Conscious Sedation for Gastroscopy: Patient Tolerance and Cardiorespiratory Parameters

Transcription

1 GASTROENTEROLOGY 1995;108: Conscious Sedation for Gastroscopy: Patient Tolerance and Cardiorespiratory Parameters FLORIAN FROEHLICH,* WERNER SCHWIZER,* JOEL THORENS,* MANFRED K(3HLER, JEAN-JACQUES GONVERS,* and MICHAEL FRIED t *Department of Gastroenterology, University Hospital Policlinique M6dicale Universitaire/Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; gpharma Biometry Consulting, Freiburg in Breisgau, Germany; and *Department of Gastroenterology, University Hospital, Zurich, Switzerland See editorial on page 932. Background/Aims: Most patients receive conscious sedation for gastroscopy. However, the benefit of the most often used combination of low-dose intravenous midazolam and topical lidocaine on patient tolerance remains poorly defined and has not been shown to outweigh cardiorespiratory risks. To respond to these issues, a randomized, double-blind, placebo-controlled prospective study was performed. Methods: Two hundred outpatients undergoing diagnostic gastroscopy were assigned to receive either (1) midazolam (35 ~g/ kg) and lidocaine spray (100 mg), (2) midazolam and placebo lidocaine, (3) placebo midazolam and lidocaine, or (4) placebo midazolam and placebo lidocaine. Results: Tolerance (visual analogue scale, points; O, excellent; 100, unbearable) improved as compared with placebo midazolam and placebo lidocaine by 23 points (95% confidence interval, 15-32) in group 1, 15 points (95% confidence interval, 7-24) in group 2, and 10 points (95% confidence interval, 2-18) in group 3. Increasing age (P < 0.001), low anxiety (P < 0.001), and male sex (P < 0.03), but not amnesia, were associated with better patient tolerance. Oxygen desaturation (<1 minute) occurred in 8.2% and was not more frequent after midazolam treatment. Hypotension was rare (2.1%), and no adverse outcome occurred. Conclusions: Both low-dose midazolam (35 ~Lg/kg) and lidocaine spray have an additive beneficial effect on patient tolerance and rarely induce significant alterations in cardiorespiratory monitoring parameters, thus supporting the widespread use of conscious sedation. pper gastrointestinal endoscopy is mostly performed under conscious sedation.t-4 The combination of a benzodiazepine and pharyngeal anesthesia is widely applied, l and midazolam administered in low doses (<3 mg intravenously) has become the standard sedative.2 5 Adverse outcomes of upper gastrointestinal endoscopy caused by conscious sedation have been reported with an incidence of 0.34% 4 and fatalities in 0.03% of patients. 1'4'6 Fifty percent of morbidity and 60% of mortality in upper gastrointestinal endoscopy are related to conscious sedation causing hypoxemia, 5 which may induce cardiopulmonary complications] -1 Therefore, risk-benefit considerations have become important because routine diagnostic gastroscopy can also be performed without sedation) 1 Conscious sedation would be justified by a distinct improvement in patient tolerance outweighing sedation-related risks. Numerous controlled and uncontrolled studies on patient tolerance to upper gastrointestinal endoscopy have been reported, including various regimens of sedation and topical anesthesia However, most of these investigations are limited by serious flaws in their study design. Pulse oximetry is a simple, reliable, and sensitive method to measure oxygen saturation 3 and is widely used nowadays for patient surveillance during endoscopic procedures. 2 Despite numerous reports dealing with pulse oximetry during upper gastrointestinal endoscopy, 6'9'23'31-4 the frequency of oxygen desaturation during routine ambulatory gastroscopy remains controversial. In particular, it remains unclear if there is a causal relationship between conscious sedation and oxygen desaturation. To our knowledge, no randomized, double-blind, placebo-controlled study has yet been performed to evaluate the effect of the currently most often used combination of intravenous sedation with midazolam 2-4 and pharyngeal anesthesia 1 with lidocaine ~7 on patient tolerance and cardiorespiratory monitoring parameters such as oxygen saturation, pulse rate, and blood pressure. In addition, in previous studies with midazolam investigating patient tolerance 14'2 '24'41 and monitoring 3.'38'39 of cardiorespiratory functions, high doses were applied (~>5 mg intravenously); nowadays, distinctly lower doses of <3 mg ad- Abbreviations used in this paper: CI, confidence interval; M-L, midazolam and lidocaine; M-pL, midazolam and placebo lidocaine; pm-l, placebo midazolam and lidocaine; pm-pl, placebo midazolam and placebo lidocaine by the American Gastroenterological Association /95/$3.00

