Med. J. Cairo Univ., Vol. 84, No. 2, March: 211-217, 2016 www.medicaljournalofcairouniversity.net Versus for Sedation in Patients Undergoing Vitero-Retinal Surgery Under Peribulbar-Block HODA H. OKASHA, M.D.; WAFAA S. HAMD, M.D.; GEHAN M. OBAYA, M.D.; ATEF K. SALAMA, M.D. and MAYADA K. MOHAMAD, M.Sc. The Department of Anesthesia, Surgical Intensive Care and Pain Management, Faculty of Medicine, Cairo University Abstract Background and Aim: Vitreo-retinal surgeriesare preferred to be done under regional anesthesia with sedation which can be provided by many drugs with a relative risk of oversedation and disorientation, confusion or increased risk of respiratory depression. The aim of this study is to compare between dexmedetomidine and propofol as regard efficacy in achieving satisfactory level of sedation without hazards. Subjects and Methods: 50 patients were received peribulbar block and randomely allocated to receive either dexmedetomidine (, n=25) or propofol (, n=25). Results: The mean time to achieve RSS 3 was significantly longer in (5.95±0.32) minutes than (2.63 ± 0.37) minutes (=0.004), themean intra-ocular pressure was significantly lower in (Before 20.8 ±2.3 after 15±2.4) cm H2O than (Before 23.3 ±6.1 after 21.8±6.2) cm H2O ( <0.001), the median pain score was significantly lower in than during the first 6 hours postoperative. Conclusion: appears to provide more cardiovascular stability, more significant reduction of intraocular pressure, better patient and surgeon satisfaction and less adverse events. Using dexmedetomidine there was a slightly longer duration in achieving RSS3 than propofol. Key Words: Peribulbar. Introduction FOR many ophthalmic surgeons, regional anesthesia has become the preferred option over general anesthesia because of the quicker rehabilitation and the avoidance of possible complications of general anesthesia. Several methods of local anesthesia for vitreo-retinal surgery have been described including retrobulbar, peribulbar, sub-tenon's block, and even topical anesthesia in some cases [1]. Although peribulbar block has a delayed onset of Correspondence to: Dr. Hoda H. Okasha, The Department of Anesthesia, Surgical Intensive Care and Pain Management, Faculty of Medicine, Cairo University action but, it is a safe needle block technique [2]. As with all anesthetic techniques, thorough knowledge of the anatomy is essential. Anatomy of the orbit and its nerve supply is necessary for the safe practice of ophthalmic regional anesthesia [3]. Most of ophthalmic intraocular procedures especially vetiro-retinal surgeries can be carried out under regional anesthesia or general anesthesia and is generally determined by the clinical judgment of the anesthesia team. Various types of regional blocks have been described and the most popular techniques used were the peribulbar block and the retrobulbar block which seems to be replaced by the first one to some extent due to fewer incidences of complications [4]. These procedures when performed under regional anesthesia sedative agents can be used to facilitate patients' cooperation and to reduce anxiety. The word sedation convey the sense of a safe, pleasant state [5]. The four stages of anaesthesia are: (I) Anxiolysis (minimal sedation); (Ii) Conscious sedation (moderate sedation analgesia); (Iii) Monitored anesthesia care or MAC (deep sedation analgesia); and (IV) General anesthesia (GA) [6]. During minimal sedation or anxiolysis, the patient feels relaxed and is at a wakeful level of consciousness with airway and protective reflexes intact. Sedation is measured by various scoring systems and the original sedation score was pioneered by Ramsay [7]. There are many sedative agents that can be used one of them is which is an alkylphenol that have hypnotic properties [8], and is rapidly metabolized in the liver by conjugation, with distribution half-life of is 2 to 8 minutes [9]. Apnea occurs after an induction dose of propofol; the incidence and duration of apnea depend on dose, speed of injection, and concomitant premedication [10]. The most prominent effect of propofol is a decrease in arterial blood pressure during induction of anesthesia [11]. 211
