Carbon monoxide production from sevoflurane breakdown: modeling of exposures under clinical conditions

Isoflurane, enflurane, sevoflurane, and especially desflurane produce carbon monoxide (CO) during reaction with desiccated absorbents. Of these, sevoflurane is the least studied. We investigated the dependence of CO production from sevoflurane on absorbent temperature, minute ventilation (VE), and fresh gas flow rates. We measured absorbent temperature and in vitro CO concentrations when desiccated Baralyme reacted with 1 minimum alveolar anesthetic concentration of (2.1%) sevoflurane at 2.3-, 5.0-, and 10.0-L VE. Mathematical modeling of carboxyhemoglobin concentrations was performed using an existing iterative method. Rapid breakdown of sevoflurane prevented the attainment of 1 minimum alveolar anesthetic concentration with low fresh gas flow rates. CO concentrations increased with VE and with absorbent temperatures exceeding 80 degrees C, but concentrations decreased with higher fresh gas flow rates. Average CO concentrations were 150 and 600 ppm at 2.3- and 5.0-L VE; however, at 10 L, over 11,000 ppm of CO were produced followed by an explosion and fire. Methanol and formaldehyde were present and may have contributed to the flammable mixture but were not quantitated. Mathematical modeling of exposures indicates that in average cases, only patients < or =25 kg, or severely anemic patients, are at risk of carboxyhemoglobin concentrations >10% during the first 60 min of anesthesia. IMPLICATIONS: Sevoflurane breakdown in desiccated absorbents is expected to result in only mild carbon monoxide (CO) exposure. Completely dry absorbent and high minute ventilation rates may degrade sevoflurane to extremely large CO concentrations. Serious CO poisoning or spontaneous ignition of flammable gases within the breathing circuit are possible in extreme circumstances.     

Physical factors affecting the production of carbon monoxide from anesthetic breakdown

BACKGROUND: Parameters determining carbon monoxide (CO) concentrations produced by anesthetic breakdown have not been adequately studied in clinical situations. The authors hypothesized that these data will identify modifiable risk factors. METHODS: Carbon monoxide concentrations were measured when partially desiccated barium hydroxide lime was reacted with isoflurane (1.5%) and desflurane (7.5%) in a Draeger Narkomed 2 anesthesia machine with a latex breathing bag substituting for a patient. Additional experiments determined the effects of carbon dioxide (0 or 350 ml/min), fresh gas flow rates (1 or 4 l/min), minute ventilation (6 or 18 l/min), or absorbent quantity (1 or 2 canisters). End-tidal anesthetic concentrations were adjusted according to a monochromatic infrared monitor. RESULTS: Desflurane produced approximately 20 times more CO than isoflurane when completely dried absorbents were used. Peak CO concentrations approached 100,000 ppm with desflurane. Traces of water remaining after a 66-h drying time (one weekend) markedly reduced the generation of CO compared with 2 weeks of drying. Reducing the quantity of desiccated absorbent by 50% reduced the total CO production by 40% in the first hour. Increasing the fresh gas flow rate from 1 to 4 l/min increased CO production by 67% in the first hour but simultaneously decreased average inspiratory concentrations by 53%. Carbon dioxide decreased CO production by 12% in completely desiccated absorbents. CONCLUSION: Anesthetic identity, fresh gas flow rates, absorbent quantity, and water content are the most important factors determining patient exposures. Minute ventilation and carbon dioxide production by the patient are relatively unimportant.     

吸入氧浓度及呼气末正压对妇科腹腔镜手术患者动脉血-呼气末二氧化碳分压差的影响

目的 评价吸入氧浓度(FiO2)及呼气末正压(PEEP)对妇科腹腔镜手术患者动脉血-呼气末二氧化碳分压差[D(a-ET) CO2]的影响.方法 择期全麻下妇科腹腔镜手术患者60例,年龄25～50岁,体重45～75 kg,体重指数＜30 kg/m2,ASA分级Ⅰ或Ⅱ级,采用随机数字表法,将其分为3组(n=20):A组纯氧机械通气,PEEP为0；B组空氧混合气体机械通气,FiO2 50％,PEEP为0；C组空氧混合气体机械通气,FiO2 50％,PEEP为5 cm H2O.机械通气中监测PE,CO2,于气管插管后即刻(T1)和气腹1 h(T2)时取桡动脉血行血气分析,计算D(a-ET) CO2及肺内分流率(Qs/Qt).结果 与A组比较,B组和C组T2时D(a-ET) CO2及Qs/Qt降低(P＜0.05)；与B组比较,C组T2时D(a-ET) CO2降低(P＜0.05),Qs/Qt差异无统计学意义(P＞0.05).结论 降低FiO2及给予PEEP 5 cm H2O可降低妇科腹腔镜手术患者D(a-ET) CO2,提高pETCO2反映PaCO2的准确性,其原因与减少肺内分流有关.     