2 698 FROEHLICH ET AL. GASTROENTEROLOGY Vol. 108, No. 3 ministered intravenously are mostly used for routine 431 diagnost,c procedures. ' Hitherto, the value of low-dose midazolam treatment in improving patient tolerance has not been investigated while simultaneously considering the impact on cardiorespiratory function. Therefore, we performed a randomized, double-blind, placebo-controlled prospective study to evaluate the effect of the standard combination for conscious sedation (namely, intravenous midazolam treatment given at a dose of 35 btg/kg and pharyngeal anesthesia with lidocaine) on patient tolerance and cardiorespiratory parame- ters during routine ambulatory upper gastrointestinal en- doscopy. Materials and Methods Study Design Two hundred consecutive outpatients referred for upper diagnostic gastrointestinal endoscopy were evaluated. All patients were included; no patient refused to participate. The patients provided written informed consent. The study protocol was approved by the ethical committee of the University of Lausanne. No patient had a history of intolerance to benzodiazepines or anesthetic spray, long-term drug addiction (benzodiazepines, opioids), severe (ASA III and IV) cardiac or respiratory diseases, 42 neuropathic or swallowing disorders, and hepatic or renal encephalopathy. Patients were randomly assigned to four study groups: (1) group M-L received both midazolam (33 btgt kg intravenously; Hoffmann-La Roche Ltd., Basel, Switzerland) and pharyngeal anesthesia with lidocaine spray 10% (10 squirts = 100 mg; Astra, S6dert~ilje, Sweden); (2) group Mr pl received midazolam intravenously and a placebo spray with a similar taste to lidocaine, achieved by the addition of tannic acid16; (3) group pm-l received placebo midazolam (0.9% saline intravenously) and lidocaine spray; and (4) group pmpl received both placebo midazolam intravenously and placebo lidocaine. One hundred milligrams of lidocaine spray has previously been shown to be more effective than 50 mg but equally as effective as 200 mg. 43 The drugs were given in a double-blind manner. In case the procedure was not well tolerated (> 2 trials to introduce the endoscope and/or heavy defense reactions), a supplemental dose of midazolam (2.5 mg intravenously) was to be administered in a nonblinded fashion. All procedures were performed by two experienced endoscopists in a standardized environment using the same type of videoendoscopy equipment (Olympus Evis, Tokyo, Japan; diameter, 9 ram). Study Population Two hundred patients entered the study. Two patients had to be excluded for the assessment of tolerance (1 because of technical failure of the endoscope and 1 because of severe esophageal stenosis precluding endoscope passage). Four additional patients were excluded from the monitoring part of the study because of incomplete recordings. Thus, 198 patients (119 men and 79 women; median age, 46 years; range, 18- Table 1. Study Population: Demographic Data and Habits M-L M-pL pm-l pm-pl (n = 49) (n = 49) (n = 51) (n =49) Sex (M/F) 34/15 29/20 27/24 29/20 Age (mean_+ SEM)(yr) _ Weight (mean + SEM)(kg) ± 2 67 ± 2 66_+ 2 Smoking (yes/no) 21/28 22/27 23/28 25/24 Alcohol (yes/no) 24/25 22/27 23/28 24/25 NOTE. n = 198 for all groups. 87 years) were evaluated for tolerance and 194 patients for monitoring parameters, respectively. Patients in the four study groups were similar in regard to demographic data (sex, age, and weight) and habits (smoking and alcohol intake) as shown in Table 1. A similar number of patients in each group had previously undergone an endoscopic procedure (group M-L, 43%, group M-pL, 39%; group pm-l, 43%; group pm-pl, 33% [not significant]). Endoscopy was performed for the following indications, which were uniformly distributed between the four study groups: dyspeptic symptoms, 61.1% (n = 121); symptoms of gastroesophageal reflux, 16.1% (n = 32); suspicion of neoplasia, 6.0% (n = 12); and other indications, 16.8% (n = 33). The following endoscopic pathological results were found (n = 98): esophagitis, 16.3%; hiatus hernia, 29.6%; gastric or duodenal ulcer, 18.4%; neoplasia, 2.0%; and others (e.g., Billroth II operation, duodenitis), 38.7%. Endoscopy was normal in 50.5% (n = 100) of the patients. Few patients had a history of cardiorespiratory disease (ASA I, 5.6%; ASA li, 6.6%) with a uniform distribution between the four study groups. No adverse outcome occurred in this study. Patients' Assessments Anxiety. Patients were asked to evaluate "fear" of the procedure before endoscopy. Answers were given on a 100- mm visual analogue scale as previously described and validated. 