dopamine 無形的殺手

Dopmaine 是使用最廣的強心增壓藥物，主要理論根據，有alfa, beta, 與 dopanergic  receptors的作用，好像是一個萬金油，大家都知道，什麼都有，就是什麼都沒有，世界上還沒有出現一種十全十美的藥物，所以在renal protection 為實驗研究所否認後，dopamine就沒有什麼優勢，在強心方面，沒有比其他inotropic來的優勢，在vasopressor方面，也比純alga agoinst弱，如果要達到升壓的目的，心跳，也毫無例外的會升高，在critical care 領域，非常忌諱心跳太快！

在一兩年前，大陸一位在美職業的陶醫師，在丁香園大聲疾呼，『多巴銨，無形的殺手』，引發極大的迴響，當然是貶大於褒，攻擊大於信服。今天m&m，一些septic shock的病人，開完刀，48小時內很快的死亡，當然是離不開有dopamine的治療，dopamine不是不能用，但要知道limintation，而不是一昧的提高劑量，也不是一味要用到矇，除了審因對症外，還要選擇不同的inotropics 或 vasopressor。

以下就抄錄陶醫師的大作：『多巴銨，無形的殺手』

最近的病例討論中，我們反復提到多巴胺的使用是否合理。我過去也談到，多巴胺在外科領域，已經沒有什麼使用價值。從個人的經驗看，多巴胺的作用太廣泛但不清楚，在提高後負荷時，對心肌刺激較大，心律失常太多，心肌氧耗增大。我個人是主張分別選用／合用，分別調節作用單一的藥物。

從理論上看，在休克治療中，去甲已經被證明效果優於多巴胺。在心衰方面，文獻中很多關於多巴胺導致更壞結果的報告。至於最為得意的腎保護，也被證明是不存在的（Lancet. 2000 Dec 23-30;356(9248):2139-43）。

就大家經常遇到的休克而言，最近一篇文章，對歐洲 98 個ICU中，3,147名感染性和非感染性病人分析，表明用多巴胺者，ICU 死亡率，30天死亡率和住院死亡率，都比不用多巴胺高（見表）。

Does dopamine administration in shock influence outcome? Results of the Sepsis Occurrence in Acutely Ill Patients (SOAP) Study.

Sakr Y, Reinhart K, Vincent JL, Sprung CL, Moreno R, Ranieri VM, De Backer D, Payen D.
Department of Intensive Care, Erasme Hospital, Free University of Brussels, Belgium.
Crit Care Med. 2006 Mar;34(3):589-97.

OBJECTIVE: The optimal adrenergic support in shock is controversial. We investigated whether dopamine administration influences the outcome from shock. DESIGN: Cohort, multiple-center, observational study. SETTING: One hundred and ninety-eight European intensive care units. PATIENTS: All adult patients admitted to a participating intensive care unit between May 1 and May 15, 2002. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were followed up until death, until hospital discharge, or for 60 days. Shock was defined as hemodynamic compromise necessitating the administration of vasopressor catecholamines. Of 3,147 patients, 1,058 (33.6%) had shock at any time; 462 (14.7%) had septic shock. The intensive care unit mortality rate for shock was 38.3% and 47.4% for septic shock. Of patients in shock, 375 (35.4%) received dopamine (dopamine group) and 683 (64.6%) never received dopamine. Age, gender, Simplified Acute Physiology Score II, and Sequential Organ Failure Assessment score were comparable between the two groups. The dopamine group had higher intensive care unit (42.9% vs. 35.7%, p=.02) and hospital (49.9% vs. 41.7%, p=.01) mortality rates. A Kaplan-Meier survival curve showed diminished 30 day-survival in the dopamine group (log rank=4.6, p=.032). In a multivariate analysis with intensive care unit outcome as the dependent factor, age, cancer, medical admissions, higher mean Sequential Organ Failure Assessment score, higher mean fluid balance, and dopamine administration were independent risk factors for intensive care unit mortality in patients with shock. CONCLUSIONS: This observational study suggests that dopamine administration may be associated with increased mortality rates in shock. There is a need for a prospective study comparing dopamine with other catecholamines in the management of circulatory shock.

同期的 Critical Care Medicine 中的編者按指出，大家好像對多巴胺的偏愛好像是社區醫院的傳統和對去甲的「懼怕」，並沒有什麼依據。「一點β ，一點 ɑ ，興許管用」。（也就是我的萬金油之說）。There is no rational evidence to support this, but one may argue that among community hospital physicians, there is a certain 「fear」 of norepinephrine and the belief that dopamine, 「a little bit β and a little bit ɑ, as inotrope or vasopressor, may do the job.」 同時，該編者按再次強調了多巴胺對腎沒有保護作用，反而增加腎氧耗。There is evidence that dopamine may increase renal oxygen consumption and may therefore jeopardize renal oxygen supply/demand balance. There is also ample evidence that the so-called renal dopamine does not change mortality, risk of renal failure, or need for extracorporeal renal replacement therapy ([24]). The evidence-based guidelines published in 2004 in this journal do not support the use of dopamine as renal protection or renal salvage agent ([27]).

隨後一篇由危重醫學高手 Pinsky 共同作者的讀書會中，指出一個尖銳的問題：多巴胺是不是無形的殺手？Could dopamine be a silent killer?（http://ccforum.com.foyer.swmed.edu/content/11/1/302#B11）他們分析了以上研究的長處和不足，並指出去甲早已被證明比多巴胺治療低血壓有效，並說明正在進行的多巴胺和去甲治療休克的臨床試驗（http://www.clinicaltrials.gov/ct/show/NCT00314704）。

雖然這一研究有其局限性，但至少說明，多巴胺已經不是什麼萬應藥。之所以有人提出疑問，進行對比研究，正是表明其副作用正在被人們注意。我已經十多年沒有在主流外科麻醉和危重醫學領域見到多巴胺了。

希望大家提高警惕。

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