Breathing pattern and respiratory mechanics in sevoflurane-anesthetized humans

In order to determine the respiratory effects of sevoflurane in humans, breathing pattern and mechanical behavior of respiratory system were investigated in ten subjects at anesthetic depth of 1MAC (minimum alveolar concentration). Average tidal volume and breathing frequency amounted to 275ml and 20.9 breaths per minute. Arterial carbon dioxide tension amounted to 45.6mmHg. Duration of inspiration was 1.06s and that of expiration was 1.92s. Mean inspiratory flow rate amounted to 259ml·s^–1. Average value of passive respiratory elastance determined by the method of Zin et al. amounted to 21.8cmH₂O·l ^–1, while those of active respiratory elastance and resistance obtained by the method of Behrakis et al. were 28.0cmH₂O·l ^–1 and 3.15cmH₂O·l ^–1·s^–1, respectively.Values of these variables were compared to those reported in halothane and enflurane anesthesia and possible explanations of the differences between the anesthetics are discussed.(Izumi Y, Kochi T, Isono S, et al.: Breathing pattern and respiratory mechanics in sevoflurane-anesthetized humans. J Anesth 4: 343–349, 1990)     

Percutaneous and Open Renal Revascularizations Have Equivalent Long-Term Functional Outcomes

Atherosclerotic renal artery stenosis is a significant cause of poorly controlled hypertension and progressive renal dysfunction leading to ischemic nephropathy and other end-organ damage. The optimal treatment of renovascular disease contributing to hypertension and renal dysfunction is not known. This study compares the anatomic and functional outcomes of both open and endovascular therapy for chronic, symptomatic atherosclerotic renal artery disease. We performed a retrospective analysis of records from patients who underwent renal arterial interventions, endovascular or open bypass, between January 1984 and January 2004. Principal indications for intervention were hypertension (51%), chronic renal insufficiency (13%), and hypertension and elevated creatinine (36%). A total of 247 patients (109 males; mean age 69±10, range 44–89 years) underwent 314 interventions (109 open procedures; 205 angioplasties, 71% with stent placement). There was a significant difference in 30-day mortality (4% vs. <1%; p < 0.005) between the open and endoluminal groups, but not at 1, 3, or 5 years. Patients in the open group had a higher primary patency rate at 5 years (83±5% vs. 76±6%; p=0.03), but patients in the endoluminal group had a higher assisted primary patency rate at 5 years (92±5% vs. 84±5; p=0.03). There was no significant difference between both treatment groups in cumulative freedom from presenting symptom or in freedom from dialysis and renal-related death. Patients who presented with hypertension were more likely to have shown improvement in their blood pressure with endoluminal intervention at 1, 3, and 5 (59±6% endoluminal vs. 83±5% open; p=0.01) years. From these results we conclude that open repair and endoluminal repair of atherosclerotic renal artery stenosis have similar immediate and long-term functional and anatomic outcomes. Patients who present with hypertension may have greater benefit with an endoluminal repair.Presented at the Twenty-ninth Annual Meeting of the Peripheral Vascular Surgery Society, Anaheim, CA, June 4-5, 2004.     

Effects of Cilostazol on Human Venous Smooth Muscle

In this study, we evaluated the effect of therapeutic doses of cilostazol on human venous smooth muscle. Saphenous vein rings (two to four per patient sample) were suspended in tissue baths for isometric tension recordings. At the beginning of the experiment, optimal tension for isometric contraction was achieved for each ring in a stepwise fashion in the presence of norepinephrine (10^–2 M). Norepinepherine was then added cumulatively in half-molar increments and isometric tension developed by the rings was measured, thereby obtaining a dose-response curve. Following washout and reequilibration, the rings were precontracted with a 30-50% submaximal dose of norepinepherine determined from the dose-response curve and allowed to contract until a stable plateau was reached. Cilostazol was then added in a cumulative manner (680-2,720 g/L), and the tension generated was recorded. A total of 76 venous rings were tested, and all relaxed in the presence of cilostazol. The amount of relaxation increased as the concentration of cilostazol increased. Relaxation of 15±1.9% (mean±SEM) at low cilostazol doses (680 g/L) to 37±3% at high cilostazol doses (2,720 g/L) was demonstrated. A second finding of this study was demonstrated when the patient samples were divided according to the presence or absence of risk factors for arteriosclerosis. The specific risk factors examined included diabetes mellitus, smoking, hypercholesterolemia, and hypertension. The presence or absence of hypertension (n=52) or hypercholesterolemia (n=18) did not affect the amount of relaxation of the venous rings. Smokers (n=46) had less relaxation 16±2.4% (680 g/L) to 41±3.6% (2,720 g/L) compared to nonsmokers (n=53) who relaxed 22±3.5% (680 g/L) to 48±5.7% (2720 g/L). This did not reach statistical significance at any concentration cilostazol (p=0.11-0.18). Diabetics (n=53) did have statistically significantly less relaxation at every concentration of cilostazol compared to nondiabetics (n=11, p < 0.05). All venous rings relaxed in the presence of cilostazol. Veins of nondiabetics relaxed statistically significantly more than those of diabetics. Smokers had less relaxation than non-smokers, but this was not statistically significant. We are the first to demonstrate that human venous smooth muscle cells undergo relaxation when exposed to therapeutic concentrations of cilostazol.     

