advanced monitoring techniques in gastrointestinal endoscopy

Gastrointest Endoscopy Clin N Am 14 (2004) 335 – 352

Extended/advanced monitoring techniques in gastrointestinal endoscopy Franco Radaelli, MD*, Vittorio Terruzzi, MD, Giorgio Minoli, MD Department of Gastroenterology, Valduce Hospital, Via Dante 11, Como 22100, Italy

Morbidity and mortality related to cardiopulmonary complications continue to be a significant concern during gastrointestinal (GI) endoscopy. Prospective data from the clinical outcome research initiative on 252,577 esophagogastroduodenoscopy (EGD)/colonoscopy patients and 8722 endoscopic retrograde cholangio pancreatography (ERCP)/endoscopic ultrasonography (EUS) patients reported the incidence of significant cardiopulmonary complications was 0.8% and 1.2%, respectively, or about half the total complications associated with GI endoscopy [1]. The true incidence of procedure-related mortality for cardiopulmonary complications is not known because most data are historic or retrospective. A retrospective review of approximately 21,000 procedures using an American Society for Gastrointestinal Endoscopy computer-based management system showed that serious cardiopulmonary complications and death associated with the use of sedation amounted to 5.4 and 0.3 per 1000 procedures, respectively [2]. A large prospective survey of 14,149 upper endoscopies from the United Kingdom reported 30-day procedure-related cardiopulmonary mortality of 0.4 per thousand [3]. The incidence of cardiopulmonary complications of endoscopy does not seem to have declined over the past 20 years despite the increasing routine use of pulse oximetry as a standard part of automated monitoring [4,5]. This is in striking contrast with anesthesia-related deaths, which have dropped to 0.04 per 1000, presumably as a result of better training standards and the widespread adoption of monitoring equipment [6]. These figures imply there is room for improvement in the cardiopulmonary safety of GI endoscopy procedures and explain gastroenterologists’ increasing interest in sedation and monitoring, which, with today’s increasingly interventional endoscopy, have become even more important. ‘‘Sedation and analgesia’’ form a continuum, from minimal sedation (anxiolysis) to general anesthesia [7,8]. * Corresponding author. E-mail address: [email protected] (F. Radaelli). 1052-5157/04/$ – see front matter D 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.giec.2004.01.008

336

F. Radaelli et al / Gastrointest Endoscopy Clin N Am 14 (2004) 335–352

Box 1. Extended/advanced monitoring techniques in GI endoscopy Noninvasive monitoring of ventilation  

Transcutaneous CO2 monitoring Capnography

EEG-based monitoring of sedation depth  

Bispectral Index Scale Narcotrend

Advanced endoscopic procedures, such as therapeutic ERCP and interventional EUS, are frequently lengthy and need the patient’s full cooperation. Sedatives or analgesics are usually titrated throughout the examination on the basis of the endoscopist’s and nurse’s assessment of the patient’s tolerance and compliance with the procedure, with the goal of achieving adequate sedation without compromising cardiopulmonary function. Multiple doses of these agents are often required to complete the procedure successfully, and this occasionally takes the patient further than intended along the continuum, resulting in deep sedation [9]. In this state, ventilation may be inadequate, normal protective reflexes may be lost, and airway patency may be impaired [7]. Any additional sedation may facilitate the transition to general anesthesia and further increase the risk of respiratory problems and adverse outcomes. Objective measures directly indicating the patient’s ventilatory status and the depth of sedation could permit safer titration of sedative/narcotic drugs, so that, for example, further sedation could be withheld if ventilation is inadequate or if a target level of sedation is overshot. Current monitoring shows some limitations in this regard. New advanced techniques, based on noninvasive monitoring of CO2 [10 –13] and electroencephalographic assessment of the brain’s hypnotic status [14,15], have been introduced for standard monitoring including these measures, with the primary aim of providing useful tools for guiding sedation and improving patient care (Box 1). This article looks at the limits of current standard monitoring for GI endoscopy and focuses on the emerging monitoring techniques and their potential use in clinical practice.

Standards of sedation and monitoring for gastrointestinal endoscopy Practice guidelines for sedation and analgesia have been issued by professional societies and national expert peer groups [7,16,17] with the aim of enabling clinicians to provide their patients with the benefits of sedation and analgesia while minimizing the risks. Current guidelines call for continuous monitoring of the patient’s consciousness and ventilatory status to facilitate the recognition

F. Radaelli et al / Gastrointest Endoscopy Clin N Am 14 (2004) 335–352

337

of oversedation and reduce the risk of adverse outcomes associated with sedation/ analgesia. The level of consciousness is typically assessed on the patient’s responsiveness to verbal and standard stimuli because we have no more reliable and objective measures of the depth of sedation. Direct observation of chest wall movements and auscultation are reliable methods for monitoring ventilatory function during sedation and analgesia but are impractical in the endoscopy suite because of the patient’s position during the examination and the darkness of the endoscopy room. Pulse oximetry has become the de facto standard of care for the detection of respiratory depression during endoscopic procedures. In addition, supplemental oxygen is widely used to minimize the degree of oxygen desaturation and its deleterious effect during endoscopy [16,17]. There are limitations, however, to the use of pulse oximetry for respiratory monitoring during sedation/analgesia [18,19]. Pulse oximetry measures arterial oxygen saturation, not alveolar ventilation, which is directly reflected by the arterial carbon dioxide tension (PaCO2) [20]. Significant hypoventilation may occur during GI endoscopy, especially in patients who require deeper sedation for lengthy, complex therapeutic procedures, and it may be undetected by clinical observation or pulse oximetry, particularly when supplemental oxygen is administered [10,11]. Hypoxemia is a relatively late manifestation of apnea related to sedation and analgesia; patients receiving supplemental oxygen may experience prolonged apnea with normal oxygen saturation [13,21]. The inability of pulse oximetry to reflect significant CO2 retention during sedation may have untoward consequences. First, elevation of PaCO2 may cause myocardial depression, arrhythmias, arterial hypotension and hypertension, intracranial hypertension, and narcosis [22,23]. Second, if respiratory depression goes unrecognized, it may be clinically significant in prolonged procedures when additional sedation may raise the risk of further respiratory impairment. Practice guidelines by the American Society of Anesthesiology Committee for Sedation and Analgesia by Non-Anesthesiologists Clinicians stress this important distinction between hypoxemia and alveolar hypoventilation and recommend that an automated ventilatory monitoring device (eg, capnography) be considered for all patients receiving deep sedation and for those receiving moderate sedation/analgesia if adequate observation of ventilatory efforts cannot be ensured [7]. With respect to these recommendations, clinicians should be aware that current standards of monitoring for advanced and prolonged endoscopic procedures are likely inadequate.

