Dexmedetomidine for Sedation During Ambulatory Colonoscopy in Older Patients

Med. J. Cairo Univ., Vol. 81, No. 1, September: 741-745, 2013 www.medicaljournalofcairouniversity.net Dexmedetomidine for Sedation During Ambulatory Colonoscopy in Older Patients MOHAMED ABD EL MONEIM MAHMOUD, M.D.* and KAMAL ALETRPY, M.D.** The Departments of Anesthesia* and Tropical Medicine**, National Hepatology & Tropical Medicine, Research Institute Abstract Aim: This study was designed to test the hypothesis that a Dexmedetomidine (DEX) infusion as a primary sedative would be non inferior to boluses of Midazolam (MDZ) in older patients undergoing ambulatory colonoscopy. Patients and Methods: Fifty ASA physical status I-IV patients undergoing colonoscopy were randomized in this study to receive either (DEX) infusions (n=25) or titrated boluses of (MDZ) (n=25). Meperidine 0.5mg/kg was administered after initial sedation but before the start of the procedure. Patient tolerance was assessed using physiologic variables and side effects associated with both drugs. Verbal pain/anxiety and patient/operator satisfaction were also assessed. Results: As a group, the physiologic characteristics demonstrated no significant differences in the response to the colonoscopy procedure. Although operator satisfaction surveys were similar between groups patient satisfaction was superior with DEX, the incidences of bradycardia and hypotension were more while the adjusted verbal pain and anxiety scores were less in the (DEX) group compared with the (MDZ) group. The total dose of Meperidine was significantly less p<0.05 during the DEX infusions. The increased incidence of nausea and vomiting in the MDZ group is the most likely explanation for the 8-minute delay in time to home readiness compared with the DEX group. Conclusion: This study demonstrates that Dexmedetomidine and Midazolam were equally well tolerated in older patients undergoing ambulatory colonoscopy when administered by an anesthesia provider. This study demonstrates that Dexmedetomidine was efficacious as a sole sedative. Patient satisfaction was superior with DEX. Key Words: Ambulatory colonoscopy Dexmedetomidine. Introduction COLONOSCOPY is one of the most commonly performed outpatient procedures for the diagnosis, serial surveillance, and treatment of gastrointestinal Correspondence to: Dr. Mohamed Abd El Moneim Mahmoud, The Department of Anesthesia, National Hepatology & Tropical Medicine, Research Institute disorders. The pain 'and anxiety associated with this procedure necessitates the use of sedationanalgesia to achieve patient comfort and cooperation [1]. Older patients undergoing colonoscopy are at the highest risk of hemodynamic instability, respiratory depression, and delays in the time to home readiness associated with the use of narcotic analgesia 121. Dexmedetomidine, a sedative with high a 2 -adrenoreceptor affinity and action in the locus ceruleus, is an alternative for sedation in intensive care units (ICUs). Dexmedetomidine may enhance patient safety and comfort in long-term sedation [3,4]. Aim of the work: This study was designed to determine the efficacy of dexmedetomidine infusion vs midazolam boluses in maintaining sedation in older patients undergoing ambulatory colonoscopy. Patients and Methods The study was performed in National Hepatology & Tropical Medicine, Research Institute in the period between December 2011 and March 2012. Institutional and ethics committee approval was obtained for this study, and all participants gave written informed consent. 50 patients scheduled for ambulatory colonoscopy were randomized to either the (DEX) or (MDZ) group. Patients were between the ages of 60 and 70yr of age and had an ASA physical status of I-IV. The main exclusion criteria were acute severe neurological disorder, mean arterial pressure less than 55mm Hg. Heart rate less than 50/min, atrioventricular-conduction grade II or III (unless pacemaker installed), and use of a 2 agonists or antagonists within 24 hours prior to randomization and if they had a history of chronic narcotic and/or benzodiazepine use, drug abuse, previous colon resection. 741

