Anesth Analg 2000;91:347-352
© 2000 International Anesthesia Research Society
NEUROSURGICAL ANESTHESIA
The Effect of Calcium Channel Blockers on Cerebral Oxygenation During Tracheal Extubation
Yuji Morimoto, MD, PhD,
Yoshiko Morimoto, MD, PhD,
Osamu Kemmotsu, MD, PhD, FCCM,
Satoshi Gando, MD, PhD,
Takaki Shibano, MD, and
Hirochika Shikama, MD
Department of Anesthesiology and Critical Care Medicine, Hokkaido University School of Medicine, Sapporo, Japan
Address correspondence and reprint requests to Yuji Morimoto, MD, PhD, Department of Anesthesiology and Critical Care Medicine, Hokkaido University Graduated School of Medicine, Sapporo, 060-8638, Japan. Address e-mail to morim2{at}med.hokudai.ac.jp
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Abstract
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Calcium channel blockers are effective in stabilizing systemic hemodynamics during tracheal extubation. However, they may increase cerebral blood flow (CBF) during tracheal extubation because of cerebral vasodilation, even if systemic arterial blood pressure decreases. In this study, we observed changes in cerebral oxygenation during tracheal extubation by using near-infrared spectroscopy and evaluated the effect of nicardipine and diltiazem on the resultant changes. We studied 45 women undergoing elective gynecologic surgery. After surgery, the patients were randomly allocated to three groups (n = 15 each): saline (control) , 0.02 mg/kg nicardipine, and 0.2 mg/kg diltiazem. After 2 min, we started to aspirate secretions for 2 min and then, extubated the trachea. Changes in cerebral oxygenated hemoglobin (HbO2) and deoxygenated hemoglobin were measured during the extubation procedure for 9 min after drug treatment. Systemic hemodynamics, including mean arterial blood pressure, heart rate, end-tidal CO2, end-tidal sevoflurane concentration, and peripheral arterial oxygen saturation were also monitored. During extubation, HbO2 increased significantly, presumably caused by the increase in CBF. Changes in deoxygenated hemoglobin were minimal. Compared with the control, nicardipine and diltiazem significantly inhibited the increase in mean arterial blood pressure. On the contrary, they significantly enhanced the increase in HbO2. In conclusion, calcium channel blockers may increase CBF during extubation, even if these drugs stabilize systemic hemodynamics.
Implications: This study is a preliminary report evaluating the changes in cerebral oxygenation during the tracheal extubation. Cerebral oxygenated hemoglobin increased significantly, presumably caused by the increase in cerebral blood flow during extubation. In addition, these changes were enhanced by calcium channel blockers.
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Introduction
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Calcium (Ca) channel blockers are effective in stabilizing systemic hemodynamics during tracheal extubation (1–3). For, example, diltiazem significantly attenuated the increases in blood pressure (BP) and heart rate (HR) during tracheal extubation. A dose of 0.2 mg/kg diltiazem was more effective than 1 mg/kg lidocaine (1).
Ca channel blockers cause cerebral vasodilation (4) and increase intracranial pressure (ICP) in animals (4–6), humans without cerebral disorders (7), and patients with intracranial hemorrhage (8).
Tracheally intubated subjects experience an increase in ICP in response to coughing or bucking (9,10). Traditionally, this was explained by an increase in cerebral venous pressure through an increase in intrathoracic pressure (9). One study, however, suggests that an increase in cerebral blood flow (CBF) by a stimulated increase in muscle afferent activity (MAA) may be attributable to this increase in ICP (11). If so, Ca channel blockers may enhance the increase in the CBF, and hence ICP, when coughing or bucking occur during tracheal extubation, even if systemic BP decreases.
