Taeko Fukuda

Minimal Effective Dose of Intrathecal Morphine for Pain Relief Following Transabdominal Hysterectomy

Intrathecal morphine is useful for relief of various types of pain. Postoperative pain relief is one of the most common indications (1). The dose range suggested for postoperative pain relief has ranged from 0.1 to 20 mg morphine (2-6), with the resulting pain relief lasting as much as 24 hours (7-10). Intrathecal morphine is also, however, accompanied by complications such as nausea, vomiting, urinary retention, pruritus, and delayed respiratory depression (1 1-15), the latter potentially life threatening (16). As side effects cannot be predicted (17) and because respiratory depression may be delayed by as much as 20 hours, careful observation for side effects is required (5,18,19). As a result, intrathecal morphine may not be as widely used as it deserves to be for postoperative pain relief because of lack of data on doseresponse relationships for intrathecal morphine, in which responses included both delayed respiratory depression as well as potentially less lethal side effects. In this study, we prospectively investigated the effects of low doses of intrathecal morphine, 0.10 mg as the maximum, on pain relief after transabdominal hysterectomy. We report the minimum effective intrathecal morphine dose defined as that amount of morphine that provides relief of postoperative pain with the least incidence of side effects.

Halothane Minimum Alveolar Anesthetic Concentration and Neuronal Nitric Oxide Synthase Activity of the Dorsal Horn and the Locus Ceruleus in Rats

UNLABELLED There is some evidence of a relationship between nitric oxide and pain control pathways. However, it is still controversial whether nitric oxide synthase (NOS) inhibitors affect minimum alveolar anesthetic concentration (MAC). We examined the effects of 7-nitro indazole (7-NI), a selective neuronal NOS (nNOS) inhibitor, on halothane MAC. With nicotinamide adenine dinucleotide phosphate diaphorase histochemistry, we also investigated the nNOS activity of the dorsal horn and the locus ceruleus in 26 Sprague-Dawley rats. 7-NI (100, 500, 1000 mg/kg intraperitoneally) reduced halothane MAC to 0.34% +/- 0.12%, 0.1% +/- 0.03%, and 0.05% +/- 0.12%, dose dependently (P < 0.01). 7-NI also reduced the number of nicotinamide adenine dinucleotide phosphate diaphorase-positive cells by 20% to 65% (P < 0.05 or 0.01) and the staining intensity of the axons in the locus ceruleus and lumbar and thoracic spinal cord as compared with the control group. 7-NI reduced the MAC observed with halothane anesthesia, which was accompanied by nNOS activity suppression in the spinal cord and the locus ceruleus. Our results support the hypothesis that the nitric oxide signaling pathway is related to MAC. IMPLICATIONS We examined the effects of a selective neuronal nitric oxide synthase inhibitor, 7-nitro indazole, on halothane minimum alveolar anesthetic concentration and measured the nitric oxide synthase activity in the spinal cord and the locus ceruleus of Sprague-Dawley rats using nicotinamide adenine dinucleotide phosphate diaphorase staining method. 7-Nitro indazole decreased both the minimum alveolar anesthetic concentration and neuronal nitric oxide synthase activity.

Free lidocaine concentrations during continuous epidural anesthesia in geriatric patients.

Background and Objectives To evaluate the effects of aging on lidocaine pharmacokinetics, the plasma concentrations of total and free lidocaine and its metabolites were measured during continuous thoracic epidural anesthesia in middle-aged (age 41 ± 9 years, n = 7) and elderly (age 72 ± 2 years, n = 7) male patients. Methods After establishment of general anesthesia, 7 mL 1.5% lidocaine with epinephrine 1:200,000 was injected into the epidural space and subsequently infused at a rate of 5 mL/h for 5 hours. Plasma concentrations of total and free lidocaine, monoethylglycinexylidide (MEGX), and glycinexylidide (GX) were measured at 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, and 300 minutes after initial lidocaine injection using high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection. Results The elderly group showed a stronger upward trend in the corrected free lidocaine concentrations and lower corrected total MEGX concentrations than the middle-aged group. Conclusions Lidocaine metabolite activity in the elderly male patients was lower than that in the middle-aged male patients. Free lidocaine concentration is prone to increase in elderly patients. Caution must be exercised during continuous thoracic epidural anesthesia combined with general anesthesia in geriatric patients.

The analgesic effect of xenon on the formalin test in rats: a comparison with nitrous oxide.

