Fluid resuscitation for refractory hypotension Valverde 2021

Question 1

When can refractory hypotension be encountered?

Answer 1

shock due to hypovolemia
or sepsis, but can also include cardiogenic, neurogenic, and anaphylactic shock

Question 2

What is the mechanism of action behind hypotension in septic shock?

Answer 2

The vasodilation that results from sepsis is the result of several
factors that enhance vasodilatory- and inhibit vasoconstrictor
mechanisms. These include an unregulated synthesis of nitric
oxide, a potent vasodilator, in response to cytokines released
during septic and hemorrhagic shock. In dogs with septic
peritonitis, levels of the inflammatory cytokines C-C motif
chemokine ligand 2 (CCL2) and interleukin 6 (IL-6) were
significantly higher than in non-septic dogs (64), which
contributes to migration and infiltration of macrophages into the
area of insult (65).

Question 3

How and where is Nitric Oxide formed?

Answer 3

Nitric oxide is produced from L-arginine by
nitric oxide synthase, present in endothelial cells, and diffuses
into the underlying smooth muscle to activate soluble guanylate
cyclase and cGMP production that dephosphorylates myosin,
via the myosin light chain phosphatase, causing vasorelaxation

Question 4

MOA vasopressin

Answer 4

Vasopressin is a
potent vasoconstrictor by acting on vasopressin-type 1a
receptors (V1a) present in vascular smooth muscle and
helps with short-term control of arterial blood pressure
under conditions of hemorrhage or sepsis, but this process
requires of high circulating concentrations of vasopressin
that depletes the stores within 1-h under conditions of
profound baroreflex stimulation

Question 5

What’s the target MAP in patient with septic shock in 2016 guidelines?

Answer 5

The most recent guidelines
for management of sepsis and septic shock in people, from 2016,
recommends an initial target mean arterial pressure of 65 mmHg
in patients with septic shock requiring vasopressors

Question 6

Which vasopressor is used a second line and why?

Answer 6

Vasopressin has been considered the second line-drug
due to its catecholamine-sparing properties (40, 54). The
vasoconstriction and increase in vascular resistance caused
by vasopressin can decrease cardiac output (26), and the
recent guidelines recommend adding either vasopressin
(weak recommendation/moderate quality of evidence) or
epinephrine (weak recommendation/low quality of evidence)
to norepinephrine to reach the target mean arterial pressure, or
adding vasopressin (weak recommendation/moderate quality of
evidence) to decrease the norepinephrine dose (72).

Question 7

Which receptors are triggered by these vasopressors?

Answer 7

• Norepinephrine: a-1, b1
• Epinephrine: α- and β-adrenergic receptors with dose-dependent actions as a sympathomimetic catecholamine. Low doses primarily activate β-receptors, enhancing bronchodilation and cardiac activity, while higher doses engage α-receptors to induce vasoconstriction and increase vascular tone.
• Vasopressin: V1a
  -Dopamine: beta-1 adrenergic effects
• Dobutamine: beta-1 adrenergic
• Phenylephrine is a pure alpha-1 agonist
  Terlipressin is a prodrug to its metabolite lysine vasopressin: V1

Question 8

Ohm’s law

Answer 8

(ABP = CO x VR)