Efficacy and safety of premedication with oral ketamine for day-case adenoidectomy compared with rectal diazepam/diclofenac and EMLA

BACKGROUND: Because of its pain-attenuating and sedative properties oral ketamine has been used as premedication in children and adults. We wanted to compare in children scheduled for adenoidectomy safety and efficacy of oral ketamine with a premedication that causes similar preoperative sedation and relief of pain at the venepuncture site. We also evaluated the effect of i.v. glycopyrrolate added to these combinations. METHODS: One hundred children between 10 and 15 kg of body weight scheduled for day-case adenoidectomy were randomly assigned to one of four groups: groups DG and DS received diclofenac 12.5 mg and diazepam 0.5 mg/kg rectally, EMLA cream at the venepuncture site, and placebo orally; groups KG and KS received ketamine 6.0 mg/kg orally, placebo cream at the puncture site, and placebo rectally; additionally, groups DG and KG received glycopyrrolate 5 microg/kg, and groups DS and KS received placebo intravenously. We recorded perioperatively scores (open scale 1-9) for stridor, sedation, bleeding, nausea, pain, heart rate, the need for analgesics and registered psychotomimesis and well-being at home. RESULTS: The children of the K-groups became more tearful during separation from their parents (P=0.0072). No other differences were found between the ketamine and diazepam/diclofenac groups before and after premedication until induction of anaesthesia. Oral ketamine produced unpleasant psychotomimesis in four out of 59 children. During the first 10 min postoperatively, the score for stridor was significantly higher in group KS than in the D-groups; stridor scores > or = 6 were seen in one child of the D-groups (DS) and in six children of the K-groups (n.s.), of whom three developed laryngospasm (one reintubation). Glycopyrrolate diminished salivation in all groups, but had no effect on stridor scores. Additionally, glycopyrrolate delayed the onset of eating at home. CONCLUSION: Premedication with racemic oral ketamine 6 mg/kg does not seem to be suitable for upper airway procedures. Addition of i.v. glycopyrrolate before the induction of anaesthesia significantly reduced the scores for salivation.     

Oral clonidine blunts the heart rate response to intravenous atropine in humans.

Clonidine, recently introduced into anesthesia practice, may cause bradycardia. Whether this bradycardia is reversible with atropine is not known. Accordingly, we studied heart rate (HR) responses to intravenous atropine in 80 patients assigned randomly to either a control group, who received no medication (n = 20), or a clonidine group, who received oral clonidine of approximately 1.2 micrograms.kg-1 (n = 20), 2.5 micrograms.kg-1 (n = 20), or 5 micrograms.kg-1 (n = 20). All patients received incremental doses of atropine, 2.5, 2.5, and 5 micrograms.kg-1, at 2-min intervals (total dose 10 micrograms.kg-1). Positive chronotropic response to the cumulative atropine dose of 10 micrograms.kg-1 was attenuated significantly only in patients given clonidine 5 micrograms.kg-1 (7 +/- 1 beats per min, mean +/- standard error) when compared with those given smaller doses of clonidine (15 +/- 2, 16 +/- 2 beats per min) or no clonidine (19 +/- 2 beats per min) (P less than 0.05). To determine whether HR hyporesponsiveness to atropine induced by clonidine can be overcome by a larger dose of atropine, the authors studied 30 additional patients given clonidine 5 micrograms.kg-1 or no medication. In all patients not receiving clonidine (n = 15), HR increased by more than 20 beats per min when atropine of 15 micrograms.kg-1 was administered, whereas in only 5 patients (33%) receiving clonidine did the HR increase by 20 beats per min after atropine 15 micrograms.kg-1 (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of Oral Clonidine on Heart Rate Changes after Neostigmine-Atropine Administration

Background: Clonidine reduces heart rate (HR) responses to atropine, whereas neostigmine causes bradycardia. This study was designed to determine whether clonidine premedication would reduce tachycardia after neostigmine-atropine administration.

