Hidekazu Setoguchi

Leukotriene C4 enhances the contraction of porcine tracheal smooth muscle through the activation of Y‐27632, a rho kinase inhibitor, sensitive pathway

An unsaturated fatty acid, leukotriene C4 (LTC4), has a potent contractile effect on human airway smooth muscle, and has been implicated in the pathogenesis of human asthma. Using front‐surface fluorometry with fura‐PE3, the effect of LTC4 on the intracellular Ca2+ concentration ([Ca2+]i) and tension were investigated in porcine tracheal smooth muscle strips. The application of LTC4 induced little or no contraction despite a small and transient increase in [Ca2+]i. In the presence of LTC4, however, the contractions evoked by high K+ depolarization or a low concentration of carbachol (CCh) were markedly enhanced without inducing any changes in the [Ca2+]i levels, thus indicating that LTC4 increases the Ca2+ responsiveness of the contractile apparatus. This LTC4‐induced increase in Ca2+ responsiveness could partly be reproduced in the permeabilized preparation of tracheal smooth muscle strips. The LTC4‐induced enhancement of contraction was accompanied by an increase in myosin light chain (MLC) phosphorylation and was blocked by a rho kinase inhibitor (Y‐27632), but not by either a PKC inhibitor (calphostin C) or a tyrosine kinase inhibitor (genistein). These results indicated that, in porcine tracheal smooth muscle, LTC4 enhances the contraction by increasing the Ca2+ responsiveness of the contractile apparatus in a MLC phosphorylation dependent manner, possibly through the activation of the rho‐rho kinase pathway.

Rapid reversal of neuromuscular blockade by sugammadex after continuous infusion of rocuronium in patients with liver dysfunction undergoing hepatic surgery.

OBJECTIVE Sugammadex rapidly reverses neuromuscular blockade (NMB) induced by rocuronium. NMB induced by rocuronium is prolonged in patients with liver dysfunction, because the drug is mainly excreted into the bile. However, the efficacy and safety of sugammadex in terms of reversing rocuronium-induced NMB in patients with liver dysfunction undergoing hepatic surgery have not been evaluated. This observational study investigated the efficacy and safety of sugammadex after continuous infusion of rocuronium in patients with liver dysfunction undergoing hepatic surgery. METHODS Remifentanil/propofol anesthesia was administered to 31 patients: 15 patients in the control group, and 16 patients from a group with liver dysfunction. Rocuronium (0.6 mg/kg) was administered, followed by continuous infusion. The enrolled patients were then subdivided into two groups according to the dose of sugammadex. In the first group a single dose of sugammadex (2.0 mg/kg) was given at the reappearance of the second twitch (T2). In the second group a single dose of sugammadex (4.0 mg/kg) was given at the first twitch response if T2 did not reappear in 15 minutes after stopping rocuronium. The primary outcome was time from administration of sugammadex to recovery of a train-of-four ratio to 0.9. RESULTS The dose of rocuronium required in the liver dysfunction group was lower than that in the control group (6.2 vs. 8.2 μg/kg/min, p = 0.002). The mean time from the administration of sugammadex to recovery of the train-of-four ratio to 0.9 was not significantly different between the liver dysfunction group and the control group (2.2 minutes vs. 2.0 minutes in the 2 mg/kg administration group, p = 0.44 and 1.9 minutes vs. 1.7 minutes in the 4 mg/kg administration group, p = 0.70, respectively). No evidence of recurarization was observed in any of the patients. Most of the adverse events were found to be mild and such events were not related to the use of sugammadex. None of the patients was eliminated from the study because of an adverse event. One patient died due to cholestatic liver cirrhosis because of repeated hepatic surgery. CONCLUSION Sugammadex can rapidly reverse NMB after continuous infusion of rocuronium in patients with liver dysfunction undergoing hepatic surgery. Sugammadex was found to be safe and well tolerated. However, further studies of sugammadex under similar conditions should be conducted involving a large number of patients with liver dysfunction undergoing hepatic surgery.

The mechanisms of the direct action of etomidate on vascular reactivity in rat mesenteric resistance arteries.