Advanced techniques for monitoring of ventilation Transcutaneous CO2 monitoring PaCo2 directly reflects alveolar ventilation, and its measurement remains the mainstay of respiratory monitoring. However, it is an impractical and invasive

338

F. Radaelli et al / Gastrointest Endoscopy Clin N Am 14 (2004) 335–352

method, requiring intermittent arterial blood sampling or intravascular sensors for blood gas analysis [20]. Transcutaneous CO2 (PtcCO2) monitoring is a noninvasive method that accurately reflects arterial PaCO2. PtcCO2 can be monitored with a pH-sensitive glass electrode placed on the skin (usually on the anterior forearm) with a silver-silver chloride reference electrode. CO2, diffusing through the skin and the semipermeable membrane attaching the sensor to the skin, causes the pH changes that result in an electrical signal that is relayed through a cable to a device for further analysis and display. Heating the PtcCO2 sensors to 42
C enhances CO2 diffusion and provides a better correlation of PtcCO2 with PaCO2 [24 –26]. Values for PtcCO2 monitoring correspond closely to those for arterial PaCO2 in patients undergoing upper endoscopy, ERCP, and colonoscopy. This is an accurate method for detecting sustained CO2 retention and alveolar hypoventilation during sedation and analgesia [10]. In a prospective, randomized, controlled trial, Nelson et al [11] investigated whether PtcCO2 monitoring as guidance for the administration of sedatives could prevent respiratory depression during endoscopy. A total of 395 patients undergoing ERCP with sedation and analgesia (a narcotic or a benzodiazepine) with PtcCO2 monitoring in addition to pulse oximetry, blood pressure, ECG, and intensive clinical observation were randomized in two groups. In the first group (PtcCO2-monitored group), results of PtcCO2 monitoring were displayed to the endoscopist team to help guide sedation and analgesia; additional sedatives or analgesics were delayed or withheld for an actively rising PtcCO2 or a PtcCO2 > 25 mm Hg above baseline. In the second group (PtcCO2-blinded group), PtcCO2 data were recorded during the procedure but were not available to the endoscopists for guiding sedation. Comparing episodes of severe CO2 retention, the primary outcome of the study, 2.6% of patients in the PtcCO2-blinded group experienced significant CO2 retention (> 40 mm Hg above baseline) compared with 0 in the monitored group (P = 0.03). Although the overall doses of medications were similar in the two groups, the PtcCO2-monitored group had a significantly shorter mean duration of inadequate sedation, probably due to more precise and timing of the doses during the procedure. Predictors for peak PtcCO2 included baseline PtcCO2, the maximum fall in oxygen saturation via pulse oximetry, the maximum supplemental nasal oxygen rate administered, the use of naloxone, and the combination of a benzodiazepine and an opioid. The authors concluded that the addition of PtcCO2 monitoring prevented severe CO2 retention more effectively than intensive clinical monitoring and pulse oximetry alone. However, this study of 395 patients did not have the power to detect whether PtcCO2 monitoring reduced clinically significant endpoints, such as the need for ventilatory resuscitation. There was only one patient in the PtcCO2-blinded group who experienced a prolonged period of apnea, but there was no need for mechanical ventilatory or cardiopulmonary resuscitation in either group. Therefore, no firm conclusion can be drawn on the utility of this approach in clinical practice. Currently technology for PtcCO2 monitoring is interesting from a research standpoint but is cumbersome and has limitations for clinical routine. Drawbacks include the need for a compressed gas source for daily calibration, a long skin

F. Radaelli et al / Gastrointest Endoscopy Clin N Am 14 (2004) 335–352

339

warm-up phase (10 –15 minutes) for sensor equilibration on each patient before the procedure, risk of skin injury at the sensor site, potential for inaccurate measurements because of poor site selection (eg, edema or obesity), sensor detachment, and vasoconstriction. In addition, PtcCO2 probes are costly (approximately $1000) and fairly fragile. All these limitations make PtcCO2 monitoring impractical for routine clinical use. A step forward in transcutaneous monitoring is achieved with a new single-ear sensor system, providing noninvasive continuous monitoring of arterial oxyhemoglobin saturation and CO2 tension [27,28]. In a pilot study on 10 patients undergoing colonoscopy with propofol, the combined ear sensor was faster than pulse oximetry in detecting changes in oxygen desaturation and useful for adjusting the propofol dose according to changes in CO2 tension [12]. Larger controlled trials are needed to confirm its accuracy and prove the clinical usefulness in endoscopic procedures. Capnography Capnography is a noninvasive technique for measuring the exhaled CO2 concentration and displaying the analog waveform during the respiratory cycle. It operates through an infrared spectrograph on the principle that CO2 absorbs infrared light at a wavelength of 4200 nm. The amount of light absorbed is proportional to the CO2 concentration in the sample. The concentration of CO2 in the patient’s breath peaks near the end of expiration, when its partial pressure approaches the end-tidal CO2—the peak partial pressure. A continuous waveform of CO2 absorption is displayed throughout the ventilatory cycle that provides a real-time display of the patient’s respiratory activity; this is known as a capnograph. Peaks in the capnograph correspond to expiration as the CO2 tension approaches end-tidal CO2. There is a rapid downstroke after the peaks during the inspiration phase (Fig. 1). The continuous measurement and display of end-tidal CO2 concentration makes capnography a sensitive indicator of ventilatory and respiratory effectiveness and helps provide an immediate indication of any change in adequate ventilation [29,30]. Capnography is a standard of care for ventilation monitoring during general endotracheal anesthesia and is mandatory during all procedures involving general anesthesia [31]. Additional applications of end-tidal CO2 monitoring include documentation of endotracheal tube placement during intubation [32], assessment of the integrity of ventilatory circuit in mechanically ventilated patients [33], and judging the effectiveness of cardiopulmonary resuscitation [34]. In all these circumstances, capnography uses a mainstream sensor, interposed between the endotracheal tube and the ventilator circuit. For procedural sedation, the clinical usefulness of noninvasive end-tidal CO2 monitoring has greatly improved with the development of the sidestream circuit. Initially beset with inaccuracies, the technique has been refined and now uses specially adapted oronasal gas sampling devices, giving more accurate end-tidal CO2 measure-