44 The left end point of the scale was defined as "not at all" and the right end point as "enormously." The distance from the left end point (in millimeters) was used to quantify the variable. 44 In addition to the general term "fear," seven specific fear items were assessed: pain, nausea, vomiting, cough, bloating, fear of injury, and asphyxia. The anxiety score was defined as the arithmetic mean of fear and the mean of the above-mentioned specific fear items. Anxiety scores (mean + SEM) before endoscopy were similar in the four study groups (group M-L, ; group M- pl, 21.5 ± 2.6; group pm-l, 25.4 _ 3.2; group pm-pl, _ 2.9 [not significant]). Tolerance Patients assessed their tolerance to the endoscopy at least 2 hours after the end of the procedure. This interval was chosen to ascertain the absence of persisting anterograde amnesia, which could potentially influence patient judgment. The patients assessed on a 100-mm visual analogue scale the ease of introduction (0, very easy; 100, extremely difficult), the overall feeling during endoscopy (0, excellent; 100, unbearable), and six specific sensations such as pain, nau-

3 March 1995 GASTROSCOPY: PATIENT TOLERANCE AND MONITORING 699 sea, cough, belching, bloating, and asphyxia (0, nonexistent; 100, unbearable). The tolerance score was defined as the arithmetic mean of ease of introduction, overall feeling during endoscopy, and the mean of the six above-mentioned specific sensations. Patients were asked whether they would be willing to repeat the examination under the same conditions. Furthermore, they indicated whether the procedure was felt to be less, more, or as unpleasant as expected. Finally, the patients' memory was assessed by asking them standardized questions about several specific circumstances of the procedure. Endoscopists' Assessment Immediately after endoscopy was performed, the operator rated the ease of the procedure on a 100-mm visual analogue scale, including ease of introduction of the instrument (0, easy; 100, extremely difficult), patient collaboration (0, excellent; 100, extremely limited), and four specific symptoms such as vomiting, cough, belching, and defense reactions (0, non-existent; 100, enormous). The score as assessed by the endoscopists was defined as the arithmetic mean of ease of introduction, patient collaboration, and the mean of the four above-mentioned specific symptoms. Electronic Monitoring Oxygen saturation (Sao2) and blood pressure were continuously monitored (Kontron Minimon 7137 B; Kontron, Watford, Herts, England) and digitally stored on a computer unit. Monitoring data were evaluated in five standardized phases: phase I, before pharyngeal anesthesia (1 minute); phase II, after pharyngeal anesthesia (1 minute); phase III, after intravenous medication (3 minutes); phase IV, during endoscopy (time variable); and phase V, after endoscopy (3 minutes). Desaturation was defined as a decrease of oxygen saturation below 90% 9'*o during three or more consecutive measurements (12-second time interval between measurements). Patients were encouraged by physicians or endoscopy nurses to breathe deeply if the oxygen saturation began to approach 90%. If oxygen saturation decreased below 85%, oxygen was given using an oxygenating mouthguard. 45 I-Iypotension was considered to be present if the mean arterial blood pressure was lower than 60 mm Hg. 46 Statistical Analysis The baseline characteristics of the four treatment groups were compared by one-way analysis of variance. The patient tolerance score to the procedure was considered to be the main variable. The impact of treatment group, age, sex, pre-endoscopic anxiety score, and previous experience of endoscopy on the main variable patient tolerance was evaluated by multiple regression analysis. To estimate the effect of the above-mentioned items on patient tolerance, simultaneous 95% confidence intervals (CI) with Bonferoni correction were calculated. Categorical variables were analyzed by Z 2 tests or exact test procedtires if appropriate. Clinically relevant oxygen desaturation events (<90%) between the four treatment groups were compared with the two-tailed Fisher's Exact Test. :E II1 +..