202501051535

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Tags: shock

Vasoplegic shock

no consensus definition of vasoplegic shock

Mechanisms

The pathophysiological mechanisms of vasoplegic shock can broadly be categorised as

• #Vasodilation
• #Vascular hyporesponsiveness
• capillary leak
• tissue hypoxia
  

Vasodilation

Inflammation leads to the increased production of endogenous vasodilators, the most important being nitric oxide.
Inflammatory cytokines cause the upregulation of the enzyme inducible nitric oxide synthase (iNOS), resulting in an increased production of nitric oxide. In the cytoplasm, nitric oxide activates guanylate cyclase, which in turn activates various protein kinases. Protein kinases increase the reuptake of calcium into the sarcoplasmic reticulum leading to the relaxation of vascular smooth muscle.

nitric oxide-induced activation of adenosine triphosphate-sensitive potassium (K-ATP) channels, which causes the hyperpolarisation of cell membranes, leading to impaired contraction of vascular smooth muscle.

Vascular hyporesponsiveness

High circulating concentrations of endogenous adrenaline (epinephrine), noradrenaline (norepinephrine) and angiotensin II lead to the downregulation of the receptors for these hormones.
Vasopressin is released from the posterior pituitary in response to decreased intravascular volume and low serum osmolarity. Sustained secretion of vasopressin results in depletion of stores in the posterior pituitary, leading to reduced release in response to hypovolaemia.

Metabolic acidaemia also contributes to activation of K-ATP channels and desensitisation of catecholamine receptors

Microcirculatory dysfunction

Vasoplegic shock is associated microcirculatory dysfunction, which encompasses capillary leak and stasis of blood flow
Release of inflammatory mediators leads to shedding of the vascular endothelial glycocalyx—the gel-like protective layer on the luminal surface of capillaries—and damages endothelial cell junctions, resulting in the translocation of fluid and plasma proteins from the intravascular space to the extravascular space.

Shedding of the glycocalyx also leads to increased expression of adhesion molecules on the luminal surface of blood vessels. The presence of adhesion molecules, along with inflammatory-mediated activation of platelets and coagulation proteins, leads to the formation of microthrombi with stasis of capillary blood flow. Reduced capillary blood flow leads to tissue hypoxia and risks ischaemia.

intravascular hypovolaemia, tissue oedema and end-organ hypoperfusion

Causes

• Sepsis
• Cardiac surgery with cardiopulmonary bypass
• Major noncardiac surgery
• Major trauma
• Pancreatitis
• Burns
• Ischaemia–reperfusion injury
• Anaphylaxis
• Adrenal insufficiency
• Liver failure
• Neuraxial anaesthesia with high block
• Toxicities (e.g. calcium channel blocker overdose)
• High spinal cord injury
  With sepsis, the initial triggers for systemic inflammation are components of the pathogenic microorganism (PAMPS)

After CPB, likely triggers are

• exposure of blood components to the extracorporeal circuit,
• surgical handling,
• tissue trauma,
• ischaemia-reperfusion
• bacterial translocation from the gut

Risk factors for vasoplegic shock after CPB include:

• impaired ventricular function,
• prolonged CPB
• preoperative use of ACEI / ARB

Haemodynamics

PAC typically shows

• high cardiac output (cardiac index >2.5 L min−1 m−2)
• low systemic vascular resistance (SVRI <800 dyne s cm−5)

Mixed venous oxygen saturation may be normal, high, or low. In the presence of microcirculatory dysfunction, reduced oxygen delivery to tissues leads to reduced oxygen extraction and (counterintuitively) a normal or high venous oxygen saturation despite the presence of tissue hypoxia.

ABP

The site of intra-arterial pressure monitoring is important, as a femoral-to-radial artery pressure gradient, (femoral MAP > radial MAP) is common in patients with vasoplegic shock, especially after cardiac surgery. Resolution of vasoplegic shock is associated with equalisation of radial and femoral blood pressure

Vasopressors

Noradrenaline

Noradrenaline is a direct α1-adrenoreceptor agonist with some activity at β1-receptors and minimal activity at β2-receptors.

