Absorption of carbon dioxide by dry soda lime decreases carbon monoxide formation from isoflurane degradation

This study was performed to determine whether the absorption of carbon dioxide (CO(2)) influences the formation of carbon monoxide (CO) from degradation of isoflurane in dry soda lime. Isoflurane (0. 5%), CO(2) (5%), a combination of the two in oxygen, and pure oxygen were separately passed through samples of 600 g of completely dried soda lime (duration of exposure, 60 min; flow rate, 5 L/min). Downstream of the soda lime, we measured concentrations of CO, isoflurane, and CO(2) as well as the gas temperature. CO(2) increased the peaks of CO concentration (842 +/- 81 vs 738 +/- 28 ppm) and shortened the rise time of CO to maximum values (12 +/- 2 vs 19 +/- 4 min). However, CO(2) inhibited total CO formation (99 +/- 10 vs 145 +/- 6 mL). At the same time, CO(2) absorption by the soda lime decreased in the presence of CO formation (from 21.4 +/- 0. 8 to 19.4 +/- 0.9 g). The temperature of the gases increased during the passage of both isoflurane and CO(2) (to 32.6 +/- 2.0 degrees C and 39.4 +/- 4.0 degrees C, respectively), but the largest increase (to 41.5 +/- 2.1 degrees C) was recorded when isoflurane and CO(2) simultaneously passed through the dry soda lime. We assume that the simultaneous reduction in CO formation and CO(2) absorption is caused by the competition for the alkali hydroxides present in most of soda lime brands. Implications: We determined, in vitro, that carbon monoxide (CO) formation from isoflurane by dry soda lime is reduced by carbon dioxide (CO(2)). We believe that the potential for injury from CO is less in the clinical milieu than suggested by data from experiments without CO(2) because of an interdependence between CO formation and CO(2) absorption.     

Amsorb: a new carbon dioxide absorbent for use in anesthetic breathing systems.

BACKGROUND: This article describes a carbon dioxide absorbent for use in anesthesia. The absorbent consists of calcium hydroxide with a compatible humectant, namely, calcium chloride. The absorbent mixture does not contain sodium or potassium hydroxide but includes two setting agents (calcium sulphate and polyvinylpyrrolidine) to improve hardness and porosity. METHODS: The resultant mixture was formulated and subjected to standardized tests for hardness, porosity, and carbon dioxide absorption. Additionally, the new absorbent was exposed in vitro to sevoflurane, desflurane, isoflurane, and enflurane to determine whether these anesthetics were degraded to either compound A or carbon monoxide. The performance data and inertness of the absorbent were compared with two currently available brands of soda lime: Intersorb (Intersurgical Ltd., Berkshire, United Kingdom) and Dragersorb (Drager, Lubeck, Germany). RESULTS: The new carbon dioxide absorbent conformed to United States Pharmacopeia specifications in terms of carbon dioxide absorption, granule hardness, and porosity. When the new material was exposed to sevoflurane (2%) in oxygen at a flow rate of 1 l/min, concentrations of compound A did not increase above those found in the parent drug (1.3-3.3 ppm). In the same experiment, mean +/-SD concentrations of compound A (32.5 +/- 4.5 ppm) were observed when both traditional brands of soda lime were used. After dehydration of the traditional soda limes, immediate exposure to desflurane (60%), enflurane (2%), and isoflurane (2%) produced concentrations of carbon monoxide of 600.0 +/- 10.0 ppm, 580.0 +/- 9.8 ppm, and 620.0 +/-10.1 ppm, respectively. In contrast, concentrations of carbon monoxide were negligible (1-3 ppm) when the anhydrous new absorbent was exposed to the same anesthetics. CONCLUSIONS: The new material is an effective carbon dioxide absorbent and is chemically unreactive with sevoflurane, enflurane, isoflurane, and desflurane.     

