SAFI Therapy Infusion Dose in ACLF
There is no standardized "SAFI therapy" recognized in major international liver disease guidelines; however, based on emerging research, response-guided Slow Albumin-Furosemide Infusion (SAFI) with vasoconstrictors uses albumin at standard doses (1.5 g/kg on day 1, then 1 g/kg on day 3) combined with furosemide, titrated to achieve urine sodium >80 mmol/day. 1
Understanding SAFI Protocol
The SAFI approach is not a guideline-endorsed therapy but represents an investigational strategy studied primarily in India for ACLF patients with significant ascites. The dosing framework derives from a single proof-of-concept study rather than established consensus recommendations. 1
Core Dosing Components
Albumin administration follows the standard dosing used for spontaneous bacterial peritonitis: 1.5 g/kg body weight on day 1, followed by 1 g/kg on day 3. 2 This albumin dosing is the only component with strong guideline support across multiple clinical scenarios in cirrhosis. 2
Furosemide is administered as a slow infusion alongside albumin, though specific dosing is not standardized in the available evidence. 1
Vasoconstrictors (terlipressin or norepinephrine) are added based on response, particularly when hepatorenal syndrome is present. 2, 1
Response-Guided Titration
The critical endpoint for SAFI therapy is achieving urine sodium >80 mmol/day, which serves as the marker of adequate response. 1 In the research cohort, all patients who failed to reach this urinary sodium threshold died, suggesting this is a crucial physiologic target. 1
Treatment continues until ascites is mobilized to grade 1 or less, typically requiring multiple days of therapy. 1
Important Clinical Caveats
SAFI is not mentioned in any major guideline (AASLD 2024, EASL 2018, Critical Care Medicine 2023) as a standard therapy for ACLF. 2 The evidence base consists of a single observational study with 136 patients in the intervention arm. 1
Standard ACLF management should take priority, including:
- Terlipressin (or norepinephrine) plus albumin for hepatorenal syndrome-AKI at standard doses 2
- Broad-spectrum antibiotics for infections 2
- Early liver transplant evaluation 2
Serious adverse events occurred in the SAFI study, including scrotal gangrene in 4 patients, highlighting the need for careful monitoring. 1
Alternative Established Therapies
For ascites management in ACLF, guidelines recommend:
- Large volume paracentesis with albumin replacement (6-8 g/L of ascites removed) 2
- Albumin infusion (1.5 g/kg day 1 g/kg day 3) for spontaneous bacterial peritonitis 2
- Vasoconstrictors plus albumin for hepatorenal syndrome 2
Extracorporeal liver support systems (MARS, Prometheus) have been studied in ACLF but showed no survival benefit in large randomized trials and are not recommended outside research protocols. 2, 3 The RELIEF trial with 189 patients found no significant survival difference with MARS therapy despite improvements in bilirubin and hepatic encephalopathy. 3
Practical Implementation Considerations
If considering SAFI based on the limited research evidence, the approach would involve:
- Day 1: Albumin 1.5 g/kg IV + furosemide infusion + terlipressin/norepinephrine if indicated
- Day 3: Albumin 1 g/kg IV + continued furosemide
- Daily monitoring: Urine sodium levels (target >80 mmol/day), ascites grade, hemodynamics
- Duration: Continue until ascites mobilization or lack of response by day 4-7
However, this protocol should only be considered in research settings or specialized centers, as it lacks validation in international guidelines and has potential for serious complications. 1 Standard evidence-based ACLF management with organ support, infection treatment, and transplant evaluation remains the priority. 2