💊 Propofol Infusion Syndrome (PRIS): A Comprehensive Review for Clinical Practice

👉👉　🇺🇸 All Posts 🇬🇧 / 🇯🇵 記事一覧 🇯🇵　👈👈

🚨 Introduction: Why Every Anesthesiologist Must Know About PRIS

Propofol has transformed modern anesthesia and critical care with its rapid onset, smooth emergence, and reliable titratability. Yet this “user-friendly” drug carries a rare but potentially fatal complication: propofol infusion syndrome (PRIS).

First reported in Denmark in 1990 and formally named by Bray in 1998, PRIS remains one of the most feared complications in the ICU, with mortality reported between 18% and 52%. Early recognition and prevention are paramount. This review is tailored for anesthesia residents preparing for board examinations (ABA Written Exam, EDAIC) and for clinicians caring for critically ill patients.

📚 What You Will Learn

📋 Definition and Diagnostic Criteria

PRIS is defined as acute heart failure (including bradyarrhythmias and cardiac arrest) occurring during or after propofol administration, accompanied by one or more of the following metabolic abnormalities (Kam & Cardone, 2007; Singh et al., 2022):

🔹 Diagnostic Criteria (at least one must be present)

❗ Critical point: Cardiac arrest is not required for diagnosis. Early manifestations often include refractory bradycardia, decreased myocardial contractility, and poor response to vasopressors. Waiting for cardiac arrest is frequently too late.

📚 CRASH Mnemonic for Board Exams

📊 Incidence and Mortality

Incidence varies by population and definition:

• Adult ICU: 0.3–1.1% (up to 1.1% in the most critically ill; Zhang et al., 2025)
• Pediatric ICU: 1–5% (higher with prolonged, high-dose infusions)
• Surgical anesthesia (short duration): extremely rare (<0.01%)

Mild cases may go unrecognized, suggesting the true incidence could be higher. Once PRIS develops, mortality ranges from 18–52%—approximately 52% in pediatric patients and 48% in adults (Yasin et al., 2023). Early detection and intervention are critical for survival.

---

♦️ Pathophysiology: The Dual Mitochondrial Insult

The core mechanism involves mitochondrial dysfunction via two primary pathways (Vasile et al., 2003; Singh et al., 2022).

1️⃣ Inhibition of the mitochondrial respiratory chain

Propofol inhibits Complex II and Complex IV, impairing electron transport and ATP production, leading to cellular energy failure (“cellular hypoxia”). High-demand tissues—cardiac and skeletal muscle—are especially vulnerable.

2️⃣ Impaired fatty acid β-oxidation

Critically ill patients often shift toward lipid metabolism. Propofol disrupts fatty acid oxidation at multiple steps, including the carnitine shuttle (CPT-1/CPT-2) and acyl-CoA dehydrogenases, causing toxic intermediate accumulation.

🔹 Integrated understanding

Put these together, and you see why PRIS escalates quickly: ATP drops while toxic metabolites build up, setting the stage for severe metabolic acidosis, myocardial dysfunction, and rhabdomyolysis.

📝 Board exam tip: When you explain PRIS, make sure you cover both arms of the problem: (1) respiratory chain inhibition → ATP depletion and (2) impaired fatty acid β-oxidation → toxic intermediate accumulation.

🔍 Risk Factors: The Five Major Categories

PRIS seldom arises from a single trigger. Risk rises when factors stack—sometimes subtly, then suddenly.

🏥 Clinical scenario: highest risk

Picture this: a patient with sepsis on vasopressors and steroids, under-fed, and receiving propofol at 4 mg/kg/hr. That combination should put you on high alert for PRIS.

⚠️ Early Recognition: Signs That Precede Cardiac Arrest

Prognosis hinges on early detection (Singh et al., 2022; Nickson, 2024). Ask yourself on rounds: “Are we seeing a pattern here?”

🚨 Early warning signs (priorities for monitoring)

🔷  Early warning signs

🚨 Advanced Stage Findings

💡 Clinical Pearl: Monitoring Strategy Limitations

Van et al. (2023) caution that following single biochemical markers (e.g., CK or lactate) can create false reassurance. Integrate clinical findings, ECG changes, and lab trends—avoid anchoring on one parameter.

📌 Note on Green Urine

“Green urine” reflects propofol metabolites (phenolic compounds) and is not specific for PRIS (Nickson, 2024). Do not use it diagnostically.

---

🏥 Management: Immediate Cessation and Aggressive Support

No specific antidote exists.
Management rests on two pillars: stop propofol immediately and provide aggressive supportive care (Singh et al., 2022). When in doubt, act.

🔷 Step 1: Immediate propofol discontinuation

At the first suspicion of PRIS, stop propofol. This is the most important—and only definitive—intervention.

✅ Alternative sedation options

• Selection should be individualized to hemodynamics, respiratory status, and sedation goals.

🔷 Step 2: Aggressive supportive care

✅ Prevention: Evidence-Based Strategies for Clinical Practice

PRIS is devastating but largely preventable through systematic risk reduction (Kam & Cardone, 2007; Fox, 2018). Think proactive, not reactive.

🔷  Strict dose and duration limits

Reminder: These are not absolute safety thresholds.

🔷 Adequate carbohydrate (glucose) administration

• Pediatrics: 6–8 mg/kg/min
• Adults: ≥ 2–4 mg/kg/min

Avoid propofol in fasting or severely malnourished patients when feasible.

🔷 Avoid use in high-risk patients

Contraindicated in:

• Known mitochondrial disease
• Fatty acid oxidation disorders (e.g., CPT or MCAD deficiency)

🔷 Reduce lipid load

Using higher-concentration (2%) propofol can reduce total lipid administration in adults.
However, 2% formulations are associated with increased risk of infusion site pain and are not recommended for pediatric patients. Both risks and benefits should be individually assessed.

🔷 Intensive monitoring (especially if high risk)

🔷 Infection control (separate from PRIS risk)

Propofol is a lipid emulsion conducive to microbial growth:

• Change infusion sets every 12 hours
• Strict aseptic technique
• Use promptly after opening

🌐 Key Guidelines for International Practice

Current practice in pediatric ICU sedation

• First-line agents: midazolam, dexmedetomidine
• Analgesia-based sedation: fentanyl or morphine with light sedation
• Short-term postoperative sedation: propofol may be used cautiously (< 24 hours)

Clinical decision-making

When propofol is considered off-label for pediatric ICU sedation:

• Exhaust alternative strategies first
• Adhere strictly to dose and duration limits
• Document informed consent discussions with families
• Implement intensive monitoring protocols

---

---

📝 Summary：Take Home Points

Especially in pediatric ICU sedation, weigh risks and benefits carefully, noting off-label status in many regions and FDA contraindications in the U.S. Propofol is not a drug to fear—but it does demand respect in use: understand the risks, prevent what you can, and act decisively when PRIS is on the table.

📚 References & Further reading