PDF: Goal-Directed Hemodynamic Therapy After SAH
(2020)Objective
To assess whether goal-directed hemodynamic therapy (GDHT), compared to standard clinical care, reduces the rate of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage
Study Summary
• The benefit persisted after adjustment for confounders.
• This is the first RCT showing that GDHT using transpulmonary thermodilution with algorithms focusing on normovolemia and induced hypertension improves outcomes after SAH without increasing complications.
• The approach achieved better hemodynamic targets without increased fluid volume, suggesting more efficient rather than excessive fluid administration.
Intervention
GDHT using transpulmonary thermodilution (PiCCO2) with predefined algorithms targeting normovolemia (MAP >70 mmHg, CPP >60 mmHg, CVP >4 mmHg, GEDI ≥640 mL/m², cardiac index ≥2.5 L/min/m²) and induced hypertension (MAP 100-120 mmHg) if vasospasm present vs standard care for 10-14 days
Inclusion Criteria
Age >18 years, aneurysmal SAH diagnosed by CT and confirmed by angiography
Study Design
Arms: GDHT vs Standard care
Patients per Arm: GDHT: 54, Control: 54
Outcome
Bottom Line
Goal-directed hemodynamic therapy significantly reduced delayed cerebral ischemia after SAH (13% vs 32%, p=0.021) and improved functional outcomes at 3 months (GOS=5: 66% vs 44%, p=0.025). The benefit persisted after adjustment for confounders. This is the first RCT showing that GDHT using transpulmonary thermodilution with algorithms focusing on normovolemia and induced hypertension improves outcomes after SAH without increasing complications. The approach achieved better hemodynamic targets without increased fluid volume, suggesting more efficient rather than excessive fluid administration.
Major Points
- Single-center prospective randomized controlled trial with blinded outcome assessment
- 108 patients enrolled between March 2013 and December 2015 (54 per group)
- GDHT used transpulmonary thermodilution (PiCCO2) with predefined algorithms for 10-14 days
- Primary outcome (DCI) significantly reduced: GDHT 13% vs control 32% (OR 0.324, 95% CI 0.11-0.86, p=0.021)
- GDHT superior after adjustment for confounders (HR 2.84, 95% CI 1.18-6.86, p=0.02)
- Favorable functional outcome (GOS=5) at 3 months: GDHT 66% vs control 44% (p=0.025)
- DCI occurred on median day 5 (4-8), vasospasm on day 4 (3-6)
- Vasospasm rates similar between groups (GDHT 50% vs control 59%, p=0.334)
- All 24 patients who developed DCI had vasospasm
- Cerebral edema trend: GDHT 15% vs control 30% (p=0.064, not significant)
- Infarctions other than DCI: GDHT 2% vs control 11% (p=0.051, not significant)
- Hyponatremia significantly lower in GDHT: 11% vs 31% (p=0.010)
- No difference in overall fluid intake between groups (median ~2900-3000 mL/day)
- Higher norepinephrine use in control group (1.08±1.81 vs 0.27±0.65 µg/min, p=0.013)
- Higher MAP and GEDI achievement rates in GDHT group during phases without vasospasm
- Early fluid balance higher in control group on days 1-3 (p=0.017)
- No difference in ICU length of stay, hospital stay, or mortality
- No serious adverse events attributed to GDHT intervention
Study Design
- Study Type
- Prospective, randomized, controlled, parallel-group, single-center clinical trial
- Randomization
- Yes
- Blinding
- Single-blind. Computer-generated randomization list. Physicians and nurses aware of group assignment. Outcome assessors blinded to treatment allocation. Neurosurgeon blinded to group assignment evaluated in-hospital outcomes. Functional outcome (GOS) at 3 months assessed by neurosurgical consultant unaware of group assignment or by telephone contact
- Sample Size
- 108
- Follow-up
- 3 months
- Centers
- 1
- Countries
- Germany
Primary Outcome
Definition: Delayed cerebral ischemia (DCI) defined as new focal neurological deficit or cerebral infarction in presence of vasospasm on radiological imaging. ≥2-point decrease in GCS or 2-point increase in NIHSS lasting ≥8 hours used for detecting DCI. Other causes excluded (hydrocephalus, rebleeding, seizures, metabolic impairment, procedure-related infarctions)
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 17/54 (32%) | 7/54 (13%) | Hazard ratio 2.84 after adjustment (OR 0.324 (95% CI 0.11-0.86); Adjusted HR (95% CI 1.18-6.86)) | 0.021 (unadjusted); 0.02 (adjusted Cox regression) |
Limitations & Criticisms
- Single-center study - limits generalizability to other clinical settings
- Unblinded treatment allocation - physicians and nurses aware of group assignment
- Potential for detection bias and performance bias
- No independent data and safety monitoring board
- Discharge criteria not predefined - may influence length-of-stay interpretation
- Study does not investigate mechanisms underlying DCI development
- Does not assess microcirculation parameters directly
- Performed by skilled team - adoption into daily practice elsewhere not tested
- Sample size of 108 may be underpowered for some secondary outcomes
- No assessment of long-term outcomes beyond 3 months
- One patient lost to 3-month follow-up in GDHT group
- Multiple comparisons in secondary outcomes without adjustment
- Difference in arterial hypertension at baseline (GDHT 57% vs control 37%, p=0.034)
- Digital data not readable in 4 GDHT and 6 control patients
- No standardized protocol for when physicians could deviate from algorithms
- Early fluid balance significantly different in days 1-3 (p=0.017) suggesting groups managed differently early on
- Vasospasm still occurred in 50% of GDHT patients - no reduction vs control 59%
- Mechanism of benefit unclear - similar MAP, GEDI, ELWI between groups in most phases
- Goal achievement rates lower in late vasospasm phase for GEDI in GDHT group
- Cardiac index actually higher in control group in late vasospasm phase
Citation
Stroke. 2020;51:2287-2296