A Controlled Trial of Corticosteroids in Children with Corrosive Injury of the Esophagus

All patients with a history of caustic ingestion from 1971 through 1988 were admitted to the Surgical Service. Those known to have swallowed ammonia or household bleach (sodium hypochlorite) were excluded from the study, since these materials usually produce only superficial burns of the mucosa and have not been reported to cause strictures in children. In the remaining 131 children thought to have ingested lye or acid, the patient's age, the interval from ingestion to hospitalization, and the type and character of the caustic agent were recorded.

Rigid esophagoscopy was performed under general anesthesia in all 131 patients within 24 hours of the ingestion and usually within 12 hours. The mouth, oropharynx, larynx, and esophagus were evaluated, but the esophagoscope was passed into the esophagus only as far as the area of the first serious burn. Injury to the esophagus was classified as follows: first degree, injury limited to erythema and edema; second degree, injury involving ulcerations with necrotic tissue and white plaques that were less than circumferential; and third degree, injury involving ulcerations, white plaques, and sloughing of the mucosa in a circumferential pattern.²¹

The patients found to have esophageal burns were randomly assigned to receive steroids or no treatment on the basis of the last digit in the patient identification number, the patients with an even number receiving steroids and those with an odd number forming the control group. Since most of the patients were between one and three years of age, the two groups were not matched for age. The decision to use steroids or not was made before the evaluation of the injury, but no medications were actually given until it was determined that an injury had occurred. This made it likely that the number of patients in each group would not be the same. Parental consent to the study was obtained in each case, and the study was approved by the institutional review board. The investigators were not blinded to the assignments of the patients to groups.

The patients assigned to treatment with steroids received prednisolone (2 mg per kilogram of body weight per day) intravenously, until oral intake was resumed. Thereafter, 2.5 mg of prednisone per kilogram per day was administered orally for a total of three weeks and then tapered over a period of 14 to 21 days. Fifty milligrams of ampicillin per kilogram per day was given intravenously, with a change to oral administration when feedings were tolerated. Treatment with antibiotics was continued as long as the patients were receiving steroids. All patients with any severity of injury had barium-swallow examinations within a few days of the injury and three weeks after the injury. Because the radiologists evaluating the resulting films were unaware of the study, no bias was introduced into their evaluation of the presence of injury or the degree of stricture.

Patients with first-degree injuries were given liquids at first and allowed to resume a regular diet within 24 to 48 hours; they were followed on an outpatient basis. Patients with second- or third-degree burns had a repeat barium swallow and repeat esophagoscopy after three weeks. If they had no stricture, they were followed as outpatients. If a patient had ingested industrial-strength lye, a Stamm gastrostomy was performed at the time of the injury assessment and used for feeding and later for retrograde dilation. In the other patients, gastrostomy was performed after the evaluation of stricture formation if it was deemed safer to perform retrograde dilation.

Strictures were classified as mild, moderate, or severe, depending on the degree of compromise of the esophageal lumen. They were treated as follows: mild strictures were dilated by the antegrade passage of Maloney dilators as necessary and followed clinically; moderate strictures were also dilated in antegrade fashion on a regular basis every two to three weeks, with the intervals between dilations increasing as the patients became able to eat solid food without dysphagia. Dilations were eventually performed only as needed if the patients had dysphagia or refused solid food.

Gastrostomy and string placement were performed after three weeks in all children with severe strictures if they had not been performed earlier. Retrograde dilations using Tucker dilators²² were performed on a regular basis and were replaced by antegrade dilation as the scars softened and allowed safe dilation from above. Patients with strictures refractory to dilation after multiple attempts over several months had esophageal replacements.

The incidence of stricture formation and the need for esophageal replacement in the steroid and control groups were analyzed by chi-square analysis and Fisher's exact test. All P values of less than 0.05 were considered to indicate significance.

The 131 patients admitted to the study who were thought to have ingested caustic material ranged in age from 11 months to 17 years, with a median age of just over 2 years. The majority (88 percent) were from 1 to 3 years of age. The oldest patient, a 17-year-old, had ingested alkali in a suicide attempt; all the other ingestions were accidental.

