What is the typical dosage of Norad (norepinephrine) for an adult patient with no significant medical history, presenting with hypotension or shock?

Norepinephrine: Indications and Dosing

Norepinephrine is the first-line vasopressor for hypotension due to septic shock, cardiogenic shock, or other distributive shock states, with an initial dose of 0.1-0.5 mcg/kg/min (approximately 8-12 mcg/min in a 70 kg adult), titrated to achieve a mean arterial pressure (MAP) of 65 mmHg. 1, 2, 3

Primary Indication

Norepinephrine is indicated for severe hypotension (systolic BP ≤70 mmHg) with low peripheral vascular resistance, particularly in septic shock where it demonstrates superior outcomes compared to dopamine or phenylephrine. 1, 2 The Surviving Sepsis Campaign strongly recommends norepinephrine as the first-choice vasopressor based on moderate quality evidence showing reduced mortality. 1

Preparation and Administration

Standard Dilution

• Add 4 mg of norepinephrine to 250 mL of D5W to yield a concentration of 16 mcg/mL 2, 3
• Alternative concentration: 4 mg in 1,000 mL yields 4 mcg/mL 3
• For anaphylaxis: 1 mg in 100 mL saline creates a 1:100,000 solution, administered at 30-100 mL/h 2

Route of Administration

• Central venous access is strongly preferred to prevent tissue necrosis from extravasation 1, 2, 3
• Peripheral IV or intraosseous administration can be used temporarily if central access is unavailable or delayed, though transition to central access should occur as soon as practical 2, 4

Dosing Protocol

Initial Dosing

• Start at 0.1-0.5 mcg/kg/min (8-12 mcg/min in a 70 kg adult) 1, 3
• Alternative starting dose: 0.02 mcg/kg/min in some protocols 2, 4
• For hepatorenal syndrome: Start at 0.5 mg/h (approximately 8 mcg/min) 2

Titration Strategy

• Titrate every 4 hours by 0.5 mg/h increments to achieve target MAP 2
• Monitor blood pressure and heart rate every 5-15 minutes during initial titration 2, 4
• Typical maintenance dose ranges from 2-4 mcg/min (0.5-1 mL/min of standard dilution) 3

Target Blood Pressure

• Target MAP of 65 mmHg for most patients 5, 1, 2, 4
• Higher targets (70-75 mmHg) may be appropriate in patients with chronic hypertension 4
• Lower targets (60-65 mmHg) may be considered in elderly patients >75 years 4

Maximum Dosing

• Standard maximum: 3 mg/h (approximately 50 mcg/min) 2
• High doses up to 68 mg base (17 vials) daily may occasionally be necessary, though occult blood volume depletion should always be suspected at these doses 3
• Doses >10 mcg/min are associated with increased mortality and should be avoided if possible 1

Critical Pre-Administration Requirements

Volume depletion must be corrected before or concurrently with norepinephrine administration. 1, 3 The following steps are mandatory:

• Administer minimum 30 mL/kg crystalloid bolus within first 3 hours 2, 4
• Use crystalloids (normal saline or balanced crystalloids like lactated Ringer's) as first choice 2
• In emergency situations with life-threatening hypotension (systolic <70 mmHg), norepinephrine can be started simultaneously with volume replacement to prevent cerebral or coronary ischemia 3, 6

Monitoring Requirements

Continuous Monitoring

• Place arterial catheter as soon as practical for continuous blood pressure monitoring 1, 4
• Monitor blood pressure and heart rate every 5-15 minutes during initial titration 2, 4
• Continuous ECG monitoring is essential 1

Perfusion Assessment

MAP alone is insufficient—assess tissue perfusion using multiple parameters: 2, 4

• Lactate clearance (repeat within 6 hours if initially elevated)
• Urine output >0.5 mL/kg/h for 2 consecutive hours
• Mental status
• Capillary refill and skin perfusion
• Normalization of heart rate for age

Escalation Strategy for Refractory Hypotension

Second-Line Vasopressor

When norepinephrine reaches 0.1-0.25 mcg/kg/min without achieving target MAP, add vasopressin 0.03-0.04 units/min 2, 4 Vasopressin should never be used as initial monotherapy—only as adjunct to norepinephrine. 4

Third-Line Options

• Add epinephrine 0.05-2 mcg/kg/min if hypotension persists, particularly when myocardial dysfunction is present due to its inotropic effects 4
• Consider dobutamine 2.5-20 mcg/kg/min if persistent hypoperfusion exists despite adequate MAP, especially when low cardiac output is evident 2, 4