Oxygenation during one-lung ventilation: the effects of inhaled nitric oxide and increasing levels of inspired fraction of oxygen

We studied whether inhaled nitric oxide (NO) would improve arterial oxygen tension (PaO(2)) and reduce the occurrence of oxygen saturation of hemoglobin (O(2)Hb) < 90% during one-lung ventilation (OLV). One-hundred-fifty-two patients were ventilated either with or without NO (20 ppm) with an inspired fraction of oxygen (FIO(2)) of either 0.3, 0.5, or 1.0 during OLV. Anesthesia was induced and maintained with propofol, remifentanil, and rocuronium IV, and lung separation was achieved with a double-lumen tube. During OLV, we set positive end-expiratory pressure at 5 cm H(2)O, peak pressure at 30 cm H(2)O, and end-tidal CO(2) at 30 mm Hg. The nonventilated lung was opened to room air and collapsed. During OLV, three consecutive measurements were performed every 10 min. The operated lung was temporarily ventilated if pulse oximetric saturation (SpO(2)) decreased to < 91%. SpO(2) <9 1% occurred in 2 of the 152 patients. SpO(2) overestimated O(2)Hb by 2.9% +/- 0.1%. NO failed to improve oxygenation or alter occurrence of O(2)Hb < 90% during OLV across all time points and all levels of FIO(2). Increasing FIO(2) increased oxygenation and decreased occurrence of O(2)Hb < 90% (P: < 0.001). At FIO(2) = 1, PaO(2) was higher (P < 0.01) and O(2)Hb < 90% rate tended to be lower (P = 0.1) during right versus left lung ventilation. PaO(2) was higher in patients undergoing pneumonectomy and lobectomy than in those undergoing metastasectomy or video-assisted operations (P < 0.05). IMPLICATIONS: Inhaled nitric oxide failed to improve oxygenation during one-lung ventilation. Oxygenation during one-lung ventilation was improved with increasing levels of FIO(2) during ventilation of the right versus the left lung and with increasing pathology of the nonventilated lung.     

Effects of cerebral perfusion pressure and increased fraction of inspired oxygen on brain tissue oxygen,lactate and glucose in patients with severe head injury

Summary ?Objective. The purpose of the study was to measure the effects of increased inspired oxygen on patients suffering severe head injury and consequent influences on the correlations between CPP and brain tissue oxygen (PtiO2) and the effects on brain microdialysate glucose and lactate. Methods. In a prospective, observational study 20 patients suffering severe head injury (GCS≤8) were studied between January 2000 and December 2001. Each patient received an intraparenchymal ICP device and an oxygen sensor and, in 17 patients brain microdialysis was performed at the cortical-subcortical junction. A 6 h 100% oxygen challenge (FIO₂ 1.0) (Period A) was performed as early as possible in the first 24 hours after injury and compared with a similar 6 hour period following the challenge (Period B). Statistics were performed using the linear correlation analysis, one sample t-test, as well as the Lorentzian peak correlation analysis. Results. FIO₂ was positively correlated with PtiO2 (p<0.0001) over the whole study period. PtiO2 was significantly higher (p<0.001) during Period A compared to Period B. CPP was positively correlated with PtiO2 (p<0.001) during the whole study. PtiO2 peaked at a CPP value of 78 mmHg performing a Lorentzian peak correlation analysis of all patients over the whole study. During Period A the brain microdialysate lactate was significantly lower (p=0.015) compared with Period B. However the brain microdialysate glucose remained unchanged. Conclusion. PtiO2 is significantly positively correlated with FIO₂, meaning that PtiO2 can be improved by the simple manipulation of increasing FIO₂ and ABGAO2. PtiO2 is positively correlated with CPP, peaking at a CPP value of 78 mmHg. Brain microdialysate lactate can be lowered by increasing PtiO2 values, as observed during the oxygen challenge, whereas microdialysate glucose is unchanged during this procedure. Extension of the oxygen challenge time and measurement of the intermediate energy metabolite pyruvate may clarify the metabolic effects of the intervention. Prospective comparative studies, including analysis of outcome on a larger multicenter basis, are necessary to assess the long term clinical benefits of this procedure. Published online June 4, 2003     

