The NEWS –NEW Science in Neurocritical Care
June 2014
Defining the optimal global end-diastolic volume index in SAH in a multicenter cohort
Tagami T, Kuwamoto K, Watanabe A, et al. Optimal range of global end-diastolic volume for fluid management after aneurysmal subarachnoid hemorrhage: a multicenter prospective cohort study. Crit Care Med 2014;42:1348-56
Summary
This study is based on the assumptions (as suggested by prior literature) that global end-diastolic volume index (GEDI) directly measures cardiac preload as a combination of end-diastolic volumes of all four cardiac chambers. Also, the authors assume that extravascular lung water index (ELWI) indicates the amount of pulmonary edema present in the lungs. In this multicenter prospective cohort study, the authors utilized pulse contour cardiac output (PiCCO) monitoring to determine whether GEDI is correlated with delayed cerebral ischemia (DCI) and pulmonary edema (PE) after aneurysmal subarachnoid hemorrhage (aSAH). They also sought to determine the GEDI threshold for appropriate fluid management. At nine Japanese university hospitals, 180 aSAH patients were included. Treatment occurred according to aSAH guidelines. PiCCO monitoring occurred in all patients. DCI was defined as symptomatic vasospasm, infarction due to vasospasm or both. Severe PE was defined as ELWI > 14ml/kg, which was two SD above the reference value in a previous neurogenic PE study. Mean values were calculated for four phases: days 1-3, days 4-7, days 8-10 and days 11-14 post SAH. The primary endpoint DCI and severe
PE within 14 days of SAH was reached in 35 (19.4%) and 47 (26.1%) of patients, respectively.
In this cohort, SAH severity (per WFNS and Fisher group) did not correlate with DCI for unknown reasons. There was no difference in the net total fluid balance during the 14 days between DCI and non-DCI patients, or PE and non-PE patients, but the mean positive fluid balance in phase 1 was higher in the DCI vs. non-DCI group (731±170ml vs. 304±64ml; p=0.01). The median age was higher for the PE group (67y) than non-PE group (62y; p=0.01) with median day of occurrence on day 6 (4-9d). Both DCI and PE developed in 4 patients (2%).
There was a significant difference in GEDI between the DCI and non-DCI patients in phase 1
(739±44 vs. 895±31ml/m
2
; p=0.04) and phase 2 (783±25 vs. 870±14ml/m
2
; p=0.007). In Phase 2
(but no other phases), GEDI was independently associated with DCI (hazard ratio for every
100ml/m
2
increase 0.72; 95% CI 0.58-0.91; p=0.006) and PE (hazard ratio 1.31; 95% CI 1.02-
1.71; p=0.03). Using ROC curves, the GEDI threshold best associated with DCI was 822ml/m
2
(73% sensitivity, 64% specificity, AUC 0.66). At 14 days, the low GEDI group (below this threshold) had a higher prevalence of DCI than the high GEDI group (31.6% vs. 94%; p<0.001).
There were no differences in GEDI in the PE or non-PE group when averaged over the study period, but GEDI was higher in the PE group than non-PE group in each phase. The GEDI
2 threshold associated with severe PE was 921 ml/m (72% sensitivity, 71% specificity, AUC
0.77). The prevalence of severe PE was higher in the high-GEDI vs. low-GEDI group (43.6% vs.
17.9%; p<0.001).
Commentary
Determined in a large multicenter cohort, this study for the first time reports quantifiable thresholds for fluid management in aSAH patients.
These findings are particularly important now after the reliability of CVP has been disproven in high quality studies, and pulmonary artery

catheters are rarely used (and also not considered reliable), thereby leading to recommendations against their use by the NCS SAH guideline. The findings may be used at the bedside as indicators “when to stop fluids”. The reported thresholds, however, rely on assumptions and
PiCCO internal algorithms that may not be applicable to all aSAH patients. For example, the authors did not report on the rates of stress cardiomyopathy. Also, CXR or hypoxemia was not used to define PE. While statistical significance was only found in phase 2, this may be due to the fact that the majority of DCI and PE occurrences were during this phase. AUC values were low, suggesting that GEDI alone does not explain the difference in DCI or PE occurrence. The definition of DCI was not in line with most aSAH studies, and SAH-severity did not correlate with DCI, questioning further the authors’ definition of DCI. Confirmation of these findings with the more widely accepted DCI definition should be undertaken.
Susanne Muehlschlegel, MD, MPH
Neurocritical Care
Departments of Neurology, Anesthesia/Critical Care and Surgery
University of Massachusetts Medical School
Worcester, MA