Propofol Adverse Effects and Management
Most Common Adverse Effects
Propofol's most clinically significant adverse effects are dose-dependent cardiovascular depression (hypotension >30% decrease in arterial pressure) and respiratory depression (apnea), which require careful monitoring and dose titration to prevent serious morbidity. 1
Cardiovascular Effects
- Hypotension is the most common complication, occurring through decreased cardiac output, systemic vascular resistance, and arterial blood pressure 2, 1
- Arterial pressure decreases are frequently >30% from baseline, particularly during induction 1
- Negative cardiac inotropism reduces cardiac output, especially with assisted or positive pressure ventilation 2
- Risk is substantially higher in elderly, debilitated, volume-depleted patients, and those with ASA-PS III or IV status 3, 1
- In cardiac procedures, persistent hypotension requiring propofol cessation occurs in approximately 13.6% of patients, with older age and female sex as risk factors 4
Respiratory Effects
- Apnea is frequent, particularly in both adult and pediatric patients 1
- Dose-dependent respiratory depression with decreased minute ventilation and increased CO2 tension 2, 1
- Transient oxygen desaturation (SpO2 <90%) occurs in 5-7% of patients 3
- Upper airway obstruction, hypoventilation, dyspnea, and cough may occur during MAC sedation 1
Injection Site Reactions
- Pain on injection affects up to 30% of patients when administered through peripheral veins 2, 3
- Phlebitis and thrombosis are infrequent despite injection pain 5
Metabolic and Systemic Effects
- Hypertriglyceridemia from the 10% lipid emulsion formulation 3, 1
- Propofol provides 1.1 kcal/mL, requiring adjustment of nutritional requirements to prevent overfeeding 3
- Pancreatitis is an uncommon complication 6
Propofol Infusion Syndrome (PRIS)
PRIS is a rare (1% incidence) but potentially fatal complication with 33% mortality that requires immediate propofol discontinuation upon suspicion. 7
Clinical Presentation
- Worsening metabolic acidosis (often the earliest sign) 7
- Hypertriglyceridemia 7
- Hypotension with increasing vasopressor requirements 7
- Cardiac arrhythmias and myocardial failure 7, 2
- Acute kidney injury and hyperkalemia 7
- Rhabdomyolysis 7
- Liver dysfunction 7
Risk Factors and Prevention
- High-dose propofol (>70 μg/kg/min) is the primary risk factor, though PRIS can occur at doses as low as 1.9-2.6 mg/kg/hr 7, 2
- Prolonged infusions (>48 hours) significantly increase risk 7
- The American College of Critical Care Medicine recommends maintaining propofol at 5-50 μg/kg/min and avoiding doses >70 μg/kg/min 7
- Daily laboratory monitoring including serum triglycerides, arterial blood gases, renal and liver function tests is crucial for early detection 7
- Switch to alternative sedatives after 48 hours: dexmedetomidine (0.2-0.7 μg/kg/hr) or midazolam-based sedation 7
Management of PRIS
- Immediately discontinue propofol upon suspicion 7, 2
- Provide supportive care focused on organ dysfunction 7
- Manage metabolic acidosis 7
- Initiate renal replacement therapy for acute kidney injury as needed 7
Allergic and Hypersensitivity Reactions
- Avoid in patients with egg, soy, or sulfite allergies due to the formulation containing 10% soybean oil and 1.2% purified egg phosphatide 2
- NOT contraindicated in sulfonamide allergy 2
- Anaphylaxis is rare but can occur 8
- Bronchospasm may occur, particularly with metabisulfite-containing formulations 6
Special Population Considerations
Elderly and Debilitated Patients
- Require approximately 50% dose reduction (start at 25 μg/kg/min instead of 50-100 μg/kg/min) 2
- Patient age correlates with maximum blood pressure drop 4
- Avoid rapid bolus administration in elderly, debilitated, or ASA-PS III/IV patients for MAC sedation 3, 1
Patients with Pulmonary Hypertension
- Use with caution due to potential for hemodynamic instability 2
CYP2B6 Poor Metabolizers
- Reduce infusion dose by approximately 50% (to 25 μg/kg/min) to avoid excessive drug exposure and prolonged sedation 2
Critical Management Strategies
Dosing Approach to Minimize Adverse Effects
- Avoid bolus loading doses in hemodynamically unstable patients 3
- If loading needed, use 5 μg/kg/min over 5 minutes only in stable patients 3
- Target light sedation (patient arousable, follows commands) rather than deep sedation 3
- Use slow infusion or slow injection techniques for MAC sedation rather than rapid bolus 1
- Allow 3-5 minute intervals between dose adjustments to assess clinical effects 1
Monitoring Requirements
- Continuous cardiorespiratory monitoring during administration 1
- Vigilance for unexplained metabolic acidosis as early PRIS indicator 7
- Monitor for signs of respiratory depression and airway obstruction 1
Overdose Management
- Immediately discontinue propofol 1
- Treat respiratory depression with artificial ventilation and oxygen 1
- Manage cardiovascular depression by repositioning (raising legs), increasing IV fluid rate, and administering pressor agents and/or anticholinergic agents 1
Important Clinical Pitfalls to Avoid
- Failing to recognize early PRIS signs (unexplained metabolic acidosis) 7
- Using high doses (>70 μg/kg/min) or prolonged infusions (>48 hours) without appropriate monitoring and consideration of alternative sedatives 7
- Administering loading doses in hemodynamically unstable patients 3
- Not accounting for propofol's 1.1 kcal/mL caloric contribution in nutritional calculations 3
- Forgetting that propofol has NO analgesic properties—must combine with short-acting opioids for painful procedures 2
- Rapid bolus administration during MAC sedation, which increases risk of hypotension, desaturation, apnea, and airway obstruction 1