Stress Ulcer in Infants and Children by alicejenny


									                    Stress Ulcer in Infants and Children*
                  ARTHUR I. CHENOWETH, M.D., ALAN R. DIMICK, M.D.
                   From the Children's Hospital and the Department of Surgery,
                      the Medical College of Alabama, Birmingham, Alabama

   THE FREQUENCY of stress ulcer in infants           The classic example of acute ulceration
and children makes it a subject of at least        of the stomach or duodenum occurring in
potential interest to anyone who treats the        the presence of other disease is the ulcer
sick or injured child. The literature dealing      associated with burns. The Curling ulcer
with stress ulcers is abundant and the re-         has been recognized as an entity since 1842.
ported incidence varies widely. Moncrief           Gastroduodenal ulceration has also been
and associates 15 reported their experience        associated with fractures and amputations,8
with gastroduodenal ulceration as a com-           cardiac surgery,' other operative proce-
plication occurring on the Burn Service at         dures 6, 12 and acute or chronic illnesses.2, 13
Brooke Army Medical Center; while the              17, 20 Cushing 4 described the association of
incidence in burns had been reported as            peptic ulcer with lesions of the mid-brain
4.35 per cent, the overall incidence at their      in 1932 and established the relationship be-
center from 1954 to 1962 was 11.65 per             tween disease of the central nervous system
cent as established by clinical or autopsy         and ulceration of the upper gastro-intestinal
evidence of ulcer. In 1962, when the sur-          tract.
gical pathologist directed attention to the                         Pathogenesis
subject, the incidence was 21.3 per cent.
   Occurrence of stress ulcers in the early            The pathogenesis of stress ulcer has been
years of life has been considered as rare,         reviewed by Friesen 7 and by Kiesewetter.1"
although many case reports of acute ulcer,         Stress causes a chain reaction involving the
gastromalacia or spontaneous perforation of        hypothalmus, anterior pituitary and the
the stomach have appeared; these lesions           adrenal cortex; the vagus nerve may be
probably occur with the same frequency in          stimulated directly or a humoral substance
the first two decades as in adult life. A          also may be involved.
series of 943 consecutive autopsies per-               Several different mechanisms probably
formed at a general hospital in Cleveland          cause this lesion in the upper gastro-intes-
was reviewed by Woldman.20 The incidence           tinal tract. Hypersecretion of acid is not
in patients under and over 21 years of age         considered as the major factor,5 yet the
was 13.5 and 14.4 per cent, respectively,          presence of acid and pepsin probably is
and the incidence in the neonatal period           necessary for the development of ulcera-
was almost equal to that in the second dec-        tion.18 According to Menguy and Masters,14
ade of life. Until recently the so-called          increased acid secretion does not cause
 spontaneous perforations of the gastro-in-         significant change by itself. By the adminis-
testinal tract in early infancy has not been       tration of cortisone to animals, they demon-
recognized as a manifestation of the stress        strated a marked reduction in the rate of
effect.                                            mucous secretion, alteration in the viscosity
      Presented before the Southern Surgical As-   and chemical properties of the mucous and
sociation, Dec. 8-10, 1964, Boca Raton, Fla.       a loss of its protective function-confirming
978                              CHENOWETH      AND DIMICK                       Annals of Surgery
                                                                                        June 1965
similar findings by Hirschowitz and associ-      sometimes very large and have been called
ates.9 There may also be an alteration in        "gastromalacia." These neonatal lesions
the local circulation to the wall of the         must now be considered as stress ulcers;
viscus, although the relationship to hemo-       many are associated with intracranial hem-
concentration, embolism, sludging or vas-        orrhage, asphyxia or other causes of hy-
cular spasm has not yet been established.        poxia.
