Endosc Int Open 2015; 03(05): E487-E493
DOI: 10.1055/s-0034-1392366
Original article
© Georg Thieme Verlag KG Stuttgart · New York

Portable inhaled methoxyflurane is feasible and safe for colonoscopy in subjects with morbid obesity and/or obstructive sleep apnea

› Author Affiliations
Further Information

Corresponding author

Nam Q. Nguyen, MD
Department of Gastroenterology and Hepatology
North Terrace
South Australia, 5000
Australia
Fax: +61-8-8222-5885

Publication History

submitted: 19 January 2015

accepted after revision: 07 May 2015

Publication Date:
24 June 2015 (online)

Background and study aims: Colonoscopy with inhaled methoxyflurane (Penthrox) is well tolerated in unselected subjects and is not associated with respiratory depression. The aim of this prospective study was to compare the feasibility, safety, and post-procedural outcomes of portable methoxyflurane used as an analgesic agent during colonoscopy with those of anesthesia-assisted deep sedation (AADS) in subjects with morbid obesity and/or obstructive sleep apnea (OSA).

Patients and methods: The outcomes of 140 patients with morbid obesity/OSA who underwent colonoscopy with either Penthrox inhalation (n = 85; 46 men, 39 women; mean age 57.2 ± 1.1 years) or AADS (n = 55; 27 men, 28 women; mean age, 54.9 ± 1.1 years) were prospectively assessed.

#

Patient satisfaction, pain, and state-trait anxiety inventory anxiety scores

Although there was no difference between the satisfaction scores of the two groups (AADS vs. Penthrox: 94 ± 6 vs. 98 ± 5; P = 0.76), 28 of 34 Penthrox patients (82 %) who had undergone a previous colonoscopy with AADS preferred Penthrox over AADS. The patients who had completed colonoscopy with Penthrox alone reported that the inhaler was easy to use, provided adequate analgesia, and allowed them to have good recall of the procedural findings, and 90 % were willing to receive Penthrox again for colonoscopy. Although the patients who received Penthrox had a higher pain score during colonoscopy (3.6 ± 0.2 vs. 0.9 ± 0.1, P < 0.001; [Fig. 3]), the pain was perceived as tolerable and short-lasting. There were no differences between the total STAI-Y anxiety (“nervousness”) scores of the two groups before and after colonoscopy ([Table 1]).

#
#

Discussion

This is the first study to show that patient-controlled analgesia with inhaled methoxyflurane as a method of relieving discomfort during colonoscopy is feasible, safe, and as effective as AADS in subjects who have morbid obesity with or without obstructive sleep apnea. Although ours is not a randomized study, this new approach to analgesia during colonoscopy has demonstrated several major advantages over conventional AADS in these patients, including the following: (i) a better safety profile with significantly fewer cardiorespiratory complications, (ii) significantly shorter preparation and procedural times with similar cecal intubation and polypectomy rates, (iii) a significantly shorter recovery time with earlier discharge, (iv) substantially greater cost-effectiveness with potentially shorter waiting lists, and (v) good patient satisfaction overall, with more than 90 % patients willing to undergo further colonoscopy with inhaled Penthrox. These findings suggest that in subjects who are morbidly obese or have OSA without liver or renal disease, colonoscopy with Penthrox inhalation is a safe and cost-effective alternative, with great potential to improve workflow and optimize the health economics of endoscopy units, especially those with long waiting lists. More importantly, when given the option, a majority of these high risk subjects (85/140, or 61 %) were willing to use Penthrox inhalation for colonoscopy, and 82 % patients who had had AADS for previous colonoscopies preferred to have Penthrox for their future colonoscopies, indicating that the clinical application of Penthrox analgesia for colonoscopy in this group is highly feasible.

Because of concerns about the potential impact of methoxyflurane on undiagnosed fatty liver disease or diabetic nephropathy, which are common co-morbidities of morbid obesity, patients were carefully screened and monitored for both renal and liver function in the current study, and these were not altered by Penthrox inhalation (3 mL in the current study; [Table 3]). It is important to recognize that the toxicity of methoxylflurane is dose-dependent, and the reported nephrotoxic and hepatotoxic effects are observed only with the much higher doses used for general anesthesia [8] [9]. As demonstrated in our previous trial [7], provided that the subject has normal liver and renal function or no known liver or renal disease, Penthrox inhalation within the recommended dosage is safe, even in patients with morbid obesity and OSA.

