Endoscopy Practice and Safety
Editor: Peter B. Cotton ed.
3. Sedation, Analgesia, and Monitoring for Endoscopy
John J. Vargo
This chapter will review the definitions encompassing the spectrum of sedation as outlined by the American Society of Anesthesiologists.
Particular emphasis will be given to the reversal of deeper than intended states of sedation. Extended monitoring of respiration
with transcutaneous carbon dioxide measurement and capnography will then be reviewed. The application of bispectral index
(BIS) monitoring, which represents a complex mathematical evaluation of electroencephalographic parameters of frontal cortex
activity will then be reviewed. Trials utilizing topical anesthetics, the bolus administration of meperidine and midazolam
via dosing nomograms as well as the use of droperidol will then be addressed. The emerging use of the anesthetic agent propofol
by non-anesthesiologists for endoscopy will then be critically reviewed.
'Sedation and analgesia' represents a continuum ranging from minimal sedation or anxiolysis through general anesthesia. In this era of open access
endoscopy, candidacy for sedation and analgesia still must take into account a thorough preprocedure assessment including
a history of present illness, past medical history, and a physical examination . New practice guidelines put forth by the American Society of Anesthesiologists Committee for Sedation and Analgesia by Non-Anesthesiologists,
have classified both moderate and deep sedation and analgesia to the continuum of sedation (Fig. 1) .
In most endoscopic cases, moderate sedation is the goal. This is defined by the patient giving a purposeful response after
verbal or tactile (not painful) sensation, and no compromise of the patient's airway, ventilation, or cardiovascular function.
In this state, patients may respond only to painful stimuli. Additionally, the patient's airway and spontaneous ventilation
may become compromised, and hence, personnel must be designated for the complete and uninterrupted observation of the patient's
respiratory and cardiovascular status.
An important component of these guidelines is that the endoscopy team must have the ability to rescue the patient from deeper
than expected levels of sedation/analgesia.
Advances in monitoring during sedation
Cardiorespiratory complications are a leading cause of morbidity and mortality associated with gastrointestinal endoscopy.
Both ventilatory depression and oxygen desaturation stemming from the medications used to achieve sedation and analgesia are
thought to be important risk factors for these complications.
Standard pulse oximetry
Pulse oximetry has become a defining standard of care during sedation and analgesia for endoscopy, owing to the evidence that clinical observation alone is inaccurate
in the detection of hypoxemia and that supplemental oxygen can minimize the degree of desaturation and hopefully its deleterious
effects. To date, neither pulse oximetry nor supplemental oxygen administration has yet been shown to decrease the severity
or incidence of cardiopulmonary complications.
It is important to point out that pulse oximetry does not measure alveolar hypoventilation, which is measured by hypercapnea
or a rise in arterial carbon dioxide pressure. Although oxygen administration may prevent hypoxemia and its deleterious effects, it will not detect the development of hypercapnea.
Deleterious consequences of alveolar hypoventilation include myocardial depression, acidosis, intracranial hypertension, narcosis,
and arterial hypertension or hypotension.
Transcutaneous CO2 monitoring
Transcutaneous CO2 monitoring (PtCO2) is a non-invasive method for measuring arterial CO2. An electrode is placed on the skin, which is heated to 'arterialize' the microcirculation. CO2 then diffuses through the skin and into an electrolyte solution at the skin/electrode interface, and so produces carbonic acid. A pH reading is then taken and the CO2 value is obtained via the Henderson-Hasselbach equation.
Nelson et al. randomized 395 patients undergoing ERCP to standard monitoring coupled with transcutaneous CO2 monitoring guiding sedation and analgesia (group 1) or to standard monitoring alone in which the endoscopist was blinded
to the PtCO2 data (group 2) . Significantly more group 2 patients experienced carbon dioxide retention > 40 mmHg above baseline values. Predictors for peak PtCO2 included baseline PtCO2 value, the use of naloxone, the maximum fall in oxygen saturation via pulse oximetry, maximum supplemental oxygen rate, and
the combination of a benzodiazepine and an opioid for sedation and analgesia. There was a poor correlation between clinical
observation and objective measures of ventilation.