Prostacyclin production by the heart: effect of nicotine and carbon monoxide

Smoking has been linked to the development and progression of atherosclerosis but the mechanism by which smoking exerts its deleterious effects remains unknown. This study was designed to examine in a systematic way the effects of nicotine and carbon monoxide on platelets, arterial walls, and the heart. Results of experiments designed to assess the effect of nicotine and carbon monoxide on the production of prostacyclin (PGI2) by the rabbit heart are reported. Animals exposed to carbon monoxide had the carboxyhemoglobin raised to at least 12% by breathing an atmosphere enriched with carbon monoxide. Nicotine was infused at 50 micrograms/kg/hr for 1 week. Nicotine was measured by gas/liquid chromatography. PGI2 was measured by radioimmunoassay of 6-keto-PGF1 alpha, and its biologic activity was assessed by inhibition of platelet aggregation. Nicotine is concentrated in the heart and blood vessel wall and causes a statistically significant reduction in PGI2 production. Carbon monoxide raised PGI2 production significantly in all chambers, and the combination of nicotine and carbon monoxide further raised PGI2 production. The difference between the effects of nitrogen and carbon monoxide alone and nitrogen and a combination of nitrogen and carbon monoxide was significant in all chambers. It is hypothesized that nicotine exerts a direct metabolic effect in lowering PGI2 production. Carbon monoxide may make the endothelial cell relatively hypoxic, a powerful stimulus of PGI2 production, or less likely exert a direct toxic effect on the endothelial cell.     

Higher fraction of inspired oxygen in anesthesia induction does not affect functional residual capacity reduction after intubation: a comparative study of higher and lower oxygen concentration

Background

Low fraction of inspired oxygen (F_IO₂) reduces the atelectasis area during anesthesia induction. However, atelectasis may occur during laryngoscopy and endotracheal intubation because lungs can collapse within a fraction of a second. We assessed the effects of ventilation with 100 and 40 % oxygen on functional residual capacity (FRC) in patients undergoing general anesthesia.

Methods

Twenty patients scheduled for elective open abdominal surgery were randomized into 40 % oxygen (GI, n = 10) and 100 % oxygen (GII, n = 10) groups and FRC was measured. Preoxygenation and mask ventilation with 40 and 100 % oxygen were used in GI and GII, respectively. In both groups, 40 % oxygen was used for anesthesia maintenance after intubation. Bilateral lung ventilation was performed with volume guarantee and low tidal volume (7 ml/kg predicted body weight) using bilevel airway pressure. We measured FRC and blood gas in all patients during preoxygenation, after intubation, and during surgery.

Results

FRC decreased from during preoxygenation (GI 2380 ml, GII 2313 ml) to after intubation (GI 1569 ml, GII 1586 ml) and significantly decreased during surgery (GI 1338 ml, GII 1417 ml) (P < 0.05). PaO₂/F_IO₂ decreased from during preoxygenation (GI 419 mmHg, GII 427 mmHg) to after intubation (GI 381 mmHg, GII 351 mmHg) and significantly decreased during surgery (GI 333 mmHg, GII 291 mmHg) (P < 0.05). No significant differences were found between the groups in both parameters.

Conclusions

FRC significantly decreased from the awake state to surgery in both groups. FRC was not influenced by F_IO₂ elevation at anesthesia induction.     

Relative intakes of tar, nicotine, and carbon monoxide from cigarettes of different yields

The relative intakes of tar, nicotine, and carbon monoxide were estimated in 2455 cigarette smokers, who freely smoked their usual brands of cigarette. The estimates were derived by using an objective index of inhaling based on the measurement of carboxyhaemoglobin divided by the carbon monoxide yield of the cigarettes smoked, after background and carry over carboxyhaemoglobin effects had been allowed for. Separate analyses were performed according to the yield and type (plain, filter, etc) of cigarette smoked. The analyses based on yield indicated that the extent of inhaling was adjusted sufficiently to achieve similar intakes of nicotine/carbon monoxide regardless of the nicotine/carbon monoxide yield. It was not, however, sufficiently increased to achieve a similar intake of tar as the tar yield of the cigarette decreased. The analyses based on type of cigarette indicated that the extent of inhaling was adjusted to achieve similar intakes of tar and nicotine regardless of the type of cigarette smoked, but that this led to a greater intake of carbon monoxide among filter cigarette smokers than that among smokers of plain cigarettes--more so than would have been expected from their relative carbon monoxide yields. Two conclusions arise from these results. Firstly, any harmful effects of nicotine/carbon monoxide are unlikely to be materially reduced by smoking cigarettes with lower yields of nicotine/carbon monoxide, but the harmful effects of tar are likely to be reduced by smoking cigarettes with lower tar yields. These predictions appear to be borne out by epidemiological observations. Secondly, any harmful effects of carbon monoxide on the cardiovascular system will be greater in smokers of modern filter cigarettes than in smokers of modern plain cigarettes, provided that these two groups of smokers are otherwise similar with respect to risk of cardiovascular disease.     