Changes of local brain tissue oxygen pressure after vasopressin during spontaneous circulation

Summary. Background. Brain tissue oxygen pressure (PbtO₂) correlates to cerebral blood flow (CBF) during spontaneous circulation, with one important regulator being nitric oxide (NO). Although it is established that arginine vasopressin (AVP) improves CBF and global cerebral oxygenation during cardiopulmonary resuscitation, it is unknown whether similar beneficial effects are present during spontaneous circulation. The purpose of this study was to investigate the effects of AVP with and without pre-treatment with the NO synthase inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME) on local brain tissue oxygenation in a beating heart model.Methods. Following approval of the Animal Investigational Committee, nine healthy piglets underwent general anaesthesia, and were instrumented with a probe in the cerebral cortex to measure PbtO₂. Each animal was assigned to receive AVP (0.4U·kg^–1), and after a wash-out period, L-NAME (25mg·kg^–1 over 20min) followed by AVP (0.4U·kg^–1). After each AVP administration, nitroglycerine (25µg·kg^–1 over 1min) as a NO donor was infused to test the vascular reactivity independently from NOS inhibition.Findings. Three minutes after administration of AVP, PbtO₂ increased significantly (P<.05; mean±SEM, 31±11 versus 43±14mmHg, +39%), compared with baseline. After pre-treatment with L-NAME, the changes of PbtO₂ after AVP were not significant (32±11 versus 28±10, –13%) when compared with the baseline.Conclusion. In this beating heart porcine model, local brain tissue oxygenation was improved after AVP alone, but not after inhibition of NO synthesis with L-NAME.     

Efficacy of landiolol in attenuating hemodynamic responses to local epinephrine infiltration in patients undergoing vaginal total hysterectomy

Purpose Local epinephrine infiltration often causes ₁-adrenoceptor-mediated tachycardia, hypertension, and arrhythmia. Landiolol, a short acting ₁-adrenoceptor blocker, may represent the most ideal agent to attenuate these adverse effects. In this study, we examined the effects of landiolol on the hemodynamic changes resulting from local infiltration of epinephrine.Methods Thirty-six patients undergoing vaginal total hysterectomy under general anesthesia were randomly assigned to one of three groups: control group (n = 12), L5 group (n = 12), and L10 group (n = 12). In the control, L5, and L10 groups, the patients were given saline, landiolol 5mg, and 10mg, respectively, just before infiltration of epinephrine(1:300000; total dose, about 100µg) into the surgical field. Blood pressure and heart rate was assessed before and 5, 10, 15, 20, 25, 30min after the initiation of epinephrine infiltration. If systolic blood pressure and heart rate exceeded 160mmHg and 120 beats·min^–1, respectively, Ca blockers of either diltiazem 5mg or nicardipine 1mg and/or 2% sevoflurane were given.Results Epinephrine infiltration significantly increased systolic blood pressure from 122 ± 15 to 170 ± 29mmHg and heart rate from 63 ± 8 to 106 ± 10 beats·min^–1. In both the L5 and L10 groups, the increase in heart rate (from 69 ± 16 to 87 ± 16 beats·min^–1, P < 0.01, and from 70 ± 18 to 76 ± 9 beats·min^–1, P < 0.01, respectively) was significantly smaller compared to the control group, but the increase in systolic blood pressure was significantly attenuated in the L10 group (from 116 ± 18 to 140 ± 27mmHg, P < 0.01). The number of patients given either Ca blockers or sevoflurane in the control group was significantly higher than that in the landiolol groups (P < 0.01).Conclusion The present study suggests that landiolol 10mg may be a more suitable dose than landiolol 5mg to antagonize hyperdynamic states induced by local administration of epinephrine.     