The Kety and Schmit method (12) is traditional for bedside CBF monitoring. CBF was calculated by the rate at which a systematically introduced substance (133xenon, nitrous oxide, heat, etc.) achieves equilibrium in the brain, or alternatively, by the rate at which an equilibrated substance is cleared. However, it is invasive, and the values are discontinuous. The transcranial Doppler method, in which Doppler shift was converted to CBF velocity, is noninvasive and continuous. However, fixation of the probe is difficult, especially when the patient’s head moves. Accordingly, the data may be inaccurate when the patient coughs or bucks during tracheal extubation. Near infrared spectroscopy is a noninvasive method for the monitoring of the regional cerebral oxygenation state. By measuring the absorption of light at several wavelengths in the near-infrared range, it is possible to monitor changes in brain tissue concentrations of oxyhemoglobin (HbO2) and deoxyhemoglobin (Hb) through the Beer-Lambert law (13) This change in method reflects CBF change indirectly (14). Moreover, the probes can be fixed at the forehead and the values rarely drift, even with head movement. A recent study also demonstrated that near-infrared spectroscopy is capable of detecting the small changes in cerebral oxygenation associated with the induction of general anesthesia (15).
The purposes of this study were to observe the changes in regional cerebral oxygenation state during tracheal extubation and to evaluate the effect of Ca channel blockers (nicardipine and diltiazem) on the changes. There has been no previous report regarding the change in cerebral oxygenation during tracheal extubation. And, if Ca channel blockers increase CBF during tracheal extubation, changes in cerebral oxygenation may be enhanced by these drugs.
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Methods
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After obtaining institutional approval and informed consent, we studied 45 women (ASA physical status I and II) undergoing elective gynecologic surgery. Patients with central nervous system, cardiovascular, or respiratory diseases were excluded. Patients were premedicated with 10 mg diazepam orally and 150 mg ranitizine orally 2 h before the induction of anesthesia. An epidural catheter was inserted preoperatively to allow for the control of postoperative pain; however, no drug treatment was performed until the end of the protocol. Anesthesia was induced with 2 mg/kg propofol and 2 µg/kg fentanyl and tracheal intubation was facilitated with 0.1 mg/kg IV vecuronium. Anesthesia was maintained with 1% to 3% sevoflurane under oxygen and air (FIO2 = 0.4).
We used a spectrometer (NIRO 500; Hamamatsu Photonics, Hamamatsu, Japan) for near-infrared spectroscopy. The optodes were secured high on one side of the forehead 4–5 cm apart and shielded from ambient light. A sampling interval of 5 s was used. The changes in HbO2 and Hb were calculated assuming an adult differential path-length factor of 6.26 (16). The values were transferred to and recorded in a personal computer. An intraarterial line was placed in the radial artery and continuous arterial pressure was monitored. Heart rate, end-tidal CO2 (ETCO2), end-tidal sevoflurane concentration (ETsevo) and peripheral arterial oxygen saturation (SpO2) were also monitored. All values at every 5 s were recorded in the personal computer simultaneously with HbO2 and Hb.
The experimental protocol schema is shown in Figure 1. After the abdominal muscle was closed and T1 component in train-of-four recovered by peripheral nerve stimulator with recording equipment (Relaxograph; Datex Helsinki, Finland), residual muscle relaxation was reversed with 0.02 mg/kg neostigmine and 0.01 mg/kg atropine. After surgery was completed, sevoflurane was discontinued and 100% oxygen was administered. We waited until the patients regained consciousness (opening eyes and hand grip on command) and muscle tone (train-of-four ratio >0.9). Then, they were randomly allocated to three groups (n = 15 each): saline (control) , 0.02 mg/kg nicardipine, or 0.2 mg/kg diltiazem (Fig. 1). The medication was prepared beforehand in equivalent volumes by an assistant and the anesthesiologist was blinded to the medications. Then, 2 min after one of each drug was injected, we aspirated secretions for 2 min and extubated. We established the aspiration period judging from the previous animal experiments (17,11) and each patient’s stress. Then, 100% oxygen was administered via face mask for 5 min and the protocol was terminated.
Baseline values of HR, BP, SpO2, ETCO2, and ETsevo were obtained at the test drug injection. At the same time, we set HbO2 and Hb values at 0 µmol/L and changes in HbO2 and Hb were monitored, thereafter. The quality of tracheal extubation was evaluated by using a 5-point rating scale: 1 = no coughing or straining, 2 = very smooth, minimal coughing, 3 = moderate coughing, 4 = marked coughing or straining, and 5 = poor extubation, very uncomfortable (18).