   Smith and Howes 18 state, "curiously, in        Woldman 20 and others have recognized
discussing ulcerogenesis today, only the         mucosal hemorrhages and hemorrhagic ero-
capacity of histamine to cause a secretion       sions in addition to frank ulcers as mani-
of acid seems to be remembered" and that         festations of the stress effect. Two or three
since ulcers in general result from local        of these variants may be identified in the
ischemia, peptic ulcer may not be an ex-         same patient at autopsy (Case 9). If these
ception. Histamine, as a powerful contract-      lesions do not lead to a serious complica-
ant of smooth muscle, is able to cause par-      tion, they are likely to heal completely and
tial occlusion of the endarteries in the wall    not be demonstrated clinically or at au-
of the stomach or duodenum. Brodie and           topsy (Case 2). Clinical recognition is often
Moreno,3 studying Polymyxin-induced ul-          not possible before a complication-either
cers in white rats, conclude that ulcers are     bleeding or perforation-takes place. Prod-
due to vascular changes in the wall of the       romal symptoms are rare. Bleeding is said
stomach reflecting the cardiovascular ac-        to occur twice as often as perforation; it
tion of released histamine. They also            varies in degree and is often massive at the
found 16 that an antihistamine prevented         outset. In our experience, perforation al-
mucosal ulcerations and ulcers after ad-         ways has been preceded by bleeding. The
ministration of Polymyxin-B in animals,          stress ulcer causes rapid and complete dis-
whereas an anticholinergic drug did not.         solution of the full thickness of the viscus
The possible role of histamine in the pro-       and erosion of the wall of an artery.
duction of stress ulcers merits further eval-
uation.                                                          Management
       Definition and Characteristics               Until recently there has been little in-
                                                 formation concerning the management of
   Fletcher and Harkins 6 described stress       stress ulcer in children. Prophylactic use of
ulcers as "shallow ulcers, often multiple,       antacids and antispasmodics in patients
without surrounding induration, which do         with burns 10 and "in conditions prone to
not show microscopic evidence of chronic         be associated with stress" 2 has been sug-
inflammation." However, this ulcer fre-          gested. Invariably the presence of a tarry
quently involves the entire thickness of the     stool or a drop in hematocrit has evoked
wall of the affected viscus and perforates       these measures-often supplemented by
into the peritoneal cavity or a neighboring      blood replacement in large amounts and
viscus (most often the pancreas). Stress         pursued until the patient's death. Many
ulcers may be single or multiple and vary        other patients have developed massive gas-
in size from punctate to very large-one
gastric ulcer reported by Breckenridge et
                                                 tro-intestinal hemorrhage while on this
al.2 being 15 cm. in diameter. The lesions       regimen.
may involve the esophagus, stomach or              Three reports from the Brooke Army
duodenum. Esophageal lesions, though not         Medical Center describe the management
common, often occur in the neonatal pe-          of these patients. In 1953 19 five cases of
riod, during which "spontaneous perfora-         acute ulcer which came to autopsy were
tions" of the stomach also occur. These are      reported; none of the patients were op-
Volume 161                   STRESS ULCER IN INFANTS AND CHILDREN
Number 6                                                                                                         979
erated    upon   but the author        suggests    "an          TABLE 1. Sutrvival Rate After IIemorrhage Wt'ith
emergency    operation may be indicated                                    and Without Perforation
when a massive gastro-intestinal hemor-                                                       No. of Patients/
rhage occurs after burns." In 1957 two pa-                                                     No. Survivals
tients with massive hemorrhage were sub-
jected to gastrectomy; 10 both died and all                                     N o.        Hemor-         and
suture lines, both visceral and parietal,                 Injury            Patients         rhage    Perforations*
failed   heal. As a result the desirability of
conservative measures and the avoidance of                Burn                   4            2/0          2/1
                                                          CNS                    5            3/1          2/2
surgical intervention was emphasized. In
1964, however, Moncrief and associates 15                 Total                  9            5/1          4/3
reported nine instances of surgical interven-               *
                                                                All operated.
tion and stated, "when it is accomplished
with dispatch and before irreversible blood
loss has occurred the individual can with-                pital for removal of a depressed skull fracture and
stand the operative procedure, heal the                   evacuation of an acute subdural hematoma. On the
suture line and abdominal wall, and es-
                                                          second postoperative day the patient vomited
                                                          coffee-ground material and the hematocrit de-
tablish oral alimentation without undue                   creased sharply. Supportive treatment was insti-
difficulty."                                              tuted and there was no evidence of further gas-
                                                          tro-intestinal bleeding. His course, however, was
               Case Reports                               gradually downhill and he expired on the eighth
   Nine cases of stress ulcer were encoun-                day after admission. No gross evidence of ulcera-
                                                          tion of the stomach or duodenum was detected at
tered at the University Hospital of the                   autopsy.
