The pharmacokinetics of anesthetic drugs and adjuvants during cardiopulmonary bypass

The institution of cardiopulmonary bypass during cardiac surgery has profound effects on the plasma concentration of drugs and thus their therapeutic effectiveness. These changes occur through acute hemodilution, altered plasma protein binding, hypotension, as well as the use of hypothermia and heparin administration. Isolation of the lungs from the circulation and the possible sequestration of drugs in the bypass circuit also affect drug plasma concentrations on bypass. The individual characteristics of the drug in question are also important in determining the final plasma concentration: Lipid soluble drugs with a high volume of distribution may be more readily taken up by bypass equipment, but the initial fall in concentration at the start of cardiopulmonary bypass may be more readily counteracted by back diffusion into plasma, if large tissue stores have accumulated. The extent of the drug's plasma protein binding is of importance as the effective free fraction in plasma for highly bound drugs will be sensitive to changes in plasma protein binding brought on by factors such as hemodilution, heparin administration as well as alpha, acid-glycoprotein binding. Clearly the fate of drugs administered before or on bypass is complex and can only be accurately determined by specific studies evaluating drug plasma concentrations. This review updates the available data on anesthetics and drugs used during cardiac surgery in order that anesthetists may predict better the likely effect of drugs administered before or during cardiopulmonary bypass.     

麻醉气体吸附器在异氟醚吸入全麻中的应用

目的　评估使用麻气体吸附对异氟醚吸入全麻的病人苏醒和对手术室污染状况的影响。方法　 30例病人 ,ASAⅠ -Ⅱ拟行异氟醚吸入麻醉。麻醉气体的吸附器安装在回路中 ,在苏醒阶段将活瓣打开 ,同时记录苏醒时间、血流动力学和血气分析各项指标。以上病人例在麻醉进行当中 ,废气排气口接废气吸收器 ,同时记录吸附器前后麻醉气体的浓度 ,计算麻醉气体的吸附率。结果　病人在清醒期苏醒时间明显缩短 ,与没有用麻醉吸附器相比 ,麻醉吸附器可以明显降低排入手术室麻醉气体的浓度。使用过程中 ,各项血流动力学指标和血气分析指标均正常。结论　麻醉气体吸附器的使用可以明显提高手术室的空气质量 ,同时在麻醉恢复期。病人的苏醒时间明显缩短而且安全可靠。     

不同剂量瑞芬太尼和芬太尼对抑制心血管反应的效果观察

目的 观察不同剂量瑞芬太尼和芬太尼对抑制心血管反应的效果.方法 选择择期手术全麻患者60例,ASA分级I～II级,随机分为瑞芬太尼组（RF组）和芬太尼组（F组）各30例,每组中根据麻醉诱导时给药剂量的不同又分为3个亚组,每组10例.瑞芬太尼和芬太尼的剂量分别是RF1（F1） 1μg /kg、RF2（F2） 1.5μg /kg、RF3（F3） 2.0μg /kg;监测病人的血压、心电图（ECG）、心率（HR）、心率变异性（HRV）、灌注指数.记录麻醉前（T0）、诱导时（T1）、插管即刻（T2）及气管插管后1min（T3）、5min（T4）、10min（T5）各时间点收缩压（SBP）、舒张压（DBP）、HR、HRV、灌注指数的变化.结果 ①60例病人与麻醉前相比,麻醉诱导时的SBP、DBP均明显下降（P＜0.01 或 0.05）;RF3组血压回升平稳,T2、T3、T4、T5时段血压比较差异无统计学意义（P＞0.05）;F1、2、3组心率与麻醉前比较明显升高（P＜0.05）,RF1、2、3组与麻醉前比较心率变化较平稳（P＞0.05）.②心率变异性RF三个剂量组T2、T3与麻醉前相比有统计学意义（P＜0.05）.灌注指数6组与麻醉前以及组间比较差异均无统计学意义（P＞0.05）.结论 瑞芬太尼作为麻醉诱导的基础用药,能有效抑制气管插管引起的心血管反应,2μg /kg瑞芬太尼复合异丙酚2mg/kg麻醉平稳,对血流动力学影响小,是气管插管的理想剂量.     

Local anesthetic systemic toxicity (LAST) – Should we not be concerned?

Local anesthetics are one of the most commonly used drugs in the field of medicine. Yet little is known about the systemic toxicity that can occur with their overdose. In the last few years, a lot of research has taken place understanding the etiology of the Local anesthetics systemic toxicity (LAST) and the role of lipid emulsion in treating it. There is a need to increase the awareness about LAST and establish a protocol to treat any serious neuro or cardiotoxicity.     