742 Dexmedetomidine for Sedation During Ambulatory Colonoscopy A modified Ramsay scale (6-point sedation scale) was used to assess the baseline sedation level and to titrate (DEX) and (MDZ) throughout the procedure [5]. DEX 0.5µg/kg load administered over 10 minutes versus midazolam (MDZ) boluses. This was followed by a maintenance infusion of DEX at 0.6pg/kg/hr and titrated to achieve desired clinical effect with doses ranging from 0.2 to 1p,g/kg/hr. The rate of the maintenance infusion should be adjusted to achieve the targeted level of sedation, versus a normal saline infusion for the midazolam group. There may be great individual variability in the hemodynamic effects (especially on heart rate and blood pressure), as well as the sedative effects of DEX. For this reason, the dose must be carefully adjusted to achieve the desired clinical effect [6]. Midazolam was given in 0.5mg increments to maintain an equivalent target level of sedation. Sedation was titrated until a score of 2 was achieved. If the patient's baseline sedation score was 2 (cooperative, oriented, tranquil), DEX or MDZ were titrated to a sedation score of 3 (responds to verbal commands). Subsequent doses of midazolam could be administered after the colonoscopy started, if: 1- Sedation score decreased to less than 2 or 3; 2- Patient's verbal rating of their anxiety level was in the moderate-to-severe range (5-10); or 3- At the request of the blinded operator. After initial sedation but before the start of the procedure, patients were administered an initial dose of Meperidine 0.5mg/kg. If patients spontaneously complained of pain or if their verbal analog score increased Meperidine was given in 0.25mg/kg increments to treat pain as needed groups. No additional doses of sedatives or Meperidine if patients experienced any of the following: Respiratory depression (respiratory rate <8 breaths per minute or Sa0 2 <94% or end-expiratory carbon dioxide >50mm Hg), hypotension (systolic blood pressure 20% less than baseline or <80mm Hg for >1 min), or bradycardia (decreases in heart rate [HR] by >30% or HR <50bpm for >lmin) Standard anesthesia monitors were used to monitor HR, blood pressure, Sa02, electrocardiogram, and end-expiratory CO 2 (at a nasal cannula without oxygen flow). The patient was continuously monitored with hemodynamic and respiratory measurements recorded every 5min throughout the procedure. Oxygen at 5L/min by simple face mask was administered throughout the procedure. Patient tolerance was assessed by recording the number of episodes of hemodynamic and respiratory disturbances throughout the study. Hemody- namic disturbances included the incidence of increased blood pressure (systolic blood pressure >20% of baseline), tachycardia (HR >110bpm or >20% of baseline), hypotension (systolic blood pressure <80mm Hg or >20% decrease from baseline), bradycardia (HR <50bpm or >30% decrease from baseline). Respiratory disturbances included respiratory rate (<8 breaths per minute) and reductions in arterial saturation (Sa0 2 <92%). The incidence of nausea, vomiting, and pruritus were also recorded. Patients were reassessed for pain and anxiety at the following anatomical points: 1- Colonoscope insertion; 2- Sigmoid; 3- Cecum; 4- Retroflexed view of the rectum; and 5- Withdrawal of scope. A blinded investigator asked each patient to assess his/her level of pain and anxiety using an 11-point (0-10) verbal pain and anxiety rating scale [7,8]. The verbal pain and anxiety scales were anchored by word pairs (e.g., no pain to severe pain, no anxiety to most severe anxiety ever). At the conclusion of the colonoscopy and no further injections were administered. A modified Aldrete score [9] of 8 defined completion of Phase I recovery and a Postanesthetic Discharge Scoring [10] of 9 defined time to home readiness [9,11]. Patient and operator satisfaction were surveyed using a four-point scale (1=poor, 2=satisfactory, 3=good, 4=excellent). Patients were surveyed 30min after the end of the procedure and on postoperative day 1 (telephone interview) to assess their satisfaction with the management of their sedation-analgesia. Patient satisfaction was assessed by asking about overall satisfaction, residual drug effects, number of hours it took before they returned to normalcy. Operator satisfaction was assessed by rating patient tolerance to the procedure, ease of examination, level of analgesia, and overall impression. Statistical analysis: Statistics were expressed as proportions (frequency count) for categoricaltype variables and Means±SD for interval (ratio)- type variables. Repeated-measures analysis of variance was performed on outcome measurements across time (physiologic variables). The results were generally consistent between groups over time and therefore were not reported. Data were analyzed by using either t-test (age, weight, procedural and recovery characteristics). The frequency data were analyzed by Fisher's exact test. A p- value of 0.05 was considered significant unless otherwise indicated.

