Hiromasa Mitsuhata

Suppressive effects of volatile anesthetics on cytokine release in human peripheral blood mononuclear cells.

This study investigated the effects of three volatile anesthetics (sevoflurane, isoflurane, and enflurane) on cytokine release by human peripheral mononuclear cells (PBMCs) stimulated by natural killer (NK)-sensitive tumor cells, K562, in vitro. PBMCs, as effector cells, obtained from 31 volunteers were randomly allocated to two groups in the first set of experiments. One group was incubated with K562 (n = 21) and the other with medium alone as a control (n = 10). In a second set of experiments, PBMCs from each volunteer (n = 21) were divided into three groups: nonanesthetic, 1.5-MAC, and 2.5-MAC groups (n = 7 for each anesthetic). After 2 h exposure to anesthetic gas or air, K562 cells were added to the effector cells. After 4 h incubation, interleukin-1 beta (IL-1 beta), interleukin-2 (IL-2), tumor necrosis factor-alpha (TNF-alpha), and interferon-alpha (INF-alpha) in the supernatant were assayed. IL-1 beta and TNF-alpha levels were significantly increased in comparison with those in the control group. IL-2 levels tended to be higher than those in the control group. No effect on IFN-alpha levels was found. After anesthetic exposure, the releases of IL-1 beta and the release of TNF-alpha were significantly inhibited compared with those after air exposure. None of the anesthetics inhibited IL-2 release. The anesthetics studied are capable of altering the release of cytokines by NK and NK-like cells in response to tumor cells.

Sevoflurane and isoflurane protect against bronchospasm in dogs.

Background Halothane and isoflurane have been shown to be effective in reversing bronchoconstriction; however, the effects of sevoflurane have not been well defined. We studied whether sevoflurane, compared with isoflurane, attenuates bronchospasm in dogs. Methods Twenty-four dogs sensitized to Ascaris suum were assigned to three groups: control (n = 8), sevoflurane (n = 8), or isoflurane (n = 8). In all dogs, anesthesia was induced with pentobarbltal. In the sevoflurane and isoflurane groups, the volatile anesthetics were administered at an end-tidal anesthetic concentration of 1 MAC throughout the study. After measurement of pulmonary resistance (RL) and dynamic pulmonary compliance (Cdyn) at baseline, A. suum antigen was administered Intravenously into the systemic circulation to Induce anaphylaxls, and RL and Cdyn were recorded continuously for 120 min after antigen challenge. Results Effects on RL and Cdyn were maximal 5 min after the start of systemic administration of antigen in all groups. Both 1 MAC sevoflurane and 1 MAC isoflurane significantly attenuated the increase in RL provoked by antigen challenge, but the attenuation from 10 to 15 min after challenge in the sevoflurane group was not significantly different from that in the control group. There was no significant difference in RL between sevoflurane and Isoflurane. For both sevoflurane and isoflurane, attenuation of the decrease in Cdyn was not statistically significant. There was no significant difference in Cdyn between sevoflurane and Isoflurane. Conclusions Sevoflurane is as effective as isoflurane in attenuating bronchoconstriction associated with anaphylaxis in dogs. Sevoflurane may be a useful alternative to halothane, enflurane, or isoflurane in the treatment of bronchospasm in asthma or anaphylaxis.

Comparison of patient-controlled epidural analgesia with and without background infusion after gastrectomy