Dose-finding study of intravenous midazolam for sedation and amnesia during spinal anesthesia in patients premedicated with intramuscular midazolam

Purpose We investigated the effective and safe dose of intravenous midazolam for sedation and amnesia during spinal anesthesia in patients premedicated with intramuscular midazolam.Methods One hundred and eighty patients aged 20–50 years scheduled for spinal anesthesia received midazolam 0.06mg·kg^–1 and atropine 0.01mg·kg^–1 intramuscularly 15min before entering the operating room. Spinal anesthesia was performed with 0.5% hyperbaric tetracaine. Five minutes after starting surgery, midazolam 0 (control group), 0.01, 0.02, 0.03, 0.04, or 0.05mg·kg^–1 was intravenously administered (30 patients each). Blood pressure, heart rate, respiratory rate, percutaneous oxygen saturation (S_{p O 2}), verbal response, eyelash reflex, and involuntary body movement were measured every 5min for 30min. Memory during surgery was also investigated.Results The number of the patients with loss of verbal response, with loss of eyelash reflex, and with no memory during surgery were significantly larger in the groups receiving midazolam 0.03mg·kg^–1, 0.04mg·kg^–1, and 0.02mg·kg^–1, respectively. The decrease in blood pressure or increase in respiratory rate with decrease in S_{p O 2} was significantly larger in the groups receiving midazolam 0.03mg·kg^–1 or 0.05mg·kg^–1, respectively.Conclusion For sedation and amnesia of the patients aged 20–50 years in spinal anesthesia with about 1h duration receiving intramuscular midazolam 0.06mg·kg^–1 as a premedication, intravenous midazolam 0.02mg·kg^–1 might be effective and safe.     

Comparison of anesthetic effects of epidural and intravenous administration of buprenorphine during operation

Thirty six patients were received epidural anesthesia with or without buprenorphine (BPN) during upper abdominal surgery. They were divided into three groups of 12 patients as follows; G-I received 20ml of 1% lidocaine epidurally, G-II received 20ml of 1% lidocaine epidurally and 0.6mg BPN intravenously, G-III received 20ml of 1% lidocaine with 0.6mg BPN epidurally. Additional 5ml of 1% lidocaine was given to any patient if systolic blood pressure or heart rate increased 10% compared to control value. Trachea was intubated following anesthetic induction with thiopental. The lungs were ventilated with a mixture of N₂O/O₂ (33%) and pancuronium was used for muscle relaxation. The total required doses of lidocaine in G-II and G-III were decreased 60% compared to control group (G-I) (P 0.05). The mean period of time until the first administration of pentazocine for postoperative pain was 13 ± 10hr (mean ± SD) in G-II and 19 ± 24hr in G-III compared to 5 ± 4hr in G-I (P 0.001). The dose of the administration of pentazocine that was required for pain relief during the first 48 postoperative hr in G-III was 54 ± 10mg (mean ± SD) compared to 150 ± 21mg in G-I (P 0.02) and 106 ± 28mg in G-II (P 0.05). Recovery from anesthesia in G-III was more rapid than that in G-I (P 0.05). The Pa_{CO 2} values in G-II and G-III increased 15% compared to control group at about 4hr and 8hr after administration of BPN, but any clinical treatment was not needed for them. Nonrespiratory side effects, e.g., nausea, vomiting, fatigue and headache, were comparably common in all groups. Mild hematuria associated with acute hypotension occurred in two patients in G-II (17%) immediately after the intravenous injection of 0.6mg of BPN. The results showed that 0.6mg of BPN given epidurally demonstrated better anesthetic and more potent postoperative analgesic effects and lesser side effects than 0.6mg of BPN given intravenously in patients undergoing upper abdominal surgery.(Yonemura E, Fukushima K.: Comparison of anesthetic effects of epidural and intravenous administration of buprenorphine during operation. J Anesth 4: 242–248, 1990)     

