Vasoplegia is a low systemic vascular resistance state that can occur after cardiopulmonary bypass and is characterized by hypotension resistant to fluid resuscitation. It increases morbidity and mortality through organ dysfunction. Treatment aims to restore blood pressure through vasopressor drugs like norepinephrine and vasopressin. Norepinephrine is usually first-line but vasopressin may be added for its vasoconstriction and sympathomimetic effects. Non-conventional vasopressors like methylene blue and angiotensin II are second-line options. Corticosteroids and cytokine filters have not proven effective for preventing or treating vasoplegia.

1. Vasoplegia after CPB
Dr Gayathri G

2. ▪ Vasoplegia is characterized by a normal or augmented
cardiac output with low systemic vascular resistance
(SVR) causing organ hypoperfusion.
▪ Incidence 5% to 40% after CPB
▪ High morbidity and mortality rates
▪ DD - sepsis, adrenal insufficiency, and hepatic failure
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3. Outcome
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More frequent postoperative bleeding;
Increased incidence of organ dysfunction:
renal, liver and respiratory failure;
Prolonged mechanical ventilation and
length of ICU/hospital stay;
Higher mortality.

4. Definition
▪ Distributive Form of Circulatory Shock 24 h after CPB
Initiation, Characterized by:
▪ (1) MAP < 65 mmHg resistant to fluid challenge
▪ (2) SVR < 800 dynes s/cm5
▪ (3) CI > 2.2 L/min/m2
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5. Predisposing factors
Patient-related
• Advanced age
• Anemia
• Low LVEF
• Renal failure
Peri-operative
drugs:
• Diuretics;
• Sympatho-
adrenergic
inotropes
• ACEI
Operative factors
• CPB/aortic
cross clamping
time
• Redo surgery
• LVAD surgery
• HTx
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6. Cellular physiology
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7. Pathophysiology
Systemic inflammatory response triggered by:
(1) Exposure of blood to the artificial surfaces of the extracorporeal
circuit;
(2) Surgical trauma;
(3) Ischemia/ reperfusion injury;
(4) Oxidative stress;
(5) Release of endotoxin from the gut;
(6) Hemolysis;
(7) Reinfusion of cell saver blood
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8. Leads to
▪ Activation of the complement cascade
▪ Expression of pro-inflammatory mediators, such as (il-1β),(il-6) and (tnfα).
▪ Il-6 increases the synthesis of camp, which promotes vasodilation by reducing
myoplasmic [ca++].
▪ Accordingly, higher circulating levels of il-6 have been associated with an
increased incidence of vs
▪ Longer cpb and aortic cross-clamping durations, combined surgery and redo
intervention all predispose to a more intense inflammatory response.
▪ Following the discontinuation of cpb, systemic reperfusion promotes the
generation of oxygen-free radicals and the amplification of the initial
inflammation.
▪ The reinfusion of cell saver blood containing hemolyzed red blood cells,
activated platelets and denatured proteins, may also contribute to this response
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9. Mechanisms of pathological vasodilation
(1) Desensitization of adrenergic receptors;
(2) Increased NO biosynthesis;
(3) Low plasma vasopressin;
(4) VSMC hyperpolarization due to opening of KATP channels;
(5) RAS dysfunction with low Ang2
(6) Excess H2S generation
(7) Endothelial glycocalyx alteration
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10. 10