To investigate the analgesic effects of xenon, we performed formalin tests in rats under 0.5 minimum alveolar anesthetic concentration xenon or nitrous oxide and stained the lumbar spinal cord for c-fos (n = 18) and the phosphorylated N-methyl-d-aspartate (NMDA) receptor (n = 24) by using the avidin-biotin-peroxidase method. After 20 min of 79% xenon, 68% nitrous oxide, or 100% inhaled oxygen, 10% formalin (100 &mgr;L) was injected into the left rear paw of the animals except for a control group. Nociceptive behavior was observed for 1 h. The rats were killed 2 h after the formalin injection, and the lumbar spinal cord was stained for c-fos or the phosphorylated NMDA receptor immunohistochemically. Animals in the xenon and nitrous oxide groups showed less nociceptive behavior than did the oxygen group. Although the number of c-fos-positive cells in the lumbar spinal cord in the nitrous oxide group was not decreased, that in the xenon group decreased. The number of phosphorylated NMDA receptor-positive cells in the xenon group was significantly less than in the nitrous oxide and oxygen groups. Inhaled xenon suppressed nociceptive behaviors, c-fos expression, and activation of the NMDA receptor during the formalin test in rats. These results confirm that xenon’s analgesic effects result from inhibition of the NMDA receptor.

The effects of 30% and 60% xenon inhalation on pial vessel diameter and intracranial pressure in rabbits.

Xenon may increase cerebral blood flow and intracranial pressure (ICP). To evaluate the effects of xenon on brain circulation, we measured pial vessel diameter changes, CO2 reactivity, and ICP during xenon inhalation in rabbits. Minimum alveolar anesthetic concentration (MAC) for xenon was established in rabbits (n = 6). By using a cranial window model, pial vessel diameters were measured at 30% and 60% xenon inhalation and in time control groups (n = 15). ICP, mean arterial blood pressure, and heart rate were recorded during 30% and 60% xenon inhalation (n = 5). Pial vessel diameters were measured during hypocapnia and hypercapnia conditions in 60% Xenon and Control groups (n = 14). MAC for xenon was 85%. Xenon (0.35 and 0.7 MAC) dilated the arterioles (10% and 18%, respectively) and venules (2% and 4%, respectively) (P < 0.05). Dilation of arterioles was more prominent than that of venules. ICP, mean arterial blood pressure, and heart rate did not change during xenon inhalation. No difference in CO2 reactivity was observed between Xenon and Control groups (P = 0.79). Sixty percent xenon (0.7 MAC) dilated brain vessels, but venule changes were small. Xenon did not increase ICP and preserved CO2 reactivity of the brain vessels.

Comparisons of tetracaine spinal anesthesia with clonidine or phenylephrine in normotensive and hypertensive humans.

To compare the hemodynamics and anesthetic effects of spinal tetracaine containing either clonidine or phenylephrine administered to normotensive or hypertensive patients, we studied 75 patients allocated to one of three groups, each of which included nine hypertensive patients: clonidine group (n = 25) received 2 mL of 0.5% tetracaine (10 mg) containing clonidine (0.15 mg); phenylephrine group (n = 25) received 2 mL of 0.5% tetracaine (10 mg) containing phenylephrine (3 mg); and control group (n = 25) received 2 mL of 0.5% tetracaine (10 mg) alone. Analgesic levels and the intensity of motor block obtained did not differ significantly among the three groups. However, the regression of sensory block (skin dermatome) was significantly slower in patients given clonidine (T9 +/- 3) or phenylephrine (T9 +/- 3) at 300 min after the injection than in those (L1 +/- 3) in the control group (P < 0.01). Between normotensive and hypertensive patients, there was no significant difference in sensory and motor block in the three groups. Mean blood pressure (MBP) in both hypertensive and normotensive patients given tetracaine-clonidine remained approximately 20% lower than that in the control group for as long as 7 h after the injection (P < 0.05). We conclude that the inclusion of clonidine can provide similar effects to that of phenylephrine with respect to prolongation of hyperbaric tetracaine spinal anesthesia, but could cause more hypotension, without bradycardia, in both normotensive and hypertensive patients for a prolonged time (i.e., 420 min).

Plasma concentrations of lidocaine and its principal metabolites during continuous epidural infusion of lidocaine with or without epinephrine.

