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Pancreatitis in pregnancy
volume
American
113 number 3 June 1, 1972
of Obstetrics and Gynecology
Journal
OBSTETRICS
Pancreatitis in pregnancy ROBERT
C.
CORLETT,
DANIEL
R.
MISHELL,
Los Angeles,
California
JR., JR.,
M.D. M.D.
Pancreatitis in pregnancy is not a rare disease and must be considered in the differential diagnosis of any patient with hyperemesis gravidarum as well as those pregnant patients with signs of an acute surgical abdominal crisis. The serum amylase and diastase tests are rapid and reliable and provide an excellent diagnostic and prognostic test for the clinician. It must be remembered that the amylase in serum is excreted rapidly and so a urinary diastase test must always be ordered concurrently. It cannot be overemphasized that the patient with pancreatitis (including severe cases) may present initially without pain or tenderness. If the diagnosis is made early, medical management is almost always successful and the prognosis for mother and fetus is good. The excellent results obtained in this series are a result of early diagnosis and rapid treatment.
PANCREATITIS in pregnancy has a reincidence of from l/3,800 to ported l/l 1,467l and is generally considered to be extremely hazardous for both mother and fetus. The most recent comprehensive review was written by Langmade and Edmundson From the Department of Obstetrics Gynecology, Los Angeles CountyUniversity of Southern California Medical Center. f;;;ived for publication December f.;;pted
for publication
January
in 1951. In this article they stated that only 53 cases had previously been reported. They then added 9 cases of their own, 8 of which occurred during a 9 year period, 1940-1948, at the Los Angeles County General Hospital. The purpose of this paper is to discuss experience with this disease obtained during the last 6 years at this institution. During this time period there were 52 patients who developed pancreatitis while pregnant or during the puerperium. There were no maternal deaths and a corrected fetal salvage rate of 89 per cent. This favorable prognosis for mother and infant is due in large part to the fact that the disease was diagnosed early and treatment instituted soon thereafter.
and
8, I,
Reprint requests: Dr. Daniel R. Mishell, Jr., Dept. of Ob./Gyn., Los Angeles County, University of Southern California Medical School, Los Angeles, California 90033.
281
282
Corlett
and Mishell
Table IA. Patients
June 1, 1972 Am. J. Obstet. Gynecol.
with
enzyme
elevations
more
than
ten times
normal -
Patient
Days hospita&ted
Complaint
Abdominal
No.
pain
of
Diagnosis
re-
mission” Gallbladder disease
CUtTtVlCC?S
7
+
9
3+
-.
S. D.
RUQ pain nausea, vomiting
F. R. M. M. M. G.
Pain, nausea, vomiting Vomiting Epigastric pain, nausea and vomiting Malaise, nausea and vomiting Nausea and vomiting, back pain Nausea and vomiting, back pain Nausea and vomiting, back pain Nausea and vomiting, back pain Vomiting, chest and abdominal pain Nausea and vomiting
14 4 7 10 6 18 27 6 7
C. R. T. G.
RUQ pain and vomiting Abdominal pain Epigastric pain/bilious
5 10 7
t 3-4+
1 1 1
R/OP Gallbladder R/OP
A. H. M. Z. B. P.
Pain and nausea Nausea and vomiting, pain Dehydration and vomiting
14 4 54
3+ t -
2 1 -
P P Diabetes
EA. J. G. 2:: A. H. V. J.
s. v.
F. D.
Pain and vomiting
*Diagnosis tFeta1
on
admission:
outcome:
Material
+, living
and
term;
+P, living
R/OP, premature:
pancreatitis SB,
methods
A retrospective review of all patients who had the diagnosis of pancreatitis established either during pregnancy or within the first 6 weeks post partum at Los Angeles County/ USC Medical Center from June, 1965, to the present time was performed. During this time period patients were classified as having mild, moderate, or severe pancreatitis based on a combination of parameters. Patients were placed in the severe category if they had one or more of the following : ( 1) required hospitalization for more than 2 weeks, (2) exhibited a slow response to medical management with persistent pain or prolonged nasogastric suction required, (3) had severe electrolyte imbalance, (4) had frequent recurrences, (5 ) required operation, (6) required antibiotics, or (7) had a major complication such as ketoacidosis or shock. Patients were considered to have mild pancreatitis if they required hospitalization for 4 days or less, had one or no recurrences, had no electrolyte derangement, and responded with minimal treatment. The patients who fit in between these cate-
was stillborn;
P H.G. R/OP R/OP R/OP R/OP P Cholecystitis H.G. Hepatitis
2+ + t +t 2+
2t
+
t
t
+
14
P, pancreatitis;
considered AB,
in spontaneous
the
on ad-
3-4 differential; abortion;
gories were defined moderate pancreatitis.
R/OP H.G.,
Tb.
disease
AB,
arbitrarily
hyperemesis
gravidarum.
therapeutic
abortion;
as having
Results During this time period there were 52 pregnant or puerperal patients with a diagnosis of pancreatitis (Tables IA, IB, and IC) and 55,416 live births-an incidence of l/1,066. The ages ranged from 16 to 37 with a mean of 24.5 and parity from 0 to 10 with a mean of 2.2. There were 42 multiparous and 9 nulliparous patients. The diagnosis was made or suspected at the time of admission in the majority of instances, 33 of 52 (Table II). Fourteen had their first attack in the first trimester, 10 in the second, 18 in the third, and 9 in the puerperium. Of 39 instances in which it was possible to determine the fate of the fetus, there were 33 fetal survivals (Table III). Of the 6 perinatal deaths, one was a therapeutic abortion pregnancy, giving a an d one an abdominal corrected fetal salvage rate of 89 per cent. Of the 52 patients, 13 had severe pancreatitis. Of these 13 patients there were 6 with
?,
Volume Number
Pancreatitis
113 3
Other Amylase/dia.stase 3,800/2,650
Bilirubin Alkaline
5,300/48,000 665/7,000 2,130/5,120 7,500/40,500 5,000/48,000 235/12,300 9,300/34,000 615/44,000 -/14,200 9,500/48,000 2,175/365/12,500 6,600/3,600 239/8,000 17,000/2 1,000 1,340/10,000 7,625/50,000 unknown
fetal
significant data = 3.3 phosphatase -
X-rays, when done
laboratory
=
=
24,200
Alkaline
?
3
-
? + ? + + + + + ? +
3 1 1 2 3 3 1 P 1 3
Jaundice
SB t t
P 3 P
Shock
+ BB
3 2 3
t
P
ileus -
Bilirubin W.B.C.
=
22
Adynamic
ileus
Operation Jaundice Jaundice -
Alkaline Bilirubin GPT =
phosphatase = 6.4 120
=
8.5 -
CHO = 510 pH = 7.0 W.B.C. = 15,700
Trimester
-
phosphatase = 8.1 = 16,300
Fetal outcome+
283
12.5 Paralytic
W.B.C.