Methods: Fifty adult patients without cardiovascular disorders who were schedule for elective surgeries were randomly assigned to receive approximately 5 [micro sign]g/kg (oral clonidine clonidine group, n = 25) or no clonidine (control group, n = 25) 90 min before induction of general anesthesia. After tracheal intubation, anesthesia was maintained with N2 O and 1-2% isoflurane in oxygen while patients were paralyzed with vecuronium and mechanically ventilated. When surgeries were completed, adequate spontaneous respiration, responses to verbal commands, and sustained tetanus by stimulating the ulnar nerve were confirmed, and patients' tracheas were extubated. Then a mixture of 0.05 mg/kg neostigmine and 0.02 mg/kg atropine was administered intravenously over 20 s under stable hemodynamic condition (systolic blood pressure and HR within +/- 5% of preceding values), and blood pressure and HR were measured noninvasively at 1-min intervals for 10 min.

Results: Increases in HR in the clonidine group were significantly less 1-4 min after neostigmine-atropine injections compared with HR values in the control group. A maximum increase in HR of the clonidine group was also significantly less than the control group (15 +/- 7 vs. 23 +/- 10 beats/min; means +/- SD), whereas absolute values of mean blood pressure were similar. Severe bradycardia (HR < 50 beats/min) developed in no patients in either group.     

Oral Clonidine Premedication Blunts the Heart Rate Response to Intravenous Atropine in Awake Children

Background: Clonidine, which is known to have analgesic and sedative properties, has recently been shown to be an effective preanesthetic medication in children. The drug may cause side effects, including bradycardia and hypotension. This study was conducted to evaluate the ability of intravenous atropine to increase the heart rate (HR) in awake children receiving clonidine preanesthetic medication.

Methods: We studied 96 otherwise healthy children, 8-13 yr old, undergoing minor surgery. They received, at random, oral clonidine 2 or 4 micro gram *symbol* kg sup -1 or placebo 105 min before scheduled induction of anesthesia. Part I (n = 48, 16 per group): When hemodynamic parameters after insertion of a venous catheter had been confirmed to be stable, atropine was administered in incremental doses of 2.5, 2.5, and 5 micro gram *symbol* kg sup -1 every 2 min. The HR and blond pressure were recorded at 1-min intervals. Part II (n = 48, 16 per group): After the recording of baseline hemodynamic values, successive doses of atropine (5 micro gram *symbol* kg sup -1 every 2 min, to 40 micro gram *symbol* kg sup -1), were administered until HR increased by 20 beats *symbol* min sup -1. The HR and blood pressure were recorded at 1-min intervals.

Results: Part I: The increases in HR in response to a cumulative dose of atropine 10 micro gram *symbol* kg sup -1 were 33 plus/minus 3%, 16 plus/minus 3%, and 8 plus/minus 2% (mean plus/minus SEM) in children receiving placebo, clonidine 2 micro gram *symbol* kg sup -1, and clonidine 4 micro gram *symbol* kg sup -1, respectively (P < 0.05). Part II: The HR in the control group increased by more than 20 beats *symbol* min sup -1 in response to atropine 20 micro gram *symbol* kg sup -1 or less. In two patients in the clonidine 4 micro gram *symbol* kg sup -1 group, HR did not increase by 20 beats *symbol* min sup -1 even after 40 micro gram *symbol* kg sup -1 of atropine.     

Propofol-ketamine vs propofol-fentanyl in short gynecologic surgery

The study was performed to investigate efficacy and tolerability of the association propofol-ketamine as alternative to propofol-fentanyl. Forty female, classified ASA I-II, aged 18-50 years and scheduled for short gynecologic procedures under general anesthesia were included in a comparative, randomized, single blind study. Patients were divided in two groups; in group K anesthesia was induced with propofol 1.5 mg/kg and ketamine 1 mg/kg i.v. In group F anesthesia was induced with propofol 2.5 mg/kg and fentanyl 1.5 micrograms/kg. Arterial blood pressure (BP), heart rate (HR), respiratory rate (RR) and arterial O2 saturation (SATO2) were measured. Though preliminary, our data suggest that the association propofol-ketamine reach an adequate level of anesthesia with few and negligible effects on cardiorespiratory system, thus allowing a better operability and safety. The incidence of post operative psychotic disturbances seems to be low and moderate. We can't draw any definitive conclusion, but we think that other studies should be performed to clarify the possible role of ketamine in propofol anesthesia.     

Effect of intravenous clonidine on the dose of thiopental required to induce anesthesia.