BACKGROUND AND OBJECTIVES The purpose of this study was to evaluate the effect of epinephrine on the absorption of lidocaine and the accumulation of active metabolites of lidocaine during continuous epidural anesthesia. METHODS Lidocaine was administered as an initial bolus of 5 mg/kg of 2% lidocaine solution followed by continuous infusion at 2.5 mg/kg/h. Patients in group I (n = 10) received lidocaine alone and patients in group II (n = 10) received lidocaine + epinephrine (5 pg/mL). Concentrations of lidocaine and its active metabolites, monoethylglycinexylidide (MEGX) and glycinexylidide (GX), were measured in plasma samples obtained after 15 minutes, 30 minutes, and 1, 2, and 3 hours of infusion using high-performance liquid chromatography with ultraviolet detection. RESULTS Plasma lidocaine concentrations were higher in group I for the first 30 minutes; however, after 1 hour the levels were the same. Plasma MEGX and GX increased continuously in both groups. MEGX levels the were significantly higher in group I, but there was no significant difference in the sum of lidocaine + MEGX after 2 hours. There was no significant difference in GX levels between the two groups. CONCLUSIONS With respect to continuous epidural administration, addition of epinephrine to lidocaine solutions is ineffective after 2 hours for reducing the potential for systemic toxicity, because the sum of the plasma concentrations of lidocaine and its principal active metabolite, MEGX, are unaffected.

Unilateral adrenalectomy attenuates hemorrhagic shock-induced analgesia in rats

PurposeTo assess the importance of the pituitary adrenal axis in producing stress-induced analgesia (SIA) after hemorrhagic shock, we performed formalin tests after hemorrhage and reinfusion in unilaterally adrenalectomized or sham-operated rats.MethodsFifty-two adult Sprague-Dawley rats were divided into seven groups: sham-operation normotensive (n = 8), sham-operation shock (n = 8), adrenalectomy normotensive (n = 7), adrenalectomy shock (n = 7), sham-operation shock + yohimbine (n = 7), sham-operation normotensive + corticosterone (n = 7), and adrenalectomy shock + corticosterone (n = 8). The left adrenal gland was cauterized 24 h before the experiment. The mean blood pressure in the shock groups was kept at 50–60 mmHg for 30 min by draining arterial blood. After the blood-reinfusion or observation period, 10% formalin was injected into the rear paw. Nociceptive behaviors and locomotion were observed and rated for 1 h, using the criteria of Dubuisson and Dennis. In 12 other sham-operated and adrenalectomized rats, plasma adrenalin, noradrenalin, and corticosterone concentrations were measured before and after hemorrhagic shock.ResultsAlthough the sham-operation shock group showed a lower pain score, the adrenalectomy shock group showed nociceptive behavior similar to that in the normotensive groups. Yohimbine did not affect the SIA; however, corticosterone administration reversed the effects of the adrenalectomy on the SIA. The plasma corticosterone levels in the unilaterally adrenalectomized rats were lower than those in the sham-operated rats and did not increase after hemorrhagic shock.ConclusionThese results suggest that adrenocortical systems play an important role in hemorrhagic shock-induced SIA.

Effect of intravenous prostaglandin E1 on pial vessel diameters and intracranial pressure in rabbits.

Background: The main advantages of prostaglandin E1 (PGE1) for induced hypotension during neurosurgery include a rapid onset of action, a quick recovery from hypotension, lack of toxicity, maintenance of adequate perfusion to vital organs, and maintenance of cerebral blood flow reactivity to carbon dioxide during hypotension. However, there is no report that shows the effect of PGE1 on cerebral microvessel diameter and only a few data are available that show the effect of PGE1 on intracranial pressure. The aim of this study was to measure cerebral arteriole and venule diameters and intracranial pressure (ICP) during PGE1‐induced hypotension to evaluate whether PGE1 is suitable for neuroanesthesia.

Arteriovenous differences of blood alcohol concentrations after celiac plexus block

After a celiac plexus block with ethyl alcohol, patients sometimes complain of symptoms of alcohol intoxication. We studied the consecutive changes of arterial and venous blood alcohol concentrations in 11 patients and investigated whether an arteriovenous difference exists. We performed a celiac plexus block with 10 ml absolute ethyl alcohol. The sampling sites were radial artery and internal jugular vein. Blood samples were collected at 0, 5, 10, 15, 30, 60, 120, 240 and 480 minutes after the block. The maximum level was reached 15 minutes after injection in both arterial and venous blood, 29.9 ± 19.4 and 27.7 ± 21.8 mg/dl (means ± SD), respectively. Arteriovenous differences were observed 5 and 10 minutes after ethyl alcohol injection (p < 0.01). There was a significant negative correlation between the ratio of arteriovenous differences to venous sampling and the time elapsed after the block (r = 0.41, p < 0.01).