The values were expressed as mean ± SD. Patient demographic data (parametric) among treatment groups were compared by using one-way analysis of variance (ANOVA). For the comparison of quality score of tracheal extubation, the Kruskal-Wallis test was performed. The types of surgeries were compared by using the 
2 test. We extracted HR, mean BP, HbO2, and Hb values at 0, 2, 3, 4, and 9 min after the test drug administration. We compared these changes in each group using one-way ANOVA and among the groups using repeated measures ANOVA. When one-way ANOVA showed significant results, the Student-Newman-Keuls test was used. When significant results showed in the repeated measures ANOVA, the contrast test was used. A P < 0.05 was considered statistically significant. We extracted SpO2 at 0, 2, 3, 4, and 9 min and ETCO2 and ETsevo values at only 0 and 2 min (before starting extubation procedure).
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Results
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There was no significant difference among the groups regarding whether the surgeries were laparotomy or gasless laparoscopy (P = 0.90 by the 2 test) (Table 1). When the surgeries were divided into five categories (laparotomic hysterectomy, laparotomic oophorectomy, laparoscopic hysterectomy, laparoscopic oophorectomy, and laparoscopic examination for sterility), there was also no significant difference among the groups (P = 0.94 by the 2 test) (Table 1).The test drug was administered at least 5 min after the injection of atropine and neostigmine and there was no significant difference in the interval (Table 1). There were no significant differences in other demographic data among the groups (Table 1).
During extubation, mean BP increased in the control group and decreased in the nicardipine and diltiazem groups, although a significant change over time was not seen in each group (P = 0.06, 0.19, or 0.08 in the control, nicardipine, or diltiazem group, respectively, by one-way ANOVA) (Fig. 2). However, a significant difference in mean BP was observed among the groups (P = 0.03 by repeated measures ANOVA). The change in the control group was significantly lower compared with changes in the nicardipine (P = 0.04) and diltiazem (P = 0.01) groups by contrast test. No significant difference was observed between the nicardipine and diltiazem groups (P = 0.67). These results indicated the dosage of both drugs was enough to reduce BP.
At 3 and 4 min, HR significantly increased in the nicardipine and diltiazem groups (P < 0.01 by one-way ANOVA, P < 0.05 by Student-Newman-Keuls test in both groups) (Fig. 2). No significant change was observed in the control group (P = 0.23 by one-way ANOVA). No significant difference in HR was observed among the groups (P = 0.06 by repeated measures ANOVA).
SpO2 values were >99% at every point in each group (Table 2). ETCO2 was between 35 and 40 mm Hg in all of the groups at either 0 or 2 min (Table 2). These findings suggested that the respiratory effect on cerebral circulation could be excluded in this study. ETsevo was <0.2% in all of the groups at either 0 or 2 min, which could also exclude the effect of sevoflurane on cerebral circulation and metabolism.
Fig. 3 shows the representative example of changes in the cerebral oxygenation state during tracheal extubation. HbO2 was significantly increased by the extubation procedure in each group (P < 0.01 by one-way ANOVA) (Fig. 4). At 2 min, HbO2 had already increased significantly in the nicardipine group only (P < 0.05 by Student-Newman-Keuls test). At 3 and 4 min, HbO2 values were significantly higher compared with the baseline values in all of the groups (P < 0.05 by Student-Newman-Keuls test). There was a significant difference in the change in HbO2 among the groups (P < 0.01 by repeated measures ANOVA). A contrast test indicated that the increase in HbO2 was significantly higher in the nicardipine and diltiazem groups than that in the control group (P < 0.01, respectively). There was no significant difference between the nicardipine and diltiazem group (P = 0.23).
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Figure 3. Representative example of changes in cerebral oxygenation state during tracheal extubation. Continuous line = change in oxygenated hemoglobin (HbO2); dotted line = change in deoxygenated hemoglobin (Hb).
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Change in Hb was minimal compared with that in HbO2; however, a significant increase was observed in the control and diltiazem groups (P = 0.02 or 0.03 in the control or diltiazem group, respectively, by one-way ANOVA) (Fig. 4). In these groups, significant increases against baseline values were seen at 9 min (P < 0.05 by Student-Newman-Keuls test). Hb showed no significant change in the nicardipine group (P = 0.51 by one-way ANOVA). No significant difference was observed among the groups (P = 0.06 by repeated measures ANOVA).
