21. Pathophysiology of HRS
Increased splanchnic blood flow
Decreased central blood flow
Activation of vasoconstrictor system
Kidney vasoconstriction – decreased GFR
22. What is new in Pathophysiology of HRS?
•
Not only Circulatory dysfunction
but also Systemic inflammation
Bacterial translocation
39. How to give Terlipressin
• IV Bolus starting dose 0.5-1mg every 4-
6hr
• Maximum dose 2mg every 4hr in non-
responder (reduction of baseline Cr-
<25%)
• Continuous infusion of Terlipressin 2-
12mg/day
• (Single Study) as efficacious as Bolus
administration
• Lower rates of adverse effects
Standard Method
• Treatment should be maintained until complete response or maximum of 14days in
cases of partial or nonresponse
Alternative Method
42. Complete response or Partial response
• Complete response – Within 0.3 mg of patient baseline sCr
• Partial response – regression of AKI stage to a final SCr ≥0.3 mg/dl
of patient baseline sCr
• For a maximum of within 14 days
43. Side effects of Terlipressin
•
•
•
• Ischaemic complications have been reported in up to 45–46% of patients when the drug was
delivered by IV boluses.
• The rate of discontinuation because of side effects, mainly cardiovascular, is around 20%.
46. 40 patients with
HRS-1
N=20
NA 0.5-1mg/hr +
Albumin
N=20
Terlipressin 0.5-2mg
6hrly +Albumin
Until reversal or completion of 15 days of Tx
47. Results
•
•
•
Serum Creatinine Group A (NA) Group B (TP)
Day 4 2.4 ± 1.2 mg/dL 2.5 ± 1.5 mg/dL
Day 8 1.6 ± 1.2 mg/dL 1.8 ± 0.9 mg/dL
Day 15 1.0 ± 0.4 mg/dL 1.2 ± 0.5 mg/dL
Responders
48. 46 HRS-1
23
Terlipressin
23
NA
RCT,
India
2011
HRS reversal could be achieved in 9 (39.1%) patients in group A and 10 (43.4%) patients in group B
(p = 0.764).
Noradrenaline is as safe and effective as terlipressin, but less expensive in the treatment of HRS
50. Terlipressin vs Noradrenaline in HRS
RCT (New Delhi, India) 2016
• Terlipressin (2-12 mg/day; n = 60) • Noradrenaline (0.5-3.0 mg/h; n = 60).
Terlipressin Vs NA
• Compared to noradrenaline, terlipressin achieved
Greater day 4 (26.1% vs. 11.7%; p = 0.03)
Greater day 7 (41.7% vs. 20%; p = 0.01) response
51. Reversal of HRS was also better with terlipressin (40% vs. 16.7%; P = 0.004)
Significant reduction in the requirement of RRT (56.6% vs. 80%; P = 0.006)
and
Improved 28-day survival (48.3% vs. 20%; P = 0.001).
Adverse events limiting use of drugs were higher with terlipressin than
noradrenaline (23.3% vs. 8.3%; P = 0.02), but were reversible.
66. US data
2002-2010
LT centre
•
•
who received acute RRT <90days before LT
9% kidney non-recovery & need chronic RRT
2112 adult deceased-donor LT-alone recipients3.6 % renal non-recovery and need chronic RRT
Who did not received RRT before LT