Neuroprotective effects of thiopental, propofol, and etomidate

In selecting an anesthetic agent to be used for neurosurgical procedures, the anesthesia provider must consider the agent's effects on intracranial pressure (ICP), cerebral blood flow (CBF), and cerebral metabolic rate of oxygen consumption (CMRO2). The anesthetic of choice for neurosurgical procedures for many decades has been thiopental. It meets the strict requirements for neurosurgical procedures because it protects the brain from ischemia and herniation by lowering ICP through decreases in CBF and CMRO However, new drugs, including etomidate and propofol, have been introduced that offer anesthesia providers comparable neuroprotective actions plus other positive attributes. The purpose of this course is to review current and benchmark literature on thiopental, propofol, and etomidate to compare researchers' reports of the effects on ICP, CMRO2, and CBF Literature was gathered using computer assistance to search PubMed, the Cumulative Index of Nursing and Allied Health Literature, and the World Wide Web. The literature showed that all 3 anesthetic agents provide favorable neurological protection. Each drug has some undesirable side effects. Knowledge of these side effects and the patient's medical and surgical history can help CRNAs determine the most suitable anesthetic in specific situations.     

The concept of a critical oxygen delivery

In healthy tissues, decreases in oxygen delivery (QO_n) do not lower oxygen consumption (VO₂) because tissue O₂ extraction increases proportionately. When delivery is reduced below a critical threshold, VO₂ falls because tissue extraction exceeds a critical threshold, and cannot compensate for the reduction in delivery. In the adult respiratory distress syndrome and perhaps in septicemia, tissue extraction capacity is impaired, leading to O₂ supply dependency despite normal or increased overall delivery. This pathologic supply dependency could be caused by a loss in autoregulatory capacity, by disrupted blood flow distribution secondary to peripheral microembolization, or to other factors interfering with efficient tissue distribution of QO₂ with respect to VO₂. Alternatively, the increased VO₂ may be consumed in biochemical pathways not associated with ATP production, or in the production of oxygen radicals or hydrogen peroxide. To the extent this abnormal dependence of VO₂ on QO₂ reflects tissue hypoxia, clinical interventions which decrease systemic delivery should be evaluated with regard to possible deleterious effects on organ system function.     

异丙酚和依托咪酯全麻诱导对重症颅脑损伤患者脑氧代谢的影响

目的观察异丙酚和依托咪酯在全麻诱导时对重症颅脑损伤患者脑氧代谢的影响。方法30例重症颅脑损伤术前经CT诊断,GCS(glasgowcomascale)评分≤7需急诊手术患者,随机分为两组,异丙酚组15例行咪唑安定0.1mg·kg-1、芬太尼4μg·kg-1、异丙酚1mg·kg-1、维库溴铵0.1mg·kg-1快诱导,依托咪酯组15例在上述基础上由依托咪酯0.2mg·kg-1代替异丙酚,观察两组患者麻醉前(T0)、诱导后2min(T1)、插管后2min(T2)插管后10min(T3)及插管后30min(T4)收缩压、舒张压、心率以及在相应时间抽取桡动脉和颈内静脉球处血液行血气分析,根据各时间的血气分析计算颈内静脉球、桡动脉处血氧含量、脑氧摄取率。结果全麻诱导后氧供明显改善,两组患者脑氧代谢率均降低,但在插管后2min异丙酚组下降更明显(P<0.05),异丙酚组血液动力学波动明显大于依托咪酯组(P<0.05)。结论异丙酚诱导对重症颅脑损伤患者血流动力学波动明显大于依托咪酯,但与依托咪酯相比更能降低患者的脑氧摄取率,可能对重症颅脑损伤患者更为有利。     

Effects of pentobarbital and etomidate on plasma catecholamine levels and spectral analysis of blood pressure and heart rate in dogs

