Analysis of cardiopulmonary stress during endoscopy : Is unsedated transnasal esophagogastroduodenoscopy appropriate for elderly patients ?

1Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine; 2New Ooe Hospital, Kyoto; 3Department of Gastrointestinal Diseases, Panasonic Health Care Center, Osaka, Japan Correspondence and reprints: Dr Kazuhiko Uchiyama, Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajiicho Hirokoji Kawaramachi Kamigyo-ku, Kyoto, Japan 602-8566. Telephone 81-75-251-5518, fax 81-75-251-0710, e-mail k-uchi@koto.kpu-m.ac.jp Received for publication August 27, 2013. Accepted September 19, 2013 Esophagogastroduodenoscopy (EGD) is widely used in Japan for the detection of upper gastrointestinal disease. However, the utility of sedation and the appropriate types of endoscope and methods remain unclear. Elderly patients generally have a higher risk of complications in EGD, including complications from sedation. Although the use of sedation during EGD has been shown to increase patient tolerance, and prevent increases in systolic blood pressure and heart rate (1,2), various adverse side effects, such as hypoxia, have been reported with sedation (3,4). Transnasal EGD has been reported to be safe without sedation (5,6). It is associated with decreased cardiopulmonary stress orIgInAl ArtIcle

during EGD (7).Unsedated transnasal EGD has also been reported to show a similar rate of tolerability compared with transoral EGD under conscious sedation (8)(9)(10)(11)(12)(13).Although endoscopy in elderly patients is being performed with increasing frequency in Japan, we have little information regarding the relative safety of transnasal and transoral EGD in these patient groups.Transnasal EGD has been reported to be safer than transoral EGD for elderly patients (14).On the other hand, transoral thin EGD has been also reported to be safe and tolerable compared with standard EGD (15,16).Elderly patients do not frequently gag or choke during transoral EGD.If transoral EGD is safe and comfortable for elderly patients, the value of transnasal EGD for elderly patients may be limited.The comparative safety and acceptability of the two techniques should, therefore, be considered carefully in the treatment of elderly patients with higher risks for gastric cancer and cardiopulmonary diseases.We compared the safety and tolerability of transnasal and transoral EGD in patients ≥75 years of age.We prospectively compared and evaluated changes in hemodynamic and pulmonary function during each method of EGD.

Study population
The study population comprised patients who underwent monitoring of respiratory and circulatory dynamics during endoscopic screening examinations without sedation at the New Ooe Hospital (Kyoto, Japan) between April 2008 and March 2009.It was determined that a standard effect size of 0.6 would be a clinically significant difference in the numerical data; it was estimated that a sample size of 46 patients per group would be required to detect this difference with 80% power at a 5% significance level.A total of 165 patients (age ≥75 years) provided written informed consent and were investigated in the present study.Patients were excluded from the study if they opted to receive sedation, had a history of undergoing sedated endoscopy or of psychiatric disease, were currently receiving anticoagulation therapy, if a therapeutic procedure was considered likely to be required or if a bleeding diathesis was identified.Patients with cardiac disease, pulmonary disease or psychological disease, and who had undergone partial or total gastrectomy were also excluded from the study.The present study was approved by the Institutional Review Board of the New Ooe Hospital.Data analyses conformed with the principles of the Declaration of Helsinki (17).
The diameter of the inserted portion of the endoscope was 6.5 mm for the GIF-XP260, 9.0 mm for the GIF-XQ260 and 5.0 mm for GIF-XP260N.All procedures were performed by three senior endoscopists with >15 years of experience each.Only topical anesthesia was used, with no sedative agents.All patients were administered antispasmodic medications 5 min before the examination.
Patients in the UO and SO groups received only local throat anesthesia with 4 mL of 2% viscous lidocaine (Xylocaine, AstraZeneca, Japan) for 5 min.Patients in the UT group received local anesthesia in the form of a nasal spray consisting of 0.5% phenylephrine and 2% Xylocaine, delivered as a fine mist using a mucosal atomization device (Wolfe Tory Medical, USA) attached to a 10 mL syringe, and cetacaine spray for pharyngeal anesthesia.

Monitoring of respiratory/circulatory hemodynamics
Duration of the examination, percutaneous arterial blood oxygen saturation and heart rate were measured at the right first finger, and blood pressure was measured at the upper right arm using a monitoring unit (MUE-200, Olympus).These parameters were evaluated at six timepoints (2 min before the examination; at four time points during insertion of the endoscope [esophagus, gastric angle to antrum, pyloric ring to the duodenal bulb and upper gastric body]; and immediately after evulsion of endoscope), then compared among groups.Blood pressure was measured according to a previous report (18).In addition, ratepressure product (pulse rate × systolic blood pressure/100) reportedly offers a useful marker of cardiac oxygen demand and was, therefore, calculated (19,20).

