routine Orders Chemistries
Treatment of Shock; Fluid and Electrolyte Balance
1. 2. 3. 1. 2. 3. 4.
5. 6.
7.
Pain Sedation
8.
Rela.ration of Sphincter of Oddi
10.
Abdominal Disient'ion and Vomiting Reduction of Pancreatic Secretions A ntiobiotics
11. 12. 13. 14.
Steroids
n.
Daily urinalysis Complete blood count Hematocrit Fasting blood glucose Blood urea Serum Cl-, K+, Na+, C02, A/G ratio Serum calcium immediately after the third day a. If deficit, calcium gluconate 10 cc. of 10% solution intravenously Type and cross match 1500 cc. blood immediately a. Give 500 cc. whole blood as soon as possible b. Additional given if shock persists 100 cc. serum albumin slowly intravenously-repeat in 4 hours if shock continues 2000 cc. 10% Travcrt's solution in N/2 NaCl with 0.3% KCl a. 1 ampule ascorbin added to clysis b. 20 units regular insulin into each bottle intravenously 20 units regular insulin for each 100 grams of glucose Demerol 50 mg. every 3 to 4 hours or p.r.n., or morphine sulfate 8 mg. (Ys grain) if Dernerol fails Luminal sodium 120 mg. (2 grains) or Doriden 500 rng. a. Demerol 50 mg. every 4 hours or p.r.n. b. Atropine 0.6 mg. (1/100 grain) c. Choice of papaverine 120 mg. (2 grains) intravcnously or nitroglycerin 0.6 mg. (I /100 grain) Nothing by mouth Insert nasogastric tube and connect to suction Chart intake and output Atropine given as above or Banthine 50 to 100 mg. every 6 hours orally or intravenously
15. a. b. 16. a. b. c.
Forticillin 400,000 units intrarnuscularly every 8 hOur8 Dihydrostreptomycin 0.5 gram every 8 hours Hydrocortisone 100 mg. Corticotropin 40 units per cc. HP Acthar Gel 20 units per cc. intramuscularly
Pain
Every effort should be made to relieve pain as quickly as possible, because severe pain is frequently accompanied by vasoconstriction which may reduce pancreatic blood supply sufficiently to convert simple edema to necrosis. Demerol in 50 mg. doses is valuable. Its use intravenously may be necessary. Morphine has been avoided because it induces spasms of the sphincter of Oddi. Nevertheless, we have found morphine to be the best drug in many instances, and have u::;ed it. Comfort has also em-
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phasized its value. It may be that the diminution of secretion by the use of the atropine-Banthine type of drug may lessen the importance of the spasm of the sphincter of Oddi under these circumstances. Relaxation of the sphincter of Oddi is desirable because of associated pain and further reflux of bile into the pancreatic duct. The most effective antispasmodic agents for this purpose are papaverine 120 mg. (2 grains) given intravenously, nitroglycerin 0.4 to 1.3 mg. (1/150 to 1/50 grain) given sublingually, amylnitrate pearls, or atropine 1.3 mg. (1/50 grain) given intramuscularly.
Fig. 69. Anteroposterior and lateral roentgenograms of thoracic and lumbar vertebrae showing position of needles for block of splanchnic nerves. Injection of 10 cc. of an ammonium sulfate-benzyl alcohol solution through each needle gave 10 months' relief of abdominal pain due to pancreatitis. (From Journal-Lancet 72: 76--83 [Feb.)
1952.)
The relief of pain can be obtained in a few patients only by repeated blocking of the sympathetic ganglia with a one per cent solution of procaine or xylocaine (Fig. 69). Ganglia T 10 to Tu are blocked bilaterally every 12 to 24 hours until symptoms have subsided. However, the paravertebral block has not been especially helpful in our hands. The method described by Pender and Lundy 20 follows: "Needles 120 mm. in length are inserted just under the twelfth rib and passed in an anteromedial direction until the tips of the needles lie on the anterior surface of the body of the first lumbar vertebra or the twelfth thoracic vertebra. The injection of 10 to 20 cc. of 0.75 per cent solution of ammonium sulfate and 0.75 per cent solution of benzyl alcohol usually aggravates the pancreatic pain for about half an hour and then gives relief. The duration of the relief is unpredictable, ranging from a few days to many months."
The use of continuous or intermittent epidural procaine anesthesia to relieve the pain in severe cases of acute pancreatitis has been very encouraging21 (Fig. 70).