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Discussion
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There are some limitations regarding the measurement of cerebral oxygenation by near-infrared spectroscopy. First, the signal from scalp and skull may be mixed into the overall signal. However, a previous study indicates that our method can detect changes in adult cerebral hemodynamics, and that the contribution of surface tissues to the signal is small (14). Second, we fixed the adult path-length factor at 6.26. However, the exact cerebral path length in each patient was unknown, so that the absolute value of each variable may not be accurate (13). Accordingly, it may be meaningless to compare absolute values among the patients. In this study, we did not compare absolute values among the groups, but compared changes in values by using repeated measures ANOVA.
The variables of cerebral oxygenation obtained from the near-infrared spectroscopy were influenced by the change in CBF, cerebral metabolism, arterial saturation, and hematocrit (13). Arterial saturation was >99% at each point in all groups. It appeared unlikely that hematocrit would change during such a short extubation time after surgery. Also, patient consciousness became clearer during the extubation procedure, which indicated that their cerebral metabolic rate increased. If so, HbO2 should have decreased because of the increase in oxygen consumption. On the contrary, HbO2 increased during the extubation procedure, indicating that the increase in CBF should occur more than the cerebral metabolic rate. Patients in this study had no hypertension and the change in mean BP was almost within the autoregulation range of CBF (19). However, Lanier et al. (17) demonstrated that that CBF increased by 35% in response to noxious stimulus to the trachea in tracheally intubated dogs. At the same time, the increase in cerebral metabolic rate for oxygen was only 7%, supposedly because of a stimulated increase in MAA in response to movement (11). The mechanism by which MAA modulates cerebral function was reviewed by Lanier et al. (17,11). Drugs or maneuvers that cause muscle stretch or contraction or directly stimulate muscle stretch receptors will result in an increase in MAA (11). The action potentials generated by the muscle afferents are transmitted to the brain (the cerebellum, the motor cortex, and the somatosensory cortex) through peripheral nerves and the dorsal spinal cord (17). An increase in MAA can influence the functional activity within large areas of brain, and hence produce luxury perfusion in excess of cerebral metabolic demand (17). Accordingly, we assumed that the excess increase in CBF during the extubation procedure caused the increase in HbO2 as was seen in our study. Hb showed almost no change during the extubation procedure, indicating passive venous congestion may not occur so severely during extubation. Lanier et al. (11) also showed that central venous pressure or superior vena caval pressure did not transfer efficiently to the intracranial vault, and that increased central venous pressure could only partially account for the ICP response.
Nicardipine and diltiazem significantly increased HbO2 compared with the control. We speculate that this results from an increase in CBF because of cerebral vasodilation. Abe et al. (20) reported that nicardipine, but not diltiazem, increased CBF during cerebral aneurysm surgery for subarachnoid hemorrhage. Hirayama et al. (8) also reported that the ratio of the decrease in cerebral perfusion pressure to the decrease in systolic BP was significantly larger with nicardipine than with diltiazem in patients with increased ICP by spontaneous intracerebral hematomas. A near spectrophotometric study using rats showed that injections of 0.005 and 0.05 mg/kg of nicardipine increased HbO2 by 13% and 29% and that the effect of diltiazem was smaller (21). These previous reports suggested that cerebral vasodilation was greater with nicardipine than with diltiazem. This may be consistent with our result showing that HbO2 significantly increased at two minutes compared with the baseline values only in the nicardipine group. At nine minutes, Hb slightly, but significantly, increased in the control and diltiazem groups. Although the mechanism is unknown, increased blood shifts from the arterial to venous compartment after extubation. Nicardipine induced venous constriction, decreasing cerebral venous blood volume (22). Accordingly, an increase in Hb may not be observed in the nicardipine group.