To assess the analgesic efficacy and side effects of concurrent infusion in patient-controlled epidural analgesia (PCEA) after upper abdominal surgery, 40 patients undergoing elective gastrectomy under general anesthesia were allocated to two groups in this randomized, double-blind study: one received a 2.5-mL incremental bolus in a solution of 0.2% bupivacaine and 10 [micro sign]g/mL fentanyl, and the other received the same bolus dose plus a 2.5-mL/h infusion of the same solution. The number of demands was smaller (P < 0.001) in the PCEA plus infusion group than in the PCEA alone group during the 48-h postoperative period. The average hourly fentanyl and bupivacaine doses were larger (P < 0.0001) in the PCEA plus infusion group than in the PCEA alone group. Visual analog scale pain scores on coughing in the PCEA plus infusion group were lower than in the PCEA alone group (P < 0.05). There was a greater incidence of pruritus in the PCEA plus infusion group (P < 0.05), but no serious side effects were observed in either group. In conclusion, a background infusion in PCEA with a mixture of fentanyl and bupivacaine decreases the incidence of postoperative pain and reduces the degree of pain associated with coughing without serious side effects after gastrectomy. Implications: A background infusion in patient-controlled epidural analgesia with a mixture of fentanyl and bupivacaine decreased the incidence of postoperative pain and reduced the degree of the pain associated with coughing without serious side effects in this randomized, double-blind study after gastrectomy. (Anesth Analg 1998;87:907-10)

Sevoflurane is equivalent to isoflurane for attenuating bupivacaine-induced arrhythmias and seizures in rats

The effects of sevoflurane on bupivacaine toxicity have not been defined.The purpose of this study was to investigate the effects of sevoflurane and isoflurane on bupivacaine-induced arrhythmias and seizures in rats. Thirty-seven Sprague-Dawley rats received bupivacaine intravenously at a constant rate of 2 mg centered dot kg (-1) centered dot min-1 until both arrhythmias and seizures occurred while electrocardiogram (ECG) and electroencephalogram (EEG) recordings were made. The cumulative doses of bupivacaine inducing arrhythmias and seizures were determined in the presence of 1 minimum alveolar anesthetic concentration (MAC) of sevoflurane (sevoflurane group, n = 14) or isoflurane (isoflurane group, n = 10) and in the absence of anesthetic (control group, n = 13). The cumulative doses of bupivacaine inducing arrhythmias and seizures were larger in the sevoflurane and isoflurane groups than in the control group and were similar in the sevoflurane and isoflurane groups. These results indicate that sevoflurane and isoflurane attenuate bupivacaine-induced arrhythmias and seizures in rats. (Anesth Analg 1996;83:570-3)

Role of nitric oxide in anaphylactic shock

Nitric oxide, synthesized from the guanidino group ofl-arginine by nitric oxide synthase, has an important role in pathophysiological changes associated with anaphylaxis. Nitric oxide production due to activation of constitutive nitric oxide synthase is detected using a nitric oxide-selective electrode in anaphylactic rabbitsin vivo. A nitric oxide synthase inhibitor attenuates hypotension and hemoconcentration and decreases venous return but does not improve cardiac depression. Nitric oxide functionally antagonizes the effects of vasoconstrictors released by anaphylaxisin vitro. In animals pretreated with a nitric oxide synthase inhibitor, the cardiac output falls significantly, although venous return is increased. Pulmonary resistance is significantly increased with a nitric oxide synthase inhibitor, andl-arginine attenuates the bronchospasm. These findings suggest that production of nitric oxide may reduce the pathophysiologic changes, except for vasodilatation, associated with anaphylaxis.

Production of nitric oxide in anaphylaxis in rabbits.

To verify production of nitric oxide (NO) in anaphylaxis, we measured NO in peripheral tissue in anaphylactic rabbits using an NO-sensitive electrode. Rabbits were sensitized to horse serum, which was later administered over 10 s into the systemic circulation to induce anaphylaxis. Blood pressure (BP), central venous pressure (CVP), heart rate, and NO were recorded continuously for 80 min after antigen challenge. The NO-sensitive electrode was placed between the superficial abdominal fascia and the rectus abdominis fascia. The NO concentration increased to 3000-4800 pA (about 3-4.8 microM NO) within 4 min after initiation of anaphylaxis, at which time BP was decreased and CVP increased; however, NO production was continuously observed 30-60 min after antigen challenge, during which time changes in BP and CVP were not correlated with changes in NO concentration. In conclusion, NO production can be detected using an NO-selective electrode in anaphylactic rabbits.