~= o u 20 0 U e 10 o b- 0 M-L T I T M-pL pm-l pm-pl Figure 1. Tolerance scores (mean score points _+ SEM) derived from patients' assessment (visual analogue scale: O, excellent; 100, unbearable) in the four treatment groups. The mean arterial blood pressure and pulse rate variables were analyzed with one-way analysis of variance, applying Bonferoni correction for multiple comparisons. Results were considered significant if P values were <0.05. Results Patient Tolerance Patients' assessment. Tolerance scores (mean + SEM) as assessed by the patients are shown in Figure 1. The combination of midazolam and lidocaine (group M- L) resulted in a marked improvement of tolerance (23 points; 95% CI, 15-32) as compared with the group receiving placebo midazolam and placebo lidocaine (pmpl), who had a score of points. Patient tolerance improved by 15 points (95% CI, 7-24) in the group receiving midazolam without pharyngeal anesthesia (MpL) and by 10 score points (95% CI, 2-18) in the group receiving pharyngeal anesthesia without midazolam (group pm-l) as compared with the placebo group (pmpl). More patients would have agreed to repeat the procedure in the two groups receiving midazolam (group M- L, 96%; group M-pL, 94%) as compared with the two groups receiving intravenous placebo (group pm-l, 75 %; group pm-pl, 74%; P < 0.001). In contrast, pharyngeal anesthesia did not enhance willingness to repeat the examination (P = 0.84). Furthermore, willingness to repeat endoscopy was related to patient tolerance. Thus, 99% of the patients with a good tolerance (score of <10) would have accepted a second endoscopy as compared with 77% of the patients with a lower tolerance (score of -->10; P < 0.001). In the two midazolam groups, more patients (group M-L, 69%; group M-pL, 57%) believed the endoscopy to be less unpleasant than they

4 700 FROEHLICH ET AL. GASTROENTEROLOGY Vol. 108, No. 3 had expected before the procedure as compared with the two groups not receiving midazolam (group pm-l, 37%; group pm-pl, 37%; P < 0.001). In contrast, patients receiving pharyngeal anesthesia did not tolerate endoscopy better than expected as compared with topical placebo. Multiple regression analysis showed that both age and the pre-endoscopic anxiety score of the patients had a highly significant (P < 0.001) impact on tolerance to the procedure. Thus, tolerance improved by 17 score points (95% CI, 12-21) in patients 40 years of age or older as compared with patients younger than 40 years of age who had a tolerance score of points. Likewise, tolerance was related to pre-endoscopic anxiety scores. Thus, a low pre-endoscopic anxiety score (<30) was an indicator of better tolerance by 17 score points (95% CI, 12-22) as compared with patients with a high score of pre-endoscopic anxiety (-->30) whose tolerance score was points. Tolerance was distinctly higher (10 score points; 95% CI, 4-15) in men than in women who had a mean tolerance score of 30 ± 2. Previous experience with endoscopy had no significant influence on patient tolerance. Supplemental doses of midazolam were necessary to achieve sufficient tolerance in 16 patients (8%) with a uniform distribution between the four groups (group M- L, 4; group M-pL, 4; group pm-l, 2; group pm-pl, 6 [not significant]). Thus, supplemental midazolam has not been used more frequently in patients receiving midazolam placebo than in patients randomized to midazolam. Midazolam-induced amnesia occurred in 33 % of patients in group M-L and in 25% in group M-pL, respectively, whereas only a few cases of amnesia were observed in the two groups without midazolam (group pm-l, 0%; group pm-pl, 8%; P < ). In the two groups receiving midazolam, amnesia tended to improve patient tolerance only slightly by 8 score points (95% CI, 0-15) as compared with the patients who did not present amnesia. Endoscopists' Assessment The ease of the procedure as judged by the endoscopists was not influenced by pharyngeal anesthesia. Thus, patient tolerance improved by only 8 score points (95% CI, 0-18 [nor significant]) in the two groups receiving pharyngeal anesthesia (groui~s