Summary— The present paper investigates the effects of two anæsthetic drugs (pentobarbital and etomidate) on both short-term variabilities of systolic blood pressure (SBP) and heart rate (HR) using fast Fourier transformation and catecholamine plasma levels. HR and BP were continuously recorded through an arterial catheter and blood samples were taken from the jugular vein. Spectral analysis was performed first in the conscious state and six minutes after induction of anæsthesia on a series of 256 consecutive BP and HR values (Δt: 2 Hz). The area under the curve (AUC) was determined in the low-frequency component of the SBP (LF: 40–150 mHz), in the high-frequency band of HR (HF: respiratory frequency ± 50 mHz) and in the total frequency spectra. Results were normalized by calculation of the ratio between AUC of LF and HF and the total AUC of the corresponding spectrum (TS). Etomidate (2 mg/kg iv) induced a significant increase in TS and LF without changing the LF/TS ratio or the HR variability when compared with the awake period. Catecholamine plasma levels did not change. In contrast, pentobarbital (30 mg/kg iv) decreased the values of LF, HF, LF/TS and HF/TS and catecholamine plasma levels. These results suggest that pentobarbital decreases the activity of the two components of the autonomic nervous system whereas etomidate induces only minimal changes.     

咪唑安定和丙泊酚联用对危重患者镇静-遗忘作用的研究

目的 观察咪唑安定和丙泊酚联用对危重患者镇静-遗忘作用的影响.方法 选择重症加强治疗病房(ICU)行机械通气2～4 d的患者60例,随机分为丙泊酚组、咪唑安定组和咪唑安定加丙泊酚联用组,每组20例.分别于用药后1、2和3 d唤醒患者并出示不同颜色、图形、数字的卡片,于患者停用机械通气完全清醒后评估药物对其镇静-遗忘作用的影响.结果 ①丙泊酚、咪唑安定和联用组分别有70%、95%和90%的患者产生遗忘,停药30 min后患者均恢复记忆.②咪唑安定组静脉推注负荷量药物起效的时间((5.1±2.8)min]和停药清醒后拔除气管插管的时间[(2.7±0.3)h]均较丙泊酚组[(2.7±1.1)min、(0.7±0.2)h]、联用组[(3.1±1.3)min、(1.2±0.6)h]明显延长(P均＜0.01);丙泊酚组和联用组药物起效时间和停药清醒后拔除气管插管时间相近,差异无统计学意义(P均＞0.05).③镇静费用咪唑安定组[(1 200±112)元]和联用组[(1 300±132)元]接近,丙泊酚组[(2 100±125)元]高于咪唑安定组约75%(P＜0.01).结论 丙泊酚与咪唑安定联合用药既可确保患者产生镇静-遗忘效应,减少各自的用量,降低药物不良反应,又有利于降低患者的住院费用,可能是ICU危重患者较好的镇静-遗忘治疗方案.     

Whole body oxygen consumption and critical oxygen delivery in response to prolonged and severe carbon monoxide poisoning

BACKGROUND: Carbon monoxide (CO) poisoning remains the leading cause of death by poisoning in the world. One of the major proposed mechanisms for CO toxicity is the binding of CO to cytochrome oxidase and interference with cellular oxygen utilization but evidence for this is inconclusive. AIM OF STUDY: This study examined the effects of prolonged CO exposure on the dynamics of whole body oxygen consumption (VO(2)) and oxygen delivery (DO(2)) in an attempt to observe if CO exposure results in a defect of oxygen utilization defect as determined by a reduction in VO(2) during the course of poisoning prior to reaching the point where VO(2) is directly dependent on DO(2). This critical level of DO(2) (DO(2)crit) produced by CO poisoning was compared to historical values produced by other insults, which decrease global body DO(2). METHODS: Five small dogs were ventilated for 2 h with 0.25% CO and room air followed by 0.5% CO until death. Cardiac index (Q), DO(2), VO(2), oxygen extraction ratio (OER), and systemic lactate were measured every 15 min until death. RESULTS: Carboxyhemoglobin (COHb) levels increased linearly over 2.5 h to values above 80% until death. VO(2) remained constant and not significantly different from baseline below a COHb of 80%. At COHb levels above 80%, VO(2) precipitously dropped. Similarly lactate levels were not significantly elevated from baseline until VO(2) dropped. DO(2) decreased by 78% (from 23+/-6 ml/kg/min to 5+/-4 ml/kg/min) over time despite an increase in Q by 58% until levels of COHb were above 80%. OER increased from 19+/-5% to 50+/-11% until death. The calculated DO(2)crit was 10.7+/-4 ml/min/kg, which is not significantly different from values ranging from 7 to 13 ml/min/kg reported in the literature due to other insults, which reduce DO(2). CONCLUSION: In this canine model of prolonged CO exposure, no gradual reduction in VO(2) or increase in systemic lactate prior to reaching DO(2)crit was noted. In addition, CO exposure does not appear to change the DO(2)crit. The combination of these findings does not support the theory that CO produces a whole body intracellular defect in oxygen utilization.     