Complications
in pregnancy
Ascites,
ileus
Ketoacidosis, hypocalcemia Fever
outcome.
associated cholelithiasis and 9 who had recurrences during this gestation. The duration of hospitalization was greater than 2 weeks in the majority (7) ; was nearly 2 months in one case who presented initially in diabetic ketoacidosis. In this group of 13, the fetal outcome was known in 12. There were 7 term, viable infants; one premature infant; one therapeutic abortion; one spontaneous abortion; one intrauterine death, and one abdominal pregnancy which also died prior to laparotomy. Of the 13 patients considered to have severe pancreatitis by clinical standards, 10 had amylase and/or diastase values greater than ten times normal (Table IA) and the remaining 3 had moderately elevated enzymes (Table IB) . None had only minimal elevations (Table IC) . There were 16 patients with moderate disease, and of these 16 the fetal outcome was known in 13. There were one premature infant, 12 term infants, and no perinatal deaths. Twenty-three patients were considered to have mild cases of pancreatitis, and 15 of these were followed to the termination of their pregnancy. There were one premature
infant, and 13 term living infants, and one spontaneous abortion. The treatment varied in relation to the severity of the disease. Those with mild disease were treated with antiemetics, anticholinergics, intravenous feedings, and allowed nothing by mouth for at least 24 hours beyond cessation of vomiting. Those with more severe symptoms of vomiting and abdominal pain, in addition to the above regimen, received analgesics and nasogastric suction until cessation of symptoms. Only a very few patients received antacids through or around the nasogastric tube. Only 4 patients were treated with antibiotics for fever and/or leukocytosis not accounted for by a concurrent illness. In this review the origin of the disease in the majority of instances was idiopathic, but gallbladder disease was present in a considerable number of patients (Table IV). There were probably more patients who had chulelithiasis but the incidence of patients who received diagnostic cholecystograms was low due to failure of the patients to return for their diagnostic test as an outpatient. It is
284
Corlett
and Mishell
Table 13. Patients with Patient
enzyme
Presenting
B. Y T. E. M. 0. J. D. A. A. I. v. ;*I? J. W. A. H. J. S. M. 0. J. P. D. P. B. D.
J. A. R. A. B. M. E.
June 1, 1972 Am. J. Ohstet. Gynecol.
R. S. G. C. P. C. S.
G. D. C. M.
elevations
between .-
complaint
three
Days hospitalired
and
ten
Abdominal pain
times
more than -_____.---.---
No. of recurrences
+ -
30
H.G.-R/OP
Nausea and vomiting, pain Nausea and vomiting, pain x 4 days Back pain, nausea and vomiting Persistent vomiting RUQ pain, nausea and vomiting Nausea and vomiting Pain and nausea Abdominal pain, nausea and vomiting Nausea and vomiting, abdominal pain Intractable vomiting
6 8 3 4 4 4 8 5 2 15
H.G.-R/OP Pancreatitis Pancreatitis H.G. Pancreatitis H.G. Gastritis R/O pain Pancreatitis H.G.
Abdominal Vomiting
12 10
Hyperemesis Pancreatitis Hyperemesis R/O pancreatitis R/O P
6
2 -
Gallbladder P
Nausea and pain, vomiting Nausea and vomiting Pain and nausea Chest pain, vomiting Vomiting, pain Vomiting, pain Vomiting, pain Vomiting, Vomiting
pain x 2 weeks
*See
footnote,
Table
IA.
tSee
footnote,
Table
IA.
difficult to prove a cause-effect relation between diuretic therapy and the development of pancreatitis. Several of these patients were receiving oral diuretics at the time of onset of the disease,but only 2 patients had been receiving those drugs for a prolonged duration. The complication rate in this series was low, although the few patients who had complications usually had more than one (Table V) . Only one patient had hypocalcemia, with a serum calcium level of 7.7 mg. per cent, and only 3 had visible jaundice. It is significant to note that there were 7 patients totalIy without pain or tenderness and another 7 who complained of minimal pain but had no abdominal tenderness on physical examination. These patients were hospitalized for severe vomiting and were
___
Diagnosis on admission*
Abdominal pain Nausea Nausea and vomiting, mild epigastric pain 12 days’ nausea and vomiting and mild abdominal pain Nausea and vomiting 2 weeks
pain
4 5 4
normal
disease
P H.G. P H.G. ? R/O pancreatitis Cholecystitis
+
2 4
1
-
P H.G.
noted thereafter to have elevated amylase and/or diastase values. The diagnosis of pancreatitis was thus confirmed. Of the 52 patients, 11 had a recurrence during this pregnancy and 27 patients had one or more recurrences at one time or another, for a recurrence rate of 52 per cent. There were 4 patients with 4 or more recurrences each. Ten of the 52 patients had diseasein the puerperium, 4 for the first time and 6 with recurrences (Table VI). Thus, the rate for recurrence in the puerperium in this serieswas only 11 per cent as compared to 73 per cent in Langmade’s series. Comment
The reported mortality rate of pancreatitis in nonpregnant individuals now varies from 5 to 15 per cent but formerly was reported
Volume Number
Amylase/ diastase 239/2,520 134/2,840 214/2,650
Pancreatitis
113 3
Other
significant data
K =
Bilirubin
120/1,900 284/2,650 -/1,340 /4,561 134/1,600 143/3,750 136/3,200 69/1,570 -/1,900 750/1,820
CHO
2 13/3,600 200/2,400
Complications
-
3.3
-
= =
-
-
-
158
K = 2.5 Na = 128 Cl = 78 Bilirubin = Hct = 22% Bilirubin =
Alkaline Bilirubin
3.2
f
2
AB
1
$ + ? ? + + ? + + Th.Ab
3 3 2 2 P 1 3 3 3 1
SB +
3 3
-
+ + + AB + + ?
2 3 3 1 3 3 2
-
* -
1 1
-
Nasogastric moved
Fever -
-
1.7
1.7 phosphatase = 2.9 -
tube reprematurely -
Neg. Neg.
Electrolyte
imbalance
Abdominal
pregnancy
-
=
8.5
Early
ileus
-
to be as high as 50 per cent.3 In Lukash’s3 series of 100 patients the mortality rate was 5 per cent and in Disco, Miller, and Copeland’s* series of 231 patients it was 5.3 per cent in patients with edematous pancreatitis and 56 per cent in patients with acute hemorrhagic pancreatitis. Thus, there is a great difference in prognosis between the two types of pancreatitis. The fact that the mortality rate in this series was zero is partially attributable to the fact that probably not more than 2 or 3 patients had disease of the hemorrhagic type. In addition, many of these patients had mild disease and adequate treatment was instituted soon after admission because of a high degree of accuracy in making the diagnosis at this time (Table II). The corrected fetal survival rate of 89 per
-
Trimester 2 3 1
Fever
-
Fetal outcome+
285
? ? ?
-
950/5,400
109/4,000 250/1,550 /2,540 95/2,520 95/2,520 125/3,950 530/3,650
X-rays when done Neg.
250/1,600
/1,900 141/4,400
laboratory
in pregnancy
cent compares favorably with earlier rep0rts.l It is believed that the fetal prognosis should be good unless the mother has a serious complication, such as ketoacidosis, hypotension, severe renal disease, etc. Walker and Diddle1 concur and state that the perinatal mortality rate should be normal, provided the maternal morbidity is not severe. From this series it may be concluded (1) that the disease may develop in any trimester, although most commonly in the third; (2) that the disease is not more common among primiparas, in contrast to other report+ *, 5; and (3) that in mast instances the etiology is idiopathic, but the commonest known cause is primary disease of the gallbladder. Stasis, increased concentration of cholesterol in bile, and changes in the physiochemi-
286
Corlett
and Mishell
June 1, 1972 Am. J. Obstct. Gynecol.
