Kazuyuki Imanaga

The effects of diltiazem on hemodynamics and seizure duration during electroconvulsive therapy.

Electroconvulsive therapy (ECT) is often associated with acute hyperdynamic responses, and we hypothesize that diltiazem can blunt this response. We measured the effect of a 10-mg dose of diltiazem on heart rate and mean arterial pressure during ECT. Furthermore, we assessed seizure duration by using both the cuff method and two-lead electroencephalogram. We studied 18 patients with a randomized, double-blinded, placebo-controlled cross-over study design. Diltiazem significantly reduced heart rate and mean arterial pressure just after medication, and it also significantly reduced the increases in these variables after ECT, as compared with the placebo. The use of diltiazem was, however, associated with a shortened seizure duration, possibly making ECT less effective. Because of the reduction in seizure duration, the routine administration of diltiazem may not be advisable because it can possibly interfere with the psychotherapeutic efficacy of ECT. However, diltiazem medication for ECT is potentially useful for reducing tachycardia and hypertension in high-risk patients.

Intravenous verapamil blunts hyperdynamic responses during electroconvulsive therapy without altering seizure activity.

IMPLICATIONS A dose of 0.1 mg/kg of verapamil, administered immediately before anesthesia, significantly reduces the increase in peak heart rate and mean arterial blood pressure after electroconvulsive therapy. Furthermore, the administration of verapamil does not reduce the duration of the seizure.

Intravenous colforsin daropate, a water-soluble forskolin derivative, prevents thiamylal-fentanyl-induced bronchoconstriction in humans

Objective Forskolin, a direct activator of adenylate cyclase, can relax airway smooth muscle, similar to other agents that increase intracellular cyclic adenine monophosphate. However, the potential usefulness of forskolin in treating bronchospasm is limited by its poor water solubility. Colforsin daropate is a novel and potent water-soluble forskolin derivative. No clinical data have been published on the bronchorelaxant effects of this drug. The aim of this study was to investigate whether intravenous colforsin daropate prevents thiamylal-fentanyl-induced bronchoconstriction. Design Double-blind, prospective, placebo-controlled randomized study. Setting University teaching hospital. Patients Thirty-six patients were allocated randomly to two groups: the control group (n = 18) and colforsin daropate group (n = 18). Interventions Intravenous administration of colforsin daropate or placebo (normal saline). Measurements and Main Results Anesthesia was induced with thiamylal 5 mg/kg and vecuronium 0.3 mg/kg. A 15 mg·kg−1·hr−1 continuous infusion of thiamylal followed anesthetic induction. Controlled ventilation was maintained, delivering 50% nitrous oxide in oxygen. Twenty minutes after the induction of anesthesia, the control group patients started to receive 7.5 mL/hr continuous infusion of normal saline, and the colforsin daropate group patients started to receive 0.75 &mgr;g·kg−1·min−1 (7.5 mL/hr) continuous infusion of colforsin daropate for 60 min. After that, both groups received fentanyl 5 &mgr;g/kg. Systolic and diastolic arterial pressure, heart rate, mean airway resistance (Rawm), expiratory airway resistance (Rawe), and dynamic lung compliance (Cdyn) were measured at the baseline, just before the administration of fentanyl (T30), at three consecutive 6-min intervals after fentanyl injection (T36, T42, and T48) and 30 min after fentanyl injection (T60). At baseline, both groups had comparable Rawm, Rawe, and Cdyn values. In the control group, Rawm increased significantly at T36–60 compared with the baseline, Rawe increased significantly at T36–48 compared with the baseline, and Cdyn decreased significantly at T36–60 compared with the baseline. In the colforsin daropate group, there were no changes in Rawm, Rawe or Cdyn at T36–60. Conclusions These observations suggest that intravenous colforsin daropate has a bronchodilator effect in humans.

