How should I prepare the norepinephrine (NE) dilution for an adult patient in circulatory shock?

Norepinephrine Dilution for Circulatory Shock

For adult patients in circulatory shock, prepare norepinephrine by adding 4 mg to 250 mL of D5W to create a standard concentration of 16 μg/mL, then initiate infusion at 0.5 mg/h (approximately 8-12 mcg/min or 0.1-0.5 mcg/kg/min) via central venous access while ensuring concurrent fluid resuscitation with at least 30 mL/kg crystalloid bolus. 1

Standard Adult Dilution Protocol

• Add 4 mg of norepinephrine to 250 mL of D5W to yield a concentration of 16 μg/mL, which is the standard adult preparation recommended for circulatory shock 1
• An alternative concentration of 10 mcg/mL can be prepared by adding 1 mg of norepinephrine to 100 mL of saline, though this is primarily used in anaphylaxis scenarios 1
• Never mix norepinephrine with sodium bicarbonate or other alkaline solutions in the IV line, as adrenergic agents are inactivated in alkaline solutions 1

Critical Pre-Administration Requirements

• Administer a minimum 30 mL/kg crystalloid bolus before or concurrent with norepinephrine initiation to avoid severe organ hypoperfusion from vasoconstriction in hypovolemic patients 1, 2
• Use balanced crystalloids (lactated Ringer's or Plasma-Lyte) preferentially over normal saline for fluid resuscitation 1
• In severe hypotension (systolic <70 mmHg), start norepinephrine as an emergency measure while fluid resuscitation continues, rather than waiting for complete volume repletion 1

Administration Route and Access

• Central venous access is strongly preferred to minimize extravasation risk and tissue necrosis 1
• If central access is unavailable or delayed, peripheral IV or intraosseous administration can be used temporarily with strict monitoring 2, 1
• Place an arterial catheter as soon as practical for continuous blood pressure monitoring 1
• When using peripheral access, place two distinct peripheral IV lines—one dedicated to vasopressor infusion and a second for other fluids—to avoid mixing incompatible solutions 1

Initial Dosing Parameters

• Start at 0.5 mg/h (approximately 8-12 mcg/min or 0.1-0.5 mcg/kg/min) via continuous IV infusion 1
• Alternative starting dose of 0.02 mcg/kg/min is supported by some guidelines 1
• Titrate every 4 hours by 0.5 mg/h increments to a maximum of 3 mg/h 1

Target Blood Pressure and Monitoring

• Target mean arterial pressure (MAP) of 65 mmHg for most patients with circulatory shock 2, 1
• Patients with chronic hypertension may require higher MAP targets, while younger normotensive patients may tolerate lower pressures 1
• Monitor blood pressure and heart rate every 5-15 minutes during initial titration 1
• Assess tissue perfusion markers: lactate clearance, urine output >50 mL/h, mental status, and capillary refill 1

Escalation Strategy for Refractory Hypotension

• When norepinephrine reaches 0.25 mcg/kg/min and hypotension persists, add vasopressin 0.03-0.04 units/min as second-line therapy rather than continuing to escalate norepinephrine alone 2, 1
• Alternatively, add epinephrine 0.1-0.5 mcg/kg/min if vasopressin is unavailable 1
• For persistent hypoperfusion despite adequate vasopressors with evidence of myocardial dysfunction, add dobutamine up to 20 mcg/kg/min 2, 1
• Consider hydrocortisone 200 mg per day (administered as infusion or intermittent doses) for refractory shock requiring high-dose vasopressors 2, 1

Pediatric Dilution and Dosing

• Use the "Rule of 6" for pediatric patients: multiply 0.6 × body weight (kg) to get the number of milligrams, then dilute to 100 mL of saline; at this concentration, 1 mL/h delivers 0.1 mcg/kg/min 1
• Start at 0.1 mcg/kg/min, titrating to desired clinical effect, with a typical range of 0.1-1.0 mcg/kg/min 1
• Maximum doses up to 5 mcg/kg/min may be necessary in some children, requiring central line placement 1

Critical Pitfalls to Avoid

• Never use dopamine as first-line therapy, as it is associated with higher mortality and more arrhythmias compared to norepinephrine 1
• Do not use low-dose dopamine for "renal protection"—it provides no benefit and is strongly discouraged 1
• Avoid phenylephrine as first-line therapy, which may raise blood pressure while worsening tissue perfusion 1
• Never use hydroxyethyl starch (HES) for fluid resuscitation with norepinephrine due to increased mortality (51% vs 43%, p=0.03) 1

Management of Extravasation

• If extravasation occurs, infiltrate phentolamine 5-10 mg diluted in 10-15 mL of saline intradermally at the site immediately to prevent tissue necrosis 1
• Pediatric phentolamine dose: 0.1-0.2 mg/kg up to 10 mg diluted in 10 mL of 0.9% sodium chloride 1
• Stop the norepinephrine infusion immediately but leave the IV catheter in place to preserve access to the extravasation site 1
• Observe patients for at least 24 hours after phentolamine treatment to confirm no further tissue injury is developing 1

Special Clinical Scenarios

• For anaphylaxis not responding to epinephrine: prepare 1 mg norepinephrine in 100 mL saline (1:100,000 solution), administered at 30-100 mL/h (0.05-0.1 mcg/kg/min) 1
• For hepatorenal syndrome: start at 0.5 mg/h, increase every 4 hours by 0.5 mg/h to maximum 3 mg/h, targeting MAP increase ≥10 mmHg and/or urine output >50 mL/h 1
• For pregnant patients with sepsis: consider more restrictive initial boluses of 1-2 L due to lower colloid oncotic pressure and higher pulmonary edema risk 1