Introduction
Colonoscopy is the gold standard technique in the investigation of colonic diseases,
especially for the prevention and detection of colorectal neoplasia [1]
[2]. In most Western countries, the procedure is performed with the patient under conscious sedation induced with a combination of fentanyl and midazolam [2]
[3]
[4]
[5]
[6], administered by the endoscopist. The major risks of conscious sedation are respiratory
depression, cardiorespiratory arrest, and a prolonged recovery time [3]
[5]. Predisposing factors that can substantially increase the risk for cardiorespiratory
adverse events after sedation are patient co-morbidities, particularly morbid obesity
(body mass index [BMI] > 35 kg/m2), obstructive sleep apnea (OSA), and cardiorespiratory disease [3]
[5]. Given that the risk for cardiorespiratory complications associated with conventional
sedation administered by the colonoscopist is substantially high in these patients,
it is recommended that the patients be assessed and the sedation be administered during
colonoscopy by a dedicated anesthesiologist [3]. In most centers in Australia, including our hospital, colonoscopy in these high
risk patients is performed in patients on anesthesia-assisted lists; the level of
sedation is often deep, achieved mainly with propofol with or without small doses
of benzodiazepines and opioid. On infrequent occasions, general anesthesia with airway
intubation is required to ensure airway protection during the procedure.
Recently, our group reported the successful use of portable inhaled methoxyflurane
(Penthrox; Medical Developments International, Springvale, Victoria, Australia); 3 mL
per inhaler) as a form of patient-controlled analgesia for colonoscopy in unselected,
medically fit subjects. In this randomized trial [7], the colonoscopic outcomes as well as the pain and anxiety scores of patients who
received Penthrox inhalation were comparable with the scores of those who received
conventional sedation. Furthermore, it was noted that respiratory depression did not
occur in the Penthrox group, whereas it did occur in the sedation group (0 vs. 4 %,
P < 0.05) [7].
Methoxyflurane is a volatile anesthetic gas that exhibits uniquely powerful analgesic
and anxiolytic effects at well below full anesthetic doses. Its use in general anesthesia,
however, was discontinued in the early 1970 s [8]
[9] because of issues with nephrotoxicity. The drug was subsequently modified to be
administered via a portable inhaler and used as an analgesic in the prehospital setting.
The dose is limited to 3 mL per inhaler, which is well below the doses associated
with renal injury. It has been used in more than 5 million outpatients with an excellent
safety profile [10]
[11]. Given the history of possible nephrotoxicity [8]
[9], it is recommended that the drug not be used in conjunction with other nephrotoxic
drugs, such as aminoglycosides and tetracyclines.
Because inhalation is the route of administration of methoxyflurane, the need for
an intravenous cannula is avoided, and therefore portable Penthrox has been widely
used in the Australasian community by ambulance services in the prehospital setting
to relieve the pain of limb and musculoskeletal injuries, chest and abdominal pain,
and the pain of back and spinal injuries [10]
[12]
[13]
[14]. The maximum recommended dose is 6 mL (2 inhalers) per day or 15 mL (5 inhalers)
per week because of the risk for cumulative dose-related nephrotoxicity [10]. The amount of drug administered is controlled by the patient via the frequency
and depth of inhalation. The onset of action is rapid and can be noticed after 3 to
6 breaths. Each inhaler (3 mL) provides analgesia for approximately 30 minutes [10]. Given that inhaled Penthrox causes no respiratory depression, we hypothesized that
it might be an attractive alternative approach, in terms of feasibility and safety,
to analgesia during colonoscopy in patients at high risk for respiratory depression.
The aim of this prospective study was to compare the feasibility, safety, and impact
on post-procedural care of Penthrox with those of anesthesia-assisted deep sedation
(AADS) for analgesia during colonoscopy in subjects with morbid obesity and/or OSA.