Questionnaire survey
After transnasal EGD had been performed, the patients, who had all previously been examined by transoral EGD using a conventional endoscope, were asked about their preferences regarding a subsequent upper gastrointestinal examination.Patients were able to select one of three options: would prefer transnasal EGD; no preference for transnasal or transoral EGD; or would prefer transoral EGD.

Statistical analysis
For statistical analysis, Statview statistical software (SAS Institute, USA) was used.Data are expressed as the mean ± SD.The Mann-Whitney U test and Wilcoxon's rank-sum tests were used; P<0.05 was considered to be statistically significant.

Patient characteristics
All patients enrolled in the study were analyzed.Characteristics of the enrolled patients in each group are summarized in Table 1.No serious complications in cardiopulmonary function occurred.There were no statistically significant differences in mean age, baseline cardiopulmonary parameters, arterial oxygen saturation, heart rate or systolic blood pressure among the groups.

duration of endoscopic procedure
The mean (± SD) duration of the endoscopic procedure was 6.09±0.28min in the SO group, 5.12±0.28min in UO group and 6.30±0.40min in UT group, with no statistical differences among them (Table 1) Changes in percutaneous oxygen saturation, heart rate and blood pressure during gastrointestinal endoscopic procedures Percutaneous oxygen saturation in the UT group (−0.947±0.308%)showed a transient drop compared with SO (0.161±0.246%) and UO (−0.258±0.213%)groups at the beginning of the endoscopic procedure (Figure 1A).Heart rate rate showed no significant differences among the SO, UO and UT groups (Figure 1B).Changes in systolic blood pressure in the UO group (−0.883±1.578mmHg) immediately after insertion (esophagus and gastric angle to antrum) were lower compared with the SO (6.475±2.098mmHg) and UT groups (4.44±2.096mmHg) (Figure 1C).The rate-pressure product in the UO group was comparable with that in the UT group during endoscopy, and the SO group showed a continuously higher level than the UO and UT groups.There was no significant difference between UO and UT groups (Figure 1D).In patients who underwent transnasal EGD (UT group), 54.4% (31 of 57) expressed a preference for transnasal EGD for their next examination.The percentage of patients who had no preference for transnasal or transoral EGD was 8.8% (five of 57), and who would prefer transoral EGD was 36.8% (21 of 57).

