Overutilization of routine gastrointestinal (GI) prophylaxis has been a focus of research for more than a decade in North American and European countries given its potential to increase costs and cause adverse clinical effects.1,2 Prescription of antacids in inpatient units and their prolonged use cause changes in the intestinal microbiota with consequent increased risk for Clostridium difficile–associated disease3–5 and nosocomial pneumonia.1,2,6,7 According to the Choosing Wisely recommendation by the Society of Hospital Medicine, routine GI prophylaxis is not recommended for adults on general medical or surgical floors.8 The American Society of Health System Pharmacists “Therapeutic Guidelines on Stress Ulcer Prophylaxis” state that patients admitted to the noncritical care hospital setting with <2 risk factors for bleeding should not receive routine stress ulcer prophylaxis.9 In pediatric patients, established risk factors for clinically significant stress ulcer–related bleeding and thus potential need for acid suppression include respiratory failure with the need for mechanical ventilation, coagulopathy, a Pediatric Risk of Mortality Score of ≥10,10 shock, and thermal injuries.11,12 There is currently a paucity of formal guidelines on GI prophylaxis outside the ICU in pediatric patients. Whether GI prophylaxis is routinely used in pediatric surgery patients outside the critical care setting without specific evidence based criteria is unknown. Given its potential to cause negative effects and inappropriately high use rates in adults on medical-surgical floors (up to 85%),13–15 we believe this is an important issue to address in the pediatric population. Therefore, the purpose of this study was to establish the current rate of postoperative GI prophylaxis in pediatric appendectomy patients on regular nursing floors in a single center and factors associated with its use. We hypothesized that a more complicated postoperative course, prolonged nothing-by-mouth status, and concomitant nonsteroidal antiinflammatory drug (NSAID) use might be associated with acid suppression prescriptions.
We conducted a retrospective single-center cohort study at Cleveland Clinic Children’s in Cleveland, Ohio, after gaining approval from the Institutional Review Board. Given that acute appendicitis is the most common diagnosis requiring an urgent general surgical procedure with an associated low risk of bleeding and an expected short uncomplicated hospital course, we decided to focus our study on this population. Patients were included if they were 2 years to 17 years old and admitted for appendectomy to regular nursing floors between January 1, 2010, and December 31, 2013. We used billing information to identify discharge dates. Any hospitalization lasting <24 hours was defined as a length of stay (LOS) of 1 day. Extended LOS was defined as LOS longer than that of at least 75% of the patients in this cohort, a LOS of >4 days. Patients were excluded if they had any indication for antacid therapy (such as previously diagnosed gastroesophageal reflux or erosive gastritis), documented previous use of antacid therapy, current steroid use other than appendectomy surgery, or if the surgery was a readmission. The following variables were recorded using the patients’ electronic medical records: demographic data, admission diagnosis, surgical procedure, history of gastroesophageal reflux, antacid prescription during admission, and concurrent use of total parenteral nutrition (TPN) and NSAIDs. To characterize our cohort in detail, we reviewed operative notes and classified the diagnosis as simple appendicitis, abscess, peritonitis, or other. The adverse events (pneumonia and C difficile infection) within 3 months of surgery were recorded.
Study data were collected and managed using REDCap (Research Electronic Data Capture) tools hosted at Cleveland Clinic.16 Data were described using medians and ranges for continuous variables and counts and percentages for categorical variables. Patients prescribed postoperative GI prophylaxis were compared with those who were not prescribed GI prophylaxis using 2-sample t tests or nonparametric Wilcoxon rank-sum tests for continuous variables as needed to meet distributional assumptions, and χ2 or Fisher’s exact tests for categorical variables. To assess which combination of factors predicted the prescription of GI prophylaxis, multiple logistic regression models for GI prophylaxis were constructed including age, sex, appendectomy diagnosis, NSAID use, TPN, and either LOS as a continuous variable or extended LOS as a binary variable. Backward selection processes were used to select predictors for a separate model for each LOS variable, and the Akaike information criterion was used to choose a final model. All analyses were performed on a complete-case basis; if a patient was missing data on a particular variable, he or she was excluded from the analysis of that variable but not from the entire study cohort. All tests were 2-tailed and performed at a significance level of .05. SAS 9.4 software (SAS Institute, Cary, NC) was used for all analyses.
Of the 377 medical records evaluated over the 3-year study period, 194 appendectomies met the inclusion criteria for analysis. Table 1 shows the demographic and clinical characteristics of pediatric appendectomy patients. Table 2 describes the clinical course of the appendectomy cohort, including concurrent use of TPN and NSAIDs in relation to GI prophylaxis prescriptions.