M-L and pm-l) as compared with the two groups that did not receive topical lidocaine (groups M-pL and pm-pl). The administration of midazolam did not affect the endoscopists' judgment of the ease of the procedure (P = 0.89). Electronic Monitoring Oxygen saturation. Oxygen saturation (SaO2) in the four treatment groups is shown in Figure 2. Before endoscopy (phase I, II, and III), mean oxygen saturation (+SD) was similar (96% + 2%) in all four groups. Midazolam (groups M-L and M-pL) caused a very small (1%- 2%) though significant (P < 0.05) decrease of mean Sao2 during and after endoscopy (phase IV and V); a clinically relevant oxygen desaturation (SaO2 < 90%) was observed in 16 patients (8.2%) and was not more common after midazolam treatment. Thus, it occurred in 3 patients in group M-L, 8 patients in group M-pL, 3 patients in group pm-l, and 2 patients in group pmpl (not significant). All desaturation events were of short duration (<1 minute). Oxygen was given in only one patient with a sustained decrease (1 minute) of the SaO 2 level below 85%. Lidocaine treatment had no effect on Sa02. Blood pressure and pulse rate. Table 2 shows mean (-+-SD) arterial blood pressure values. The mean arterial blood pressure was similar in all four study groups before endoscopy (phase I, II, and III). During endoscopy (phase IV), the mean arterial blood pressure increased in all groups (difference of mean values; millimeters of mercury): 5 (group M-L), 11 (group M-pL), 9 (group pm-l), and 17 (group pm-pl; P < 0.001). During and after endoscopy, the mean arterial blood pressure (+SD) was slightly lower (P < 0.05) in the group receiving midazolam and lidocaine spray (phase IV, ; phase V, ) as compared with the group receiving placebo midazolam and placebo lidocaine (phase IV, ; phase V, ). Short (<1 minute) episodes of hypotension (mean arterial blood pressure < 60 mm Hg) were observed in 4 patients (2.1%): 2 in group M-pL (59 mm Hg in both cases), 1 in group pm- L (46 mm Hg), and 1 in group pm-pl (58 mm Hg). In all patients, the blood pressure normalized without medical intervention. No clinically manifest events related to blood pressure changes occurred in any group. Pulse rate (mean beats/min + SD) was comparable in all four groups before and after spray application (phase I and II) and after intravenous sedation (phase III). The most important increase in pulse rate (difference of mean values) was observed during endoscopy (phase IV): 7 (group M-L), 16 (group M-pL), 14 (group pm-l), and 18 (group pm-pl; P < 0.001). Discussion The present study shows that both low-dose intravenous midazolam and topical lidocaine treatment have an independent distinct beneficial effect on patient tolerance. Moreover, patient tolerance was markedly better if midazolam and pharyngeal anesthesia were given together, showing an additive effect of intravenous midazolam and topical lidocaine treatment. Willingness to repeat the procedure was distinctly higher in patients

5 March 1995 GASTROSCOPY: PATIENT TOLERANCE AND MONITORING I00 o ~ 2 9 c- ~) A I I I I I before after after iv during aher spray spray sedation endoscopy endoscopy 0 p ~ 9o e- 0 B I I I before after after iv spray spray sedation I during after endoscopy endoscopy 100 c- O,,6-. p -~ 9O e ~ 911 e- O~ 80 C I I I I I before after arer iv during a~er spray spray sedation endoscopy endoscopy D I I I I I before after after iv during a~ter spray spray sedatlon endoscopy endoscopy Figure 2. Oxygen saturation (percent; median, minimal, maximal, 25th and 75th percentile values) during five monitoring phases in the four treatment groups: (A) group M-L, (B) group M-pL, (C) group pm-l, (D) group pm-pl. receiving midazolam as compared with patients receiving intravenous placebo. The results of this study therefore support the widespread use of a combinatiop of intravenous midazolam, given at a low dose of 35 btg/kg, and pharyngeal anesthesia for routine upper gastrointestinal endoscopy. Various combinations of intravenous sedatives and pharyngeal anesthesia have previously been tested for their ability to improve patient tolerance. The results of these studies are contradictory. Many trials have shown a beneficial effect of benzodiazepines zs'25 or pharyngeal anesthesia 1<17'47 on patient tolerance, whereas others did not find any benefit for benzodiazepines ~3'.5m or topical spray. 