Tadahiko Ishiyama

Direct effects of ropivacaine and bupivacaine on spinal pial vessels in canine. Assessment with closed spinal window technique.

Background: Ropivacaine produces a vasoconstriction of cutaneous vessels in contrast to vasodilation produced by bupivacaine. To evaluate direct spinal microvascular actions of these local anesthetics, the authors investigated the concentration‐related effects of ropivacaine and bupivacaine on spinal pial vascular diameters using the spinal window technique. Methods: Anesthetized dogs (n = 14) divided into two groups (ropivacaine, n = 7; bupivacaine, n = 7) were prepared for measurement of spinal pial vessel diameters by intravital microscopy in a spinal window preparation. The authors administered six concentrations of each drug (10 sup ‐8 ‐10 sup ‐3 M) under the window and directly measured the spinal pial arteriolar and venular diameters at sequential times. Physiologic data including mean arterial blood pressure (MAP) and heart rate (HR) were determined before and after topical application of each concentration of the drugs. In additional experiments (n = 18), the action of topical ropivacaine and bupivacaine solution on spinal vessels was evaluated in the presence of yohimbine, prazosin, and propranolol. Results: Ropivacaine significantly constricted whereas bupivacaine dilated pial arterioles and venules, both in a concentration‐dependent manner. Microvascular alteration was not blocked with any of the adrenoceptor antagonists tested (yohimbine, prazosin, propranolol), each of which per se did not affect pial vessel diameters. Topical application of ropivacaine or bupivacaine did not induce any change in MAP or HR. Conclusions: The present results indicate that ropivacaine constricts and bupivacaine dilates the pial vessels of the spinal cord in a concentration‐dependent fashion, and the mechanisms involved in such actions do not seem to be mediated via alpha‐ or beta‐adrenoceptor of spinal vasculature.

Mechanisms of dexmedetomidine-induced cerebrovascular effects in canine in vivo experiments

Dexmedetomidine decreases cerebral blood flow without significantly affecting cerebral oxygen consumption in anesthetized dogs.To assess the direct cerebrovascular effects of dexmedetomidine, we investigated the responses of vasomotor tone to topical application of dexmedetomidine to pial vessels in vivo, using a parietal cranial window. Forty-one dogs were anesthetized with pentobarbital. In 20 dogs, we topically applied six concentrations of dexmedetomidine solution (10-8, 10-7, 10 (-6), 10-5, 10-4, 10-3 M) and directly measured pial arterial and venous diameters. In 10 dogs, the inhibitory effects of pretreatment of pial vessels with 10-5 M yohimbine were examined after the application of 10-5 M dexmedetomidine. In the remaining 11 dogs, the effects of 10-3 M dexmedetomidine were evaluated in the presence of Nomega-nitro-L-arginine methyl ester (L-NAME), glibenclamide, or propranolol. Dexmedetomidine significantly constricted pial arteries and veins in a concentration-dependent manner (10-7 M to 10-4 M; P < 0.05). Yohimbine blocked dexmedetomidine-induced constriction of pial vessels (both large and small arteries and large veins P < 0.0001; small veins P < 0.005). However, when the highest concentration of dexmedetomidine (10-3 M) was administered under the window, pial vessel diameter was not significantly altered. In the presence of glibenclamide, 10-7 and 10-3 M dexmedetomidine induced a significant decrease in pial arterial diameter compared with 10-7 and 10-3 M dexmedetomidine solution alone, respectively (P < 0.05). L-NAME or propranolol did not affect the dexmedetomidine-induced constriction. Although yohimbine, glibenclamide, or propranolol did not change pial vascular diameter, L-NAME significantly constricted both pial arteries and veins (P < 0.05). Our study demonstrates that topical application of dexmedetomidine constricts both pial arterial and venous vessels in a concentration-dependent manner. The vasoconstrictor effects of dexmedetomidine appear to be mediated via activation of alpha2-adrenoceptors, although this action is accompanied by activation of adenosine triphosphate sensitive K+-channels as a counterbalancing vasodilatory effect. The present results also suggest that the resting tone of pial arteries and veins does not depend on alpha (2-and) beta-adrenergic control, but is influenced by nitric oxide. (Anesth Analg 1995;81:1208-15)

Ephedrine, but not phenylephrine, increases bispectral index values during combined general and epidural anesthesia.