Hospital Readmissions Following Abdominal Aortic Aneurysm Repair

In-hospital outcomes associated with abdominal aortic aneurysm (AAA) repair are well described. However, little is known about post-discharge readmission rates, lengths of stay, associated mortality, and costs. We examined 206 consecutive patients who underwent AAA repair at two American hospitals between 1998 and 2000. Index hospitalization and 6-month readmission data were extracted from a resource and cost accounting system used by both hospitals. Among the 206 patients, 183 survived until discharge (mortality rate 11.2%). Among the surviving patients, 38 (21.0%) were readmitted within 6 months. Half of the readmissions occurred within two weeks of discharge, with patients presenting with a diverse array of complications. Nonelective repair and diabetes mellitus were independent predictors of hospital readmission (OR=2.83, 95% CI=1.25-6.40, p=0.01; OR=6.60, 95% CI=1.02-42.4, p=0.047, respectively). For each readmission, the mean length of stay was 10.7±2.5 days and the mean cost was $13,397±3,381. The cumulative number of hospital days during the 6 months post-discharge was 17.7±3.5 days for each readmitted patient and the mean per-patient total cost was $23,262±5,478. The mortality rate among readmitted patients was 13.2%. Overall, readmissions following AAA repair accounted for a cost >50% over and above the cost of the readmitted patients index hospitalization. Hospital readmissions are common during the 6 months following AAA repair. Patients who are readmitted experience long lengths of stay and high mortality rates, and their care incurs high costs.Dr. Eisenberg is a Physician-Scientist of the Quebec Foundation for Health Research. Dr. Pilote is a Physician-Scientist of the Canadian Institutes for Health Research.     

Comparison of the epinephrine-induced arrhythmogenic effect of sevoflurane with isoflurane and halothane

The effect of sevoflurane on cardiac arrhythmias induced by the infusion of epinephrine into dogs was compared with those of isoflurane and halothane. The arrhythmogenic doses of epinephrine determined in this comparative study were expressed by both infusion rates of epinephrine and the corresponding plasma levels obtained by a series of three-minute epinephrine infusions during sevolurane, isoflurane, and halothane anesthesia at 1.25 MAC. The mean values of the arrythmogenic infusion rates of epinephrine and the corresponding plasma levels were 17.3µg/kg/min and 275.7ng/ml for sevoflurane, 6.7µg/kg/min and 149.2ng/ml for isoflurane and 1.9µg/kg/min and 39.1ng/ml for halothane, respectively. These results indicate that the arrythmogenic doses of epinephrine during sevoflurane and isoflurane anesthesia were significantly higher than those during halothane anesthesia.(Imamura S et al.: Comparison of the epinephrine-induced arrhythmogenic effect of sevoflurane with isoflurane and halothane. J Anesth 1: 62–68, 1987)     

Wakefulness during the induction with high-dose fentanyl and oxygen anesthesia

The purpose of this study was to investigate the state of wakefulness during the induction of anesthesia with high-dose fentanyl using the isolated forearm technique. Ten patients scheduled for elective cardiovascular surgery were premedicated with morphine (0.15mg/kg) and scoploamine (0.3–0.4mg) intramuscularly one hour before induction. The induction of anesthesia was performed by intravenous administration of 100µg/kg of fentanyl in 15min or over. The pneumatic tourniquet applied on the left upper arm was inflated to 220–240mmHg after 10µg/kg of fentanyl was given and then pancuronium was administered. Verbal commands were given to the patient after 25, 50, 75 and 100µg/kg of fentanyl was administered. Eight patients out of 10 responded to the verbal commands after administration of 25µg/kg of fentanyl. Six patients also responded after administration of 100µg/kg of fentanyl and diazepam 5mg was given to prevent tachycardia and rigidity during endotracheal intubation. Muscle rigidity and tachycardia were noticed in three and four patients respectively. These complications disappeared by diazepam administration.It was noted that wakefulness frequently occurred during the induction by high-dose fentanyl and oxygen anesthesia. To prevent such wakefulness therefore, it is necessary to use anesthetic supplements which do not cause cardiovascular depression.(Watanabe A, Namiki A, Ujike Y et al.: Wakefulness during the induction with high-dose fentanyl and oxygen anesthesia. J Anesth 2: 165–169, 1988)     

Efficacy of prophylactic intravenous granisetron in postoperative emesis in adults