The effects of sevoflurane and isoflurane anesthesia on renal tubular function in patients with moderately impaired renal function.

Increasing evidence indicates that sevoflurane anesthesia does not impair renal function in healthy patients despite higher concentrations of plasma inorganic fluoride.However, whether sevoflurane further affects renal tubular function in patients with impaired renal function is not known. We compared the effect of sevoflurane anesthesia with that of isoflurane anesthesia on renal tubular function in patients with moderately impaired renal function. Fourteen patients with creatinine clearance between 10 and 55 mL/min were anesthetized with either sevoflurane or isoflurane using a semiclosed circuit system. Plasma inorganic fluoride concentrations and urine N-acetyl-beta-D-glucosaminidase (NAG), gamma-glutamyltranspeptidase (gamma-GTP), and beta2-microglobulin (beta2 MG) excretions were measured up to postanesthetic day 14. Although both the peak plasma inorganic fluoride concentrations and the areas under the curve of plasma inorganic fluoride concentration versus time were significantly greater in the sevoflurane group than in the isoflurane group, urine NAG, gamma-GTP, and beta2 MG excretions per day did not differ between the two groups. These results indicate that sevoflurane and isoflurane may have similar effects on the renal tubules in patients with moderately impaired renal function. (Anesth Analg 1996;82:909-13)

Heparin-protamine complexes cause pulmonary hypertension in goats

Background Protamine reversal of heparin-induced anticoagulation causes thromboxane release followed by pulmonary vasoconstriction in sheep and pigs. The aim of this study was to determine whether heparin-protamine (H-P) complexes are causative agents of thromboxane release followed by pulmonary hypertension associated with protamine reversal of heparin.

Sugammadex and rocuronium-induced anaphylaxis

Perioperative anaphylaxis is a life-threatening clinical condition that is typically the result of drugs or substances used for anesthesia or surgery. The most common cause of anaphylaxis during anesthesia is reportedly neuromuscular blocking agents. Of the many muscle relaxants that are clinically available, rocuronium is becoming popular in many countries. Recent studies have demonstrated that succinylcholine (but also rocuronium use) is associated with a relatively high rate of IgE-mediated anaphylaxis compared with other muscle relaxant agents. Sugammadex is widely used for reversal of the effects of steroidal neuromuscular blocking agents, such as rocuronium and vecuronium. Confirmed cases of allergic reactions to clinical doses of sugammadex have also been recently reported. Given these circumstances, the number of cases of hypersensitivity to either sugammadex or rocuronium is likely to increase. Thus, anesthesiologists should be familiar with the epidemiology, mechanisms, and clinical presentations of anaphylaxis induced by these drugs. In this review, we focus on the diagnosis and treatment of anaphylaxis to sugammadex and neuromuscular blocking agents. Moreover, we discuss recent studies in this field, including the diagnostic utility of flow cytometry and improvement of rocuronium-induced anaphylaxis with the use of sugammadex.

Nitric oxide synthase inhibition is detrimental to cardiac function and promotes bronchospasm in anaphylaxis in rabbits.

ABSTRACT We studied the effects of a nitric oxide synthase (NOS) inhibitor, Nω-nitro-l-arginine-methyl ester (l-NAME), on cardiac depression and bronchospasm provoked by systemic anaphylaxis in vivo in rabbits. Animals pretreated with l-NAME showed lower survival rates than control animals pretreated with normal saline. The survival rate in l-NAME-pretreated animals was increased by the administration of l-arginine after initiation of anaphylaxis. Cardiac output fell significantly in animals pretreated with l-NAME compared with controls, although venous return was increased. In animals pretreated with l-NAME, pulmonary resistance was significantly increased, and administration of arginine attenuated the bronchospasm. In conclusion, these results, along with the low survival rates in the l-NAME-treated animals, suggest that NO production may be beneficial to cardiac depression and bronchospasm in anaphylaxis in vivo.