What are the recommended dilutions and infusion rates for ICU drugs in critically ill patients with cardiovascular instability, septic shock, and ARDS?

ICU Drug Dilutions for Infusion

Vasopressors and Inotropes

Norepinephrine should be initiated as the first-choice vasopressor to maintain MAP ≥65 mmHg in septic shock, with standard dilution of 4-16 mg in 250 mL (16-64 mcg/mL) administered via central line. 1

Norepinephrine

• Standard concentration: 16-64 mcg/mL (4-16 mg in 250 mL D5W or NS) 1
• Initial infusion rate: 0.05-0.1 mcg/kg/min, titrate to MAP ≥65 mmHg 1
• Administration: Requires central venous access for optimal safety; peripheral administration acceptable temporarily during resuscitation 2

Epinephrine

• Standard concentration: 16-64 mcg/mL (4-16 mg in 250 mL D5W or NS) 2
• Dosing: 0.05-0.5 mcg/kg/min for cold shock with low blood pressure in pediatrics; consider as second-line agent in adults 2
• Indication: Cold shock unresponsive to dopamine, or as additional agent when norepinephrine alone insufficient 2, 1

Dopamine

• Standard concentration: 1600-3200 mcg/mL (400-800 mg in 250 mL D5W or NS) 2
• Dosing range: 5-20 mcg/kg/min 2
• Note: Reserved for highly selected patients (low risk of tachyarrhythmias, absolute/relative bradycardia) 1

Vasopressin

• Standard concentration: 0.4-1 unit/mL (20-40 units in 50-100 mL NS or D5W) 2
• Dosing: 0.03-0.04 units/min (fixed dose, not titrated) 2
• Use: Warm shock with persistent hypotension despite norepinephrine 2

Neuromuscular Blocking Agents

Cisatracurium should be diluted to 0.1 mg/mL (10 mg/100 mL) or 0.4 mg/mL (40 mg/100 mL) in D5W, NS, or D5NS for continuous infusion in mechanically ventilated ARDS patients. 3

Cisatracurium

• Standard dilutions: 0.1 mg/mL or 0.4 mg/mL 3
• Compatible diluents: 5% Dextrose, 0.9% Sodium Chloride, or 5% Dextrose/0.9% Sodium Chloride 3
• Initial infusion rate: 3 mcg/kg/min to counteract spontaneous recovery, then 1-2 mcg/kg/min for maintenance 3
• Reduction required: Decrease infusion rate by 30-40% during isoflurane or enflurane anesthesia 3
• Stability: Diluted solutions stable for 24 hours refrigerated or at room temperature 3
• Indication: Recommended for ≤48 hours in sepsis-induced ARDS with PaO2/FiO2 <150 mmHg 2

Infusion Rate Tables for Cisatracurium (0.1 mg/mL concentration)

• 70 kg patient at 2 mcg/kg/min: 84 mL/hr 3
• 100 kg patient at 2 mcg/kg/min: 120 mL/hr 3

Sedation

Minimize continuous sedation in mechanically ventilated sepsis patients, targeting specific endpoints rather than deep sedation. 2

General Principles

• Strategy: Use intermittent boluses preferentially over continuous infusions 2
• Protocolized approach: Daily sedation interruption or systematic titration to predefined endpoints reduces mechanical ventilation duration 2
• Avoid: Deep sedation associated with prolonged ICU stay 2

Tranexamic Acid

For major trauma with mild-to-moderate TBI, administer 1 g IV over 10 minutes within 3 hours of injury, followed by 1 g over 8 hours, OR 2 g IV over 20 minutes as single bolus. 2

Trauma Dosing

• Loading dose: 1 g IV over 10 minutes within 3 hours of injury 2
• Maintenance: 1 g IV over 8 hours 2
• Alternative: 2 g IV over 20 minutes as single bolus within 3 hours 2

Postpartum Hemorrhage

• Initial dose: 1 g IV over 10 minutes within 3 hours of bleeding onset 2
• Repeat dose: 1 g IV if bleeding continues after 30 minutes or restarts within 24 hours 2

