Perforated peptic ulcer disease in children: Association of corticosteroid therapy

Perforated Peptic Ulcer Disease Association of Corticosteroid ByStephen

W. Bickler, Marvin W. Harrison, and John R. Campbell Portland, Oregon

0 Four children were treated at the Oregon Health Sciences University for perforated peptic ulcer disease over the last 15 years. All children were being treated for other severe underlying diseases at the time of perforation. All of the children were receiving corticosteroids; one was receiving ulcer prophylaxis. Presenting symptoms were those of a perforated viscus, and pneumoperitoneum was present in all patients. Simple closure and omental patching of the ulcer resulted in no operative mortality or morbidity. None of the ulcers have recurred. In reviewing the literature, corticosteroids were associated with perforated peptic ulcer disease in 17.8% of children with perforated peptic ulcer. Despite controversy regarding the role of corticosteroids in the causation of peptic ulcer, we recommend prophylaxis for all children receiving corticosteroids. Copyright o 1993 by W.B. Saunders Company INDEX WORDS:

Peptic ulcer disease, corticosteroids

effect.

A

LTHOUGH the precise etiology of perforated peptic ulcer disease remains to be defined, several factors including stress,’ severe underlying disease,* salicylates,3 nonsteroidalantiinflammatory drugs (NSAIDS),~ and corticosteroids5 have been implicated. The association of corticosteroids and peptic ulceration remains controversial.6 Our clinical impression, however, is that corticosteroids are associated with perforated peptic ulcer disease. The common practice among pediatricians and oncologists at this institution is that ulcer prophylaxis is not necessary with corticosteroid therapy. The pediatric surgery literature, however, favors ulcer prophyIaxis.7 We present four cases of perforated peptic ulcer treated at the Oregon Health Sciences University over the last 15 years. CASE

in Children: Therapy

REPORTS

Case 1 A 13-month-old girl (weighing 8.95 kg) undergoing treatment for acute lymphocytic leukemia was admitted for treatment of a thumb abscess. On hospital day 7, the patient developed lethargy, hypotension, and oliguria. Physical examination showed a distended abdomen without guarding or rigidity. Rectal examination showed guaiac-positive stool. Laboratory studies were remarkable for a white blood cell count of 1.8 x 103/mm3. An abdominal radiograph demonstrated pneumoperitoneum. Medications at the time of perforation included prednisone (5 mg bid), vincristine, and L-asparagine amidohydrolase. Exploratory celiotomy showed a sharply demarcated perforated ulcer along the greater curvature of the stomach near the antrum. Simple closure of the ulcer and omental patching were performed. Chemotherapy including corticosteroids was continued and antacids were used postoperatively. Journaloff’ed~afric Surgery, Vol 28, No 6 (June), 1993: pp 785-787

The postoperative course was uncomplicated and there has been no evidence of recurrence at 7 years’ follow-up. Case

2

An S-year-old boy (weighing 22 kg) presented with increasing abdominal girth. Exploratory celiotomy showed Burkett’s lymphoma with diffuse involvement of the liver, peritoneum, and small bowel. Seventeen days following celiotomy and resection of the obstructed segment of ileum and 14 days after beginning chemotherapy (cytoxin and vincristine), he developed abdominal pain. Physical examination showed tachycardia and abdominal distension. An abdominal radiograph demonstrated pneumoperitoneum. The white blood cell count was 1.7 x 10s/mm3. Celiotomy showed a 2-mm perforated ulcer of the lesser curvature in the proximal duodenum. At time of perforation he was receiving prednisolone (50 mg IV daily). Simple closure and omental patching were used to close the ulcer. He was treated with ranitidine hydrochloride. The postoperative course was uncomplicated, and at l-year follow-up there is no evidence of ulcer recurrence. Case