340

F. Radaelli et al / Gastrointest Endoscopy Clin N Am 14 (2004) 335–352

60 mmHg 40 C B 20 A

D

Exhalation phase Inhalation phase Fig. 1. Normal capnography demonstrating respiratory activity. Each waveform represents a single respiratory cycle. The first segment of the waveform is the flat area near the beginning of exhalation (A). This indicates gas exhaled from the dead space. Because this air does not participate in gas exchange, the CO2 level stays flat. The waveform begins to rise sharply as air from the alveoli mixes with the dead space air (B). It plateaus as alveolar gas is exhaled. The end-tidal CO2 level is measured at the end of this plateau (C). At inspiration, the wave quickly returns to baseline (D). The cycle begins again with the next breath. (Note: The y axis represents partial pressure of CO2, expressed in mm Hg.)

ments and enhanced waveform quality in nonintubated patients, with and without oxygen supply [35]. Two studies from the Cleveland Clinic suggest that sidestream capnography is useful for detecting early respiratory depression during endoscopic procedures. The first study [13] was aimed at assessing the frequency of apnea (defined as a cessation of respiratory activity for  30 seconds) and disordered respiration (defined as a 45-second interval that contained at least 30 seconds of cumulative apneic activity) during prolonged upper endoscopy, the sensitivity of pulse oximetry and observation in their detection, and whether capnography could provide any improvement over accepted monitoring techniques. Forty-nine patients undergoing ERCP, EUS, or esophageal stent placement were sedated with midazolam and meperidine and monitored in a standard fashion with pulse oximetry, blood pressure cuff, and visual assessment. An independent physician monitored the ventilatory activity with a pretracheal stethoscope and a sidestream end-tidal CO2 monitoring device. Comparison of simultaneous respiratory rate obtained by capnography and by auscultation with a pretracheal stethoscope showed that capnography was an excellent indicator of respiratory rate. Fifty-four episodes of apnea or disordered respiration episodes occurred in 28 (57%) patients. Only half of these episodes were detected by pulse oximetry, and in all instances hypoxemia occurred on overage 45 seconds after the episode. None of episodes was detected by visual assessment.

F. Radaelli et al / Gastrointest Endoscopy Clin N Am 14 (2004) 335–352

341

In the second study [21], which assessed whether the routine use of supplemental oxygen during endoscopy interfered with the recognition of apnea, capnography was used for extended monitoring in a case series of 80 patients undergoing advanced upper endoscopic procedures. Forty patients began the procedure breathing room air. The remaining patients received supplemental oxygen via nasal cannula. All were monitored in a standard fashion by the endoscopist and the nursing staff, who were blinded to the capnography data. Apnea occurred roughly equally in the two groups, affecting 16 patients in the room air group (47 total apneic events) and 14 patients in the supplemental oxygen group (49 total events). However, in the group receiving supplemental oxygen, significantly more episodes of apnea were missed (93% versus 58%, P < 0.001) and were followed by further sedative doses within 3 minutes of the episodes (37% versus 10%, P < 0.05). Three conclusions can be drawn from these studies: (1) They demonstrate that apneic episodes are common during advanced endoscopy and are infrequently detected with standard monitoring techniques, especially when supplemental oxygen is administered; (2) visual assessment contributes little to detecting apneic events, so guidelines calling for an extra GI assistant in the procedure room to monitor respiration add cost without benefit; and (3) capnography is equivalent to a precordial stethoscope and is far superior to pulse oximetry in the early detection of apnea due to sedation and analgesia. Hypoxemia, as detected with pulse oximetry, can be a late marker of respiratory depression, especially if supplemental oxygen is being administered. Capnography provides a real-time indication of any change in adequate ventilation, before desaturation develops, and can serve as an early warning system for impending respiratory impairment. If these findings are confirmed in controlled trials in unselected patient populations, capnography could be useful, as an adjunct to pulse oximetry and visual assessment of the patient, for preventing respiratory risk in patients undergoing sedation and analgesia for GI endoscopy. Capnography has several advantages over other techniques of ventilation monitoring (eg, transcutaneous CO2), and its interpretation is intuitive; in fact, the pattern of respiratory activity and not the absolute CO2 value is the main feature in its interpretation. Apnea is easily detected with a glance at the monitor because the regular end-expiratory CO2 peaks in the normal capnogram are replaced with a flat line (Fig. 2). The capnography monitoring array is also equipped with an audible alarm indicating the presence of apnea. This technology is inexpensive and is becoming an optional on most physiologic monitors available for use in the endoscopy unit. The cost of using a monitor specifically for graphic assessment of respiratory activity by capnography includes a one-time software activation fee ($150), an in-line dehumidifying module ($23) that is changed weekly, and a disposable special adapted device ($5 per patient) for continuous CO2 sampling from the nose or the mouth, allowing concurrent oxygen administration without dilution of the exhaled sample. These features add to the potential of capnography for routine monitoring in clinical practice.

342

F. Radaelli et al / Gastrointest Endoscopy Clin N Am 14 (2004) 335–352

A

a

b

c

B

a

b c Fig. 2. (A) Physiologic monitoring with electrocardiogram (tracing a), respiratory activity with capnography (tracing b), and pulse oximetry curve (tracing c). Tracing b is a normal capnography curve demonstrating a stable respiratory pattern. (B) Prolonged apnea: Tracing b indicates total absence of respiratory activity.