Safety of 80% vs 30–35% fraction of inspired oxygen in patients undergoing surgery: a systematic review and meta-analysis

Background

Evidence-based guidelines from the World Health Organization (WHO) have recommended a high (80%) fraction of inspired oxygen (FiO₂) to reduce surgical site infection in adult surgical patients undergoing general anaesthesia with tracheal intubation. However, there is ongoing debate over the safety of high FiO₂. We performed a systematic review to define the relative risk of clinically relevant adverse events (AE) associated with high FiO₂.

The effect of cigarette smoke, nicotine, and carbon monoxide on the permeability of the arterial wall

The association between cigarette smoking and the development of atherosclerosis is well established, but the mechanism that makes cigarettes such a potent "risk factor" is not understood. There is normally a constant insudation of plasma macromolecules into the arterial wall. Fibrinogen and lipids are two of the large molecules involved in atherosclerosis. Therefore we studied the effect of cigarette smoke, nicotine, and carbon monoxide on the permeability of the canine arterial wall to 125I-labeled fibrinogen. The results show that inhaled cigarette smoke significantly and rapidly increases the permeability of the arterial wall to fibrinogen and that this effect can be produced with carbon monoxide alone but not with intravenous nicotine.     

Effectiveness of 80% vs 30–35% fraction of inspired oxygen in patients undergoing surgery: an updated systematic review and meta-analysis

Background

In 2016, the World Health Organization (WHO) strongly recommended the use of a high fraction of inspired oxygen (FiO₂) in adult patients undergoing general anaesthesia to reduce the risk of surgical site infection (SSI). Since then, further trials have been published, trials included previously have come under scrutiny, and one article was retracted. We updated the systematic review on which the recommendation was based.

IPPB and hypercapnia in respiratory failure: The effect of different concentrations of inspired oxygen on arterial blood gas tensions

Fourteen patients with acute exacerbations of chronic bronchitis and hypercapnia received two treatment periods with Intermittent Positive Pressure Breathing, the ventilator being driven by gas containing about 24% or about 45% oxygen. Arterial PO2 and PCO2 were measured before, during and after each treatment. The results demonstrated that increasing hypercapnia did not, as a rule, occur when 45% oxygen was used as the driving gas. When hypercapnia did occur it appeared to be independent of the inspired oxygen concentration. The importance of short treatment periods, correct ventilator settings and supervision of the patient during and after treatment is emphasised.     

The effect of a bellows leak in an Ohmeda 7810 ventilator on room contamination, inspired oxygen, airway pressure, and tidal volume

We investigated the effect of a small bellows leak (bellows full at end-expiration) on inspired oxygen fraction (Fio(2)), exhaled tidal volume (Vt), airway pressure, and room contamination in an oxygen-driven anesthesia ventilator (Ohmeda 7810, Madison, WI). CO(2) concentration at the ventilator exhalation valve, Fio(2), Vt, and airway pressure were measured (n = 3) while ventilating a CO(2)-producing test lung at 8 breaths/min and an inspiratory/expiratory ratio of 1:2, with and without a bellows leak (4-mm-long tear). Set Vt was 400, 600, 800, and 1000 mL. Fresh gas flow (FGF) was 0.3 L/min O(2) and (a) 5.0 L/min air, (b) 2.0 L/min air, and (c) 0.2 L/min nitrogen. There was no clinical difference in Fio(2), Vt, PIP (peak inspiratory pressure) and PEEP (positive end-expiratory pressure), with and without a 4-mm bellows tear, at all FGFs and Vt settings. CO(2) at the ventilator exhalation valve was always nonzero with a bellows leak, indicating that CO(2)-laden circuit gas was contaminating the drive gas via the bellows leak. A 4-mm bellows tear in an Ohmeda 7810 ventilator allows anesthetic gases to contaminate ambient air but does not cause clinically significant changes in Fio(2), exhaled Vt, PIP, or PEEP.     