Guidelines recommend using noradrenaline as the first line agent in septic shock.
The starting dose is as an i.v. infusion at 0.05–0.1 μg/kg/min

Contemporary data show an associated mortality of 40% with high-dose noradrenaline (>1 μg/kg/min)

compared with vasopressin, noradrenaline is associated with an increased risk of tachyarrhythmias, particularly atrial fibrillation

Adrenaline

Adrenaline is a direct α- and β-adrenoreceptor agonist. Compared with noradrenaline, adrenaline has increased β1 activity and also has activity at α2-adrenoreceptors

β-Receptor activity predominates at lower doses (0.01–0.1 μg/kg/min) and mediates vasodilation and metabolic effects (β2-adrenoreceptors) and chronotropy and inotropy (β1-adrenoreceptors)

α1 Activity (vasoconstriction of systemic arterioles and venous capacitance vessels) predominates at higher doses (>0.1 μg/kg/min)

The main disadvantages of adrenaline are adverse metabolic effects and an increased potential for tachyarrhythmias. β1-Adrenoreceptor-mediated tachyarrhythmias are most pronounced in the first 4–24 h

β2-Adrenoreceptor-mediated metabolic complications are common. Adrenaline antagonises the effects of insulin via gluconeogenic, glycogenolytic and lipolytic effects, causing hyperglycaemia and insulin resistance. Accelerated aerobic metabolism can cause or exacerbate hyperlactataemia.
Increased lactate can make it difficult to evaluate the patient's response to supportive treatments and is most pronounced in the first 4–24 h

Dopamine

Dopamine is a mixed, direct and indirect catecholamine precursor and has dose-dependent activity at dopamine-1 and β1-and α1-adrenoreceptors

Vasopressin

typically used as a noradrenaline-sparing agent when the dose of noradrenaline exceeds 0.2 μg/kg/min

usual dose of vasopressin is 0.02–0.04 units/min

Trial data have confirmed the safety of vasopressin in septic shock when used in combination with noradrenaline at doses <0.06 unit/min

Compared with catecholamines, vasopressin tends to cause less increase in pulmonary vascular resistance (PVR) and reduced rates of atrial fibrillation

vasopressin is associated with a higher risk of digital ischaemia than adrenaline and noradrenaline and should be used with caution in patients with peripheral vascular disease
When used in the dose range of <0.06 unit min−1, the incidence of mesenteric ischaemia is comparable to noradrenaline

Methylene blue

Methylene blue is a direct inhibitor of nitric oxide synthetase, with selectivity for iNOS
Methylene blue also binds to the haem moiety of guanylate cyclase, thereby inhibiting the activation of protein kinases

Vasoconstriction with methylene blue occurs in the presence of vasoplegia and is largely absent in patients with normal vascular tone

The dose is 1–2 mg/kg as an i.v. bolus over 15–30 min or an infusion over ≥1 h.

MAGIC trial: ongoing

Caution

Methylene blue causes green urine, caused by drug eliminated renally mixing with yellow urobilin compounds in the urine

Methylene blue is used as a treatment for methaemoglobinaemia

in patients with G6PD deficiency and other haemoglobinopathies, methylene blue induces oxidative stress and can cause methaemoglobinaemia and haemolytic anaemia and should be avoided

Methylene blue can also contribute to serotonin syndrome

Doses >7 mg/kg are associated with splanchnic hypoperfusion

Methylene blue should be used with caution in patients with ↑ PVR, although, doses <2 mg/kg are probably safe

Angiotensin II

Angiotensin II has a very short half-life and is given by a continuous infusion.
The usual dose range is 20–40 ng/kg/min
may be titrated to a maximum dose of around 200 ng/kg/min

ATHOS-3 trial: ↓ SOFA score cf further ↑ norad

Hydroxycobalamin

Hydroxocobalamin is an established treatment for cyanide toxicity

The possible mechanisms of action of hydroxocobalamin include inhibition of iNOS and enhancing the elimination of hydrogen sulphide, an endogenous vasodilator that hyperpolarises cell membranes by acting on K-ATP channels

For vasoplegia, a dose of 5 g, given as an i.v. infusion over 10–15 min, may be used. If effective, a decrease in requirements for conventional vasopressors is observed within 15 min.

Dark orange-red urine can be seen after an infusion of hydroxocobalamin, which may persist for up to 6 weeks

The ‘blood leak alarm’ in some renal replacement machines can be activated, caused by a false concern about rupture of the dialyser membrane

Hypokalaemia has been described in patients with vitamin B12 deficiency

Use of hydroxocobalamin can lead to errors in blood testing, including of creatinine, glucose, liver function tests and coagulation tests

Adjuncts

HC

References

Management of vasoplegic shock - BJA Education
Management of Vasoplegic Shock - BJA Ed