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Medical Complications of Acute Pancreatitis
Medical Complications of Acute Pancreatitis LLOYD G. BARTHOLOMEW, M.D. JAMES C. CAIN, M.D.
IN A RECENT ABSTRACT for a course in internal medicine sponsored by the American College of Physicians and the Mayo Clinic, this statement appeared: "The rapid advances in science within the past decade have made it essential that the internist and surgeon work more closely together." In no other disease is this statement more pertinent than in acute pancreatitis. Its veracity is obvious when one studies the comparative mortality statistics. Mortality following surgical intervention in acute pancreatitis has been reported as ranging from 24 to 80 per cent in contrast to 10 to 20 per cent with medical treatment alone. When the diagnosis of acute pancreatitis is made and substantiated, it is to be considered primarily a medical disease unless and until certain complications become apparent. 1 Almost any surgeon who has seen acute pancreatitis, either as a postoperative complication or as an acute disease not diagnosed until exploration, will attest to the difficulty of doing anything definitive at this stage. Surgical manipulation of the edematous, hemorrhagic, and necrotic tissue can lead only to further complications. Experience has led most surgeons to do no more than confirm the diagnosis and abandon exploration. The dangers of prolonged shock and the development of pancreatic fistula need no further comment. It is not within the province of this paper to go into the differential diagnosis, but certain facts related to it are best considered at this time. Sometimes the establishment of a diagnosis of acute pancreatitis is extremely difficult, and in a small percentage of cases surgical exploration is necessary to distinguish this from other acute conditions within the abdomen, especially a perforated viscus. Primarily, however, it is the duty of the internist to make and substantiate as well as possible the diagnosis of acute pancreatitis. No significant major developments have occurred in the realm of specific laboratory tests, but more experience with studies of urinary amylase has made this one of the most helpful diagnostic indicators
1031
1032
LLOYD
Table 1.
G.
BAR'l'HOLOMEW, JAMES C. CAIN
Medical Complications of Acute Pancreatitis Unnecessary abdominal operation Shock Electrolyte imbalance Sepsis and formation of abscess Intestinal obstruction Jaundice Diabetes mellitus Recurrent acute pancreatitis Chronic pancreatitis Painless pancreatitis Relapsing pancreatitis Addiction to alcohol and narcotics
available. It has the advantage of remaining elevated for many days after the serum amylase has returned to normal. Anyway, it is preferable to delay surgical intervention if possible, even when it is obvious that one is dealing with secondary pancreatitis, such as is seen occurring with common-duct stones. The internist's job fundamentally is to help the surgeon not only in the diagnosis but in the conservative management of acute pancreatitis. We are concerned not only with avoiding the so-called medical complications wherever possible but also with obviating the added insult--or, if you will, the complication-of surgical intervention. It may be argued that some of these so-called complications (Table 1) are part of the basic disease, but that is a matter of semantics only. Shock may develop for a number of reasons, not the least of which are pain, ischemic necrosis, and hemorrhage into the retroperitoneal area. One must bear in mind that occasionally pancreatitis presents the features of profound shock with few or no localizing abdominal signs. Under such circumstances the diagnosis becomes apparent only in retrospect, though it is possible to make the diagnosis earlier if pancreatitis is considered as a possibility in these unusual circumstances. Careful examination of the abdomen may reveal evidence of peritoneal irritation. The physician's immediate concern, however, is to combat the shock. This is best done by the use of whole blood, serum albumin, or other plasma expanders. When pain is a contributing factor, generous amounts of analagesics must be given. Often large doses of meperidine (Demerol) are necessary to relieve this type and degree of pain. The prevention of further shock and other complications also depends upon putting the pancreas at complete physiologic rest. The use of gastric suction, abstinence from oral ingestion of food and fluids, and the administration of anticholinergic drugs have beneficial effects. There may be some disagreement in the use of such drugs by those who claim that "drying up" the pancreatic secretions may cause more obstruction to the pancreatic duct by inspissated material. In practice there seems little to
ill!edical Complications of Acute Pancreatitis
1033