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Fig. 70. Continuous epidural analgesia. Note position of catheter in epidural space in relation to origin of nerve supply to pancreas. In placing the needle in the epidural space the procedure as described by Hingson and South worth is followed. A wheal is made in the skin over the chosen lumbar or thoracic interspace and the subcutaneous tissues down to the ligament are infiltrated with 1 per cent procaine solution. A special 16 gauge Huber pointed needle is inserted in a slightly upward direction until the point meets the ligament. A 2 cc. syringe, filled with 1 per cent procaine solution, is then attached to the needle and gentle pressure is made on the plunger with the thumb while the needle is slowly advanced. When the epidural space is entered there is a sudden give to the plunger. The syringe is disconnected from the needle and the needle is carefully observed for any flow of spinal fluid. It is then checked again by attaching an empty syringe to the needle and making sure that no spinal fluid can be withdrawn. A No. 372 F. ureteral catheter is then threaded through the needle and advanced to the desired level within the epidural space, and small amounts of solution are injected as the tip of the catheter is advanced so as to separate the epidural tissues and facilitate the passage of the catheter. A test dose of 5 cc. is given to be certain that the catheter is not in the subarachnoid space. Subsequently, 5 to 10 cc. of 1 per cent procaine is injected every 30 minutes as required. It is better, in our experience, to give frequent small doses than to depend upon larger amounts at longer intervals. In order to produce anesthesia of the nerves supplying the pancreas, the tip of the ureteral catheter should be placed at the level of the eighth thoracic spinal segment. To reach this level it should lie at a point between the spinous processes of the fifth and sixth thoracic vertebrae. (From Cattell, R. B. and Warren, K. W.: Surgery of the Pancreas.)
Shock Every effort should be made to overcome the shocklike picture by the administration of plasma or whole blood in the indicated amounts checked by proper laboratory procedures. The use of serum albumin has recently been reported by KenweII22 as a most important aid in the treatment of acute pancreatitis. It is suggested that its value is on the basis of an antitrypsinogen factor. Recent studies23 . 24 provide no evidence
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that the albumin inhibits trypsin. However, during the acute phasn of pancreatitis there is a definite whole blood volume deficit, plasma volume deficit and a definite depletion of red cell masl:l. With the above I:lhoclclike picture and a definite plasma volume deficit, serum albumin in amounts of 100 to 200 cc. intravenously in an adult of average size is a valuable adjunct in the immediate treatment of shock in acute pancreatitis. The frequent use of serum albumin il:l definitely indicated to dissipate the associated shock picture. 25 Fluid and Electrolyte Balanee
Nothing by mouth is permitted to these patients, hence it is paramount. that fluid and electrolyte balance be maintained to promote adequate renal function. Normal saline is given parenterally to offset sodium and chloride loss due to vomiting and intubation, plus adequate potassium to avoid hypopotassemia. Glucose solutions are contraindicated unless covered by adequate amounts of insulin. AbdOlninal Distention and VOlniting
This is best controlled by the insertion of an indwelling nasogastric or intestinal tube connected to a Wangensteen suction apparatul:l. Suppuration
The use of antibiotics in the prevention of suppuration is difficult to evaluate, but past experience justifies their prophylactic use. In our hands a combination of penicillin and streptomycin has been most effective, and the inevitable presence of peritonitis warrants their use in every case to avert bacterial growth in a rnactive fluid. Reduction of Pancreatic Secretions (HornlOnal and Nervous StiIllulation)
The hormonal stimulation of the pancreas is inhibited by restricting food and liquids by mouth. Pancreatic secretions are also subjected to nervous stimulation mediated via the vagus nerve. Such drugs as atropine 0.6 mg. (1/100 grain) or Banthine 50 to 100 mg. intramuscularly can depress the vagal activity and reduce secretion. Drugs such as prostigmine, which stimulate the vagus nerves and thus pancreatic secretion, are withheld. H ypocalceIllia
Blood calcium studies should be carried out daily, and calcium gluconate administered upon the appearance of calcium deficit. Calcium gluconate intravenously, 1 gram daily, usually is adequate. Diabetes Mellitus
It is imperative that the blood and the urine be examined at frequent intervals since some of these patients develop diabetes and require insulin
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therapy. The insulin therapy must also be closely watched and insulin shock avoided, because hypoglycemic stimulation of the vagal mechanism of pancreatic secretions may prove deleterious. Permanent diabetes is a common after-effect of acute pancreatitis. Steroids
