CICM Second Part Exam Practice SAQs 08102020

VASOPLEGIA

OVERVIEW

• No consensus definition
• Characterised by
  • Decreased SVR
  • due to arteriolar dilatation
  • due to decreased vascular smooth muscle (VSM) constriction
  • normal or hyperdynamic cardiac function (however cardiac dysfunction can co-exist with vasoplegia)
• May or may not involve vasoplegic shock (distributive shock), characterised by hyperfusion (high lactate carries worse prognosis)
• Often associated with relative hypovolaemia from increased venous capacitance and capillary leak
• Has multifactorial causes, is common in ICU, and is associated with morbidity and mortality

MECHANISMS

• Contractile state of VSM is primarily determined by intracellular calcium, which is affected by ATP-sensitive K channels that determine depolarisation state
• Factors affecting vascular smooth muscle contractility are:
  • EXTRINSIC
    • Sympathetic nervous system
    • Endocrine
      • Glucocorticoids
      • Catecholamines
      • Thyroid hormones
      • Vasopressin
  • INTRINSIC
    • Endothelial secretions
      • NO
      • PGI2
      • ET1
    • Metabolites
      • Acidemia
      • Hypoxia
      • ROS
    • Autacoids
      • 5HT
      • Prostaglandins
      • TXA2
• These processes are dysregulated in pathological states by cytokine cascades triggered by DAMPS (damage-associated molecular patterns, e.g. HSPs, nucleic acids) and PAMPS (pathogen-associated molecular patters, e.g. LPS) that bind PRR (pattern recognition receptors, e.g. Toll-like receptors), as well as other mechanisms PAMPS – sepsis
  • PAMPS and DAMPS – post-op, post-bypass, post-arrest, transfusion, pancreatitis
  • DAMPS – burns, trauma, any other cause of shock
  • Other – GA, epidural, neurogenic, anaphylaxis, vasodilatory drugs and toxins

TREATMENT

• Seek and treat underlying cause
  • E.g. antibiotics for infection, stop vasodilatory drugs
• Determine appropriate MAP target
  • E.g. >65 mmHg for septic shock (SSC guidelines) and most patients
  • Can individualise to patient (but evidence lacking)
    • E.g. tolerate MAP >60 if no shock, otherwise well and likely short-lived cause to prevent SEs/ complications of vasopressors
    • E.g. higher DBP target if known CAD to ensure coronary perfusion
    • E.g. MAP 80 may be preferred in neurogenic shock from spinal cord injury
• Correct hypovolaemia and metabolic state
  • E.g. up to 30 mL/kg IBW for septic shock
  • Consider HCO3/ RRT for severe acidemia (controversial, unclear thresholds)
  • O2 therapy to targt SpO2 92-96% in most patients
  • Thiamine if suspected deficiency or hyperlactemia
  • Calcium if hypocalcemia
• Noradrenaline is usual first line agent (e.g. supported by SSC guidelines)
  • Alpha >> beta effects
    • Increased SVR -> increased DBP & MAP, drives perfusion
    • Increased venous tone -> preload
  • If possible, avoid:
    • pure alpha agonists (e.g. phenylephrine, midodrine, metaraminol)
      • Worse outcomes in septic shock
      • Less “ventriculo-arterial matching”
      • Acceptable if low dose, likely short-term, and cause is pure vasodilation (e.g. peri-operative)
    • Epinephrine
      • Increased lactate and heart rate
      • Acceptable alternative in low resource settings or inotropic effect required
    • Dopamine
      • Increased dysrhythmias
• Second line agents are vasopressin and hydrocortisone
  • Useful if:
    • Apparent catecholamine resistance
    • Avoid side effects of high dose single agent (e.g. catecholamines)
  • Vasopressin
    • Early use may be beneficial in some settings (e.g. VANCS trial for cardiac surgery; if coexistent pulmonary hypertension as has less pulmonary vascular constriction) but unclear evidence in septic shock
  • Hydrocortisone
    • Likely decreases NO/ NOS in VSM
    • ADRENAL study showed decreased vasopressor duration in septic shock
• Refractory vasoplegia
  • Exclude/ treat other causes of shock
  • Consider “NO antagonists” (improve vasoplegia but evidence is lacking for improved outcomes)
    • Methylene blue (CI: serotonin syndrome, G6PD deficiency)
    • Hydroxcobalamin
• Future/ experimental agents include:
  • Angiotensin (ATHOS3 trial)
  • Ascorbic acid
  • Adrenomedullin