PDF: EARLYDRAIN
(2023)Objective
To determine the effectiveness of early lumbar cerebrospinal fluid drainage added to standard of care in patients after aneurysmal subarachnoid hemorrhage
Study Summary
• Patients treated with lumbar drain had fewer secondary infarctions at discharge (28.5% vs 39.9%, P=0.04)
• Number needed to treat was 8.3 to prevent one unfavorable outcome
Intervention
Lumbar cerebrospinal fluid drainage at 5 mL per hour started within 72 hours of SAH and continued for up to 8 days, in addition to standard of care
Inclusion Criteria
Age ≥18 years, acute aneurysmal SAH diagnosed by CT with confirmed intracranial aneurysm, aneurysm treatment within 48 hours
Study Design
Arms: Lumbar drain (5 mL/hour for up to 8 days) vs Standard of care only
Patients per Arm: Lumbar drain n=144, Standard of care n=143
Outcome
• Secondary infarctions: 28.5% vs 39.9% (RR 0.71, 95% CI 0.49-0.99, P=0.04)
• Mortality at 6 months: 13.2% vs 17.5% (NS)
Bottom Line
In this pragmatic multicenter randomized trial of 287 patients with aneurysmal subarachnoid hemorrhage of all clinical grades, prophylactic lumbar drainage at 5 mL per hour for up to 8 days lessened the burden of secondary infarction and decreased the rate of unfavorable outcome at 6 months (32.6% vs 44.8%, RR 0.73, P=0.04). The number needed to treat was 8.3.
Major Points
- Pragmatic, multicenter, open-label RCT with blinded endpoint evaluation at 19 centers in Germany, Switzerland, and Canada
- Included 287 patients with aneurysmal SAH of all clinical grades (Hunt-Hess 1-5, WFNS 1-5)
- Lumbar drainage started at median day 2 after SAH at 5 mL/hour for up to 8 days
- Primary outcome (mRS 3-6 at 6 months) significantly reduced: 32.6% lumbar drain vs 44.8% standard care (RR 0.73, 95% CI 0.52-0.98, P=0.04)
- Secondary infarctions at discharge significantly reduced: 28.5% vs 39.9% (RR 0.71, 95% CI 0.49-0.99, P=0.04)
- No significant difference in vasospasm rates by clinical assessment, TCD, or angiography
- Patients in lumbar drain group had significantly lower intracranial pressure
- No difference in mortality at 6 months (13.2% vs 17.5%, NS)
- Consistent benefit across prespecified subgroups
- Per-protocol and as-treated sensitivity analyses confirmed findings
- Lumbar drainage more efficient at removing blood from basal cisterns due to gravity effect
Study Design
- Study Type
- Pragmatic, multicenter, parallel-group, open-label randomized clinical trial with blinded end point evaluation
- Randomization
- Yes
- Blinding
- Open-label for acute care providers, but blinded outcome assessment at 6 months by masked assessors; radiologists evaluating scans for secondary infarctions also blinded to treatment groups
- Sample Size
- 287
- Follow-up
- 6 months after hemorrhage
- Centers
- 19
- Countries
- Germany, Switzerland, Canada
Primary Outcome
Definition: Rate of unfavorable neurological outcome at 6 months after subarachnoid hemorrhage measured with modified Rankin Scale (mRS). mRS dichotomized to 0-2 (good outcome) or 3-6 (unfavorable outcome including death). Score obtained by investigator not involved in acute care and blinded to clinical course via telephone interview or personal visit.
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 64/143 (44.8%, 95% CI not specified) | 47/144 (32.6%, 95% CI not specified) | - (RR 0.73 (95% CI 0.52-0.98)) | P=0.04 |
Limitations & Criticisms
- Open-label design for acute care providers may introduce bias, though mitigated by blinded outcome assessment
- Significant crossover: 35 of 144 (24%) lumbar drain patients did not receive protocol-compliant treatment; 2 of 143 (1.4%) standard care patients received high-volume lumbar drainage
- Unable to secure sufficient funding for timely completion, prohibiting hiring of dedicated personnel
- No data collected on preexisting hypertension and other premorbid prognostic factors
- No detailed information on thickness of clots or amount of intraparenchymal/intraventricular blood on initial CT
- Did not record medical complications during clinical course
- Did not investigate additional application of clot thrombolysis or irrigation of subarachnoid space
- Unable to evaluate benefit of higher drainage rates than 5 mL/hour
- More than half of patients recruited from 2 centers, though investigators believe results are generalizable
- Baseline imbalances: higher proportion of WFNS grades 1-2 in lumbar drain group; less intracerebral and intraventricular hemorrhages in standard care group
- No adjustment for multiple testing on secondary endpoints - exploratory analyses only
- Secondary infarction detection mainly by CT, which is less sensitive than MRI
- Did not use current composite definition for delayed cerebral ischemia
Citation
JAMA Neurol. 2023;80(8):833-842