Ephedrine and phenylephrine are used to treat hypotension during combined general and epidural anesthesia, and they may change anesthetic depth. In the current study, we evaluated the effects of ephedrine versus phenylephrine on bispectral index (BIS) during combined general and epidural anesthesia. After injection of ropivacaine through the epidural catheter, general anesthesia was induced with propofol and vecuronium, and was maintained with 0.75% sevoflurane. Approximately 10 min after the intubation, BIS was recorded as a baseline value. Patients with decreases in arterial blood pressure <30% of the preanesthetic values were defined as control group (n = 9). Patients who had to be treated for larger decreases in arterial blood pressure were randomly assigned to receive ephedrine 0.1 mg/kg (n = 17) or phenylephrine 2 &mgr;g/kg (n = 17). BIS values were recorded at 1-min intervals for 10 min. BIS in the ephedrine group was significantly larger from 7 to 10 min than that in the control and phenylephrine groups (P < 0.05). Seven patients in the ephedrine group had BIS >60, whereas no patient in the control and phenylephrine groups had BIS >60 (P < 0.005). Ephedrine, but not phenylephrine, increased BIS during general anesthesia combined with epidural anesthesia.

The effects of topical and intravenous ropivacaine on canine pial microcirculation

To assess the direct cerebrovascular effects of ropivacaine, we studied pharmacological responses to its topical and intravenous (IV) administration on vasomotor tone of pial vessels in in vivo experiments using a parietal cranial window in 24 dogs anesthetized with pentobarbital.We directly measured the diameters of pial arteries and veins after the administration of five different concentrations of ropivacaine solution (10-7 to 10-3 mol/L) randomly given into the window (n = 10). In six dogs, after pretreating the pial vessels with yohimbine (10-5 mol/L), the inhibitory action of yohimbine was examined after the application of ropivacaine (10-3 mol/L). The effects of IV ropivacaine (1 and 4 mg/kg) were also evaluated in the remaining eight dogs. Ropivacaine produced significant constriction of the pial arteries in a concentration-dependent manner (10-7 to 10-3 mol/L, P < 0.05) and only exerted a constrictive action on small veins (P < 0.05) at 10-3 mol/L. Yohimbine had no effect on ropivacaine-induced constriction of pial vessels. IV ropivacaine, 4 mg/kg but not 1 mg/kg, caused pial vascular constriction (large arteries P < 0.005, small arteries P < 0.0001, large veins P < 0.01, small veins P < 0.005) associated with decrease in heart rate (P < 0.001). The results indicate that topical application of ropivacaine constricts pial arterial vessels in a concentration-dependent manner. A large dose of IV ropivacaine produced pial vasoconstriction associated with a decrease in heart rate and no decrease in mean arterial blood pressure. These effects do not appear to be mediated via the mechanism that depends on the activation of alpha2-adrenoceptors. We conclude that ropivacaine in high concentrations could, perhaps directly, cause significant constriction of the central nervous system vasculature. (Anesth Analg 1997;85:75-81)

The vascular effects of topical and intravenous alpha2-adrenoceptor agonist clonidine on canine pial microcirculation.

To assess the direct cerebrovascular effects of clonidine, we investigated the pharmacological responses of pial vessels to its topical and IV administration using a cranial window.Forty-six dogs anesthetized with pentobarbital had the cranial window implanted. We administered six different concentrations of clonidine (10-8, 10-7, 10-6, 10-5, 10-4, 10-3 mol/L) dissolved in artificial cerebrospinal fluid under the window and measured the pial arterial and venous diameters. After pretreating pial vessels with either yohimbine, an alpha2-adrenoceptor antagonist, or glibenclamide, an adenosine triphosphate-sensitive K+-channel blocker, their action was examined after applying clonidine. We also evaluated the effects of IV clonidine (5 [micro sign]g/kg) on pial vascular tone. Topical clonidine produced significant constriction of the pial large and small arteries and veins in a concentration-dependent manner (P < 0.05). Yohimbine abolished the clonidine-induced pial arterial (large P < 0.005; small P < 0.0005) and venous constriction (large and small P < 0.0001). Glibenclamide potentiated the clonidine-induced pial arterial constriction (P < 0.05). IV clonidine did not cause significant changes in pial arteries, but it caused significant constriction of small veins. These were associated with a significant decrease in heart rate and an increase in serum potassium level and glucose concentration. In the present study, we demonstrate that the topical application of clonidine constricts both pial arterial and venous vessels in a concentration-dependent manner and suggest that mechanisms of such action are caused by the activation of alpha2-adrenoceptors and adenosine triphosphate-sensitive K+-channels, whereas IV clonidine constricts only pial small veins. Implications: In this study, we describe the direct and IV effects of clonidine on pial vessels using a cranial window in anesthetized dogs. The topical application of clonidine constricts pial vessels. This is mediated by the activation of alpha2-adrenoceptors and adenosine triphosphate-sensitive K+-channels. IV clonidine constricts only pial small veins. (Anesth Analg 1998;86:766-72)