Do induced hypertension and hypotension affect stroke volume variation in man

STUDY OBJECTIVE To investigate changes in stroke volume variation (SVV) by both induced hypertension (pressor test) and hypotension (depressor test), and also by induced hypotensive anesthesia in patients with good cardiac function. DESIGN Prospective, controlled clinical study. SETTING University hospital. PATIENTS 31 ASA physical status 1 and 2 patients, aged 39-62 years, who were scheduled for elective surgery. INTERVENTIONS We conducted three studies: a pressor test study, a depressor test study, and an induced hypotensive anesthesia study. In the pressor test, patients received a bolus of phenylephrine 0.001 mg/kg to increase systolic arterial pressure (SAP) by 30% to 40% compared with baseline. In the depressor test, patients received a bolus of nitroglycerine 0.005 mg/kg to decrease SAP by 30% to 40% compared with baseline. In the induced hypotensive anesthesia test, patients received intravenous (IV) nitroglycerine continuously until mean arterial pressure (MAP) was reduced to 60-70 mmHg. MEASUREMENTS When arterial pressure reached the target pressure for each study type, SVV and other parameters were recorded. MAIN RESULTS Induced hypertension (pressor test) decreased SVV, while induced hypotension (depressor test) and induced hypotensive anesthesia increased SVV. CONCLUSIONS SVV does not misinterpret preload dependency assessment of patients receiving medications to increase or to lower blood pressure.

Oral tizanidine, an α2-Adrenoceptor agonist, reduces the minimum alveolar concentration of sevoflurane in human adults

UNLABELLED Tizanidine, an alpha2-adrenoceptor agonist, has an antinociceptive effect in animals. In humans premedicated with oral tizanidine, the increase in blood pressure associated with laryngoscopy and intubation was attenuated, and the amount of midazolam required for loss of consciousness was significantly reduced. We speculated that the oral administration of tizanidine might reduce the minimum alveolar anesthetic concentration (MAC) of sevoflurane. Fifty-two ASA physical status I-II patients, aged 24-56 yr, were randomly allocated into two groups: a Control group (n = 26) and a Tizanidine group (n = 26). As premedication, the Control group received a placebo, and the Tizanidine group received 4 mg of oral tizanidine 90 min before surgical skin incision. Anesthesia was induced in all patients by using vital capacity rapid inhaled induction with sevoflurane (5%). Loss of consciousness was defined as both the loss of the eyelid reflex and the lack of a response to a verbal command. MAC was determined by a technique adapted from the conventional up-down method for quantal responses. The MAC of sevoflurane was 2.2% +/- 0.2% in the Control group and 1.8% +/- 0.2% in the Tizanidine group (P = 0.0004). The time to loss of consciousness in the Tizanidine group (60.2 +/- 22.5 s) was significantly shorter than that in the Control group (73.7 +/- 26.3 s) (P = 0.03). The oral administration of tizanidine 4 mg successfully reduced the MAC of sevoflurane by 18% in human adults. IMPLICATIONS Oral tizanidine (4 mg), an alpha2-adrenoceptor agonist, reduces the minimum alveolar concentration of sevoflurane by 18%.

Changes in hemodynamic variables and catecholamine levels after rapid increase in sevoflurane or isoflurane concentration with or without nitrous oxide under endotracheal intubation