Elman has stated correctly that the use of cortisone is still quite experimental. He has seen it used most effectively in dosages of 200 mg. a day. A good lead might be an eosinophil count which, if high in the presence of severe symptoms, might suggest the absence of adrenocortical stimulation and therefore the administration of cortisone, or preferably hydrocortisone, parenterally. Cattell and Warren13 state that cortisone orally caused no appreciable change of water, potassium or sodium values in the pancreatic juice. There was a decrease in volume output for the first two days. Stephenson, Pfeffer and Saypo12 6 report a patient with acute hemorrhagic pancreatitis who was in a serious, almost moribund state but recovered following the use of cortisone. All of the factors associated with shock, which may produce a depletion of the cortical steroids, may be present and supplemental administration indicated. Duration of Therapy
The duration of medical therapy depends upon the progress of the patient. The clinical and physical findings are the best guides. The rapidity of recovery from the shocklike state, the return of the temperature to normal, a drop in the leukocyte count and the decrease of evidences of abdominal disease are the most important guides. A careful watch must be kept for complications such as hematoma, acute cyst formation, abscess formation or spreading peritonitis, any of which require surgical intervention. These complications are suggested by persistence of fever, particularly of an intermittent type, for more than a week and the presence of a mass which can be detected by palpation or x-ray study showing displacement of the stomach. Indications for Surgical Intervention in Acute Pancreatitis
Once the diagnosis of acute pancreatitis is firmly established, conservative treatment is the therapy of choice. However, if any doubt exists as to the exact diagnosis, immediate surgical intervention is indicated, since all other conditions simulating acute pancreatitis may be amenable to surgical therapy. If an operation is performed and acute pancreatitis is found, it is our opinion that the abdomen should be closed immediately unless definite disease is found in the biliary tract. Routine drainage of the nonpathologic gallbladder or common duct is of no avail if the acute pancreatitis
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is on a vascular basis rather than due to disease of the biliary tract~and this in our opinion is often the case. Once nonsurgical treatment is instituted, operation is performed only for the complications of the disease such as lesser sac abscess or cyst. Surgical procedures on the biliary tract are never indicated either in the acute or quiescent stage of pancreatitis unless definite biliary tract disease is demonstrated. When at all possible the operation, if indicated, should be performed when the acute phase of the pancreatitis has completely subsided. PROGNOSIS
Some years ago we reported a series of cases of acute pancreatitis in which patients subjected to immediate operation showed a mortality of 35 per cent, while in those in whom operation was delayed or omitted the mortality rate was 5 per cent. These figures do not reflect the present use of improved combative measures. Bockus27 in a recent communication reports a total mortality of 4.3 per cent. There was, however, a 37 per cent mortality in eight cases in which laparotomy was done during the acute phase. There were no deaths of patients who had an elective operation after the acute symptoms subsided, and one death among 82 patients treated medically during the acute phase of the disease. O'Brien and Thayer2 had an initial mortality of 8 per cent in 108 cases treated conservatively. A further follow-up revealed a total mortality of 13 per cent. Twenty-six of their patients had only one attack; 74 per cent had further attacks. REFERENCES Especially recommended are the excellent text by Warren and Cattell (ref. 13), the annual reviews of the pancreas by Elman appearing each year in Gastroenterology, the enlightening review of the subject by Machella in the Veterans Administration Technical Bulletin of March 2, 1953 (ref. 28), and the numerous outstanding contributions on fundamentals and clinical aspects by Mandred Comfort. 1. Paxton, J. R. and Payne, J. H.: Acute Pancreatitis: Statistical Review of 307 Established Cases of Acute Pancreatitis. Surg., Gynec. & Obst. 89: 69-75
(Jan) 1948.
2. O'Brien, J. J. and Thayer, T. R.: Pancreatitis. New England J. Med. 253 (9):
355 (Sept. 1) 1955. 3. Sigmund, W. J. and Shelley, W. B.: Cutaneous Manifestations of Acut(Pancreatitis. New England J. Med. 251 (21): 851 (Nov. 18) 1954. 4. Fallis, L. S.: Acute Pancreatitis. Proc. Royal Soc. Med. 46: 113, 1953. 5. Elman, R., Arneson, N. and Graham, E. A.: Value of Blood Amylase Estimations in Diagnosis of Pancreatic Disease: Clinical Study. Arch. Surg. 19: 943 (Pt. 1) 1929. 6. Smogyi, M.: Micromethods for Estimation of Diastase. J. BioI. Chem. 125: 399414 (Sept.) 1938. 7. Keith, L. M. Jr., Zollinger, R. M. and McCleery, R. J.: Peritoneal Fluid Amylase Determinations as Aid in Diagnosis of Acute Pancreatitis. Arch. Surg. 61: 930, 1950.