.. 8 I
I
I
IIIII
fj >
cal nature of bile salt-all factors believed important in the formation and deposition of biliary calculi, normally occur in pregnancy.” Therefore it is not surprising that pancreatitis commonly occurs in association with gallbladder disease.6> T It has been shown by cholecystography that during pregnancy the gallbladder appears larger than normal, empties sluggishly, and is hypomotile. The resultant stasis increases the likelihood of precipitation of solids in bile.6 In addition, there is evidence that the lymphatic system may be involved in the transmission of inflammatory disease from one organ to another in the pancreaticobiliary system. Since the liver, biliary tract, and pancreas originate from a common primordium in the foregut, it is not surprising that the lymphatic circulation of these organs would be intimately interrelated.? It is interesting to note that in Lukash’s series of 100 nonpregnant patients with pancreatitis 66 per cent were caused by alcohol abuse, 23 per cent by biliary tract disease, and only 7 per cent were idiopathic. Cornish, McClellan, and Johnson,8 in 1961, showed that daily administration of chlorothiazides can cause an increase in serum amylase levels. They reported 4 cases of pancreatitis secondary to thiazide therapy.8 In this series there were only 2 cases of pancreatitis attributed to diuretics. The role of pregnancy per se as an etiologic factor was discussed in the early literature on the disease, but is controversial. In 1959 the Survey of Obstetrics and Gynecology stated that “acute pancreatitis is one of the rarest complications of pregnancy and I have only seen 1 case (that one a fatality, presented without pain but severe vomiting and inanition) .“5 However, it was reported by Bernabco in 1931 that of 957 women with acute pancreatic necrosis 18 per cent were pregnant, and a high incidence of pregnancy in pancreatitis was also shown by Katsch and GU~ZOW.~ Zollingerg includes pregnancy in his list of etiologic factors in pancreatitis but does not elaborate on its mechanisms. The importance of the effect of pregnancy upon the prognosis is also controversial. Rabkin’O reported 2 cases of severe pancrea-
Volume Number
113 3
Pancreatitis
Table If. Classification admission
according
in pregnancy
287
Table IV. EtioIogy
to
diagnosis
Pancreatitis(primary diagnosis) Possible pancreatitis Hyperemesis gravidarum Cholecystitis and/or cholelithiasis Diabetes Hepatitis Gastrititis Unknown
14 19 8 5 1
Total
52
: 3
1. Cholelithiasis a. Proved by operation b. Proved by cholecystogram c. Suggestive history and elevation of bilirubin and alkaline phosphatase 2. Alcohol abuse 3. Other gastrointestinal disorder (peptic ulcer disease) 4. Abdominal pregnancy 5. Diuretics 6. Idiopathic
12 5 4 3 2 1 1 2 34
Total
Table
52
III. Fetal outcome Term, living infant Spontaneous abortion Therapeutic abortion Stillborn Premature Abdominal pregnancy Unknown outcome Total
(SB)
31 2 1 2 2 1 13 52
titis in pregnancy and in both a remarkable recovery immediately post partum was noted. He concluded that any pregnant female with acute pancreatitis who does not respond adequately to medical management should have the pregnancy terminated-by hysterotomy if necessary. The only death in Langmade’s series of 9 followed a therapeutic abortion performed because of the patient’s worsening condition. Walker and Diddle1 state that the outcome of the disease should not be altered by pregnancy. In this series there was only one therapeutic abortion (for a psychiatric indication) yet all patients survived. The results of this study indicate that pregnancy most likely does not adversely affect the prognosis. Thus there does not appear to be any reason to terminate pregnancy in patients who develop pancreatitis. The place of laparotomy in the therapy of pancreatitis in pregnancy is also somewhat controversial. Von Ellen5 reported upon 2 patients with pancreatitis while pregnant, both of whom had abdominal deliveries. She stated that in both cases the diagnosis could have been confused with abruptio placentae and advocated cesarean section and abdominal exploration when the diagnosis of pancreatitis is made in term gestation. With the
Table V. Complications Jaundice Ascites Fever Hypocalcemia Pneumonia Hemorrhagic Ketoacidosis Cholelithiasis Hypokalemia Hypochloremia Antibiotics
3
requiring (3.0 mg.
antepartum ‘36 )
operation
required
Total
18
Table VI. Patients Recurrence Recurrence puerperium Recurrence Recurrence Recurrence pregnant Recurrence pregnant TotaI
: 1 1 1 1 1 2 1 4
No.
during during
with this this
recurrent
pregnancy pregnancy
in puerperium only in another pregnancy before this pregnancy
disease 9 and
in 2 4 2
when
not 9
after
this
pregnancy
when
not 1
with
recurrences
27
use of the pathognomonic laboratory tests such confusion should no longer exist. In Langmade’s review of 53 pregnant women with this disease, 38 patients had laparotomies and 8 died. In Fogerson and Shedd’sll series there were 16 deaths following 17 laparotomies in nonpregnant patients. Only 3 patients in this series required a laparotomy; the first for an abdominal pregnancy, one for severe cholelithiasis not resolved with medical management, and the third for a repeat, elective cesarean section. The latter patient developed a recurrence in the puerperium before cholecystectomy was
288
Corlett
and
Mishell
performed. The results of this series indicate that laparotomy is only indicated when the diagnosis is not definite or an etiologic factor can be rectified by an operative procedure. During this time period one pregnant patient was treated for pancreatitis for several days before the true diagnosis of small bowel obstruction was established. Her declining physical state, fever, leukocytosis, and x-ray picture of small bowel ischemia led to a laparotomy and excision of a large segment of infarcted small intestine. The pathognomonic finding of an elevated serum amylase and/or urine diastase makes the diagnosis relatively easy to establish; however it must be realized that there are other causes of hyperamylasemia. Small bowel obstruction, perforated duodenal ulcer, mesenteric vascular occlusion, acute cholecystitis, ruptured aortic aneurysm, advanced renal insufficiency as well as mumps may all produce a hyperamylasemia. Since analgesics themselves may cause a rise in serum amylase levels, the blood for this determination should be obtained prior to analgesic administration. It must be remembered that in acute pancreatitis there is a peak in amylase levels 6 to 12 hours after the onset of symptoms. This serum enzyme then returns to normal within 24 to 72 hoursl’ The diastase values, on the other hand, remain elevated for 7 to 10 days. There are numerous other laboratory parameters that are altered, but all are of secondary diagnostic importance. Serum lipase values may become elevated in 12 to 24 hours, but performance of the lipase test requires 16 to 24 hours’? and is thus not clinically useful. About 50 per cent of all patients with acute pancreatitis? have hypoglycemia. Hypocalcemia is an important indicator of a poor prognosis, although it must be remembered that the serum calcium normally is depressed in pregnancy.* In a previous report from this institution of a series of nonpregnant patients with pancreatitis, death resulted in all those whose serum calcium fell below 7.0 mg. per centI The white blood cell count generally cannot be considered as a useful diagnostic aid. In this series it was greater than 15,000 in
