| 摘要: | 吸入性全身麻醉劑發展與臨床應用訴求，主要在提昇臨床麻醉品質與確保病人麻醉的安全。有效快速的誘導麻醉、方便簡單的麻醉劑供給以維持穩定麻醉深度、確保手術完成後麻醉病人能快速安全的甦醒乃是吸入性全身麻醉的基本要求。新型吸入性全身麻醉劑脱氟醚可以滿足有效快速誘導麻醉與甦醒、提供病人安全有效的全身麻醉，目前是臨床普遍使用的經常使用的吸入性全身麻醉劑之一。分析吸入性全身麻醉劑脱氟醚(desflurane)藥物動力學， 使臨床麻醉專業人員執行全身麻醉時更易掌握脱氟醚全身麻醉劑進出身體、腦部組織過程，提供病人在麻醉手術中、後照護重要的參考根據。理論上脱氟醚自肺吸入，進入肺泡後再進入血循環系統過程中，直接受到下列生理與藥物直接影響，包括吸入濃度肺、通氣量、氣血分配係數與心輸出量等。尤其以血液循環系統參數(心輸出血量)與肺系統參數(肺泡通氣量)為最重要的兩大因素。乃是決定麻醉吸入性全身麻醉劑進出病人身體達到足夠的麻醉狀態、麻醉維持與恢復甦醒的過程中影響藥物動力學的重要關鍵。
過去傳統吸入性全身麻醉劑的藥物動力學的觀念，主要是依“吐氣末(end-tidal)吸入性全身麻醉劑濃度代表腦部的濃度”作為定義吸入性全身麻醉劑的臨床作用深度與體內攝取的指標基礎。麻醉專業人員與學者認為吐氣末(end-tidal)吸入性全身麻醉劑的濃度與時間的變化曲線以下的面積可以直接表示吸入性全身麻醉劑身體濃度與體內攝取程度。最近藥物動力學的研究結果發現，吸入性全身麻醉劑的吸入濃度與麻醉時間才是決定吸入性全身麻醉體內與腦部攝取的重要決定因素，而非過去認為應依吐氣末(end-tidal)濃度作為體內濃度與攝取的標準。實驗發現以“吐氣末代表動脈血或腦部組織濃度”臨床麻醉操作概念，在臨床麻醉操作與病人麻醉判斷有明顯偏差。因此，我們希望透過吸入性全身麻醉劑脱氟醚藥物動力學的研究，透過血中脱氟醚藥物測定分析，確認此新型吸入性麻醉劑從身體與腦部排除過程與肺功能殘氣量在吸入性全身麻醉劑排除初期扮演重要角色。理論基礎需要進一步導正與根據本實驗室在分析釐清的主要目的與對於吸入性全身麻醉劑在麻醉維持過程中，必須透過肺泡通氣(alveolar ventilation)與血液循環系統攜帶進入身體各部分組織。
過去本實驗室已完成相關吸入性全身麻醉劑體內與腦部攝取的藥物動力學研究。本實驗將針對脱氟醚分析呼吸與循環生理等重要因素，如何影響吐氣末與血中脱氟醚濃度改變。進而分析甦醒過程血中脱氟醚的清醒濃度，可作為麻醉甦醒時預估麻醉病人正確甦醒時間與濃度的依據。本實驗主要的研究方向可以分成三個重點：一、針對不同肺泡通氣量參數變化造成血液中脱氟醚體內攝取濃度變化之藥物動力學影響的探討。實驗結果發現,在病人誘導過程中提高肺泡通氣量將有效使血中脱氟醚濃度上昇的速率加快。二、觀察分析脱氟醚麻醉手術完成後病人麻醉甦醒過程中動靜脈血液系統中與吐氣末脱氟醚濃度之藥物動力學變化。觀察血中與吐氣末脱氟醚濃度改變之藥物動力學變化模式, 確認脱氟醚自各部位血管血液系統與肺部排除途徑不同而有顯著差異, 利於臨床麻醉病人自脱氟醚麻醉甦醒血中或估計的腦濃度變化準確判斷與應用。三、針對脱氟醚麻醉手術後病人甦醒時間與血中與吐氣末脱氟醚濃度的相關性分析並比較其預測甦醒時間的準確性。脱氟醚麻醉手術後病人甦醒時間與血中與吐氣末脱氟醚濃度的相關性分析比較，發現測定動脈血脱氟醚濃度以預測病人甦醒時間較吐氣末準確性。
本實驗結果提供誘導麻醉維持過成判斷麻醉病人腦中脱氟醚的濃度間接參考的判斷基礎，利於臨床監視脱氟醚的濃度以確定病人甦醒時間與濃度的判斷，提昇臨床全身麻醉操作與監視參數的準確性的，大幅增進臨床麻醉安全與服務品質。
The inhaled anesthetics have been shown to be both safe and effective in inducing and maintaining anesthesia. These agents differ in potency, adverse-effect profile, and cost. Newer anesthetic gases, such as sevoflurane and desflurane, appear to have more favorable physico-chemical properties. These factors, as well as patient characteristics and duration and type of procedure, must be considered when selecting an inhaled anesthetic. Desflurane possesses favorable pharmacokinetic and pharmacodynamic properties and is closer to the definition of an ideal agent. Its lowest blood and tissue solubility enables rapid onset of induction and emergence from anesthesia, thus enhancing patient safety and comfort. Theoretically, the passage of the desflurane from alveolar space into the blood stream depends on several factors, including inspired anesthetic concentration, ventilation volume, its blood-gas partition coefficient, and cardiac output.
According to the conventional concept of uptake of inhalation anesthetics, the volatile anesthetics uptake into body was defined as it dissolves from the gaseous phase in the alveoli into the pulmonary capillary blood. The rate of uptake is primarily determined by the alveolar to mixed venous anesthetic partial pressure difference. In addition, the fundamental assumption of minimal alveolar concentration (MAC) was the alveolar concentration equal to arterial blood concentration, and suggested that the arterial blood concentration shoud be equal to brain concentration. However, several studies demonstrated that the end-tidal inhalation anesthetic is