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The centrally acting alpha2-adrenoceptor agonists clonidine and dexmedetomidine have been used with success to provide haemodynamic stability for patients undergoing surgery. Particularly in the case of patients with overt or underlying cardiac disease the actions of alpha2-adrenoceptor agonists, which include maintenance of stable systemic blood pressure and low heart rate and a reduction in overall oxygen consumption, can be expected to reduce the risk of procedure-related cardiac events. This expectation has been corroborated in clinical trials with clonidine, dexmedetomidine and mivazerol and meta-analyses; additional large controlled trials would be instructive in establishing a robust estimate of the scale of the benefit. In addition, alpha2-adrenoceptor agonists used as premedication have been shown to substantially reduce anaesthetic requirements among surgical patients, and the use of these agents has been associated with a reduced risk of postoperative delirium, which may be expected to improve considerably the postoperative course for at-risk patients. Dexmedetomidine is the only alpha2-adrenoceptor agonist currently approved for use in the intensive care unit. A distinctive feature of dexmedetomidine in that setting is that in addition to haemodynamic stability it confers a distinctive and advantageous quality of sedation: patients are tranquil but responsive to requests from attending staff. This review examines the pharmacological principles underlying the use of alpha2-adrenoceptor agonists as adjuncts to surgery and clinical experience in that indication.

This study was designed to investigate whether clonidine could attenuate the increase in oxygen consumption (VO2), arterial pressure (AP) and plasma catecholamines in response to the cold pressor test (CPT), an intense stimulation of the sympathetic nervous system. Six volunteers were given clonidine (2 micrograms kg-1 and 4 micrograms kg-1) and placebo i.m. in a random, double-blind, cross-over manner. Both clonidine doses decreased plasma catecholamine concentrations (P < 0.01), but only the higher dose of clonidine attenuated the CPT-induced absolute increase in plasma catecholamine concentration compared with the placebo group (P < 0.01). VO2 and AP decreased and were less after clonidine 4 micrograms kg-1 when compared with clonidine 2 micrograms kg-1 and placebo (P < 0.05) throughout the observation period. Thus, although clonidine 4 micrograms kg-1 attenuated the catecholamine response, the increases in VO2 and AP in response to CPT were similar in all groups.

Unlabelled: The use of ketamine as a sole anesthetic induces marked central sympathetic stimulation, causing increased heart rate, blood pressure (BP), and oxygen consumption (VO2). Both alpha 2-agonists and benzodiazepines have been used to attenuate these potentially harmful ketamine-induced responses. This double-blind, randomized, placebo-controlled study was designed to compare the perioperative metabolic, hemodynamic, and sympathoadrenal responses to IM clonidine (2 micrograms/kg) and midazolam (70 micrograms/kg) premedication during ketamine anesthesia. VO2 was measured continuously using indirect calorimetry in 30 ASA physical status I patients. The patients received ketamine, mivacurium, and fentanyl for the induction of anesthesia. Anesthesia was maintained using a ketamine infusion and fentanyl boluses i.v. Preoperatively, both VO2 and BP decreased significantly after the administration clonidine and midazolam compared with placebo (P < 0.01). Intraoperatively, VO2 was higher in the midazolam group than in the placebo and clonidine groups (P < 0.05). Postoperatively, there were no significant differences in BP and VO2, although they stayed at lower level in the clonidine group during the whole postoperative period. Clonidine decreased pre- and postoperative plasma catecholamine concentrations (P < 0.05). Our results indicate that a midazolam-ketamine combination may induce potentially harmful metabolic stimulation, whereas the sympatholytic effects of clonidine on ketamine-anesthetized patients may be beneficial, as perioperative VO2 was decreased., Implications: Ketamine causes sympathetic stimulation with an ensuing increase in oxygen consumption. Anticipating that clonidine might attenuate this response, we measured oxygen consumption in patients undergoing surgery during ketamine anesthesia. Patients treated with a clonidine-ketamine combination had lower intra- and postoperative oxygen consumption than those treated with a midazolam-ketamine combination.