Agents to Avoid

• Do not use dopamine as first-line therapy—it is associated with higher mortality and more arrhythmias compared to norepinephrine 5, 1, 4
• Dopamine should only be used in highly selected patients with low risk of tachyarrhythmias and absolute or relative bradycardia 1, 4
• Do not use low-dose dopamine for "renal protection"—this provides no benefit and is strongly discouraged 5, 4
• Phenylephrine is not recommended as first-line therapy and should only be used in specific circumstances such as when norepinephrine causes serious arrhythmias 4

Precautions and Contraindications

Relative Contraindications

• Hypovolemia is a relative contraindication—always correct volume depletion before or concurrently with norepinephrine 1
• Use cautiously in patients with ischemic heart disease as it may increase myocardial oxygen requirements 1

Extravasation Management

If extravasation occurs, immediately infiltrate 5-10 mg of phentolamine diluted in 10-15 mL of saline into the site to prevent tissue necrosis 1, 2, 3 Pediatric dose: 0.1-0.2 mg/kg up to 10 mg. 2

Drug Incompatibilities

• Do not mix with sodium bicarbonate or other alkaline solutions in the IV line—adrenergic agents are inactivated in alkaline solutions 2, 3
• Avoid contact with iron salts, alkalis, or oxidizing agents 3

Special Clinical Scenarios

Septic Shock

• Norepinephrine is the mandatory first-choice vasopressor with strong recommendation and moderate quality evidence 5, 2
• Early administration (within first hour) increases shock control rate and reduces fluid overload 7, 6, 8
• In the CENSER trial, early norepinephrine achieved shock control in 76.1% vs 48.4% with standard treatment by 6 hours 8

Cardiogenic Shock

• Norepinephrine dosage range: 0.2-1.0 μg/kg/min 1
• Use with caution and only transiently due to risk of increasing afterload 1
• Often combined with dobutamine to improve hemodynamics 1

Pediatric Dosing

• Start at 0.1 mcg/kg/min, titrating to desired clinical effect 2
• Typical range: 0.1-1.0 mcg/kg/min 5, 2
• Maximum doses up to 5 mcg/kg/min may be necessary in some children 5, 2
• "Rule of 6" for pediatric preparation: 0.6 × body weight (kg) = number of milligrams diluted to 100 mL saline; then 1 mL/h delivers 0.1 mcg/kg/min 2

Obstetric Patients

• Start at 0.02 mcg/kg/min to maintain MAP ≥65 mmHg 2
• Consider more restrictive initial fluid boluses of 1-2 L due to lower colloid oncotic pressure and higher pulmonary edema risk 2
• Add vasopressin 0.04 units/min for refractory shock with fetal monitoring when appropriate 2

Hepatorenal Syndrome

• Start at 0.5 mg/h, increase every 4 hours by 0.5 mg/h to maximum of 3 mg/h 2
• Goal: increase MAP by ≥10 mmHg and/or urine output >50 mL/h for at least 4 hours 2

Timing Considerations

Early administration of norepinephrine is beneficial and should be considered in specific situations: 7, 6

• Profound hypotension with diastolic BP ≤40 mmHg or diastolic shock index (HR/DBP) ≥3 6
• Life-threatening hypotension where relying only on fluids may unduly prolong hypotension 6
• Patients at risk for fluid accumulation (ARDS, intra-abdominal hypertension) 6
• Median time from emergency room arrival to norepinephrine should be minimized—in the CENSER trial, early administration at 93 minutes vs 192 minutes improved outcomes 8

Weaning Protocol

• Decrease norepinephrine dose by 25% of current dose every 30 minutes as tolerated 1
• Continue infusion until adequate blood pressure and tissue perfusion are maintained without therapy 3
• Reduce gradually, avoiding abrupt withdrawal 3
• Treatment duration may extend up to 6 days in some cases of vascular collapse 3

Adverse Effects

• Increased myocardial oxygen consumption 1
• Tissue necrosis if extravasation occurs 1
• Arrhythmias at higher doses 1
• Excessive vasoconstriction leading to end-organ hypoperfusion 1
• Transient increase in serum lactate (not clinically relevant) 5

Key Clinical Pearls

• Norepinephrine may paradoxically improve renal blood flow and urine output in septic shock despite causing renal vasoconstriction in other contexts 1
• Early administration increases cardiac output and improves microcirculation by increasing mean systemic filling pressure 6, 9
• In elderly patients (median age 81), peripheral administration showed better survival than expected (ward mortality 27.5%, SMR 0.443) 10
• Duration and depth of hypotension strongly worsen outcomes—rapid restoration of MAP is critical 7, 6