Medical College of Alabama, the Birming-
ham Children's Hospital and the Lloyd                         Case 3. A 17-year-old boy was admitted to
                                                          University Hospital after sustaining a severe head
Noland Hospital in Birmingham (Table 1).                  injury in an automobile-motorcycle collision. Be-
Information concerning the first five pa-                 cause of his critical condition, tracheostomy was
tients was derived entirely from the hos-                 performed and hypothermia induced by means
                                                          of an ice mattress. The course progressively de-
pital records.                                            teriorated. On the fifth day after admission bright
     Case 1. A 21-year-old girl was admitted to           red blood was aspirated from the stomach and
University Hospital directly after sustaining hot         the hematocrit decreased sharply. He expired on
water burns of the right arm, right and left leg          the tenth hospital day. There had been no further
and neck; the total burn area was about 15 to 20          evidence of gastro-intestinal bleeding. Permission
per cent of the body surface, chiefly second de-          for autopsy was denied.
gree. On the fourth post-bum day she developed
evidence of gross sepsis; cultures of the wounds              Case 4. A 7-year-old was admitted to Uni-
yielded Staphylococcus aureus and Pseudomonas             versity Hospital after being struck by an auto-
aeruginosa. On the tenth post-burn day the patient        mobile. He sustained a severe intracranial injury
vomited a small amount of dark blood, followed            manifest by classical decerebrate response. Treat-
by a sharp decrease in hematocrit. There was              ment consisted of tracheostomy, blood transfusions
marked abdominal distention without significant           and hypothermia. Artificial respiration was neces-
tendemess. Despite supportive measures the pa-            sary for a short time. Despite the severity of the
tient died on the twelfth post-bum day. Post-             injuries, he gradually improved. On the third day
mortem examination disclosed sevcral small super-         after admission considerable coffee-ground mate-
ficial gastric ulcers as well as infarcts of both lungs   rial was aspirated from the indwelling stomach
and edema of the brain of moderate degree.                tube, followed by sharp reduction in hematocrit.
                                                          On conservative management, including supportive
    Case 2. A 15-year-old boy involved in a motor-        blood transfusions, gastro-intestinal bleeding ceased
cycle-automobile accident sustained extensive frac-       but recurred on several occasions. After several
tures of the skull with severe intracranial injury.       weeks he was discharged as improved although
Craniectomy was carried out at University Hos-            there was some residual neurologic deficit.
 980                                  CHENOWETH AND DIMICK                                   Annals of Surgery
                                                                                                    June 1965
     Case 5. A 3-year-old girl was admitted to          operative correction of this condition he has re-
the Lloyd Noland Hospital 2 hours after sustain-        mained well.
ing a flame bum covering 55 per cent of body
surface. Her condition became stabilized after the          Case 8. A 14-month-old girl was admitted to
first few hospital days and grafts were applied to      Children's Hospital 5 hours after a hot water burn
portions of the burned area. On the 21st post..burn     of the left side of the face, neck, left arm and
day she developed melena and during the next            anterior chest involving about 15 per cent of body
few days hemoglobin decreased to 8.9 Gm./100            area, chiefly second degree with several areas of
ml. despite supportive blood transfusions. Inten-       third degree bums. Temperature was 39.4° C. on
sive supportive therapy was continued but she           admission. The bumed areas were cleaned and
expired on the 30th post-burn day. Autopsy dis-         dressed under anesthesia. The day following ad-
closed an ulcer in the first portion of the duo-        mission the infant had a generalized convulsion,
denum on the posterior wall, 2 cm. in diameter, at      the cause of which was never established, after
the base of which was an artery with an opening         which intravenous fluids were administered. The
about 2 mm. in diameter.                                evening of the second day after admission coffee-
                                                        ground material was vomited. A nasogastric tube
    Case 6. (University Hospital) A 2-year-old boy     recovered a small amount of bright red blood.
was subjected to suboccipital craniectomy for re-       Examination of the abdomen disclosed findings
moval of a very large tumor within the fourth           typical of generalized peritonitis and x-ray studies
ventricle. Total operative time was 7 to 8 hours.      revealed air under both leaves of the diaphragm.