11. Adrenoreceptor desensitization
1. Reduced α1-adrenoreceptor expression due to suppressed promoter activity at
the level of gene transcription
2. Excessive release of catecholamines in response to baroreceptor and
cytokine-dependent stimulation of CNS
- sustained adrenergic stimulation induces phosphorylation of G-protein
coupled adrenoreceptor through the activation of GPCR kinases, inhibiting
catecholamine binding and downstream signaling
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12. Increased NO biosynthesis
▪ Cytokines stimulate expression of inducible NO synthase through activation of
nuclear factor kappa B
▪ Unlike constitutive calcium dependent NOS isoform, this calcium independent
iNOS has ability to produce larger amounts of NO over prolonged periods.
▪ Increased generation of NO is proportional to CPB time
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13. NO
▪ Activates soluble guanylyl cyclase in vsmcs leading to MLC
dephosphorylation.
▪ No (via cgmp) activates (katp) in vsmcs, causing k+ efflux and
membrane hyperpolarization.
▪ Results in closure of voltage-activated (ca++) channels, reduction in
cytosolic ca++ and vasodilation.
▪ No-cgmp promote k+ efflux by activating the vascular calcium-
activated potassium channels (kca++).
▪ Generation of peroxynitrite, a strong oxidant and nitrating species
formed from the rapid reaction of no with the superoxide anion radical
(o2 −)
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14. Relative vasopressin deficiency
▪ Inflammatory cytokines and sustained baroreceptor stimulation cause
overactivation of CNS and hypothalamic pituitary axis - higher release of
NE, ADR, cortisol, vasopressin
▪ Persistent shock and hypotension - progressive decline of blood levels of
vasopressin
▪ Circulating vasopressin levels during CPB have been measured by
Colson et al. in sixty-four consecutive patients. Patients developing VS
displayed a significant drop of plasma vasopressin 8 h after CPB in
comparison to non-VS patients. Comparable results have been reported
in patients with septic shock.
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15. VSMC hyperpolarization
▪ NO release, vasopressin deficiency, hypoxia, acidosis and increased H2S
cause activation of KATP(ATP sensitive K+ channels causes membrane
hyperpolarization
▪ Results in inhibition of Ca channel dependent cellular Ca influx - vasodilation
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16. RAS dysfunction
▪ Under conditions of impaired ACE 1 activity (pulmonary dysfunction), ang2
formation is prevented, and ang1 is converted into the vasodilating derivative
ang1–7 by the type 2 ACE
▪ During the pulmonary exclusion associated with CPB there is reduced ACE 1
activity and ang2 formation, while increasing ang1 and ang1–7.
▪ Process may be amplified by the enhanced secretion of renin, triggered in
response to low ang2 and reduced blood pressure, which further increases
ang1 formation (“high renin shock”)
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17. Endothelial glycocalyx alteration
▪ Glycocalyx - complex layer of glycosaminoglycans and proteoglycans coating
the endothelial cell surface with components - heparan sulfate and syndecan-1.
▪ Boer et al. - “glycocalyx thickness was significantly reduced after the initiation
of CPB, a change which persisted after weaning and was associated with
microcirculatory impairment”
▪ Abou-Arab et al. - “plasma levels of syndecan-1 increased after CPB,
consistent with glycocalyx shedding.”
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18. Excess H2S production
▪ H2S activates KATP - membrane hyperpolarization and enhances NO signalling
▪ Hydroxycobalamin can bind H2S and increase BP in patients with severe VS
post CPB
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19. 19

20. Management
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21. Prevention
▪ Hemodynamic optimization
▪ Improvement of renal function
▪ Minimal extracorporeal circulation (MECC) and
biocompatible, heparin-coated short circuits
▪ Titration of drugs
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22. Fluid and Blood Product Resuscitation
▪ Recognize and correct hypovolemia
▪ Avoid over resuscitation beyond 20- 30 ml/kg
▪ Guided by dynamic indices like pulse pressure variation, echographic
indices of stroke volume variation
▪ Transfusion - liberal (Hb 9 g/dL) vs. restrictive (Hb 7.5 g/dL) strategy
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23. Vasoactive Drugs
▪ Target MAP of 65–70 mm Hg
▪ Conventional Vasopressors : Norepinephrine; Vasopressin;
▪ Non-conventional Vasopressors : Methylene Blue; Hydroxocobalamin;
Angiotensin 2.
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24. Noradrenaline
▪ First line vasopressor agent
▪ Side effects such as tachycardia, atrial fibrillation, increased myocardial
oxygen consumption, and hyperlactatemia
▪ High doses NE may result in immunosuppression predisposing to
secondary infections
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25. Vasopressin
▪ Promotes vasoconstriction via V1-receptor-dependent increase in
cytosolic ca++,
▪ Modulation of NO signaling
▪ Improvement of catecholamine sensitivity. There is reduced circulating
levels of VP reported in
▪ In patients with VS after CPB there is reduced circulating levels of VP
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26. VANCS trial
▪ 300 patients with VS after cardiac surgery
▪ directly compared NE (10–60 mcg/min) with VP (0.01–0.06 U/min) as first line
vasopressor to maintain a MAP of 65 mm Hg
▪ Patients in the VP arm had a significant reduction in 30 days mortality or severe
complications mostly due to a marked reduction in acute renal failure
▪ In addition, VP was associated with a lower incidence of atrial fibrillation and did not
result in a greater occurrence of digital, mesenteric, or myocardial ischemia
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28. Angiotensin 2
▪ The possibility that a disturbed renin angiotensin system leading to
reduced Ang2 generation participates to VS after CPB suggests that
exogenous Ang2 might be a therapeutic option in this setting
▪ Several case reports and small case series reported safe and successful
administration of Ang2, with significant hemodynamic improvement and
vasopressor sparing effect, in vasoplegic patients following cardiac
surgery
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29. ▪
▪

