What is the best course of action for a patient with hypotension (low blood pressure) who is not responding to noradrenaline (norepinephrine) therapy, with a non-recordable blood pressure?

Management of Refractory Hypotension on Norepinephrine

When a patient on norepinephrine has non-recordable blood pressure, immediately add vasopressin 0.03-0.04 units/min as second-line therapy while ensuring adequate volume resuscitation with crystalloid boluses (minimum 30 mL/kg if not already given), and consider adding epinephrine 0.1-0.5 mcg/kg/min if hypotension persists. 1, 2

Immediate Assessment and Interventions

Verify Adequate Volume Resuscitation

• Address hypovolemia first - give crystalloid fluid boluses (minimum 30 mL/kg) if not already administered, as vasoconstriction in hypovolemic patients causes severe organ hypoperfusion despite attempts to raise blood pressure 1, 2
• Use balanced crystalloids (lactated Ringer's or Plasma-Lyte) preferentially over normal saline 1
• In severe hypotension with non-recordable BP, continue fluid resuscitation while simultaneously escalating vasopressor therapy rather than waiting for complete volume repletion 1

Confirm Blood Pressure Measurement

• Place an arterial catheter immediately for continuous monitoring, as non-invasive measurements may be unreliable in severe shock 3, 2
• Verify central venous access for vasopressor delivery to prevent tissue necrosis and ensure reliable drug delivery 1, 2

Assess Organ Perfusion

• Evaluate tissue perfusion markers: mental status, urine output (target >50 mL/h), capillary refill, skin temperature, and lactate clearance 3, 1, 2
• Consider pulmonary artery catheterization in patients refractory to pharmacological treatment to characterize hemodynamic pattern and identify inadequate left ventricular filling pressure 3

Vasopressor Escalation Algorithm

Add Vasopressin as Second-Line Agent

• When norepinephrine reaches 0.25 mcg/kg/min and hypotension persists, add vasopressin 0.03-0.04 units/min rather than continuing to escalate norepinephrine alone 1, 2
• Do not increase vasopressin above 0.03-0.04 units/min, reserving higher doses for salvage therapy only 1

Add Epinephrine if Needed

• If hypotension persists despite norepinephrine plus vasopressin, add epinephrine 0.1-0.5 mcg/kg/min as a third agent 1, 2
• Epinephrine may be particularly useful if there is evidence of myocardial dysfunction 2

Consider Inotropic Support

• Add dobutamine up to 20 mcg/kg/min if persistent hypoperfusion exists despite adequate vasopressors, particularly with evidence of myocardial dysfunction 1, 2
• Start dobutamine at 2.5 mcg/kg/min, doubling the dose every 15 minutes according to response, with titration usually limited by excessive tachycardia, arrhythmias, or ischemia 1

Target Blood Pressure Goals

• Target mean arterial pressure (MAP) of 65 mmHg for most patients 1, 2
• For patients with chronic hypertension, increase target MAP to ≥70 mmHg or maintain within 40 mmHg of baseline systolic pressure 2, 4
• Titrate vasopressors based on both MAP and markers of tissue perfusion (lactate clearance, urine output, mental status, capillary refill) rather than MAP alone 1, 2

Consider Alternative Diagnoses and Mechanical Support

Rule Out Alternative Causes

• Consider pulmonary embolism, acute mechanical problems (cardiac tamponade, tension pneumothorax), and severe valve disease (particularly aortic stenosis) in patients with persistently low blood pressure 3
• Reassess for adequate left ventricular filling pressure using pulmonary artery catheterization if available 3

Mechanical Circulatory Support

• Consider intra-aortic balloon pump or other mechanical circulatory support in patients without contraindications who remain in refractory shock despite maximal vasopressor therapy 3
• Ventricular assist devices may be used as a "bridge to decision" in selected patients 3

Critical Pitfalls to Avoid

• Never use dopamine as first-line agent - it is associated with higher mortality and more arrhythmias compared to norepinephrine 1, 2
• Do not use phenylephrine as first-line therapy - it may raise blood pressure while worsening tissue perfusion and cardiac output 1, 2
• Avoid low-dose dopamine for "renal protection" - it provides no benefit and is strongly discouraged 1, 2
• Do not rely on blood pressure numbers alone - assess organ perfusion markers to guide therapy 3, 1, 2
• Never delay mechanical ventilation if there is worsening hypoxemia, failing respiratory effort, or increasing confusion 3