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What Is Known
- Recent data show that fever is the second most frequent reported adverse event following gastrointestinal endoscopy in children.
- Postendoscopy fever can cause concern for perforation and infection, leading to significant health care use.
What Is New
- Postendoscopy fever rarely represents significant infection.
- A clinical care guideline may reduce unnecessary care while maintaining patient safety.
Endoscopy has become a common procedure to diagnose and manage gastrointestinal (GI) disease in pediatric patients. Despite the prevalent use of pediatric endoscopy, there is still a relative dearth of published research on associated adverse events (AEs). In particular, there has been limited review of fever in the postendoscopy patient, although this AE is relatively common (1) and can raise significant concern in providers and families, even in the absence of other concerning symptoms.
Although there is limited published literature on post-endoscopy fever (PEF), there is substantial research on the related entity of postoperative fever (2–4). Although there are important differences between the postendoscopy and postsurgical patients (eg, degree of tissue injury, duration of procedure, and sometimes the type of anesthetic used), it can be helpful to use the postoperative state as a surrogate for discussing fever following endoscopy. Several studies have demonstrated that early postoperative fever is uncommonly due to infection, but that it still results in a variety of costly tests (2–4). One large prospective observational study in adult patients demonstrated a high incidence of postoperative fever—24% (245/1032) of their inpatient surgery subjects experienced early postoperative fever (within the first 72 hours) (2). Of the patients who underwent fever evaluation, 82% had no identified infectious source despite extensive testing (including blood cultures, urine cultures, and chest radiographs, among other tests).
In terms of endoscopy in children, recent data from our institution demonstrated that 21.6% of all AEs reported were related to fever (by parental report or measured by a health care provider) (1). Our study aimed to examine rates of PEF over an 8-year period, describe clinical outcomes associated with PEF, and evaluate the effect of a care algorithm in managing these cases. We hypothesized that, like postoperative fever, PEF usually does not represent significant infection. In recognition of the generally benign nature of PEF in children, we sought to develop and implement a clinical care guideline (CCG) to manage these complaints, designed to minimize unnecessary diagnostic evaluation and treatment of these patients (Table 1).
TABLE 1 -
Characteristics of postendoscopy fever cases before and after implementation of the clinical care guideline
||Pre-CCG (n = 41)
||Post-CCG (n = 109)
||Total (n = 150)
|Mean age (SD)
||6.53 y (±5.33 y)
||8.21 y (±5.05 y)
||7.76 y (±5.18 y)
||M = 27 (65.9%)F = 14 (34.1%)
||M = 59 (54.1%)F = 50 (45.9%)
||M = 86 (57.3%)F = 64 (42.7%)
|Procedures done by GI fellow
|Identified endoscopy-related infection
|Rate of postendoscopy fever
CCG = Clinical care guideline; M = Male; F = Female; GI = Gastrointestinal.
A prospective database of all AEs following endoscopy in pediatric patients was collected over an 8-year period (July 2010 through December 2018) at a single, academic, freestanding children's hospital. The study was approved by the Organizational Research Risk and Quality Improvement Review Panel at Children's Hospital of Colorado. A separate study has been published from the data collected in the first 48 months, the purpose of which was to comprehensively review all postendoscopic AEs and categorize the events by the level of intervention required (1). In comparison, the present study specifically tracks febrile episodes occurring within 72 hours of endoscopy, spans a significantly longer data collection period, and involves the introduction and analysis of a CCG to help direct PEF management. The database was created by recording each parental notification of postendoscopy symptoms, emergency department (ED) visits, and hospital admissions following endoscopic procedures (procedure center staff did not reach out to caregivers to inquire about these symptoms). The database included all outpatient endoscopies in addition to inpatients who underwent endoscopy during hospital admission.
“Fever” was defined by parent report, and no clear numerical definition or validation method was required for inclusion in the database. The providers and nursing staff receiving calls from caregivers or medical providers reported the information to one of the authors, and that information was then entered into the database. Additionally, automated queries of the hospital electronic medical record were performed and reviewed quarterly to identify patients who underwent endoscopy and subsequently had an ED visit or hospital admission in the institution's network of care. The cases of PEF were reviewed in detail and further information was collected on where the evaluation took place (ie, over the phone, in the office, or in the ED), what further workup, if any, was performed, and the outcomes of each of these febrile cases.