Although the potential risks associated with occupational exposure to volatile methoxyflurane used routinely in clinical endoscopy has always been a concern for the staff, no occupational adverse effects have been reported from the 5 million units used since 1975 (60 % in the ambulance setting) at the recommended dose [10] [11]. Even in the small air space of an ambulance, the exposure to methoxyflurane over an 8-hour work day is extremely small (ranging from 0.1 to 0.6 ppm) [11]. In rats, prolonged exposure to a concentration of 50 ppm is required to cause any potential hepatotoxicity or nephrotoxicity [21]. Given that endoscopy rooms are much larger (4 to 5 times the size of an ambulance) and have better ventilation systems, it is expected that occupational exposure to Penthrox in an endoscopy unit would be substantially smaller than that in a paramedical setting. Furthermore, unlike one in an ambulance setting, a Penthrox Inhaler in an endoscopy suite is always used with an activated carbon chamber, which can further reduce the concentration of exhaled methoxyflurane. Methoxyflurane has a characteristically fruity odor, and any inadvertent leakage, therefore, can be detected easily and rapidly.

It is important to recognize that the incidence of cardiorespiratory complications is substantially lower in patients undergoing Penthrox-assisted colonoscopy than in those receiving AADS, with essentially no risk for respiratory depression. This is most likely related to the minimal, if any, sedative effect of Penthrox inhalation, giving it a safety profile that is highly desirable for subjects who are at high risk for respiratory complications during sedation of any level. Similarly, it is likely that propofol was the agent that caused the greater incidence of hypotension and related arrhthymias in the AADS group. Furthermore, the nonsedative property of Penthrox, in contrast to AADS, enables subjects to be awake and use the drug at their discretion, have a better recall of the colonoscopy findings, and recover at an “ultrafast” pace. This may explain the preference for Penthrox over AADS for future colonoscopy in the 82 % of patients who had prior colonoscopy with AADS.

The substantially better cost-effectiveness of Penthrox inhalation than of AADS for colonoscopy in the current study has major health economic implications, given the current demand for colonoscopy for bowel cancer screening and surveillance in an epidemically obese population. The significantly shorter procedural time with Penthrox colonoscopy not only would allow more procedures to be performed in a list or over a year but also would also avoid the need for anesthesia-assisted lists, reducing the waiting time for colonoscopy in these high risk patients. This advantage is particularly relevant for endoscopy units where the anesthesia service resources for endoscopy are limited and often conserved for interventional endoscopy lists. At present in these centers, the waiting lists for diagnostic upper and lower gastrointestinal endoscopic procedures to be performed with AADS are usually longer than the lists for procedures to be performed with conscious sedation (approximately 6 – 9 vs. 3 months). The waiting time can be further prolonged for these subjects because priority is often given to patients undergoing interventional procedures, such as endoscopic mucosal resection, endoscopic retrograde cholangiopancreatography, endoscopic ultrasound, and balloon enteroscopy. Therefore, provided that liver and renal function is normal, the issue of long waiting lists for these patients can be overcome with the use of Penthrox inhalation.

Potential weaknesses of the current study are its lack of randomization, modest sample size, and selection bias toward “healthy” morbidly obese patients without liver or renal disease. Before a large randomized trial in these high risk subjects is considered, it was deemed important to perform a pilot study to ensure that Penthrox-assisted colonoscopy is feasible and safe in these patients. Although the assessment of patients during recovery by the nursing staff may have been influenced by the fact that the nurses were not blinded to the type of analgesia or sedation used, we had a standardized protocol for assessing and recording time to awake, time to oral intake, time to readiness for discharge, and time to actual discharge. The assessments were based on alertness and vital signs, which are very objective.

Although portable Penthrox inhalation is currently not available anywhere in the world apart from Australasia, applications for its use in Europe and Asia are currently in progress. Given that nitrous oxide is more widely available and has been shown to have comparable analgesic properties in dental procedures [22], a comparison of outcomes with Penthrox and with nitrous oxide in colonoscopy would be clinically relevant and warranted. Although there are no available data on the use of Penthrox inhalation for colonic endoscopic mucosal resection or dissection, it is likely to be feasible, and further evaluation is warranted given that these procedures do not normally cause significant discomfort. Similarly, the application of this modality of analgesia during other upper gastrointestinal endoscopic procedures has not been explored.

#

Conclusions

In patients who have morbid obesity and/or sleep apnea, colonoscopy with patient-controlled inhaled Penthrox is feasible and safe, with a 99 % procedural success rate, high patient satisfaction scores, no respiratory complications, significantly shorter procedural and recovery times, and greater cost-effectiveness. The findings indicate that colonoscopy with Penthrox analgesia in these high risk subjects may facilitate workflow, shorten waiting lists, and improve cost-effectiveness in busy endoscopy units, and the benefits warrant further evaluation in a large randomized trial.

#
#

Competing interests: None

Corresponding author

Nam Q. Nguyen, MD
Department of Gastroenterology and Hepatology