Management of Refractory Hypotension

Initial Management

For patients with persistent hypotension despite maximum doses of epinephrine and norepinephrine, consider adding vasopressin (up to 0.03 U/min) to the treatment regimen, as recommended by the American College of Critical Care Medicine and the British Journal of Anaesthesia 1, 2
Vasopressin can be added as a bolus 1-2 IU followed by an infusion at 0.03 U/min, according to the British Journal of Anaesthesia 2

Ensure adequate volume status with crystalloid boluses (up to 20-30 ml/kg), using balanced crystalloids or normal saline based on patient needs, as recommended by the British Journal of Anaesthesia and the American College of Critical Care Medicine 1, 2
Consider albumin in addition to crystalloids when patients require substantial amounts of fluid, as suggested by the American College of Critical Care Medicine 1
Administer initial fluid bolus (1-2 L normal saline for adults) before vasopressor initiation if hypovolemia is suspected, as recommended by the Journal of Allergy and Clinical Immunology 3
Fluid bolus should be given at 5-10 mL/kg in the first 5 minutes for adults, with monitoring for signs of volume overload in patients with heart failure or renal disease 3

Norepinephrine is typically started at 0.1-0.5 mcg/kg/min, with careful monitoring of blood pressure response and targeting a mean arterial pressure (MAP) of 65 mmHg, as recommended by the American Heart Association 4, 5
Epinephrine is typically started at 0.1 mcg/kg/min, with a range of 0.1-1.0 mcg/kg/min, as recommended by the American Academy of Pediatrics 6
Consider adding IV glucagon 1-2 mg for patients on beta-blockers, as recommended by the British Journal of Anaesthesia 2
If inadequate response after 10 minutes, consider doubling the bolus dose of epinephrine, as suggested by the British Journal of Anaesthesia 2
Consider starting an epinephrine infusion (0.05-0.1 μg/kg/min) if more than three epinephrine boluses have been administered, according to the British Journal of Anaesthesia 2

In Grade IV reactions (cardiac or respiratory arrest), follow advanced life support guidelines including IV epinephrine 1 mg, as recommended by the British Journal of Anaesthesia 2
Consider extracorporeal life support where available for patients with persistent shock despite all interventions, as suggested by the British Journal of Anaesthesia 2

Consider adding dobutamine if there is evidence of persistent hypoperfusion despite adequate fluid loading and vasopressor use, according to the American College of Critical Care Medicine 1
Norepinephrine remains first-line, but adding vasopressin can help decrease norepinephrine dosage and potentially improve outcomes, as suggested by the American College of Critical Care Medicine 1
Dopamine can be used as an alternative vasopressor at 2-20 mcg/kg/min to maintain renal and splanchnic circulation while increasing blood pressure in patients with refractory hypotension, as recommended by the American College of Cardiology 3
The choice of vasopressor depends on the underlying condition, with norepinephrine being the first-line agent for septic shock and epinephrine being used as a second-line agent or in cardiogenic shock, as recommended by the Society of Critical Care Medicine 7

Continuous cardiac monitoring, frequent blood pressure measurements, and regular assessment of tissue perfusion are essential when using vasopressors, with potential adverse effects including tachyarrhythmias, increased myocardial oxygen consumption, lactic acidosis, and hyperglycemia, as reported by the Society of Critical Care Medicine 7
Tissue necrosis can occur if extravasation happens, and immediate infiltration with phentolamine may prevent this, as recommended by the American Academy of Pediatrics 6
Norepinephrine can cause supraventricular arrhythmias, with a risk 7.25 times higher compared to vasopressin, in patients with certain cardiac conditions, and increased myocardial oxygen consumption may worsen ischemia in patients with coronary artery disease, thus requiring cautious use in such patients 5, 4
Contraindications for peripheral noradrenaline administration include uncorrected hypovolemia, anticipated need for prolonged use (>24 hours), inability to monitor adequately, and severe peripheral arterial disease 4