At 33 months into the study period, a PEF CCG was developed in attempt to decrease unnecessary referrals for care (Fig. 1). The CCG was designed for use by the GI clinic triage nurse line as well as the on-call GI fellows to guide decision-making on management of patients with PEF. It was developed through collaborative work from the primary investigator and GI nursing leadership, approved by the GI faculty as a whole, and implemented via education for faculty, nurses, and fellows. The CCG stratifies patients into three risk zones—Green (lowest risk), Yellow (medium risk), and Red (higher risk)—based on patient characteristics, including American Society of Anesthesiologists (ASA) classification, interventional versus diagnostic procedure, steroid use, fever duration, general appearance and activity level of the patient, presence or absence of upper respiratory symptoms and/or sick contacts, new GI signs or symptoms (such as abdominal pain, blood in stool, vomiting, etc.), and hydration status. Based on the presence or the absence of these characteristics, patients are classified into one of the three risk zones, which then guides subsequent management. The most high-risk patients, including those with a central line, patients on immunosuppression (other than corticosteroids), and transplant patients are excluded from the guideline, as fever in these high-risk patient groups is generally treated very differently.
Student t-test and chi-squared analysis were used to compare patient characteristics before and after implementation of the CCG and to compare the rates of health care use before and after implementation. Furthermore, rates of fever were compared for diagnostic and interventional procedures using chi-squared analysis. Interventional procedures included endoscopic retrograde cholangiopancreatography, balloon or bougie dilations (any site), foreign body removal, polypectomy, endoscopic management of bleeding (variceal and nonvariceal), endoscopic placement of feeding tubes, esophageal stent placement, and small bowel balloon enteroscopy. Biopsies were performed for all diagnostic procedures. These different procedure categories were meant as a surrogate for the length and invasiveness of the endoscopy, with interventional procedures generally being lengthier and more invasive, although the actual duration of the procedure was not recorded.
There were 150 reported cases of fever in the 27,100 pediatric endoscopic procedures performed during the study period, amounting to an overall rate of 0.55%. There was no significant difference between the rates of PEF before and after implementation of the CCG (0.66% and 0.52%, P = 0.20; Table 2). The patient/procedure characteristics of the PEF group (including age, gender, percentage of interventional procedures, and percentage of procedures done by GI fellows) were not significantly different before and after CCG implementation (Table 2). Of the 150 patients who experienced fever following endoscopy, only 6 patients had identified endoscopy-related infection, amounting to 4.0% of fever cases and 0.02% of all endoscopies. Of these 6, 1 patient was found to have positive blood cultures and, of note, had percutaneous liver biopsy that showed cholangitis at the same time as endoscopy; 2 patients had fever attributable to aspiration pneumonia following anesthesia; and 3 of these were found to have perforation (after presenting with fever and abdominal pain).
TABLE 2 -
Postendoscopy fever outcomes before and after implementation of the CCG
||Pre-CCG (n = 41)
||Post-CCG (n = 109)
|Grade 1: Phone call/Observation
|Grade 2: ED/Office visit
|Grade 3: Admission/Antibiotics
|Grade 4: PICU/Surgery
This table demonstrates the percentage of fever cases which resulted in phone call/observation only, ED/office visit, hospital admission/antibiotic use, and PICU/surgery before and after implementation of the CCG.CCG = Clinical care guideline; ED = Emergency department; PICU = Pediatric intensive care unit.
∗indicates values that are statistically significant, with a P value of < 0.05.
Fever cases were categorized as Grade 1 (patients who were managed over the phone/observed at home), Grade 2 (patients who were seen in the ED or GI office), Grade 3 (patients admitted to the hospital), and Grade 4 (patients who required pediatric intensive care unit [PICU] admission or surgery). After implementation of the CCG, the rate of fever cases in the greater than or equal to Grade 2 (≥Grade 2) category decreased by 52.1% (P < 0.0001; Table 3). Specifically, ED or office visits decreased by 43.6% (P = 0.01) and hospital admissions decreased by 76.4% (P = 0.004) for patients who experienced PEF. The percentage of cases requiring PICU admission or surgery (Grade 4) did not change after implementation of the CCG (2.4% vs 1.8%, P = 0.81). The rate of fever was significantly higher for interventional procedures (0.81%) than for diagnostic procedures (0.51%, P = 0.02; Table 3).