AbstractPurpose. Rapid increases in concentrations of isoflurane and desflurane in oxygen have been shown to increase sympathetic activity. The aim of this study was to determine whether concomitant administration of nitrous oxide would reduce these sympathomimetic effects of volatile anesthetics. Methods. Eighty healthy patients in whom the trachea was intubated and mechanically ventilated were given 15 min of anesthesia with either N2O (67%)-O2-sevoflurane (GOS), O2-sevoflurane (OS), N2O (67%)-O2-isoflurane (GOI), or O2-isoflurane (OI) (n = 20 per group). The inspired concen-tration of sevoflurane was 0.85% (0.5 minimum alveolar concentration [MAC]), and that of isoflurane was 0.6% (0.5 MAC). Fifteen minutes after endotracheal intubation, baseline and arterial blood sample data were obtained. Immediately after that, a sudden administration of 2.9 MAC volatile anesthetics was performed. Systolic and diastolic arterial pressures, heart rate, and end-tidal carbon dioxide concentration were obtained at 0.5, 1, 1.5, 2, 3, 4, and 5 min after that. To measure catecholamine levels, arterial blood samples were obtained 2 and 5 min after the trial started. Results. Except for the OI group, systolic and diastolic arterial pressure progressively decreased after the abrupt increase in the concentration of volatile anesthetics. Except for the OS group, the heart rate increased after the abrupt increase in the concentration of volatile anesthetics. In the OI group, the end-tidal concentration of carbon dioxide increased at 0.5 and 1 min, suggesting that a slight hyperdynamic state occurred. However, it decreased progressively after the abrupt increase in volatile anesthetic concentration in the other groups. Plasma norepinephrine levels increased progressively in all groups. Conclusion. Even if nitrous oxide was added to isoflurane or sevoflurane, the increase in heart rate could not be avoided. Contrary to previous reports, severe hyperdynamic circulation was not observed after a rapid increase in isoflurane concentration.

Intravenous landiolol, a novel β1-adrenergic blocker, reduces the minimum alveolar concentration of sevoflurane in women

STUDY OBJECTIVE To investigate the effect of intravenous (IV) landiolol, a novel β(1)-adrenergic blocker, on the minimum alveolar concentration (MAC) of sevoflurane in adult women. DESIGN Prospective, randomized study. SETTING University hospital. PATIENTS 42 ASA physical status 1 and 2 women, aged 24-57 years, who were scheduled to undergo elective abdominal surgery. INTERVENTIONS Anesthesia was induced in all patients by vital capacity rapid inhalation induction of sevoflurane. In the landiolol group, administration of landiolol began when patients took a vital-capacity breath: 0.125 mg/kg/min for one minute and then 0.04 mg/kg/min. Normal saline was administered in the control group. MEASUREMENTS MAC was determined by a technique adapted from the conventional up-down method. MAIN RESULTS The MAC of sevoflurane was 2.2% ± 0.2% in the control group and 1.7% ± 0.2% in the landiolol group, a statistically significant difference (P = 0.0005). CONCLUSIONS IV landiolol reduces the MAC of sevoflurane in women by approximately 20%.

Intravenous nicorandil prevents thiamylal-fentanyl-induced bronchoconstriction in humans.

ObjectiveNicorandil has a hybrid property between nitrates and potassium channel openers and has been reported to cause a concentration-dependent relaxation of isolated guinea pig trachealis. Experimental asthma in a guinea pig model was also inhibited by nicorandil. However, no clinical data on the bronchorelaxant effects of this drug have been published. The aim of this study was to investigate whether intravenous nicorandil prevents thiamylal-fentanyl–induced bronchoconstriction. DesignDouble-blind, prospective, placebo-controlled, randomized study. PatientsA total of 36 patients were randomly allocated to two groups: a control group (n = 18) and a nicorandil group (n = 18). InterventionsIntravenous administration of nicorandil or a placebo (normal saline). Measurements and Main ResultsAnesthesia was induced with 5 mg/kg thiamylal and 0.3 mg/kg vecuronium. A continuous infusion of 15 mg·kg−1·hr−1 thiamylal was then used to maintain the anesthesia. Controlled ventilation was maintained, delivering 50% nitrous oxide in oxygen. At 20 mins after the induction of anesthesia, the control group patients were given a 6 mL/hr continuous infusion of normal saline and the nicorandil group patients were given a 6 mg·hr−1 (6 mL/hr) continuous infusion of nicorandil for 60 mins. At 30 mins after the start of the study, both groups received a 5-&mgr;g/kg dose of fentanyl. Systolic and diastolic arterial pressure, heart rate, mean airway resistance, expiratory airway resistance, and dynamic lung compliance were measured for the baseline condition, just before the administration of fentanyl (T30), at three consecutive 6-min intervals after the fentanyl injection (T36, T42, and T48) and 30 mins after the fentanyl injection (T60). Both groups had comparable baseline values for mean airway resistance, expiratory airway resistance, and dynamic lung compliance. In the control group, both mean airway resistance and expiratory airway resistance increased significantly at T36–60, compared with the baseline values, and dynamic lung compliance decreased significantly at T36–60, compared with the baseline value. In the nicorandil group, no changes in mean airway resistance, expiratory airway resistance, or dynamic lung compliance occurred at T36–60. ConclusionsOur observations suggest that the intravenous administration of nicorandil has a bronchodilator effect in humans.

