Air embolism secondary to endoscopy in hospitalized patients: results from the National Inpatient Sample (1998-2013)

Introduction

Air embolism occurs during endoscopic procedures when air is inadvertently introduced into the vasculature. Air embolism rarely complicates endoscopy; however, it entails a high risk of leading to severe or even fatal outcomes if not diagnosed and treated promptly, and death can occur even with aggressive interventions to treat this problem [1,2]. Though most commonly associated with endoscopic retrograde cholangiopancreatography (ERCP), air embolism can complicate any endoscopic procedure [3-5].

Plausible mechanisms for air embolism following endoscopic procedures include, but are not limited to the following: insufflated air under pressure entering into an exposed vessel through a compromised mucosal barrier; mechanical manipulation of the bile ducts; the presence of biliary venous shunts; direct passage of air into the portal venous system during biliary manipulation; and inability of the pulmonary circulation to remove air emboli [6]. The risk of post-endoscopic air embolism appears to be increased by the following factors: a) biliary interventions; b) portosystemic shunts; c) hepatobiliary tumors; d) blunt/penetrating trauma to the liver; e) high pressure insufflation; and f) inflammatory lesions, including hepatic abscess, inflammatory bowel disease, and mesenteric ischemia [7-10].

The true incidence of air embolism is difficult to ascertain. Most studies of air embolism in the literature are case reports and there is a paucity of data on the incidence of post-endoscopic air embolism, especially in hospitalized patients. The aim of this study was to describe the incidence and outcomes of air embolism after inpatient endoscopic procedures in the United States during the 16-year period from 1998-2013, using a large national database: the National Inpatient Sample (NIS).

Patients and methods

Study sample

We queried the database for all endoscopic procedures using the International Classification of Diseases, 9th revision, Clinical Modification (ICD-9-CM) coding system. ICD -9-CM codes used to extract relevant data are listed in Supplementary Table 1.

Supplementary Table 1 Procedures and ICD-9-CM codes used for data selection

Results

Patient demographics and hospital characteristics

We identified 2,245,291 endoscopies that were performed as index procedures on hospitalized patients in the United States between 1998 and 2013. A total of 1,264,471 patients (56%) were female and 1,279,653 (57%) were Caucasians. Mean age at the time of procedure was 62.5 years. Nearly all hospitalizations were non-elective admissions (91%). Similarly, most hospitalizations/endoscopic procedures (89%) occurred in urban hospitals. Most patients were treated in the South (35%) and Midwest (20%) regions (Table 1).

Table 1 Population baseline characteristics and type of endoscopy

Post-endoscopic air embolism

Post-endoscopic air embolism occurred in 13 cases, producing a rate of 0.57 per 100,000 endoscopic procedures. Per procedure, air embolism was most common after ERCP, occurring in 3.32 per 100,000 procedures, compared with 0.44 and 0.38 per 100,000 procedures for EGD and colonoscopy, respectively (P<0.05). We recorded no cases of air embolism after sigmoidoscopy. The mean age of patients with air embolism was 49.5±20.5 years. The primary diagnoses in cases that developed post-endoscopic air embolism are presented in Table 2. On bivariate analysis, ERCP was the only endoscopic procedure significantly associated with post-endoscopic air embolism (OR 7.45, 95%CI 2.25-24.86; P<0.001) (Table 3).

Table 2 Diagnosis and demographics for air embolism cases

Table 3 Odds of air embolism by endoscopy type

Inpatient mortality

Inpatient mortality after endoscopy was 1.4%. Patient and hospital characteristics were significantly associated with inpatient mortality included age, sex, race, comorbid status and payer type (Table 4).

Table 4 Logistic regression estimating the effect of air embolism on inpatient mortality

For patients who had an air embolism after endoscopy, the case fatality rate was 15.4%. On bivariate analysis, post-endoscopic air embolism was significantly associated with greater odds of inpatient mortality (OR 12.85, 95%CI 2.85-58.01; P=0.01). After adjusting for covariates, the occurrence of air embolism after endoscopy was an independent predictor of inpatient mortality (OR 10.35, 95%CI 1.21-88.03; P<0.03) (Table 4).

Discussion

Air embolism is usually an iatrogenic phenomenon. In some cases, it runs a subclinical course and is probably underdiagnosed [4,21]. However, severe cases often manifest with cardiopulmonary and cerebrovascular symptoms and are associated with high morbidity and mortality outcomes. While neurologic sequelae appear to be more common, cases with cardiopulmonary symptoms are at a greater risk of death [22]. Studies show mortality rates due to air embolism range from 12-30%, comparable to our finding of 15.4%. More than half of these patients die within the first 48 h [22,23].