3

A female infant was delivered by cesarean section at 27 weeks gestation following premature rupture of membranes. The clinical course was remarkable for respiratory distress syndrome, patent ductus arteriosis, and staphlococcal and candida sepsis. At age 10 weeks, while on decadron (1.6 mg PO daily) for bronchopulmonary dysplasia, surgical consultation was obtained for suspected necrotizing enterocolitis. Physical examination showed an ill-appearing infant weighing 1.61 kg with a distended abdomen, tachycardia, tachypnea, and a guaiac-positive stool. The white blood cell count was 6.8 x 10”/mm3. Pneumoperitoneum was seen on an abdominal radiograph. Exploratory celiotomy showed a perforated proximal duodenal ulcer. Simple closure and placement of an omental patch were performed. Postoperatively, she was treated with ranitidine hydrochloride, and the corticosteroids were discontinued. The postoperative course was uncomplicated, and there has heen no recurrence of ulcer disease at 7 years’ follow-up. Case 4 A .7-year-old boy (weighing 15.4 kg) ingested an alkaline commercial dairy equipment cleaner. Esophagoscopy confirmed severe esophageal injury and he was treated with broad-spectrum antibiotics, corticosteroids (decadron, 2 mg IV every 6 hours), and ranitidine hydrochloride. He was discharged home on the 7th day feeling well and eating enthusiastically. He returned on the 8th day

From the Division of Pediatnc Surgery, Department of Surgery, School of Medicine, Oregon Health Sciences University, Portland, OR. Presented at the 25th Annual Meeting of the Pacific Association of Pediatric Surgeons, Albuquerque, New Mexico, May 17-21, 1992. Address reprint requests to Marvin W Harrison, MO, Division of Pediatric Surgery, L223, Oregon Health Sciences Universify, 3181 SW Sam Jackson Park Rd, Portland, OR 97201. Copyright Q I993 by W.E. Saunders Campany 0022-3468/9312806-0007$03.00/O 785

BICKLER,

postinjury complaining of abdominal pain and respiratory distress. Abdominal examination showed distention and diffuse tenderness. The white blood cell count was 27.7 x 103/mm3. Pneumoperitoneum was noted on an abdominal roentgenogram. After fluid resuscitation, exploratory celiotomy showed a 15cm perforation on the posterior wall of the midbody of the stomach. The ulcer was debrided and closed in layers. Postoperatively, the corticosteroids were discontinued and he was treated with ranitidine hydrochloride, sucralfate, and antacid. His recovery was complete. Subsequent esophageal substitution has been performed. There has been no recurrence of peptic ulcer disease at 2 years’ follow-up. DISCUSSION

Perforation is an uncommon complication of peptic ulcer disease in children. We describe four cases of perforated peptic ulcer treated at the Oregon Health Sciences University over the last 15 years. The perforations in these four patients were all associated with other severe diseases. All were being treated with corticosteroids at the time of perforation. Two children were receiving corticosteroids as part of chemotherapy regimens for malignancy, a third was receiving corticosteroids for bronchopulmonary dysplasia, and the fourth was being treated with corticosteroids for caustic esophageal injury. None was receiving concommittant NSAJD therapy. One of the patients was receiving ulcer prophylaxis at the time of perforation. Presenting symptoms were those of a perforated viscus. Pneumooeritoneum was present in all cases. The surgical management was successful in all instances and consisted of simple closure and omental patching of the ulcer in three patients and two-layer closure in one. There was no mortality or morbidity, and there has been no recurrence of the ulcer disease. The relationship of perforated peptic ulcer disease to ulcerogenic drugs deserves further discussion, as it bears directly on the need for ulcer prophylaxis in children taking corticosteroids. In reviewing the literature, we found 90 cases of perforated peptic ulcer disease in which a determination of corticosteroid use could be made (Table I).‘-‘” Sixteen (17.8%) were Table 1. Association of Corticosteroid

Use and Perforated Peptic

Ulcer Disease in Children

investigators Adeyemi et aI7 Bell et al* Morden Johnson Kumar

et aI9 et allo et all1

Deckelbaum Present Total

series

et alI2

No. of Patients

No. of Patients Receiving Corticosteroids (“A)

Those With Severe Underlying Disease (“/.)