A randomized, double-blind, controlled trial was conducted to investigate the influence of intravenous clonidine on thiopental dose requirements when used for induction of anesthesia and associated hemodynamic effects. Sixty ASA physical status I or II patients were randomly allocated to one of three treatment groups: normal saline solution (control, n = 20); clonidine (2.5 micrograms/kg, n = 20); or clonidine (5 micrograms/kg, n = 20). The test drug was administered 15 min before induction of anesthesia with intravenous thiopental. The dose of thiopental to produce loss of lash reflex was recorded as well as mean arterial blood pressure and heart rate at 3-min intervals up to induction of anesthesia and then at 1-min intervals for 5 min. Significant decreases in thiopental dose were observed in both groups receiving clonidine compared with the control group, but there was no significant difference between clonidine groups. With dosage calculated according to total body mass, the control group required 5.50 +/- 1.15 mg/kg (mean +/- SD) of thiopental, whereas those who received 2.5 micrograms/kg of clonidine required 4.15 +/- 1.46 mg/kg of thiopental (a reduction of 25%), and those who received 5.0 micrograms/kg of clonidine required 3.48 +/- 1.06 mg/kg of thiopental (a reduction of 37%). When thiopental dose was adjusted for lean body mass, similar reductions were obtained. Clonidine, in both doses, produced more sedation than control, and the 2.5-mg/kg dose produced less sedation than the larger dose. Mean arterial blood pressure was lower in the groups receiving clonidine. There were no significant differences in heart rate among the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparative effects of oral clonidine and intravenous esmolol in attenuating the hemodynamic response to epinephrine injection.

STUDY OBJECTIVE: To evaluate oral clonidine and intravenous esmolol in blunting hemodynamic changes associated with intranasal injection of an epinephrine-containing local anesthetic solution during general anesthesia. DESIGN: Prospective, randomized, double-blind, placebo-controlled study. SETTING: University Medical Center. PATIENTS: 61 consenting ASA physical status I and II outpatients undergoing endoscopic sinus and septoplasty surgery with general anesthesia. INTERVENTIONS: All patients were assigned to receive either a placebo (P) tablet or a similar-appearing tablet containing either clonidine 0.2 mg (C2) or 0.4 mg (C4) orally 1 hour prior to entering the operating room. Prior to the intranasal injection of epinephrine, patients were administered either saline, 0.03 ml.kg-1 followed by an infusion of 0.016 ml.kg-1.min-1, or esmolol (E) 300 micrograms.kg-1 followed by a continuous infusion of 160 micrograms.kg-1.min-1. MEASUREMENTS AND MAIN RESULTS: Arterial blood pressure and heart rate (HR) values were recorded preoperatively, immediately before induction of anesthesia, and at 1-minute intervals after induction of anesthesia until 15 minutes after injection of an epinephrine-containing solution. Level of sedation was assessed using a linear visual analog scale (VAS) prior to oral premedication, immediately before induction of anesthesia, and 30 minutes after anesthesia. There were no significant differences in sedation scores among the four treatment groups. HR following injection of epinephrine-containing solution was significantly less in the C2, C4, and E groups than the placebo group. Compared to P and E treatment groups, MAP values were significantly lower in the C4 treatment group. CONCLUSION: In this healthy, young, nonsmoking outpatient population, premedication with oral clonidine, 0.2 to 0.4 mg, was effective in blunting the acute hemodynamic changes associated with injection of an epinephrine-containing local anesthetic solution during endoscopic sinus or septoplasty surgery.     

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. IMPLICATIONS: 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 on the intrapulmonary right-to-left shunt in one-lung ventilation in the dog