Differential protective effects of volatile anesthetics against renal ischemia-reperfusion injury in vivo

BACKGROUND: Volatile anesthetics protect against cardiac ischemia-reperfusion injury via adenosine triphosphate-dependent potassium channel activation. The authors questioned whether volatile anesthetics can also protect against renal ischemia-reperfusion injury and, if so, whether cellular adenosine triphosphate-dependent potassium channels, antiinflammatory effects of volatile anesthetics, or both are involved. METHODS: Rats were anesthetized with equipotent doses of volatile anesthetics (desflurane, halothane, isoflurane, or sevoflurane) or injectable anesthetics (pentobarbital or ketamine) and subjected to 45 min of renal ischemia and 3 h of reperfusion during anesthesia. RESULTS: Rats treated with volatile anesthetics had lower plasma creatinine and reduced renal necrosis 24-72 h after injury compared with rats anesthetized with pentobarbital or ketamine. Twenty-four hours after injury, sevoflurane-, isoflurane-, or halothane-treated rats had creatinine (+/- SD) of 2.3 +/- 0.7 mg/dl (n = 12), 1.8 +/- 0.5 mg/dl (n = 6), and 2.4 +/- 1.2 mg/dl (n = 6), respectively, compared with rats treated with pentobarbital (5.8 +/- 1.2 mg/dl, n = 9) or ketamine (4.6 +/- 1.2 mg/dl, n = 8). Among the volatile anesthetics, desflurane demonstrated the least reduction in plasma creatinine after 24 h (4.1 +/- 0.8 mg/dl, n = 12). Renal cortices from volatile anesthetic-treated rats demonstrated reduced expression of intercellular adhesion molecule 1 protein and messenger RNA as well as messenger RNAs encoding proinflammatory cytokines and chemokines. Volatile anesthetic treatment reduced renal cortex myeloperoxidase activity and reduced nuclear translocation of proinflammatory nuclear factor kappaB. Adenosine triphosphate-dependent potassium channels are not involved in sevoflurane-mediated renal protection because glibenclamide did not block renal protection (creatinine: 2.4 +/- 0.4 mg/dl, n = 3). CONCLUSION: Some volatile anesthetics confer profound protection against renal ischemia-reperfusion injury compared with pentobarbital or ketamine anesthesia by attenuating inflammation. These findings may have significant clinical implications for anesthesiologists regarding the choice of volatile anesthetic agents in patients subjected to perioperative renal ischemia.     

Ex vivo carbon monoxide prevents cytochrome P450 degradation and ischemia/reperfusion injury of kidney grafts

Renal ischemia/reperfusion injury is a major complication of kidney transplantation. We tested if ex vivo delivery of carbon monoxide (CO) to the kidney would ameliorate the renal injury of cold storage that can complicate renal transplantation. Orthotopic syngeneic kidney transplantation was performed in Lewis rats following 24 h of cold preservation in University of Wisconsin solution equilibrated without or with CO (soluble CO levels about 40 microM). Ischemia/reperfusion injury in control grafts resulted in an early upregulation of inflammatory mediator mRNAs and progressive deterioration of graft function. In contrast, the grafts preserved with CO had significantly less oxidative injury and this was associated with improved recipient survival compared to the control group. Renal injury in the control group showed considerable degradation of cytochrome P450 heme proteins, active heme metabolism and increased detrimental intracellular free heme levels. Kidney grafts preserved in CO-equilibrated solution maintained their cytochrome P450 protein levels, had normal intracellular heme levels and had less lipid peroxidation. Our results show that CO-mediated suppression of injurious heme-derived redox reactions offers protection of kidney grafts from cold ischemia/reperfusion injury.     

Influence of volatile anesthetics on myocardial contractility in vivo: desflurane versus isoflurane

The direct effects of desflurane on myocardial contractility in vivo have not been characterized. Therefore, the purpose of this investigation was to systematically examine the effects of desflurane on myocardial contractile function and compare these actions to equianesthetic concentrations of isoflurane in chronically instrumented dogs. Contractility was evaluated using an established index of inotropic state, the preload recruitable stroke work (PRSW) versus end-diastolic segment length (EDL) relationship. Since autonomic nervous system tone may influence the hemodynamic effects of the volatile anesthetics in vivo, experiments were performed in the presence of pharmacologic blockade of the autonomic nervous system. Two groups of experiments were performed with seven dogs instrumented for measurement of aortic and left ventricular pressure, the maximum rate of increase of left ventricular pressure (dP/dt), subendocardial segment length, coronary blood flow velocity, and cardiac output. After autonomic nervous system blockade, ventricular pressure-segment length loops were generated using preload reduction via partial inferior vena caval occlusion. The PRSW versus EDL relation was calculated from the pressure-length loops. Dogs were then anesthetized with 1.0 or 1.5 MAC desflurane or isoflurane in a random fashion, and measurements were repeated after 30 min of equilibration at each anesthetic concentration. The PRSW versus EDL slope reflected similar changes in contractile state when desflurane or isoflurane was administered (53 +/- 4 during control to 26 +/- 4 erg.cm-2 x 10(-3).mm-1 at 1.5 MAC desflurane, and 57 +/- 5 during control to 31 +/- 3 erg.cm-2 x 10(-2).mm-1 at 1.5 MAC isoflurane). In conclusion, desflurane and isoflurane produced equivalent direct decreases in myocardial contractility.     