We reversed muscle relaxation by using atropine and neostigmine. Cholinergic pathways related to the nicotinic receptors are mainly activated by this procedure. There are no reports regarding whether activation of nicotinic pathways affects the cerebral stimulation by MAA. In animals, cerebral vasodilation was mediated by an activation of the nicotinic receptors (23). In humans, however, the nature and effect of cerebral cholinergic pathways on cerebral circulation are not well understood (24) and their physiological significance is still questionable in humans (25). Although nicardipine blocked the effects of superfused nicotinic agonist on nicotinic receptors in frog skeletal muscle (26), the interaction of nicotinic effect and nicardipine- or diltiazem-induced cerebral vasodilation has not been demonstrated. Moreover, the interval between the injection of muscle relaxant antagonists and test drugs was almost equal among the groups. Accordingly, the effect of muscle relaxant antagonists should be negligible in this study.
We treated diazepam as premedication. Benzodiazepines cause reduction in CBF in humans (24). Diazepam also blocks voltage-gated Ca channels (27). However, the interaction of diazepam and nicardipine- or diltiazem- induced cerebral vasodilation has not been demonstrated. Accordingly, there was no difference in the effect of diazepam among the groups, although the increase in CBF during tracheal extubation may have been inhibited in all of the groups.
Previous reports demonstrated that Ca channel blockers, especially, nicardipine, increased CBF and ICP in patients with cerebral disorders (20,8). In this study, the patients had no cerebral disorders, so we could not determine the change in the cerebral oxygenation state in patients, such as those with increased ICP.
In conclusion, our near-infrared spectrometric study indicated that cerebral oxygenated hemoglobin increased probably because of an increase in CBF during tracheal extubation. Ca channel blockers, nicardipine, and diltiazem enhanced the increase in CBF, and hence, changes in cerebral oxygenated hemoglobin were accelerated, although these drugs stabilized systemic hemodynamics.
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Acknowledgments
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The authors thank N. Yoshida, H. Murayama, and Y. Osaki for their technical assistance.
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Footnotes
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Presented, in part, at the annual meeting of the American Society of Anesthesiologists, Orlando, FL, October 17–21, 1998.
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References
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|---|
-
Nishina K, Mikawa K, Maekawa N, Obara H. Attenuation of cardiovascular responses to tracheal extubation with diltiazem. Anesth Analg 1995;80:1217–22.[Abstract]
-
Mikawa K, Nishina K, Maekawa N, Obara H. Attenuation of cardiovascular responses to tracheal extubation: Verapamil versus diltiazem. Anesth Analg 1996;82:1205–10.[Abstract]
-
Mikawa K, Nishina K, Takao Y, et al. Attenuation of cardiovascular responses to tracheal extubation: Comparison of verapamil, lidocaine, and verapamil-lidocaine combination. Anesth Analg 1997;85:1005–10.[Abstract]
-
Takenaka T, Handa J. Cerebrovascular effects of YC-93, a new vasodilator, in dogs, monkeys and human patients. Int J Clin Pharmacol Biopharm 1979;17:1–11.[Medline]
-
Griffin JP, Cottrell JE, Hartung J, Shwiry B. Intracranial pressure during nifedipine-induced hypotension. Anesth Analg 1983;62:1078–80.[Abstract/Free Full Text]
-
Mazzoni P, Giffin JP, Cottrell JE, et al. Intracranial pressure during diltiazem-induced hypotension in anesthetized dogs. Anesth Analg 1985;64:1001–4.[Abstract/Free Full Text]
-
Nishikawa T, Omote K, Namiki A, Takahashi T. The effects of nicardipine on cerebrospinal fluid pressure in humans. Anesth Analg 1986;65:507–10.[Abstract/Free Full Text]
-
Hirayama T, Katayama Y, Kano T, Tsubokawa T. Control of systemic hypertension with diltiazem, a calcium-antagonist, in patients with a mildly elevated intracranial pressure: A comparative study. Neurol Res 1994;16:97–9.[Medline]
-
White PF, Schlobohm RM, Pitts LH, Lindauer JM. A randomized study of drugs for preventing increases in intracranial pressure during endotracheal suctioning. Anesthesiology 1982;57:242–4.[Web of Science][Medline]
-
Lanier WL, Iaizzo PA, Milde JH. Cerebral function and muscle afferent activity following intravenous succinylcholine in dogs anesthetized with halothane: the effects of pretreatment with a defasciculating dose of pancuronium. Anesthesiology 1989;71:87–95.[Medline]
-
Lanier WL, Albrecht RF, Laizzo PA. Divergence of intracranial and central venous pressures in lightly anesthetized, tracheally intubated dogs that move in response to a noxious stimulus. Anesthesiology 1996;84:605–13.[Medline]
-
Kety SS, Schmidt CF. The nitrous oxide method for the quantitative determination of cerebral blood flow in man: Theory, procedure and normal values. J Clin Invest 1948;27:476–83.