Of 194 appendectomy patients, 142 (73%) had uncomplicated appendicitis; 29 (15%) patients had appendicitis with peritonitis, 19 (10%) patients had appendicitis with intraabdominal or appendicular abscess, and 4 patients (2%) had other diagnoses requiring an appendectomy. All of the patients had laparoscopic appendectomies with the majority performed via a single port, except for 2 patients with intraabdominal or appendicular abscess.
Forty (21%) appendectomy patients had an acid suppression prescription postoperatively: 29 with histamine-2 blocker alone, 4 with proton pump inhibitors alone, and 7 patients with both. Standard weight-based dosing of acid suppressant agents were prescribed, and the dose was similar among the patients. The duration of antacid administration ranged from 1 to 12 days in those prescribed with median of 3 days.
Concurrent Use of TPN and NSAIDs
During their hospitalization for appendectomy, 145 patients (75%) were prescribed NSAIDs, and 36 of these patients (25%) received GI prophylaxis. Five patients (3%) of the cohort were on TPN, and 4 of these patients were prescribed acid suppression. Patients treated with TPN were more likely to receive GI prophylaxis than those not treated with TPN (4 of 5 = 80% vs 36 of 189 = 19%, P = .007), as were patients treated with NSAIDs compared with those not treated with NSAIDs (36 of 145 = 25% vs 4 of 49 = 8%, P = .013). One patient who received GI prophylaxis in the appendectomy group developed C difficile–associated disease.
The median LOS for all patients was 2 days (range 1–27 days); the LOS was longer in the prescription group (median of 6 days vs 1 day, P < .001). Patients with an extended LOS of >4 days were more likely to be prescribed GI prophylaxis (22 of 47 = 47%) than those with a LOS of ≤4 days (18 of 147 = 12%, P < .001). In a multiple logistic regression model for GI prophylaxis (described in Table 3), treatment with NSAIDs and extended LOS were significantly associated with GI prophylaxis, with odds ratios (95% confidence intervals) of 3.3 (1.1–10.3) and 6.0 (2.8–12.9), respectively; all other factors were not significantly associated with GI prophylaxis and were dropped from the model.
The findings from our study demonstrate that at least 20% of non–critically ill pediatric surgical patients in our children’s hospital received postoperative GI prophylaxis prescriptions. Our study found lower rates of use of GI prophylaxis than studies in adults possibly because children undergoing appendectomies are generally healthy and do not have underlying chronic medical conditions that adult patients have.1,13,17
A unique strength of our study is that it provides an initial insight into the current practice of routine acid suppression in pediatric appendectomy patients in a single center, addressing the data gap on current acid suppression therapy practice in this selected pediatric surgical population. Results of our study support the hypothesis that having complicated appendicitis is associated with GI prophylaxis. The fact that a majority of patients with perforated appendicitis were prescribed GI prophylaxis postoperatively raises the question of whether the use of acid suppression is done with the purpose of promoting healing. Overall, GI prophylaxis use was significantly associated with complicated cases (associated with peritonitis or abscess), NSAID use, longer LOS, and prolonged postoperative course.
We did not have a way to determine if these patients had mucosal disease associated with acute illness as was described in previous studies.18 Possibly having a complex surgical procedure, more postoperative nausea and vomiting, or simply abdominal discomfort could result in more liberal GI prophylaxis. There might be legitimate reasons for using antacid prophylaxis in patients with more complicated surgeries or those with multiple factors predisposing the patient to stress ulcer development; however, there is no compelling evidence that these are absolute criteria to routinely use antacid therapy. Developing evidence-based guidelines about indications for GI prophylaxis in the pediatric population would be warranted because for some patients, GI prophylaxis would be of merit.
Limitations of our study include the retrospective design and its focus on pediatric appendectomy patients in a single center. GI prophylaxis in more complex patients might be a significant confounder for LOS. We were unable to determine if these patients were more acutely ill because all patients included in our study were hospitalized on regular nursing floors. Postoperative nothing-by-mouth status was not collected as a variable, so it might not have correlated with TPN administration.
Our study suggests that postoperative antacid suppression is used in pediatric appendectomy patients admitted to the regular nursing floor without risk factors for GI bleeding. Prolonged LOS in a sicker patient, with or without TPN and NSAIDs is frequently an indication for adding a histamine-2 blocker. Future multicenter studies might look into GI prophylaxis prescription using the National Surgical Quality Improvement Program-Pediatrics or Pediatric Health Information System data to understand this phenomenon on a larger scale and in other surgical patient populations.
FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.
FUNDING: No external funding.
POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.
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- ↵ASHP Commission on Therapeutics and approved by the ASHP Board of Directors on November 14, 1998. ASHP Therapeutic Guidelines on Stress Ulcer Prophylaxis. Am J Health Syst Pharm. 1999;56(4):347–379
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- Copyright © 2017 by the American Academy of Pediatrics