Interaction of extracellular albumin and intravenous anaesthetics, etomidate and propofol, on calcium signalling in rat airway smooth muscle cells

It has been shown in vitro that general anaesthetics modify airway responsiveness via, at least partially, a direct inhibitory effect on calcium signalling in airway smooth muscle cells. However, in vivo, these anaesthetic compounds bind serum proteins. We have investigated the effect of exposure to extracellular albumin of freshly isolated airway smooth muscle cells on the propofol- and etomidate-induced inhibitory effect on calcium signalling. [Ca2+]i was measured by microspectrofluorimetry in rat isolated tracheal smooth muscle cells using the fluorescent dye indo-1. Propofol (3 x 10(-4) M) and etomidate (10(-4) M) were the lowest 'effective' concentrations that altered the [Ca2+]i response. This alteration consisted of a decrease in both the amplitude of the [Ca2+]i peak (from 358 +/- 13 nM to 65 +/- 15 and 108 +/- 27 nM for propofol and etomidate, respectively) and the percentage of responding cells (from 80% to 37 and 25% respectively) in response to the low concentration of ACh and a decrease in the Ca2+ oscillation frequency (from 9.9 +/- 0.3 min(-1) to 4.7 +/- 0.4 and 6.9 +/- 0.4 min(-1), respectively) in response to the high concentration of ACh. Increasing the concentration of albumin reduced the inhibitory effect of etomidate and propofol on the [Ca2+]i response to ACh. When extracellular albumin concentration was kept constant (20 g/L), increasing the concentration of etomidate by one log restored its inhibitory effect on the calcium signal. This study indicates that increasing the concentration of extracellular albumin reduces the inhibitory effect of intravenous anaesthetics on calcium signalling in airway smooth muscle cells. This report suggests that, in extrapolating in vitro dose-response relationships to those from in vivo conditions, the effect of the concentration of extracellular protein can be estimated.     

乳剂依托咪酯和丙泊酚治疗全麻后苏醒期躁动的疗效分析

目的观察术后应用乳剂依托咪酯和丙泊酚治疗全麻后苏醒期躁动的疗效。方法选择ASAⅠ或Ⅱ级全麻下行胃癌根治术且术毕出现苏醒期躁动患者40例,随机分为Ⅰ、Ⅱ两组,每组20例。两组术后均用芬太尼总量0．02mg／kg（0．4ug&#183;kg^-1&#183;h^-1）行病人自控静脉镇痛,当苏醒期躁动评分≥2分时,Ⅰ组静注乳剂依托咪酯0．15mg／kg．Ⅱ组静注丙泊酚1．5mg／kg。观察两组抗躁动起效时间和清醒时间、两组患者的Ramsay镇静评分及副作用。结果Ⅰ、Ⅱ两组镇静深度均在4分以上,抗躁动疗效均达100％;Ⅱ组比Ⅰ组起效快,但差异无统计学意义（t=1．41,P〉0．05）,两组清醒时间比较差异亦无统计学意义（t=0．57,P〉0．05）;Ⅰ组有1例、Ⅱ组8例发生循环呼吸抑制,差异有统计学意义（x。=5．16,P〈0．05）;两组患者均未发生恶心呕吐和肌颤。结论乳剂依托咪酯和丙泊酚均可有效地治疗全麻后苏醒期躁动,乳剂依托咪酯更安全。     

Effects of dextran infusion on cardiac output, oxygen delivery, and oxygen utilization in piglets during the first month of life.

