202207112346

Status: #idea

Vasopressin

Background

Vasopressin is a non-catecholaminergic nonapeptide with activity on vasopressin V1 (vascular smooth muscle contraction) and V2 (antidiuretic effects) receptors

Vasoconstrictor effects are seen at higher plasma concentrations (10–200 pg/ml)

Vasopressin leads to inactivation of K-ATP channels, potentiates the effects of catecholamines and reduces iNOS production

Receptors

V1 = V1a

acting on vascular smooth muscle cell
→ vasoconstriction

V2

acting on renal collecting ducts
→ antidiuretic effect → free water resorption

release vWF & F8

V3 = V1b

pituitary stimulation → ACTH production

(cross reactivity with oxytocin)

Analogues

Vials: synthetic vasopressin

desmopressin

= DDAVP (brand name)
synthetic analogue of ADH
D-arginine for L-arginine at position 8; position 1 deaminated
→ V2 specificity
for DI, vWF & F8

Terlipressin

V1 specificity

V1/V2 ratio ~2.2
- (cf vasopressin 1:1)
  longer acting
  labelled for HRS

Trauma

AVERT shock trial

Septic shock

2021 SSC guidelines note that: initiating vasopressin when the patient requires between 0.25 - 0.5 μg/kg/min of norepinephrine “seems sensible.”

exogenous administration of vasopressin in patients with septic shock may be considered hormone replacement therapy ∵ the findings that:

AVP concentrations appropriately ↑ in the early phase of septic shock
then quickly ↓ to subtherapeutic concentrations within the first 24 h after shock onset

limiting exogenous catecholamine dose

Catecholamines exert their hemodynamic effects through activity at adrenergic α-receptors and β-receptors. These receptors are susceptible to downregulation and desensitization in states of shock, often necessitating higher doses to sustain hemodynamic augmentation

other ADR from catecholamine e.g. arrhythmia, immunomodulation

Norepinephrine enhances antiinflammatory IL-10 response and attenuates the proinflammatory cytokine tumor necrosis factor alpha, whereas vasopressin exhibits no immunomodulatory effects

Important trials

VASST 2008

septic shock
NA vs NA + AVP
overall no difference in mortality
?lower all cause mortality in some subgroups

VANISH 2016

septic shock
NA vs AVP as 1st vasopressor
no difference in mortality & kidney failure-free days
but ↓ RRT?

(3rd trial in abstract form: Oliveira et al 2014)

Meta-analysis: ↓ mortality a/w AVP agonist use

Important research questions

Can patients who will respond to vasopressin’s initiation be identified preemptively?
When is the most ideal time during the course of shock to initiate vasopressin in a patient?
What clinical marker should be used as an indicator for vasopressin’s initiation?
What is the maximum safe vasopressin dose?
Should the vasopressin dosage be titrated?
What therapeutic intervention should be undertaken in individuals who do not respond to vasopressin initiation?
How should vasopressin be discontinued in patients in the convalescent phase?

Drug dose

DI

AVP 0.25 - 1 unit/hour
DDAVP
- PO 0.1mg daily to 0.3mg TDS
  - unpredictable absorption

Shock

AVP 0.03 - 0.04 units/min
= 1.8 - 2.4 units/hour
(high dose than DI)

Haemostasis

one off IV DDAVP 0.3 - 0.4 µg/kg
(beware of fluid overload)
approx. 20-40 µg
→ ~10x higher than DI dose
effect max in ~30min

Push dose AVP

EM Case report used 1 unit dilute to 1 unit/ml in post-arrest hypotension
recommends 0.5-1 u every 2-5 minutes, onset ~2 minutes, duration 5-20 minutes

Mixing Instructions from J Emerg Med Case Report (1 U/mL))

Obtain a 20 mL syringe filled with 19 mL of 0.9% saline
Inject one mL of vasopressin (20 unit per mL) into the syringe.
Shake syringe well. This will now give you one unit per mL. Administer 0.5-1 mL (0.5-1 unit) every two to five minutes titrating to desired blood pressure.

Mixing Instructions from Perioperative Push-Dose Pressor Paper (0.4 U/mL)

Use 2 vials of 20 unit/mL vasopressin to draw 2 mL total into a 3 mL syringe
Inject into 100 mL NS bag
Draw up 10 mL from mixture in 10 mL syringe for administration
Final concentration 0.4 units/ml
They use an initial dose of 1-2 units

initial bolus 2-4 units

4u in haemorrhagic shock as physiological replacement, restoring AVP level from 0 to normal
- endogenous reserve from the posterior pituitary can be depleted after 30-40 minutes

References

EMCrit 382 - A Deep Dive on Vasopressin — Timing, Push Dose Vaso and the Vasopressin Load Test

NeuroEMCrit - The Many Aliases and Uses of ADH by Casey Albin

Vasopressin A Review of Therapeutic Applications

Vasopressin and Its Analogues in Shock States A Review

Optimizing Vasopressin Use and Initiation Timing in Septic Shock