Pharmacotherapeutic options for complex regional pain syndrome

Introduction: Complex regional pain syndromes (CRPS) are rare painful conditions characterized by considerable variability in possible triggering factors, usually traumatic, and in the clinical scenario. The limited knowledge of the pathophysiological mechanisms has led to countless treatment attempts with multiple conservative and surgical options that act by different mechanisms of action.

Areas covered: In this narrative review, the authors discuss key points about CRPS definitions, diagnostic criteria and pitfalls, pathophysiological hypotheses, and treatment strategies with particular reference to pharmacotherapy. The article was based on a literature search using PubMed while the available guidelines for the management of CRPS were also examined.

Expert opinion: According to the quality of evidence, pharmacological interventions for CRPS seem to be more effective all the more so when they act on peripheral mechanisms, particularly on nociceptive pain, and when applied early in the disease, while reliable evidence about central mechanisms of chronic pain in CRPS is lacking. In our opinion, drug therapy should be preferred as early as possible, particularly in warm forms of CRPS to prevent significant functional limitation, psychological distress, and social and economic fallout.     

Combination of a reduced dose of an intrathecal local anesthetic with a small dose of an opioid: A meta-analysis of randomized trials

We tested whether the combination of a reduced dose of a local anesthetic (LA) with an opioid compared with a standard dose of the same LA alone guaranteed adequate intraoperative anesthesia and postoperative analgesia and decreased LA-related adverse effects. We systematically searched (to November 2012) for randomized comparisons of combinations of a reduced dose of an LA with a concomitant opioid (experimental) with a standard dose of the LA alone (control) in adults undergoing surgery with single-injection intrathecal anesthesia without general anesthesia. We included 28 trials (1393 patients). In experimental groups, the median decrease in LA doses was 40% (range, 12%–70%). There was no difference between experimental and control groups in the need for intraoperative opioids or general anesthesia for failed block or in the duration of postoperative analgesia. With experimental interventions, there was evidence of a reduction in the duration of motor blockade postoperatively (average, −50 minutes), time to discharge from hospital or PACU (−33 minutes), time to ambulation (−28 minutes), and time to urination (−14 minutes). There was also evidence of a decrease in the risk of shivering (risk ratio [RR]: 0.26; 95% confidence interval [CI]: 0.12–0.56), nausea (RR: 0.45; 95% CI: 0.31–0.66), and arterial hypotension (RR: 0.52; 95% CI: 0.35–0.78). The risk of pruritus was increased (RR: 11.7; 95% CI: 6.2–21.9). Adding an opioid to a reduced dose of an intrathecal LA can decrease LA-related adverse effects and improve recovery from the spinal block without compromising intraoperative anesthesia or duration of postoperative analgesia.     

Inhibition of Nav1.7 channels by methyl eugenol as a mechanism underlying its antinociceptive and anesthetic actions

Aim:

Methyl eugenol is a major active component extracted from the Chinese herb Asari Radix et Rhizoma, which has been used to treat toothache and other pain. Previous in vivo studies have shown that methyl eugenol has anesthetic and antinociceptive effects. The aim of this study was to determine the possible mechanism underlying its effect on nervous system disorders.

Methods:

The direct interaction of methyl eugenol with Na⁺ channels was explored and characterized using electrophysiological recordings from Na_v1.7-transfected CHO cells.

Results:

In whole-cell patch clamp mode, methyl eugenol tonically inhibited peripheral nerve Na_v1.7 currents in a concentration- and voltage-dependent manner, with an IC₅₀ of 295 μmol/L at a −100 mV holding potential. Functionally, methyl eugenol preferentially bound to Na_v1.7 channels in the inactivated and/or open state, with weaker binding to channels in the resting state. Thus, in the presence of methyl eugenol, Na_v1.7 channels exhibited reduced availability for activation in a steady-state inactivation protocol, strong use-dependent inhibition, enhanced binding kinetics, and slow recovery from inactivation compared to untreated channels. An estimation of the affinity of methyl eugenol for the resting and inactivated states of the channel also demonstrated that methyl eugenol preferentially binds to inactivated channels, with a 6.4 times greater affinity compared to channels in the resting state. The failure of inactivated channels to completely recover to control levels at higher concentrations of methyl eugenol implies that the drug may drive more drug-bound, fast-inactivated channels into drug-bound, slow-inactivated channels.

Conclusion:

Methyl eugenol is a potential candidate as an effective local anesthetic and analgesic. The antinociceptive and anesthetic effects of methyl eugenol result from the inhibitory action of methyl eugenol on peripheral Na⁺ channels.