The effect of cardiopulmonary bypass and inspired oxygen concentration on left ventricular contrast opacification with optison, a second-generation ultrasound contrast agent

OBJECTIVE: To investigate the influence of cardiopulmonary bypass (CPB) and fraction of inspired oxygen (F(I)O(2)) on the contrast effect of Optison, a second-generation ultrasound contrast agent, in humans during coronary artery bypass graft (CABG) surgery with transesophageal echocardiography (TEE). DESIGN: Prospective, observational, repeated-measures design. SETTING: A single university hospital. PARTICIPANTS: Ten patients who underwent elective CABG surgery. INTERVENTIONS: A transgastric, midpapillary, short-axis view of the left ventricle was obtained with TEE in the conventional imaging mode. A central injection of 0.3 mL of Optison was administered at 4 stages: after induction of anesthesia at F(I)O(2) = 1.0 and F(I)O(2) = 0.43 +/- 0.02 and after protamine administration at F(I)O(2) = 1.0 and F(I)O(2) = 0.52 +/- 0.09. Background-corrected maximal pixel intensity (PImax(corr)) in the left ventricle was determined with videodensitometry. To estimate the magnitude of change in pixel intensities, point estimates of differences in PImax(corr) and their 95% and 99% confidence intervals were calculated after repeated measures analysis of variance. MEASUREMENTS AND MAIN RESULTS: Decreasing the F(I)O(2) from 1.0 to <1 did not alter PImax(corr) significantly before or after CPB (mean change = -4.2 and 0.8; SE = 2.0 and 1.9; p = 0.06 and 0.68). Values for PImax(corr) before and after CPB were not significantly different at either F(I)O(2) = 1.0 or F(I)O(2) <1 (mean change = -3.3 and 1.7; SE = 2.4 and 2.7; p = 0.26 and 0.54). Mean differences from initial values ranged from a 10% decrease to a 5% increase. CONCLUSION: In patients who undergo CABG surgery, the contrast opacification of Optison in the left ventricle is not changed by CPB or alterations in F(I)O(2) during intraoperative TEE. The application of Optison for enhancement of the endocardial border is not limited during cardiac surgery.     

Rates of awakening from anesthesia with I-653, halothane, isoflurane, and sevoflurane: a test of the effect of anesthetic concentration and duration in rats

The low blood solubility of two new inhaled anesthetics, I-653 (human blood/gas partition coefficient, 0.42) and sevoflurane (0.69), suggested that awakening from these agents should be more rapid than awakening from currently available anesthetics such as isoflurane (1.4) and halothane (2.5). This prediction proved valid in a study of these four agents in rats given 0.4, 0.8, 1.2, or 1.6 MAC for 2.0 hr or 1.6 MAC for 0.5 or 1.0 hr. At a given dose and duration, awakening was most rapid with the least soluble agent and longest with the most soluble agent. For example, recovery of muscle coordination at 1.2 MAC administered for 2 hr required 4.7 +/- 3.0 min (mean +/- SD) with I-653, 14.2 +/- 8.1 min with sevoflurane, 23.2 +/- 7.6 min with isoflurane, and 47.2 +/- 4.7 min with halothane.     

Cross-sectional internal diameters of radial, thoracodorsal, and dorsalis pedis arteries in children: relationship to subject sex, age, and body size

The purpose of this study was to determine the average diameter of the radial, thoracodorsal, and dorsalis pedis arteries in a pediatric population and to evaluate the relationship of these measurements to the subject's age, sex, height, weight, and body mass index (BMI). The internal diameters of the radial, thoracodorsal, and dorsalis pedis arteries were non-invasively studied in 45 normotensive, presumed normal children of various ages (4 to 14 years) with the use of a Doppler system. The average diameters of the radial, thoracodorsal, and dorsalis pedis arteries in females and males were as follows: radial artery 1.39 (SD +/- 0.18) mm and 1.57 (SD +/- 0.18) mm; thoracodorsal artery 1.27 (SD +/- 0.11) mm and 1.36 (SD +/- 0.2) mm; and dorsalis pedis artery 1.22 (SD +/- 0.08) mm and 1.34 (SD +/- 0.12) mm. These were correlated with the age, height, weight, and BMI. Gender had a strong influence on the diameter of these arteries. In a linear regression model, weight was found to be statistically the best independent variable for predicting radial and dorsalis pedis diameters, whereas age was the best predictor for the diameter of the thoracodorsal artery. The diameters of these three arteries in an age group of 4 to 14 years ranged between 1 to 2 mm. The age and weight of the children predicted the diameters of the peripheral arteries.