Capnography for propofol administration Propofol is an ultra-short-acting sedative hypnotic that is attracting attention among gastroenterologists because it provides effective sedation with faster postprocedure recovery than other commonly used sedatives [36 – 42]. Because of its short half-life (t1/2 distribution 2 –4 minutes), propofol has to be continuously titrated by continuous intravenous infusion or intermittent bolus injection to maintain the desired hypnotic effect. The use of propofol by nonanesthesiologists in endoscopic units remains controversial, mostly because of its safety profile. The drug has a narrow therapeutic window, and the transition from moderate

F. Radaelli et al / Gastrointest Endoscopy Clin N Am 14 (2004) 335–352

343

to deep sedation and general anesthesia may easily occur. Furthermore, this agent is a respiratory depressant, and in large endoscopy series its use has been associated with prolonged episodes of apnea requiring temporary ventilatory support [36,43]. Current recommendations for propofol limit its administration to specially trained personnel who are independent of the procedural team and skilled in basic and advanced cardiac life support [9]. Current monitoring standards for endoscopy do not reliably detect early signs of respiratory depression and tend to recognize apnea due to sedation well after its onset. This delay is unacceptable if an agent such as propofol is used for sedation. Could the real-time graphic picture of respiratory activity provided by capnography be useful for safer administration of propofol by a properly trained gastroenterologist during endoscopy? In a case series of 10 patients undergoing advanced upper endoscopic with propofol infusion, Vargo et al [44] investigated the usefulness of capnography, as an adjunct to pulse oximetry, blood pressure cuff, and electrocardiography, for adjusting the propofol dosages. Six patients experienced periods of apnea (defined as a cessation of breathing for 10 seconds or longer) lasting from 10 to 45 seconds. These episodes of apnea preceded any episodes of hypoxemia by a median of 105 seconds (range 30– 180 seconds). An immediate downward titration or temporary discontinuation of the propofol infusion whenever the graphic display of respiratory activity indicated apnea resulted in a rapid normalization of respiratory activity with no significant hypoxemia, hypotension, arrhythmias, or the development of more significant respiratory depression. The safety of gastroenterologist-administered propofol using the extended monitoring provided by capnography was confirmed in a randomized controlled trial specifically designed to compare propofol with midazolam and meperidine for ERCP and EUS [41]. The use of specially trained personnel, together with the graphic assessment of respiratory activity provided by capnography, meant that patients receiving propofol had a safety profile better than those given conventional sedation and analgesia, with superior recovery parameters and similar levels of patient and endoscopist satisfaction. These studies suggest that the use of capnography should be endorsed when propofol is administered by nonanesthesiologists during endoscopy. The true test of its real clinical utility will be whether the information gained translates into improvements in patient care and outcome, but this can only be established by further clinical research.

Electroencephalogram-based techniques for monitoring the depth of sedation Until recently, anesthesiologists lacked the ability to monitor the effects of sedative and anesthetic agents on the brain in terms of ‘‘depth’’ or ‘‘adequacy’’ of anesthesia. Surrogate measures of autonomic activity, such as changes in blood pressure and heart rate, have always been used to evaluate the adequacy of

344

F. Radaelli et al / Gastrointest Endoscopy Clin N Am 14 (2004) 335–352

anesthetic effect. However, these indicators presumably arise from anatomic structures located below the cortex reflex as responses to noxious stimuli and often correlate unreliably with the state of consciousness [45,46]. For more than four decades, anesthesiologists have considered the electroencephalogram (EEG) clinically useful for assessing the depth of sedation, based on the observation that alterations of cerebral function caused by sedatives or anesthetics are reflected in the EEG rhythm. Nevertheless, multiple technical problems and clinical complexities in analyzing the raw EEG have precluded its routine use in a procedure suite or operating room to monitor anesthetic effect. With the advent of microcomputer technology, it is now possible to compress the data from an EEG and obtain various processed derivatives. Numerous EEG parameters, such as spectral edge frequency and median power frequency, have been investigated as indicators of anesthetic effects, but their low sensitivity and specificity in reflecting the depth of anesthesia in individual patients limit their application in clinical practice [47 – 49]. Modern monitors providing processed EEG parameters (eg, the bispectral index scale [BIS] [50,51] and the patient state index [52]) that serve as accurate and clinically validated measures of the hypnotic effect for a broad range of anesthetics and sedatives in different patients have significantly expanded the use of brain monitoring. They are gaining acceptance by anesthesiologists because their application in operating room has proved useful for intraoperative patient assessment and guidance on the precise titration of sedative agents. Their use is also spreading from the strictly perioperative environment to clinical areas where sedative use is common. However, there is little information on the use of the EEG-based techniques for monitoring procedures under conscious sedation. Bispectral index monitoring BIS is a continuously processed EEG parameter specifically developed to provide a reliable measure of depth of consciousness with a variety of anesthetic and sedative agents. BIS technology uses a disposable sensor placed on the patient’s forehead to capture EEG signals that are translated by a sophisticated computer algorithm, constructed by analyzing a large database of EEG recordings during various sedation or anesthetic conditions, into a single number, from 0 to 100, reflecting the patient’s state of hypnosis and responsiveness. A BIS value near 100 represents an ‘‘awake’’ clinical state, and 0 denotes a total lack of cortical activity (ie, isoelectric EEG). In general, the BIS scale reflects the awake state at values exceeding 95, a state of sedation at BIS values of 65 to 85, and a state of depressed arousal suited for general endotracheal anesthesia at BIS values of 40 to 65, and burst suppression patterns become evident at BIS levels below 40 (Fig. 3) [53]. The only commercially available stand-alone BIS monitor is the A-2000 (Aspect Medical Systems, Natick, Massachusetts), although a number of ICU monitors have BIS modules available. In addition to the BIS, the monitors display an indicator of electromyographic (EMG) activity from the patient’s frontalis

F. Radaelli et al / Gastrointest Endoscopy Clin N Am 14 (2004) 335–352

345

100 Awake, Memory Intact

80 Sedation

60 General Anesthesia “Deep” Hypnosis, Memory Function Lost 40 “Near” Suppression Increasing Burst Suppression 20

0

Cortical Silence

Fig. 3. BIS (version 3.0 and higher) is a dimensionless scale from 0 (complete cortical EEG suppression) to 100 (awake). BIS values of 65 to 85 have been recommended for sedation, whereas values of 40 to 65 have been recommended for general anesthesia. (From Johansen JW, Sebel PS. Development and clinical application of electroencephalographic bispectral monitoring. Anesthesiology 2000;93:1336 – 44; with permission.)