212 Versus for Sedation in Patients by continuous infusion provides the ability to titrate to a desired level of sedation and provide a rapid recovery after infusion is terminated, regardless of the duration of the infusion [12]. One of the sedative agents is which is a highly selective alpha-2 agonist that provides anxiolysis and cooperative sedation without respiratory depression [13]. After Intravenous (IV) injection, dexmedetomidine has an onset of action after approximately 15 minutes. Peak concentrations are usually achieved within 1 hour after continuous IV infusion [14] IV doses of dexmedetomidine induced dose-dependent decreases in systolic and diastolic blood pressure and in heart rate and substantial decreases in plasma norepinephrine levels. However, at high-bolus IV doses (50-75 gg), a transient initial hypertensive response may be seen [15]. also produces dosedependent decreases in vigilance and increases in sedation that correlate well with electroencephalogram (EEG)-based spectral entropy monitoring [16]. There is a risk for excessive bradycardia and even sinus arrest when dexmedetomidine is administered in combination with sympatholytic or cholinergic agents [17]. Sedation induced by dexmedetomidine has the respiratory pattern and EEG changes correspond with natural sleep [18]. Material and Methods The study was carried out in the Research Institute of Ophthalmology in Egypt from year 2011 to 2014. After obtaining approval from the Institutional Ethics Committee and written informed consent from 50 adult patients (ASA I-II) of both sexes who were scheduled for vitero-retinal surgery the patients were enrolled in this randomized double-blinded comparative clinical trial in which the excepected time of surgery to be less than 2 hours. Included patients who are graded as ASA (I-II) and age (20-60), while excluded patients were those with age less than 18 years, the usual contraindications for regional anesthesia as patient refusal of local anesthesia, clotting abnormalities, impaired mental status, and allergy to any of the study medications, patients with severe cardiac disease, chronic obstructive lung disease, history of sleep apnea, serum creatinine >200umol/L or advanced liver disease. The patients were randomely allocated to one of the two groups to receive either dexmedetomidine (, n=25) or propofol (, n=25) after insertion of a peripheral IV cannula (22G) under standard monitoring, with oxygen delivery via a nasal cannula. Intraocular pressure will be measured by (TONOMETER N. Prof. Schiotez) before starting loading dose of the sedative drug and after giving the drug. Sedation level will be assessed every 5 minutes by using the Ramsy sedation scale which will be explained to the patient during the preoperative visit. patients will receive dexmedetomidine (Precedex, 200ug per 2ml; Abbot, USA) diluted with 0.9% NaCl to concentration of 4ug/ml in 50ml syringe in a loading dose of 1ug/kg IV over 10 minutes using infusion syringe pump (ATOM 1235 Monoject) followed by continuous infusion of dexmedetomidine 0.2 to 0.6ug/kg/h starting at 0.4ug/kg/h and titrated every 5 minutes in steps of 0.1ug/kg/h. After completing the loading dose of the study drug, peribulbar block will be performed. patients will receive an initial dose of propofol (propofol 1% fresinus, containing 10mg/ml) will be infused IV over 10 minutes at 0.7mg/kg followed by maintenance infusion of 0.5 to 2mg/kg/h by using infusion syringe pump (AT- OM 1235 Monoject) after completing the loading dose of the study drug, peribulbar block will be performed. Peribulbar block is perfomed by using 10ml of mixture of bupivacaine 0.25%, and lidocaine 2% and hyalurinidase 75 unit. Sites of injections: Infratemporal, medial canthus and Supra nasal site. During the procedure if bradypnea (RR<10 BPM) or SpO2 is 92% or less, or hypotension (MAP<50 mmhg) were recorded 4L/min of supplemental oxygen will be administrated via the nasal cannula, and 0.9% saline will be infused respectively with reducing the rate of infusion of the drug aiming to awake the patients to resume his normal breath. If bradycardia (HR <45 beat/ min.) 0.5mg atropine will be given. The infusion pump will be stopped at the end of the procedure. The following measures were assessed throughout the proceducre: 1- Measurment of intraocular pressure before and after induction of sedation. 2- The time to achieve adequate sedation level to achieve Ramsy sedation score of 3. 3- Heart rate, mean arterial pressure,and oxygen saturation every 5min. 4- In the recovery room, Alderet score will be determinded every 5 minutes until discharge. 5- The degree of pain will be assessed by using a 1 0cm visual analogue scale for pain where 0=no pain, 10=intolerable pain at 1, 2, 3, 4, 5 and 6 hours after the end of surgery. The time at which the patient asked for analgesia is recorded.
Hoda H. Okasha, et al. 213 6- All adverse events including, but not limited to, bradycardia (HR<45 beat/min), hypotension (MAP<50 mmhg sustained for > 1 0min), respiratory depression (RR<10 BPM) or oxygen desaturation (SpO2 <92%) will be recorded. Table (1): Ramsay score of sedation. Score Patient response 1 Patient is anxious and agitated or restless, or both 2 Patient is co-operative, orientated, and tranquil 3 Patient responds to commands only 4 Patient exhibits brisk response to light glabellar tap or loud auditory stimulus. 5 Patient exhibits a sluggish response to light glabellar tap or loud auditory stimulus 6 Patient exhibits no response Statistical analysis: Data were summarized and analyzed; and the results were reported as mean ± SD. Comparison of the means of the 2 study groups was done using the student t-test. Non parametric variables were compared using Mann Whitney test. Comparisons against baseline values were performed using oneway analysis of variance (ANOVA). of 0.05 or below was considered statistically significant. Assuming an α level of 0.05, a sample size of 50 patients equally allocated into 2 groups (25 patients per each). Estimation of sample size was performed by using G*Power program. Results 50 adult patients were recruited to undergo vitero-retinal eye surgery; these patients were divided into two groups randomly using doubleblind comparative clinical trial, who received dexmedetomidine sedative drug, Group P who received propofol sedative drug. The demographic data, medical and surgical history did not show any statistically significance difference between the two groups (Table 2). The time to achieve RSS 3 achieved was longer in than and the difference was statistically significant (=0.004) (Table 3). As regards reduction of intra-ocular pressure, comparing the two groups the patients in Group D showed more reduction in the IOP than Group P and. This reduction was statistically significant ( <0.001) (Table 4). Table (2): Demographic data. Age: Mean (±SD) 49.1 (±8.4) 48.3 (±8.1) Gender: Male 15 (60%) 13 (52%) Female 10 (40%) 12 (48%) Allergy: No 25 (100%) 24 (96%) Yes 0 (0%) 1 (4%) A SA: I 15 (60%) 13 (52%) II 10 (40%) 12 (48%) Table (3): Time to induce Ramsy sedation score. Time to induce 5.95 (±0.32) 2.63 (±0.37) 0.004 RSS3 Mean±SD (MIN) Table (4): Effect of the two sedative drugs on intraocular pressure. Effect on IOP (CmH2O) Mean (±SD) 0.001 Before 20.8 (±2.3) 23.3 (±6.1) After 15 (±2.4) 21.8 (±6.2) As regards heart rate, the mean heart rate of was statistically significant higher than ( <0.00) (Fig. 1). As regards the mean arterial blood pressure, there was no statistically significant difference between and ( ) (Fig. 2). Comparing the mean oxygen saturation of and, there was a statistically significant difference all the times (=0.003) except at T0 and POT3 (Fig. 3). As regards Aldret score and recovery and by comparing both groups, there was a statistically significant difference ( <0.001) at T 1 and T2 while at T3 and T4 there was a statistical nonsignificant difference between and Group D ( ) (Table 5). As regards VAS, shows a statistically significant difference as compared to ( p- value <0.001) (Table 6).
214 Versus for Sedation in Patients By comparing the occurrence of adverse events between the two groups, in there was adverse event in the form of hypotension that affected 3 patients however in there was no adverse events ( <0.001) (Table 7). Oxygen saturation SPO2 MAP mmhg Heart Rate BPm 89 87 85 83 81 79 77 75 73 71 69 67 65 104 102 100 98 96 94 92 90 88 86 84 T0 T1 T2 T3 T4 T5 T6 POT POT POT 1 2 3 Time Fig. (1): Mean heart rate of the two groups. T0: Before induction. T5: 25 minutes thereafter. T1: 5 minutes therafter. T6: 30 minutes thereafter. T2: 10 minutes thereafter. POT1: 5 minutes post-operative. T3: 15 minutes thereafter. POT2: 10 minutes postoperative. T4: 20 minutes thereafter. POT3: 15 minutes postoperative. 