confirm this, since the vagi control the thick, viscous fluid, which is rich in enzymes and small in amount. The great majority of pancreatic juice is water and sodium bicarbonate, and apparently is chiefly under hormonal control. Electrolyte imbalance results partly from the primary disease and partly from the forms of treatment necessary-continuous gastric suction, abstinence from food, and so on. The amount of fluid and electrolytes to be replaced varies from patient to patient and from day to day in the same patient. Careful estimation of the losses and prediction of requirements can be fairly accurate. The serum calcium may have a unique position in the pathologic physiology of acute pancreatitis. During the initial insult to the pancreas, the serum concentration may decrease occasionally to extremely low levels; and an estimate of the severity of the attacks of pancreatitis may be suggested by the levels that it reaches. It is unusual to see recovery occur if the serum calcium falls below 7 mg. per 100 ml. The available serum calcium apparently is poured into necrotic fatty tissues, helping to form innocuous calcium compounds. Usually an original injury to the pancreas severe enough to cause a lowering of the serum calcium to 7 mg. or less means necrosis too extensive for hope of recovery. Many times, fortunately, there is not such a severe injury to the pancreas; and even though the serum calcium diminishes to lower levels than usual, compensatory mechanisms are able to function and bring about mobilization of the vast body stores of calcium. Intravenous administration of calcium may be necessary early in the disease to prevent tetany; but it should always be used cautiously, as there is some evidence to suggest it is one of the activators of trypsinogen, which in turn may be a factor in the production of pancreatitis. Paradoxically, in some forms of pancreatitis serum calcium levels may have an entirely different significance. In recent years 2 the association of hyperparathyroidism with pancreatitis has been brought to light. Whether the co-existence of these entities is merely a coincidence is not definite at this time. Although the number of cases is small (probably less than 25), there may be a definite causal relationship between the two diseases. In many cases one of the most plausible explanations of their relationship is that an initial hyperparathyroidism has led to the development of pancreatitis. The alkalinity of the external pancreatic secretions seems to favor the precipitation of calciu~ salts within the pancreatic ducts and parenchyma. It is known that the concentration of calcium in the human pancreatic juice approximates the concentration of the serum calcium. If this equality persists in the situation of hypercalcemia, then one might predict the deposition of calcium salts in the pancreas and the development of pancreatitis. Continued observation and many more studies must be made before this idea can be fully accepted. For the purpose of this paper, however, the
1034
LLOYD
G.
BARTHOLOMEW, JAMES C. CAIN
lesson to remember is to test the serum calcium not only during the attack of acute pancreatitis but also when the patient has recovered. Surprising differences may be evident in these two situations. When concerned with changes in the blood chemistry, one should remember also to check the plasma lipids. On rare occasions hyperlipemia has been associated with acute pancreatitis clinically, and also experimentally in rabbits. Sepsis and abscess formation in the past were frequent medical complications of acute pancreatitis. With the present availability of broadly effective antibiotics, they no longer are common. It goes without saying that prophylactic use of such drugs should be a routine procedure in acute pancreatitis. In rare instances where abscesses and pseudocysts develop, surgical procedures are not only indicated but are indispensable. Intestinal obstruction may occur almost any time during the attack of acute pancreatitis. The initial symptoms of acute pancreatitis may be marked abdominal distention, associated shock, and very little pain. The only treatment additional to that previously mentioned is the passage of a long intestinal tube and adequate suction. This tube may be extremely difficult to manipulate into the distended small bowel because of the lack of motility in the obvious adynamic ileus. Fortunately in most circumstances correction of the shock, relief of pain, and replacement of electrolytes help enough so that the short gastric tube suffices without the other. Later on in the disease, true organic obstruction may develop as a result of the permanent damage to the pancreas. Constriction of the duodenum or upper jejunum results rarely from involvement in the acute inflammatory process (Fig. 1) or more commonly from the later development of pseudocysts. Fortunately these difficulties can be dealt with when the patient has improved and can tolerate the surgeon's abdominal exploration without a prohibitive risk. Jaundice may appear early in pancreatitis, apparently as a result of an associated or contiguous inflammatory process in the liver. This often means extensive and severe involvement of the pancreas and restricts the physician to a very guarded prognosis. No specific therapy is available, and only the treatment already described need be instituted. If, early in the disease, it is on an obstructive basis, it usually subsides as the edema of the head of the pancreas decreases. Almost always the development of jaundice later in the disease is on an obstructive basis. To be desired here again is properly planned surgical treatment when the patient is a better surgical risk. Diabetes mellitus is an uncommon complication of acute pancreatitis. In some cases its development may be so insidious that it goes completely unrecognized. When considering fluid and electrolyte replacement, one must keep in mind the possibility of at least transient diabetes and take care not to place an excessive load on the pancreas by intravenous
Medical Complications of Acute Pancreatitis
1035
Fig. 1. Obstruction of the second portion of the duodenum, resulting from acute pancreatitis.