Many vasoactive drugs--vasoconstrictors as well as vasodilators--impair the efficiency of hypoxic pulmonary vasoconstriction (HPV) and may cause dangerous hypoxemia during one-lung ventilation (1-LV). The effect of clonidine, a widely used alpha 2-agonistic antihypertensive agent, on intrapulmonary right-to-left shunt (Qs/Qt) during 1-LV has not yet been studied. METHODS. Twenty anesthetized beagle dogs were instrumented with a 7F Swan-Ganz catheter and an arterial line. A left thoracotomy in the lateral position was performed and the left main bronchus was prepared for clamping. Intravenous clonidine (5 micrograms/kg) was administered to 10 dogs. Anesthesia was maintained with either thiopental and fentanyl or halothane (0.8 insp. vol%) and fentanyl. The ventilatory frequency (100% O2, tidal volume 150 ml/kg) was adjusted to obtain an end-expiratory CO2 of 4.5%. Each dog underwent the following experimental sequence: (1) baseline measurements with 2-LV; (2) 20 min 1-LV (left lung atelectasis was achieved by clamping the left main bronchus); and (3) 20 min 2-LV. After allowing 30 min for conversion from i.v. to halothane anesthesia or vice versa, the procedure was repeated (5 dogs in each group received first i.v. and 5 dogs first halothane anesthesia). RESULTS. Qs/Qt was slightly but not significantly higher under halothane anesthesia in both groups during 1-LV as well as 2-LV (Table 1). No differences existed between the halothane and i.v. groups with regard to arterial pO2 and cardiac index. In the control group (i.v. or halothane, n = 20) Qs/Qt increased during 1-LV from 10.8 +/- 2.8% (mean +/- S.D.) to 26.6 +/- 5.5%, and in the clonidine group (i.v. or halothane, n = 20) from 7.2 +/- 2.3% to 18.3 +/- 5.4%. These differences between the control and clonidine groups are significant (P less than 0.001) for 1-LV as well as 2-LV. Arterial pO2 during 1-LV was reduced less in the clonidine group (573 +/- 48 to 390 +/- 99 mmHg) than in the control group (550 +/- 44 to 323 +/- 94 mmHg) (P less than 0.05). During 1-LV no significant differences between the two groups could be detected with regard to pulmonary artery pressure, mixed-venous pO2, pCO2, and pH. Heart rate, cardiac index, and oxygen uptake were significantly lower and arteriovenous O2 difference was significantly greater in the clonidine group, indicating better control of sympathoadrenergic activity under clonidine. CONCLUSIONS. We conclude that pretreatment with clonidine improves HPV during 1-LV. This effect of clonidine is probably due to reduced sympathetic nervous system activity.     

Ketamine reduces swallowing-evoked pain after paediatric tonsillectomy

BACKGROUND: Ketamine efficacy as an analgesic adjuvant has been studied in several clinical settings with conflicting results. The aim of this study was to investigate the effect of ketamine on spontaneous and swallowing-evoked pain after tonsillectomy. METHODS: Fifty children were randomized to receive premedication with either ketamine 0.1 mg kg(-1) i.m. or placebo given 20 min before induction of a standard general anaesthesia. All children received rectal diclofenac 2 mg kg(-1) and fentanyl 1 micro g kg(-1) i.v. before surgery. RESULTS: The ketamine group showed significantly lower pain scores both at rest and on swallowing, with less total paracetamol consumption (P < 0.05) during the 24 h after surgery. Significantly more patients required postoperative morphine titration in the control group (P < 0.05). The time to the first oral intake, and duration of i.v. hydration, were significantly shorter and the quality of oral intake was significantly better in the ketamine group (P < 0.05). There were no differences in the incidence of vomiting or dreaming between the groups. CONCLUSION: Premedication with a small dose of ketamine reduces swallowing-evoked pain after tonsillectomy in children who received an analgesic regimen combining an opioid and a NSAID.     

Oral clonidine premedication for elderly patients undergoing intraocular surgery.

In a randomized double-blind study, the effects of clonidine premedication as a sedative, anxiolytic, analgesic and oculohypotensive agent were studied in 100 elderly patients (62 to 65 +/- 10 years, ASA grade I-II) undergoing elective intraocular surgery under local anaesthesia. The control group (Group A, n = 50) received oral diazepam 0.15 mg/kg 120 min before surgery and Group B (n = 50) received oral clonidine 300 micrograms 120 min before surgery. Two hours after the premedication, there was significantly more sedation (P less than 0.05) and less subjective anxiety (P less than 0.05) in the clonidine group than in the control group. There was a significant fall in intraocular pressure (IOP) from 20 +/- 0.5 to 13 +/- 0.5 mmHg (P less than 0.05) and significant reduction in systolic and diastolic blood pressure (BP) and heart rate (HR) (P less than 0.05) in the clonidine group as compared to the control group. Perioperatively, significantly more supplementation with i.v. diazepam was given in the control group than in the clonidine group (P less than 0.01). The incidence of intra-operative hypertension (P less than 0.01) and tachycardia (P less than 0.05) was significantly greater in the control group than in the clonidine group. A significantly larger number of patients in the clonidine group scored a Post-Anaesthesia Recovery (PAR) score of 10 as compared to the control group (P less than 0.01). There was no statistical difference in the postoperative Visual Analogue Scale (VAS) scores for pain, number of analgesic requests and emesis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intrathecal clonidine does not reduce post-spinal shivering