The effective time and concentration of nitrous oxide to reduce venipuncture pain in children

STUDY OBJECTIVE To investigate the time of administration and concentration of inhaled nitrous oxide (N(2)O) needed to reduce the pain associated with intravenous (i.v.) cannulation in children. DESIGN Prospective, randomized study. SETTING Operating room of a childrens hospital. PATIENTS 73 ASA physical status I and II children, aged 6-15 years, scheduled for elective day or non-day surgery. INTERVENTIONS Children were randomly allocated to one of 4 groups prior to i.v. insertion of a 24-gauge catheter in the dorsum of the hand: Group 1 (n = 18): 50% N(2)O in O(2) for three minutes; Group 2 (n = 18): 50% N(2)O in O(2) for 5 minutes; Group 3 (n = 18): 70% N(2)O in O(2) for three minutes; or Group 4 (n = 19): 70% N(2)O in O(2) for 5 minutes. MEASUREMENTS Just after the venous cannulation, degree of pain was assessed by examining the faces of the patient by the parent and an operating room nurse. MAIN RESULTS Pain scores obtained from parents of children in Groups 3 and 4 were significantly lower than from those in Groups 1 and 2. Pain scores from the nurse in Group 3 was significantly lower than those in Group 1. However, there was no significant difference in pain score between Group 3 and Group 4. Frequency of side effects was similar among the 4 groups. CONCLUSIONS Seventy percent N(2)O in O(2) given for three minutes was effective for reducing venipuncture pain in children.

The direct effects of propofol on pial microvessels in rabbits.

Propofol is widely used for neurosurgical anesthesia; however, its effects on the pial microvasculature are unknown. We therefore evaluated the direct effects of propofol on pial microvessels in rabbits. Pial microcirculation was visualized using a closed cranial window technique in 20 Japanese white rabbits. In the first experiment (n=14), after baseline hemodynamic measurements, the cranial window was superfused with 5 increasing concentrations of propofol (10−8, 10−7, 10−6, 10−5, 10−4 mol/L; n=8) or intralipid (at comparable concentrations; n=6) dissolved in artificial cerebrospinal fluid for 7 minutes each. A typical anesthetic concentration of 5 μg/mL corresponds to 10−6 mol/L. In the second experiment (n=6), phenylephrine 10−6 mol/L and nitroglycerin 10−6 mol/L were applied topically for 7 minutes under pentobarbital anesthesia. In the third experiment (n=3), electroencephalogram and bispectral index were measured under pentobarbital anesthesia. Diameters of selected pial arterioles and venules were visualized with a microscope-video capture unit combination and subsequently measured with a digital video analyzer. Topical application of propofol at 10−8, 10−7, 10−6, or 10−5 mol/L did not alter the diameters of the pial microvessels; however, at 10−4 mol/L propofol induced dilation in large and small arterioles, along with venular dilation. Intralipid alone did not have any significant effect on vessel diameters. Phenylephrine and nitroglycerin produced pial arteriolar and venular constriction and dilation, respectively. Phenylephrine constricted and nitroglycerin dilated pial arterioles and venules. Pentobarbital did not produce either burst suppression or an isoelectric electroencephalogram. The results confirm our hypothesis: clinically relevant concentrations of propofol, that is, approximately 10−6 mol/L, do not dilate pial arterioles or venules.