Comparison of the effects of volatile anesthetics on brain glucose metabolism in rats

The objective of this investigation was to compare the effects of the commonly used volatile anesthetics on concentrations of plasma and cerebral glucose and cerebral intermediary metabolites. Fasted male Long-Evans rats were anesthetized with a volatile anesthetic and, after tracheostomy and paralysis, were mechanically ventilated. Each of three groups received one MAC concentration of anesthesia with halothane, enflurane, or isoflurane. At the end of 60-75 min of anesthesia, blood was sampled for arterial blood gas and plasma glucose analysis, and the brain was rapidly sampled and frozen for analysis of energy metabolites. Physiologic variables were maintained as follows: PaCO2 30-40 mmHg, pHa 7.20-7.40, PaO2 greater than 60 mmHg, MAP greater than 60 mmHg, and rectal temperature 37.5-38.5 degrees C. Mean plasma glucose concentrations in the three groups were as follows (muMol/ml +/- SEM): halothane, 7.45 /- .62; enflurane, 6.95 +/- .22; isoflurane, 10.11 +/- 1.00. Mean brain glucose concentrations in the three groups were (muMol/gm wet weight): halothane, 2.04 +/- .20; enflurane, 2.07 +/- .26; isoflurane, 3.04 +/- .31. Plasma and brain glucose levels were significantly increased in the isoflurane group compared to the other two groups (P less than .05) with no differences occurring in the brain/plasma glucose ratio among the three groups. No differences were present between groups in brain lactate, pyruvate, fructose diphosphate, malate, alpha-ketoglutarate, phosphocreatine, or adenine nucleotides. Thus, at one MAC concentration, major differences between volatile anesthetics on brain energy availability are not present, although isoflurane raised cerebral glucose levels.     

Decrease in dose requirement of d-tubocurarine by volatile anesthetics.

Volatile anesthetics are known to decrease the requirements for neuromuscular blocking agents. To obtain a quantitative measure of the extent of this drug interaction, studies were performed on isolated guinea pig nerve--lumbrical muscle preparations exposed to methoxyflurane, halothane, isoflurane, diethyl ether, fluroxene, and enflurane in concentrations equal to MAC. From the relationship between indirect twitch height and d-tubocurarine concentration, the concentration depressing the twitch height by 50 per cent was determined. In the presence of MAC levels of anesthetic, the ED50 was decreased by the following fractional amounts: methoxyflurane, 0.311; halothane, 0.334; isoflurane, 0.335; diethyl ether, 0.462; fluroxene, 0.580; enflurane, 0.697. Comparison of the fractional decrease of d-tubocurarine dose requirement by an anesthetic at MAC and previously obtained values for the fractional depression of end-plate depolarization by an anesthetic at MAC showed that the more the anesthetic depresses depolarization, the smaller the d-tubocurarine dose requirement. Thus, clinically observed decreases in dose requirements may be explained by the effects of the anesthetics on chemosensitivity of the end-plate region.     