muscles, whose presence may interfere with EEG signal acquisition and contaminate the BIS calculation. The frequency spectrum of EMG activity (30- to 300-Hz band) partially overlaps with the top end of the EEG frequencies (0.5- to 30-Hz band). As a consequence, in the presence of a significant EMG activity, lowfrequency EMG signals may be interpreted as high-frequency waves, and this may falsely raise the BIS value. The EMG readout on the BIS monitor is therefore a key to correct interpretation of the BIS value, especially in sedated or lightly anesthetized patients in whom significant EMG activity may be present. Clinical practice and numerous clinical trials have shown that outcomes improve when BIS is used to guide titration of a variety of anesthetic agents, except ketamine [54], during general anesthesia; there was a reduction in the amounts of anesthetic drug used, faster wake-up times, improved recovery, and significant cost savings [55,56]. BIS monitoring is the only technology approved by the

346

F. Radaelli et al / Gastrointest Endoscopy Clin N Am 14 (2004) 335–352

US Food and Drug Administration for marketing as an EEG-based measure of the depth of anesthesia. Recent investigations of its use in ICU sedation have shown a significant correlation between the BIS index and the most widely used clinical rating scales [57], and BIS monitoring is being explored as a means of optimizing sedation management and reducing costs in the ICU [58,59]. The role of BIS monitoring for procedural sedation and analgesia is under investigation. In clinical research, it has shown early promise to improve sedation protocols for dental surgery in outpatients [60,61] and for invasive procedures in the emergency department [62]. There are few data on the use of BIS for GI endoscopy. Bower et al [14] compared the temporal relationship of BIS levels with the Observer’s Assessment of Alertness/Sedation (OAA/S) scale for sedation to evaluate whether BIS monitoring provided an objective measure of sedation during endoscopy and proposed an optimal BIS range corresponding with appropriate levels of sedation. Fifty consecutive adults undergoing upper EGD, colonoscopy, and ERCP receiving intravenous sedation with diazepam and meperidine were monitored with BIS in addition to standard automated monitoring. BIS levels (0– 100) and OAA/S scores (1– 5; 1, no response to shaking; 2, responds only to shaking; 3, responds only to name called loudly; 4, lethargic response to name called in normal tone; 5, responds readily to name spoken in normal tone) were recorded every 3 minutes by a single trained observer; also recorded were the heart rate, mean arterial blood pressure, arterial oxygen saturation by pulse oximetry, and percent EMG interference from the patient’s frontalis muscles through the BIS monitor. This study found a significant correlation between mean BIS levels and OAA/S score but no correlations between BIS levels or OAA/S score and standard parameters such as pulse oximetry, blood pressure, or heart rate. BIS levels and OAA/S scores consistently paralleled the need for additional sedation during the procedure, as clinically determined by the endoscopists based on the patient’s general intolerance of the procedure and discomfort. Finally, a BIS in the range of 75 to 85 indicated a probability of  96% that the patient would be appropriately sedated for endoscopy; this means an OAA/S score of 3 or more, approximately corresponding to the ASA/JCAHO definition of moderate sedation and analgesia. The study also pointed out some limitations of the BIS technology for procedural sedation. The BIS score tended to vary more with deeper levels of sedation. There was also significant EMG interference from patient’s frontalis muscles, potentially interfering with precise BIS calculation. This was particularly evident with minimal sedation (BIS > 90) and was much less evident with progressively deeper sedation. In spite of these limitations, the authors concluded that BIS monitoring provided an objective, reproducible measure of sedation during endoscopy that might be clinically useful for optimizing the sedation level and increasing patient satisfaction and acceptance of the endoscopic procedure. However, the full clinical utility of BIS monitoring for conscious sedation during endoscopy needs to be verified in large randomized prospective trials, comparing patients undergoing endoscopy with and without BIS monitoring.

F. Radaelli et al / Gastrointest Endoscopy Clin N Am 14 (2004) 335–352

347

In a small, uncontrolled pilot study, Leslie et al [63] used BIS during endoscopy as a control variable in a ‘‘closed-looped’’ (automated) propofol sedation delivery system. Sixteen patients undergoing colonoscopy were sedated with propofol; initially the medication was administered by a target-controlled infusion at a blood concentration of 2 mg mL 1 and was manually increased in steps of 0.5 mg mL 1 until moderate sedation (OAA/S rating of 3) was reached. The BIS value when the sedation target was reached was noted, and closed-loop control of sedation was started using the BIS value as the set point, with the goal of maintaining conscious sedation throughout the procedure. The performance of the system was excellent. During endoscopy, all patients were drowsy but rousable, with a median BIS setpoint of 80 (range 75– 85). No patient became apneic or experienced significant oxygen desaturation and hemodynamic instability while sedated. Patient and endoscopist satisfaction were high. The authors concluded that BIS might be a suitable control variable for closed-loop control of sedation with propofol. However, this technique needs to be compared with standard practice propofol administration before any firm conclusion can be drawn on its clinical utility. Narcotrend Narcotrend (MT Monitor Technik, Bad Bramstedt, Germany) is an EEG monitor developed by a research group at Hanover Medical School to measure the depth of sedation and anesthesia. It uses three standard self-adhesive ECG electrodes placed over the patient’s forehead to capture the EEG signal. The system makes an automated analysis of EEG segments of 20 seconds’ duration. After extensive artifact analysis, these are automatically classified by multivariate statistical procedures into different stages corresponding to different degrees of cortical suppression. The EEG stages are classified on an established six-letter scale proposed by Kugler, ranging from A (awake, EEG alpha activity) to F (very deep level of anesthesia, increasing burst suppression activity), with 14 substages (A, B0-2, C0-2, D0-2, E0-1, F0-1) (Table 1) [64]. Validation studies have shown that Narcotrend provides an accurate assessment of hypnotic depth during propofol sedation compared with other EEGprocessed parameters (eg, median and spectral edge frequency, BIS) [65]. Its use for the guidance of propofol titration during intravenous anesthesia allows faster recovery and a reduction of propofol consumption [66]. Wehrmann et al [15] investigated the efficacy of EEG monitoring during propofol sedation for ERCP. In a prospective, randomized, controlled trial, 80 consecutive patients undergoing elective ERCP with propofol were monitored with Narcotrend in addition to standard automated monitoring (oxygen saturation, heart rate, blood pressure, and electrocardiogram). Patients were randomly allocated to two groups. In the first group (conventional sedation group), sedation was titrated by intermittent bolus injection on the basis of procedure tolerance and conventional monitoring data. In the Narcotrend group, EEG monitoring was used to guide propofol administration to maintain a preselected sedation level. EEG stages D0 to D2, corresponding to moderate to deep sedation, were chosen as the tar-