We determined the effects of volume infusion on cardiac output, oxygen delivery (Do2), oxygen consumption (Vo2), and oxygen extraction (O2 extr) in piglets at ages 5 to 14 days and 3 to 5 wk. Eighteen piglets were anesthetized, intubated, and mechanically ventilated. Six piglets (5 to 14 days old) and six piglets (3 to 5 wk old) received iv dextran (MW 70,000 daltons; 30 to 40 ml/kg) sufficient to raise mean left atrial pressure (LAP) from approximately 4 to 15 mm Hg over 30 min. Six piglets received 0.9% NaCl at 4 ml/kg.h to maintain LAP constant at 4 mm Hg over a 30-min period. All piglets receiving dextran had increased cardiac output (mean elevation 39 +/- 16 [SD]%; range +19% to +73%; p less than .005). This response was mediated entirely by an elevation in stroke volume, as heart rate did not change significantly. However, all piglets receiving dextran reduced Hgb concentration (10.1 +/- 1.5 to 7.5 +/- 1.4 g/dl, p less than .001), a decrease which completely offset the increase in cardiac output. Consequently, Do2 did not increase after dextran infusion (17.4 +/- 1.8 to 18.4 +/- 2.8 ml/min.kg). Neither Vo2 nor O2 extr changed significantly after dextran. No differences were noted in the response to dextran infusion comparing 5 to 14-day-old piglets with 3 to 5-wk-old piglets. Unlike fetal lambs, newborn piglets are able to elevate cardiac output significantly in response to volume loading. However, if these data can be extrapolated to human infants, volume infusion without concurrent blood transfusion is likely to increase systemic cardiac output but not improve Do2.     

Non-invasive cardiac output and oxygen delivery measurement in an infant with critical anemia

Objective

To assess the combination of a non-invasive blood oxygen content (CaO₂) monitor and a non-invasive cardiac output (CO) monitor to continuously measure oxygen delivery (DO₂; DO₂ = CaO₂ × CO).

Methods

DO₂ was assessed during blood transfusions in an infant with acute hemolytic anemia following admission (~48 h). CaO₂ was measured by Pulse Co-Oximetry, which also provides estimates of hemoglobin (Hgb) concentration and percent oxygen saturation. CO was measured by Electrical Velocimetry, which also provides an estimate of stroke volume (SV). Lactate levels, an indirect measure of adequate DO₂, were assessed during the initial 8 h following admission.

Results

Incremental blood transfusions during the first 36 h increased Hgb from 2.7 to 9.5 g/dL during which time heart rate (HR) normalized from 156 to 115 beats/min. Lactate levels decreased from 20 to 0.8 mmol/L in the first 7 h. Non-invasive Hgb and CaO₂ measurements were well correlated with invasive Hgb and CaO₂ measures (r ² = 0.88; P = 0.019; r ² = 0.86; P = 0.0074, respectively). CO decreased from 2.47 ± 0.06 to 1.28 ± 0.02 L/min and SV decreased from 15.9 ± 0.4 to 11.1 ± 0.2 mL/beat. Mean arterial blood pressure was stable throughout the admission with systemic vascular resistance increasing from 407.6 ± 15.2 to 887.7 ± 30.1 dynes-s/cm⁵. DO₂ was estimated to increase from 120.2 ± 18.9 to 182.4 ± 5.6 mL O₂/min.

Conclusions

Non-invasive contin- uous CO and CaO₂ monitors are shown in this single case to provide continuous DO₂ measurement. The ability to assess DO₂ may improve hemodynamic monitoring during goal directed therapies.     