19'2 '29 Major flaws in the study design are apparent in these studies. First, most studies are not placebocontrolled,12,14,22,24,26.27,29,41,48 double_blind,13,ts,2~ 23,27,29 or performed in a randomized fashion. 18'29 Moreover, in most studies evaluating pharyngeal anesthesia, benzodiazepines have been used in both the placebo and the verum group. The resulting amnesia may obscure the assessment of topical spray. 16"19'2 '28'47'49 Second, in some trials, variable doses of the sedative agent were applied. 14J8'23"27'41 Finally, in numerous studies, the effect of diazepam on patient tolerance has been evaluated, 12'.3'15'16'18'19'21'22'25 whereas midazolam is currently the most used agent for sedation in gastrointestinal endoscopy. 2-5 In our study, the aforementioned methodological difficulties were avoided by applying a random- ized double-blind design. To clarify the independent placebo effect of midazolam and lidocaine spray and the impact of midazolam-induced amnesia on tolerance, a placebo group was introduced for both agents. In previous studies, the effect of high midazolam doses (-->5 mg intravenously) on patient tolerance has been examined. 14'2 '24'41 The present study shows that midazolam treatment improves patient tolerance even when used in low doses (35 btg/kg) as compared with placebo. These low doses are recommended by several endoscopic societies 5 and the manufacturer of the drug and are currently mostly applied for conscious sedation in routine upper gastrointestinal endoscopy, as recently shown in a United States survey. 4 Cardiorespiratory complications are related to sedation-induced hypoxemia, 5'7-1 the frequency Table 2. Blood Pressure Measurements Mean arterial blood pressure (mean _+ SD) (mm Hg) M-L M-pL pm-l pm-pl Before spray 91 _+_ ± _ After spray _ ± ± 16 After intravenous sedation ± ± 17 During endoscopy 94 +_ 20 a 98 +_ _ _+ 25 a After endoscopy ± ± ± 17 b a.~p < 0.05.

6 702 FROEHLICH ET AL. GASTROENTEROLOGY Vol. 108, No. 3 of which is likely to be correlated to the dose of midazolam used. Therefore, the finding that a low dose of midazolam is highly effective in improving patient tolerance is important because the use of lower doses may contribute to the reduction of sedation-related complications in upper gastrointestinal endoscopy. We found amnesia only in a minority of patients receiving midazolam, although this benzodiazepine has frequently been reported to induce amnesia. 14'24 This may be explained by the fact that the dose of midazolam used is two to three times smaller as compared with previous studies that found amnesia in more than 90% of the patients. 14'24 Patient acceptance of upper gastrointestinal endoscopy is assumed to be directly related to the degree of amnesia induced by the sedation. ~4'24 However, we found similar tolerance scores in patients with and without amnesia in the two groups receiving midazolam. The beneficial effect of low-dose midazolam on patient tolerance is therefore not mainly explained by the induction of amnesia, suggesting that other factors, such as anxiolysis, may be important. Previous studies have shown that apprehensive individuals have an impaired tolerance to gastroscopy 4s and that less sedation is required if patient anxiety before endoscopy is low. 51 In our study, a high degree of fear before the procedure resulted in a lower patient tolerance in all study groups, confirming these previous reports. Furthermore, we found that tolerance increased in patients older than 40 years of age and that men tolerated endoscopy distinctly better than women, corresponding to the results of a previous investigation) 8 Our study implies that young, apprehensive women can be expected to benefit most from conscious sedation and pharyngeal anesthesia. Previous endoscopic experience did not influence patient tolerance, which is in contrast to the findings of other investigators..s'52 However, these earlier studies were neither double-blind nor randomized. In several trials, tolerance has been evaluated by the endoscopists 11'24 or an independent observer. 23 These evaluations may not reflect the patients' opinion because the correlation between the tolerance assessment of patients and endoscopists is reported to be poor. 52'53 The endoscopists' ratings of the ease of the procedure were in this study neither influenced by pharyngeal anesthesia nor influenced by the use of midazolam, contrasting with the assessments of the patients. Most complications of upper gastrointestinal endoscopy are of cardiopulmonary origin 5 as a consequence of hypoxemia, 5 which may be related to the procedure itself, 23'54'55 to conscious sedation, 7'% or to a combined effect. 