BACKGROUND: After general or epidural anesthesia, clonidine is known to be effective in suppressing established shivering. The aim of this study was to assess the preventive effect of intrathecal clonidine on post-spinal shivering compared with intravenous (i.v.) clonidine. METHODS: One hundred and fifty patients scheduled for orthopedic surgery were randomly allocated into three groups to receive either 1 microg/kg clonidine i.v. (IV group) or the same volume of isotonic saline (control and IT groups) at 5 min before spinal anesthesia. Spinal anesthesia was performed with 12-15 mg hyperbaric bupivacaine 0.5% plus either 1 ml of saline (control and IV groups) or 150 microg clonidine (IT group). Shivering was evaluated for a period of 90 min and graded as none, mild, moderate, and severe. RESULTS: Twenty patients (40%) in the control group and 17 patients (34%) in the IT group showed shivering compared with four (8%) in the IV group. Patients with moderate-to-severe shivering were only seen in the control and IT group, and the maximal intensity of shivering was not different between the two groups. Patients in the IV group were significantly more sedated than the other groups. CONCLUSIONS: The intrathecal administration of clonidine 150 microg fails to prevent post-spinal shivering; by contrast, we have confirmed that i.v. clonidine 1 microg/kg is an effective method to prevent shivering in patients undergoing spinal anesthesia for orthopedic surgery.     

Preoperative clonidine attenuates stress response during emergence from anesthesia

STUDY OBJECTIVES: To investigate whether a single preoperative IV dose of clonidine blunts the hemodynamic and hyperadrenergic responses not only to intubation, but also to extubation. DESIGN: Randomized, double-blind, placebo-controlled study. PATIENTS: 29 ASA physical status I and II patients (ages 18-65) who were scheduled for noncardiac, elective surgery. Patients were randomly assigned to either receive clonidine 3 microg/kg IV immediately before anesthesia induction or placebo. INTERVENTIONS: Insertion of a 14 G cannula in a large cubital vein for the determination of plasma catecholamines using local anesthesia. Insertion of a radial artery catheter for measuring blood pressure (BP) using local anesthesia. Transthoracic echocardiography to determine cardiac output (CO). MEASUREMENTS: Heart rate (HR), mean arterial pressure (MAP), CO, and plasma catecholamine concentrations. Measurements were performed: before induction (baseline), during intubation, 10 min after intubation, after surgery, during extubation, and 10 min after extubation. MAIN RESULTS: During intubation MAP, HR, and CO were lower in the clonidine group. Compared with baseline measurements, MAP and CO increased less in the clonidine group during intubation. During extubation, MAP was lower in the clonidine group. CO and MAP increased less as compared with baseline measurements in the clonidine group. Compared with the measurements after surgery CO less in the clonidine group during extubation (p < 0.05 for all results). CONCLUSIONS: A single preoperative IV dose of clonidine (3 microg/kg) blunts the hemodynamic responses due to extubation in noncardiac surgery of intermediate duration.     

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.     

Clonidine for the prevention of emergence agitation in young children: efficacy and recovery profile

BACKGROUND: Emergence agitation (EA) is a common postoperative problem in young children who have received sevoflurane and isoflurane for general anesthesia. This randomized, double-blinded study evaluated the efficacy of intraoperative clonidine in reducing EA, and describes its recovery profile. METHODS: With Institutional Review Board approval and informed consent, children undergoing brief, minimally painful procedures were studied. All children received preemptive analgesia with acetaminophen and ketorolac, sevoflurane for induction, and isoflurane for maintenance of anesthesia. Children received either 2 microg.kg(-1) clonidine or placebo intravenously (i.v.) following induction of anesthesia. Children were observed postoperatively for behavior and side effects, and their parents were telephoned the next day to determine postdischarge recovery characteristics. RESULTS: One hundred and twenty children were included in this study: 59 of whom received clonidine, and 61 placebo; 41% of those in the placebo group exhibited moderate-severe EA compared with only 22% of those in the clonidine group (P < 0.03). Compared with those who received placebo, children who received clonidine awakened more slowly (22 min vs 14 min), had a longer postanesthesia care unit stay (57 min vs 46 min), and experienced sleepiness more frequently after discharge (75% vs 39%; all comparisons significant at P < 0.03). There were no adverse cardiorespiratory events in either group. CONCLUSIONS: Findings demonstrate that i.v. clonidine administered after induction of anesthesia significantly reduces the incidence of EA in young children, but is associated with sleepiness postoperatively.     

