Kiyokazu Kagawa

The Effects of Preanesthetic Oral Clonidine on Total Requirement of Propofol for General Anesthesia

STUDY OBJECTIVE To investigate the effects of preanesthetic oral clonidine on total propofol requirement for uniform minor surgery (breast conservative surgery: breast cancer removal with axillary lymph node dissection), and to compare the action of clonidine with that of preanesthetic oral diazepam, a commonly used benzodiazepine. DESIGN Randomized double-blinded study. SETTING Operating room ASA physical status I and II room and recovery room of the cancer center. PATIENTS 80 breast cancer patients scheduled for surgery. INTERVENTIONS Patients were randomized to one of four treatment groups (placebo, clonidine 75 micrograms, or 150 micrograms of clonidine, or 10 mg of diazepam were orally administered 60 min before induction of anesthesia); n = 20 per group. After evaluating the sedation and anxiety levels of patients using a visual analog scale, anesthesia was induced with propofol (1.5 mg/kg), and maintained with oxygen (O2): nitrous oxide (N2O) (30:70) with a continuous infusion of propofol. The propofol infusion was started at 10 mg/kg/h for 10 minutes, then decreased to 8 mg/kg/h, and 6 mg/kg/h thereafter, and the rate of infusion was adjusted to obtain adequate anesthesia (maintaining hemodynamic parameters within 20% of that prior to premedication). Fentanyl 0.2 mg (each 0.1 mg was given for intubation and axillary lymph node dissection, respectively) was administered. MEASUREMENTS AND MAIN RESULTS Preanesthetic oral clonidine (150 micrograms) and diazepam (10 mg) induced anxiolysis without sedation. The total requirement (the mean infusion rates) of propofol in placebo, clonidine 75 micrograms, clonidine 150 micrograms, and 10 mg of diazepam groups were 841 +/- 70 (9.0 +/- 0.3), 720 +/- 63 (7.1 +/- 0.4), 491 +/- 39 (5.6 +/- 0.2), and 829 +/- 77 mg (7.9 +/- 0.4 mg/kg/h), respectively. The cost of propofol in these groups was

Interactions Between Neuronal Histamine and Halothane Anesthesia in Rats

51.0 +/- 3.8,

Evaluation of diagonal earlobe crease as a marker of coronary artery disease: the use of this sign in pre-operative assessment*

45.5 +/- 3.2,

The Effect of Imidazoline Receptors and α2-adrenoceptors on the Anesthetic Requirement (MAC) for Halothane in Rats

33.5 +/- 2.3, and

Identification of the central imidazoline receptor subtype involved in modulation of halothane-epinephrine arrhythmias in rats

50.5 +/- 4.4, respectively. CONCLUSIONS Preanesthetic oral clonidine (150 micrograms) but not diazepam (10 mg) reduced the total requirement of propofol while stabilizing hemodynamic parameters. In addition, 150 micrograms of oral clonidine attenuates the hemodynamic responses associated with tracheal intubation.

Supraspinal, Not Spinal, α2 Adrenoceptors Are Involved in the Anesthetic-sparing and Hemodynamic-stabilizing Effects of Systemic Clonidine in Rats

Abstract: Using an in vivo microdialysis method, we measured the release of histamine in the anterior hypothalamic area (AHy) of rats under several concentrations of halothane anesthesia (1, 0.5, and 0.2%). The release of histamine increased to 341 and 325% at halothane concentrations of 0.5 and 0.2%, compared with the basal level at anesthesia induced by 1% halothane. α‐Fluoromethylhistidine (100 mg/kg i.v.), a specific and irreversible inhibitor of histidine decarboxylase, reduced the histamine release to <35% of the basal value at 1% halothane anesthesia in the AHy, and also decreased the anesthetic requirement for halothane, evaluated as the minimum alveolar concentration (MAC), by 26%. Furthermore, pyrilamine (20 mg/kg i.v.), a brain‐penetrating H1 antagonist, and zolantidine (20 mg/kg i.v.), a brain‐penetrating H2 antagonist, reduced the MAC for halothane by 28.5 and 16%, respectively. Although thioperamide (5 mg/kg i.v.), an antagonist of presynaptic H3 autoreceptor, induced an approximate twofold increase in the level of histamine release in conscious freely moving rats, the same dose of thioperamide had little effect on the release of histamine under 1% halothane anesthesia in the AHy. Furthermore, thioperamide did not change the anesthetic requirement (MAC) for halothane. The present findings indicate that halothane anesthesia inhibits the release of neuronal histamine and that histaminergic neuron activities change the anesthetic requirement (MAC) for halothane through H1 as well as H2 receptors.

Diabetes attenuates the minimum anaesthetic concentration (MAC) and MAC-blocking adrenergic response reducing actions of clonidine in rats

In this study, we examined the usefulness of the earlobe crease sign as a marker of coronary artery disease in the pre‐operative assessment of patients. We were interested in evaluating this sign for use in emergency patients. We investigated 530 patients, aged > 40 years, undergoing elective surgery. If the electrocardiogram was abnormal or the patient reported symptoms suggesting coronary artery disease, further cardiac examinations were performed. Patients who demonstrated evidence of coronary artery disease in the additional investigations or had a clear history of coronary artery disease were classified as the abnormal coronary group. Other patients with no history and/or normal investigations were classified as the normal coronary group. The assessment of earlobe crease sign was performed prior to anaesthesia, and the sensitivity, specificity and positive predictive value of this sign were calculated. We found that the sensitivity and specificity was high regardless of age, except for specificity in patients > 70 years old. The data suggest that the earlobe crease sign may be a useful marker for the presence of coronary artery disease in patients undergoing emergency operations in which little or no history and investigations are available. However, more work is required to assess the use of this sign in other ethnic groups.

