臨床研究 輸血 Cardiac Surgery Hb 7.5 g/dL vs 9.0 g/dL

Liberal or restrictive transfusion after cardiac surgery.
Murphy GJ, Pike K, Rogers CA, Wordsworth S, Stokes EA, Angelini GD, Reeves BC; TITRe2 Investigators. Collaborators (79)
N Engl J Med. 2015 Mar 12;372(11):997-1008. doi: 10.1056/NEJMoa1403612.

＜松田直之 コメント＞
日本では，白血球除去製剤として赤血球製剤（MAP製剤）が使用できます。
特に，心機能低下症例では，酸素需給の適正化のために，Hb 10g/dLレベルのHb濃度を維持することが大切と考えます。

BACKGROUND:
Whether a restrictive threshold for hemoglobin level in red-cell transfusions, as compared with a liberal threshold, reduces postoperative morbidity and health care costs after cardiac surgery is uncertain.
METHODS:
We conducted a multicenter, parallel-group trial in which patients older than 16 years of age who were undergoing nonemergency cardiac surgery were recruited from 17 centers in the United Kingdom. Patients with a postoperative hemoglobin level of less than 9 g per deciliter were randomly assigned to a restrictive transfusion threshold (hemoglobin level <7.5 g per deciliter) or a liberal transfusion threshold (hemoglobin level <9 g per deciliter). The primary outcome was a serious infection (sepsis or wound infection) or an ischemic event (permanent stroke [confirmation on brain imaging and deficit in motor, sensory, or coordination functions], myocardial infarction, infarction of the gut, or acute kidney injury) within 3 months after randomization. Health care costs, excluding the index surgery, were estimated from the day of surgery to 3 months after surgery.
<font size="3">RESULTS:
A total of 2007 patients underwent randomization; 4 participants withdrew, leaving 1000 in the restrictive-threshold group and 1003 in the liberal-threshold group. Transfusion rates after randomization were 53.4% and 92.2% in the two groups, respectively. The primary outcome occurred in 35.1% of the patients in the restrictive-threshold group and 33.0% of the patients in the liberal-threshold group (odds ratio, 1.11; 95% confidence interval [CI], 0.91 to 1.34; P=0.30); there was no indication of heterogeneity according to subgroup. There were more deaths in the restrictive-threshold group than in the liberal-threshold group (4.2% vs. 2.6%; hazard ratio, 1.64; 95% CI, 1.00 to 2.67; P=0.045). Serious postoperative complications, excluding primary-outcome events, occurred in 35.7% of participants in the restrictive-threshold group and 34.2% of participants in the liberal-threshold group. Total costs did not differ significantly between the groups.
CONCLUSIONS:
A restrictive transfusion threshold after cardiac surgery was not superior to a liberal threshold with respect to morbidity or health care costs. (Funded by the National Institute for Health Research Health Technology Assessment program; Current Controlled Trials number, ISRCTN70923932.).





参考資料

Transfusion Indication Threshold Reduction (TITRe2) randomized controlled trial in cardiac surgery: statistical analysis plan.
Pike K, Nash RL, Murphy GJ, Reeves BC, Rogers CA.
Trials. 2015 Dec;16(1):564. doi: 10.1

Restrictive versus liberal transfusion strategy for red blood cell transfusion: systematic review of randomised trials with meta-analysis and trial sequential analysis.
Holst LB, Petersen MW, Haase N, Perner A, Wetterslev J.
BMJ. 2015 Mar 24;350:h1354. doi: 10.1136/bmj.h1354.

総説 線維化と多臓器不全

Fibrosis--a common pathway to organ injury and failure.
Rockey DC, Bell PD, Hill JA.
N Engl J Med. 2015;372:1138-49.

＜松田直之 コメント＞
現在，当講座が全身管理として注目している病態は，炎症後の臓器内線維症です。
この診療および研究が重要と評価し，特に線維芽細胞のリセッティングをターゲットとした研究も推進中です。
救急・集中治療領域における新規病態学・創薬のターゲットと考えています。
炎症を軽減する方策を戦略化一方で，炎症後の線維化増強を正常化させるのです。
当講座は，2015年春季抄読会で，この総説を取り上げる予定です。

Disease-related injury in any organ triggers a complex cascade of cellular and molecular responses that culminates in tissue fibrosis. Although this fibrogenic response may have adaptive features in the short term, when it progresses over a prolonged period of time, parenchymal scarring and ultimately cellular dysfunction and organ failure ensue.

We and others have proposed four major phases of the fibrogenic response. First is initiation of the response, driven by primary injury to the organ. The second phase is the activation of effector cells, and the third phase is the elaboration of extracellular matrix, both of which overlap with the fourth phase, during which the dynamic deposition (and insufficient resorption) of extracellular matrix promotes progression to fibrosis and ultimately to end-organ failure.

The fact that diverse diseases in different organ systems are associated with fibrotic changes suggests common pathogenic pathways. This “wounding response” is orchestrated by complex activities within different cells in which specific molecular pathways have emerged. Cellular constituents include inflammatory cells (e.g., macrophages and T cells), epithelial cells, fibrogenic effector cells, endothelial cells, and others. Many different effector cells, including fibroblasts, myofibroblasts, cells derived from bone marrow, fibrocytes, and possibly cells derived from epithelial tissues (epithelial-to-mesenchymal transition) have been identified; there is some controversy regarding the identity of specific effectors in different organs. Beyond the multiple cells essential in the wounding response, core molecular pathways are critical; for example, the transforming growth factor beta (TGF-β) pathway is important in virtually all types of fibrosis.

As fibrosis progresses, myofibroblasts proliferate and sense physical and biochemical stimuli in the local environment by means of integrins and cell-surface molecules; contractile mediators trigger pathological tissue contraction. This chain of events, in turn, causes physical organ deformation, which impairs organ function. Thus, the biology of fibrogenesis is dynamic, although the degree of plasticity appears to vary from organ to organ.

Although we understand many of the cellular and molecular processes underlying fibrosis, there are few effective therapies and fewer that target fibrogenesis specifically. These facts highlight the need for a deeper comprehension of the pathogenesis of fibrogenesis and the translation of this knowledge to novel treatments.

総説 糖尿病性ケトアシドーシス

Acid-base problems in diabetic ketoacidosis.
Kamel KS, Halperin ML.
N Engl J Med. 2015;372:546-54.

＜松田直之 コメント＞
我々の救急・集中治療部にも，年間で4例程度の重症な糖尿病性ケトアシドーシスの搬入があります。
とても良く記載されている素晴らしい総説です。

This review focuses on three issues facing clinicians who care for patients with diabetic ketoacidosis; all of the issues are related to acid–base disorders. The first issue is the use of the plasma anion gap and the calculation of the ratio of the change in this gap to the change in the concentration of plasma bicarbonate in these patients; the second concerns the administration of sodium bicarbonate; and the third is the possible contribution of intracellular acidosis to the development of cerebral edema, particularly in children with diabetic ketoacidosis. In this article, we examine the available data and attempt to integrate the data with principles of physiology and metabolic regulation and provide clinical guidance.










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2015年3月27日　松田直之

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記載：2015年3月27日，追記：2020年4月5日