七氟醚安氟醚对犬单肺通气期间肺分流与氧供及氧耗的影响

目的 观察犬单肺通气时,不同浓度七氟醚,安氟醚对Ｑｓ／Ｑｔ和氧供及氧耗等氧合指标的影响。方法 １４只健康杂种犬,诱导后插入双腔气管内导管,股动静脉分别置管监测血气和各自压力。随机分为两组,Ａ组吸入０．５ＭＡＣ、１．０ＭＡＣ安氟醚,待完全排除后再顺序吸入七氟醚;Ｂ组反之,各时相均分为双肺通气（ＴＬＶ）和单肺通气（ＯＬＶ）阶段,分别于ＴＬＶ、ＯＬＶ１５分钟后测量ＱＱｔ及氧供（ＤＯ２）、氧耗（ＶＯ２）等     

Effects of ketamine and propofol on oxygen status and blood content of the brain in children

Near infrared spectroscopy (NIRS) was used for noninvasive measurement of oxyhemoglobin (O2Hb) and total hemoglobin (tHb) in cerebral tissue and for evaluating local hemoglobin saturation with oxygen (rSO2) and cytochrome oxidase (Cytaa3) redox status in 68 children (6-14 years) during intravenous induction anesthesia with various anesthetics. Monoanesthesia with ketamine essentially increased the level of tHb and rSO2 and decreased the oxidized Cytaa3 fraction. Combined induction with ketamine and midazolame and propofol induction did not cause notable changes in the values of cerebral oxymetry.     

丙泊酚靶控输注联合依托咪酯在无痛胃肠镜检查中的应用

目的 探讨丙泊酚靶控输注(target-controlled infusion,TCI)联合依托咪酯应用于无痛胃肠镜检查的临床效果和安全性.方法 选择2018年8月至2019年8月期间于福建省立医院接受无痛胃肠镜检查的患者300例,随机分成丙泊酚组(P组)、丙泊酚复合0.1mg/kg依托咪酯组(0.1EP组)和丙泊酚复...     

Effects of maximizing oxygen delivery on morbidity and mortality in high-risk surgical patients

OBJECTIVE: To evaluate the effects of maximizing the oxygen delivery on morbidity and mortality in patients >60 yrs of age and/or with chronic diseases of vital organs who underwent major elective surgery. DESIGN: Prospective, randomized, controlled trial. SETTING: A 24-bed general intensive care unit of a teaching hospital. PATIENTS: Thirty-seven high-risk patients who underwent major surgery. INTERVENTIONS: The hemodynamic and oxygen transport variables and outcomes in 18 patients (control group) treated to maintain normal values of oxygen delivery were compared with 19 patients (protocol group) treated to maintain "supranormal" values. Therapy in both groups consisted of volume expansion and, when necessary, dobutamine to reach target values, during the surgery and 24 hrs postoperatively. MEASUREMENTS AND MAIN RESULTS: We interrupted the study because of a significant difference in the 60-day mortality rate. The mortality rate in the control group was significantly higher when compared with the protocol group (9/18 [50%] vs. 3/19 [15.7%], p < .05). The prevalence of clinical and infectious complications was higher in the control group than in the protocol group (67% and 31% respectively; relative risk, 0.47; 95% confidence interval, 0.226-0.991; p < .05) and there was a trend toward more severe organ dysfunction in nonachievers patients (17/24 [71%] vs. 6/13 [46%], relative risk, 0.65; 95% confidence interval, 0.343-1.237; NS). CONCLUSION: Older patients with existing cardiorespiratory illness undergoing major surgery have a reduced morbidity and mortality when dobutamine is used to maximize oxygen transport.     