Age and solubility of volatile anesthetics in blood

The more rapid rate of rise of alveolar anesthetic partial pressure in children compared with adults may be explained in part by an increasing solubility of volatile anesthetics in blood with age. To investigate this possibility, the authors measured the blood-gas partition coefficients of isoflurane, enflurane, halothane, and methoxyflurane in four groups of fasting subjects: 10 full-term newborns (at delivery), 11 children (3-7 years old), 11 adults (20-40 years old), and 10 elderly adults (75-85 years old). The blood-gas partition coefficients were greatest in adults: isoflurane 1.46, enflurane 2.07, halothane 2.65, and methoxyflurane 16.0; and least in newborns: 1.19, 1.78, 2.14, 13.3, respectively. The blood-gas partition coefficients in children (1.28, 1.78, 2.39, 15.0, respectively), which were intermediate between those in newborns (P less than 0.005) and those in adults (P less than 0.005), were not significantly different from those in elderly adults (1.29, 1.79, 2.41, 15.0, respectively). The blood-gas partition coefficients of both isoflurane and enflurane correlated directly with the serum albumin and triglyceride concentrations; that of halothane correlated directly with the serum cholesterol, albumin, triglyceride, and globulin concentrations; and that of methoxyflurane correlated directly with the serum cholesterol, albumin, and globulin concentrations. The authors conclude that age significantly affects blood-gas partition coefficients, and the lower blood-gas partition coefficients in children explain in part the more rapid rise of alveolar anesthetic partial pressure in this age group.     

Electrophysiologic effects of volatile anesthetics,sevoflurane and halothane,in a canine myocardial infarction model

The effects of sevoflurane and halothane on the effective refractory period (ERP) and ventricular activation were examined in a canine myocardial infarction model. Sevoflurane (1 MAC) reduced the heart rate and prolonged ERP in both normal and infarcted zones. A prolongation of ERP with sevoflurane was observed also during atrial pacing at a fixed rate, but the effect was less than during sinus rhythm. Sevoflurane either further delayed or blocked the delayed activation entirely in the infarcted zones with only slight effects on the activation of the normal zones. Halothane (1 MAC) prolonged ERP during sinus rhythm and atrial pacing, but to a lesser extent during the latter. Halothane also depressed ventricular activation in the infarcted zone during atrial pacing. In conclusion, sevoflurane as well as halothane selectively depresed the delayed activation and the prolongation of ERP in myocardial infarction, which may inhibit ventricular arrhythmias in myocardial infarction.     

Absorbents differ enormously in their capacity to produce compound A and carbon monoxide

Concern persists regarding the production of carbon monoxide (CO) and Compound A from the action of carbon dioxide (CO(2)) absorbents on desflurane and sevoflurane, respectively. We tested the capacity of eight different absorbents with various base compositions to produce CO and Compound A. We delivered desflurane through desiccated absorbents, and sevoflurane through desiccated and moist absorbents, then measured the resulting concentrations of CO from the former and Compound A from the latter. We also tested the CO(2) absorbing capacity of each absorbent by using a model anesthetic system. We found that the presence of potassium hydroxide (KOH) and sodium hydroxide (NaOH) increased the production of CO from calcium hydroxide (Ca[OH](2)) but did not consistently affect production of Compound A. However, the effect of KOH versus NaOH was not consistent in its impact on CO production. Furthermore, the effect of KOH versus NaOH versus Ca(OH)(2) was inconsistent in its impact on Compound A production. Two absorbents (Amsorb) [Armstrong Medica, Ltd, Coleraine, Northern Ireland], composed of Ca(OH)(2) plus 0.7% polyvinylpyrrolidine, calcium chloride, and calcium sulfate; and lithium hydroxide) produced dramatically lower concentrations of both CO and Compound A. Both produced minimal to no CO and only small concentrations of Compound A. The presence of polyvinylpyrrolidine, calcium chloride, and calcium sulfate in Amsorb appears to have suppressed the production of toxic products. All absorbents had an adequate CO(2) absorbing capacity greatest with lithium hydroxide. Implications: Production of the toxic substances, carbon monoxide and Compound A, from anesthetic degradation by carbon dioxide absorbents, might be minimized by the use of one of two specific absorbents, Amsorb (Armstrong Medica, Ltd., Coleraine, Northern Ireland) (calcium hydroxide which also includes 0.7% polyvinylpyrrolidine, calcium chloride, and calcium sulfate) or lithium hydroxide.     