Capnography is based on the principle that carbon dioxide absorbs light in the infrared region of the electromagnetic spectrum. Quantification of the absorption leads to the generation of a curve, which represents a real-time display of the patient's
respiratory activity. In a case series of 49 patients undergoing prolonged upper endoscopic procedures, capnography was found
to be more sensitive than pulse oximetry or visual assessment in the detection of apneic episodes . In a series of 80 colonoscopy patients who were randomized to undergo the procedure with and without supplemental oxygen,
extended monitoring with capnography was employed . The endoscopist and nursing personnel were blinded to the capnography data. Though the number of apneic events was similar
between the two groups, significantly more episodes of apnea were missed in the group receiving oxygen (7% vs. 42%, p < 0.001). Moreover, significantly more patients receiving supplemental oxygen received sedation following an apneic episode.
Capnography has also been utilized to allow the safe titration of propofol by a qualified gastroenterologist during ERCP and
Endoscopic Ultrasonography (EUS).
Bispectral index (BIS) monitoring represents a complex mathematical evaluation of electroencephalographic parameters of frontal
cortex activity, corresponding to varying levels of sedation. The BIS scale varies from 0 to 100 (0, no cortical activity
or coma; 4060, unconscious; 7090, varying levels of conscious sedation; 100, fully awake). Theoretically this index should reflect the same level of sedation
regardless of the medications used, except for ketamine. In a preliminary observational study involving 50 patients undergoing
ERCP, colonoscopy, and upper endoscopy, BIS levels were found to correlate with a commonly used score for the degree of sedation
. A BIS range of 7585 demonstrated a probability of >= 96% that the patient would exhibit an acceptable sedation score. However, there was increasing variability of the BIS score
with deeper levels of sedation. Additionally, there was no correlation between the BIS score and standard physiologic parameters
such as pulse oximetry, blood pressure, or heart rate.
Topical anesthetics: are they worth the effort?
Prospective, randomized controlled trials addressing the use of topical anesthetics during upper endoscopy for improved patient
tolerance have been mixed (Fig. 2) mixed . Existing study designs differ in the presence of double-blinding, the type of topical anesthetic employed, endoscope diameter,
and the use of conscious sedation. Soma et al. recently conducted a study of 201 Japanese patients who were randomized to receive either 2% lidocaine or placebo . No conscious sedation was employed. Multivariate analysis found that the use of topical anesthesia reduced the relative
risk of discomfort by 44% (95% CI: 0.311.01). Patient age less than 40 was associated with a higher relative risk of discomfort (RR 2.22, 95% CI: 1.044.74). Subgroup analysis found that patients less than 40 years of age who were pretreated or those undergoing endoscopy for
the first time benefited most from topical anesthesia.
Titration vs. bolus administration of sedation and analgesia
Practice guidelines call for the call for the careful titration of sedative medications using small, incremental doses and
allowing sufficient time between doses to assess effect . Morrow et al.,utilizing a dosing nomogram based on the age and weight, performed a prospective, randomized, double-blind trial comparing
bolus vs. titration dosing of meperidine and midazolam for outpatient colonoscopy . Exclusion criteria included age < 18 years or > 65 years, active use of narcotics or benzodiazepines, pulmonary disease requiring home oxygen, end-stage liver or kidney disease,
and a New York State Heart Association class III or IV congestive heart failure. The groups were well matched in terms of
demographics. Patient tolerance scores were equivalent between both groups. Physician time was significantly shorter in the
bolus group (20.1 vs. 32.2 min, p < 0.001). Episodes of oxygen desaturation occurred significantly more often in the titration group. Further evaluation of bolus
administration is needed for patients undergoing upper endoscopy and prolonged therapeutic procedures such as ERCP and endoscopic
Propofol is classified as an ultrashort acting sedative hypnotic agent that provides amnesia, but minimal levels of analgesia.
Propofol rapidly crosses the bloodbrain barrier, and causes a depression in consciousness that is thought to be related to a potentiation of the γ-aminobutyric acid activity in the brain. Typically, the time from injection to the onset of hypnosis is 3060 s, which is essentially the time for one armbrain circulatory pass . The plasma half-life ranges from 1.3 to 4.13 min. Dose reduction is required in patients with cardiac dysfunction and in the elderly due to decreased clearance of the
drug. Propofol potentiates the effects of narcotic analgesics and sedatives such as benzodiazepines, barbiturates, and droperidol
and therefore the dose requirements may be reduced.
Problems with propofol
Pain at the injection site is the most frequent local complication, occurring in up to 5% of patients.