On the third postoperative day the infant passed       Laparotomy was carried out immediately under
a tarry stool and packed cell volume decreased          general anesthesia. A small ulcer on the posterior
from 42 to 24. Several additional tarry stools were    aspect of the duodenum, adjacent to the head of
passed on this day. The following day the child        the pancreas, had perforated, and there was fluid
became fretful and presented a board-like ab-          in the lesser peritoneal sac and general peritoneal
domen. X-ray studies indicated air beneath the         cavity. The ulcer was plicated with only moderate
diaphragm. Laparotomy was immediately carried          difficulty. Her postoperative course was marked by
out and a single ulcer, approximately 5 X 7 mm.        oliguria due to preoperative fluid deficit and by
in size, was found on the antero-inferior surface      intermittent moderate bleeding from the upper
of the pylorus. There was no induration in the         gastro-intestinal tract as detected by the returns
wall of the viscus. The perforation was plicated       from nasogastric suction. This ceased spontane-
with 4-0 silk. Subsequently there was recurrent        ously within a few days, during which time
gastro-intestinal bleeding. Nasogastric suction was    atropine was given parenterally. She was dis-
maintained, blood replacement was induced and          charged after the burned areas had healed and
anticholinergic medication given. The patient was      is now well.
eventually discharged from the hospital as well.         The last case illustrates several pertinent
    Case 7.** A 2-month-old boy was admitted to        aspects of treatment.
Children's Hospital because of repeated convul-             Case 9. A 3-year-old girl was admitted to
sions on his right side. On the second hospital day    Children's Hospital immediately after deep second
the infant vomited coffee-ground material. The         or third degree flame bum which involved about
following day he vomited bright red blood and          50 per cent of body area including the anterior
hematocrit level decreased. He also developed          surface of the abdomen. Supportive therapy con-
signs of an acute abdomen despite no evidence of       sisted chiefly of lactated Ringer's solution, guided
free air by x-ray studies. Laparotomy disclosed a      in part by the presence of a central venous line by
perforated ulcer on the posterior wall of the duo-     way of the external jugular vein. During the first
denum draining into the lesser peritoneal sac. The     three days her course was considered as satisfac-
ulcer was plicated and right lumbar gutter drained.    tory. On the morning of the fourth day after ad-
His postoperative course was stormy but there was      mission she passed a large tarry stool and the
no evidence of further bleeding. Subdural hema-        packed cell volume was 17. Blood was replaced
toma was treated by repeated subdural taps. The        in large quantities during continued bleeding for
patient recovered and was discharged from the          the next 48 hours. She was on a regimen of milk
hospital. He was readmitted a few days later with      and antacids by mouth and atropine intramuscu-
acute intestinal obstruction due to adhesions. After   larly. On the sixth post-burn day, as bright red
                                                       blood was recovered by the Levine tube, immedi-
    * Reported by courtesy of Dr. John M.              ate operation was considered mandatory. The pa-
Slaughter.                                             tient had become pallid to the point of trans-
     "* Reported by courtesy of Dr. Marshall Pitts.    parency, central venous pressure had fallen to zero
Number 6                                                                                        981
 and blood was pouring around the Levine tube.        pine; hematocrit should be determined
Attempts to replace blood by manual pumping           at frequent intervals and large quantities
were fruitless. However a faint carotid pulsation
was detectable and there was shallow but spon-
                                                      of blood made available. The abdomen
taneous respiration. The abdomen was opened           should be examined frequently for possible
without anesthesia through an upper midline in-       perforation of the upper gastro-intestinal
cision (through areas of third degree bum), there     tract. A central venous line should be ready
being no bleeding from the wound edges. The           in case large volumes of fluids are neces-
stomach was markedly distended with blood and
was quickly opened by a longitudinal incision in
                                                      sary. Hematocrit should be maintained
the antrum extending beyond the pylorus. A very       above 36. These supportive measures may
large artery, presumably the pancreaticoduodenal,     eliminate bleeding, although hemorrhage
was bleeding profusely in the base of an ulcer        may recur.