Effects of epidural fentanyl and intravenous flurbiprofen for visceral pain during cesarean section under spinal anesthesia

AbstractPurpose. Despite adequate levels of sensory blockade, patients sometimes complain of abdominal pain during cesarean section performed under spinal anesthesia. The aim of this study was to evaluate the effects of epidural fentanyl and intravenous flurbiprofen on visceral pain during cesarean section in patients having spinal anesthesia. Methods. Thirty ASA physical status I and II patients undergoing elective cesarean section were studied. Spinal-epidural anesthesia was performed in all groups. Group A received no additional analgesics, group B received epidural fentanyl 100 μg, and group C received flurbiprofen 50 mg i.v. immediately after the delivery. Postdelivery, intraoperative visceral pain was evaluated by using the visual analog scale. Incidence and visual analog scale scores of visceral pain and incidence of intraoperative nausea and vomiting were obtained from each patient. Results. Visual analog scale scores of pain were significantly lower in group B than in the other groups (P < 0.05). The incidence of nausea was comparable in all groups. The incidence of intraoperative vomiting was lower in group C than in the other groups (P < 0.05). Conclusion. Epidural fentanyl, but not intravenous flurbiprofen, decreases the incidence and severity of visceral pain during cesarean section.

The effects of bupivacaine and ropivacaine on baroreflex sensitivity with or without respiratory acidosis and alkalosis in rats.

Systemic toxicity of local anesthetics causes cardiac and central nervous system (CNS) depression that could be enhanced in the presence of respiratory acidosis.We examined a potential suppression of baroreflex function with bupivacaine and ropivacaine during hypercapnic acidosis or hypocapnic alkalosis. Baroreflex sensitivity (BRS) was randomly tested in rats with one of 13 conditions during intravenous administration of saline (control), bupivacaine 1, 2, or 3 mg/kg, or ropivacaine 2, 4, or 6 mg/kg. The effects of bupivacaine (3 mg/kg) or ropivacaine (6 mg/kg) on BRS were also examined during hypercapnic acidosis or hypocapnic alkalosis. The BRS was assessed using a value of Delta heart rate/Delta mean arterial pressure after infusion of phenylephrine (3 micro g/kg). Both bupivacaine and ropivacaine (at the largest dose) significantly suppressed BRS. Acute respiratory acidosis (pHa 7.24 +/- 0.04, PaCO2 63 +/- 4 mm Hg) enhanced BRS. The BRS enhanced during acidosis was also suppressed with bupivacaine and ropivacaine, but less so than in the absence of acidosis. The presence of hypocapnic alkalosis (pHa 7.55 +/- 0.03, PaCO2 25 +/- 2 mm Hg) did not affect BRS and reversed BRS suppression caused by both drugs. Thus, bupivacaine and ropivacaine affect neuronal control mechanisms for maintaining cardiovascular stability, and acute changes of respiration could significantly modify such suppression. (Anesth Analg 1997;84:398-404)

Urinary bladder and oesophageal temperatures correlate better in patients with high rather than low urinary flow rates during non-cardiac surgery

Background and objective: To investigate the effect of urinary flow rate on the urinary bladder temperature, we compared the accuracy and precision of urinary bladder temperature with oesophageal temperature at both high and low urine flow rates. Methods: Twenty‐four patients ASA physical status I or II who were undergoing tympanoplasty were randomly assigned to two groups with different intravenous fluid volumes: high (10 mL kg−1 h−1, n = 12) and low (3 mL kg−1 h−1, n = 12). General anaesthesia was induced with propofol and maintained with sevoflurane (1.5‐2.5%) in nitrous oxide and oxygen. Urinary bladder temperature was measured using a Foley urinary catheter; distal oesophageal temperature was measured using a stethoscope thermocouple. These temperatures were measured every 5 min during surgery and the accuracy and precision of urinary bladder temperature with oesophageal temperature were determined using regression and Bland and Altman analyses. Results: The correlation coefficient for oesophageal and urinary bladder temperature was 0.90 in the high urinary volume group and 0.75 in the low urinary volume group. The offset (oesophageal‐urinary bladder) was −0.13 ± 0.32°C and −0.46 ± 0.45°C, respectively. Conclusion: Urinary bladder temperature appears to be more accurate at high urinary flow rates than at low urinary flow rates for clinical use.