Episodes of severe respiratory depression necessitating temporary ventilatory support have occurred in large series utilizing
propofol for endoscopic procedures . Capnography has been successfully used to graphically assess the respiratory activity in patients receiving gastroenterologist-administered
propofol for therapeutic upper endoscopy [19,20]. Monitoring with graphic assessment of respiratory activity detected early phases of respiratory depression, resulting in
a timely decrease in the propofol infusion without significant hypoxemia, hypercapnea, hypotension, or arrhythmias.
Specific training for use of propofol
Propofol has a narrow therapeutic windowits administration, even in the hands of an anesthesiologist, does not prevent the occurrence of severe respiratory compromise
. It cannot be overemphasized enough that personnel specifically trained in the administration of propofol with expertise
in emergency airway management need to be present during the procedure, constantly monitoring the patient's physiologic parameters.
In this author's opinion, the use of propofol usually results in a state of deep sedation and analgesia. It is our practice
to utilize nasopharyngeal capnography to detect early signs of respiratory depression such as apnea, which would otherwise,
go undetected by standard pulse oximetry [19,20]. The presence of a person who is dedicated to the administration of propofol and the uninterrupted monitoring of the patient's
physiologic parameters is another important requirement [19,20].
Contraindications of propofol
Specific contraindications to propofol administration include allergies to propofol or any of the emulsion components, pregnant
or lactating females, and patients with an American Society of Anesthesiologists IV or V physical status classification .
Clinical trials of propofol
Propofol or midazolam?
In a randomized study, 90 patients received a bolus administration of propofol or midazolam both before and during upper endoscopy
. The propofol treatment arm was superior in terms of patient tolerance, maximum level of sedation achieved, and shorter recovery
room times. In contrast, a smaller series of 40 patients randomized to receive the same medications before upper endoscopy
found that propofol provided a more rapid recovery room time, but was also associated with pain at the injection site, reduced
patient acceptance, and a shorter amnesia span .
Two randomized, controlled trials have compared propofol alone to midazolam specifically for ERCP [16,23]. In one study, an anesthesiologist administered propofol; in the second study, an assisting physician who was not involved
in the endoscopic procedure administered propofol. In both studies, patients receiving propofol exhibited significantly improved
quality of sedation and shorter recovery times. Untoward effects such as hypotension and hypoxemia occurred equally in both
treatment groups. However, it is important to point out that in both series, one patient in the propofol group developed prolonged
apnea that necessitated discontinuation of the procedure and temporary ventilatory support.
Upper endoscopy and colonoscopy
Koshy et al. compared the combination of propofol and fentanyl to midazolam and meperidine in a non-randomized group of 274 patients undergoing
upper endoscopy and colonoscopy . Propofol and fentanyl led to better patient comfort and deeper sedation without an increase in untoward side-effects. There
was not, however, a significant difference in the recovery times between the two groups.
Propofol with or without midazolam
A prospective, randomized trial compared the efficacy of propofol alone to the combination of midazolam and propofol in 239
patients undergoing therapeutic upper endoscopy or ERCP . While sedation efficacy and the incidence of hypotension and hypoxemia were comparable in both groups, patients receiving
midazolam and propofol exhibited a significantly longer mean recovery time.
Patient-controlled administration of propofol
Patient-controlled sedation and analgesia (PCS) with propofol has recently gained in popularity. Kulling et al. randomized 150 patients to three sedation arms: PCS with propofol/alfentanil (group I), continuous propofol/alfentanil infusion (Group II), and nurse-administered midazolam/meperidine (Group III) . Group I exhibited a higher degree of patient satisfaction and more of a complete recovery at 45 min when compared to conventional sedation and analgesia. In a similar study, Ng and colleagues randomized 88 patients undergoing
colonoscopy to PCS with propofol alone or midazolam . Patients receiving propofol PCS exhibited significantly shorter recovery times (43.3 min vs. 61.0 min) and improved satisfaction with overall level of comfort. PCS for ERCP however, has not been as successful. In a pilot
study utilizing a software system designed to deliver a 'ceiling' for the plasma propofol concentration, only 80% of patients received a safe and fully effective sedation .
The safety and experience with propofol administered by registered nurses has been addressed in a case series including 2000
patients undergoing elective EsophagoGastroDuodenoscopy (EGD) and/or colonoscopy . All patients were ASA class I or II. No extended monitoring was used and all patients received 3 L of nasal cannula oxygenation.