8 Despite the potential cardiorespiratory risks related to sedative agents, most patients are endoscoped with conscious sedation) '2 The results of this placebo- controlled, double-blind prospective study show that conscious sedation with midazolam given at a low dose (3 5 btg/kg) rarely induces significant alterations of cardiorespiratory function during routine gastroscopy in average-risk outpatients. Thus, episodes of significant oxygen desaturation were rare (8%), of short duration (< 1 minute), and equally distributed in the four study groups. Therefore, this study shows that the beneficial effect of conscious sedation on patient tolerance outweighs cardiorespiratory risks, which is of significant clinical importance. Previously marked decreases of oxygen saturation have been reported to occur with a highly variable frequency ranging from 7% to 40% of gastroscopies. 6'9'31-36 However, methodological limitations are apparent in the majority of these reports. First, most trials are either not placebo-controlled 3~'~v'38 or not performed in a doubleblind fashion) v'38 Second, in several studies, high doses of midazolam ranging from 6 to 8 mg were given, 31'38'39 whereas low (<3 mg) starting doses of midazolam are actually recommended and generally used for endoscopy. 4'4 Third, no defined doses were applied in some studies, 23'35 precluding conclusions concerning the relative potency of the drug in inducing oxygen desaturation. Finally, in several studies, a benzodiazepine and an opioid were given simultaneously. 9'32'34'3v'% This combination frequently causes oxygen desaturation 5'3 '5 '57-59 but is seldom used for routine gastroscopy. 1'2'3'3 Most endoscopists in the United States monitor their patients by pulse oximetry. 2'6 The routine use of electronic monitoring for endoscopic procedures has been generally recommended, 45'5 '6-65 but there is no proof that routine monitoring in average-risk patients reduces morbidity and mortality of gastrointestinal endoscopy. 5 '66 The present study shows that significant alterations of cardiorespiratory function are rare and short-lived during gastroscopy performed in average-risk outpatients, suggesting that routine monitoring in average-risk patients undergoing upper gastrointestinal endoscopy might not improve patient outcome) 7'6v Likewise, no adverse outcome was observed in our study in the patients presenting a significant oxygen desaturation, suggesting that oxygen desaturation alone (of short duration in particular) does not inevitably induce clinically relevant complications) v'6v-69 However, a very large number of patients would be necessary to answer the question whether electronic monitoring has an impact on patient morbidity and mortality. We found similar blood pressure values for each monitoring phase in the four study groups. Only a few (2.1%) episodes of hypotension (mean blood pressure of <60 mm Hg) without clinical manifestations were observed, confirming the results of a previous study. 46 Pulse rates

7 March 1995 GASTROSCOPY: PATIENT TOLERANCE AND MONITORING 703 increased during endoscopy in all groups, which is a known physiological stress response to gastroscopy. 4<7 Accordingly, the acceleration of pulse rate during endoscopy tended to be lower in patients having received both midazolam and pharyngeal anesthesia as compared with placebo. In conclusion, this double-blind, randomized, placebocontrolled study shows that midazolam treatment at a low dose of 35 btg/kg and topical anesthesia with lidocaine spray have a marked independent and additive effect on patient tolerance to upper gastrointestinal endoscopy. Regarding cardiorespiratory risks, clinically significant oxygen desaturation and hypotension occurred rarely, and no adverse outcome was observed. We found that the benefit of conscious sedation outweighs the risks, endorsing the current widespread use of conscious sedation. References 1. Daneshmend TK, Bell GD, Logan RFA. 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The authors thank the nursing staff of the endoscopy unit, Policlinique M6dicale Universitaire, Lausanne, for assistance with this study and Susan Giddons for expert editorial assistance.