administration of large amounts of glucose. Occasional determination of the concentration of blood sugar will provide a warning if needed. It may be advisable at times to give small amounts of regular insulin (5 to 10 units) in each bottle of replacement fluid that contains glucose. Again as with other complications, the development of diabetes mellitus early in pancreatitis may signify that the latter is rather extensive. The development of recurrent attacks of acute prancreatitis also may be considered in the realm of medical complications. Careful diagnostic studies should be planned during the quiescent phase following an exaberbation of acute pancreatitis. Roentgenograms of the gallbladder and common bile duct, as well as the stomach, must be made. When attacks of pancreatitis recur despite normal findings from interim studies, surgical exploration of the biliary tree is recommended. The exact procedure to be carried out must depend, of course, on the surgical findings. Unfortunately, in some instances chronic pancreatitis may emerge as a complication of acute pancreatitis. How and when this change takes place is uncertain, for usually acute pancreatitis subsides completely, leaving the pancreas apparently normal. This chronic form of the disease may be heralded by recurrent acute attacks of pain commonly referred to as chronic relapsing pancreatitis. In about 5 per cent of the cases that become chronic, the disease is mild and appears to be a continuous lowgrade inflammatory process with no acute exacerbation of pain. This form
1036
LLOYD
G.
BARTHOLOMEW, JAMES C. CAIN
makes up the so-called chronic painless pancreatitis, which manifests itself chiefly with evidence of pancreatic insufficiency--particularly steatorrhea, diabetes mellitus, and pancreatic calcification. Finally, one of the most distressing medical complications of acute pancreatitis is the development of addiction to alcohol and narcotics. The former, of course, continually threatens the production of more pancreatic inflammation and the latter brings problems so obvious that they need no further discussion. Under no circumstances should narcotics be given to patients with chronic pancreatitis except by administration under the direct supervision of a physician. SUMMARY
In conclusion, acute pancreatitis is primarily a medical problem. The role of the internist is to establish the diagnosis, to give treatment for the primary process and the complications as they arise, and to seek the aid of the surgeon in the treatment of later sequelae. REFERENCES 1. Bartholomew, L. G., and Cain, J. C.: Medical Management of Pancreatitis.
J.A.lVLA. 175: 299-301 (Jan. 28) 1961. 2. Gross, J. B.: Some Recent Developments Pertaining to Pancreatitis. Ann. Int. Med. 49: 796-819 (Oct.) 1958.
IN A RECENT ABSTRACT for a course in internal medicine sponsored by the American College of Physicians and the Mayo Clinic, this statement appeared: "The rapid advances in science within the past decade have made it essential that the internist and surgeon work more closely together." In no other disease is this statement more pertinent than in acute pancreatitis. Its veracity is obvious when one studies the comparative mortality statistics. Mortality following surgical intervention in acute pancreatitis has been reported as ranging from 24 to 80 per cent in contrast to 10 to 20 per cent with medical treatment alone. When the diagnosis of acute pancreatitis is made and substantiated, it is to be considered primarily a medical disease unless and until certain complications become apparent. 1 Almost any surgeon who has seen acute pancreatitis, either as a postoperative complication or as an acute disease not diagnosed until exploration, will attest to the difficulty of doing anything definitive at this stage. Surgical manipulation of the edematous, hemorrhagic, and necrotic tissue can lead only to further complications. Experience has led most surgeons to do no more than confirm the diagnosis and abandon exploration. The dangers of prolonged shock and the development of pancreatic fistula need no further comment. It is not within the province of this paper to go into the differential diagnosis, but certain facts related to it are best considered at this time. Sometimes the establishment of a diagnosis of acute pancreatitis is extremely difficult, and in a small percentage of cases surgical exploration is necessary to distinguish this from other acute conditions within the abdomen, especially a perforated viscus. Primarily, however, it is the duty of the internist to make and substantiate as well as possible the diagnosis of acute pancreatitis. No significant major developments have occurred in the realm of specific laboratory tests, but more experience with studies of urinary amylase has made this one of the most helpful diagnostic indicators
1031
1032
LLOYD
Table 1.
G.