The propofol dosage was an initial bolus of 2040 mg, followed by 1020 mg to maintain sedation. Five episodes of oxygen desaturation to < 85%, four of which required temporary mask ventilation,
occurred. Four of these episodes occurred during upper endoscopy. Propofol has been compared in a prospective, randomized
trial to midazolam and meperidine in 80 ASA Class I or II outpatients undergoing elective colonoscopy . Propofol was superior in terms of the rapidity and depth of sedation, recovery times, and overall satisfaction. Additionally,
patients receiving propofol exhibited improved recovery of psychometric function
Vargo et al. completed a randomized, controlled trial of gastroenterologist-administered propofol vs. meperidine and midazolam for elective
ERCP and EUS . In this study, a separate gastroenterologist, who was trained in propofol administration, was utilized. Additionally, capnography
was used to detect apnea or hypercapnea, and thus adjust the propofol dosing accordingly. This study was also the first to
address issues of cost effectiveness from an institutional standpoint. Visual analog scales (VAS) were used to address patient
and endoscopist satisfaction. Patients randomized to propofol exhibited a faster mean recovery time (18.6 vs. 70.5 min), could perform independent transfer following the procedure and were able to achieve a baseline return to a baseline
food intake and activity level (71% vs. 16%). Cost effectiveness data with a sensitivity analysis found that nurse-administered
propofol to be the dominant strategy, when compared to standard sedation and analgesia.
Droperidol, a narcoleptic of the butyrophenone class, produces a dissociative state while enhancing the effects of other sedative
medications. It is routinely used in some centres as a premedication for patients undergoing ERCP. Other indications include:
a history of alcohol use or withdrawal, narcotic use, and a history of paradoxical agitation to conventional conscious sedation.
In a retrospective study involving 1102 procedures, droperidol was found to be a safe adjunct to the combination of narcotics
and benzodiazepines .
In a prospective, double-blind, placebo-controlled trial, in 140 patients undergoing elective upper endoscopy, droperidol
led to a 10% reduction in procedure time and significantly reduced meperidine and midazolam requirements . However, four patients in the droperidol group received naloxone for excessive drowsiness. Rizzo et al. addressed the use of different doses of droperidol in patients undergoing EUS . When compared to placebo, 5 mg of droperidol led to significantly less medication costs, while at the same time, not affecting the mean recovery time.
Complications attributable to droperidol occurred in 1.5% of procedures and was comprised mainly of hypotension, responsive
to IV fluids. Reports of QT interval prolongation and torsades des pointes have occurred, at or below the recommended doses
resulting in death. Some of these cases have occurred in patients without risk factors for QT interval prolongation. This
prompted the Food and Drug Administration to issue a 'black box' warning which will severely curtail the use of this drug in the endoscopy suite .
Outstanding issues and future trends
The importance of preprocedural assessment and appropriate monitoring cannot be overemphasized. The endoscopist must have
a thorough knowledge of the pharmacology of the agents used for sedation and the training necessary to recognize and manage
oversedation. Numerous regulatory groups are carefully scrutinizing the practice of sedation and analgesia. It appears that
ventilatory monitoring will be required for at least a subset of our patients. Although both hypercapnea and apnea can be
reliably measured, the most important questions to be answered are: will such monitoring affect patient outcomes, and which
patients are at risk for apnea and alveolar hypoventilation?
The use of propofol for gastrointestinal endoscopy has been shown to be safe in experienced hands. Its narrow therapeutic
window demands that specially trained personnel who are not directly involved in the endoscopic procedure administer it. Controversy
exists over nurse-administered propofol. Currently only a minority of states allow this practice. The use of anesthesia personnel
to administer propofol while safe and increasing the throughput of the endoscopy suite is quite costly. It is doubtful that
third-party payers will approve of this practice on a large scale. Extended monitoring with capnography appears to offer an
advantage over conventional monitoring in that it can detect early phases of respiratory depression, which can allow for a
timely adjustment in the propofol infusion and thus prevent significant respiratory depression. Emerging cost effectiveness
data suggests that propofol is superior to conventional sedation and analgesia, even with the use of added personnel. In the
future, 'smart machines' which utilize software-driven algorithms, based on the physiologic feedback from standard and extended monitoring devices
may lead to the practical, safe, and universal acceptance of propofol in the endoscopy suite.
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