Patients and methods
Subjects
All subjects with morbid obesity (BMI ≥ 35 kg/m
2
) and/or OSA who were referred to the tertiary endoscopic center of the Royal Adelaide
Hospital for colonoscopy between June 2013 and June 2014 were included. Inclusion
criteria were age 18 to 75 years, the ability to give informed consent, and the ability
to understand adequately the use of the Penthrox Inhaler. All subjects underwent screening
blood tests to check liver and renal function and were excluded if any of the results
were abnormal. Exclusion criteria were the following: (i) known history of liver or
renal disease, (ii) hypersensitivity to fluorinated agents, (iii) previous head injury,
(iv) difficulty in following instructions (including language barrier), (v) concurrent
use of any potentially nephrotoxic drugs (e. g., aminoglycosides or tetracyclines),
and (vi) a personal or a family history of malignant hyperthermia.
A subject was withdrawn from the study if an adverse event occurred, the subject wished
to withdraw, or the presence of significant pain made it necessary for the subject
to request extra analgesia (fentanyl) and/or sedation (midazolam). The study was approved
by the Human Research Ethics Committee of the Royal Adelaide Hospital, and written
consent was obtained from all patients. All authors had access to the study data and
reviewed and approved the final manuscript.
Study protocol
Patients with morbid obesity/OSA who were referred to our unit for colonoscopy between
June 2013 and June 2014 were invited to participate in the study and were given the
choice of either AADS or sedation with Penthrox inhalation. The analgesic/sedative
approach for the colonoscopy was determined by the patient’s preference. To minimize
technical variability, colonoscopies were performed only by a consultant gastroenterologist.
All colonoscopies were performed with standard technique and carbon dioxide insufflation.
Procedures were deemed complete if the cecum or terminal ileum was reached. For those
who underwent colonoscopy with Penthrox inhalation, liver and renal function tests
were repeated 1 month after the procedure.
After a subject had agreed to participate in the study, his or her levels of pain
and anxiety were assessed in the waiting room before colonoscopy with the visual analogue
scale (VAS) [7]
[15] and the Spielberger state-trait anxiety inventory, form Y (STAI Y-1) [7]
[16]
[17], respectively. Intravenous access was implemented only in subjects receiving AADS,
not those receiving Penthrox. Throughout the procedure, the patient's vital signs,
oxygen saturation, and hemodynamics were monitored closely and recorded every 3 minutes
by a registered nurse, as were signs of excessive sedation, such as drowsiness, pallor,
and unresponsiveness. Continuous supplementary oxygen was given only to subjects who
received AADS, not those who received Penthrox. Hypotension was defined as a reduction
in systolic blood pressure to below 80 % of baseline and/or below 100 mmHg [7]
[18]. A heart rate over 100 beats per minute was defined as tachycardia. Respiratory
depression was defined as the need for a high flow oxygen supply (8 – 10 L) because
of oxygen desaturation to below 90 % (SpO2 < 90 %) that continued for more than 20 seconds [7]
[19]. Patients in both groups were encouraged to increase their respiration rate when
oxygen desaturation occurred.
Details of the colonoscopy procedure, such as duration, time to reach the cecum, need
for endoscopic therapy (i. e., polypectomy, argon plasma coagulation), and the occurrence
of complications or adverse events, were recorded. The endoscopist was also asked
to complete a questionnaire to assess each patient’s levels of pain, anxiety, and
cooperation as well the level of technical difficulty related to the colonoscopy.
In recovery, the patient’s vital signs, alertness, mental state, and abdominal symptoms
were monitored. Once patients were alert and able to obey commands appropriately,
they were allowed to sit up in bed and resume oral intake. At this time, the patients
were asked to complete a questionnaire to assess their current levels of pain and
anxiety, and to assess retrospectively their pain and anxiety during the colonoscopy.
The patients were then assessed for their ability to be discharged home. They were
asked to report any adverse events occurring up to 30 days after study participation.
The research nurse contacted all patients at 24 to 48 hours and at 30 days after the
colonoscopy to check for the occurrence of any adverse events related to either the
drugs or the colonoscopy.