unequal to the arterial blood or brain concentration.The determination of blood desflurane concentration using gas chromatography makes it possible to elucidate the pharmacokinetic of desflurane uptake, elimination from circulating blood. Thus, our study attempted to investigate the effect of ventilation on the change of blood desflurane concentration, which should be more likely the target organ-brain. The present study also determine the the blood desflurane concentration over time curve during elimination of desflurane anesthesia. The awkening arterial blood concentration will be determined when patient was awakening spontaneously.
Under a constant inspired concentration, the uptake of a volatile anesthetic into arterial blood should be governed mainly by alveolar ventilation under the assumption of that a patient’s cardiac output remaining stable during anesthesia. The effect of change in alveolar ventilation arterial desflurane concentration could be determined under different ventilation status with constant cardiac output. Our present study demonstrated the hyperventilation accelerated the rate of rise in Ades after desflurane administration, which was time-dependent in respect to different alveolar ventilations levels. Investigation of desflurane elimination from blood and respiratory gas would provide useful information with respect to patient’s recovery from anesthesia. Thus, our study will design to characterize the pharmacokinetics of desflurane elimination after cardiac surgery. The present study demonstrated that there were two distinct components, an initial 5-minute fast component and the subsequent 15-minute slow elimination component for desflurane concentration-time curves during elimination. The desflurane elimination from lungs is the fastest, as indicated by the CEdes, than from circulating blood. The initial 5-min rapid desflurane washout reflected the diluting effect of functional residual capacity of lungs. Since the arterial blood concentration provides us a steadier and more reliable process of elimination to represent the concentration in the brain and thus to reflect its pharmacological effect. The simultaneous measurement of desflurane concentration in the circulating arterial blood and respiratory gas will facilitate anesthesiologist to predict the awakening desflurane concentration appropriately during emergence period. The time to awakening was independent of the duration of desflurane anesthesia within 4 hours. With well-assisted ventilation, the end-tidal concentration was proven to represent the arterial blood concentration during elimination and could clinically be a feasible predicator for emergence from general anesthesia.
These study results would not only provide important information about alveolar ventilations on the body uptake and arterial blood concentration of desflurane and also help to adjust the ventilation at initial administration of desflurane and also predict patient to be emergence from desflurane anesthesia. Our study result would provide safe and adequate anesthesia during surgery and comfort emergence in the clinical anesthesia. |