Purpose This randomized, double-blind, placebo-controlled trial evaluated the efficacy, safety, and optimal dose of granisetron in the prophylactic control of postoperative nausea and vomiting in patients undergoing gynecologic surgery or cholecystectomy.Methods Three-hundred and fifteen patients (age, 20–65 years) received intravenous granisetron (1mg or 3mg) or placebo immediately before the end of anesthesia. After treatment, patients were observed for 24h, and the occurrence of nausea and vomiting was recorded and safety was assessed. The no-vomiting rate, time-to-first vomiting episode, and severity of nausea were recorded.Results The no-vomiting rates in patients receiving granisetron 1mg and 3mg were significantly higher than that in the placebo group (83.7%, 78.8%, and 57.9%, respectively; P = 0.0004 for 1mg vs placebo, P = 0.001 for 3mg). Time-to-first vomiting episode was longer in the granisetron 1-mg and 3-mg groups than in the placebo group (time-to-event analysis, Kaplan-Meier, log-rank test; 83.2%, 80.1%, and 59.1%, respectively; P = 0.0002 and P = 0.0010). The severity of nausea was also less in granisetron-treated patients (25.2%, 11.5%, and 15.4% severe nausea incidence for placebo, granisetron 1mg, and granisetron 3mg, respectively; P = 0.00003 and P = 0.002). Fewer rescue medications were required in the two granisetron-treated groups compared with those receiving placebo. Adverse events were similar in all groups. No differences in efficacy or safety were observed between granisetron doses.Conclusion Granisetron is well-tolerated and more effective than placebo in the prophylactic control of nausea and vomiting after surgery. This study suggests that the optimum dose of granisetron is 1mg.*See Appendix.     

EnHurane supresses phrenic nerve-diaphragm Transmissionin vivo

We examined the effects of enflurane on the diaphragmatic function in 15 pentobarbital-anesthetized, mechanically ventilated dogs. They were divided into three groups of five animals each, according to the administered concentration of enflurane. The diaphragmatic function was assessed from transdiaphragmatic pressure (Pdi) and integrated diaphragmatic electromyography (Edi) developed at functional residual capacity against an occluded airway during bilateral supramaximal phrenic nerve stimulation at 0.5, 10, 20, 50 and 100Hz under quasiisometric condition. After a control measurement, enflurane was administered at a constant end-expired concentration (0, 0.5 and 1MAC) and the measurement was repeated after 1 hour of exposure. The Pdi amplitude generated by single twitch (0.5Hz) and during 10, 20 and 50Hz stimulation was unchanged between the groups. No change in Pdi during 100Hz stimulation was noted during 0 and 0.5MAC exposure, while it was reduced by 1MAC of enflurane. When the values of Pdi were expressed as % of maximum Pdi (%Pdi,max) that developed during control measurement and analyzed in terms of %Pdi,max—stimulus frequency relationship, a significant decrease in %Pdi,max was noted for 100Hz stimulation in 0.5 and 1MAC groups compared to the control. Similarly, Edi during 100Hz stimulation obtained in 0.5 and 1MAC groups was markedly depressed compared to the control. Edi during 50Hz stimulation was also decreased at 1MAC. Relative changes in Edi following enflurane administration were greater than the corresponding changes of Pdi. These results demonstrate that enflurane impairs diaphragmatic function through its inhibitory effects on neuromuscular transmission.(Kochi T, Ide T, Isono S, et al.: Enflurane supresses phrenic nerve-diaphragm transmission in vivo. J Anesth 5: 260–267, 1991)     

Effects of calcium and temperature on tension in isolated canine coronary artery

The effects of calcium and temperature on the tension of isolated canine coronary arterial strips were studied.In 20mEq·l ^–1 K solution, the tension was significantly increased from 0mg with 0mEq·l ^–1 Ca to 33 ± 18mg with 0.2mEq·l ^–1 Ca at 37°C, from –40 ± 18mg with 0mEq·l ^–1 Ca to –17 ± 11mg with 0.2mEq·l ^–1 Ca at 30°C, from –77 ± 19mg with 0mEq·l ^–1 Ca to –52 ± 17mEq·l ^–1 with 1mEq·l ^–1 Ca at 25°C, from –88 ± 13mg with 0mEq·l ^–1 Ca to –41 ± 18mg with 2mEq·l ^–1 Ca at 20°C, from –125 ± 16mg with 0mEq·l ^–1 Ca to –116 ± 13mg with 2mEq·l ^–1 Ca at 15°C. Ca higher than 0.2mEq·l ^–1 produced a dose-dependent increase in tension between 37°C and 15°C. In spite of the presence of 4mEq·l ^–1 Ca, the development of tension was strongly supressed by lowering the temperature below 20°C, and completely inhibited at 10°C. The rate of a decrease in tension caused by cooling was about 5.5mg·°C^–1.This study demonstrated that Ca²⁺ produced a dose-dependent increase in tension in high-K solution, which was suppressed as the temperature was lowered.(Yoshida K, Fujii Y, Ina H, et al.: Effects of calcium and temperature on tension in isolated canine coronary artery. J Anesth 5: 172–176, 1991)     