Seventy-one patients (54 percent) had no esophageal injury, but 57 of these had oral burns. Sixty children (46 percent) had esophageal injury, and all of them had burns to the mouth or pharynx. Two patients had airway obstruction, one requiring endotracheal intubation for 48 hours. The other patient had severe laryngeal injury and required a permanent tracheostomy.

Figure 1. Figure 1. Relation of the Severity of Esophageal Injury to the Type of Caustic Agent Ingested.

Solid bars denote first-degree burns, hatched bars second-degree burns, and stippled bars third-degree burns. The causative agent was known in 55 of 60 children with esophageal injuries. The difference between injuries caused by the ingestion of solids and those caused by the ingestion of liquids was not statistically significant.

Of the 60 burns, 55 were caused by known agents, and 43 of these (78 percent) were caused by alkali. Seven children were burned by dishwasher detergent, and five by acid. One child was burned by Clinitest tablets. Although there appeared to be a trend toward less severe esophageal injury with the ingestion of solid caustic agents, the difference in the degree of injury in patients who swallowed liquid as compared with solid material was not statistically significant (Fig. 1).

Table 1. Table 1. Relation of Steroid Treatment to Stricture Formation and the Need for Esophageal Replacement, According to the Degree of Esophageal Injury.

After the evaluation and classification of their burns, 31 children were treated with steroids immediately after esophagoscopy, and 29 served as controls (see Methods). Strictures developed in 10 of the 31 steroid-treated patients and 11 of the 29 controls (Table 1). There was no significant difference between the two groups in the frequency of strictures. Nine of the 10 patients in the steroid group in whom strictures formed had third-degree injuries, and 1 patient had a second-degree burn; all 11 patients with strictures in the control group had third-degree injuries (Table 1). Twenty-one patients who received steroids and 18 controls did not have strictures (P>0.05). With one exception, all these patients had first- or second-degree burns.

Table 2. Table 2. Stricture Formation and the Need for Esophageal Replacement, According to the Degree of Esophageal Injury.

No patient with a first-degree burn had a stricture. Of the 20 patients with second-degree burns, only 1 had a stricture. This patient was treated with steroids. Twenty of the 21 patients who had third-degree injuries had strictures — a significant proportion as compared with that in the patients with milder burns (P<0.001) (Table 2). The use of steroids did not change the incidence of strictures among the patients with third-degree injuries (9 of 10 in the steroid group and all 11 in the control group) (Table 1).

Of the 21 patients with strictures, 11 (52 percent) required esophageal replacement — 4 patients treated with steroids and 7 controls. Of these 11 patients, 7 had multiple dilations for up to 15 months, without reestablishment of an adequate lumen. In the other four patients, the strictures obliterated the esophageal lumen within a few weeks of the ingestion and could not be dilated subsequently. The difference between the two study groups, though suggesting a trend in favor of steroid treatment, was not statistically significant (Table 1). As with the formation of strictures, the need for esophageal replacement correlated with the degree of injury. Only 1 patient of 20 with second-degree burns needed replacement (5 percent), whereas 10 of 21 patients with third-degree injuries (48 percent) had undilatable strictures and required esophageal replacement (P<0.0001). The one patient who had second-degree injury and needed replacement was treated with steroids. Replacement was performed by the insertion of a gastric tube in seven patients, colon interposition in three, and localized esophageal resection and anastomosis in one.

In the group treated with steroids, there was one serious side effect. Several weeks after the ingestion of caustic material and steroid treatment, a three-year-old boy was found to have a brain abscess that required open drainage. He recovered but later needed esophageal replacement after esophageal dilation failed.