BACKGROUND: Etomidate minimally influences hemodynamics at a standard induction dose in young healthy patients, but can cause significant systemic hypotension at higher doses for induction or electroencephalographic burst suppression (i.e., cerebral protection) in patients with advanced age or heart disease, and during cardiopulmonary bypass. However, less is known about its action on systemic resistance arteries. METHODS: Using an isometric force recording method and fura-2-fluorometry, we investigated the action of etomidate on vascular reactivity in small mesenteric arteries from young (7–8 wk old, n = 179) and aged (96–98 wk old, n = 10) rats. RESULTS: In the endothelium-intact strips from young rats, etomidate enhanced the contractile response to norepinephrine or KCl (40 mM) at 3 &mgr;M but inhibited it at higher concentrations (≥10 &mgr;M). The enhancement was still observed after treatment with NG-nitro l-arginine, tetraethylammonium, diclofenac, nordihydroguaiaretic acid, losartan, ketanserin, BQ-123, or BQ-788, but was not observed in aged rats. In the endothelium-denuded strips from young rats, etomidate (≥10 &mgr;M) consistently inhibited the contractile response to norepinephrine or KCl without enhancement at 3 &mgr;M. In the fura-2-loaded, endothelium-denuded strips from young rats, etomidate inhibited norepinephrine- or KCl-induced increases in both intracellular Ca2+ concentration ([Ca2+]i) and force. Etomidate still inhibited the norepinephrine-induced increase in [Ca2+]i after depletion of the intracellular Ca2+ stores by ryanodine, which was sensitive to nifedipine. Etomidate had little effect on norepinephrine- or caffeine-induced Ca2+ release from the intracellular stores or Ca2+ uptake into the intracellular stores. During stimulation with norepinephrine or KCl, etomidate had little effect on the [Ca2+]i-force relation at low concentrations (≤30 &mgr;M) but caused its downward shift at 100 &mgr;M. CONCLUSIONS: In small mesenteric arteries, etomidate influences the contractile response to norepinephrine or membrane depolarization through endothelium-dependent enhancing and endothelium-independent inhibitory actions. The enhancement is at least in part independent of nitric oxide, endothelium-derived hyperpolarizing factor, cyclooxygenase products, lipoxygenase products, angiotensin II, serotonin, or endothelin-1, but may involve some signaling pathway that is impaired by aging. The endothelium-independent inhibition is due to decreases in both the [Ca2+]i and myofilament Ca2+ sensitivity in vascular smooth muscle cells. The decrease in [Ca2+]i would be due mainly to inhibition of voltage-gated Ca2+ influx. The observed inability of lower concentrations (1–3 &mgr;M) of etomidate to cause significant vasodilation is consistent with minimal changes in hemodynamics during induction of anesthesia with etomidate in young subjects, whereas the observed vasodilator action of higher concentrations of etomidate might underlie systemic hypotension caused by higher doses of etomidate in the clinical setting.

Anesthetic management of a patient with aortocaval fistula

Aortocaval fistula is a rare complication of ruptured abdominal aortic aneurysm (AAA), and patients with an aortocaval fistula show multiple symptoms. We report an 87-year-old man who was diagnosed as having an AAA with aortocaval fistula and who developed refractory hypotension after induction of anesthesia. Following a phenylephrine injection for slight hypotension induced by anesthetic induction, he developed severe hypotension and bradycardia, and his skin became cyanotic. Vasopressor agents had no immediate effect on the hypotension, but blood pressure gradually increased in about 30 min with continuous infusion of dopamine and noradrenaline. Transesophageal echocardiography (TEE) showed right ventricle (RV) hypokinesis and massive tricuspid regurgitation (TR). Central venous pressure (CVP) showed a remarkably high value. After the repair of the aortocaval fistula, the hemodynamics became stable, RV motion was improved, TR was reduced, and CVP became normal. Anesthetic management of the repair of an aortocaval fistula is very difficult. The hemodynamics changed dramatically throughout anesthesia in our patient with this disorder, even though low-dose anesthetics were used. For the successful treatment of this disorder, preparation for the operation is required before the induction of anesthesia, and urgent closure of the fistula is necessary after the induction of anesthesia. TEE is a useful tool for monitoring hemodynamics in such patients.

Geriatric Patients Presenting to the Emergency Department of a Japanese University Hospital

To evaluate the trend of elderly patients visiting the emergency department of a Japanese University Hospital, out patient-based records were reviewed of the emergency department of Kyushu University Hospital from 2000 to 2004. A total number of 7610 emergency patients visited the department during the five year period. The median (25%, 75%) of age was 32 (22, 56). Patients aged 65 years and over accounted for 16% of all attendances. All the patients were classified into 6 groups according to the diagnosis, (1) Respiratory, (2) Circulatory, (3) Central nervous system, (4) Abdominal, (5) Trauma, and (6) Others. The median age in each group was (1) 27 (15, 49), (2) 66 (53, 76), (3) 51 (27, 67), (4) 33 (22, 56), and (5) 26 (20, 46), respectively. There was a statistically significant difference observed, reciprocally except between (1) and (5) (P < 0.05). The patients showed statistically significant difference in the annual transition of the disease (P < 0.0001). In the elderly, the annual transition of the disease showed statistically significant decreases in Circulatory (P = 0.0015) and in Central nervous (P < 0.0001), and an increase in Abdominal (P < 0.0001), respectively. Death rate at the outpatient clinic in the elderly showed much higher than in the younger (P < 0.0001). Admission rate was also much higher in the elderly than in the younger (P < 0.0001). Elderly emergency patients have both internal and external intrinsic factors. They have to be treated carefully since their condition easily deteriorates. Provisions for the problems surrounding the elderly should be made as a nationwide effort.