Treatment of acute right coronary artery occlusion during anesthesia

Background: Recent evidences have documented that several pharmacologic actions of alpha2 ‐adrenoceptor agonists are mediated via activation of not only alpha2 ‐adrenoceptors, but also by imidazoline receptors, which are nonadrenergic receptors in the central nervous system. However, the effect of imidazoline receptors on the anesthesia is not well known, and it is important to clarify the effects of both receptors on anesthesia. Methods: Seventy‐two rats were anesthetized with halothane, and the anesthetic requirement for halothane was evaluated as minimum alveolar concentration (MAC). The MAC for halothane was determined in the presence of dexmedetomidine (0, 10, 20, and 30 micro gram/kg, intraperitoneally [IP]), a selective alpha2 ‐adrenoceptor agonist with weak affinity for imidazoline receptors. Then, the authors evaluated the inhibitory effect of rauwolscine (20 mg/kg, IP), an alpha sub 2 ‐adrenoceptor antagonist with little affinity for imidazoline receptors, on the MAC‐reducing action of dexmedetomidine (30 micro gram/kg). Further, the effect of rilmenidine (20, 50, 100, 1000 micro gram/kg, IP), a selective imidazoline receptor agonist, on the MAC for halothane was also investigated. Results: Dexmedetomidine decreased the MAC for halothane dose‐dependently, and this MAC‐reducing action of dexmedetomidine was completely blocked by rauwolscine. Rilmenidine alone did not change the MAC for halothane. Conclusions: The present data indicate that the anesthetic sparing action of dexmedetomidine is most likely mediated through alpha2 ‐adrenoceptors, and the stimulation of imidazoline receptors exerts little effect on the anesthetic requirement for halothane.

Artificial ventilation-induced diffuse alveolar damage in rabbits: preliminary study of early detection on expiratory high-resolution computed tomography.

We previously reported that imidazoline receptors in the central nervous system are involved in modulation of halothane-epinephrine arrhythmias. These receptors have been subclassified as I1 and I2 subtypes, but it is not known which receptor subtype is involved in halothane-epinephrine-induced arrhythmias. We designed the present study to clarify the involvement of central imidazoline receptor subtype in the modulation of halothane-epinephrine-induced arrhythmias. Rats were anesthetized with halothane and monitored continuously for systemic arterial blood pressure and premature ventricular contractions. The arrhythmogenic dose of epinephrine was defined as the smallest dose that produces three or more premature ventricular contractions within a 15-s period. Intracisternal moxonidine dose-dependently inhibited the epinephrine-induced arrhythmias during halothane anesthesia. Intracisternal efaroxan, a selective I1 antagonist with little affinity for I2 subtype, but not rauwolscine, an &agr;2 antagonist without affinity for imidazoline receptors, blocked the antiarrhythmic effect of moxonidine. Intracisternal BU 224 and 2-BFI, selective I2 ligands, also inhibited the epinephrine-induced arrhythmias dose-dependently; however, these effects were abolished by efaroxan. We conclude that central I1, but not I2, receptors play an important role in inhibition of halothane-epinephrine arrhythmia.

Body position does not influence the location of ventilator-induced lung injury

Clonidine, an &agr;2 agonist, reduces the anesthetic requirement and attenuates harmful hemodynamic responses to noxious stimuli. We examined the responsible sites of action in the central nervous system for the minimum alveolar anesthetic concentration (MAC) and MAC blocking adrenergic response (MAC-BAR) reducing effects of systemically administered clonidine in halothane-anesthetized rats. The MAC for halothane was determined by the tail clamp method, and MAC-BAR was defined as the MAC which attenuated hemodynamic responses within 10% after the tail clamp. We examined the effect of IV clonidine in the presence of rauwolscine, an &agr;2 antagonist given through IV, intrathecal (IT), intracisternal (IC), or intracerebroventrical (ICV) routes. IV clonidine reduced MAC and MAC-BAR dose-dependently. IV and ICV rauwolscine antagonized the MAC-reducing effect of clonidine, whereas IC and IT rauwolscine did not. In comparison, IV, ICV, and IC rauwolscine antagonized the MAC-BAR-reducing effect of clonidine; IT rauwolscine had no effect. Our data demonstrate that the &agr;2 adrenoceptors in the regions above mesencephalon and both the regions above mesencephalon and the lower brainstem are responsible for the MAC and MAC-BAR-reducing effect of systemic clonidine in rats, respectively. However, the spinal &agr;2 adrenoceptors were not involved in these effects of clonidine. Implications: In the regions above mesencephalon, &agr;2 adrenoceptors were the most responsible for the minimum alveolar concentration-reducing effect and both the lower brainstem and regions above mesencephalon were involved in the minimum alveolar concentration blocking adrenergic response-reducing effect of clonidine. The spinal &agr;2 adrenoceptors did not significantly contribute to these effects of clonidine.