Reduction in Halothane Anesthetic Requirement by Clonidine, an Alpha-Adrenergic Agonist

Bloor, B. C.; Flacke, Werner

doi:10.1213/00000539-198209000-00005

Cited by 164 publications

(52 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Recently, the alpha-2-adrenergic agonists, which decrease central sympathetic outflow, have been the focus of attention for their potential stabilising effect on cardiovascular dynamics in the peri-operative period. 13 An increase in catecholamine levels has been noted during laryngo~copy,'~ and a more logical approach to the attenuation of such responses might be the reduction of sympathetic outflow. Clonidine is the only clinically available agent in the UK at present.…”

Section: Discussionmentioning

confidence: 99%

Cardiovascular effects of intravenous clonidine

Carabine¹,

Wright²,

Howe³

et al. 1991

Anaesthesia

View full text Add to dashboard Cite

SummaryThe effect of clonidine on the pressor and heart rate response to tracheal intubation was studied in a placebo-controlled, randomised, double-blind trial. Thirty patients were pretreated with either clonidine 1.25 pgglkg, or clonidine 0.625 pgglkg or an equivalent volume of normal saline, given intravenously 15 minutes before induction of anaesthesia. The attenuation of the pressor response to intubation of both clonidine groups was statistically signijicant compared to the saline group. Neither dose of clonidine completely abolished the increase in either heart rate or blood pressure. There was no dlfference in attenuation between the clonidine treatments; this indicated that the lower dose may be the more appropriate. Key wordsIntubation; tracheal. Pharmacology; clonidine.The haemodynamic responses to laryngoscopy and tracheal intubation, namely hypertension, arrhythmias and tachycardia, are of considerable importance to anaesthetists.l.* A variety of agents have been used to attenuate this response, including local anaesthetics,' opioids; calcium channel blockers,5 beta blocker^^,^ and vasodilators.8 No single agent has been estabished as the most appropriate for this purpose. Clonidine, an alpha-2-adrenoceptor agonist, is an antihypertensive agent which decreases central sympathetic outflow thereby reducing blood pressure and heart rate.' Recent studies indicate that clonidine improves haemodynamic stability during cardiac surgery." Oral clonidine has been shown to produce anxiolysis and sedation when administered as a premedicant." While it may not be of use as a routine premedicant, it may be indicated where swings in blood pressure and heart rate might be potentially harmful.The aim of this study is to examine the efficacy of two doses of intravenous clonidine, in decreasing the pressor and heart rate response to a standardised induction, laryngoscopy and tracheal intubation sequence. MethodsThis study was approved by the local Ethics Committee and informed consent was obtained from all patients.Healthy ASA 1 subjects were premedicated with temazepam 20 mg administered orally 60-90 minutes before operation. Venous access was established and the patients were randomly allocated to one of three equal treatment groups: group A patients received clonidine 1.25 pg/kg, group B clonidine 0.625 pg/kg and group C an equivalent volume of normal saline. Each treatment was administered intravenously 15 minutes before induction of anaesthesia. Sedation was noted during this period.Before administration of the test drug, a 22-gauge radial arterial cannula was sited using local anaesthesia. A Hewlett Packard monitor provided a continuous display of the arterial waveform, and a printout of blood pressure was produced at the set time intervals. Heart rate was measured using lead I1 of the ECG, and tissue oxygen saturation was monitored using a pulse oximeter.Baseline values for heart rate and blood pressure were recorded before the administration of the test drug. Further readings were recorded at one-minute interv...

show abstract

Section: Discussionmentioning

confidence: 99%

Cardiovascular effects of intravenous clonidine

Carabine¹,

Wright²,

Howe³

et al. 1991

Anaesthesia

View full text Add to dashboard Cite

show abstract

“…They also demonstrated that the administration of clonidine subcutaneously for 3 days reduced the MAC of halothane by 15% in rabbits [128]. Bloor & Flacke [129] also reported an anaesthetic-sparing effect in dogs, the administration of clonidine decreasing the MAC of halothane by a maximum of 50%. In addition the dose of thiopentone required for induction of anaesthesia is reduced by clonidine premedication [130].…”

Section: Anaesthetic Requirementsmentioning

confidence: 95%

Alpha‐2 and imidazoline receptor agonistsTheir pharmacology and therapeutic role

Khan¹,

Ferguson²,

Jones³

1999

Anaesthesia

598

423

View full text Add to dashboard Cite

SummaryClonidine has proved to be a clinically useful adjunct in clinical anaesthetic practice as well as in chronic pain therapy because it has both anaesthetic and analgesic-sparing activity. The more selective alpha-2 adrenoceptor agonists, dexmedetomidine and mivazerol, may also have a role in providing haemodynamic stability in patients who are at risk of peri-operative ischaemia. The side-effects of hypotension and bradycardia have limited the routine use of alpha-2 adrenoceptor agonists. Investigations into the molecular pharmacology of alpha-2 adrenoceptors have elucidated their role in the control of wakefulness, blood pressure and antinociception. We discuss the pharmacology of alpha-2 adrenoceptors and their therapeutic role in this review.