only 5 cases and greater than 10,000 in an additional 11. Disco, Miller, and Copeland reported a little more than one third of their 231 patients with pancreatitis had normal leukocyte counts and only 32 an elevation greater than 20,000. Fever is unusual in the absence of another complication, and only 3 patients in this series had a temperature above 100° F. Most people feel that there is a poor c.orrelation between the degree of enzyme elevation and the severity of the disease. In this series, however, there seemed to be a good correlation as all of those with severe disease had marked or moderate elevation of enzymes and of those with mild disease, none had marked increase in enzymes. Metheny, Roberts, and Stranahanl’ reported the incidence of proteinuria to be 100 per cent. Langmade and Edmundsot? did not find that every patient had proteinuria, and their findings are in agreement with those reported in this survey. Blood electrdytes are usually deranged in proportion to the severity of vomiting. In the presence of primary biliary tract disease liver function tests are usually abnormal. A nonspecific ileus is the most common abdominal roentgenographic finding. Various types of x-ray abnormalities are reported to occur with an incidence varying from 45 per cent” to 100 per cent2 Authoritative texts frequently mention the presence of a sentinel loop of small bowel, but it was seen infrequently in this series. A left pleural effusion occurs in about 20 per cent of cases with acute pancreatitis according to Zollinger.g Treatment for pancreatitis in pregnancy is no different than in the nonpregnant state. The main objectives of therapy are aimed at diminishing pancreatic activity. Continuous nasogastric suction with or without antacids administered through the nasogastric tube contribute the most to diminishing the production of pancreatic juice which may reach as high as 2,700 ml. per day-l5 If gastric contents are drained by a nasogastric tube, this may be reduced to 5 to 10 ml. per day. This is accomplished by ( 1) preventing gastric distention; (2) averting the secretion-
Volume Number
113 3
Pancreatitis
stimulation effect of acid contents on the duodenum; and (3) avoiding pancreozymin stimulation by peptones and other digestive products. Vagal stimulation is reduced by administering therapeutic doses of anticholinergics which may result in moderately severe dryness of the mouth and blurred vision. Our choice is usually propantheline 15 to 30 mg. every 6 to 8 hours. The use of anticholinergics has not been shown conclusively to diminish pancreatic secretion and according to Goodman and Gilman16 “atropine has little effect on the secretion of pancreatic juice bile or succus entericus . . . processes largely under hormonal rather than vagal control. However, most gastroenterologists writing on the subject17-1” do recommend its use, and IngelfingerzO in his discussion on the use of anticholinergics in gastrointestinal disorders states that “a bout of pancreatitis is possibly the only gastrointestinal condition in which general agreement exists about the value of using anticholinergics.” Analgesics, intravenous fluids, and antiemetics are also administered in the management of the disease. Meperidine is the analgesic of choice, since morphine is known to increase the resistance of the sphincter of Oddil” to a greater degree than meperidine, and this may worsen the disease process. Langmade has stated, with good reasoning, that since blood glucose levels directly influence pancreatic enzyme secretion?* normal saline should be given during the acute phase of the disease and when the acute phase is subsiding a solution of 2.5 per cent dextrose in normal saline should be given instead of hypertonic or isotonic glucose solution. Since dextran has been shown to decrease pancreatic secretion, its intravenous use might be considered.z2 In severe cases of pancreatitis (usually the acute necrotizing or hemorrhagic type) colloidal rather than crystalloid solutions may be necessary to adequately replace the intra-
REFERENCES
1.
B. E.,
OBSTET.
GYNECOL.
and
Diddle, 105: 206,
A. W.: 1969.
AM.
289
vascular volume. The “third-spacing” occurring in this disease is similar to thermal injuries and may require large amounts of plasma, albumin, or whole blood. Monitoring of the central venous pressure may be necessary in cases such as these. The role of antibiotics in therapy is still controversial and is not settled. Disco, Miller, and Copeland state they may have some effect in preventing the late septic complications of acute pancreatitis and Langmade used penicillin in the acute phase in several patients, as he believed this would prevent the strong possibility of secondary bacterial invasion following the initial chemical insult. Antibiotics were not used routinely in this series and, in fact, only 4 patients all with severe pancreatitis received antibiotics. The predilection for recurrences in this disease has been well documented. In Langmade and Edmundson’s series 73 per cent had a recurrence in the puerperium. Walker and Diddle1 state that nearly 50 per cent of all patients with pancreatitis have recurrences. The recurrence rate of 52 per cent in this series agrees with their finding. The complication rate in this series was low in comparison to that of other reports. In Lukash’s5 series of 100 nonpregnant patients there was a 38 per cent complication rate including a 10 per cent incidence of obstructive jaundice. Walker and Diddle,* in a group of nonpregnant patients, report a 25 per cent incidence of jaundice with a 10 per cent rate of ultimate pseudocyst development and a 13 per cent rate of diabetic coma. They theorize that complications result secondary to either (1) local inflammation and the necrotic effects of pancreatic enzymes on peripancreatic tissues or (2) a remote effect of circulating enzyme. Most complications occur in patients with the hemorrhagic type of pancreatitis. A major factor contributing to the low incidence of complications in this series was the low incidence of this severe form of the disease.
2.
Walker,
in pregnancy
J. 3.
Langmade, C. F., and Edmundson, Gynecol. Obstet. 92: 43, 1956. Lukash, W. A.: GP 40: 103, 1969.
H.:
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Disco, J., Miller, L., and Copeland, E. M.: Surp. Gvnecol. Obstet. 129: 265. 1969. Von Ellen, E.: Obstet. Gynecol. Surv. 14: 845, 1959. Guttmacher, A. F., and Rovinsky, J. J.: Medical, Surgical and Gynecological Complications of Pregnancy, Baltimore, 1960, The Williams & Wilkins Company. Weiner, S., Gramatica, L., Voegle, L., Hauman, R., and Anderson, M.: Am. J. Surg. 119: 55, 1970. Cornish, A., McClellan, J, J., and Johnson, D. H.: N. Engl. J. Med. 265: 673, 1961. Zollinger, R. M.: Postgrad. Med. 49: 91, 1971. Rabkin, R.: Obstet. Gynecol. 31: 508, 1968. Fogerson, V., and Shedd, D. P.: Surg. Gynecol. Obstet. 101: 578, 1955. Hayes, T. A.: Postgrad. Med. 44: 39, 1968. Edmundson, H. A., and Berne, C.: Surg. Gvnecol. Obstet. 79: 240. 1944. Mktheny, D., Roberts, E.‘Q., and Stranahan, A.: Surg. Gynecol. Obstet. 79: 504, 1944. u
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I
16.
17. 18.
19.
20. 21.
22.
Texter, E. C., Chou, C., Laurette, H. C., and Van Trappen, G. R.: Physiology of the Gastrointestinal Tract, St. Louis, 1968, The C. V. Mosby Company. Goodman, L. S., and Gilman, A.: The Pharmacological Basis of Therapeutics, New York, 1970, The Macmillan Company. Conn, H. F.: Current Therapy, Philadelphia, 1968, W. B. Saunders Company. Harrison, T. R.: Principles of Internal Medicine, New York, 1962, McGraw-Hill Book Co., Inc. Bockus, H. L.: Gastroenterology, Philadelphia, 1965, W. B. Saunders Company., vol. III. Ingelfinger, F. J.: N. Engl. J. Med. 268: 1454, 1963. Rabkin, B. P.: Secretory Mechanism of the Digestive Glands, New York, 1944, Paul B. Hoeber, Inc. Nardi, G. L.: N. Engl. J. Med. 268: 1065, 1963.