BAR'l'HOLOMEW, JAMES C. CAIN
Medical Complications of Acute Pancreatitis Unnecessary abdominal operation Shock Electrolyte imbalance Sepsis and formation of abscess Intestinal obstruction Jaundice Diabetes mellitus Recurrent acute pancreatitis Chronic pancreatitis Painless pancreatitis Relapsing pancreatitis Addiction to alcohol and narcotics
available. It has the advantage of remaining elevated for many days after the serum amylase has returned to normal. Anyway, it is preferable to delay surgical intervention if possible, even when it is obvious that one is dealing with secondary pancreatitis, such as is seen occurring with common-duct stones. The internist's job fundamentally is to help the surgeon not only in the diagnosis but in the conservative management of acute pancreatitis. We are concerned not only with avoiding the so-called medical complications wherever possible but also with obviating the added insult--or, if you will, the complication-of surgical intervention. It may be argued that some of these so-called complications (Table 1) are part of the basic disease, but that is a matter of semantics only. Shock may develop for a number of reasons, not the least of which are pain, ischemic necrosis, and hemorrhage into the retroperitoneal area. One must bear in mind that occasionally pancreatitis presents the features of profound shock with few or no localizing abdominal signs. Under such circumstances the diagnosis becomes apparent only in retrospect, though it is possible to make the diagnosis earlier if pancreatitis is considered as a possibility in these unusual circumstances. Careful examination of the abdomen may reveal evidence of peritoneal irritation. The physician's immediate concern, however, is to combat the shock. This is best done by the use of whole blood, serum albumin, or other plasma expanders. When pain is a contributing factor, generous amounts of analagesics must be given. Often large doses of meperidine (Demerol) are necessary to relieve this type and degree of pain. The prevention of further shock and other complications also depends upon putting the pancreas at complete physiologic rest. The use of gastric suction, abstinence from oral ingestion of food and fluids, and the administration of anticholinergic drugs have beneficial effects. There may be some disagreement in the use of such drugs by those who claim that "drying up" the pancreatic secretions may cause more obstruction to the pancreatic duct by inspissated material. In practice there seems little to
ill!edical Complications of Acute Pancreatitis
1033
confirm this, since the vagi control the thick, viscous fluid, which is rich in enzymes and small in amount. The great majority of pancreatic juice is water and sodium bicarbonate, and apparently is chiefly under hormonal control. Electrolyte imbalance results partly from the primary disease and partly from the forms of treatment necessary-continuous gastric suction, abstinence from food, and so on. The amount of fluid and electrolytes to be replaced varies from patient to patient and from day to day in the same patient. Careful estimation of the losses and prediction of requirements can be fairly accurate. The serum calcium may have a unique position in the pathologic physiology of acute pancreatitis. During the initial insult to the pancreas, the serum concentration may decrease occasionally to extremely low levels; and an estimate of the severity of the attacks of pancreatitis may be suggested by the levels that it reaches. It is unusual to see recovery occur if the serum calcium falls below 7 mg. per 100 ml. The available serum calcium apparently is poured into necrotic fatty tissues, helping to form innocuous calcium compounds. Usually an original injury to the pancreas severe enough to cause a lowering of the serum calcium to 7 mg. or less means necrosis too extensive for hope of recovery. Many times, fortunately, there is not such a severe injury to the pancreas; and even though the serum calcium diminishes to lower levels than usual, compensatory mechanisms are able to function and bring about mobilization of the vast body stores of calcium. Intravenous administration of calcium may be necessary early in the disease to prevent tetany; but it should always be used cautiously, as there is some evidence to suggest it is one of the activators of trypsinogen, which in turn may be a factor in the production of pancreatitis. Paradoxically, in some forms of pancreatitis serum calcium levels may have an entirely different significance. In recent years 2 the association of hyperparathyroidism with pancreatitis has been brought to light. Whether the co-existence of these entities is merely a coincidence is not definite at this time. Although the number of cases is small (probably less than 25), there may be a definite causal relationship between the two diseases. In many cases one of the most plausible explanations of their relationship is that an initial hyperparathyroidism has led to the development of pancreatitis. The alkalinity of the external pancreatic secretions seems to favor the precipitation of calciu~ salts within the pancreatic ducts and parenchyma. It is known that the concentration of calcium in the human pancreatic juice approximates the concentration of the serum calcium. If this equality persists in the situation of hypercalcemia, then one might predict the deposition of calcium salts in the pancreas and the development of pancreatitis. Continued observation and many more studies must be made before this idea can be fully accepted. For the purpose of this paper, however, the
1034
LLOYD
G.
