Schedule H

Intravenous (IV)

• Emulsion for injection 1% w/v (10 mg/mL): 20 mL, 50 mL, 100 mL ampoules/vials

• Emulsion for injection 2% w/v (20 mg/mL): 50 mL vials (for prolonged ICU sedation)

Note: Formulations available with or without preservatives — preservative-free for single use; preserved formulations for multi-dose ICU use. Refer to product label.

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Induction of General Anaesthesia

Adults (Healthy, ASA I-II):

Parameter Recommendation

Starting dose 1.5–2.5 mg/kg IV bolus over 20–40 seconds

Titration Administer in 20–40 mg increments every 10 seconds until loss of consciousness

Usual maintenance dose Not applicable (induction only)

Maximum dose 2.5 mg/kg for single induction bolus

Key Clinical Notes:

• Onset of anaesthesia: 30–60 seconds

• Duration of single bolus effect: 5–10 minutes

• Reduce dose by 20–50% in elderly, debilitated, or haemodynamically compromised patients

• Pre-oxygenation mandatory; airway equipment must be immediately available

1. Maintenance of General Anaesthesia

Adults:

Parameter Recommendation

Starting dose 4–6 mg/kg/hour IV infusion immediately after induction

Titration Adjust by 1–2 mg/kg/hour increments every 5–10 minutes based on surgical stimulus and depth of anaesthesia

Usual maintenance dose 4–12 mg/kg/hour IV continuous infusion

Maximum dose 12 mg/kg/hour

Alternative (Intermittent Bolus for Short Procedures):

• 20–50 mg IV bolus every 3–5 minutes as required

Key Clinical Notes:

• Combine with opioid analgesics for balanced anaesthesia

• Reduce infusion rate with concurrent nitrous oxide or volatile agents

• Monitor depth of anaesthesia (clinical signs, BIS if available)

1. Sedation in Intensive Care Unit (Mechanically Ventilated Adults)

Parameter Recommendation

Starting dose 0.3–0.5 mg/kg/hour IV infusion

Titration Increase by 0.3–0.5 mg/kg/hour every 5–10 minutes to achieve target sedation level (RASS -2 to -3)

Usual maintenance dose 0.3–4 mg/kg/hour IV infusion

Maximum dose 4 mg/kg/hour; avoid exceeding 48 hours at high doses

Key Clinical Notes:

• Daily sedation interruption ("sedation vacation") recommended to assess neurological status

• Monitor for Propofol Infusion Syndrome (PRIS) — especially with doses >4 mg/kg/hour or duration >48 hours

• Consider lipid load contribution to parenteral nutrition calculations

• Not recommended for ICU sedation in children

Secondary Indications – Adults Only (Off-label)

1. Procedural Sedation (Endoscopy, Cardioversion, Minor Procedures) — OFF-LABEL

• Starting dose: 0.5–1 mg/kg IV bolus over 20–30 seconds

• Titration: Additional 10–20 mg IV every 30–60 seconds until adequate sedation

• Usual maintenance dose: Repeat boluses of 10–20 mg as needed OR infusion 1.5–4.5 mg/kg/hour

• Maximum dose: Individualized; avoid cumulative doses causing prolonged apnoea

• Duration: Procedure-dependent (typically 10–30 minutes)

• Specialist only (Anaesthesiologist or trained intensivist with airway management capability)

• Evidence: Indian hospital protocols; international RCTs support safety in trained hands

1. Refractory Status Epilepticus — OFF-LABEL

• Starting dose: 1–2 mg/kg IV bolus

• Titration: Continuous infusion 2–10 mg/kg/hour, titrated to burst suppression on EEG

• Usual maintenance dose: 2–5 mg/kg/hour

• Maximum dose: 10 mg/kg/hour (higher doses increase PRIS risk)

• Duration: 24–48 hours; wean gradually

• Specialist only (Neurologist/Intensivist in ICU setting)

• Evidence: ICMR/AIIMS epilepsy protocols; international guidelines

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

1. Induction of General Anaesthesia (Age ≥3 years)

3–8 years 2.5–3.5 mg/kg IV over 20–30 seconds Additional 1 mg/kg increments every 20 seconds until induction 4 mg/kg

8–16 years 2.5–3 mg/kg IV over 20–30 seconds Additional 1 mg/kg increments as needed 3.5 mg/kg

Key Clinical Notes:

• Children typically require higher mg/kg doses than adults

• Rapid recovery profile advantageous for day-case surgery

• Pre-oxygenation and airway equipment mandatory

1. Maintenance of General Anaesthesia (Age ≥3 years)

Parameter Recommendation

Starting dose 9–12 mg/kg/hour IV infusion

Titration Adjust by 2–3 mg/kg/hour based on depth of anaesthesia

Usual maintenance dose 9–15 mg/kg/hour

Maximum dose 15 mg/kg/hour

Key Clinical Notes:

• Higher infusion rates required compared to adults

• Limit duration to <60 minutes when possible

• Monitor for hypotension and bradycardia

• Avoid prolonged infusions (>4 hours) due to increased PRIS risk in children

Secondary Indications – Paediatric Doses (Off-label)

1. Procedural Sedation (MRI, CT, Painful Procedures) — Age ≥3 years — OFF-LABEL

• Starting dose: 1 mg/kg IV over 20–30 seconds

• Titration: Additional 0.5 mg/kg every 30–60 seconds until adequate sedation

• Usual maintenance dose: 1–2 mg/kg/hour infusion OR intermittent boluses

• Maximum dose: 4 mg/kg/hour

• Duration: Procedure-dependent

• Specialist only (Paediatric anaesthesiologist)

• Evidence: AIIMS protocols; WHO essential anaesthesia recommendations

Safety Monitoring (All Paediatric Use):

• Continuous SpO2, ECG, and blood pressure monitoring

• Capnography recommended

• Resuscitation equipment and trained personnel immediately available

• Nil per oral status confirmed before sedation

• Post-procedure observation until full recovery

NOT recommended below 3 years of age for any indication except under specialist paediatric anaesthesia supervision in tertiary centres. Contraindicated for ICU sedation in children of any age (PRIS risk).

• No dosage adjustment required in renal impairment

• Propofol is primarily hepatically metabolized; renal excretion of metabolites is not clinically significant

• Monitor metabolic parameters during prolonged infusions in patients with concurrent renal dysfunction

• Mild impairment (Child-Pugh A): Use standard doses with caution; slower titration recommended

• Moderate impairment (Child-Pugh B): Reduce induction dose by 20–30%; use lower end of maintenance infusion range; prolonged recovery expected

• Severe impairment (Child-Pugh C): Use with extreme caution; significantly reduced doses required; monitor for prolonged sedation, metabolic acidosis, and triglyceride accumulation; avoid prolonged infusions

• Known hypersensitivity to propofol or any component of the emulsion formulation

• Hypersensitivity to egg lecithin, soybean oil, or glycerol (formulation-specific)

• Severe haemodynamic instability or cardiogenic shock (as sole induction agent)

• Children <3 years for anaesthesia induction/maintenance

• ICU sedation in children (any age) — contraindicated due to PRIS risk

• Patients with disorders of fat metabolism (e.g., primary hyperlipidaemia, diabetic hyperlipidaemia, pancreatitis with hyperlipidaemia)

• Mitochondrial disorders

• Cardiovascular disease — risk of hypotension and bradycardia

• Hypovolaemia or dehydration — correct before induction

• Elderly or debilitated patients — increased sensitivity

• Raised intracranial pressure — may reduce cerebral perfusion pressure; ensure adequate MAP

• Epilepsy — may lower seizure threshold during recovery phase

• Respiratory compromise — requires controlled ventilation capability

• Prolonged infusions (>48 hours) — increased risk of PRIS

• Concurrent parenteral lipid administration — account for lipid load (1.1 kcal/mL from propofol 1%)

• Pancreatitis history — monitor triglycerides

Parameter Recommendation

Risk category No formal Indian classification; use only when essential

Placental transfer Crosses placenta rapidly; neonatal CNS depression possible

Preferred alternatives Thiopentone for obstetric general anaesthesia (traditional first choice)

When may be used Emergency situations when benefits outweigh risks; rapid sequence induction if thiopentone unavailable

Monitoring Maternal blood pressure, fetal heart rate, uterine tone; neonatal Apgar scores and respiratory status

Parameter Recommendation

Compatibility Compatible with breastfeeding after single-dose use

Expected drug levels in milk Very low; rapid clearance from maternal plasma

Preferred alternatives No specific alternative needed for short procedures

Infant monitoring Observe for sedation and feeding difficulties if breastfeeding within 4 hours of administration

Note: No delay in breastfeeding required after single-dose procedural use once mother is fully recovered.

• Starting dose (induction): 1–1.5 mg/kg IV (reduce by 30–50% from adult dose)

• Titration: Slower administration rate (over 30–60 seconds); longer intervals between increments

• Maintenance infusion: 3–6 mg/kg/hour (lower end of adult range)

• Extra risks:

• Pronounced hypotension — ensure adequate hydration before induction

• Bradycardia — especially with concurrent opioids

• Prolonged recovery time

• Increased sensitivity to respiratory depression

• Consider reduced total dose requirement

Interacting Drug Effect Mechanism Management

Opioids (fentanyl, morphine, remifentanil) Synergistic CNS and respiratory depression; enhanced hypotension Pharmacodynamic potentiation Reduce propofol dose by 20–50%; monitor ventilation closely

Benzodiazepines (midazolam, diazepam) Profound sedation; prolonged recovery Additive CNS depression Reduce doses of both agents