crater, 1>2x 1 cm., in the posterior wall of the         Operative intervention is undertaken
first portion of the duodenum. The ulcer had
perforated the entire thickness of the duodenal       when: 1) there is evidence of perforation
wall and communicated freely with the peritoneal      of the gastro-intestinal tract, a condition
cavity, as detected by the presence of milk in the    which may be masked by hemorrhage (as
upper abdomen. The bleeding was temporarily           in our Case 9) or 2) bright red blood is
controlled by digital pressure as more blood was      recovered via nasogastric suction over a
pumped manually into the circulation by way of
the central venous line. After a short time three     period of several hours; however, the dura-
figures-of-eight silk sutures were placed in such a   tion and volume of bleeding prior to op-
way as to control the bleeding completely. Within     eration cannot be quantitated. If bleeding
a short time, as blood was replaced by transfusion,   continues 48 hours and large-volume re-
the patient's color improved and the wound edges      placement is required or when bright red
began to bleed. Antrectomy and a Hofmeister
anastomosis were promptly carried out.                blood is passed by rectum, operation is
     At the conclusion of the operation the pa-       mandatory; recurrence of massive hemor-
tient's color was good, the pulse strong though       rhage is another indication. These ulcers
rapid and the central venous pressure was about       may perforate a viscus or erode a large
150. During the 3 hours of operation 190 cc. of       vessel quite rapidly.
urine was passed. By the third postoperative day
the patient's condition had stabilized. The Levine       Once elected, operation should be car-
tube was removed and she was allowed milk and         ried out with dispatch. Factors to be con-
cream by mouth which was well tolerated and           sidered in selecting the procedure are the
gradually increased.                                  condition of the patient at operation and
     On the fourth postoperative day Pseudomonas      the characteristics of stress ulcers, espe-
was recovered from the burned leg. She de-
veloped pseudomonas septicemia and died on the        cially their tendency to be multicentric. A
14th day after burn, the 8th day after operation.     second ulcer often requires reoperation; in
Autopsy revealed the anastomosis to be intact.        at least three of our cases there was re-
There were several small superficial erosions of      current bleeding after operation, although
the mucosa of the stomach.                            no patient in our series required a second

                  Discussion                          operation.
                                                         This is indeed a problem. Small patients,
  Awareness of the frequency with which               very ill, often uncooperative, often disori-
acute ulcer occurs in the sick or injured             ented, with abdomens sometimes encased
child, as well as the sudden and devastating          in massive dressings or in casts-all of
complications, may be more effective in               these factors make diagnosis difficult. Very
preventing serious consequences than the              ill patients, often recently in shock or still
routine administration of anticholinergic             in precarious balance, many with extensive
drugs and antacid. Tarry stools, coffee-              burns of the abdominal wall-all of these
ground emesis or abdominal distention are             factors press one to pursue conservative
indications for nasogastric suction and atro-         therapy. We believe, however, that it is
982                                  CHENOWETH AND DIMICK                                   Annals of Surgery
possible to save more of these young pa-                6. Fletcher, D. G. and H. N. Harkins: Acute
                                                             Peptic Ulcer as a Complication of Major
tients by being more alert to the diagnosis,                 Surgery, Stress or Trauma. Surgery, 36:212,
more aware of the catastrophic nature of                     1954.
                                                        7. Friesen, S. R.: The Genesis of Gastro-duo-
the complications and more aggressive in                     denal Ulcer Following Burns. Surgery, 28:
our willingness to undertake surgical inter-                 123, 1950.
                                                        8. Friesen, S. R., K. A. Morendino, I. D. Baronof-
vention.                                                     sky, F. B. Mears and 0. H. Wangensteen:
                  Summary                                    The Relationship of Bone Trauma to the
                                                             Development of Acute Gastro-duodenal Le-
   Occurrence of stress ulcer in infants and                 sions in Experimental Animals and in Man.
                                                             Surgery, 24:134, 1948.
children is not as rare as commonly be-                 9. Hirschowitz, B. I., H. P. Streeten, H. M.
lieved. Pathogenesis and management of                       Pollard and H. A. Boldt, Jr.: Role of Gastric
                                                             Secretions in Activation of Peptic Ulcers by
this condition is reviewed.                                  Corticotropin. J.A.M.A., 158:27, 1955.
   Nine cases are reported. Tarry stools,              10. Hummel, R. P., G. F. Lanchantin and C. P.