Hydrocortisone

Administer IV hydrocortisone 200 mg per day only if adequate fluid resuscitation and vasopressor therapy fail to restore hemodynamic stability in septic shock. 2

• Dose: 200 mg/day IV (typically divided as 50 mg IV every 6 hours) 2
• Indication: Refractory septic shock unresponsive to fluids and vasopressors 2
• Pediatric consideration: Use in patients at risk for absolute adrenal insufficiency 2

Antibiotics - Empirical Sepsis Coverage

Administer broad-spectrum IV antibiotics within 1 hour of recognizing sepsis or septic shock. 1

First-Line Regimens

• Piperacillin/tazobactam: 4.5 g IV every 6-8 hours 4
• Ceftriaxone: 2 g IV daily for sepsis 4
• Cefepime: 2 g IV every 8-12 hours 4

Combination Therapy

• Add gentamicin: 5-7 mg/kg IV daily (once-daily dosing) to cephalosporins initially, de-escalate after 48-72 hours 4

Fluid Resuscitation

Administer at least 30 mL/kg IV crystalloid rapidly within first 3 hours for sepsis-induced hypoperfusion, using 20 mL/kg boluses over 5-10 minutes in pediatrics. 1, 2

Adult Dosing

• Initial bolus: 30 mL/kg IV crystalloid within 3 hours 1
• Target: MAP ≥65 mmHg, urine output ≥0.5 mL/kg/hr, lactate normalization 1

Pediatric Dosing

• Bolus size: 20 mL/kg isotonic crystalloid or albumin over 5-10 minutes 2
• Repeat: Up to 60 mL/kg total until perfusion improves or hepatomegaly/rales develop 2
• Switch to inotropes: If hepatomegaly or rales present, do not continue fluid boluses 2

ARDS Patients

• Conservative strategy: Minimize fluid infusion targeting CVP <4 mmHg or PAWP <8 mmHg once shock resolved 2
• Rationale: Reduces mechanical ventilation days and ICU length of stay without increasing renal failure 2

Blood Products

Transfuse RBCs only when hemoglobin decreases to <7.0 g/dL in adults with sepsis, targeting 7-9 g/dL, unless myocardial ischemia, severe hypoxemia, or acute hemorrhage present. 2, 1

RBC Transfusion

• Threshold: Hemoglobin <7.0 g/dL 2
• Target range: 7-9 g/dL 1
• Exceptions: Active myocardial ischemia, severe hypoxemia, acute hemorrhage 2
• Pediatric threshold: Hemoglobin <7.0 g/dL; target >10 g/dL in septic shock if ScvO2 <70% 2

Platelet Transfusion

• Prophylactic threshold: <10,000/mm³ without bleeding 2
• With bleeding risk: <20,000/mm³ 2
• Active bleeding/procedures: ≥50,000/mm³ 2

Drug Compatibility Considerations

Cisatracurium is incompatible with propofol and ketorolac for Y-site administration; use separate IV lines. 3

Compatible Solutions

• Cisatracurium compatible with: D5W, NS, D5NS, sufentanil, alfentanil, fentanyl, midazolam, droperidol 3
• Cisatracurium incompatible with: Propofol, ketorolac 3

pH Considerations

• Cisatracurium pH: 3.25-3.65 (acidic); incompatible with alkaline solutions pH >8.5 (e.g., barbiturates) 3
• Standardization principle: Group drugs by pH, medical indication, and chemical structure to minimize incompatibility 5

Common Pitfalls to Avoid

• Do not delay antibiotics beyond 1 hour while obtaining cultures 1
• Do not use β-agonists routinely in sepsis-induced ARDS without bronchospasm (increased mortality) 2
• Do not attempt to normalize blood pressure during active hemorrhage; accept lower MAP with volume resuscitation alone 2
• Do not continue aggressive fluid resuscitation in ARDS patients once shock resolved; switch to conservative strategy 2
• Do not use pulmonary artery catheters routinely in sepsis-induced ARDS 2
• Do not mix incompatible drugs through same IV lumen; standardize drug groupings by compatibility 5