Reduction of regional cerebral oxygen saturation coincidental with a perioperative focal motor seizure

previous left hemiparetic attacks, at 3 years 2 months, 1year 5 months, and 8 months before admission. Theonly neurological deficit was a slight sensory distur-bance in the left leg. The brain computed tomographic(CT) scan indicated lacunar infarctions at the bilateralbasal ganglia. However, the Xe-enhanced CT scanfailed to reveal any significant decreases in cerebralblood flow. In addition, cerebral arteriography did notreveal any significant stenotic lesions. She had no appar-ent history of epileptic attacks. In spite of the previousdiagnosis of HT, the blood pressure preoperativelymeasured in the ward was 100–126/64–88mmHgwithout any treatment. She was slightly anemic due togenital bleeding (Hb 10.6g·dl

Required time for setting up an anaesthesia machine mounted on a movable ceiling pendant

The present study was performed to evaluate the duration of time required to set up an anaesthesia machine mounted on an automated or manually movable ceiling pendant. Nurses moved the machine’s position according to the surgical site (right or left). The duration of time required to set up the anaesthesia machine for surgery was compared between automated and manual operation and among nurses with varying years of work experience. Movement of the anaesthesia machine from the right to left position took longer for the automated (278 ± 11s) than manual (188 ± 63s) method. However, no difference was observed between automated (288 ± 11s) and manual (267 ± 140s) movement of the machine from the left to right position. Experienced nurses took less time in both directions. Manual movement took less time than automated movement in the right-to-left direction, which may be advantageous when nurses are in a hurry or have musculoskeletal system disorders and may allow them to perform other operating room preparation tasks. Either automated or manual movement may be used depending on the situation. Both the larger deviations with manual movement and the shorter time required by experienced nurses suggest that training and experience shorten the manual set-up time.

The relationship between seizure in electroconvulsive therapy and pupillary response using an automated pupilometer

ObjectivesSeizure duration and morphology, postictal suppression, and sympathetic nervous system activation are all recommended as assessments of adequate seizure in electroconvulsive therapy (ECT). However, blood pressure and heart rate are not typically assessed as part of sympathetic nervous system activation because of the administration of anesthetic or cardiovascular agents during ECT. Although the pupils are known to reflect to the activity of autonomic nervous system and the degree of brain damage, previous studies have not examined the relationship between seizure of electroconvulsive therapy and pupillary response.MethodsWe conducted 98 sessions of ECT with 13 patients, divided into two groups according to seizure quality: (1) adequate or (2) inadequate. Pupillary light reflex [% constriction = (maximum resting pupil size {MAX} − minimum pupil size after light stimulation)/MAX × 100] was measured using a portable infrared quantitative pupilometer before anesthesia induction and immediately after electrical stimulation.ResultsThe number regarded as adequate was 67 times and as inadequate was 31 times. Maximum pupil size at the control and immediately after electrical stimulation was similar between the adequate and inadequate groups. Pupillary light reflex was similar at the control between both groups, but significantly smaller immediately after stimulation in the adequate group (2.5 ± 3.6%) compared with the inadequate group (10.6 ± 11.5%). Receiver operating characteristic curve analysis revealed that pupillary light reflex (> 5.5%) predicted adequate seizure.ConclusionsThe current findings suggest that pupillary constriction immediately after ECT could provide a helpful method for assessing the efficacy of ECT.

Effects of Forced Air Warming on Airflow around the Operating Table

Background: Forced air warming systems are used to maintain body temperature during surgery. Benefits of forced air warming have been established, but the possibility that it may disturb the operating room environment and contribute to surgical site contamination is debated. The direction and speed of forced air warming airflow and the influence of laminar airflow in the operating room have not been reported. Methods: In one institutional operating room, we examined changes in airflow speed and direction from a lower-body forced air warming device with sterile drapes mimicking abdominal surgery or total knee arthroplasty, and effects of laminar airflow, using a three-dimensional ultrasonic anemometer. Airflow from forced air warming and effects of laminar airflow were visualized using special smoke and laser light. Results: Forced air warming caused upward airflow (39 cm/s) in the patient head area and a unidirectional convection flow (9 to 14 cm/s) along the ceiling from head to foot. No convection flows were observed around the sides of the operating table. Downward laminar airflow of approximately 40 cm/s counteracted the upward airflow caused by forced air warming and formed downward airflow at 36 to 45 cm/s. Downward airflows (34 to 56 cm/s) flowing diagonally away from the operating table were detected at operating table height in both sides. Conclusions: Airflow caused by forced air warming is well counteracted by downward laminar airflow from the ceiling. Thus it would be less likely to cause surgical field contamination in the presence of sufficient laminar airflow.

Abstract PR375: Management of Patients with Antiplatelet Therapy Undergoting Elective Non-Cardiac Surgery in University Hospital

Background & Objectives: The American College of Cardiology (ACC) and the American Heart Association (AHA) released clinical practice guidelines in 2014 recommending the optimal timing of surgery and the perioperative antiplatelet management in patients with percutaneous coronary intervention (PCI). The purpose of this study is to demonstrate changes in perioperative continuation or discontinuation of antiplatelet drugs since the release of ACC/AHA guidelines, in addition, to evaluate the perioperative management of patients with previous PCI especially using a drug-eluting stent (DES).