4

2 (50%)

75%

61

4 (6.6%)

80%

2

1 (50%)

100%

2

1 (50%)

100%

9

1 (11%)

80%

8

3 (37.5%)

100%

4

4 (100%)

100%

so

16 (17.8%)

HARRISON,

AND

CAMPBELL

receiving corticosteroids at the time of perforation. In the largest series, Bell et al8 reviewed 26 citations in the English language literature of children with duodenal perforation in the first year of life. Only four were being treated with corticosteroids. In all series, a high percentage of patients had a significant serious underlying illness. A 17.8% incidence of corticosteroid usage in children is similar to the corticosteroid usage rate in adults with perforated peptic ulcer disease. In a retrospective review of 151 patients, Dayton et al l3 found that 17% of patients with perforated peptic ulcerations were associated with corticosteroid use. Six of 8% patients described by Gunshefski et all4 with perforated peptic ulcer disease were receiving corticosteroids alone. Of interest is that five of the six patients with perforation in their series were receiving either antacids or histamine HZ-receptor antagonists (HZ blockers) at the time of perforation. These data suggest that most patients develop stress induced ulcers while not taking corticosteroids, and that prophylaxis with antacid or Hz blockers is not effective. The pathogenesis of stress-induced gastrointestinal ulceration remains controversial. Mucosal ischemia, defects in acid secretion, or failure of the mucosal barrier may each play an important role.’ The effects of corticosteroids on cytoprotective prostaglandins, gastric mucous secretion, gastric acidity, platelet activating factor, and leukotrienes are summarized in a recent review article by Guslandi and Tittobello.” Clinical studies have been unable to show a clearcut relationship between corticosteroids and peptic ulceration. In a pooled analysis in 1976, Conn and Blitzer15 reviewed 26 placebo-controlled double-blind studies of corticosteroid therapy. There was no association between corticosteroid use and ulcers (relative risk, 1.4; 95% confidence interval, 0.7 to 2.6). In 1983, Messner et a1,5 using metaanalysis on 71 controlled randomized trials, detected a twofold increase in the risk of peptic ulcer disease during treatment with systemic corticosteroids or adrenocorticotropic hormones. Both of these studies have recently been criticized because they were not prospective, and variable criteria for diagnosing ulcer disease were used.6 A recent large case control study in the United States confirmed that patients taking corticosteroids had twice the chance of developing ulcer disease, but also showed that the risk was confined to patients concurrently taking NSAID (relative risk, 4.4; 95% confidence level, 2.0 to 9.7).lh Patients taking corticosteroids alone had an incidence of peptic ulceration similar to the control population.

787

PERFORATED PEPTIC ULCER IN CHILDREN

Whether antacids or Hz blockers are effective prophylaxis against peptic ulceration in patients receiving corticosteroids is currently unknown. The use of antacids and Hz blockers is effective in preventing stress ulceration in patients with central nervous system disorders. I7 In patients with burns, continuous feeding with an elemental diet has been recommended because it is thought that this will reduce gastric acidity and the incidence of Curling’s ulcer.‘* We conclude that: (1) children with severe disease,

and probably those receiving corticosteroids, are at risk for perforated peptic ulcer; (2) early recognition and prompt surgical intervention are key elements in successful management; (3) simple closure and omental patching of perforated ulcer is the procedure of choice and results in low morbidity and mortality and acceptable long-term outcome; and (4) children receiving corticosteroids and those at high risk for peptic ulcer disease should receive prophylaxis with either antacids or H2 blockers.

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RE, et al: Changing Am Surg 56:270-274,

15. Conn HO, Blitzer BL: Nonassociation of adrenocorticosteroid therapy and peptic ulcer. N Engl J Med 294:473-478. 1976 16. Piper JM, Ray WA. Daugherty JR. et al: Corticosteroid use and peptic ulcer disease: Role of nonsteroidal anti-inflammatory drugs. Ann Intern Med 114:735-740. 1991 17. Halloran LG, Zfass A, Gayle WE, et al: Prevention of acute gastroentestinal complications after severe head injury: A controlled trial of cimetidine prophylaxis. Am J Surg 13944-48, 1980 IX. Solem LD, Strate RG, Fischer RB: Antacid therapy and nutritional supplementation in the prevention of Curling’s ulcer. Surg Gynecol Obstet 148:367-370. 1979