Mohamed A. Mahmoud & Kamal Aletrpy 743 Results Fifty patients (45 male, 5 female) were randomized for this study. Patient demographics are illustrated in Table (1). The most common indication for colonoscopy was follow-up for colonic polyps (65%). The overall procedural characteristics for patients receiving monitored anesthesia care in both treatment groups are demonstrated in Table (2). Doses of MDZ and DEX used are consistent with those reported in other studies in patients undergoing colonoscopy [12]. Table (1): Patient demographics. No. 25 25 Gender (F/M) 2/23 3/22 Age (yr) 64±9.6 65±14.1 Weight (kg) 92±18.4 93±19.0 ASA classification III 9 (36) 11 (44) Smoker 19 (76) 20 (80) Diabetes 7 (28) 5 (20) Hypertension 16 (64)* 11 (44) Coronary artery disease 5 (20)* 2 (8) Data are expressed as Mean±SD (age, weight) or actual number and percentage (%) of all patients in each treatment group. *p<0.05. DEX = Dexmedetomidine group; MDZ = Midazolam group. Table (2): Procedure characteristics. No. 25 25 Colonoscopy time 31±15 33±19 Monitored anesthesia care time 59±29 59±21 Midazolam (mg) 2.5±1.0 Meperidine (mg) 139±71 78±51* Dexmedetomidine (tig) 91±29 Number of dosage increases 2.3±1.9* 2.0±1.7 Postanesthesia recovery score 8.9±1.1 9.3±0.8 Postanesthesia discharge score 8.4±0. 8 8.6±0.7 Time to home readiness (min) 48±28 40±25 Data are expressed as Mean±SD. *p<0. 05. DEX = Dexmedetomidine group; MDZ = Midazolam group. Table (3): The mean cardiopulmonary changes over the course of procedure to each regimen. Variable DEX MDZ p-value MAP 88±9.66 98±12.03 =0.02 HR 66±6.06 85±6.12* 0.01 RR 16±1.07 17±1.06 =0.02 E e CO 2 38±2.04 36±2.03 =0.02 Sao 2 97.8±1.02 98.2±1.01 =0.02 MAP = Mean arterial pressure (mm Hg); HR = Heart rate; RR = Respiratory rate; E e CO 2 = End expiratory carbon dioxide; Sao 2% = Arterial oxygen saturation. DEX = Dexmedetomidine group; MDZ = Midazolam group. Data are expressed as Mean±SD. *p.0.01 between the two groups. Table (4): Episodes of adverse hemodynamic events. Tachycardia 6 (32)* 2 (10) Hypotension 4 (12) 7 (18)* Bradycardia 2 (11) 6 (22)* Increased blood pressure 5 (15)* 4 (9) Data represent number of patients experiencing an adverse hemodynamic event in each treatment group. The total number of adverse events for each treatment group are indicated in parenthesis. *p>0.05 indicates that the total number of adverse hemodynamic events was significantly increased. DEX = Dexmedetomidine group; MDZ = Midazolam group. The cardiopulmonary response to each regimen is shown in Table (3). Although there was no significant difference in group variability, significant changes over the course of procedure were found for mean arterial pressure, respiratory rate, and end-tidal carbon dioxide by using two-way analysis of variance (p=0.02). The number of episodes of adverse hemodynamic events are depicted in Table (4). The incidence of respiratory rates <8 breaths/min was similar between groups. The incidence of nausea (3vs 8; p=0.03), vomiting (0 vs 5; p=0.06), and pruritus (1 vs 3; p=0.75) also tended to be decreased in the DEX group compared with those receiving MDZ. 6 Co 3 -- o 8 co 6. a- > 4. 2- o DEX gp a MD7 ip * * * it BASE BOLUS INSERT SIGMOID CECUM RETRO END Fig. (1): Comparison of level of verpal anxiety (VAS) and pain scale (VPS) befor, during, and after colonoscopy. Baseline (Base), immediately after sedative & analgesic loading (Bolus), after colonoscope insertion (Insert), level of sigmoid flexure (Sigmoid), level of cecum before removal of colonoscope during retroflexion to examine the anus (Retro) and after completion of procedure (End). Data are expressed as Mean±SD. DEX = Dexmedetomidine group; MDZ = Midazolam group. The MDZ values increase significantly in comparison to the DEX values. *p<0.05 between the two groups. Fig. (1) illustrates the verbal anxiety and pain scores for each group before, during, and after the procedure. Compared with the DEX group, the baseline anxiety (p=0.02) and pain scores (p=0.06) were increased in MDZ group. Even after normalizing the values in each group, the adjusted verbal pain scores for the MDZ group were higher than t I w x z a z R a.