Combined effects of Inversed Ratio Ventilation (IRV) with positive end-expiratory pressure ventilation (PEEP) on cardiorespiratory function in acute respiratory failure

Combined effects of inversed ratio ventilation (IRV) with positive end-expiratory pressure (PEEP) on cardiorespiratory function were examined in 24 patients with acute respiratory failure. Patients were divided into two groups: the IRV group (n = 12) who showed no significant increase in Pa_{O 2} with a 6cmH₂O of PEEP and PEEP group (n = 12) who were ventilated mechanically with PEEP only at maximum level of 10cmH₂O. In IRV group step-wise prolongation of the I:E ratio from 1:1.9 to 2.6:1 or 4:1 was applied as a Pa_{O 2} was improved and in PEEP group also level of PEEP was increased from 0, 5 to 10cmH₂O after one hour period irrespective of Pa_{O 2}. Inversed ratio ventilation and PEEP increased significantly Pa_{O 2}/Fi _{O 2}, the increase being observed 6hrs (I:E = 2:1) and 2hrs (10cmH₂O) after starting IRV or PEEP. Further improvement of oxygenation was not observed in IRV even if I:E ratio was prolonged up to 2.6:1 or 4:1. These results suggested that combinations of IRV with PEEP were effective and an I:E ratio of 2:1 may be optimal, and IRV is advantageous compared to PEEP, but will take more long time to improve oxygenation than PEEP.(Sari A, Toriumi T, Yamashita S, et al.: Combined effects of inversed ratio ventilation (IRV) with positive end-expiratory pressure ventilation (PEEP) on cardiorespiratory function in acute respiratory failure. J Anesth 5: 105–113, 1991)     

Enzyme inhibition by analgesic and hypnotic agents on anaerobic dehalogenation of halothane

Enzyme inhibition on anaerobic dehalogenation of halothane by various analgesic or hypnotic agents was investigated in vitro using rat liver microsomal fraction. The production rate of chloro-difluoro-ethylene (CDE) and chloro-trifluoro-ethane (CTE), anaerobic metabolites of halothane, was measured when various concentrations of analgesic or hypnotic agents (fentanyl, morphine, pentazocine, buprenorphine, ketamine, diazepam, chlorpromazine and hydroxyzine) were supplemented. Inhibitor constant (Ki) of each agent was calculated and compared with each other. The activity of NADPH-cytochrome c reductase (fp₂) and NADH-ferricyanide reductase (fp₁) was measured when each agent was added. The values of inhibitor constants (Ki) for CDE and CTE formation were in the following order from large to small values; morphine (656µM and 2570µM), chlorpromazine (49.7µM and 68.1µM), ketamine (24.9µM and 64.4µM), fentanyl (23.9µM and 34.6µM), hydroxyzine (19.2µM and 50.8µM), diazepam (17.0µM and 13.9µM), buprenorphine (11.2µM and 22.4µM), and pentazocine (1.96µM and 6.67µM) respectively. Pentazocine inhibited the formation of CDE 300 fold greater than morphine. The activity of fp₂ and fp₁ did not change by the addition of these analgesic or hypnotic agents. These results indicate that various analgesic or hypnotic agents, which are commonly used with halothane in clinical anesthesia, suppress the anaerobic dehalogenation of halothane in vitro. They also imply that the suppression of production of halothane metabolites is the result of direct enzyme inhibition on cytochrome P-450, since these agents did not affect the activity of fp₂ and fp₁ which are flavoproteins existing in the microsomal electron transport system.(Yamanoue T, Kikuchi H, Fujii K, et al.: Enzyme Inhibition by Analgesic and Hypnotic Agents on Anaerobic Dehalogenation of Halothane. J Anesth 5: 331–337, 1991)     

Erythemas caused by electrodes while monitoring neuromuscular blockade: three cases

Skin erythemas formed in three patients during surgery at the sites where negative electrodes had been attached to stimulate the ulnar nerve for a neuromuscular transmission monitor (Relaxograph). The patients were all women, aged 52, 62, and 74 years, and general anesthesia lasted 8h 20min, 4h 50min, and 8h 45min, respectively. The electrodes used were disposable ECG electrodes in the first two patients and one designed for a neuromuscular monitor in the third; all were carbon-coated and then covered with gel. However, when the electrodes were detached from the lesion, they all showed loss or damage of the carbon coating under the gel. We recommend balancing the merit of monitoring with the risk of complications, even when applying an apparently safe, noninvasive monitor.     