BARTHOLOMEW, JAMES C. CAIN
lesson to remember is to test the serum calcium not only during the attack of acute pancreatitis but also when the patient has recovered. Surprising differences may be evident in these two situations. When concerned with changes in the blood chemistry, one should remember also to check the plasma lipids. On rare occasions hyperlipemia has been associated with acute pancreatitis clinically, and also experimentally in rabbits. Sepsis and abscess formation in the past were frequent medical complications of acute pancreatitis. With the present availability of broadly effective antibiotics, they no longer are common. It goes without saying that prophylactic use of such drugs should be a routine procedure in acute pancreatitis. In rare instances where abscesses and pseudocysts develop, surgical procedures are not only indicated but are indispensable. Intestinal obstruction may occur almost any time during the attack of acute pancreatitis. The initial symptoms of acute pancreatitis may be marked abdominal distention, associated shock, and very little pain. The only treatment additional to that previously mentioned is the passage of a long intestinal tube and adequate suction. This tube may be extremely difficult to manipulate into the distended small bowel because of the lack of motility in the obvious adynamic ileus. Fortunately in most circumstances correction of the shock, relief of pain, and replacement of electrolytes help enough so that the short gastric tube suffices without the other. Later on in the disease, true organic obstruction may develop as a result of the permanent damage to the pancreas. Constriction of the duodenum or upper jejunum results rarely from involvement in the acute inflammatory process (Fig. 1) or more commonly from the later development of pseudocysts. Fortunately these difficulties can be dealt with when the patient has improved and can tolerate the surgeon's abdominal exploration without a prohibitive risk. Jaundice may appear early in pancreatitis, apparently as a result of an associated or contiguous inflammatory process in the liver. This often means extensive and severe involvement of the pancreas and restricts the physician to a very guarded prognosis. No specific therapy is available, and only the treatment already described need be instituted. If, early in the disease, it is on an obstructive basis, it usually subsides as the edema of the head of the pancreas decreases. Almost always the development of jaundice later in the disease is on an obstructive basis. To be desired here again is properly planned surgical treatment when the patient is a better surgical risk. Diabetes mellitus is an uncommon complication of acute pancreatitis. In some cases its development may be so insidious that it goes completely unrecognized. When considering fluid and electrolyte replacement, one must keep in mind the possibility of at least transient diabetes and take care not to place an excessive load on the pancreas by intravenous
Medical Complications of Acute Pancreatitis
1035
Fig. 1. Obstruction of the second portion of the duodenum, resulting from acute pancreatitis.
administration of large amounts of glucose. Occasional determination of the concentration of blood sugar will provide a warning if needed. It may be advisable at times to give small amounts of regular insulin (5 to 10 units) in each bottle of replacement fluid that contains glucose. Again as with other complications, the development of diabetes mellitus early in pancreatitis may signify that the latter is rather extensive. The development of recurrent attacks of acute prancreatitis also may be considered in the realm of medical complications. Careful diagnostic studies should be planned during the quiescent phase following an exaberbation of acute pancreatitis. Roentgenograms of the gallbladder and common bile duct, as well as the stomach, must be made. When attacks of pancreatitis recur despite normal findings from interim studies, surgical exploration of the biliary tree is recommended. The exact procedure to be carried out must depend, of course, on the surgical findings. Unfortunately, in some instances chronic pancreatitis may emerge as a complication of acute pancreatitis. How and when this change takes place is uncertain, for usually acute pancreatitis subsides completely, leaving the pancreas apparently normal. This chronic form of the disease may be heralded by recurrent acute attacks of pain commonly referred to as chronic relapsing pancreatitis. In about 5 per cent of the cases that become chronic, the disease is mild and appears to be a continuous lowgrade inflammatory process with no acute exacerbation of pain. This form
1036
LLOYD
G.
BARTHOLOMEW, JAMES C. CAIN
makes up the so-called chronic painless pancreatitis, which manifests itself chiefly with evidence of pancreatic insufficiency--particularly steatorrhea, diabetes mellitus, and pancreatic calcification. Finally, one of the most distressing medical complications of acute pancreatitis is the development of addiction to alcohol and narcotics. The former, of course, continually threatens the production of more pancreatic inflammation and the latter brings problems so obvious that they need no further discussion. Under no circumstances should narcotics be given to patients with chronic pancreatitis except by administration under the direct supervision of a physician. SUMMARY
In conclusion, acute pancreatitis is primarily a medical problem. The role of the internist is to establish the diagnosis, to give treatment for the primary process and the complications as they arise, and to seek the aid of the surgeon in the treatment of later sequelae. REFERENCES 1. Bartholomew, L. G., and Cain, J. C.: Medical Management of Pancreatitis.
J.A.lVLA. 175: 299-301 (Jan. 28) 1961. 2. Gross, J. B.: Some Recent Developments Pertaining to Pancreatitis. Ann. Int. Med. 49: 796-819 (Oct.) 1958.