Data from: Small volume plasma exchange for Guillain-Barré syndrome in resource-limited settings: a phase II safety and feasibility study

OBJECTIVE: To assess the safety and feasibility of small volume plasma exchange (SVPE) as an alternative to standard plasma exchange (PE) or intravenous immunoglobulin (IVIg) for Guillain-Barré syndrome (GBS) patients. DESIGN: Non-randomized, single arm, interventional trial. SETTING: National Institute of Neurosciences and Hospital, Dhaka, Bangladesh. PARTICIPANTS: Twenty adult (>18 years) patients with GBS presented within 2 weeks of onset of weakness who were unable to walk unaided for more than 10 meters. INTERVENTIONS: SVPE involves blood cell sedimentation in a blood bag and removal of supernatant plasma after blood cells are re-transfused. This procedure was repeated three to six times a day, for eight consecutive days. OUTCOME MEASURES: Serious adverse events (SAE) were defined as severe sepsis and deep venous thrombosis related to the central vein catheter (CVC) used during SVPE. SVPE was considered safe if less than 5/20 patients experienced a SAE, and feasible if 8 L plasma could be removed within 8 days in at least 15/20 patients. RESULTS Median patient age 33 years (IQR 23-46; range 18-55); 13 (65%) were male. Median MRC sum score was 20 (IQR 0-29; range 0-36); three (15%) patients required mechanical ventilation. One patient developed SAE (severe sepsis, possibly related to CVC). Minor adverse effects were transient hypotension in 10 (50%) patients; CVC-associated bleeding in 10 (50%); transfusion reaction to fresh frozen plasma in 4 (20%); and hypo-albuminemia, anaemia or electrolyte imbalance in 4 (20%). Removal of 8 L plasma was possible in 15 (75%) patients. GBS disability score improved by at least one grade in 14 (70%) patients four weeks after SVPE started. No patients died. CONCLUSION: SVPE seems a safe and feasible alternative treatment to standard PE or IVIg for GBS; further studies of clinical efficacy in low-resource developing countries are warranted. TRIAL REGISTRATION: Clinicaltrials.gov NCT02780570 on May 23, 2016. Strength and limitations of the study: 1. The strength of this study underlies the novel and simple technique of SVPE, which is much less expensive than conventional immunotherapies (plasma exchange and intravenous immunoglobulin). 2. SVPE is corroborated as safe and feasible for the first time in a prospective and standardized cohort of patients with Guillain-Barré syndrome (GBS). 3. The intrinsic limitations of this study are its non-randomized, single arm nature, which is conducted in a single center with a limited sample size of GBS patients. 4. Clinical efficacy of SVPE on patients with GBS was a secondary end-point assessment and therefore deserves a randomized controlled trial in future to assess the clinical efficacy of SVPE for the patients with GBS.

研究目的：评估小容量血浆置换（small volume plasma exchange, SVPE）作为吉兰-巴雷综合征（Guillain-Barré syndrome, GBS）患者替代标准血浆置换（standard plasma exchange, PE）或静脉注射免疫球蛋白（intravenous immunoglobulin, IVIg）治疗方案的安全性与可行性。
研究设计：非随机单臂干预性试验。
研究机构：孟加拉国达卡国立神经科学研究所及附属医院。
研究对象：20名成年（年龄≥18岁）吉兰-巴雷综合征患者，发病2周内出现肢体无力，且无法独立行走超过10米。
干预措施：小容量血浆置换（SVPE）指将血液置于血袋中进行细胞沉降，待血细胞回输后去除上层血浆。该操作每日重复3~6次，连续进行8天。
结局指标：严重不良事件（serious adverse events, SAE）定义为与SVPE术中使用的中心静脉导管（central vein catheter, CVC）相关的重度脓毒症及深静脉血栓形成。若20例患者中严重不良事件发生数少于5例，则认为SVPE安全；若20例患者中至少15例可在8天内完成8L血浆置换量，则认为SVPE可行。
研究结果：患者中位年龄33岁（四分位间距23~46岁，年龄范围18~55岁）；其中13例（65%）为男性。中位医学研究委员会（Medical Research Council, MRC）总评分20分（四分位间距0~29分，范围0~36分）；3例（15%）患者需机械通气。1例患者发生严重不良事件（重度脓毒症，可能与中心静脉导管相关）。轻度不良事件包括：10例（50%）出现一过性低血压；10例（50%）出现中心静脉导管相关出血；4例（20%）出现新鲜冰冻血浆（fresh frozen plasma）输血反应；4例（20%）出现低白蛋白血症（hypo-albuminemia）、贫血（anaemia）或电解质紊乱（electrolyte imbalance）。15例（75%）患者可完成8L血浆置换量。SVPE启动后4周，14例（70%）患者的吉兰-巴雷综合征残疾评分至少提升1个等级。无患者死亡。
研究结论：相较于标准血浆置换或静脉注射免疫球蛋白，小容量血浆置换似乎是吉兰-巴雷综合征患者安全且可行的替代治疗方案；有必要在资源匮乏的发展中国家开展进一步临床疗效研究。
试验注册：Clinicaltrials.gov注册号NCT02780570，注册日期2016年5月23日。
研究优势与局限性：1. 本研究的优势在于其采用的小容量血浆置换技术新颖且操作简便，相较于传统免疫治疗方案（血浆置换与静脉注射免疫球蛋白）成本显著更低。2. 本研究首次在标准化前瞻性吉兰-巴雷综合征患者队列中证实小容量血浆置换的安全性与可行性。3. 本研究固有局限性为非随机单臂设计，且仅在单中心开展，样本量有限。4. 小容量血浆置换对吉兰-巴雷综合征患者的临床疗效仅作为次要终点评估，因此未来有必要开展随机对照试验以进一步验证其临床疗效。