How to prevent Propofol-Related Infusion Syndrome (PRIS) complication in patients undergoing Total Intravenous Anesthesia (TIVA) with propofol, especially in those with critical illness or high-risk factors?

Prevention and Management of Propofol Infusion Syndrome (PRIS) in TIVA

Limit propofol infusion to <70 μg/kg/min (ideally 5-50 μg/kg/min) and switch to alternative sedation after 48 hours of continuous use to prevent PRIS, which carries a mortality rate of 33-37%. 1, 2

Understanding PRIS Risk

PRIS is a constellation of metabolic derangements and organ failures characterized by:

• Severe metabolic acidosis with elevated lactate 1, 3
• Cardiac dysfunction (arrhythmias, heart failure) and hypotension requiring escalating vasopressors 1, 3
• Rhabdomyolysis with elevated creatine kinase 1, 2
• Hyperkalemia and acute kidney injury 1, 3
• Hypertriglyceridemia (present in 100% of cases) 2
• Hepatomegaly and liver dysfunction 3, 4

The FDA warns that PRIS has been associated with fatal outcomes in both adult and pediatric ICU patients, with the syndrome developing even with large-dose, short-term infusions during surgical anesthesia. 3

Primary Prevention Strategy: Dose and Duration Limits

Maintain propofol at 5-50 μg/kg/min during TIVA, avoiding doses >70 μg/kg/min. 1 The American College of Critical Care Medicine explicitly recommends this dosing ceiling, though the FDA label states administration should not exceed 4 mg/kg/hour (approximately 67 μg/kg/min) unless benefits outweigh risks. 1, 3

For procedures or sedation extending beyond 48 hours, transition to alternative sedatives. 1 This is the single most important preventive measure, as prolonged high-dose propofol (>48 hours) is a major risk factor for PRIS development. 3, 5

High-Risk Patient Identification

Major risk factors requiring heightened vigilance include: 3, 5

• Critical illness with decreased oxygen delivery to tissues 3
• Serious neurological injury or sepsis 3
• High-dose vasoconstrictors, steroids, or inotropes 3
• Young age (particularly <3 years) 4
• Carbohydrate depletion or fasting states 5

PRIS can occur at lower doses (as low as 1.3-1.9 mg/kg/hr or approximately 22-32 μg/kg/min) in critically ill patients, so dose limits alone do not guarantee safety. 6, 7

Alternative Sedation After 48 Hours

When propofol has been used for 48 hours, switch to: 1

Dexmedetomidine (preferred option):

• Load with 1 μg/kg over 10 minutes 1
• Maintain at 0.2-0.7 μg/kg/hr (up to 1.5 μg/kg/hr as tolerated) 1
• Monitor for bradycardia and hypotension 1
• Provides minimal respiratory depression with different mechanism of action 1

Midazolam (alternative option):

• Load with 0.01-0.05 mg/kg 1
• Maintain at 0.02-0.1 mg/kg/hr 1

Lorazepam (use with caution):

• Load with 0.02-0.04 mg/kg 1
• Maintain at 0.01-0.1 mg/kg/hr 1
• Monitor for propylene glycol toxicity with prolonged use 1

Mandatory Monitoring During Propofol Use

Daily laboratory surveillance must include: 1

• Arterial blood gases (for metabolic acidosis) 1
• Serum triglycerides 1
• Creatine kinase 1
• Renal function (creatinine, BUN) 1
• Liver function tests 1
• Serum potassium 1
• Serum lactate 1

Continuous monitoring requirements: 3

• ECG for arrhythmias (watch for Brugada-like ST elevation, bradycardia) 3
• Hemodynamic parameters with immediate vasopressor availability 3
• BIS monitoring targeting 40-60 to avoid excessive depth 8

Early Warning Signs Requiring Immediate Action

Unexplained metabolic acidosis is the earliest and most common sign (present in 79% of PRIS cases), appearing at a median of 125 hours after propofol initiation. 2 Other red flags include: 1, 2

• Increasing vasopressor requirements to maintain blood pressure 1
• Rising creatine kinase levels 2
• New cardiac arrhythmias or ECG changes 3, 2
• Escalating propofol dose requirements to maintain sedation 3

If any of these occur, immediately suspect PRIS and discontinue propofol. 1, 3

Management of Established PRIS

Stop propofol infusion immediately upon suspicion—this is the most critical intervention. 1, 5 Do not wait for confirmatory testing, as PRIS mortality reaches 36-37% even with treatment. 2, 6

Provide aggressive supportive care: 1, 5

• Correct metabolic acidosis with sodium bicarbonate 1
• Initiate renal replacement therapy for acute kidney injury and hyperkalemia 1, 5
• Provide hemodynamic support with vasopressors and inotropes as needed 5
• Consider extracorporeal membrane oxygenation (ECMO) for refractory cardiac failure 5
• Treat rhabdomyolysis with aggressive fluid resuscitation 1

Critical Pitfalls to Avoid

Never abruptly discontinue propofol without transitioning to alternative sedation, as this causes rapid awakening with anxiety, agitation, and ventilator dyssynchrony. 3 Instead, initiate alternative sedation before weaning propofol. 1

Do not dismiss early metabolic acidosis as simply related to critical illness—PRIS is frequently underdiagnosed due to overlap with ICU complications. 2 The median cumulative propofol dose at PRIS onset is 276.5 mg/kg, but cases occur at lower cumulative doses in high-risk patients. 2

PRIS can develop during TIVA for elective surgery, not just ICU sedation, particularly with large-dose infusions. 3, 7 Maintain vigilance even in otherwise healthy surgical patients receiving prolonged TIVA.

Special Considerations for TIVA

For elective surgical TIVA: 8

• Target effect-site concentration of 0.5-1 mcg/ml for propofol maintenance 8
• Avoid bolus dosing to prevent hemodynamic instability 8
• Use processed EEG monitoring (BIS 40-60) to prevent excessive depth 8
• Have vasopressors immediately available 8

In elderly patients (>60 years), reduce propofol doses by approximately 20% and avoid BIS values <35 to reduce delirium risk. 8 Elderly patients are more sensitive to propofol's cardiovascular effects. 8