体内镁合金的降解和成骨反应的动物实验探索

[目的]研究动物股骨干内植入镁合金后,在镁合金降解过程中,金属-骨界面的骨质反应机制. [方法]在SD大鼠的股骨干中横向植入镁合金金属棒,术后抗炎,自由活动,9周后处死取材,分别在金相显微镜下观察金属-骨界面的宏观改变,扫描电镜(SEM)下观察金属-骨界面的微观改变,应用能谱分析(EDS)技术确定元素组成;并且将骨棒做脱钙切片染色,光镜下观察金属-骨界面的组织学变化. [结果]随着股骨内镁合金的降解,周围骨表面和镁合金降解表面同时发生骨质反应,在金属-骨界面形成紧密相邻的金属层、降解层、新生骨层3个层次,新生骨质表面未见炎性细胞浸润,可见少量间断性纤维结缔组织. [结论]金属-骨界面的骨质反应完全符合正常骨质愈合过程,新生骨质与正常骨质的形态结构完全一致;因此可以推断镁合金具有良好的降解性、成骨性及组织相容性,其降解过程与新骨成骨过程具有良好的同步性.     

麻醉药在低流量紧闭麻醉环路内分布的实验研究

对低流量紧闭麻醉环路内注药的分布，以及环路外挥发器释出药物及其环路内稀释进行实验研究。结果显示，吸入段注入 １ｍｌ三种含氟麻醉药液体产生较高的吸入浓度峰值，均在 １％或更多，呼出段注药２ｍｌ则不然，最高不过１．７％，但可控性差。注药１ｍｌ后３０分，环路内橡皮和塑料对麻醉药的吸收以安氟醚最大（３０％），而新鲜钠石灰对麻醉药的摄取则是七氟醚最多（６２％）。环路外挥发器在５００ｍｌ／ｍｉｎ的低流量下，开至刻度“５”，经稀释后的吸入浓度上升缓慢，５分时安氟醚的吸入浓度仍不足１％，难以适应麻醉诱导的需要。     

The elimination of sodium and potassium hydroxides from desiccated soda lime diminishes degradation of desflurane to carbon monoxide and sevoflurane to compound A but does not compromise carbon dioxide absorption.

Normal (hydrated) soda lime absorbent (approximately 95% calcium hydroxide [Ca(OH)2], the remaining 5% consisting of a mixture of sodium hydroxide [NaOH] and potassium hydroxide [KOH]) degrades sevoflurane to the nephrotoxin Compound A, and desiccated soda lime degrades desflurane, enflurane, and isoflurane to carbon monoxide (CO). We examined whether the bases in soda lime differed in their capacities to contribute to the production of these toxic substances by degradation of the inhaled anesthetics. Our results indicate that NaOH and KOH are the primary determinants of degradation of desflurane to CO and modestly augment production of Compound A from sevoflurane. Elimination of these bases decreases CO production 10-fold and decreases average inspired Compound A by up to 41%. These salutary effects can be achieved with only slight decreases in the capacity of the remaining Ca(OH)2 to absorb carbon dioxide. IMPLICATIONS: The soda lime bases used to absorb carbon dioxide from anesthetic circuits can degrade inhaled anesthetics to compounds such as carbon monoxide and the nephrotoxin, Compound A. Elimination of the bases sodium hydroxide and potassium hydroxide decreases production of these noxious compounds without materially decreasing the capacity of the remaining base, Ca(OH)2, to absorb carbon dioxide.     

Hematocrit and the solubility of volatile anesthetics in blood

To clarify the effect of hematocrit on the solubility of volatile anesthetics in blood, we measured the blood-gas partition coefficients of isoflurane, enflurane, halothane, and methoxyflurane concurrently at 37 degrees C in blood from four adults. We measured the blood-gas partition coefficients in the plasma (hematocrit 0%) and packed red cell fractions (hematocrit 80%), and in four mixtures of these two fractions (hematocrits 10%, 25%, 40%, and 55%). The mixtures were prepared by recombining appropriate amounts of plasma and packed red cells from each adult. As hematocrit increased, the blood-gas partition coefficient of isoflurane decreased linearly (P less than 0.01), whereas that of enflurane increased linearly (P less than 0.05). The partition coefficient for isoflurane in plasma was 20% greater than that in packed red cells, whereas the partition coefficient for enflurane in plasma was 10% less than that in packed cells. The blood-gas partition coefficients of halothane and methoxyflurane did not change significantly between measurements in plasma and packed red cells. We conclude that hematocrit exerts a statistically significant effect on the blood-gas partition coefficient of isoflurane and enflurane.     

Effects of volatile anesthetics on directly and indirectly stimulated skeletal muscle.