Anethesia-assisted deep sedation
AADS was provided by the anesthesia team, which consisted of a qualified anesthesiologist
and an anesthesia nurse. Depending on the anesthesiologist's preference, a small intravenous
bolus injection of opioid (fentanyl or remifentanil [Ultiva; Bioniche Pharma]) and
midazolam was often given at the initiation of sedation. Thereafter, an initial bolus
of propofol (0.5 mg/kg of body weight) was given intravenously. Sedation was maintained
with repeated doses of 10 to 20 mg of propofol or as an infusion based on the patient’s
body weight. The goal was deep sedation, based on American Society of Anesthesiologists
levels and the Observer's Assessment of Alertness/Sedation Scale [20], on which a purposeful response to a painful stimulus (e. g., a trapezius squeeze)
but failure to respond to verbal or light tactile stimuli indicates deep sedation.
Penthrox inhalation
With specific instruction from a dedicated research nurse, the subject was asked to
inhale slowly and gently through the Penthrox Inhaler for approximately 2 minutes
to become accustomed to its sweet smell. Once the colonoscopy had started, the subject
was encouraged to inhale more deeply to optimize drug delivery and obtain sufficient
analgesia. In instances when Penthrox did not provide sufficient analgesia or at the
patient’s request, the procedure was terminated early and rescheduled to be done with
an AADS approach.
Measured outcomes
Primary end points were (i) the rate of adverse events and (ii) the recovery time.
Given that the discharge of patients from endoscopy units is often prolonged by issues
related to delayed pickup, need for transportation, and other nonmedical issues, both
time to “actual discharge” and time to “ready for discharge” were recorded. Time to
“ready for discharge” was defined as the time until the caring nurses and physician
deemed it to be “medically safe” for the patient to leave the endoscopy unit, whereas
time to “actual discharge” was the time until the patient left the endoscopy unit.
Secondary end points were (i) the successfully completed colonoscopy rate, (ii) the
pain and anxiety scores during colonoscopy, (iii) the polyp detection rate, (iv) the
total colonoscopy procedural time, (v) changes in renal and liver function test results,
(vi) cost-effectiveness, and (vii) patient satisfaction.
Cost analysis
The cost analysis of each colonoscopy for patients in both groups was undertaken by
a professional health economist, who used data related to the cost of the consumables,
drugs, and labor required to perform a colonoscopy as well as the time taken to complete
the colonoscopy by each approach. Specifically, the labor cost per patient was estimated
by dividing the total cost of all staff involved in operating the unit for a typical
day by the estimated number of colonoscopies that could be undertaken in the morning
and afternoon sessions with either Penthrox or AADS.
Data analysis
Based on our previous study [7], power calculation with a two-sided significance level of 0.05 and a power of 90 %
was performed, and a sample size of at least 50 subjects in each arm was required
to demonstrate the differences between the outcomes of the two approaches. Data were
expressed as mean ± standard deviation (SD). Fisher’s exact test was used for the
comparison of categorical data and independent Student’s t test for continuous data. Analyses were performed with GraphPad Prism 6 statistical
software (GraphPad Software, La Jolla, California, USA). A P value of less than 0.05 was considered to indicate statistical significance.
Results
Over 12 months, 140 high risk subjects with morbid obesity and/or OSA were recruited,
of whom 85 (61 %) underwent colonoscopy with the Penthrox Inhaler and 55 (39 %) with
AADS. The groups did not differ in gender, BMI, proportion of patients with OSA, pre-colonoscopy
pain and anxiety scores, colonoscopist perception of patient anxiety level, and indications
for colonoscopy ([Table 1]).
Table 1
Comparison between demographics, initial pain and anxiety scores, sedative doses,
and procedural indications of patients who received anesthesia-assisted deep sedation
(AADS) and those of patients who received Penthrox analgesia during colonoscopy.
