Association of Fluid Balance and Hemoglobin Decline With Neurological Outcome After Aneurysmal Subarachnoid Hemorrhage

Abstract

Objectives: To explore the relationship between fluid balance and hemoglobin decline with secondary infarctions and neurologic outcome in aneurysmal subarachnoid hemorrhage (aSAH) patients.

Design: Secondary analysis of the Earlydrain trial, a prospective randomized controlled study investigating prophylactic lumbar drain use in aSAH patients.

Setting: Patients with aSAH treated in ICUs at 19 tertiary hospitals in Germany, Switzerland, and Canada.

Patients: From January 2011 to January 2016, 287 patients were enrolled in the Earlydrain trial. Only files with complete information on both daily hemoglobin and balance values were used, leaving 237 patients for analysis.

Interventions: Investigation of fluid balance management and hemoglobin levels during the initial 8 days post-aSAH to establish thresholds for unfavorable outcomes and assess their impact on secondary infarctions and 6-month neurologic outcome on the modified Rankin Scale (mRS).

Measurements and main results: Patients with unfavorable outcome after 6 months (mRS > 2) showed greater hemoglobin decline and increased cumulative fluid balance. A significant inverse relationship existed between fluid balance and hemoglobin decline. Thresholds for unfavorable outcome were 10.4 g/dL hemoglobin and 4894 mL cumulative fluid balance in the first 8 days. In multivariable analysis, fluid balance, but not fluid intake, remained significantly associated with unfavorable outcome, while the influence of hemoglobin lessened. Fluid balance but not hemoglobin related to secondary infarctions, with the effect being significant after inverse probability of treatment weighting. Transfusion was associated with unfavorable outcomes.

Conclusions: Increased fluid balance influences hemoglobin decline through hemodilution. Fluid overload, rather than a slight decrease in hemoglobin levels, appears to be the primary factor contributing to poor outcomes in aSAH patients. The results suggest aiming for euvolemia and that a modest hemoglobin decline may be tolerated. It may be advisable to adopt a restrictive approach to transfusions, as they can potentially have a negative effect on outcome.

Trial registration: ClinicalTrials.gov NCT01258257.

Figure 1.

Hemoglobin, fluid balance, and fluid intake trends. Hemoglobin trend (A), cumulative fluid balance (B), and cumulative fluid intake (C) in patients grouped by the modified Rankin Scale (mRS) score after 6 mo (dashed and dash-dotted lines) as well as in patients grouped by the dichotomized mRS score (0–2 vs. 3–6) after 6 mo (solid lines with confidence bands; daily means shown as blue dots [mRS, 0–2] and red triangles [mRS, 3–6]).

Figure 2.

Correlation of fluid intake and balance with hemoglobin (hb) levels. Correlation of cumulative fluid balance (A) and cumulative fluid intake (B) with lowest hb level grouped by the dichotomized modified Rankin Scale (mRS) score 6-mo post-subarachnoid hemorrhage (0–2 vs. 3–6).

Figure 3.

Fluid balance and hemoglobin (hb) thresholds for worse neurological outcome and secondary infarctions. Receiver operator characteristic curves determining threshold of lowest hb level (g/dL) recorded during the first 8 d after aneurysmal subarachnoid hemorrhage (aSAH) (area under the curve [AUC], 62.8%) (A) and cumulative fluid balance (mL) 8 d after aSAH (AUC, 69.2%) predicting poor neurologic outcome with modified Rankin Scale (mRS) scores greater than 2 (B). Receiver operating characteristic curves determining threshold of lowest hb level (g/dL; AUC, 60.9%) (C) and cumulative fluid balance (mL) 8 d after aSAH (AUC, 65.3%) predicting secondary infarctions after aSAH (D).