744 Dexmedetomidine for Sedation During Ambulatory Colonoscopy those for the DEX group at the sigmoid flexure (p=0.03) and cecum (p=0.03). The adjusted verbal anxiety scores were also increased in the MDZ group after the initial dose (p=0.03), sigmoid flexure (p=0.04), and cecum (p=0.03). The total dose of Meperidine was significantly less p<0.05 during the DEX infusions. There was no significant difference between the percentages operators that rated the conditions as excellent or good versus satisfactory or poor. Patient satisfaction was superior with DEX. Discussion This study demonstrates that Dexmedetomidine infusions and Midazolam boluses are equally well tolerated in older patients undergoing ambulatory colonoscopy when administered by an anesthesia provider. Although the patient and operator surveys revealed overall satisfaction in both groups, patients in the MDZ group had more side effects (i.e., hypertension, tachycardia, nausea) and had higher adjusted verbal pain and anxiety scores during parts of the procedure. There were no significant differences in the variability of several physiologic variables between the two treatment groups. The differences in HR between the two treatment groups are most likely related to the known chronotropic effects and doses of meperidine and suggests that bolus dosing of the drugs in the MDZ group may not be the most hemodynamically stable method of administering sedation-analgesia in patients with significant cardiovascular disease. The incidence of hypotension and brdyachycardia in the DEX group is likely related to its alpha2 adrinirgic agonist effect. A multicenter trial in predominantly medical ICU patients found earlier extubation and reduced delirium with dexmedetomidine compared with midazolam [3]. The significant increase in the baseline verbal anxiety scores in the group MDZ was surprising. The trend toward a higher level of cardiovascular disease in the MDZ group could have contributed to this unexpected finding. The decreased level of anxiety may have had an influence on the decreased verbal pain scores noted in the DEX group during portions of the procedure [13,14]. The administered of DEX over 10 minutes followed by a maintenance infusion of at 0.6µg/kg/hr suggests that the lower verbal anxiety scores may also have been because of sufficient analgesia/sedation during portions of the procedure. Overall, the gastroenterologist could not distinguish between treatment groups and noted that in general the quality of sedation-analgesia was much better in patients participating in the study. Sedation-analgesia for colonoscopy is most commonly administered under the supervision of a gastroenterologist using bolus doses of meperidine [14]. Our decision to use of a double-blinded design to compare the tolerance of using DEX and MDZ for colonoscopy in a nonoperating room environment necessitated the use of anesthesia providers. Indeed, the current package insert for DEX recommends that the administration should be limited to anesthesia providers [15]. Unfortunately, the economic implications of using an anesthesia provider to administer DEX for routine colonoscopies severely limit its broadest application. The use of DEX in older patients may be made more economically viable in patients requiring monitored anesthesia care for significant coexisting medical disease [16]. In summary, DEX infusions or MDZ boluses with meperidine boluses were equally well tolerated in older patients undergoing ambulatory colonoscopy when administered by an anesthesia provider. 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