American
113 number 3 June 1, 1972
of Obstetrics and Gynecology
Journal
OBSTETRICS
Pancreatitis in pregnancy ROBERT
C.
CORLETT,
DANIEL
R.
MISHELL,
Los Angeles,
California
JR., JR.,
M.D. M.D.
Pancreatitis in pregnancy is not a rare disease and must be considered in the differential diagnosis of any patient with hyperemesis gravidarum as well as those pregnant patients with signs of an acute surgical abdominal crisis. The serum amylase and diastase tests are rapid and reliable and provide an excellent diagnostic and prognostic test for the clinician. It must be remembered that the amylase in serum is excreted rapidly and so a urinary diastase test must always be ordered concurrently. It cannot be overemphasized that the patient with pancreatitis (including severe cases) may present initially without pain or tenderness. If the diagnosis is made early, medical management is almost always successful and the prognosis for mother and fetus is good. The excellent results obtained in this series are a result of early diagnosis and rapid treatment.
PANCREATITIS in pregnancy has a reincidence of from l/3,800 to ported l/l 1,467l and is generally considered to be extremely hazardous for both mother and fetus. The most recent comprehensive review was written by Langmade and Edmundson From the Department of Obstetrics Gynecology, Los Angeles CountyUniversity of Southern California Medical Center. f;;;ived for publication December f.;;pted
for publication
January
in 1951. In this article they stated that only 53 cases had previously been reported. They then added 9 cases of their own, 8 of which occurred during a 9 year period, 1940-1948, at the Los Angeles County General Hospital. The purpose of this paper is to discuss experience with this disease obtained during the last 6 years at this institution. During this time period there were 52 patients who developed pancreatitis while pregnant or during the puerperium. There were no maternal deaths and a corrected fetal salvage rate of 89 per cent. This favorable prognosis for mother and infant is due in large part to the fact that the disease was diagnosed early and treatment instituted soon thereafter.
and
8, I,
Reprint requests: Dr. Daniel R. Mishell, Jr., Dept. of Ob./Gyn., Los Angeles County, University of Southern California Medical School, Los Angeles, California 90033.
281
282
Corlett
and Mishell
Table IA. Patients
June 1, 1972 Am. J. Obstet. Gynecol.
with
enzyme
elevations
more
than
ten times
normal -
Patient
Days hospita&ted
Complaint
Abdominal
No.
pain
of
Diagnosis
re-
mission” Gallbladder disease
CUtTtVlCC?S
7
+
9
3+
-.
S. D.
RUQ pain nausea, vomiting
F. R. M. M. M. G.
Pain, nausea, vomiting Vomiting Epigastric pain, nausea and vomiting Malaise, nausea and vomiting Nausea and vomiting, back pain Nausea and vomiting, back pain Nausea and vomiting, back pain Nausea and vomiting, back pain Vomiting, chest and abdominal pain Nausea and vomiting
14 4 7 10 6 18 27 6 7
C. R. T. G.
RUQ pain and vomiting Abdominal pain Epigastric pain/bilious
5 10 7
t 3-4+
1 1 1
R/OP Gallbladder R/OP
A. H. M. Z. B. P.
Pain and nausea Nausea and vomiting, pain Dehydration and vomiting
14 4 54
3+ t -
2 1 -
P P Diabetes
EA. J. G. 2:: A. H. V. J.
s. v.
F. D.
Pain and vomiting
*Diagnosis tFeta1
on
admission:
outcome:
Material
+, living
and
term;
+P, living
R/OP, premature:
pancreatitis SB,
methods
A retrospective review of all patients who had the diagnosis of pancreatitis established either during pregnancy or within the first 6 weeks post partum at Los Angeles County/ USC Medical Center from June, 1965, to the present time was performed. During this time period patients were classified as having mild, moderate, or severe pancreatitis based on a combination of parameters. Patients were placed in the severe category if they had one or more of the following : ( 1) required hospitalization for more than 2 weeks, (2) exhibited a slow response to medical management with persistent pain or prolonged nasogastric suction required, (3) had severe electrolyte imbalance, (4) had frequent recurrences, (5 ) required operation, (6) required antibiotics, or (7) had a major complication such as ketoacidosis or shock. Patients were considered to have mild pancreatitis if they required hospitalization for 4 days or less, had one or no recurrences, had no electrolyte derangement, and responded with minimal treatment. The patients who fit in between these cate-
was stillborn;
P H.G. R/OP R/OP R/OP R/OP P Cholecystitis H.G. Hepatitis
2+ + t +t 2+
2t
+
t
t
+
14
P, pancreatitis;
considered AB,
in spontaneous
the
on ad-
3-4 differential; abortion;
gories were defined moderate pancreatitis.
R/OP H.G.,
Tb.
disease
AB,
arbitrarily
hyperemesis
gravidarum.
therapeutic
abortion;
as having
Results During this time period there were 52 pregnant or puerperal patients with a diagnosis of pancreatitis (Tables IA, IB, and IC) and 55,416 live births-an incidence of l/1,066. The ages ranged from 16 to 37 with a mean of 24.5 and parity from 0 to 10 with a mean of 2.2. There were 42 multiparous and 9 nulliparous patients. The diagnosis was made or suspected at the time of admission in the majority of instances, 33 of 52 (Table II). Fourteen had their first attack in the first trimester, 10 in the second, 18 in the third, and 9 in the puerperium. Of 39 instances in which it was possible to determine the fate of the fetus, there were 33 fetal survivals (Table III). Of the 6 perinatal deaths, one was a therapeutic abortion pregnancy, giving a an d one an abdominal corrected fetal salvage rate of 89 per cent. Of the 52 patients, 13 had severe pancreatitis. Of these 13 patients there were 6 with
?,
Volume Number
Pancreatitis
113 3
Other Amylase/dia.stase 3,800/2,650
Bilirubin Alkaline
5,300/48,000 665/7,000 2,130/5,120 7,500/40,500 5,000/48,000 235/12,300 9,300/34,000 615/44,000 -/14,200 9,500/48,000 2,175/365/12,500 6,600/3,600 239/8,000 17,000/2 1,000 1,340/10,000 7,625/50,000 unknown
fetal
significant data = 3.3 phosphatase -
X-rays, when done
laboratory
=
=
24,200
Alkaline
?
3
-
? + ? + + + + + ? +
3 1 1 2 3 3 1 P 1 3
Jaundice
SB t t
P 3 P
Shock
+ BB
3 2 3
t
P
ileus -
Bilirubin W.B.C.
=
22
Adynamic
ileus
Operation Jaundice Jaundice -
Alkaline Bilirubin GPT =
phosphatase = 6.4 120
=
8.5 -
CHO = 510 pH = 7.0 W.B.C. = 15,700
Trimester
-
phosphatase = 8.1 = 16,300
Fetal outcome+
283
12.5 Paralytic
W.B.C.
