What are the management and prevention strategies for propofol infusion syndrome?

From the Guidelines

Propofol infusion syndrome (PRIS) management requires immediate discontinuation of propofol upon suspicion and switching to alternative sedatives, as the mortality rate from PRIS can be as high as 33% 1. The prevention and management of PRIS involve a multifaceted approach to minimize the risk of this potentially life-threatening condition.

Key Prevention Strategies:

• Limiting propofol infusion rates to less than 4 mg/kg/hr, which is equivalent to 70 μg/kg/min, as rates above this threshold are associated with a higher risk of PRIS 1
• Avoiding prolonged infusions, particularly those exceeding 48 hours, as the risk of PRIS increases with the duration of propofol administration 1
• Using the lowest effective dose of propofol to achieve the desired level of sedation, thereby reducing the risk of PRIS and other adverse effects 1

Monitoring and Supportive Care:

• Regular monitoring of creatine kinase, lactate, triglycerides, and acid-base status is essential, with checks recommended every 12-24 hours during prolonged infusions to facilitate early detection of PRIS 1
• Patients receiving high-dose or prolonged propofol should have daily electrocardiograms to detect arrhythmias, which can be a sign of PRIS 1
• Adequate carbohydrate intake, with a minimum of 6-8 mg/kg/min of glucose, helps prevent metabolic derangements that can contribute to the development of PRIS 1

High-Risk Patients:

• Risk factors requiring extra vigilance include young age, critical illness, high catecholamine or glucocorticoid states, low carbohydrate intake, and concomitant use of vasopressors, as these factors can increase the risk of PRIS 1

Management of PRIS:

• If PRIS develops, supportive care includes hemodynamic support, correction of metabolic acidosis, hemodialysis for severe cases, and potentially extracorporeal membrane oxygenation for refractory cardiac dysfunction 1
• Early recognition is crucial, as PRIS carries a high mortality rate, with most deaths resulting from refractory cardiac failure and metabolic acidosis 1

From the FDA Drug Label

The following appear to be major risk factors for the development of these events: decreased oxygen delivery to tissues; serious neurological injury and/or sepsis; high dosages of one or more of the following pharmacological agents: vasoconstrictors, steroids, inotropes and/or prolonged, high-dose infusions of propofol (greater than 5 mg/kg/h for greater than 48h) In the setting of prolonged need for sedation, increasing propofol dose requirements to maintain a constant level of sedation, or onset of metabolic acidosis during administration of a propofol infusion, consideration should be given to using alternative means of sedation The syndrome has also been reported following large-dose, short-term infusions during surgical anesthesia.

The management and prevention strategies for Propofol Infusion Syndrome include:

• Avoiding high dosages of propofol (greater than 5 mg/kg/h for greater than 48h) 2
• Monitoring for early signs of hypotension, apnea, airway obstruction, and/or oxygen desaturation
• Considering alternative means of sedation in the setting of prolonged need for sedation, increasing propofol dose requirements, or onset of metabolic acidosis
• Avoiding co-administration of propofol with vasoconstrictors, steroids, inotropes
• Maintaining a light level of sedation through the weaning process or evaluation of sedation level
• Daily evaluation of sedation levels and titration to clinical response are important during use of propofol infusion for ICU sedation, especially when it is used for long durations 2

From the Research

Management Strategies for Propofol Infusion Syndrome

• Immediate discontinuation of propofol infusion is crucial in managing overt propofol infusion syndrome 3
• Supportive management, including hemodialysis, hemodynamic support, and extracorporeal membrane oxygenation, may be necessary in refractory cases 3
• Cardiocirculatory stabilization and correction of metabolic acidosis should be initiated promptly if propofol infusion syndrome is suspected 4

Prevention Strategies for Propofol Infusion Syndrome

• Clinicians should consider alternative sedative regimes to prolonged propofol infusions 3
• Propofol doses should be kept within recommended maximal dose limits to minimize the risk of propofol infusion syndrome 3, 5
• Monitoring for early signs of propofol infusion syndrome, such as metabolic acidosis, cardiac dysfunction, and rhabdomyolysis, is essential in patients on prolonged propofol infusion 6
• A prospective screening protocol, including daily serum creatine phosphokinase (CPK) and lactate measurements, can be effective in preventing propofol infusion syndrome 7
• Propofol should be used with caution in critically ill children and adults, as well as for long-term anesthesia in otherwise healthy patients, and doses exceeding 4-5 mg/kg/h for long periods (>48 h) should be avoided 5, 4

Risk Factors for Propofol Infusion Syndrome

• Certain risk factors, such as high-dose propofol, carbohydrate depletion, severe illness, and concomitant administration of catecholamines and glucocorticosteroids, can increase the risk of developing propofol infusion syndrome 3, 5
• Prolonged propofol infusion (>48 hours) and high doses (>4 mg/kg/h) can also increase the risk of propofol infusion syndrome 5, 4