show abstract

“…Clinically, clonidine has been used extensively for the treatment of severe, acute (Tamsen & Gordh, 1984;Eisenach et al, 1989a;Mendez et al, 1990) and chronic (Coombs et al, 1986;Max et al, 1988;Eisenach et al, 1989b) pain conditions following either epidural or spinal administration. Clonidine (Bloor & Flacke, 1982) and Dex (Segal et al, 1988) have also been found to be useful adjuncts to general anaesthetics by reducing the anaesthetic requirement during surgery. However, while e ective analgesia is obtained by these restricted routes of administration, widespread use for the treatment of pain following systemic administration is precluded by a series of adverse side-e ects including sedation, profound systemic hypotension and bradycardia (Bonnet et al, 1989;Eisenach et al, 1989a;Maze & Tranquilli, 1991).…”

mentioning

confidence: 99%

Assessment of the role of α₂‐adrenoceptor subtypes in the antinociceptive, sedative and hypothermic action of dexmedetomidine in transgenic mice

Hunter¹,

Fontana²,

Hedley³

et al. 1997

British J Pharmacology

246

139

View full text Add to dashboard Cite

1 The role of a 2 -adrenoceptor (AR) subtypes in the modulation of acute nociception, motor behaviour and body temperature, has been investigated by determining the activity of the a 2 AR selective agonist dexmedetomidine (Dex) in mice devoid of individual a 2 AR subtypes through either a point (a 2A ) or null (a 2B /a 2C ) mutation (`knock-out').2 In a rodent model of acute thermal nociception, the mouse tail immersion test, Dex, in wild type (WT) control animals, produced a dose-dependent increase in the threshold for tail withdrawal from a 528C water bath with mean ED 50 values of 99.9+14.5 (a 2A ), 94.6+17.8 (a 2B ) and 116.0+17.1 (a 2C ) mg kg 71 , i.p. 3 In comparison to the WT controls, Dex (100 ± 1000 mg kg 71 , i.p.), was completely ine ective as an antinociceptive agent in the tail immersion test in the a 2A AR D79N mutant animals. Conversely, in the a 2B AR and a 2C AR knock-outs, Dex produced a dose-dependent antinociceptive e ect that was not signi®cantly di erent from that observed in WT controls, with ED 50 values of 85.9+15.0 (P40.05 vs WT control) and 226.0+62.7 (P40.05 vs WT control) mg kg 71 i.p., respectively. 4 Dex (10 ± 300 mg kg 71 , i.p.) produced a dose-dependent reduction in spontaneous locomotor activity in the a 2A , a 2B and a 2C AR WT control animals with ED 50 values of 30.1+9.0, 23.5+7.1 and 32.3+4.6 mg kg 71 , i.p., respectively. Again, Dex (100 ± 1000 mg kg 71 , i.p.) was ine ective at modulating motor behaviour in the a 2A AR D79N mutants. In the a 2B AR and a 2C AR knock-out mice, Dex produced a dose-dependent reduction in spontaneous locomotor activity with ED 50 values of 29.1+6.4 (P40.05 vs WT control) and 57.5+11.3 (P40.05 vs WT control) mg kg 71 , respectively. 5 Dex was also found to produce a dose-dependent reduction in body temperature in the a 2A , a 2B and a 2C AR WT control mice with ED 50 values of 60.6+11.0, 16.2+2.5 and 47.2+9.1 mg kg 71 , i.p., respectively. In the a 2A AR D79N mutants, Dex had no e ect on body temperature at a dose (100 mg kg 71 , i.p.) that produced a signi®cant reduction (76.2+0.58C; P50.01 vs vehicle) in temperature in WT controls. However, higher doses of Dex (300 and 1000 mg kg 71 , i.p) produced a small, but statistically signi®cant decrease in temperature corresponding to 71.7+0.48C and 72.4+0.38C (both P50.01 vs vehicle), respectively. In the a 2B AR and a 2C AR knock-out mice, Dex produced a dose-dependent reduction in body temperature with ED 50 values of 28.4+4.8 (P40.05 vs WT control) and 54.1+8.0 (P40.05 vs WT control) mg kg 71 , respectively. 6 In conclusion, the data are consistent with the a 2A AR being the predominant subtype involved in the mediation of the antinociceptive, sedative and hypothermic actions of Dex. This pro®le would appear to indicate that an a 2A AR subtype selective analgesic will have a narrow therapeutic window, particularly following systemic administration.

show abstract

Reduction in Halothane Anesthetic Requirement by Clonidine, an Alpha-Adrenergic Agonist

Cited by 164 publications

References 0 publications

Cardiovascular effects of intravenous clonidine

Cardiovascular effects of intravenous clonidine

Alpha‐2 and imidazoline receptor agonistsTheir pharmacology and therapeutic role

Assessment of the role of α₂‐adrenoceptor subtypes in the antinociceptive, sedative and hypothermic action of dexmedetomidine in transgenic mice

Contact Info

Product

Resources

About

Reduction in Halothane Anesthetic Requirement by Clonidine, an Alpha-Adrenergic Agonist

Cited by 164 publications

References 0 publications

Cardiovascular effects of intravenous clonidine

Cardiovascular effects of intravenous clonidine

Alpha‐2 and imidazoline receptor agonistsTheir pharmacology and therapeutic role

Assessment of the role of α2‐adrenoceptor subtypes in the antinociceptive, sedative and hypothermic action of dexmedetomidine in transgenic mice

Contact Info

Product

Resources

About

Assessment of the role of α₂‐adrenoceptor subtypes in the antinociceptive, sedative and hypothermic action of dexmedetomidine in transgenic mice