348

F. Radaelli et al / Gastrointest Endoscopy Clin N Am 14 (2004) 335–352

Table 1 EEG stages classified by Narcotrend and the corresponding degree of cortical suppression EEG stages

Leading EEG features

Sate

A B0 B1 B2 C0 C1 C2 D0 D1 D2 E0 E1

Alpha activity Beta or theta activity

Awake Sleepiness, light level of anesthesia

Increasing theta activity

Flat to moderate level of anesthesia

Increasing delta activity

Moderate to deep level of anesthesia

Nearly continuous delta activity Very slow delta waves and beginning burst suppression Burst suppression patterns nearly continuous or continuous EEG suppression

Deep level of anesthesia Very deep level of anesthesia

F0 F1

Very profound cortical suppression

Abbreviation: EEG, electroencephalogram. Adapted from Wehrmann T, Grotkamp J, Stergiou N, Riphaus A, Kluge A, Lembcke B, et al. Electroencephalogram monitoring facilitates sedation with propofol for routine ERCP: a randomized, controlled trial. Gastrointest Endosc 2002;56:817 – 24.

get sedation level. These levels have been found to be optimal with regard to patient tolerance and avoidance of cardiorespiratory side effects during interventional endoscopic procedures [64]. The present study found that extended monitoring with EEG to guide sedation more constantly achieved a proper level of sedation. The predefined target level of sedation was maintained during 75% of the procedure time in Narcotrend group but in only 58% of the time in conventional sedation group; in the latter group, deeper sedation (stages E through F) was reached significantly more often (25% versus 11% of the procedure time). This was reflected in a significantly lower total propofol dose and, accordingly, faster patient recovery, without any difference in sedation efficacy, as assessed by the endoscopist, or patient tolerance. No significant differences between the two groups were noted with regard to the incidence of adverse cardiopulmonary adverse effects, except for the mean decrease in arterial blood pressure, which was significantly lower in the Narcotrend group. No patient in either group experienced prolonged apnea requiring temporary ventilatory support. However, the use of extended EEG monitoring, by reducing the risk of oversedation, is believed to be associated with a lower incidence of propofol-induced respiratory depression. In conclusion, Wehrmann et al [15] found that additional EEG monitoring made for more effective titration of propofol dosages for sedation during interventional endoscopic procedures. The additional cost of EEG monitoring (in Germany the Narcotrend monitor costs about $10,000) might theoretically be

F. Radaelli et al / Gastrointest Endoscopy Clin N Am 14 (2004) 335–352

349

counterbalanced by the need for less propofol and faster patient recovery, but costeffectiveness studies are needed.

Summary The practice of sedation and analgesia is under increasing scrutiny by numerous regulatory agencies, with the aim of making these procedures safer and reducing the incidence of cardiopulmonary complications during GI endoscopy. As we move toward more evidence-based medicine, new technologies will have to be assessed in a manner that demonstrates their efficacy and utility in clinical practice. Although there have been no controlled studies examining whether more intensive monitoring during endoscopy improves outcomes, extended monitoring with capnography seems to offer an advantage over conventional monitoring in that, by providing a real-time indication of any change in adequate ventilation before oxygen desaturation occurs, it can detect early phases of respiratory depression, which can allow a more precise and safer titration of medications. There is a close agreement among experts that capnography may reduce the risk of adverse outcomes during deep sedation; therefore, its use should be required for patients undergoing advanced endoscopic procedures with the potential for deep sedation [7]. Extended monitoring with capnography should also be endorsed whenever propofol is considered as an alternative to standard sedation with a benzodiazepine or narcotic [9]. Our understanding of the clinical application of techniques for monitoring of depth of sedation is in its infancy, and its full contribution to the practice of endoscopy has yet to be determined. Their potential role in improving sedation practice during endoscopy needs to be confirmed by controlled trials. If we consider the lack of proven efficacy of these emerging monitoring techniques in reducing the adverse outcomes associated with sedation and analgesia, the importance of appropriate monitoring cannot be overemphasized. However, it is vital for the endoscopist to be thoroughly familiar with the type of sedation chosen, to be able to recognize the various levels of sedation, and, above all, to rescue patients should they unintentionally progress to a deeper level of sedation than intended [7].

References [1] Sharma VK, Nguyen CC, De Garmo P, Hentz JG, Fleischer DE. Cardiopulmonary complications after gastrointestinal endoscopy: the clinical outcomes research initiative (CORI) experience [abstract]. Gastrointest Endosc 2002;55. [2] Arrowsmith JB, Gerstman BB, Fleischer DE, Benjamin SB. Results from the American Society for Gastrointestinal Endoscopy/US Food and Drug Administration collaborative study on complications rates and drugs during gastrointestinal endoscopy. Gastrointest Endosc 1991;37: 421 – 7.