                                                             Artz: Clinical Experiences and Studies in
vomiting of coffee-ground material or ab-                    Curling's Ulcer. J.A.M.A., 164:141, 1957.
dominal distention, followed by decrease               11. Kiesewetter, W. B.: Spontaneous Rupture of
                                                             the Stomach in the Newborn. J. Dis. Child.,
in hematocrit, were encountered in most                      91:162, 1956.
patients.                                              12. McDonnell, W. V. and J. F. McCloskey: Acute
                                                             Peptic Ulcers as Complications of Surgery.
   Recovery of bright red blood via naso-                    Ann. Surg., 137:67, 1953.
gastric suction or by rectum or recurrence             13. Mears, F. B.: Autopsy Survey of Peptic Ulcer
                                                             Associated with Other Diseases. Surgery, 34:
of hemorrhage are indications for operation.                 640, 1953.
   The survival rate was 1 of 5 patients               14. Menguy, R. and Y. F. Masters: Effect of
                                                             Cortisone on Mucoprotein Secretion by Gas-
with hemorrhages and 3 of 4 patients with                    tric Antrum of Dogs: Pathogenesis of Steroid
hemorrhage and perforation.                                  Ulcer. Surgery, 54:19, 1963.
                                                       15. Moncrief, J. A., W. E. Switzer and C. Teplitz:
                                                             Curling's Ulcer. J. Trauma, 4:481, 1964.
                   References                          16. Moreno, 0. M. and D. A. Brodie: Effects of
                                                             Drugs on Gastric Hemorrhages Produced by
 1. Berkowitz, D., B. M. Wagner and J. F.                    the Administration of Polymyxin-B. J. Pharm.
      Uricchio: Acute Peptic Ulceration After Car-           Exp. Therap., 135:259, 1962.
      diac Surgery. Ann. Intern. Med., 46:1015,        17. Schlumberger, H. G.: Coexistent Gastro-duo-
      1957.                                                  denal and Cerebral Lesions in Infancy and
 2. Breckenridge, I. M., E. W. Walton and W. F.              Childhood. Arch. Path., 52:43, 1951.
      Walker: Stress Ulcers in the Stomach. Brit.      18. Smith, G. V. and E. L. Howes: Absence
      Med. J., 2:1362, 1959.                                 of Histamine-Reserpine Ulcers in Pyloric
 3. Brodie, D. A., R. W. Marshall and 0. M.                  Pouches Free of Acid. Surgery, 55:262, 1964.
      Moreno: The Effect of Ulcerogenic Drugs          19. Weigel, A. E., C. P. Artz, Eric Reiss, J. H.
      on Gastric Acidity in the Rat with Chronic             Davis and W. H. Amspacher: Gastro-intesti-
      Fistula. Gastroenterology, 43:675, 1962.               nal Ulcerations Complicating Burns. Surgery,
 4. Cushing, H.: Peptic Ulcers and the Midbrain.             34:826, 1953.
      Surg. Gynec. & Obstet., 55:1, 1932.              20. Woldman, E. E.: Acute Ulcers of Upper Gas-
 5. Drye, J. C. and A. M. Schoen: Studies on the             tro-intestinal Tract: Their Relation to Sys-
      Activation of Peptic Ulcer After Non-Spe-              temic Stress and Adrenal Damage. J.A.M.A.,
      cific Trauma. Ann. Surg., 147:738, 1958.               149:984, 1952.

                    DISCUSSION                         the crater, although we do not see the bleeding
    DR. JOHN WEBB (New York City): The first           vessel. There was only one ulcer in this patient,
slide shows these stress ulcers have very little re-   and of course he could have been cured by proper
action about them, and although these are in           surgical treatment.
adults and not in children; I think the problem is          (Slide) This shows the nature on section of
the same. This is a postmortem specimen of a pa-       these ulcers. Again, this illustrates the minimal re-
tient whose diagnosis was missed, and the patient      action about these acute ulcers.
bled to death.                                              (Slide) This is simply to show, as has already
    (Slide) This is simply an enlarged photograph      been pointed out, so many of these patients have
of the same ulcer. Again one sees this minimal in-     multiple ulcers. I suspect, but do not know, that
flammation about the ulcer. We see the blood in        perhaps in the beginning these people have only

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