Clinical evaluation of clonidine added to lidocaine solution for epidural anesthesia

The effects of clonidine added to lidocaine solution used for epidural anesthesia were assessed in 92 women scheduled for surgery and premedicated with diazepam 10 mg po. Patients received 18 ml 2% lidocaine with clonidine 5 micrograms.ml-1 (group C-5, n = 26), with clonidine 10 micrograms.ml-1 (group C-10, n = 20), with epinephrine 5 micrograms.ml-1 (group E, n = 26), or plain (group P, n = 20). No significant difference in the number of segments of analgesia was found at any observation period among the four groups of patients. The decreases in mean blood pressure (BP) observed 20 min after epidural injection in those given clonidine (5 +/- 8% for C-5, 10 +/- 11% for C-10, mean +/- SD) were similar to those given plain lidocaine (7 +/- 12%) but significantly less than those given epinephrine (18 +/- 12%, P less than 0.01 vs. C-5 or P). The response of BP to ephedrine given for restoring BP during anesthesia was not attenuated in patients who received epidural clonidine. Heart rate (HR) decreased significantly in patients given clonidine 10 micrograms.ml-1 (7 +/- 8%, P less than 0.01), but not in those given clonidine 5 micrograms.ml-1, whereas HR increased significantly in those given lidocaine plain or with epinephrine (10 +/- 8% and 28 +/- 14%, respectively, P less than 0.01). The incidence of sinus bradycardia was similar among the four groups of patients. Significant differences were also observed in sedation score between clonidine groups and groups P or E; sedation appeared approximately 10-20 min after epidural injection in both clonidine groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

A comparison of oral clonidine and oral midazolam as preanesthetic medications in the pediatric tonsillectomy patient

We compared the effects of oral clonidine (4 microg/kg) and midazolam (0.5 mg/kg) on the preanesthetic sedation and postoperative recovery profile in children during tonsillectomy with or without adenoidectomy. In a double-blinded, double-dummy study design, 134 ASA physical status I-II children aged 4-12 yr were randomized to receive a combination of either clonidine and placebo (Group A), or placebo and midazolam (Group B) at 60-90 min and 30 min, respectively, before the induction of anesthesia. Children in the clonidine group exhibited more intense anxiety on separation and during induction of anesthesia via a mask as measured by the modified Yale Preoperative Anxiety Scores. They also had significantly lower mean intraoperative arterial blood pressures, shorter surgery, anesthesia, and emergence times, and a decreased need for supplemental oxygen during recovery compared with the midazolam group. However, the clonidine group had larger postoperative opioid requirements, maximum excitement and pain scores based on the Children's Hospital of Eastern Ontario scale in the Phase 1 postanesthetic care unit. There were no differences between the two groups in the times to discharge readiness, postoperative emesis, unanticipated hospital admission rates, postdischarge maximum pain scores, and 24 h analgesic requirements. The percentage of parents who were completely satisfied with the child's preoperative experience was significantly higher in the midazolam group. There were no differences in parental satisfaction with the recovery period. We conclude that under the conditions of this study, oral midazolam is superior to oral clonidine as a preanesthetic medication in this patient population. Implications: We compared preanesthetic sedation and postoperative recovery after oral clonidine (4 microg/kg) and midazolam (0.5 mg/kg) in children during tonsillectomy. The clonidine group had greater preoperative anxiety and shorter surgery and anesthesia times, but required more postoperative analgesia. Delayed recovery and discharge times did not differ. Midazolam was superior to clonidine as oral preanesthetic medication for these patients.     

Effects of intramuscular clonidine on hemodynamic and plasma beta-endorphin responses to gynecologic laparoscopy