350

F. Radaelli et al / Gastrointest Endoscopy Clin N Am 14 (2004) 335–352

[3] Quine MA, Bell GD, McCloy RF, Charlton JE, Devlin HB, Hopkins A. Prospective audit of upper gastrointestinal endoscopy in two regions of England: safety, staffing, and sedation methods. Gut 1995;36:462 – 7. [4] Smith MR, Bell GD. Routine oxygen during endoscopy? An editorial review. Endoscopy 1993; 25:298 – 300. [5] Bell GD. Monitoring and safety in endoscopy. Baillieres Clin Gastroenterol 1991;5:79 – 88. [6] Keats AS. Anesthesia mortality in perspective. Anesth Analg 1990;71:113 – 9. [7] American Society of Anesthesiologists Task Force on Sedation and Analgesia by Non-Anesthesiologists. Practice guidelines for sedation and analgesia for non-anesthesiologists. Anesthesiology 2002;96:1004 – 17. [8] Joint Commission on Accreditation of Healthcare Organizations. Standards and intents for sedation and anesthesia care: comprehensive accreditation manual for hospitals. Oakbrook Terrace: Joint Commission on Accreditation of Healthcare Organizations; 2001. [9] Faigel DO, Baron TH, Goldstein JL, Hirota WK, Jacobson BC, Johanson JF, et al. Standards Practice Committee, American Society for Gastrointestinal Endoscopy. Guidelines for the use of deep sedation and anesthesia for gastrointestinal endoscopy. Gastrointest Endosc 2002;56: 613 – 7. [10] Freeman ML, Hennessy TJ, Cass OW, Pheley AM. Carbon dioxide retention and oxygen desaturation during gastrointestinal endoscopy. Gastroenterology 1993;105:331 – 9. [11] Nelson DG, Freeman ML, Silvis SE, Cass OW, Yakshe PN, Vennes J, et al. A randomized, controlled trial of transcutaneous carbon dioxide monitoring during ERCP. Gastrointest Endosc 2000;51:288 – 95. [12] Heuss LT, Schnieper P, Hayoz J, Tschupp A, Beglinger C. Patient surveillance with a new combined transcutaneous pulse oximetry and carbon dioxide tension single ear sensor during colonoscopy: a pilot study [abstract]. Gastrointest Endosc 2003;57:AB78. [13] Vargo JJ, Zuccaro Jr G, Dumot JA, Conwell DL, Morrow JB, Shay SS. Automated graphic assessment of respiratory activity is superior to pulse oximetry and visual assessment for the detection of early respiratory depression during therapeutic upper endoscopy. Gastrointest Endosc 2002;5:826 – 31. [14] Bower AL, Ripepi A, Dilger J, Boparai N, Brody FJ, Ponsky JL. Bispectral index monitoring of sedation during endoscopy. Gastrointest Endosc 2000;52:192 – 6. [15] Wehrmann T, Grotkamp J, Stergiou N, Riphaus A, Kluge A, Lembcke B, et al. Electroencephalogram monitoring facilitates sedation with propofol for routine ERCP: a randomized, controlled trial. Gastrointest Endosc 2002;56:817 – 24. [16] ASGE Standards of Practice Committee. Sedation and monitoring of patients undergoing gastrointestinal endoscopic procedures. Gastrointest Endosc 1995;42:626 – 9. [17] Bell GD, McCloy RF, Charlton JE, Campbell D, Dent NA, Gear MW, et al. Recommendations for standard of sedation and patient monitoring during gastrointestinal endoscopy. Gut 1991; 32:823 – 7. [18] Davidson JA, Hosie HE. Limitations of pulse oximetry: respiratory insufficiency: a failure of detection. BMJ 1993;307:372 – 3. [19] Holm C, Rosemberg J. Pulse oximetry and supplemental oxygen during gastrointestinal endoscopy: a critical review. Endoscopy 1996;28:703 – 11. [20] Tobin MJ. Respiratory monitoring. JAMA 1990;264:244 – 51. [21] Zuccaro G, Radaelli F, Vargo JJ, Morrow JB, Dumot JA, Conwell DL, et al. Routine use of supplemental oxygen prevents recognition of prolonged apnea during endoscopy [abstract]. Gastrointest Endosc 2000;51:AB141. [22] West JB. Respiratory physiology: the essentials. 4th edition. Baltimore: Williams & Wilkins; 1990. [23] Stoelting RK. Pharmacology and physiology in anesthetic practice. Philadelphia: Lippincott; 1987. [24] Weingarten M. Respiratory monitoring of carbon dioxide and oxygen: a ten-year perspective. J Clin Monit 1990;6:217 – 25.

F. Radaelli et al / Gastrointest Endoscopy Clin N Am 14 (2004) 335–352

351

[25] Reid CW, Martineau RJ, Miller DR, Hull KA, Baines J, Sullivan PJ. A comparison of transcutaneous end-tidal and arterial measurements of carbon dioxide during general anaesthesia. Can J Anaesth 1992;39:31 – 6. [26] Weingarten M. Respiratory monitoring of carbon dioxide and oxygen: a ten-year perspective. J Clin Monit 1990;6:217 – 25. [27] Tschupp A, Fanconi S. A combined ear sensor for pulse oximetry and carbon dioxide tension monitoring: accuracy in critically ill children. Anesth Analg 2003;96:82 – 4. [28] Rohling R, Biro P. Clinical investigation of a new combined pulse oximetry and carbon dioxide tension sensor in adult anaesthesia. J Clin Monit Comput 1999;15:23 – 7. [29] Schmitz BD, Shapiro BA. Capnography. Respir Care Clin N Am 1995;1:107 – 17. [30] Stock MC. Capnography for adults. Crit Care Clin 1995;1:219 – 32. [31] American Society of Anesthesiology. Standards for basic anesthetic monitoring. Park Ridge (IL): American Society of Anesthesiologists; 1998. [32] Kannan S, Manji M. Survey of use of end-tidal carbon dioxide for confirming tracheal tube placement in intensive care units in the UK. Anaesthesia 2003;58:476 – 9. [33] McArthur CD. AARC clinical practice guideline: capnography/capnometry during mechanical ventilation – 2003 revision & update. Respir Care 2003;48:534 – 9. [34] Levine RL, Wayne MA, Miller CC. End-tidal carbon dioxide and outcome of out-of-hospital cardiac arrest. N Engl J Med 1997;337:301 – 6. [35] Colman Y, Krauss B. Microstream capnography technology: a new approach to an old problem. J Clin Monit Comput 1999;15:403 – 9. [36] Wehrmann T, Kokabpick S, Lembcke B, Caspary WF, Seifert H. Efficacy and safety of intravenous propofol sedation during routine ERCP: a prospective, controlled study. Gastrointest Endosc 1999;49:677 – 83. [37] Seifert H, Schmitt TH, Gultekin T, Caspary WF, Wehrmann T. Sedation with propofol plus midazolam versus propofol alone for interventional endoscopic procedures: a prospective, randomized study. Aliment Pharmacol Ther 2000;14:1207 – 14. [38] Jung M, Hofmann C, Kiesslich R, Brackertz A. Improved sedation in diagnostic and therapeutic ERCP: propofol is an alternative to midazolam. Endoscopy 2000;32:233 – 8. [39] Koshy G, Nair S, Norkus EP, Hertan HI, Pitchumoni CS. Propofol versus midazolam and meperidine for conscious sedation in GI endoscopy. Am J Gastroenterol 2000;95:1476 – 9. [40] Krugliak P, Ziff B, Rusabrov Y, Rosenthal A, Fich A, Gurman GM. Propofol versus midazolam for conscious sedation guided by processed EEG during endoscopic retrograde cholangiopancreatography: a prospective, randomized, double-blind study. Endoscopy 2000;32:677 – 82. [41] Gillham MJ, Hutchinson RC, Carter R, Kenny GN. Patient-maintained sedation for ERCP with a target-controlled infusion of propofol: a pilot study. Gastrointest Endosc 2001;54:14 – 7. [42] Vargo JJ, Zuccaro Jr G, Dumot JA, Shermock KM, Morrow JB, Conwell DL, et al. Gastroenterologist-administered propofol versus meperidine and midazolam for advanced upper endoscopy: a prospective, randomized trial. Gastroenterology 2002;123:8 – 16. [43] Nelson DB, Barkun AN, Block KP, Burdick JS, Ginsberg GG, Greenwald DA, et al. American Society for Gastrointestinal Endoscopy. Technology Committee. Propofol use during gastrointestinal endoscopy. Gastrointest Endosc 2001;53:876 – 9. [44] Vargo JJ, Zuccaro Jr G, Dumot JA, Shay SS, Conwell DL, Morrow JB. Gastroenterologistadministered propofol for therapeutic upper endoscopy with graphic assessment of respiratory activity: a case series. Gastrointest Endosc 2000;52:250 – 5. [45] Heier T, Steen PA. Assessment of anaesthesia depth. Acta Anaesthesiol Scand 1996;40: 1087 – 100. [46] Drummond JC. Monitoring depth of anesthesia: with emphasis on the application of the bispectral index and the middle latency auditory evoked response to the prevention of recall. Anesthesiology 2000;93:876 – 82. [47] Rampil IJ. A primer for EEG signal processing in anesthesia. Anesthesiology 1998;89:980 – 1002. [48] Levy WJ, Shapiro HM, Maruchak G, Meathe E. Automated EEG processing for intraoperative monitoring: a comparison of techniques. Anesthesiology 1980;53:223 – 36.