dISCUSSIoN
In the present study, we investigated cardiocirculatory changes and tolerance during EGD in elderly patients using three different types of endoscopy with oral or transnasal insertion.Among elderly patients, transoral thin EGD demonstrated fewer cardiocirculatory effects than transnasal EGD without sedation.Based on the questionnaire survey, the percentage of elderly patients who preferred transnasal EGD was lower than previously reported.Our results indicate that transnasal EGD is not always the safest or most tolerable procedure for elderly patients partially because of transient decreases in oxygen saturation at the time of endoscope insertion.Moreover, from a cardiocirculatory perspective, transoral thin EGD is as safe as transnasal EGD and is well tolerated by elderly patients without sedation.
In a study investigating transnasal EGD in elderly patients, Yuki et al (14) reported that unsedated transnasal EGD was safer than conventional transoral EGD in elderly patients.In that study, they defined patients ≥65 years of age as elderly and used conventional transoral EGD as a control, while in our study, we defined patients ≥75 years of age as elderly and used transoral thin EGD as a comparator with transnasal EGD.These differences in patients and methods may explain the difference in results between that study and ours.
Although the the prevalence of Helicobacter pylori has recently been lower in younger generations in Japan, the mortality rate of gastric cancer in the elderly generation has remained high (21).Because the mortality rate of gastric cancer remains high in elderly patients, screening EGD is essential for these patients in Japan.Although survey data from the United States suggest that >98% of EGDs and colonoscopies are performed with sedation (22,23), approximately 30% of EGD is commonly performed without sedation in Japan (24).Similarly, >75% of EGDs are performed without sedation in many European countries (25).Thus, tolerable and safe unsedated EGD is needed for screening in elderly patients.
Before discussing calibre size and endoscope insertion method, we should consider physiological parameters in elderly patients.In general, aging is associated with significant cardiopulmonary modifications, both structural and functional.Apart from the decrease in total blood volume and the increase in total peripheral resistance, elderly individuals have altered cardiovascular homeostasis including increases in spontaneous blood pressure variability and decreases in heart rate variability (26).Pulmonary function is also affected by aging.Physiological aging of the respiratory system correlates with dilation of alveoli, enlargement of airspaces, decrease in surface exchange area and loss of supporting tissue for peripheral airways.The strength of respiratory muscle also decreases with aging; consequently, adaptability for exercise or acute disease is also reported to be diminished (27,28).Endoscopy in elderly patients may be less effective given these physiological pulmonary and cardiovascular changes.
Regarding calibre size, Preiss et al (29) indicated that unsedated transoral thin EGD is well tolerated, feasible and as safe for patients as the transnasal EGD without sedation.If the use of transoral thin endoscopes (diameter <6 mm) becomes more widely adopted, the need for sedation during EGD may decrease.A multicentre randomized controlled trial in a United States population comparing unsedated endoscopy using transoral thin endoscopes with sedated endoscopy found no significant differences in physician satisfaction, technical ease of the procedure, patient satisfaction or patient willingness to repeat the procedure (30).Other studies have also reported that patients may be able to undergo transoral thin EGD without sedation (15,16).
Using the transnasal insertion route is also considered whenever a thin endoscope is used in the endoscopic examination.Transnasal EGD is known to induce less frequent gagging episodes, nausea, choking sensation and pharyngeal discomfort compared with transoral EGD (7,8).For this reason, unsedated transnasal EGD has been reported to be safer and more tolerable than transoral EGD (31)(32)(33) in younger and older generations.
In our study, however, the advantages of transnasal EGD for elderly patients (age ≥75 years) was not confirmed.Even when lower pulmonary function in elderly patients is considered, transnasal EGD may not be suitable due to its effect on pulmonary function (5).
Our results suggest that transoral thin EGD without sedation represents a safe and acceptable approach in elderly patients.

Figure 1 )
Figure 1) A Changes in percutaneous oxygen saturation during the course of esophagogastroduodenoscopy (EGD) (*P<0.05compared with UT group; # P<0.05 compared with SO group).B Changes in heart rate during the course of EGD (*P<0.05compared with UT group; # P<0.05 compared with UO group).C Changes in systolic blood pressure during the course of EGD (*P<0.05compared with UT group; # P<0.05 compared with UO group).d Change in rate-pressure product (pulse rate × systolic blood pressure)/100 during the course of EGD.•SO group -transoral EGD using standard endoscope; ■UO group -transoral EGD using thin endoscope; □UT group -transnasal EGD using thin endoscope.1: 2 min before examination; 2: Esophagus; 3: Gastric angle to antrum; 4: Pyloric ring to the duodenal bulb; 5: Upper gastric body; 6: Immediately after evulsion of endoscopy

Table 1 Patient characteristics and baseline cardiopulmonary parameters in the study groups
This study was supported by the staff of New Ooe Hospital; Tomoko Kinugawa, Yaeno Miyakawa, Yukiko Sato, Youko Kato, Sachiko Igaki, Hiromichi Furukawa and Kazuya Itagaki.The authors greatly appreciate Prof Richard Kozarek, Virginia Mason Medical Center, USA, for his thoughtful advice to our study.This work was supported by a Grant-in-Aid for Scientific Research (B) to TY (No 21390184); a Grant-in-Aid for Challenging Exploratory Research to YN (No 08101559); a Grant-in-Aid for Young Scientists (B) to KU (No 21790688) from the Japan Society for the Promotion of Science; the City Area Program to TY and YN from the Ministry of Education, Culture, Sports, Science and Technology, Japan; and the Adaptable and Seamless Technology Transfer Program through target-driven R&D to YN from the Japan Science and Technology Agency.Yoshito Itoh and Nobuaki Yagi have an affiliation with a donation-funded department from AstraZeneca Co, Ltd; Eisai Co, Ltd; Otsuka Pharmaceutical Co, Ltd; MSD KK; Dainippon Sumitomo Pharma Co, Ltd; Chugai Pharmaceutical Co, Ltd; FUJIFILM Medical Co, Ltd; and Merck Serono Co, Ltd.Yuji Naito has received scholarship funds from Otsuka Pharmaceutical Co, Ltd, and Takeda Pharmaceutical Co, Ltd.Yoshito Itoh has received scholarship funds from MSD KK and Bristol-Myers KK.The other authors have no financial disclosures or conflicts of interest to declare. dISCloSUrES: