Oral Clonidine Premedication Research Articles

The effect of oral clonidine premedication on blood loss and the quality of the surgical field during endoscopic sinus surgery: a placebo-controlled clinical trial

Bleeding during functional endoscopic sinus surgery (FESS) remains a challenge for both surgeons and anesthesiologists despite several modalities available for improving the surgical field. This study was conducted to evaluate the effect of oral clonidine premedication on blood loss and the quality of the surgical field in FESS. In a placebo-controlled clinical trial, a total of 84 American Society of Anesthesiologists (ASA) physical status I-II patients undergoing endoscopic sinus surgery for chronic sinusitis were randomly allocated to receive either oral clonidine 0.2mg or identical-looking placebo tablets 90min before arrival at the operating room. Blood loss in the clonidine group was 214±67ml on average and that in the placebo group was 276±78ml (mean±SD, p<0.01). The median (range) bleeding score in the clonidine group was significantly lower than that in the placebo group (2 (1-3) vs. 2.5 (2-4), p<0.0001). Accordingly, the surgeon was more satisfied with the surgical field in the clonidine group than with that in the placebo group (median score, 4 (3-5) vs. 3 (1-5), p<0.001). In conclusion, premedication with oral clonidine 0.2mg can effectively reduce bleeding during FESS.

Effect of oral clonidine premedication on perioperative haemodynamic response and post-operative analgesic requirement for patients undergoing laparoscopic cholecystectomy

Clonidine has anti-hypertensive properties and augments the effects of anaesthesia, hence we considered it to be an ideal agent to contain the stress response to pneumoperitoneum. We studied the clinical efficacy of oral clonidine premedication in patients undergoing laparoscopic cholecystectomies. Fifty patients scheduled for elective laparoscopic cholecystectomy under general anaesthesia were randomly allocated to receive premedication with either oral clonidine 150 μg (Group I, n = 25) or placebo (Group II, n = 25) 90 minutes prior to induction. The patients were managed with a standard general anaesthetic. The two groups were compared with respect to haemodynamic parameters, isoflurane concentration, pain and sedation scores, time to request of analgesic and cumulative analgesic requirements. Oral clonidine was found to be significantly better in terms of maintaining stable haemodynamics, having an isoflurane sparing effect and having a prolonged time interval to the first request of analgesia postoperatively compared to the control group. Administration of oral clonidine 150 μg as a pre-medicant in patients undergoing laparoscopic cholecystectomy results in improved perioperative haemodynamic stability and a reduction in the intra-operative anaesthetic and post-operative analgesic requirements.

Effects of Oral Clonidine Premedication on Haemodynamic Response to Laryngoscopy and Tracheal Intubation: A Clinical Trial

The objective of this study was to evaluate the efficacy of pre-anesthetic orally administration of clonidine on pulse rate and blood stress response to laryngoscopy and tracheal intubation. In a double-blinded, randomized study, 274 ASA I and II subjects with age of 18 to 45 years scheduled for elective surgery under general anesthesia were enrolled. They were randomly allocated to receive oral clonidine (0.2 mg) or placebo as premedication 90-120 min before surgery. All the patients received Succinylcholine (1.5 mg kg(-1)) after induction of anesthesia with Fentanyl (50 microg) and Thiopentone (5 mg kg(-1)). The anesthesia was maintained with halothane (1.5 Mac) in 50% mixture of N2O/O2. Heart rate and systolic blood pressure were recorded before, immediately after and then every 5 min after intubation until 20 min. The Clonidine group showed a significant superiority over placebo in the prevention of increase in systolic blood pressure as well as heart rate over the intubation. A significant difference was observed in both heart rate and systolic blood pressures were significantly higher in Control group at three subsequent measurements following intubation. The results of this study suggest that orally administered clonidine in preanesthetic period, provides more haemodynamic stability and attenuates the stress response to laryngoscopy and intubation.

Study Of Comparative Effects Of Oral Clonidine Vs Oral Diazepam Pre-Medication On The Extent And Duration Of Sensory Blockade In Patients Undergoing Vaginal Hysterectomy Under Spinal Anaesthesia

Clonidine stimulates alpha 2 adrenergic inhibitory neurons in medullary vasomotor centre which decreases sympathetic outflow. Decreased sympathetic nervous system activity is manifested as decreases in systemic blood pressure, heart rate and cardiac output. Our results show that there was significant difference in the time of onset of anaesthesia, which coincides with the study done by Herbhej singh, George, Y .Gaines and Paul .F.White, in which they concluded that oral Clonidine shortened the onset time of tetracaine’s sensory block & prolonged the duration of sensory & motor block. There are more studies, which also show that oral clonidine premedication prolong the sensory as well as motor blockade from Lignocaine & Tetracaine spinal anaesthesia. The antinociceptive effect produced by the orally administered 2adrenergic agonist is mainly caused by direct spinal activation due to spread of the drug via the systemic circulation into the spinal cord. Neuraxial Clonidine inhibits spinal substance P release and nociceptive neuron firing produced by noxious stimuli. Clonidine modifies function of K channels in the CNS causing cell membrane hyperpolarization which decreases anaesthetic requirements.

DECREASE IN PAIN OF PROPOFOL INJECTION AFTER ORAL CLONIDINE

Objective: To assess the potential of oral Clonidine premedication indecreasing patient discomfort during the injection of Propofol. Design: This was a comparative study of 80 ASA class1 and II. Place and Duration of study: This study was carried out at Combined Military Hospital, Kharian. Patients andMethods: This was a study of 80 ASA class 1 and 2 patients of similar age group. Patients selected were from amongstthose undergoing elective gynaecological surgery, specifically Diagnostic Dilatation and Curettage. These patients wereselected by non-probability convenience sampling. The patients were randomly assigned, by means of a random table,to one of the two groups of 40 patients each. Group ‘A’ patients were given oral Clonidine, 300mg two hours beforeinduction of anaesthesia by Propofol injection. Group B’ patients were given 0.01 to 0.02mg/kg plain Lidocaine justbefore Propofol induced anaesthesia. Non-invasive systolic arterial blood pressure (ni-SBP), non-invasive diastolicarterial blood pressure (ni-DBP) and heart rate were recorded in the ward about 120 min [before administration of oralClonidine in group-A] in both groups. Measurements were repeated in the operating theatre before induction ofanaesthesia. Patients in Group-A were given one tablet Catapres [Clonidine, 300mg] with a sip of water, two hoursbefore induction of anaesthesia and they were observed in the Post Anaesthesia Care Unit during this period, whiletheir pulse and blood pressure were monitored. Patients in group-B were not premedicated with Clonidine. They wereinjected 0.01 to 0.02mg/kg injection plain lidocaine, through the injection port of an 18-gauge cannula, as premedicationjust before propofol monitoring was done as for group-A. Before administration of propofol, the patient was requestedto rate immediately any sensation of pain during injection as none (0), mild (1), moderate (2) or severe (3), also calledthe Verbal Rating Scale (VRS). Results: The results showed both groups to have similar pain score, and differenceswere deemed statistically not significant by the analysis. Conclusion: Our results imply that Clonidine makes anexcellent premedication with Propofol for short gynaecological procedures.

Effect of clonidine premedication on postoperative sore throat and hoarseness after total intravenous anesthesia

To determine the effect of oral clonidine premedication on postoperative sore throat and hoarseness, we evaluated the incidence and severity of each of these complications in patients who underwent elective surgery in the supine position. The subjects were 82 patients, American Society of Anesthiologists (ASA) status I-III, aged 15-82 years. They were premedicated with either 150 microg oral clonidine and 20 mg raftidine (clonidine group; n = 41) or with 20 mg raftidine only (control group; n = 41) 2 h before anesthesia induction. General anesthesia was maintained with propofol, ketamine, fentanyl, and vecuronium, with or without epidural anesthesia. Postoperative sore throat and hoarseness were evaluated immediately after surgery and on the day after surgery. The incidences of sore throat and hoarseness tended to be higher in the clonidine group than in the control group; however, the difference did not reach statistical significance. There were no significant differences in the severity of these symptoms between the two groups. In conclusion, oral premedication with 150 microg clonidine did not prevent postoperative sore throat or hoarseness, and may have exacerbated these symptoms.

Oral clonidine premedication reduces minimum alveolar concentration of sevoflurane for laryngeal mask airway insertion in children

Sevoflurane is widely employed for inhalational induction in children. Clonidine deepens volatile anesthetics and reduces several types of MAC of sevoflurane. Laryngeal mask airway is a useful device for pediatric anesthesia. The aim of the current study was to determine whether oral clonidine premedication can reduce MAC of sevoflurane for an LMA insertion in children. Fifty-six ASA physical status I patients (3-11 years) scheduled for general anesthesia were randomly divided into two groups of 28 patients each. One group (clonidine group) received clonidine 4 microg x kg(-1) approximately 100 min before anesthesia, and the other (control) group did not. Anesthesia was induced with sevoflurane. Each concentration of sevoflurane, at which an LMA insertion was attempted, was predetermined according to the modification of Dixon's up-and-down method with 0.25% as a step size and held constant for at least 20 min before the trial. All responses ('movement' or 'no movement') to an LMA insertion were assessed. Minimum alveolar concentration values of sevoflurane for an LMA insertion were lower in the clonidine group (1.31% +/- 0.18% [mean +/- sd]) than in the control group (2.00% +/- 0.16%). Logistic regression analysis revealed that sevoflurane EC95 values were 1.79% and 2.49% in the clonidine and control groups, respectively. Oral clonidine premedication reduced the MAC (EC50) and EC95 values of sevoflurane for LMA insertion by 38% and 28%, respectively.

Clonidine premedication effects on inhaled induction with sevoflurane in adults: a prospective, double‐blind, randomized study

The purpose of this study was to evaluate whether oral clonidine premedication becomes an alternative to N2O in terms of shortening the induction time and attenuation of the adrenergic response to tracheal intubation during inhalation induction with sevoflurane, and to evaluate the quality of anesthetic induction according to the patient's satisfaction. We studied 84 female patients who were randomly allocated into four study groups: Groups I and II received a placebo orally, and Groups III and IV received clonidine at 150 and 300 microg, respectively, 90 min before induction of anaesthesia. Patients were anesthetized using a triple-deep-breath technique with 5% sevoflurane in Groups I, III and IV, and with 60% N2O-5% sevoflurane in group II. Induction time was significantly longer (P < 0.05) in Group I. Increases in mean blood pressure and heart rate after tracheal intubation were significantly suppressed in Groups III and IV but not in Group II compared with Group I. Comfort and impression of anesthesia was better in Groups III and IV than in Groups I and II. In volatile anesthetic induction, pre-anesthetic clonidine may become an alternative to N2O and may provide more comfort than with N2O.

Clonidine Premedication in Patients with Sleep Apnea Syndrome: A Randomized, Double-Blind, Placebo-Controlled Study

Patients with sleep apnea often present with cardiac diseases and breathing difficulties, with a high risk of postoperative respiratory depression. We conducted a randomized, double-blind, prospective study in 30 adult patients with obstructive sleep apnea, undergoing elective ear-nose-throat surgery. The patients were randomly assigned to receive placebo or clonidine (2 microg/kg oral) the night before and the next morning 2 h before surgery. Spo2, heart rate, mean arterial blood pressure, snoring, and oronasal airflow were monitored for 36 h. A standard anesthesia was used consisting of propofol and remifentanil. Anesthetic drug consumption, postoperative analgesics, and pain score were recorded. In the clonidine group, mean arterial blood pressures were significantly lower during induction, operation, and emergence from anesthesia. Both propofol dose required for induction (190 +/- 32.2 mg) and anesthesia (6.3 +/- 1.3 mg . kg(-1).h(-1)) during surgery were significantly reduced in the clonidine group compared with the placebo group (induction 218 +/- 32.4, anesthesia 7.70 +/- 1.5; P < 0.05). Piritramide consumption (7.4 +/- 5.1 versus 14.2 +/- 8.5 mg; P < 0.05) and analgesia scores were significantly reduced in the clonidine group. Apnea and desaturation index were not different between the groups, whereas the minimal postoperative oxygen saturation on the day of surgery was significantly lower in the placebo than in the clonidine group (76.7% +/- 8.0% versus 82.4% +/- 5.8%; P < 0.05). We conclude that oral clonidine premedication stabilizes hemodynamic variables during induction, maintenance, and emergence from anesthesia and reduces the amount of intraoperative anesthetics and postoperative opioids without deterioration of ventilation.

The effects of prostaglandin E1 or oral clonidine premedication on blood loss during paranasal sinus surgery

The effects of prostaglandin E1 or oral clonidine premedication on blood loss during paranasal sinus surgery

Intravenous Clonidine Prolongs Spinal Anesthesia after Hyperbaric Bupivacaine

Background: The prolonging effects of oral clonidine premedication on spinal anesthesia are known. We hypothesized that intravenous clonidine might have the same effect even if administered after an intrathecal local anesthetics injection. Methods: To assess the prolonging effect of intravenous clonidine on spinal anesthesia, we designed a double-blinded, placebo-controlled, prospective study. Patients scheduled for orthopedic surgery were studied. All patients received 12 mg of hyperbaric bupivacaine intrathecally and were allocated to three groups. Group 1 (n = 26) was the control. Group 2 (n = 26) and Group 3 (n = 26) received 3/kg intravenous clonidine at the same time and 50 minutes after intrathecal hyperbaric bupivacaine injection. Sensory block was evaluated by pinprick and the duration was defined as the time needed for regression to L1 dermatome. Duration of motor blockade was defined as the time needed for recovery of knee flexion. Results: The duration of sensory block was longer in Group 2 (196 42 minutes) and 3 (179 41 minutes) than Group 1 (125 25 minutes). The Duration of motor blockade was longer in Group 2 (153 26 minutes) than Group 1 (131 29 minutes). The lowest heart rate and mean blood pressure were not different among the groups. Conclusions: Intravenous clonidine after an intrathecal hyperbaric bupivacaine injection prolonged spinal anesthesia without added complications.

Oral Clonidine Premedication Enhances the Propofol Hypnotic Effect as Measured by the Bispectral IndexTM

Oral Clonidine Premedication Enhances the Propofol Hypnotic Effect as Measured by the Bispectral IndexTM

Prevention of Sevoflurane-Induced Agitation with Oral Clonidine Premedication

To the Editor: We read with great interest the article by Kulka et al. (1) who concluded that IV clonidine prevents sevoflurane-induced agitation and suggested investigation into whether clonidine influences discharge-ready time. However, IV formulation is commercially unavailable in many countries, including the US and Japan. Thus, we present our previously collected data to support their conclusion and resolve the problem. After institutional approval and informed parental consent, children aged 2–11 yr undergoing minor (urological, ophthalmological, otological, and orthopedic) surgery received one of oral clonidine (2 or 4 μg/kg, up to 150 μg), midazolam (0.5 mg/kg, up to 10 mg), diazepam (0.4 mg/k, up to 10 mg), and placebo 30–60 min before anesthesia. Rectal diclofenac (12.5 or 25 mg) was given to each child immediately after induction of anesthesia, which was maintained with sevoflurane and nitrous oxide administered through an orotracheal tube. After anesthesia, the patients were transferred to wards. We blindly recorded agitation score during and after emergence from anesthesia (0 = sleep, 1 = calm, 2 = agitated but consolable, and 3 = severely agitated and inconsolable) and the time when children met discharge criteria (stable vital signs, ambulation, minimal bleeding, minimal pain, and minimal nausea/vomiting) (2) for determining home readiness. Oral clonidine 4 μg/kg reduced agitation scores; the other premedicants failed to do so (Table 1). These data strengthen the recent report by Kulka et al. (1). Clonidine did not prolong the time to meet home discharge criteria (Table 1). Oral clonidine premedication attenuates pain and emesis after pediatric anesthesia (3,4). These favorable properties may have offset possible extension of discharge ready time associated with postoperative sedative effects. Inclusion of the time to drink clear fluids in discharge criteria may have provided different results, although we believe that oral intake is not an absolute prerequisite for discharge from hospital. Our find- ings indicate that oral clonidine (4 μg/kg) premedication may be an alternative to intraoperative IV clonidine for the relief of sevoflurane-induced agitation without influencing discharge ready time in children.Table 1: Patient Characteristics, Agitation Score, and Discharge-Ready TimeKatsuya Mikawa, MD Kahoru Nishina, MD Makoto Shiga, MD

Oral clonidine premedication reduces the awakening concentration of propofol.

To investigate the effects of oral clonidine premedication on emergence from propofol/fentanyl anesthesia, we studied 72 healthy male patients who were undergoing elective orthopedic surgery: the Control group, the 2.5 microg/kg Clonidine group, and the 5.0 microg/kg Clonidine group (n = 24 each). Nothing was administered to the Control group. Clonidine (2.5 or 5.0 microg/kg) was orally administered 90 min before the induction of anesthesia in the Clonidine groups. Patients were anesthetized with computer-assisted continuous infusion of propofol and fentanyl, with the three groups receiving the same concentrations of propofol (3 microg/mL) and fentanyl (1 ng/mL) starting 20 to 30 min before the end of surgery. Propofol infusion was then abruptly discontinued at the end of surgery in all patients. After propofol was discontinued, the response to verbal commands was evaluated every 30 s, and arterial blood samples for propofol and clonidine concentrations were taken when the patients opened their eyes. The time required to respond to a verbal command was 14.9 plus/minus 8.3 min for the 5.0 microg/kg Clonidine group, and this was significantly longer than the Control (8.2 plus/minus 5.0 min) and the 2.5 microg/kg Clonidine (9.0 plus/minus 3.7 min) groups (P < 0.01). Serum propofol concentration at awakening in the 5.0 microg/kg Clonidine group was 1.0 plus/minus 0.4 microg/mL, which was significantly smaller than the Control (1.6 plus/minus 0.4 microg/mL) and the 2.5 microg/kg Clonidine (1.4 plus/minus 0.3 microg/mL) groups (P < 0.01). The blood clonidine concentration was associated with a decrease in the awakening propofol concentration. In conclusion, 5 microg/kg oral clonidine premedication decreases the awakening propofol concentration and delays arousal from propofol/fentanyl anesthesia. Preanesthetic medication with 5 microg/kg oral clonidine, but not 2.5 microg/kg clonidine, is associated with prolonged recovery from propofol/fentanyl anesthesia.

The Effect of Clonidine Premedication on Hemodynamic Responses to Microlaryngoscopy and Rigid Bronchoscopy

The usual hemodynamic response to laryngoscopy and bronchoscopy is an increase in heart rate and arterial blood pressure. Previous work has reported that 10%-18% of the patients develop ischemic ST segment changes during the procedure. Therefore, we performed a prospective, randomized, double-blinded study in 36 patients scheduled for elective microlaryngeal and bronchoscopic surgical procedures to evaluate the effects of 300-microg oral clonidine premedication (n = 18) or placebo (n = 18) on the hemodynamic alterations and the incidence of perioperative myocardial ischemic episodes. Myocardial ischemia was assessed by using continuous electrocardiographic monitoring, beginning 30 min before, and lasting until 24 h after the operation. During the procedure, patients receiving placebo exhibited a significant increase (mean +/- SD) in arterial blood pressure (the systolic increasing from 137+/-11 to 166+/-17 mm Hg, the diastolic increasing from 80+/-11 to 97+/-14 mm Hg) and heart rate (increasing from 79+/-15 to 97+/-12 bpm) compared with the baseline and with the clonidine group. A dose of 300-microg clonidine blunted the hemodynamic response to endoscopy. Ventricular arrhythmias were more frequent in patients who were not premedicated with clonidine. Two patients in the control group, but none in the clonidine group, had evidence of myocardial ischemia. These data should encourage routine premedication with clonidine in patients undergoing microlaryngoscopic and bronchoscopic procedures.

The Awakening Concentration of Sevoflurane in Children

Sevoflurane is frequently used as a rapidly acting drug for the induction of anesthesia. We investigated the awakening concentration (MAC-awake) of sevoflurane in ASA physical status I children (age range 2–10 yr). We also investigated the effects of two different doses of clonidine (2 and 4 μg/kg) on the MAC-awake of sevoflurane. Subjects were randomly divided into three groups and received placebo (n = 24), clonidine 2 μg/kg (n = 17), or clonidine 4 μg/kg (n = 22) orally, 100 min before the induction of anesthesia. Sedation scores were estimated, by using a five-point scale, after entry into the operating room, and anesthesia was induced and maintained with sevoflurane in oxygen and balanced nitrogen, without an additional anesthetic. After surgery, end-tidal sevoflurane was decreased stepwise by 0.2% at 15-min intervals, a standardized verbal command was played to the patients, and the MAC-awake was determined. The MAC-awake of sevoflurane alone was 0.78% ± 0.24% (mean ± sd), which decreased to 0.36% ± 0.09% and 0.36% ± 0.16% (both P <0.0001, compared with the control group) after premedication with the small and large doses of clonidine, respectively. The lack of any dose-response relationship might be explained by a plateau effect. Implications The awakening concentration of sevoflurane in unpremedicated children was 0.78%. Oral clonidine premedication at a dose of 2 μg/kg reduced the awakening concentration to 0.36%. However, an additional decrease in this value was not observed after the administration of the larger dose of clonidine premedication (4 μg/kg).

Effects of oral clonidine premedication on side effects of intravenous ketamine anesthesia: a randomized, double-blind, placebo-controlled study

Study Objective: To determine the effects of oral clonidine premedication on hemodynamic changes during the entire course of ketamine anesthesia and incidence of postoperative adverse reactions. Design: Randomized, prospective, double-blind, placebo-controlled study. Setting: Department of Anesthesiology, University of Tsukuba Hospital, Ibaraki, Japan. Patients: 39 ASA physical status I and II patients undergoing superficial surgeries. Interventions: Placebo, clonidine 2.5 μg/kg, and clonidine 5 μg/kg groups received respective doses of oral clonidine 90 minutes prior to surgery. Anesthesia was induced with ketamine 2 mg/kg intravenously (IV), trachea was intubated, and anesthesia was maintained with 67% nitrous oxide, oxygen, and supplemental ketamine (1 mg/kg) when systolic blood pressure and heart rate (HR) exceeded 180 mmHg and 100 bpm, respectively. Measurements and Main Results: In the clonidine 2.5 μg/kg group, HR response to tracheal intubation was significantly less, while in the clonidine 5 μg/kg group both mean arterial pressure and HR responses were significantly suppressed, compared with the placebo group. Intraoperative coefficients of variations of HR were significantly less in both clonidine groups than the placebo group. Incidence of nightmare and degree of salivation were significantly less in the clonidine 5 μg/kg group than in the placebo group. Conclusion: Oral clonidine 2.5 μg/kg and clonidine 5 μg/kg attenuates cardiostimulatory effects, while clonidine 5 μg/kg was associated with reduced incidence and severity of nightmare and salivation attributable to IV ketamine.

The Effect of Oral Clonidine Premedication on Lumbar Cerebrospinal Fluid Pressure in Humans.

Alpha-2 adrenergic agonists including clonidine decrease cerebral blood flow. The specific actions of clonidine on cerebrospinal fluid (CSF) pressure in humans remain to be elucidated. We evaluated the effect of oral clonidine premedication on lumbar CSF pressure in patients without intracranial disease. Seventy-four patients undergoing subarachnoidal block were divided randomly into either a clonidine or a control group. In the clonidine group, the patients were premedicated orally with 5 microg/kg clonidine 60 min before arrival in the operating room. Subarachnoidal puncture was performed via midline approach using a 23-gauge needle at the L2-3 or L3-4 intervertebral space with the patient in the lateral decubitus position. Before the injection of local anesthetic, lumbar CSF pressure was measured. Lumbar CSF pressure was 8.1+/-2.4 mmHg in the clonidine group, which was significantly lower than that in the control group (9.4+/-2.8 mmHg, p<0.05). The cerebral perfusion pressures were 76.2+/-12.5 mmHg in the clonidine group and 91.7+/- 15.4 mmHg in the control group (p<0.001). In the clonidine group, preanesthetic mean blood pressure had a significant correlation with lumbar CSF pressure (r=0.619, p=0.019). We conclude that Lumbar CSF pressure was attenuated by oral premedication with 5 microg/kg clonidine. Clonidine also contributed to a significant correlation between preanesthetic mean blood pressure and CSF pressure.

Oral Clonidine Premedication Enhances Postoperative Analgesia by Epidural Morphine

This study was designed to evaluate the effects of oral clonidine premedication on postoperative analgesia by epidural morphine in a prospective, randomized, double-blinded design. Sixty consenting patients, scheduled for total abdominal hysterectomy, were randomly assigned to one of three groups (n = 20 each); the clonidine-morphine group received oral clonidine 5 μg/kg 90 min before arriving in the operating room and epidural morphine 2 mg before induction of general anesthesia, the clonidine-placebo group received oral clonidine 5 μg/kg and no epidural morphine, and the placebo-morphine group received no clonidine and epidural morphine 2 mg. An epidural catheter was placed at the L1-2 or L2-3 interspace, and 1.5% lidocaine was used for surgical anesthesia in all patients. General anesthesia was then induced with propofol, and maintained with a continuous infusion of propofol and 67% nitrous oxide in oxygen during surgery. Four patients were subsequently withdrawn from the study. After surgery, patient-controlled analgesia using IV morphine was used to assess analgesic requirement. Morphine consumptions determined every 6 h after surgery in the clonidine-morphine and placebo-morphine groups were significantly less than the clonidine-placebo group until 12 h after surgery, whereas those of the clonidine-morphine group were significantly less than the placebo-morphine group from 13 to 42 h after surgery. Visual analog (pain) scale (VAS) scores in the clonidine-morphine group were significantly lower than the placebo-morphine group at 48 h at rest, and at 1, 24, 36, and 48 h with movement. Similarly, VAS scores in the clonidine-morphine group were significantly lower than the clonidine-placebo group at 1 and 6 h both at rest and with movement, whereas VAS scores in the clonidine-placebo group were significantly lower than the placebo-morphine group at 24, 36, and 48 h at rest and with movement. The incidence of nausea and pruritus was similar between groups. We conclude that the combination of oral clonidine and epidural morphine produces more potent and longer lasting postoperative analgesia than either drug alone without increasing the incidence of adverse effects after major gynecologic surgeries. Implications A small dose of epidural morphine is often used for postoperative analgesia. We found that oral clonidine premedication 5 μg/kg improves the analgesic efficacy of epidural morphine without increasing the incidence of adverse side effects.

ORAL PREMEDICATION ENHANCES THE POSTOPERATIVE ANALGESIA BY EPIDURAL MORPHINE

S338 INTRODUCTION: It is controversial whether preoperative clonidine administration reduces postoperative morphine requirements [1,2]. We have previously reported that oral clonidine premedication potentiates postoperative analgesia from intrathecal morphine [3]. This study was designed to prospectively assess the effect of oral clonidine premedication on postoperative analgesia by epidural morphine. METHOD: After institutional approval, 56 consented patients, undergoing gynecological surgeries, were randomly assigned to one of three groups; Clonidine-Morphine group (n=19) received oral clonidine 5 mcg/kg 90 min before arriving at the operating room and epidural morphine 2 mg, Placebo-Morphine group (n=20) received no clonidine and epidural morphine, Clonidine-Placebo group received clonidine and no epidural morphine. Epidural catheters were placed at L1-2 or L2-3 interspace, and tested with 3 ml 1.5 % lidocaine containing 15 mcg epinephrine followed by 12 ml 1.5 % lidocaine solution with or without 2 mg morphine. General anesthesia was induced with propofol and maintained with 67 % nitrous oxide and propofol. Lidocaine 10 ml was injected into the epidural space every hour without any other analgesic. After surgery, IV-PCA morphine was started (no continuous infusion, PCA bolus dose of 2 mg morphine, lockout interval of 10 min, maximal 1 hour dose of 12 mg). Postoperative pain was evaluated using the VAS at 1, 6, 12, 18, 24, 36 and 48 h. Nausea and pruritus were also assessed at the same interval. Unpaired Student's t-test and Mann-Whitney U-test were used for data analysis. P<0.05 was considered statistically significant. RESULTS: The three groups were similar in terms of age, height, weight, duration of surgery and doses of lidocaine. Cumulative morphine requirements in the Clonidine-Morphine group were significantly less than the other two groups (Figure 1). VAS scores in the Clonidine-Morphine group were lower than the Placebo-Morphine group at 48 h at rest, and also were lower than the Placebo Morphine group at 1, 24, 36 and 48 h at moving. There were no significant differences in the incidence of nausea and pruritus among groups.Figure 1: Cumulative morphine doses in the Clonidine-Morphine group were less than those in the Clonidine-Placebo group throughout study period and than those in the Placebo-Morphine group from 20 to 48 h. * P < 0.05 vs the Placebo-Morphine group.CONCLUSION: Our results suggest that oral clonidine premedication enhances postoperative analgesia by epidural morphine.