Premedication has been shown to affect both oxygen consumption and metabolic rate. We have compared the perioperative metabolic and haemodynamic effects of two alpha 2-agonists, clonidine and the more selective dexmedetomidine, in 30 ASA I patients undergoing plastic surgical procedures under general anaesthesia. Patients were premedicated with clonidine 4 micrograms kg-1 (n = 10), dexmedetomidine 2.5 micrograms kg-1 (n = 10) or saline (n = 10) i.m. The doses of clonidine and dexmedetomidine were intended to be equipotent. The maximum decrease in preoperative oxygen consumption was 8% and decreases in systolic and diastolic arterial pressures were 11% from baseline after clonidine and dexmedetomidine. During operation, the maximum reduction in heart rate was 18% in the clonidine and dexmedetomidine groups compared with the placebo group. After operation, the maximum decrease in systolic arterial pressure was 11%, diastolic arterial pressure 15% and oxygen consumption 17% in the clonidine and dexmedetomidine groups compared with placebo. In summary, both clonidine 4 micrograms kg-1 and dexmedetomidine 2.5 micrograms kg-1 decreased perioperative oxygen consumption effectively, with a similar haemodynamic profile.

In this double-blind placebo controlled study the preoperative cardiovascular and metabolic effects of intramuscular (i.m.) clonidine and midazolam are assessed. Forty-five ASA Grade I patients (n = 15 per group) undergoing plastic surgical procedures were randomly allocated to receive either placebo, clonidine 4 micrograms kg-1 or midazolam 70 micrograms kg-1. Drugs were administered into the deltoid muscle approximately 90 min prior to the scheduled induction of anaesthesia. The metabolic measurements were performed using an indirect calorimetry device. Heart rate and blood pressure were measured noninvasively. Pre-operative subjective anxiety, dryness of mouth and tiredness were assessed using visual analogue scales (VAS). Clonidine increased subjective tiredness significantly more than placebo. Clonidine also induced moderate decreases in blood pressure and heart rate. Oxygen consumption (VO2), CO2 production and energy expenditure (EE) decreased significantly after clonidine and midazolam. The decrease in VO2 and EE was maximally 11-14% on average from the base-lines after clonidine and midazolam. These effects were of longer duration after clonidine and lasted until the end of the 90 min study period. In conclusion, both clonidine and midazolam are effective as a means of decreasing pre-operative VO2 and EE.

This pilot study compared the metabolic effects of placebo and 6 mg and 12 mg of oral tizanidine in random double-blind cross-over fashion in five healthy volunteers. The metabolic measurements were made with a portable metabolic chart (Deltatrac, Datex/Instrumentarium, Helsinki, Finland). Heart rate (HR), systolic (BPS), mean (BPM) and diastolic (BPD) blood pressure were measured noninvasively. Subjective assessment of tiredness and dryness of mouth were measured by using visual analogue scales (VAS). There were no statistically significant differences in tiredness or dryness of mouth between the groups. BPD decreased significantly after both doses of tizanidine when compared to placebo (by an average of 12% after 6 mg of tizanidine and 15% after 12 mg of tizanidine from the baseline). Oxygen consumption and energy expenditure decreased significantly after 6 and 12 mg of tizanidine when compared to placebo. The average decrease in oxygen consumption was 3% after 6 mg of tizanidine and 8% after 12 mg of tizanidine, when compared to the baseline. Energy expenditure decreased by an average of 5% after 6 mg of tizanidine and 9% after 12 mg of tizanidine, when compared to the baseline. There were no other statistically significant differences between the groups. This study indicates that 6 and 12 mg of oral tizanidine can be useful for reducing energy expenditure and oxygen consumption without prominent cardiovascular effects.

The centrally acting α2-adrenoceptor agonists clonidine and dexmedetomidine have been used with success to provide haemodynamic stability for patients undergoing surgery. Particularly in the case of patients with overt or underlying cardiac disease the actions of α2-adrenoceptor agonists, which include maintenance of stable systemic blood pressure and low heart rate and a reduction in overall oxygen consumption, can be expected to reduce the risk of procedure-related cardiac events. This expectation has been corroborated in clinical trials with clonidine, dexmedetomidine and mivazerol and meta-analyses; additional large controlled trials would be instructive in establishing a robust estimate of the scale of the benefit. In addition, α2-adrenoceptor agonists used as premedication have been shown to substantially reduce anaesthetic requirements among surgical patients, and the use of these agents has been associated with a reduced risk of postoperative delirium, which may be expected to improve considerably the postoperative course for at-risk patients. Dexmedetomidine is the only α2-adrenoceptor agonist currently approved for use in the intensive care unit. A distinctive feature of dexmedetomidine in that setting is that in addition to haemodynamic stability it confers a distinctive and advantageous quality of sedation: patients are tranquil but responsive to requests from attending staff. This review examines the pharmacological principles underlying the use of α2-adrenoceptor agonists as adjuncts to surgery and clinical experience in that indication. [ABSTRACT FROM AUTHOR]