|
AADS (n = 55)
|
Penthrox (n = 85)
|
P value
|
|
Age, mean ± SD, y
|
54.9 ± 1.1
|
57.2 ± 1.1
|
0.68
|
|
Male-to-female ratio
|
27:28
|
46:39
|
0.35
|
|
Body mass index, mean ± SD, kg/m2
|
37.8 ± 0.5
|
40.2 ± 0.9
|
0.45
|
|
Patients with OSA, n (%)
|
33 (60)
|
41 (48)
|
0.36
|
|
VAS pain score (0 – 10) before colonoscopy, mean ± SD
|
0.52 ± 0.13
|
0.46 ± 0.10
|
0.84
|
|
STAI-Y anxiety score, mean ± SD
Before colonoscopy
Total score
Nervousness score
After colonoscopy
Total score
Nervousness score
|
45.7 ± 0.9
15.8 ± 0.5
46.9 ± 0.9
15.2 ± 0.5
|
46.1 ± 0.6
14.9 ± 0.5
48.0 ± 0.8
15.3 ± 0.5
|
0.86
0.79
0.48
0.96
|
|
Colonoscopist's perception of patient’s anxiety state (VAS), mean ± SD; 0, very calm;
100, most anxious
|
60 ± 3
|
53 ± 3
|
0.24
|
|
Indications for colonoscopy, n
Polyp surveillance
Bowel cancer screening (including positive FOBT)
Rectal bleeding
Abdominal pain
IBD-related
Diverticular disease-related
Investigation of diarrhea
Anemia, including iron deficiency anemia
Unexplained weight loss
|
14
10
7
3
8
2
5
4
2
|
22
28
12
5
6
3
2
5
2
|
0.58
0.87
0.82
0.74
0.69
0.90
0.68
0.59
0.47
|
SD, standard deviation; OSA, obstructive sleep apnea; STAI-Y, state-trait anxiety
inventory, form Y; VAS, visual analogue scale; FOBT, fecal occult blood test; IBD,
inflammatory bowel disease.
All colonoscopies with Penthrox inhalation were successful with the use of only 1
inhaler (i. e., 3 mL of methoxyflurane) and did not require any additional administration
of intravenous midazolam, fentanyl, fluid therapy, or oxygen supplementation. None
of the Penthrox-assisted colonoscopies was discontinued prematurely because of procedural
discomfort. In contrast, all the subjects with AADS received intravenous fluid and
oxygen therapy during and after colonoscopy ([Table 2]). In the patients who had colonoscopy with AADS, 286 ± 19 mg of intravenous propofol
was used over a mean procedural time of 25.9 ± 1.7 minutes, with the additional use
of midazolam in 44 %, fentanyl in 60 %, and remifentanil in 12 % of subjects.
Table 2
Comparison of procedural performance characteristics and adverse events in patients
who received anesthesia-assisted deep sedation (AADS) and those who received Penthrox
analgesia for colonoscopy.
|
AADS
(n = 55)
|
Penthrox (n = 85)
|
P value
|
|
In-room preparation time, mean ± SD, min
|
16.5 ± 1.8
|
4.8 ± 0.2
|
< 0.01
|
|
Cecal arrival time, mean ± SD, min
|
11.6 ± 1.0
|
8.8 ± 0.5
|
< 0.01
|
|
Total colonoscopy time, mean ± SD, min
|
25.9 ± 1.7
|
18.4 ± 0.9
|
< 0.01
|
|
Total in-room time, mean ± SD, min
|
51.6 ± 1.3
|
23.9 ± 0.9
|
< 0.001
|
|
Patients with polypectomy, n (%)
|
23 (44)
|
46 (54)
|
0.18
|
|
Patients with incomplete colonoscopy, n (%)
due to severe sigmoid diverticulosis
due to significant looping
due to poor preparation
|
3 (5)
1
1
1
|
1 (1)
0
1
0
|
0.39
|
|
Patients requiring intravenous fluid therapy during and after colonoscopy, n (%)
|
55 (100)
|
0[1]
|
< 0.001
|
|
Patients requiring oxygen supplementation to maintain SaO2 > 90 %, n (%)
|
55 (100)
|
0[1]
|
< 0.001
|
SD, standard deviation.
1
P < 0.01 vs. AADS.