30. Methylene blue
▪ Thiazine dye used as an antidote to treat methemoglobinemia
▪ Acts by inhibiting no-dependent vasodilation via:
▪ Direct scavenging of NO
▪ Inhibition of NO synthase
▪ Inhibition of guanylyl cyclase
▪ Data on clinical outcome with MB remain scarce
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31. Hydroxocobalamin
▪ Hydroxocobalamin (vitamin B12) is used for the therapy of
pernicious anemia and in cyanide poisoning
▪ Increase vascular tone by:
▪ Inhibition of NOS enzymes
▪ Direct NO inactivation
▪ Reduction in H2S toxicity through direct binding
▪ Evaluated for the treatment of refractory VS after CPB
▪ 5 g administered by IV infusion over 15 min
▪ Can cause haemolytic anemia in G6PD deficient patients
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32. 32

33. Vitamin C
▪ Co-factor for several enzymes involved in the
biosynthesis of endogenous catecholamines
▪ Increases the sensitivity of adrenoreceptors
▪ Free radical scavenger therefore reduces oxidant-
mediated tissue injury, inflammation and endothelial
dysfunction
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34. LOVIT Trial
▪ Did not find any benefit from Vitamin C (50 mg/kg q6 h for up to 96h)
▪ In contrast, patients treated with Vitamin C displayed significantly higher
risk of death or persistent organ dysfunction
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35. Corticosteroids
▪ Anti-inflammatory effects, leading notably to a reduced expression of
inflammatory cytokines, inos and cyclooxygenase-2
▪ To enhance the synthesis of catecholamines and to increase the
expression and sensitivity of adrenoreceptors
▪ In cardiac surgery, two large trials (SIRS trial -7507 patients, and DECS
trial—4494 patients) evaluated the effects of high doses corticosteroids
(intraoperative methyprednisolone or dexamethasone) on mortality and
major complications, and did not report any significant effects of the
intervention
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36. Extracorporeal cytokine adsorption therapy
(ECAT)
▪ Technique of extracorporeal blood purification using specifically
designed filters able to adsorb and remove inflammatory mediators from
the circulation
▪ This strategy has been applied to decrease inflammation in sepsis
▪ Limited evidence
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38. Modulation of the sympathetic system
▪ During a shock state, the inappropriate activation of
the sympathetic system is associated with receptor
desensitization
▪ α2 Agonists
▪ Selective β1 blockade
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39. Future

40. Selepressin
▪ Short-acting selective V1a receptor agonist
▪ Bypasses undesirable side effects through V2 stimulation (fluid
accumulation, microvascular thrombosis, vasodilation)
▪ Furthermore, selepressin does not induce release of the procoagulant
Willebrand fact
▪ Still in trial phase
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41. SUMMARY
▪ Restore organ perfusion pressure and adequate oxygen delivery, by
ensuring appropriate preload and by the administration of vasoactive
drugs, with the aim to maintain a MAP of 65 mm hg
▪ Norepinephrine is generally considered as the standard of care.
Vasopressin should be added to norepinephrine in case of untoward side
effects (tachycardia, atrial fibrillation) related to excessive sympathetic
stimulation, or could be used as the initial vasopressor
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42. SUMMARY
▪ Non-conventional vasopressors, including methylene blue, angiotensin 2
and hydroxocobalamin, should only be introduced as a rescue therapy,
on a caseby- case basis.
▪ Evidence of low dose corticosteroids for their use in post-cpb has not
been demonstrated.
▪ Vitamin C and cytokine adsorption filters should not be used, owing to
possible deleterious effects
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43. Thank you
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