Effect of Prophylactic Bronchodilator Treatment with Intravenous Colforsin Daropate, a Water-soluble Forskolin Derivative, on Airway Resistance after Tracheal Intubation

Background After induction of anesthesia, lung resistance increases. The authors hypothesized that prophylactic bronchodilator treatment with intravenous colforsin daropate, a water-soluble forskolin derivative, before tracheal intubation would result in decreased lung resistance and increased lung compliance after tracheal intubation when compared with placebo medication. Methods Forty-six adult patients were randomized to placebo or colforsin daropate treatment. Patients in the control group received normal saline; patients in the colforsin group received 0.75 &mgr;g · kg−1 · min−1 colforsin daropate intravenously until the study ended. Thirty minutes after the study began, the authors administered 5 mg/kg thiamylal and 5 &mgr;g/kg fentanyl for induction of general anesthesia and 0.3 mg/kg vecuronium for muscle relaxation. A 15-mg · kg−1 · h−1 continuous infusion of thiamylal followed anesthetic induction. Four, 8, 12, and 16 min after tracheal intubation, mean airway resistance (Rawm), expiratory airway resistance (Rawe), and dynamic lung compliance (Cdyn) were measured. Results Patients in the colforsin group had significantly lower Rawm and Rawe and higher Cdyn after intubation than those in the control group. Differences in Rawm, Rawe, and Cdyn between the two groups persisted through the final measurement at 16 min. At 4 min after intubation, smokers had a higher Rawm and a lower Cdyn than nonsmokers in the control group. After treatment by intravenous colforsin daropate, Rawm, Rawe, and Cdyn values were similar for smokers and nonsmokers after tracheal intubation. Conclusions Prophylactic treatment with colforsin daropate produced lower Rawm and Rawe and higher Cdyn after tracheal intubation when compared with placebo medication. Pretreatment before intubation may be beneficial and advantageous for middle-aged smokers.

Vigilance of hemodynamic changes immediately after transferring patients is crucial

PurposeA decrease in blood pressure is sometimes observed when a postsurgical patient is transferred to another bed after recovering from anesthesia. However, the mechanism behind this hypotension has not been completely elucidated. The purpose of this study was to investigate and compare changes in hemodynamic properties for possible causes of hypotension before and after transfer to another bed of postsurgical patients receiving general anesthesia, combined epidural and general anesthesia, or combined spinal and general anesthesia.MethodsWe studied 69 patients undergoing elective surgery who were randomized to receive anesthesia by one of the three methods. After surgery, the tracheal tube was removed, and each patient was transferred to another bed. Hemodynamic data recorded immediately before and after transfer of the patient to another bed were compared.ResultsAfter transfer of patients receiving general anesthesia or combined epidural and general anesthesia, systolic arterial pressure (SAP), diastolic arterial pressure (DAP), and cardiac output (CO) decreased; heart rate (HR) and systemic vascular resistance (SVR) did not change. However, after transfer of patients receiving combined spinal and general anesthesia, SAP, DAP, HR, and CO decreased, but SVR did not change.ConclusionThe decrease in blood pressure observed after transfer of a postsurgical patient to another bed after general, combined epidural and general, and combined spinal and general anesthesia was associated with a decrease in CO and no change in SVR, but HR decreased after combined spinal and general anesthesia, whereas it was unchanged after general and combined epidural and general anesthesia. The decrease in blood pressure is assumed to be caused by a decrease in venous return, and several reflexes might participate in this decrease of blood pressure, especially after combined spinal and general anesthesia.