Infusion of radiocontrast agents induces exaggerated release of urinary endothelin in patients with impaired renal function

Background The aim of the study was to examine the role of endothelin in radiocontrast-induced nephropathy (RCN) in patients with chronic renal failure.Methods We measured plasma endothelin-1 (ET) and the urinary excretion of endothelin-like immunoreactivity before and after infusion of radio contrast medium (CM) in patients with normal renal function (group N; n = 6; mean serum creatinine concentration, 0.8 ± 0.1 (SEM) mg/dl), and in another group, with renal dysfunction (group R; n = 6; 2.7 ± 0.5mg/dl). Half-normal saline (0.45% NaCl solution) was continuously infused in all patients for 25h, at a rate of 100ml/h; starting from 5h before the infusion of CM.Results Plasma ET in group R (5.2 ± 1.4pg/ml) was significantly higher than in group N (0.9 ± 0.3; P 0.01). Urinary endothelin excretion corrected by creatinine concentration (uET/Cr) in group R (7.9 ± 2.4mg/g Cr) was significantly higher than in group N (1.5 ± 0.4mg/g Cr; P 0.05). Urinary excretion levels of N-acetyl--d-glucosaminidase (NAG) and 2-microglobulin (2M) were also significantly higher in group R (0.8 ± 0.2mU/g Cr and 670 ± 400mg/g Cr, respectively) than in group N (0.3 ± 0.1 and 7.5 ± 2.2, respectively). After CM infusion, uET/Cr in group R significantly increased, to 10.7 ± 2.6mg/g Cr on the next day and returned to baseline level on the third day. NAG and 2M showed a similar pattern, but a significant change in NAG was observed on the second day in group R. In group N, uET/Cr, NAG, and 2M did not change after CM infusion. Plasma ET remained unchanged throughout the observation period of 4 days in both groups. No patient developed pulmonary edema or a significant rise in serum creatinine (more than 0.5mg/dl), caused by infusion of the amount of half-normal saline used.Conclusions In the present study, uET/Cr increased after the administration of CM only in the patients with renal impairment. This difference in endothelin reaction may be a causal one, in that patients with renal insufficiency readily develop RCN. The infusion of half-normal saline starting before CM infusion causes no side effects and is safe for the prevention of CM-induced acute renal failure.     

Bench test assessment of the new Raumedic Neurovent-P ICP sensor: a technical report by the BrainIT group

Summary. Background. In clinical practice, fiberberoptic and piezo-electric ICP probes are often used for measuring intracranial pressure (ICP). A number of similar technologies, although performing well in bench test studies, have been shown to exhibit unacceptable zero drift, fragility or both during trials conducted under clinical conditions. Recently, a new technology has become available, the Neurovent-P (Raumedic AG+CO, Raumedic, Germany). As a pre-requisite for a clinical trial, we have conducted and report on bench test studies to confirm the manufacturers long term zero-drift performance for this technology.Method. In a test rig static tests (recording of 20mmHg pressure) and dynamic tests, ranging from 5 to 50mmHg have been performed.Findings. 10 ICP probes have been tested for a total of 60 days. All the catheters, after the connection with the ICU monitor displayed a static pressure of 0±1mmHg and did not required pre-insertion alteration. At five days, mean zero drift was 0.6±0.9mmHg. Overall, zero drift ranged from 0 to 2mmHg. At a fixed static pressure of 20mmHg, the mean recorded value was 20.6±0.8mmHg, ranging from 19 to 23mmHg. A regression analysis of the relationship between the applied pressure and the recorded pressure during the dynamic tests of the 10 catheters yielded a correlation coefficient R² of 0.997. Applying the Altman and Bland method to assess the bias and confidence limits for the Raumedic catheter responses during the dynamic tests against the applied gold-standard hydrostatic column pressures, the average bias of –0.66±0.85mmHg, with 95% CLs of –2mmHg and 1mmHg.Conclusions. Mean zero drift, after five days, was very small and long-term continuous recording of a stable pressure was very precise. The response at dynamic tests, i.e. the changes of pressure in a wide range, was excellent. The average bias of the Raumedic catheter compared with the hydrostatic column is very small. After this bench test, the next and most critical step will be to conduct a trial of this promising technology under more demanding clinical environment.     