Complications
in pregnancy
Ascites,
ileus
Ketoacidosis, hypocalcemia Fever
outcome.
associated cholelithiasis and 9 who had recurrences during this gestation. The duration of hospitalization was greater than 2 weeks in the majority (7) ; was nearly 2 months in one case who presented initially in diabetic ketoacidosis. In this group of 13, the fetal outcome was known in 12. There were 7 term, viable infants; one premature infant; one therapeutic abortion; one spontaneous abortion; one intrauterine death, and one abdominal pregnancy which also died prior to laparotomy. Of the 13 patients considered to have severe pancreatitis by clinical standards, 10 had amylase and/or diastase values greater than ten times normal (Table IA) and the remaining 3 had moderately elevated enzymes (Table IB) . None had only minimal elevations (Table IC) . There were 16 patients with moderate disease, and of these 16 the fetal outcome was known in 13. There were one premature infant, 12 term infants, and no perinatal deaths. Twenty-three patients were considered to have mild cases of pancreatitis, and 15 of these were followed to the termination of their pregnancy. There were one premature
infant, and 13 term living infants, and one spontaneous abortion. The treatment varied in relation to the severity of the disease. Those with mild disease were treated with antiemetics, anticholinergics, intravenous feedings, and allowed nothing by mouth for at least 24 hours beyond cessation of vomiting. Those with more severe symptoms of vomiting and abdominal pain, in addition to the above regimen, received analgesics and nasogastric suction until cessation of symptoms. Only a very few patients received antacids through or around the nasogastric tube. Only 4 patients were treated with antibiotics for fever and/or leukocytosis not accounted for by a concurrent illness. In this review the origin of the disease in the majority of instances was idiopathic, but gallbladder disease was present in a considerable number of patients (Table IV). There were probably more patients who had chulelithiasis but the incidence of patients who received diagnostic cholecystograms was low due to failure of the patients to return for their diagnostic test as an outpatient. It is
284
Corlett
and Mishell
Table 13. Patients with Patient
enzyme
Presenting
B. Y T. E. M. 0. J. D. A. A. I. v. ;*I? J. W. A. H. J. S. M. 0. J. P. D. P. B. D.
J. A. R. A. B. M. E.
June 1, 1972 Am. J. Ohstet. Gynecol.
R. S. G. C. P. C. S.
G. D. C. M.
elevations
between .-
complaint
three
Days hospitalired
and
ten
Abdominal pain
times
more than -_____.---.---
No. of recurrences
+ -
30
H.G.-R/OP
Nausea and vomiting, pain Nausea and vomiting, pain x 4 days Back pain, nausea and vomiting Persistent vomiting RUQ pain, nausea and vomiting Nausea and vomiting Pain and nausea Abdominal pain, nausea and vomiting Nausea and vomiting, abdominal pain Intractable vomiting
6 8 3 4 4 4 8 5 2 15
H.G.-R/OP Pancreatitis Pancreatitis H.G. Pancreatitis H.G. Gastritis R/O pain Pancreatitis H.G.
Abdominal Vomiting
12 10
Hyperemesis Pancreatitis Hyperemesis R/O pancreatitis R/O P
6
2 -
Gallbladder P
Nausea and pain, vomiting Nausea and vomiting Pain and nausea Chest pain, vomiting Vomiting, pain Vomiting, pain Vomiting, pain Vomiting, Vomiting
pain x 2 weeks
*See
footnote,
Table
IA.
tSee
footnote,
Table
IA.
difficult to prove a cause-effect relation between diuretic therapy and the development of pancreatitis. Several of these patients were receiving oral diuretics at the time of onset of the disease,but only 2 patients had been receiving those drugs for a prolonged duration. The complication rate in this series was low, although the few patients who had complications usually had more than one (Table V) . Only one patient had hypocalcemia, with a serum calcium level of 7.7 mg. per cent, and only 3 had visible jaundice. It is significant to note that there were 7 patients totalIy without pain or tenderness and another 7 who complained of minimal pain but had no abdominal tenderness on physical examination. These patients were hospitalized for severe vomiting and were
___
Diagnosis on admission*
Abdominal pain Nausea Nausea and vomiting, mild epigastric pain 12 days’ nausea and vomiting and mild abdominal pain Nausea and vomiting 2 weeks
pain
4 5 4
normal
disease
P H.G. P H.G. ? R/O pancreatitis Cholecystitis
+
2 4
1
-
P H.G.
noted thereafter to have elevated amylase and/or diastase values. The diagnosis of pancreatitis was thus confirmed. Of the 52 patients, 11 had a recurrence during this pregnancy and 27 patients had one or more recurrences at one time or another, for a recurrence rate of 52 per cent. There were 4 patients with 4 or more recurrences each. Ten of the 52 patients had diseasein the puerperium, 4 for the first time and 6 with recurrences (Table VI). Thus, the rate for recurrence in the puerperium in this serieswas only 11 per cent as compared to 73 per cent in Langmade’s series. Comment
The reported mortality rate of pancreatitis in nonpregnant individuals now varies from 5 to 15 per cent but formerly was reported
Volume Number
Amylase/ diastase 239/2,520 134/2,840 214/2,650
Pancreatitis
113 3
Other
significant data
K =
Bilirubin
120/1,900 284/2,650 -/1,340 /4,561 134/1,600 143/3,750 136/3,200 69/1,570 -/1,900 750/1,820
CHO
2 13/3,600 200/2,400
Complications
-
3.3
-
= =
-
-
-
158
K = 2.5 Na = 128 Cl = 78 Bilirubin = Hct = 22% Bilirubin =
Alkaline Bilirubin
3.2
f
2
AB
1
$ + ? ? + + ? + + Th.Ab
3 3 2 2 P 1 3 3 3 1
SB +
3 3
-
+ + + AB + + ?
2 3 3 1 3 3 2
-
* -
1 1
-
Nasogastric moved
Fever -
-
1.7
1.7 phosphatase = 2.9 -
tube reprematurely -
Neg. Neg.
Electrolyte
imbalance
Abdominal
pregnancy
-
=
8.5
Early
ileus
-
to be as high as 50 per cent.3 In Lukash’s3 series of 100 patients the mortality rate was 5 per cent and in Disco, Miller, and Copeland’s* series of 231 patients it was 5.3 per cent in patients with edematous pancreatitis and 56 per cent in patients with acute hemorrhagic pancreatitis. Thus, there is a great difference in prognosis between the two types of pancreatitis. The fact that the mortality rate in this series was zero is partially attributable to the fact that probably not more than 2 or 3 patients had disease of the hemorrhagic type. In addition, many of these patients had mild disease and adequate treatment was instituted soon after admission because of a high degree of accuracy in making the diagnosis at this time (Table II). The corrected fetal survival rate of 89 per
-
Trimester 2 3 1
Fever
-
Fetal outcome+
285
? ? ?
-
950/5,400
109/4,000 250/1,550 /2,540 95/2,520 95/2,520 125/3,950 530/3,650
X-rays when done Neg.
250/1,600
/1,900 141/4,400
laboratory
in pregnancy
cent compares favorably with earlier rep0rts.l It is believed that the fetal prognosis should be good unless the mother has a serious complication, such as ketoacidosis, hypotension, severe renal disease, etc. Walker and Diddle1 concur and state that the perinatal mortality rate should be normal, provided the maternal morbidity is not severe. From this series it may be concluded (1) that the disease may develop in any trimester, although most commonly in the third; (2) that the disease is not more common among primiparas, in contrast to other report+ *, 5; and (3) that in mast instances the etiology is idiopathic, but the commonest known cause is primary disease of the gallbladder. Stasis, increased concentration of cholesterol in bile, and changes in the physiochemi-
286
Corlett
and Mishell
June 1, 1972 Am. J. Obstct. Gynecol.