-
Kurth CD, Uher B. Cerebral hemoglobin and optical path length influence near-infrared spectroscopy measurement of cerebral oxygen saturation. Anesth Analg 1997;84:1297–305.[Abstract]
-
Elwell CE, Owen-Reece H, Wyatt JS, et al. Influence of respiration and changes in expiratory pressure on cerebral haemoglobin concentration measured by near-infrared spectroscopy. J Cereb Blood Flow Metab 1996;16:353–7.[Medline]
-
Lovell AT, Owen-Reece H, Elwell CE, et al. Continuous measurement of cerebral oxygenation by near-infrared spectroscopy during induction of anesthesia. Anesth Analg 1999;88:554–8.[Abstract/Free Full Text]
-
Duncan A, Meek JH, Clemence M, et al. Optical path length measurements on adult head, calf and forearm and the head of the newborn infant using phase resolved optical spectroscopy. Phys Med Biol 1995;40:295–304.[Web of Science][Medline]
-
Lanier WL, Iaizzo PA, Milde JH, Sharbrough FW. The cerebral and systemic effects of movement in response to a noxious stimulus in lightly anesthetized dogs: Possible modulation of cerebral function by muscle afferents. Anesthesiology 1994;80:392–401.[Web of Science][Medline]
-
Nishina K, Mikawa K, Maekawa N, Obara H. Fentanyl attenuates cardiovascular responses to tracheal extubation. Acta Anaesthesiol Scand 1995;39:85–9.[Medline]
-
Michenfelder JD. Cerebral blood flow and metabolism. In: Cucchiara RF, Michenfelder JD, eds. Clinical neuroanesthesia. New York:Churchill Livingston, 1990:1–40.
-
Abe K, Iwanaga H, Inada E. Effect of nicardipine and diltiazem on internal carotid artery blood flow velocity and local cerebral blood flow during cerebral aneurysm surgery for subarachnoid hemorrhage. J Clin Anesth 1994;6:99–105.[Web of Science][Medline]
-
Hazeki O, Tamura M. Quantitative analysis of hemoglobin oxygenation state of rat brain in situ by near-infrared spectrophotometry. J Appl Physiol 1988;64:796–802.[Abstract/Free Full Text]
-
Koyama K, Mito T, Takashima S, Suzuki S. The effects of prostaglandin E1 and nicardipine on cerebral blood flow, blood volume and oxygenation in young rabbits. Brain Dev 1991;13:32–5.[Web of Science][Medline]
-
Uchida S, Kagitani F, Nakayama H, Sato A. Effect of stimulation of nicotinic cholinergic receptors on cortical cerebral blood flow and changes in the effect during aging in anesthetized rats. Neurosci Lett 1997;228:203–6.[Web of Science][Medline]
-
Drummond JC, Patel PM. Cerebral physiology and the effects of anesthetics and techniques. In: Miller RD, ed. Anesthesia. Philadelphia:Churchill Livingston, 2000:695–733.
-
Hoffman BB, Lefkowitz RJ, Taylor P. Neurotransmission: The autonomic and somatic motor nervous systems. In: Hardman JG, Limbird LE, Molinoff PB, et al., eds. Goodman and Gilman’s the pharmacological basis of therapeutics. New York:McGraw-Hill, 1996:105–39.
-
Adam LP, Henderson EG. Calcium channel effectors are potent non-competitive blockers of acetylcholine receptors. Pflugers Arch 1990;416:586–93.[Medline]
-
Nakazawa K, Inoue K, Ohara IM, et al. Inhibition of Ca-channels by diazepam compared with that by nicardipine in pheochromocytoma PC12 cells. Brain Res 1991;553:44–50.[Medline]
Accepted for publication April 10, 2000.
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Abstract
Introduction
= nicardipine group; 
= diltiazem group. #Significant compared with baseline values by Student-Newman-Keuls test. HR = heart rate; BP = blood pressure