Caustic injury to the esophagus remains a serious health problem in children. At highest risk are curious toddlers between one and three years of age, who are exploring the world and resisting the efforts of parents to restrict them from any part of the house or its hazards. Despite legislated changes in the allowable concentration of many household cleaners, there continue to be an estimated 5000 accidental ingestions of caustic agents per year.² This is probably an understated figure, since only 10 percent of such ingestions are reported.¹ Even with the cooperation of manufacturers of household goods, industrial-strength lye and similar products are still available in rural environments in containers that are not childproof.²³

The use of steroids in the treatment of caustic ingestion remains controversial. Since the report in 1950 by Spain et al.⁹ of the effect of steroids on the inflammatory response in mice, there have been many studies of the effect of steroids on stricture formation in the esophagus.^{3 , 4 , 12 13 14 15 16 17 18 19 20 21} Haller and Bachman¹⁰ demonstrated in cats that steroids, coupled with antibiotics, decreased stricture formation, but the effects of steroids in other animal models have not been so clear.¹¹ The few controlled studies of the effect of steroids^{5 , 16} have been short, with few patients. Only rarely have these studies been restricted to children.^{19 , 20} This study of 131 children encompasses an 18-year experience with a prospective, controlled trial of steroids. The depth of the burn was evaluated mainly by a single observer who had the opportunity to follow each patient to the conclusion of treatment.

All patients thought to have esophageal burns had esophagoscopy within 24 hours after ingesting a caustic agent.⁴ We used general endotracheal anesthesia in all cases to avoid the risk of perforation in a struggling child or of aspiration in a sedated child. Examination of the esophagus is safely performed early after ingestion if the esophagoscope is passed up to but not beyond the most proximal observed injury. Flexible endoscopy is claimed to be safer than rigid endoscopy, and it has the additional advantage of permitting the entire esophagus as well as the stomach and duodenum to be evaluated. Children swallow caustic materials by accident, and they usually stop swallowing once they feel pain. Although at this point it is often too late to avoid esophageal injury, the stomach and duodenum are usually spared. This was true in our series, even in the patients who ingested acid. In adults, in whom suicidal gestures are the most common reason for the ingestion of caustic material, more distal evaluation is probably advisable.

If steroid treatment is to be helpful, it should be started early; because of the potential side effects of these drugs, however, we did not want to give them to patients who did not have esophageal injury. All patients therefore underwent esophagoscopy within 24 hours after the injury and before starting steroid treatment. This made the two groups potentially unequal, and in fact it happened that more patients with second-degree burns were assigned to the steroid-treated group. However, the use of steroids was determined in each patient before evaluation. There were similar numbers of patients with third-degree injuries in the two study groups, and since the degree of the burn proved to be the most important factor in the outcome, the two groups were comparable. Since all but six of the patients were between one and three years old, it was impossible to compare the outcomes in different age groups.

It appears from Figure 1 that there was a difference between solid and liquid caustic agents with respect to the severity of injury, but the difference was not statistically significant. It is perhaps less likely that a solid would be swallowed, because it would stick in the mouth and the child would stop swallowing at the first feeling of pain. Children often gulp their food, however, especially if they think they are eating candy, and they may therefore be unable to stop the swallowing reflex. If solid agents reach the esophagus, they can inflict injuries as serious as those caused by liquids, and therefore all patients require a thorough evaluation.

Of 60 children with esophageal injuries, 21 (35 percent) had strictures. Of these patients, 10 were treated with steroids and 11 were not, with no significant difference between the two groups. Eleven of the 21 children required esophageal replacement, including 4 of the 10 in the steroid group and 7 of the 11 in the control group. In all these children, the critical factor in the development of strictures appeared to be the degree of initial injury (P<0.001). Even though steroid treatment was begun within 24 hours of the ingestion of the caustic substance, the development of strictures was not affected by the use of these agents. Only one patient with less than a third-degree burn had a stricture. In this patient, the classification of the injury as second degree may have been an error. Alternatively, since we examined only the first burn encountered, there may have been a more distal unseen injury that was deeper. In the children with strictures who were treated with steroids, there was a trend toward less frequent need for esophageal replacement (4 of 10 in the steroid group vs. 7 of 11 in the control group). The number of patients was too small, however, for the difference to be statistically significant. Thus, the value of steroids in the treatment of esophageal injury is unproved.