352

F. Radaelli et al / Gastrointest Endoscopy Clin N Am 14 (2004) 335–352

[49] Todd MM. EEGs, EEG processing, and the bispectral index [editorial]. Anesthesiology 1998;89: 815 – 7. [50] Rosow C, Manberg PJ. Bispectral index monitoring. Anesthesiol Clin North Am 2001;19: 947 – 66. [51] Johansen JW, Sebel PS. Development and clinical application of electroencephalographic bispectrum monitoring. Anesthesiology 2000;93:1336 – 44. [52] Drover DR, Lemmens HJ, Pierce ET, Plourde G, Loyd G, Ornstein E, et al. Patient State Index: titration of delivery and recovery from propofol, alfentanil, and nitrous oxide anesthesia. Anesthesiology 2002;97:82 – 9. [53] Sigl JC, Chamoun NG. An introduction to bispectral analysis for the electroencephalogram. J Clin Monit 1994;10:392 – 404. [54] Suzuki M, Edmonds HL, Tsueda K, Malkani AL, Roberts CS. Effect of ketamine on bispectral index and level of sedation. J Clin Monit 1998;14:373 – 4. [55] Gan TJ, Glass PS, Windsor A, Payne F, Rosow C, Sebel P, et al. Bispectral index monitoring allows faster emergence and improved recovery from propofol, alfentanil, and nitrous oxide anesthesia. BIS Utility Study Group. Anesthesiology 1997;87:808 – 15. [56] Struys M, Versichelen L, Byttebier G, Mortier E, Moerman A, Rolly G. Clinical usefulness of the bispectral index for titrating propofol target effect-site concentration. Anaesthesia 1998;53: 4 – 12. [57] Mondello E, Siliotti R, Noto G, Cuzzocrea E, Scollo G, Trimarchi G, et al. Bispectral Index in ICU: correlation with Ramsay Score on assessment of sedation level. J Clin Monit Comput 2002; 17:271 – 7. [58] De Deyne C, Struys M, Decruyenaere J, Creupelandt J, Hoste E, Colardyn F. Use of continuous bispectral EEG monitoring to assess depth of sedation in ICU patients. Intensive Care Med 1998; 24:1294 – 8. [59] Gilbert TT, Wagner MR, Halukurike V, Paz HL, Garland A. Use of bispectral electroencephalogram monitoring to assess neurologic status in unsedated, critically ill patients. Crit Care Med 2001;29:1996 – 2000. [60] Sandler NA. The use of bispectral analysis to monitor outpatient sedation. Anesth Prog 2000; 47:72 – 83. [61] Sandler NA, Hodges J, Sabino M. Assessment of recovery in patients undergoing intravenous conscious sedation using bispectral analysis. J Oral Maxillofac Surg 2001;59:603 – 11. [62] Gill M, Green SM, Krauss B. A study of the Bispectral Index Monitor during procedural sedation and analgesia in the emergency department. Ann Emerg Med 2003;41:234 – 41. [63] Leslie K, Absalom A, Kenny GN. Closed loop control of sedation for colonoscopy using the Bispectral Index. Anaesthesia 2002;57:693 – 7. [64] Schultz B, Grouven U, Schultz A. Automatic classification algorithms of the EEG monitor Narcotrend for routinely recorded EEG data from general anaesthesia: a validation study. Biomed Tech (Berl) 2002;47:9 – 13. [65] Kreuer S, Biedler A, Larsen R, Schoth S, Altmann S, Wilhelm W. The Narcotrend: a new EEG monitor designed to measure the depth of anaesthesia. A comparison with bispectral index monitoring during propofol-remifentanil-anaesthesia. Anaesthesist 2001;50:921 – 5. [66] Wilhelm W, Kreuer S, Larsen R, Narcotrend-Studiengruppe. Narcotrend EEG monitoring during total intravenous anaesthesia in 4.630 patients. Anaesthesist 2002;51:980 – 8.