Ninety women undergoing gynecologic laparoscopy were randomly given clonidine 3 or 4.5 micrograms/kg or saline intramuscularly 45-60 min prior to induction of anesthesia. Anesthesia was induced with thiopental 3.5 mg/kg and maintained with 0.3% end-tidal isoflurane in nitrous oxide and oxygen. The laparoscopy did not begin sooner than 20 min after tracheal intubation. Arterial blood pressure and heart rate were monitored with an automatic oscillometer. When compared with the baseline values, clonidine 4.5 micrograms/kg significantly (P less than 0.001) decreased the mean arterial pressure (MAP) measured before induction of anesthesia. In all three groups, blood pressure and heart rate increased after tracheal intubation and after beginning of laparoscopy (P less than 0.001), but the increments were significantly greater in the control group than in the study groups. During anesthesia alone without surgical stimulation, and again in the recovery room, MAP and heart rate were lower in the study groups than in the control group. Plasma beta-endorphin immunoreactivity (ir beta-E) was measured for ten control-group women and ten women receiving clonidine 4.5 micrograms/kg before premedication, before and after induction of anesthesia, during laparoscopy, and 1 h after the procedure. The plasma ir beta-E increased significantly after the beginning of laparoscopy in both the control group and those given clonidine, but the increase was significantly less (P less than 0.05) in the women premedicated with clonidine. The blunting effect of clonidine on hemodynamics and plasma beta endorphin may reflect a deeper level of anesthesia in those women receiving clonidine as preanesthetic medication or can be explained by an interaction of clonidine with endogenous opiates. The authors conclude that intramuscularly administered clonidine premedication effectively prevents the maximal hemodynamic responses to tracheal intubation and to gynecologic laparoscopy. Further clinical studies on the clinical importance of the role of clonidine preanesthetic medication are warranted.     

Hemodynamic stability during induction of anesthesia and tracheal intubation with propofol plus fentanyl, ketamine, and fentanyl-ketamine

Purpose. This study was conducted to investigate hemodynamic and cardiac stability during anesthesia induction and intubation, using propofol plus fentanyl, propofol plus ketamine, and propofol plus fentanyl and ketamine. Methods. Forty-five adult patients were randomly allocated to one of three groups according to the agents used for induction: propofol (2 mg/kg) plus fentanyl (3 μg/kg) (PF), propofol (2 mg/kg) plus ketamine (0.1 mg/kg) (PK), and propofol (2 mg/kg) plus fentanyl (3 μg/kg) plus ketamine (0.1 mg/kg) (PFK). Hemodynamic responses were assessed by measuring changes in blood pressure (BP), heart rate (HR), and cardiac output (CO; using dye dilution combined with pulse dye densitometry [PDD]). Results. BP and HR changes during the induction of anesthesia tended to be greater in the PK group than in the PF and PFK groups. After the injection of propofol, the cardiac index (CI) fell significantly below baseline values in the PF and PFK groups, but remained unchanged in the PK group. After tracheal intubation, BP and HR increased significantly only in the PF and PK groups, and reached a level significantly above baseline values only in the PK group. The CO responses to tracheal intubation were: PK group > PF group > PFK group. Conclusion. A combination of propofol plus fentanyl plus ketamine would provide greater reduction of fluctuations in hemodynamic variables associated with induction of anesthesia and tracheal intubation than combinations of propofol plus fentanyl or propofol plus ketamine. Received: January 22, 2001 / Accepted: June 19, 2001     

Oral clonidine premedication reduces induction dose and prolongs awakening time from propofol-nitrous oxide anesthesia

PURPOSE: To evaluate whether oral clonidine premedication affects the induction dose of propofol and awakening time from epidural and propofol anesthesia. METHODS: Thirty-nine female patients (ASA I or II) were randomly allocated to receive 5 microg x kg(-1) clonidine p.o. or no clonidine 90 min before induction of anesthesia. After epidural anesthesia was achieved with lidocaine, general anesthesia was induced with continuous i.v. infusion of propofol at a rate of 50 mg x min(-1) until loss of eyelash reflex and responses to verbal commands, which were judged by a blinded observer. After a laryngeal mask airway was inserted, anesthesia was maintained with N2O 67%, O2 33% and propofol adjusted to maintain hemodynamic stability. After completion of surgery, a blinded observer recorded the time from discontinuance of propofol and N2O until the patient was awake and responsive (awakening time), and then, the laryngeal mask airway was removed. RESULTS: The induction dose of propofol in the clonidine group (1.4 +/- 0.3 mg) was less than that in the control group (1.9 +/- 0.4 mg, P < 0.05), while the awakening time of the clonidine group (470 +/- 145 sec) was longer than that of the control group (329 +/- 123 sec, P < 0.05). CONCLUSION: Premedication with 5 microg x kg(-1) clonidine p.o. reduced the induction dose of propofol, but delayed emergence from propofol anesthesia.