In comparison to surgical or endovascular interventions, air embolism rarely complicates endoscopy. McCarthy et al observed that endoscopy accounted for only 2 of 67 cases of air embolism over a 25-year period of hospital records [22]. Likewise in this study, we observed that air embolism complicated approximately 1 in 175,000 endoscopic procedures. The risk for air embolism was, however, higher in ERCP procedures, being 7.5- and 8.8-fold greater compared to EGD and colonoscopy, respectively. Furthermore, ERCP was the only endoscopic procedure significantly associated with developing an air embolism (OR 7.45, 95%CI 2.25-24.86; P<0.001). This finding is well described in the literature, and may be explained by air entering the arterial or venous system of the liver during ERCP maneuvers [4].

Compared to diagnostic ERCP, therapeutic ERCPs involve more invasive and aggressive instrumentation of the biliary system and entail a higher risk for air embolism [24]. It is believed that a combination of high pressure from air insufflation and mechanical trauma to the bile ducts by instruments during therapeutic ERCP could potentiate entry of air into the circulation through the biliary tree.

Albert et al observed that the use of small-diameter endoscopes and air insufflation for direct intraductal biliary endoscopy promotes the development of air embolism [25]. The authors strongly recommended that only CO₂ be used for insufflation during intraductal biliary endoscopy.

Though air embolism even with CO₂ has been documented, CO₂ has been shown to have an overall better safety profile as compared to room air [4,8,26]. CO₂ was also recommended in a recent report by the American Society for Gastrointestinal Endoscopy’s technology committee [27].

Air embolism can occur even with an intact mucosal barrier [28]. However, a pre-existing breach in the gastrointestinal mucosa is a commonly implicated factor in developing air embolism after endoscopy. The first reported case of endoscopy-related cerebral air embolism occurred during an EGD and involved a patient with a duodenal ulcer and duodenocaval fistula [29]. Other reported cases of air embolism after endoscopy include perforated gastric ulcer, esophageal biopsy, Crohn’s disease with fistulas and erosive esophagitis [8,30-32]. Similarly, in our study we demonstrate that most cases of air embolism after endoscopy occurred in relation to gastrointestinal disorders involving a breach to the gastrointestinal mucosa or vasculature (Table 2). Therefore, it is imperative for endoscopists to maintain a high index of suspicion for air embolism when performing endoscopy involving these gastrointestinal disorders.

In this study, we report an all-cause inpatient mortality rate of 1.4%. In addition, we observed that the risk of inpatient mortality was much higher in patients with more comorbidities. The case fatality rate after air embolism was 15.4%. After controlling for comorbidities amongst other relevant factors, we observed that air embolism after endoscopy independently increased the risk of inpatient mortality. This finding underscores the need for increased awareness of air embolism during endoscopy and the prompt implementation of appropriate therapeutic measures when air embolism is diagnosed.

Air embolism can be considered in the differential diagnosis when patients experience unexpected, sudden and significant hemodynamic instability during endoscopy. Prompt supportive treatment, including resuscitation and high-flow oxygen (if not already being delivered) and cardiopulmonary support as needed, should be implemented, even before air embolism is confirmed if the level of suspicion is high. Fluid resuscitation increases central venous pressure and may prevent further entry of air into the venous system. Hyperbaric oxygen therapy may improve outcomes in patients with cerebral air embolism [33].

Our study has several limitations, most of which are inherent to the administrative nature of the NIS database. While the NIS is an established database used in many published analyses, it is subject to data misclassification, incomplete documentation, and other coding difficulties. Furthermore, the NIS applies only to an inpatient population and our findings cannot be generalized to the overall population. The NIS lacks data on the severity of gastrointestinal disease and we could therefore not include this in our analysis. However, despite these limitations, most of our study findings are consistent with the previous literature.

In conclusion, air embolism after endoscopy is rare. However, it has a high potential for adverse outcomes and its occurrence independently predicts patient mortality. Endoscopists should maintain increased awareness for air embolism, especially in patients undergoing high-risk procedures like therapeutic ERCP. Larger studies are needed to quantify the risk of post-endoscopic air embolism, especially in disorders that involve a breach in the gastrointestinal mucosa.