TABLE 3 -
Rates of fever for different procedure types
||Rate of fever
|Diagnostic procedures (n = 23,150)
|Interventional procedures (n = 3950)
|Total procedures (n = 27,100)
With the increasing emphasis on improvement in the quality of health care delivery, based on the Institute of Medicine's (IOM) strategies (5), attention to the safety and efficiency of invasive procedures is critical. Safe, as defined by the IOM, is “avoiding injuries to patients from the care that is intended to help them”, and efficient is defined as “avoiding waste, including waste of equipment, supplies, ideas, and energy.” Our previous work in capturing, classifying, and characterizing the spectrum of postendoscopy AEs in children (1) has naturally lead to a desire to develop interventions to improve safety and efficiency based on the insights obtained. As one of the most common AEs identified after endoscopy, and with an appreciation that this symptom leads to unnecessary care in many patients, PEF became the obvious first target for intervention.
To review the physiology of fever, it is an increase in core temperature mediated by circulating pyrogens, namely, IL-1, IL-6, and TNF-alpha, which causes an increase in the thermoregulatory set point in the hypothalamus (6,7). Endogenous pyrogens may be released in response to infectious exogenous pyrogens, but they are also released in response to noninfectious inflammatory states, tissue damage, and toxins (8). Again using postoperative fever as an analogy, we refer to a prospective study that showed that in postoperative patients without identified infection, 25% had maximum temperatures ≥38.5°C in the first 24 hours after surgery (4). Plasma concentration of IL-6 was 2 to 3 times greater in these patients, suggesting that tissue injury and perioperative stress play a role in the common development of postoperative fever. Although even interventional endoscopy is typically less invasive than most surgeries, it is possible that some extent of tissue damage and physiologic stress may contribute to the development of early PEF.
There are some causes of fever that are unique to endoscopy itself (9–12). Lee et al (9) reported a case-control study of patients who experienced postpolypectomy fever (PPF), defined as elevated temperature after polypectomy without evidence of other explainable fever foci . They excluded patients who developed perforation or had significant associated abdominal pain, distinguishing the PPF that they encountered from the complete clinical syndrome known as postpolypectomy coagulation syndrome (PPCS). PPCS is characterized by fever, abdominal pain, leukocytosis, and peritoneal tenderness without radiographic evidence of perforation and is thought to be due to the transmural burn, which can occur with electrocautery of colonic polyps. The authors hypothesize that PPF may represent a milder spectrum of PPCS, that it may be due to transient bacteremia, or that the fever may be caused by an inflammatory mechanism rather than infection (as the infectious workup is generally negative).
Review of our data does reveal that rates of PEF are significantly higher in interventional cases than purely diagnostic endoscopy. The data support the hypothesis that fever in the majority of these cases may be related to release of inflammatory cytokines, proportional to the degree and/or duration of mucosal contact. However, the fact that rates of perforation are significantly higher with interventional compared to diagnostic cases (1) supports using this as a factor in stratifying risk in the CCG. Nevertheless, in only 10.7% of PEF cases did additional workup result in enough concern for admission and/or administration of intravenous antibiotics, with only 6 cases (4.0% of PEF cases) identified as having a potential endoscopy-related infectious source for their fever. In 1 case, a percutaneous liver biopsy was performed at the same time as the endoscopy and this patient was subsequently diagnosed as having cholangitis; therefore, the identified infection is more likely related to complications of the liver biopsy than the endoscopy and could even be reasonably considered for exclusion from the present study. Two cases were diagnosed with aspiration pneumonia associated with vomiting after anesthesia and presented with fever in addition to respiratory symptoms. These cases serve as a reminder to consider other non-GI sources of infection following a procedure. Finally, 3 fever cases were found to have perforation, all of which were following an interventional procedure. It is interesting to note that of the 23 cases of perforation reported during the study period, only 3 (or 13.0%) had fever as a part of their presenting complaints.