101 100 99 98 97 96 95 94 93 92 T0 T1 T2 T3 T4 T5 T6 POT 1 Time T0 T1 T2 T3 T4 T5 T6 POT 1 Time POT POT 2 3 Fig. (2): Mean arterial pressure of the two groups. T0: Before induction. T5: 25 minutes thereafter. T1: 5 minutes therafter. T6: 30 minutes thereafter. T2: 10 minutes thereafter. POT1: 5 minutes post-operative. T3: 15 minutes thereafter. POT2: 10 minutes postoperative. T4: 20 minutes thereafter. POT3: 15 minutes postoperative. POT POT 2 3 Fig. (3): The oxygen saturation of the two groups. T0: Before induction. T5: 25 minutes thereafter. T1: 5 minutes therafter. T6: 30 minutes thereafter. T2: 10 minutes thereafter. POT1: 5 minutes post-operative. T3: 15 minutes thereafter. POT2: 10 minutes postoperative. T4: 20 minutes thereafter. POT3: 15 minutes postoperative. Table (5): Aldret score of the two groups. Aldret score Median (Range) T1 T2 T3 T4 T1: 5 minutes post operative. T2: 10 minutes postoperative. 8 (7-9) 9 (8-10) 9 (8-9) <0.001 <0.001 T3: 15 minutes postoperative. T4: 20 minutes postoperative. Table (6): Visual analogue scale of the two groups. VAS Median (Range) T1 1 (0-1) 2 (1-3) <0.001 T2 1 (1-2) 3 (2-4) <0.001 T3 1 (1-2) 3 (2-4) <0.001 T4 1 (1-2) 3 (2-4) <0.001 T5 1 (1-2) 3 (2-4) <0.001 T6 1 (1-2) 3 (2-4) <0.001 T1: 1 hour post operative. T4: 4 hours postoperative. T2: 2 hours postoperative. T5: 5 hours postoperative. T3: 3 hours postoperative. T6: 6 hours postoperative. Table (7): Adverse events between and. Adverse event Frequency (%) No 25 (100%) 22 (88%) <0.001 Yes 0 (0%) 3 (12%) <0.001 Total 25 (100%) 25 (100%) <0.001 Discussion Sedation is regarded as an important adjunct to ophthalmic anesthesia. Pharmacological sedation results in depression of the level of consciousness that is sufficient to achieve anxiolysis, amnesia and somnolence without loss of verbal communication. Administration of a wide array of sedative agents warrants careful prior consideration of the nature of ophthalmic surgery, type of local anesthesia used (both akinetic and non-akinetic techniques), and patient and surgeon preferences [19]. In the current study there was a significant difference between and as regards the time required from the start of the infusion of the study drugs to achieve the target levels of sedation (Ramsy sedation score 3) which was significantly longer in the dexmedetomidine group than in the propofol group. These results were in line with Ashraf Ghaliand his colleagues who performed prospective, single-blind, randomized study on sixty patients who underwentvitero-retinal surgeryundersub-tenon's block in 2011 [20].
Hoda H. Okasha, et al. 215 In the present study there was a significant difference between the groups as regards intraocular pressure measurement after induction of sedation and before performing peribulbar block where there was a great reduction in intraocular pressure in which was in line with Ewen Mac- Donald and his colleagues in 1992 who performeda study in rabbits and measured IOP showing marked reduction in IOP. The mechanisms by which a2- agonists produce their hypotensive effects in the eye are still far from clear because levo-isomer is devoid of a2-activity, the efficacy of dexmedetomidine occur via the a2-mediated mechanism of action which are located pre -junctionally on ocularactivity, sympathetic nerve fibers and postjunctionally in the ciliarybody [21]. The mild reduction in was in line with Sean Neel [22] and his colleagues who performed a study on twenty patients undergoing cataract surgery and measured IOP and foundmoderat reduction in IOP after induction of sedation using propofol. The mechanism by which propofol decreases intraocular pressure is postulated to be its ability to depress the ocular centre of the Brain. Depression of these CNS ocular centres could cause a decrease in intraocular pressure by decreasing extraocular muscle tone, facilitating aqueous drainage, or both. In the present study as regards hemodynamics, we found that, there was a similar significant reduction in heart rate compared with the baseline values, and intra operative heart rate in was significantly higher than in all the times. The same results were reported by Kaygusuz et al., [23] demonstrated a powerful inhibitory effect of propofol on sympathetic outflow [24]. The decrease in the HR might be attributed to the sympatholytic effects and in part because of a vagal mimetic effect [25]. In the present study as regards