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）的治疗方案的安全性与可行性。
研究设计：非随机单臂干预试验。
研究地点：孟加拉国达卡国家神经科学研究所及医院。
研究对象：20名成年（≥18岁）吉兰-巴雷综合征患者，发病后2周内出现肌无力症状，且无法独立行走超过10米。
干预措施：小容量血浆置换指在血袋中完成血细胞沉降，待血细胞回输后移除上清血浆。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）定义为与小容量血浆置换术中使用的中心静脉导管（central vein catheter, CVC）相关的严重脓毒症及深静脉血栓形成。若20名患者中严重不良事件发生数少于5例，则认为小容量血浆置换安全；若20名患者中至少15例可在8天内完成8L血浆置换量，则认为其具备可行性。
研究结果：患者年龄中位数为33岁（四分位间距23~46，范围18~55）；其中13名（65%）为男性。医学研究委员会总评分中位数为20分（四分位间距0~29，范围0~36）；3名（15%）患者需接受机械通气。1名患者出现严重不良事件（严重脓毒症，可能与中心静脉导管相关）。轻微不良反应包括：10名（50%）患者出现一过性低血压；10名（50%）出现中心静脉导管相关出血；4名（20%）出现新鲜冰冻血浆输血反应；4名（20%）出现低白蛋白血症、贫血或电解质紊乱。15名（75%）患者可完成8L血浆置换量。开始小容量血浆置换后4周，14名（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：对于吉兰-巴雷综合征患者，小容量血浆置换似乎是标准血浆置换或静脉注射免疫球蛋白的安全可行替代治疗方案；未来有必要在资源匮乏的发展中国家开展其临床疗效相关研究。
试验注册：2016年5月23日于Clinicaltrials.gov注册，编号NCT02780570。
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简便，相较传统免疫治疗方案（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具备安全性与可行性。3. 本研究固有局限性为非随机单臂研究设计，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为次要终点评估，因此未来有必要开展随机对照试验以评估其临床疗效。