丙泊酚联合依托咪酯用于无痛肠镜的安全性与可行性分析

目的探讨丙泊酚联合依托咪酯静脉注射用于无痛肠镜的安全性和可行性。方法前瞻性选取2018年12月至2019年5月在首都医科大学附属北京友谊医院消化内镜中心行择期诊断性无痛肠镜检查的606例患者作为研究对象,按照随机数字表法分成单用异丙酚组(P组,304例),异丙酚联合依托咪酯组(P+E组,302例)。收集并分析两组患者基线临床资料,比较两组患者麻醉诱导前(T0)、结肠镜进肛门(T1)、结肠镜过脾区(T2)、结肠镜进回盲部(T3)、结肠镜退出时(T4)、患者清醒时(T5)、患者离室前(T6)时的血压、心率、脉搏氧饱和度(SpO₂)以及操作时间、恢复时间、麻醉及血管活性药等用量和不良事件等。结果两组患者基线数据无统计学差异(P> 0.05)。两组患者T0时收缩压、舒张压、平均动脉压、心率、SpO₂差异无统计学意义(P> 0.05);诱导后两组患者血压、心率均有不同程度的下降,T1时P+E组的心率、舒张压、平均动脉压均明显高于P组,T2时P+E组的收缩压、舒张压、平均动脉压均明显高于P组,T3时P+E组的收缩压明显高于P组,差异均有统计学...     

The comparison of the effects of anesthetic doses of ketamine,propofol, and etomidate on ischemia–reperfusion injury in skeletal muscle

The fact that a considerable amount of clinical conditions suffering from ischemia–reperfusion injury (IRI) occur under general anesthesia has triggered researchers to focus on the effects of anesthetic drugs on IRI. Hence, the aim of this study was to compare the use of different anesthetic drugs in a skeletal IRI model. Tourniquet IRI method was performed and two experimental groups were established as sham‐control and IRI group. Rats in each group were anesthetized either with thiopental, ketamine, propofol or etomidate. Malondialdehyde, superoxide dismutase, catalase, and glutathione peroxidase were measured in skeletal muscle via a spectrophotometer. Zinc, iron, copper, and selenium were evaluated by atomic absorption spectrophotometer. In rats anesthetized with thiopental (40 mg/kg, i.p.), malondialdehyde values in IRI group were higher and glutathion peroxidase levels were lower compared to sham‐control group. However, superoxide dismutase and catalase activities were identical. On the other hand, while the level of zinc in IRI group attenuated, no differences in iron and copper values were determined. Rats anesthetized with ketamine (60 mg/kg), propofol (100 mg/kg), or etomidate (20 mg/kg) did not show increased malondialdehyde levels in comparison with control levels. While the drugs did not cause a distinction in the levels of superoxide dismutase, catalase, glutathion peroxidase, iron, and copper, zinc was in a lower level in IRI group compared to sham‐control. In conclusion, ketamine, propofol, and etomidate, with anesthetic doses, denoted efficacious effects on IRI; hence the drugs might be preferred in certain operations with the risk of IRI.     

靶控输注依托咪酯与异丙酚在肠镜检查中的应用

目的 探讨靶控输注依托咪酯或异丙酚在肠镜检查中应用的安全性、有效性和对血流动力学的影响,寻找一种更适合肠镜检查的麻醉方式.方法 患者随机分为3组(n=30):E组患者静脉注射芬太尼1μg/kg,1 min后静脉靶控输注依托咪酯,设定效应室浓度为0.3μg/mL(Arden模型);P组患者静脉注射芬太尼1μg/kg,1 min后静脉靶控输注异丙酚,设定效应室浓度为3μg/mL(Marsh模型);C组为对照组(未进行麻醉).观察并记录患者术中血流动力学变化以及SPO2变化、镇静及镇痛评分、不良反应及满意度评估.结果 与C组相比,E组和P组的内镜操作时间均明显缩短(P＜0.05),疼痛评分均明显降低(P＜0.05).E组和P组的内镜操作时间、恢复时间、镇静评分、不良反应及满意度差异均无显著性(P＞0.05).E组患者术中血流动 力学无显著变化(P＞0.05);P组患者术中MAP持续下降,T3、T4时刻分别较给药前显著下降(P＜0.05);C组患者术中T3、T4时刻MAP和HR较给药前显著升高(p＜0.05).E、P组患者术后满意度显著高于C组(P＜0.05).结论 靶控输注依托咪酯或异丙酚均可安全应用于肠镜检查麻醉,且靶控输注依托咪酯对血流动力学的影响更轻微,更适于肠镜检查患者.