.. 8 I
I
I
IIIII
fj >
cal nature of bile salt-all factors believed important in the formation and deposition of biliary calculi, normally occur in pregnancy.” Therefore it is not surprising that pancreatitis commonly occurs in association with gallbladder disease.6> T It has been shown by cholecystography that during pregnancy the gallbladder appears larger than normal, empties sluggishly, and is hypomotile. The resultant stasis increases the likelihood of precipitation of solids in bile.6 In addition, there is evidence that the lymphatic system may be involved in the transmission of inflammatory disease from one organ to another in the pancreaticobiliary system. Since the liver, biliary tract, and pancreas originate from a common primordium in the foregut, it is not surprising that the lymphatic circulation of these organs would be intimately interrelated.? It is interesting to note that in Lukash’s series of 100 nonpregnant patients with pancreatitis 66 per cent were caused by alcohol abuse, 23 per cent by biliary tract disease, and only 7 per cent were idiopathic. Cornish, McClellan, and Johnson,8 in 1961, showed that daily administration of chlorothiazides can cause an increase in serum amylase levels. They reported 4 cases of pancreatitis secondary to thiazide therapy.8 In this series there were only 2 cases of pancreatitis attributed to diuretics. The role of pregnancy per se as an etiologic factor was discussed in the early literature on the disease, but is controversial. In 1959 the Survey of Obstetrics and Gynecology stated that “acute pancreatitis is one of the rarest complications of pregnancy and I have only seen 1 case (that one a fatality, presented without pain but severe vomiting and inanition) .“5 However, it was reported by Bernabco in 1931 that of 957 women with acute pancreatic necrosis 18 per cent were pregnant, and a high incidence of pregnancy in pancreatitis was also shown by Katsch and GU~ZOW.~ Zollingerg includes pregnancy in his list of etiologic factors in pancreatitis but does not elaborate on its mechanisms. The importance of the effect of pregnancy upon the prognosis is also controversial. Rabkin’O reported 2 cases of severe pancrea-
Volume Number
113 3
Pancreatitis
Table If. Classification admission
according
in pregnancy
287
Table IV. EtioIogy
to
diagnosis
Pancreatitis(primary diagnosis) Possible pancreatitis Hyperemesis gravidarum Cholecystitis and/or cholelithiasis Diabetes Hepatitis Gastrititis Unknown
14 19 8 5 1
Total
52
: 3
1. Cholelithiasis a. Proved by operation b. Proved by cholecystogram c. Suggestive history and elevation of bilirubin and alkaline phosphatase 2. Alcohol abuse 3. Other gastrointestinal disorder (peptic ulcer disease) 4. Abdominal pregnancy 5. Diuretics 6. Idiopathic
12 5 4 3 2 1 1 2 34
Total
Table
52
III. Fetal outcome Term, living infant Spontaneous abortion Therapeutic abortion Stillborn Premature Abdominal pregnancy Unknown outcome Total
(SB)
31 2 1 2 2 1 13 52
titis in pregnancy and in both a remarkable recovery immediately post partum was noted. He concluded that any pregnant female with acute pancreatitis who does not respond adequately to medical management should have the pregnancy terminated-by hysterotomy if necessary. The only death in Langmade’s series of 9 followed a therapeutic abortion performed because of the patient’s worsening condition. Walker and Diddle1 state that the outcome of the disease should not be altered by pregnancy. In this series there was only one therapeutic abortion (for a psychiatric indication) yet all patients survived. The results of this study indicate that pregnancy most likely does not adversely affect the prognosis. Thus there does not appear to be any reason to terminate pregnancy in patients who develop pancreatitis. The place of laparotomy in the therapy of pancreatitis in pregnancy is also somewhat controversial. Von Ellen5 reported upon 2 patients with pancreatitis while pregnant, both of whom had abdominal deliveries. She stated that in both cases the diagnosis could have been confused with abruptio placentae and advocated cesarean section and abdominal exploration when the diagnosis of pancreatitis is made in term gestation. With the
Table V. Complications Jaundice Ascites Fever Hypocalcemia Pneumonia Hemorrhagic Ketoacidosis Cholelithiasis Hypokalemia Hypochloremia Antibiotics
3
requiring (3.0 mg.
antepartum ‘36 )
operation
required
Total
18
Table VI. Patients Recurrence Recurrence puerperium Recurrence Recurrence Recurrence pregnant Recurrence pregnant TotaI
: 1 1 1 1 1 2 1 4
No.
during during
with this this
recurrent
pregnancy pregnancy
in puerperium only in another pregnancy before this pregnancy
disease 9 and
in 2 4 2
when
not 9
after
this
pregnancy
when
not 1
with
recurrences
27
use of the pathognomonic laboratory tests such confusion should no longer exist. In Langmade’s review of 53 pregnant women with this disease, 38 patients had laparotomies and 8 died. In Fogerson and Shedd’sll series there were 16 deaths following 17 laparotomies in nonpregnant patients. Only 3 patients in this series required a laparotomy; the first for an abdominal pregnancy, one for severe cholelithiasis not resolved with medical management, and the third for a repeat, elective cesarean section. The latter patient developed a recurrence in the puerperium before cholecystectomy was
288
Corlett
and
Mishell
performed. The results of this series indicate that laparotomy is only indicated when the diagnosis is not definite or an etiologic factor can be rectified by an operative procedure. During this time period one pregnant patient was treated for pancreatitis for several days before the true diagnosis of small bowel obstruction was established. Her declining physical state, fever, leukocytosis, and x-ray picture of small bowel ischemia led to a laparotomy and excision of a large segment of infarcted small intestine. The pathognomonic finding of an elevated serum amylase and/or urine diastase makes the diagnosis relatively easy to establish; however it must be realized that there are other causes of hyperamylasemia. Small bowel obstruction, perforated duodenal ulcer, mesenteric vascular occlusion, acute cholecystitis, ruptured aortic aneurysm, advanced renal insufficiency as well as mumps may all produce a hyperamylasemia. Since analgesics themselves may cause a rise in serum amylase levels, the blood for this determination should be obtained prior to analgesic administration. It must be remembered that in acute pancreatitis there is a peak in amylase levels 6 to 12 hours after the onset of symptoms. This serum enzyme then returns to normal within 24 to 72 hoursl’ The diastase values, on the other hand, remain elevated for 7 to 10 days. There are numerous other laboratory parameters that are altered, but all are of secondary diagnostic importance. Serum lipase values may become elevated in 12 to 24 hours, but performance of the lipase test requires 16 to 24 hours’? and is thus not clinically useful. About 50 per cent of all patients with acute pancreatitis? have hypoglycemia. Hypocalcemia is an important indicator of a poor prognosis, although it must be remembered that the serum calcium normally is depressed in pregnancy.* In a previous report from this institution of a series of nonpregnant patients with pancreatitis, death resulted in all those whose serum calcium fell below 7.0 mg. per centI The white blood cell count generally cannot be considered as a useful diagnostic aid. In this series it was greater than 15,000 in