intraoperative mean arterial blood pressure readings in, there was initial increase then decrease in MAP and this was in line with Ashraf Darwish [26] and his colleague who performed a comparative study on one hundred patients undergoing cataract surgery divided into two groups one receiving propofol and the other receiving dexmedetomidine under preipulbar block. Although large doses (1 or 2 gg/ kg) of dexmedetomidine produced the initial increase of arterial pressure temporarily, presumably due to peripheral vasoconstriction [27] and then reduction in MAP similar to and this was in line with Ashraf Ghalli andhis colleagues [20]. This is due to dexmedetomidine decrease sympathetic outflow [28]. As regards intra-operative oxygen saturation in our current study by comparing the mean oxygen saturation of and, there was a significant difference all the times except at the baseline reading. There was less change from baseline values in, while there was significant reduction in the oxygen saturation in the compared with the baseline values and this was in line with Ashraf Darwish [26] and his colleagues. In the present study, Aldret score and recovery showed a significant difference in which there was a rapid return to a full recovery state in while there was a gradual return to full recovery state in. This was in line with the study of Ashraf Darwish and his colleagues [26] which stated that achieved Aldret score 10 faster than this may be attributed to that dexmedetomidine have longer elimination have life of 2 hours. In the current study and as regards assessment of pain and analgesic effect of the test drug by using Visual Analogue Scale (VAS), there was more analgesic effects of patients receiving dexmedetomidine than propofol. This was in line with Ashraf Ghalli and his colleagues [20], who described that dexmedetomidine has analgesia sparing effects when used for sedation in the ICU [29]. The halflife of dexmedetomidine has been described as 2h, would likely to explain why the analgesic sparing properties persisted postoperatively [30]. In present study and as regards adverse event, there was no adverse events in, there were minimal adverse events in in the form of mild hypotension but they were not clinically significant this was in line with J Allhashemi [31]. References 1- CHARLES S. and FANNING G.L.: Anesthesia considerations for vitreoretinal surgery. Ophthalmologist Clin. North Am. June, 19: 239-43, 2006. 2- KUMAR C.M. and DODDS C.: Ophthalmic regional block. Ann. Acad. Med. Singapar, 35: 158-67, 2006. 3- BEARD C. and QUICKERT M.H.: Anatomy of the orbit: A dissection manual. 3 rd ed. Birmingham, AL: Aesculapius Publishing Co, 4: 75-90, 1988. 4- REACH G., BODENHAM A.R. and BRAITHWAITE: Peribulbar anesthesia using a mixture of local anesthetic and vecuronium. Anesthesia, 53: 551-4, 1998. 5- OSTERMANN M.E., KEENAN S.P., SEIFERLING R.A. and SIBBALD W.J.: Sedation in the intensive care unit: A systematic review. JAMA, 283: 1451-59, 2000. 6- Joint Commission on Accreditation of Healthcare Organizations. Standards for moderate and deep sedation and
216 Versus for Sedation in Patients anaesthesia hospital accreditation standards. Oakbrook Terrace, Ill.: JCAHO, 108-111, 2002. 7- De JONGHE B., COOK D., APPERE-De-VECCHI C., GUYATT G., MEADE M. and OUTIN H.: Using and understanding sedation scoring systems: A systematic review. Intensive Care Med., 26: 275-85, 2000. 8- JAMES R. and GLEN J.B.: Synthesis, biological evaluation, and preliminary structure-activity considerations of a series of alkylphenols as intravenous anesthetic agents. J. Med. Chem., 23: 1350-57, 1980. 9- SIMONS P., COCKSHOTT I. and DOUGLAS E.: Blood concentrations, metabolism and elimination after a subanesthetic intravenous dose of (14) C-propofol (Diprivan) to male volunteers. Postgrad. Med. J., 61: 64, 1985. 10- GOODMAN N.W., BLACK A.M., CARTER J.A., TAY- LOR M.B., GROUNDS R.M., MULROONEY P.D. and MORGAN M.: Ventilatory effects of propofol during induction of anesthesia: Comparison with thiopentone. Anesthesia, 41: 816-20, 1986. 11- LARSEN R., RATHGEBER J., BAGDAHN A., et al.: Effects of propofol on cardiovascular dynamics and coronary blood flow in geriatric patients: A comparison with etomidate. Anesthesia, 43 (Suppl): 25-31, 1988. 