The relaxing effects of barbiturates in vascular smooth muscle of rat aorta

The effects of thiamylal and pentobarbital on contractions mediated through the influx of extracellular Ca⁺⁺ and the release of intracellularly stored Ca⁺⁺ were compared in rat aortic strips. Thiamylal (3 × 10^–5M to 10^–3M) and pentobarbital (10^–4 to 10^–3M) significantly attenuated the contraction induced by KCl (20mM), and shifted the dose-response curve for Ca⁺⁺ of KCl (20mM)-treated strips downwards and to the right. Caffeine (10^–2M)-induced contraction was significantly attenuated by thiamylal at concentrations greater than 10^–4M and by pentobarbital at 3 × 10^–4M. Only a high concentration (10^–3M) of these barbiturates significantly inhibited the contractions induced by norepinephrine (NE, 10^–6M) in Ca⁺⁺-free medium. Contraction of strips without endothelium by a Ca⁺⁺ ionophore, A23187 (5 × 10^–6M), in the presence of a Ca channel blocker, was relaxed by high concentrations of thiamylal (3 × 10^–4M to 10^–3M) and pentobarbital (10^–3M). It is concluded that thiamylal inhibits contraction through an intracellular action as well as a Ca channel-blocking action in vascular smooth muscle of rat aorta. However, the intracellular action of pentobarbital is less potent than that of thiamylal.(Nishiwada M, Nakamura K, Hatano Y, et al.: The relaxing effects of barbiturates in vascular smooth muscle of rat aorta. J Anesth 5: 380–387, 1991)     

Sustained effects of plasma norepinephrine levels on femoral-radial pressure gradient after cardiopulmonary bypass

In order to determine the influence of the sympathetic nervous system upon the femoral-radial artery pressure gradient after cardiopulmonary bypass (CPB), we examined plasma norepinephrine levels in 34 adult male patients undergoing coronary artery bypass grafting. Cardiovascular parameters, including systolic arterial pressure, mean arterial pressure, cardiac index (CI), systemic vascular resistance index (SVRI), pulmonary artery pressure (PAP), hemoglobin (Hb) and peak dP/dt of radial and femoral artery pressures were measured after sternotomy, and immediately after the discontinuation of CPB and 90min after CPB. Plasma norepinephrine levels were measured after sternotomy, after aortic declamping and 90min after CPB.The patients were divided into two groups. Group A consisted of 17 patients whose femoral minus radial systolic pressure difference was 15mmHg or more at 90min after CPB, while Group B consisted of 17 patients with the difference less than 15mmHg. Group A patients had significantly longer time values in the duration of both CPB (Group A 175 ± 10min; Group B 115 ± 12min, P 0.001) and aortic cross clamping (Group A 116 ± 7min, Group B 71 ± 9min, P 0.001).Although there was no significant difference in Hb or PAP of 90min after CPB in Groups A and B, the following values, listed in the order of A to B, were obtained; CI, 2.79 ± 0.10 versus 3.46 ± 0.16l·min^–1·m^–2 (P 0.01); mean radial artery pressure (MRP), 58.7 ± 2.4 versus 65.1 ± 1.8mmHg (P 0.05); peak dP/dt of radial artery pressure, 568 ± 64 versus 1026 ± 61mmHg·sec^–1 (P 0.001); and plasma norepinephrine concentration, 1.81 ± 0.25 versus 0.98 ± 0.10ng·ml^–1 (P 0.01), which were statistically significant.The higher femoral-radial artery pressure gradient after CPB was observed in patients with both a longer CPB time and a higher plasma norepinephrine concentration. These results suggest that a marked constriction of peripheral arteries might have produced a damped transmission of the pressure pulse to the radial artery.(Nakayama R, Goto T, Kukita I, et al.: Sustained effects of plasma norepinephrine levels on femoral-radial pressure gradient after cardiopulmonary bypass. J Anesth 7: 8–15, 1993)