only 5 cases and greater than 10,000 in an additional 11. Disco, Miller, and Copeland reported a little more than one third of their 231 patients with pancreatitis had normal leukocyte counts and only 32 an elevation greater than 20,000. Fever is unusual in the absence of another complication, and only 3 patients in this series had a temperature above 100° F. Most people feel that there is a poor c.orrelation between the degree of enzyme elevation and the severity of the disease. In this series, however, there seemed to be a good correlation as all of those with severe disease had marked or moderate elevation of enzymes and of those with mild disease, none had marked increase in enzymes. Metheny, Roberts, and Stranahanl’ reported the incidence of proteinuria to be 100 per cent. Langmade and Edmundsot? did not find that every patient had proteinuria, and their findings are in agreement with those reported in this survey. Blood electrdytes are usually deranged in proportion to the severity of vomiting. In the presence of primary biliary tract disease liver function tests are usually abnormal. A nonspecific ileus is the most common abdominal roentgenographic finding. Various types of x-ray abnormalities are reported to occur with an incidence varying from 45 per cent” to 100 per cent2 Authoritative texts frequently mention the presence of a sentinel loop of small bowel, but it was seen infrequently in this series. A left pleural effusion occurs in about 20 per cent of cases with acute pancreatitis according to Zollinger.g Treatment for pancreatitis in pregnancy is no different than in the nonpregnant state. The main objectives of therapy are aimed at diminishing pancreatic activity. Continuous nasogastric suction with or without antacids administered through the nasogastric tube contribute the most to diminishing the production of pancreatic juice which may reach as high as 2,700 ml. per day-l5 If gastric contents are drained by a nasogastric tube, this may be reduced to 5 to 10 ml. per day. This is accomplished by ( 1) preventing gastric distention; (2) averting the secretion-
Volume Number
113 3
Pancreatitis
stimulation effect of acid contents on the duodenum; and (3) avoiding pancreozymin stimulation by peptones and other digestive products. Vagal stimulation is reduced by administering therapeutic doses of anticholinergics which may result in moderately severe dryness of the mouth and blurred vision. Our choice is usually propantheline 15 to 30 mg. every 6 to 8 hours. The use of anticholinergics has not been shown conclusively to diminish pancreatic secretion and according to Goodman and Gilman16 “atropine has little effect on the secretion of pancreatic juice bile or succus entericus . . . processes largely under hormonal rather than vagal control. However, most gastroenterologists writing on the subject17-1” do recommend its use, and IngelfingerzO in his discussion on the use of anticholinergics in gastrointestinal disorders states that “a bout of pancreatitis is possibly the only gastrointestinal condition in which general agreement exists about the value of using anticholinergics.” Analgesics, intravenous fluids, and antiemetics are also administered in the management of the disease. Meperidine is the analgesic of choice, since morphine is known to increase the resistance of the sphincter of Oddil” to a greater degree than meperidine, and this may worsen the disease process. Langmade has stated, with good reasoning, that since blood glucose levels directly influence pancreatic enzyme secretion?* normal saline should be given during the acute phase of the disease and when the acute phase is subsiding a solution of 2.5 per cent dextrose in normal saline should be given instead of hypertonic or isotonic glucose solution. Since dextran has been shown to decrease pancreatic secretion, its intravenous use might be considered.z2 In severe cases of pancreatitis (usually the acute necrotizing or hemorrhagic type) colloidal rather than crystalloid solutions may be necessary to adequately replace the intra-
REFERENCES
1.
B. E.,
OBSTET.
GYNECOL.
and
Diddle, 105: 206,
A. W.: 1969.
AM.
289
vascular volume. The “third-spacing” occurring in this disease is similar to thermal injuries and may require large amounts of plasma, albumin, or whole blood. Monitoring of the central venous pressure may be necessary in cases such as these. The role of antibiotics in therapy is still controversial and is not settled. Disco, Miller, and Copeland state they may have some effect in preventing the late septic complications of acute pancreatitis and Langmade used penicillin in the acute phase in several patients, as he believed this would prevent the strong possibility of secondary bacterial invasion following the initial chemical insult. Antibiotics were not used routinely in this series and, in fact, only 4 patients all with severe pancreatitis received antibiotics. The predilection for recurrences in this disease has been well documented. In Langmade and Edmundson’s series 73 per cent had a recurrence in the puerperium. Walker and Diddle1 state that nearly 50 per cent of all patients with pancreatitis have recurrences. The recurrence rate of 52 per cent in this series agrees with their finding. The complication rate in this series was low in comparison to that of other reports. In Lukash’s5 series of 100 nonpregnant patients there was a 38 per cent complication rate including a 10 per cent incidence of obstructive jaundice. Walker and Diddle,* in a group of nonpregnant patients, report a 25 per cent incidence of jaundice with a 10 per cent rate of ultimate pseudocyst development and a 13 per cent rate of diabetic coma. They theorize that complications result secondary to either (1) local inflammation and the necrotic effects of pancreatic enzymes on peripancreatic tissues or (2) a remote effect of circulating enzyme. Most complications occur in patients with the hemorrhagic type of pancreatitis. A major factor contributing to the low incidence of complications in this series was the low incidence of this severe form of the disease.
2.
Walker,
in pregnancy
J. 3.
Langmade, C. F., and Edmundson, Gynecol. Obstet. 92: 43, 1956. Lukash, W. A.: GP 40: 103, 1969.
H.:
Surg.
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6.
7.
8. 9. 10. 11. 12. 13. 14.
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Mishell
Disco, J., Miller, L., and Copeland, E. M.: Surp. Gvnecol. Obstet. 129: 265. 1969. Von Ellen, E.: Obstet. Gynecol. Surv. 14: 845, 1959. Guttmacher, A. F., and Rovinsky, J. J.: Medical, Surgical and Gynecological Complications of Pregnancy, Baltimore, 1960, The Williams & Wilkins Company. Weiner, S., Gramatica, L., Voegle, L., Hauman, R., and Anderson, M.: Am. J. Surg. 119: 55, 1970. Cornish, A., McClellan, J, J., and Johnson, D. H.: N. Engl. J. Med. 265: 673, 1961. Zollinger, R. M.: Postgrad. Med. 49: 91, 1971. Rabkin, R.: Obstet. Gynecol. 31: 508, 1968. Fogerson, V., and Shedd, D. P.: Surg. Gynecol. Obstet. 101: 578, 1955. Hayes, T. A.: Postgrad. Med. 44: 39, 1968. Edmundson, H. A., and Berne, C.: Surg. Gvnecol. Obstet. 79: 240. 1944. Mktheny, D., Roberts, E.‘Q., and Stranahan, A.: Surg. Gynecol. Obstet. 79: 504, 1944. u
5.
and
15.
I
16.
17. 18.
19.
20. 21.
22.
Texter, E. C., Chou, C., Laurette, H. C., and Van Trappen, G. R.: Physiology of the Gastrointestinal Tract, St. Louis, 1968, The C. V. Mosby Company. Goodman, L. S., and Gilman, A.: The Pharmacological Basis of Therapeutics, New York, 1970, The Macmillan Company. Conn, H. F.: Current Therapy, Philadelphia, 1968, W. B. Saunders Company. Harrison, T. R.: Principles of Internal Medicine, New York, 1962, McGraw-Hill Book Co., Inc. Bockus, H. L.: Gastroenterology, Philadelphia, 1965, W. B. Saunders Company., vol. III. Ingelfinger, F. J.: N. Engl. J. Med. 268: 1454, 1963. Rabkin, B. P.: Secretory Mechanism of the Digestive Glands, New York, 1944, Paul B. Hoeber, Inc. Nardi, G. L.: N. Engl. J. Med. 268: 1065, 1963.