Isolated guinea pig nerve-lumbrical muscle preparations were exposed to halothane, methoxyflurane, isoflurane, enflurane, fluroxene, and diethyl ether. The temporal courses of the effects on indirectly and directly elicited twitch responses were determined over a range of concentrations for each agent. When the anesthetics were compared at concentrations equivalent in terms of minimum alveolar concentration (MAC), a spectrum was observed in which halothane, methoxyflurane and isoflurane depressed the indirect twitch response at 3.5--5 MAC and the direct twitch response at 8--10 MAC. Diethyl ether and fluroxene depressed the indirect twitch response at 2--3.5 MAC and the direct twitch response at 3--6 MAC. Enflurane depressed the indirect response at 1.5--2.5 MAC and the direct response at 6--8 MAC. When the anesthetics were compared at concentrations equivalent in terms of their abilities to depress end-plate depolarization, however, all anesthetics were equipotent. Depression of the indirect twitch response occurred only when anesthetic concentrations were great enough to depress depolarization by 50 per cent.     

Production of compound A and carbon monoxide in circle systems: an in vitro comparison of two carbon dioxide absorbents

Two new generation carbon dioxide absorbents, DrägerSorb^® Free and Amsorb^® Plus, were studied in vitro for formation of compound A or carbon monoxide, during minimal gas flow (500 ml.min^?1) with sevoflurane or desflurane. Compound A was assessed by gas chromatography/mass spectrometry and carbon monoxide with continuous infrared spectrometry. Fresh and dehydrated absorbents were studied. Mean (SD) time till exhaustion (inspiratory carbon dioxide concentration ≥ 1 kPa) with fresh absorbents was longer with DrägerSorb^® Free (1233 (55) min) than with Amsorb^® Plus (1025 (55) min; p < 0.01). For both absorbents, values of compound A were < 1 ppm and therefore below clinically significant levels, but were up to 0.25 ppm higher with DrägerSorb^® Free than with Amsorb^® Plus. Using dehydrated absorbents, values of compound A were about 50% lower than with fresh absorbents and were identical for DrägerSorb^® Free and Amsorb^® Plus. With dehydrated absorbents, no detectable carbon monoxide was found with desflurane.     

Thermogenesis inhibition in brown adipocytes is a specific property of volatile anesthetics

BACKGROUND: This investigation examined the possibility that the inhibitory effect of halothane on nonshivering thermogenesis (heat production) in brown adipocytes is not a universal effect of all anesthetic agents but related to the type of anesthetic. METHODS: Brown adipocytes from hamster were isolated with a collagenase digestion method and incubated with anesthetic agents. The rate of oxygen consumption was measured with an oxygen electrode. The effect of clinically relevant (and higher) doses of anesthetics of different classes on basal and norepinephrine-induced thermogenesis (oxygen consumption) was tested. RESULTS: Two distinct groups of anesthetics could be distinguished: thermogenesis inhibitors and noninhibitors. Thermogenesis inhibitors include volatile anesthetics such as halothane (IC(50), 1.1 mm), ether (IC(50), 20 mm), and chloroform (IC(50), 2.2 mm) (nominal concentrations), but also tribromoethanol (IC(50), 0.6 mm), all inducing inhibition of norepinephrine-induced thermogenesis without affecting the EC for norepinephrine. Thermogenesis noninhibitors include the nonvolatile anesthetics pentobarbital, propofol, ketamine, and urethane, the inhalation anesthetic nitrous oxide, and, notably, also the volatile nonanesthetics (nonimmobilizers) 1,2-dichlorohexafluorocyclobutane and 2,3-dichlorooctafluorobutane; none of these compounds had any effect on norepinephrine-induced thermogenesis at any concentration tested. CONCLUSIONS: There are two distinct classes of anesthetics with regard to effects on thermogenesis, thermogenesis inhibitors and thermogenesis noninhibitors. The results are important for the interpretation of studies in thermal biology in general; specifically, they indicate that conclusions concerning regulation of nonshivering thermogenesis during anesthesia depend on the type of anesthetic used. Of clinical importance is that the volatile anesthetics are inhibitory for nonshivering thermogenesis and thus for an alternative heat production when myorelaxants prevent shivering. As the distinction between thermogenesis inhibitors and thermogenesis noninhibitors corresponds to the distinction between volatile and nonvolatile anesthetics, it may be related to the mode of action of the volatile anesthetics.