Procedural success
Although there was no difference between the cecal intubation rates of the two groups
(Penthrox vs. AASD: 99 % vs. 95 %, P = 0.30), the in-room preparation time (4.8 ± 0.2 vs. 16.5 ± 1.8 minutes, P < 0.01), cecal arrival time (8.8 ± 0.5 vs. 11.6 ± 1.0 minutes, P < 0.01), and total colonoscopy time (18.4 ± 0.9 vs. 25.9 ± 1.7 minutes, P < 0.01) were significantly shorter in the Penthrox group than in the AADS group. There
were no differences between the rates of polyp detection and polypectomy in the two
groups ([Table 2]). In 1 of the 4 colonoscopies that failed to reach the cecum, failure was related
to poor pain relief; the reasons for failure are summarized in [Table 2]. Of these patients, 3 had subsequent computed tomographic colonography (2 AADS and
1 Penthrox) and 1 had a second colonoscopy after extended bowel cleansing.
Adverse events and impact on liver and renal function
Although intravenous fluid therapy and oxygen supplementation were given to all patients
who had AADS, there were more intraprocedural events of hypotension (42 % vs. 1 %),
respiratory depression (26 % vs. 0 %), and tachyarrhythmia (15 % vs. 1 %) in the patients
who received AADS than in those who received Penthrox inhalation ([Fig. 1]). Overall, intraprocedural cardiorespiratory adverse events were substantially more
frequent in the AADS group than in the Penthrox group (56 % vs. 2 %, P < 0.001). At telephone follow-up 24 hours and 30 days after colonoscopy, no patient
reported being readmitted or was found to have been readmitted to the hospital because
of abnormal renal or liver function test results indicating nephrotoxicity or hepatotoxicity.
Penthrox inhalation did not result in any increases in serum levels of creatinine,
liver enzymes, or bilirubin after 1 month ([Table 3]).
Fig. 1 Differences between the cardiorespiratory complication rates of patients who had
colonoscopy with anesthesia-assisted deep sedation and those of patients who had colonoscopy
with Penthrox analgesia.
Table 3
Comparison of parameters of renal and liver function before and 1 month after Penthrox
inhalation for colonoscopy.
|
Before Penthrox
|
After Penthrox
|
P value
|
|
Renal function
Creatinine, mean ± SD, µmol/L (NR 50 – 120)
|
70.5 ± 2.7
|
73.1 ± 3.3
|
0.77
|
|
Liver function
Bilirubin , mean ± SD, µmol/L (NR 2 – 24)
GGT, mean ± SD, U/L (NR < 60)
ALP, mean ± SD, U/L (NR 30 – 110)
AST, mean ± SD, U/L (NR < 45)
ALT, mean ± SD, U/L (NR < 55)
|
10.5 ± 1.0
49.7 ± 4.5
83.9 ± 4.0
27.2 ± 2.5
31.5 ± 4.2
|
10.0 ± 0.9
46.8 ± 6.1
86.6 ± 4.5
25.0 ± 1.3
27.5 ±2.2
|
0.89
0.62
0.43
0.58
0.28
|
SD, standard deviation; NR, normal range; GGT, gamma-glutamyltransferase; ALP, alpha-fetoprotein;
AST, aspartate aminotransferase; ALT, alanine aminotransferase.
Recovery and discharge time
The patients who received Penthrox had significantly shorter times to being awake,
oral intake, readiness for discharge, and actual discharge than did those who received
AADS ([Fig. 2]). Overall, the patients who had Penthrox were ready to be discharged at least 60
minutes earlier than those who had AADS.
Fig. 2 Differences between the recovery and discharge times of patients who received anesthesia-assisted
deep sedation (AADS) and those of patients who received Penthrox analgesia for colonoscopy.
Cost analysis
In the morbidly obese patients, the cost of colonoscopy with Penthrox inhalation was
less than half that of colonoscopy with AADS ($ 331.79 AUD vs. $ 725.41 AUD). The
significantly shorter procedural time with Penthrox was estimated to have allowed
more procedures to be performed in patients on a 4-hour list (8 vs. 4 cases, P < 0.05). Based on these outcomes, as well as the lower incidence of adverse events,
the use of Penthrox for colonoscopy was found to be a “superior” strategy for these
high risk subjects, with a cost saving of approximately $ 400 AUD for each additional
complication avoided.
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]).
Fig. 3 Differences between the visual analogue scale (VAS) pain scores before, during, and
after colonoscopy of patients who had anesthesia-assisted deep sedation (AADS) and
those of patients who had Penthrox analgesia for colonoscopy.
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.