12- ZHOU Y., JIN X. and KANGY.: Midazolam and propofol used alone or sequentially for long term sedation in critically ill, mechanically ventilated patients a prospective randomized study. Critical Care, 18: 2-9, 2014. 13- SCHEININ H., AANTAA R., ANTTILA M., et al.: Reversal of the sedative and sympatholytic effects of dexmedetomidine with a specific alpha2-adrenoceptor antagonist atipamezole: A pharmacodynamic and kinetic study in healthy volunteers. Anesthesiology, 89: 574-84, 1998. 14- VENN R.M., KAROL M.D. and GROUNDS R.M.: Pharmacokinetics of dexmedetomidine infusions for sedation of postoperative patients requiring intensive care. Br. J. Anaesth., 88: 669-75, 2002. 15- TALKE P., RICHARDSON C.A., SCHEININ M., et al.: Postoperative pharmacokinetics and sympatholytic effects of dexmedetomidine. Anesth. Analg., 85: 1136-42, 1997. 16-BULOW N.M., BARBOSA N.V. and ROCHA J.B.: Opioid consumption in total intravenous anesthesia is reduced with dexmedetomidine: A comparative study with remifentanil in gynecologic video laparoscopic surgery. J. Clin. Anesth., 19: 280-85, 2007. 17- JALOWIECKI P., RUDNER R., GONCIARZ M., et al.: Sole use of dexmedetomidine has limited utility for conscious sedation during outpatient colonoscopy. Anesthesiology, 103: 269-73, 2005. 18- HSU Y.W., CORTINEZ L.I., ROBERTSON K.M., et al.: pharmacodynamics: Part I: Crossover comparison of the respiratory effects of dexmedetomidine and remifentanil in healthy volunteers. Anesthesiology, 101: 1066-76, 2004. 19- KATZ J., FELDMAN M.A., BASS E.B., LUBOMSKI L.H., TIELSCH J.M., PETTY B.G., et al.: Adverse intra- operative medical events and their association with anesthesia management strategies in cataract surgery. Ophthalmology, 108: 17, 2001. 20- GJALLI A., MAHFOUZ A., et al.: versus propofol for sedation in patients undergoing vitreoretinal surgery under sub-tenon's anesthesia. Saudi J. Anesthesia Jan.-Mar., 5: 36-41, 2011. 21- JAANA VARTIAINEN, EWEN MacDONALD, AR- TOURTTI, THARRIROUHIAINEN and RAIMO VIR- TANEN: -lnduced Ocular Hypotension in Rabbits with Normal or Elevated Intraocular Pressures Invest. Ophthalmol. Vis. Sci., 33: 2019-23, 1992. 22- SEAN NEEL, ROBERT DEITCHJR, S. SMOORTHY, STEPHEN DIERDORF and ROBERT YEE: Changes in intraocular pressure during low dose intravenous sedation with propofol before cataract surgery. Br. J. Ophthalmol., 79: 1093-7, 1995. 23- KAYGUSUZ K., GOKCE G., GURSOY S., AYAN S., MIMAROGLU C. and GULTEKIN Y.: A comparison of sedation with dexmedetomidine or propofol during shockwave lithotripsy: A randomized controlled trial. Anesth. Analg., 3: 106-14, 2008. 24- WEIW, QIANGCHEN and LIANGCHENGZHANG: versus midazolam for sedation in upper gastrointestinal endoscopy. Journal of International Medical Research, 1: 1-7, 2014. 25- De JONGE A., TIMMERMANS P.B. and VAN ZWIETEN P.A.: Participation of cardiac presynaptic alpha 2-adrenoceptots in the bradycardiac effects of clonidine and analogues. Naunyn Schmiedebergs Arch. Pharmacol., 317: 8-12, 1981. 26- ASHRAF DARWISH, REHAB SAMI, MONA RAAFAT, RASHAD AREF and MOHAMED HISHAM: versus for Monitored Anesthesia Care In Patients Undergoing Anterior Segment Ophthalmic Surgery Under Peribulbar Medial Canthus Anesthesia. Life Sci. J., 9: 789-93, 2012. 27- BLOOR B.C., WARD D.S., BELLEVILLE J.P. and MAZE M.: Effects of intravenous dexmedetomidine in humans. Hemodynamic changes. Anesthesiology, 77: 1134-42, 1992. 28- TALKE P., CHEN R., THOMAS B., AGGARWALL A., GOTTLIEB A., THORBORG P., et al.: The hemodynamic and adrenergic effects of perioperative dexmedetomidine infusion after vascular surgery. Anesth. Analg., 90: 834-9, 2000. 29- EKE T. and THOMPSON J.: The national survey of local anesthesia for ocular surgery. I. Survey methodology and current practice. Eye, 13: 189-95, 1999. 30- KHAN Z.P., FERGUSON C.N. and JONES R.M.: Alpha- 2 and imidazoline receptor agonists: Their pharmacology and therapeutic role. Anesthesia, 54: 146-65, 1999. 31- ALHASHEMI J.A.: vs midazolam for monitored anesthesia care during cataract surgery Br. J. Anaesth., 96: 722-6, 2006.
Hoda H. Okasha, et al. 217