Nevertheless, efforts to stratify risk to help determine which patients warrant additional evaluation seem well justified. The resultant CCG used factors felt to be the most important to discriminate those patients whose fever had the greatest likelihood of having a serious infectious source and would benefit from additional evaluation. These factors included ASA level of the patient, whether an interventional procedure had been performed, whether they were on any corticosteroid therapy, the duration/persistence of fever, whether there were concomitant upper respiratory symptoms, if there were new-onset GI symptoms, their hydration status, and their overall appearance. These factors were used to provide reassurance that either a non-GI source was likely or that the general appearance of the child would allow for continued phone follow-up, without the need for further health care use.
Implementation of this CCG resulted in a significant shift in the prevalence of Grade 2 and above (requiring hospital use) to Grade 1 (clinical observation and reassurance) AEs, dropping ED visits and admissions by 43.6% and 76.4%, respectively, for the PEF patients. This shift was not associated with any negative patient outcomes and resulted in a reduction in charges/costs related to the management of postendoscopy AEs at our institution. This demonstrates an improvement in the efficiency of our postendoscopy care with the implementation of this CCG. In addition, the decrease in referrals for evaluation of fever did not result in any known missed diagnoses. The stability of rates of level 4 cases suggests that this CCG did not have an adverse effect on the safety of evaluating these cases. However, the power of the present study with 120 PEF cases and only 6 identified endoscopy-related sources limits the ability to comment on overall safety of a CCG. It should also be noted that approximately half of the ED referrals for PEF after implementation of this CCG were parental self-referrals that occurred despite advice from GI providers and staff to continue monitoring at home. This affirms the importance of providing appropriate anticipatory guidance before endoscopy around the topic of fever to help preemptively assuage parental anxiety if their child is otherwise well appearing.
Although the results of the present study were both reassuring that PEF is rarely related to significant infection and that a CCG may reduce unnecessary care, there are several limitations to be considered. First, the database used does not include demographic data from the other 26,950 patients who underwent endoscopies at our institution and did not experience PEF. Therefore, no comparison can be made between the PEF group and the endoscopy population at large in terms of the ASA level, procedure time, age, gender, or other characteristics. Without this information, we are unable to evaluate whether rates of PEF are higher in patients with more serious comorbidities, which may likely be the case. Similarly, the present study lacks data on anesthetic technique (such as the type of airway or type of anesthetic used), which also may affect rates of PEF. The methodology for collecting PEF cases likely underestimates the true prevalence, where caregivers either did not check or did not notify us of any fever, or received care for this at an outside institution. Furthermore, the methodology for measuring and defining fever was not standardized for the purpose of the present study; some caregiver reports of “fever” may not have had objective evidence of true fever, whereas other PEF may have been missed due to the child otherwise being well and the caregiver not measuring their temperature. Finally, as an academic, single center study, applicability to other sites of practice is questionable. The strengths of the present study, however, are the prospective design, the longitudinal nature of the study population, the large patient numbers, and the robust infrastructure for the capture of AE data.
In summary, results such as these support the generally benign nature of PEF in children and the opportunity to decrease unnecessary hospital use. Further study is needed, however, ideally in the form of a multicenter comprehensive database of endoscopic procedures in children. This type of collaborative work would allow for a more accurate determination of the true prevalence of AEs and encourage data-driven improvement in the quality of endoscopy in children. Specifically for PEF, a prospective study analyzing procedure time and postendoscopy temperature would help support the contention that mucosal exposure time correlates with PEF risk.
PEF is one of the most common types of endoscopy-related AE encountered in children and is rarely related to a defined serious infection. As has been shown in postsurgical fever, the majority of PEF may be associated with the release of inflammatory cytokines, proportional to the degree of tissue injury and/or physiologic stress from the procedure itself. Additional care for the assessment of PEF is costly and may result in unneeded hospital admissions, further diagnostic testing, and patient/parental anxiety. Implementation of a clinical care guideline designed to stratify risk may reduce unnecessary care while maintaining patient safety.
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