Abstract

Importance

After aneurysmal subarachnoid hemorrhage, the use of lumbar drains has been suggested to decrease the incidence of delayed cerebral ischemia and improve long-term outcome.

Objective

To determine the effectiveness of early lumbar cerebrospinal fluid drainage added to standard of care in patients after aneurysmal subarachnoid hemorrhage.

Design, Setting, and Participants

The EARLYDRAIN trial was a pragmatic, multicenter, parallel-group, open-label randomized clinical trial with blinded end point evaluation conducted at 19 centers in Germany, Switzerland, and Canada. The first patient entered January 31, 2011, and the last on January 24, 2016, after 307 randomizations. Follow-up was completed July 2016. Query and retrieval of data on missing items in the case report forms was completed in September 2020. A total of 20 randomizations were invalid, the main reason being lack of informed consent. No participants meeting all inclusion and exclusion criteria were excluded from the intention-to-treat analysis. Exclusion of patients was only performed in per-protocol sensitivity analysis. A total of 287 adult patients with acute aneurysmal subarachnoid hemorrhage of all clinical grades were analyzable. Aneurysm treatment with clipping or coiling was performed within 48 hours.

Intervention

A total of 144 patients were randomized to receive an additional lumbar drain after aneurysm treatment and 143 patients to standard of care only. Early lumbar drainage with 5 mL per hour was started within 72 hours of the subarachnoid hemorrhage.

Main Outcomes and Measures

Primary outcome was the rate of unfavorable outcome, defined as modified Rankin Scale score of 3 to 6 (range, 0 to 6), obtained by masked assessors 6 months after hemorrhage.

Results

Of 287 included patients, 197 (68.6%) were female, and the median (IQR) age was 55 (48-63) years. Lumbar drainage started at a median (IQR) of day 2 (1-2) after aneurysmal subarachnoid hemorrhage. At 6 months, 47 patients (32.6%) in the lumbar drain group and 64 patients (44.8%) in the standard of care group had an unfavorable neurological outcome (risk ratio, 0.73; 95% CI, 0.52 to 0.98; absolute risk difference, −0.12; 95% CI, −0.23 to −0.01; P = .04). Patients treated with a lumbar drain had fewer secondary infarctions at discharge (41 patients [28.5%] vs 57 patients [39.9%]; risk ratio, 0.71; 95% CI, 0.49 to 0.99; absolute risk difference, −0.11; 95% CI, −0.22 to 0; P = .04).

Conclusions and Relevance

In this trial, prophylactic lumbar drainage after aneurysmal subarachnoid hemorrhage lessened the burden of secondary infarction and decreased the rate of unfavorable outcome at 6 months. These findings support the use of lumbar drains after aneurysmal subarachnoid hemorrhage.

Key Points

Question Does prophylactic lumbar cerebrospinal fluid drainage improve clinical outcomes measured by the modified Rankin Scale score among patients with aneurysmal subarachnoid hemorrhage?

Findings In this pragmatic randomized clinical trial including 287 patients at 19 sites in 3 countries, the rate unfavorable neurologic outcome was 32.6% in the lumbar drainage group (47 of 144) and 44.8% in the standard of care group (64 of 143), a significant difference.

Meaning  In this trial, among patients with aneurysmal subarachnoid hemorrhage, lumbar drainage improved clinical neurological outcomes at 6 months.

요약

소개

예방적 요추 배액(prophylactic lumbar drainage)이 뇌동맥류 파열에 의한 지주막하 출혈(aneurysmal subarachnoid hemorrhage) 후 지연성 뇌허혈(delayed cerebral ischemia)의 발생률을 감소시키고 장기적인 결과를 개선할 수 있다고 제안되고 있다. 이에 따라, 이 연구는 뇌동맥류 파열 후 표준 치료에 조기 예방적 요추 뇌척수액 배액을 추가했을 때의 임상적 효과의 개선을 평가하는 것을 목표로 한다.

방법

이 EARLYDRAIN 연구는 독일, 스위스 및 캐나다의 19개 센터에서 수행된 실용적인 다기관, 병행군, 오픈라벨 무작위 임상 시험으로, 결과 평가자는 블라인드 방식으로 진행되었다.

총 144명의 환자가 뇌동맥류 치료 후 추가적인 요추 배액을 받는 그룹에 무작위 배정되었고, 143명의 환자는 표준 치료군에 배정되었다. 조기 요추 배액은 출혈 후 72시간 이내에 시간당 5mL의 속도로 시행되었다.

주요 임상결과(primary outcome)은 치료 6개월 후 평가된 mRS 점수로, 좋지 않은 결과인 mRS 3~6점인 환자의 비율로 설정하였다.

결과

1. 치료 6개월 후, 요추 배액 그룹에서는 47명(32.6%)이, 표준 치료 그룹에서는 64명(44.8%)이 좋지 않은 신경학적 결과를 보였다.

2. 요추 배액을 받은 환자 그룹은 퇴원 시 이차 경색의 비율이 더 적었다.

결론 및 의의

이 연구에서는 뇌동맥류 파열 후 예방적 요추 배액이 이차 경색의 발생을 줄이고 6개월 후 좋지 않은 임상적 결과의 비율을 감소시켰음을 보여주었다. 이러한 결과는 뇌동맥류 파열 후 요추 배액의 사용을 지지하는 근거로 사용될 수 있다.