Background

Blood loss and subsequent red blood cell transfusions are common in liver surgery. Hypovolaemic phlebotomy is associated with decreased red blood cell transfusion in observational studies. This trial aimed to investigate whether hypovolaemic phlebotomy is superior to usual care in reducing red blood cell transfusions in patients undergoing liver resection.

Methods

PRICE-2 was a multicentre, single-blind, superiority randomised controlled trial. Patients at a higher risk of blood loss undergoing liver resection for any indication at four Canadian academic tertiary-care hospitals were randomised to receive hypovolaemic phlebotomy or usual care. Hypovolaemic phlebotomy consisted of the removal of 7–10 mL/kg of whole blood, without volume replacement, before liver transection. Patients were randomised centrally using permuted blocks of randomly variable length, stratified by centre. The randomisation sequence was computer-generated by an independent statistician. Surgeons, patients, and outcome assessors were masked to treatment allocation. The primary outcome was perioperative red blood cell transfusion to 30 days post-randomisation, analysed in all randomly assigned patients who underwent liver resection. PRICE-2 trial was registered with ClinicalTrials.gov (NCT03651154) and is completed.

Findings

Between Oct 1, 2018, and Jan 13, 2023, 486 individuals were randomly assigned to receive hypovolaemic phlebotomy (n=245) or usual care (n=241). 22 individuals in the hypovolaemic phlebotomy group and 18 in the usual care group did not undergo liver resection and were thus excluded from the primary analysis population. 223 patients were included in the hypovolaemic phlebotomy group (mean age 61·4 years [SD 13·0]; 137 [61%] men) and 223 in the control group (62·1 years [12·1]; 114 [51%]). 17 (8%) of 223 patients allocated to hypovolaemic phlebotomy and 36 (16%) of 223 patients allocated to usual care had a perioperative red blood cell transfusion by 30 days (difference –8·8 percentage points [95% CI –14·8 to –2·8]; adjusted risk ratio [aRR] 0·47 [95% CI 0·27 to 0·82]). Severe complications to 30 days occurred in 37 (17%) patients allocated to hypovolaemic phlebotomy and 36 (16%) allocated to usual care (aRR 1·06 [95% CI 0·70–1·61]). Overall complications to 30 days occurred in 135 (61%) of 223 patients allocated to hypovolaemic phlebotomy and 116 (52%) of 223 patients allocated to usual care (1·08 [0·92–1·25]). There was no postoperative mortality to 90 days.

Interpretation

In patients undergoing liver resection, hypovolaemic phlebotomy reduced perioperative red blood cell transfusion and improved operative conditions, with no statistically significant increase in the incidence of complications compared with usual care. Hypovolaemic phlebotomy should be considered for routine use in patients undergoing liver resection at higher risk of bleeding.

Funding

Canadian Institutes of Health Research (PJT–156108).

中文翻译：

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失血风险较高的肝切除术患者的低血容量性静脉切开术 （PRICE-2）：一项随机对照试验

 背景

失血和随后的红细胞输注在肝脏手术中很常见。在观察性研究中，低血容量性静脉切开术与红细胞输注减少有关。该试验旨在探讨在减少肝切除术患者的红细胞输注方面，低血容量性静脉切开术是否优于常规护理。

 方法

PRICE-2 是一项多中心、单盲、优效性随机对照试验。在加拿大四家学术三级医院接受任何适应症肝切除术的失血风险较高的患者被随机分配接受低血容量性静脉切开术或常规护理。低血容量性静脉切开术包括在肝横切前去除 7-10 mL/kg 全血，无需补血量。患者使用随机可变长度的置换块集中随机分配，按中心分层。随机化序列由独立统计学家计算机生成。外科医生、患者和结果评估者对治疗分配不知情。主要结局是围手术期红细胞输注至随机分组后 30 天，对所有接受肝切除术的随机分配患者进行分析。PRICE-2 试验已在 ClinicalTrials.gov （NCT03651154） 注册并已完成。

 发现

在 2018 年 10 月 1 日至 2023 年 1 月 13 日期间，486 人被随机分配接受低血容量性静脉切开术 （n=245） 或常规护理 （n=241）。低血容量性静脉切开组 22 例和常规护理组 18 例未接受肝切除术，因此被排除在主要分析人群之外。低血容量性静脉切开组 223 例患者 （平均年龄 61·4 岁 [SD 13·0];137 [61%] 男性）和对照组 223 例 （62·1 岁 [12·1];114 [51%]）。分配到低血容量性静脉切开术的 223 名患者中有 17 名 （8%） 和分配到常规治疗的 223 名患者中有 36 名 （16%） 在 30 天前接受了围手术期红细胞输注（差异 -8·8 个百分点 [95% CI -14·8 至 -2·8];调整后风险比 [aRR] 0·47 [95% CI 0·27 至 0·82]）。37 例 （17%） 分配到低血容量性静脉切开术组的患者和 36 例 （16%） 分配到常规护理组的患者发生 30 天严重并发症 （aRR 1·06 [95% CI 0·70–1·61]）。分配到低血容量性静脉切开术的 223 名患者中有 135 名 （61%） 发生到 30 天的总体并发症，分配到常规护理组的 223 名患者中有 116 名 （52%） 发生 （1·08 [0·92–1·25]）。术后 90 天无死亡率。

 解释

在接受肝切除术的患者中，低血容量性静脉切开术减少了围手术期红细胞输注并改善了手术条件，与常规护理相比，并发症的发生率没有统计学意义增加。对于出血风险较高的接受肝切除术的患者，应考虑常规使用低血容量性静脉切开术。

 资金

加拿大卫生研究院 （PJT–156108）。