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8. Meyers, S. G., Brown, J. R., Boone, R. and Henderson, H.: Clinical Manifestations of Pancreatitis. Gastroenterology 28 (5): 803 (May) 1955. 9. Elman, R.: Acute Pancreatitis and the Laboratory. Surg., Gynec. & Obst. 100 (2): 241 (Feb.) 1955. 10. Lagerlof, H.: Normal Esterases and Pancreatic Lipase in Blood; Study with New Chemical and Clinical Methods (Second Secretin Test). Acta med. Scandinav. 120: 407, 1945. 11. Gross, J. B., Comfort, M. W., Mathieson, D. W. and Power, M. D.: Elevated Values for Serum Amylase and Lipase Following Administration of Opiates. Preliminary Report. Proc., Staff Meet., Mayo Clin. 26: 81, 1951. 12. Wapshaw, H.: Lancet 1: 373,1953. 13. Cattell, R. B., and Warren, K. W.: Surgery of Pancreas. Philadelphia, W. B. Saunders Co., 1953. 14. Edmondson, H. A. and Fields, 1. A.: Relation of Calcium and Lipids to Acute Pancreatic Necrosis; Report of 15 Cases in One of Whieh Embolism Occurred. Arch. Int. Med. 67: 177-190 (Feb.) 1942. 15. Poppel, M. H.: Roentgen Manifestations of Pancreatic Disease. Springfield, Ill., C. C Thomas, 1951. 16. Gottesman, J., Casten, D. and Beller, A. J.: Changes in Electrocardiogram Induced by Acute Pancreatitis. J.A.M.A. 123: 892, 1943. 17. Gubner, R. S.: Electrocardiographic Changes in Abdominal Disease. J.A.M.A. 124: 122-123 (Jan. 8) 1944. 18. Bauerlein, T. C. and Stobbe, L. H. 0.: Acute Pancreatitis Simulating Myocardial Infarction with Characteristic Electrocardiographic Changes. Gastroenterology 27 (6): 861 (Dec.) 1954. 19. Raffensperger, E. C.: Elevated Serum Pancreatic Enzyme Values without Primary Intrinsic Pancreatic Disease. Ann. Int. Med. 35: 342, 1951. 20. Pender, J. W. and Lundy, J. S.: Diagnostic and Therapeutic Nerve Blocks. Journal-Lancet 72: 76 (Feb.) 1952. 21. Orr, R. B., and Warren K. W.: Continuous Epidural Analgesia in Acute Pancreatitis. Lahey Clin. Bull. 6: 204-210, 1950. 22. Kenwell, H. N. and Wels, P. B.: Acute Hemorrhagic Pancreatitis. Report of 11 Consecutive Cases Treated with Human Serum Albumin. Surg., Gynec. & Obst.96: 169, 1953. 23. Keith, L. M. Jr., and Watman, R. N.: Blood Volume Deficits in Pancreatitis. Surgical Forum, Clinical Congress of American College of Surgeons, 1954. Philadelphia, W. B. Saunders Co., p. 380. 24. Elliott, D. W.: Mechanism of Benefit Derived from Concentrated Human Serum Albumin in Experimental Acute Pancreatitis. Surgical Forum, Clinical Congress of American College of Surgeons, 1954. Philadelphia, W. B. Saunders Co., p. 384. 25. ElIiott, D. W., Zollinger, R. M., Moore, R. and Ellison, E. H.: The Use of Human Serum Albumin in the Management of Acute Pancreatitis. Gastroenterology 28 (4): 563 (April) 1955. 26. Stephenson, H. E., Pfeffer, R. B. and Saypol, G. M.: Acute Hemorrhagic Pancreatitis. Arch. Surg. 62: 307, 1952. 27. Bockus, H. L., KaIser, M. H., Roth, J. L. A. and Bogoch, A. L.: Clinical Features of Acute Inflammation of Pancreas. A.M.A. Arch. Int. Med. 96 (3): 308 (Sept.) 1955. 28. Machella, T. E.: Veterans Administration Technical Bulletin, TB 10-87, March 2, 1953. 40 W. North Street Buffalo 2, New York