What are the guidelines for using Propofol (propofol) for sedation and anesthesia?

Propofol for Sedation and Anesthesia

Propofol should be administered intravenously in small, incremental doses or by continuous infusion, titrating to desired endpoints while maintaining vascular access and continuous cardiorespiratory monitoring throughout the procedure. 1

Administration Technique

Intravenous Dosing Strategy

• Administer propofol in small, incremental doses or by infusion, allowing sufficient time between doses (minimum 20-30 seconds) to assess peak effect before subsequent administration. 1
• For short procedures: use bolus dosing (10-60 mg initial bolus, followed by 10-20 mg increments as needed). 2
• For longer procedures: initiate with intravenous bolus followed by continuous infusion at 50-100 mcg/kg/min. 1, 3
• Maintain vascular access throughout the procedure and until the patient is no longer at risk for cardiorespiratory depression. 1

Onset and Duration

• Onset of action: 30-45 seconds (arm-brain circulation time). 3, 2
• Duration of effect: 4-8 minutes after single bolus dose. 3, 2
• Terminal half-life: 1-3 days after prolonged infusion. 2

Clinical Efficacy by Procedure Type

Pediatric Emergency Department Sedation

• For painful procedures in children: combine propofol with opioid agents (Level B recommendation). 1
• For painless diagnostic studies: propofol alone is likely effective (Level C recommendation). 1
• Propofol produces mean sedation levels of 5.5-5.6 on the 6-point Ramsay scale in pediatric patients. 1

Comparative Effectiveness

• Propofol alone provides shorter sedation and recovery times compared to benzodiazepine-opioid combinations. 1
• Propofol combined with opioids produces lower pain scores than propofol alone. 1
• Propofol shows equivocal outcomes compared to ketamine for sedation scores, pain, recovery, and vital signs. 1

Critical Safety Monitoring

Mandatory Continuous Monitoring

• Monitor heart rate, blood pressure, and pulse oximetry continuously during propofol administration. 3, 4
• Use processed EEG monitoring (BIS 40-60) during neurosurgical procedures to prevent awareness and avoid excessive depth. 3

Cardiovascular Effects

• Propofol causes dose-dependent decreases in cardiac output, systemic vascular resistance, and arterial pressure. 3, 4, 2, 5
• Clinically insignificant transient hypotension occurs in some patients, though intervention is rarely required. 1
• Have vasopressors immediately available (ephedrine or metaraminol) to treat hypotension. 3

Respiratory Depression

• Propofol causes dose-dependent respiratory depression and potential apnea. 4, 2, 6
• Hypoxia (defined variably as SpO2 <90-95%) occurs in 2-31% of pediatric patients receiving propofol. 1
• Most hypoxic episodes respond to minimal interventions (head repositioning, supplemental oxygen). 1
• The effect-site concentration for respiratory depression (EC50) is 3.99 mcg/ml. 7

Drug Combinations and Interactions

Synergistic Effects

• Co-administration of opioids and other CNS depressants potentiates propofol's sedative effect—reduce doses of each component accordingly. 1, 2
• Propofol combined with ketamine produces deeper sedation but increases respiratory depression and hypoxemia risk. 1
• Propofol combined with midazolam produces deeper sedation levels and more episodes of deep sedation. 1

Analgesic Considerations

• Propofol has minimal to no analgesic properties—combine with short-acting opioids (fentanyl, alfentanil, sufentanil, or remifentanil) for painful procedures. 3, 2, 6

Contraindications and Special Populations

Absolute Contraindications

• Avoid propofol in patients with egg, soy, or sulfite allergies (formulation contains 10% soybean oil and 1.2% purified egg phosphatide). 3, 2
• Propofol is NOT contraindicated in sulfonamide allergy. 3, 2

High-Risk Populations Requiring Extreme Caution

• Use propofol with extreme caution in patients with pulmonary hypertension due to risk of significant hemodynamic instability and worsening right ventricular function. 4
• In hypovolemic patients and those with limited cardiac reserve, even small doses (0.75-1.5 mg/kg IV) can produce profound hypotension. 8
• Reduce propofol dose by 20-80% when combined with sedative/analgesic agents and in elderly or debilitated patients. 8

CYP2B6 Poor Metabolizers

• Reduce propofol infusion dose by approximately 50% (to 25 mcg/kg/min) in CYP2B6 poor metabolizers to avoid excessive drug exposure and prolonged sedation. 2

Propofol Infusion Syndrome (PRIS)

Recognition and Prevention

• PRIS typically occurs with doses >70 mcg/kg/min for >48 hours, but has been reported at doses as low as 1.9-2.6 mg/kg/hr. 2
• Syndrome presents with metabolic acidosis, rhabdomyolysis, arrhythmias, myocardial failure, and renal failure. 2, 6
• Mortality rate: up to 33%. 2
• Immediately discontinue propofol if PRIS is suspected (worsening metabolic acidosis, hypertriglyceridemia, hypotension with increasing vasopressor requirements, arrhythmias). 2

Aseptic Technique and Handling (FDA Requirements)

Critical Safety Protocols

• Propofol is a single-use vial—never access more than once or use on multiple patients. 9
• Disinfect vial rubber stopper with 70% isopropyl alcohol before accessing. 9
• Draw propofol into sterile syringe immediately after vial is opened using sterile vent spike. 9
• Administration must commence promptly and be completed within 12 hours after vial is opened. 9
• Discard all unused portions, reservoirs, tubing, and solutions containing propofol at 12 hours or end of procedure, whichever occurs sooner. 9

Rationale for Strict Protocols

• Propofol contains benzyl alcohol (1.5 mg/mL) and sodium benzoate (0.7 mg/mL) to inhibit microbial growth up to 12 hours, but can still support microorganism growth. 9
• Failure to use aseptic technique has been associated with microbial contamination, fever, infection/sepsis, and death. 9
• Transmission of bloodborne pathogens (Hepatitis B, Hepatitis C, HIV) has been reported from unsafe injection practices. 9

Common Adverse Effects

Injection Site Pain

• Pain on injection occurs in up to 30% of patients receiving intravenous bolus. 3, 2

Other Adverse Effects

• Hypertriglyceridemia and pancreatitis are uncommon complications. 6
• Allergic complications (including bronchospasm) reported with metabisulfite-containing formulations. 6

Neurosurgical Applications

Neuroprotective Properties

• Propofol decreases cerebral blood flow, cerebral metabolic rate for oxygen, and intracranial pressure. 3
• Has potent anticonvulsant properties. 6
• Acts as potent antioxidant with anti-inflammatory properties. 6

Pharmacokinetic Advantages

Favorable Recovery Profile

• Rapid, clear emergence and lack of cumulative effects even after prolonged administration. 5, 10
• Pharmacokinetics not significantly affected by cirrhosis or renal failure. 3, 2
• Rapidly metabolized in liver by conjugation to glucuronide and sulfate, producing hydrophilic compounds excreted by kidneys. 2