Inhalational anaesthetics (sevoflurane, isoflurane) Additive cardiovascular depression; hypotension Pharmacodynamic potentiation Reduce propofol maintenance infusion rate

Droperidol, other antipsychotics Enhanced hypotension and CNS depression Additive effects Reduce propofol dose; close haemodynamic monitoring

High-dose vasodilators (nitroprusside, nitroglycerin) Severe hypotension Additive vasodilation Avoid concurrent boluses; careful titration

Interacting Drug Effect Management

Beta-blockers (metoprolol, esmolol) Increased risk of bradycardia and hypotension Monitor heart rate; have atropine available

Neuromuscular blocking agents (atracurium, vecuronium) Enhanced depth of anaesthesia No dose adjustment needed; monitor paralysis reversal

Phenytoin, carbamazepine May increase propofol metabolism Higher propofol doses may be needed; monitor depth of anaesthesia

Valproate Reduced propofol requirements Lower propofol doses may suffice

Corticosteroids (prolonged use) Additive hypertriglyceridaemia with prolonged propofol infusion Monitor triglycerides

Rifampicin Increased propofol clearance Higher doses may be required

• Pain at injection site (up to 70%) — most common adverse effect

• Hypotension (dose-related)

• Bradycardia

• Apnoea during induction (transient)

• Nausea and vomiting (post-procedure)

• Involuntary movements during induction

• Headache (post-procedure)

• Green discolouration of urine (harmless; due to phenolic metabolites)

• Thrombophlebitis at injection site

• Propofol Infusion Syndrome (PRIS): Metabolic acidosis, rhabdomyolysis, hyperkalaemia, cardiac failure, renal failure, lipaemia — associated with high doses (>4 mg/kg/hour) for prolonged periods (>48 hours); requires immediate discontinuation and supportive care; potentially fatal

• Severe hypotension with cardiovascular collapse: Especially in hypovolaemic, elderly, or cardiac-compromised patients

• Respiratory arrest: Particularly with rapid bolus or concurrent opioids

• Anaphylaxis/anaphylactoid reactions: Rare; may occur in patients with soy or egg allergies

• Pancreatitis: Rare; associated with prolonged use and hypertriglyceridaemia

• Laryngospasm/bronchospasm: Rare; more common in children and during light anaesthesia planes

• Seizure-like activity: Rare; usually during induction or emergence

Baseline (Before Administration):

• Airway assessment

• Cardiovascular status (blood pressure, heart rate, ECG)

• Respiratory function

• Fasting status confirmation

• Lipid profile (if prolonged ICU use anticipated)

During Administration:

• Continuous SpO2 and ECG monitoring

• Blood pressure every 2–3 minutes during induction; every 5 minutes during maintenance

• End-tidal CO2 monitoring (if intubated or during procedural sedation)

• Depth of anaesthesia assessment (clinical signs, BIS if available)

• Airway patency

Long-term ICU Use (>24 hours):

• Daily: Serum triglycerides (target <4.5 mmol/L or 400 mg/dL)

• Daily: Arterial blood gases (monitor for metabolic acidosis)

• Every 24–48 hours: Serum creatine kinase (CK)

• Daily: Lactate levels

• Assess for signs of PRIS: unexplained metabolic acidosis, ECG changes (Brugada-like pattern, arrhythmias), rising CK, cardiac dysfunction

• Diprivan (Aspen/AstraZeneca)

• Neorof (Neon Laboratories)

• Propofol-Lipuro (B. Braun)

• Pofol (Samarth Life Sciences)

• Profol (Claris/Baxter)

• Recofol (Baxter)

• Fresofol (Fresenius Kabi)

• Propovan (Themis Medicare)

Note: Preserved formulations (contain EDTA/sodium metabisulphite) for multi-dose ICU use; preservative-free formulations for single-use in operating theatre.

• 1% (10 mg/mL) 20 mL ampoule: ₹80–₹150

• 1% (10 mg/mL) 50 mL vial: ₹180–₹320

• 1% (10 mg/mL) 100 mL vial: ₹350–₹550

• 2% (20 mg/mL) 50 mL vial: ₹400–₹600

• Not included in NLEM 2022

• Not under NPPA price control

• Available in government hospital supplies for operation theatres and ICUs

• Injection site pain: Pre-treat with lignocaine 20–40 mg IV through the same cannula 30–60 seconds before propofol; alternatively, use large-bore cannula in antecubital vein

• Aseptic handling is critical: Propofol emulsion supports microbial growth — discard unused portion within 6 hours of opening (preservative-free) or 12 hours (preserved formulation); never pool vials

• Propofol provides no analgesia: Always combine with opioids or regional anaesthesia for painful procedures

• PRIS vigilance: Suspect PRIS if unexplained metabolic acidosis, arrhythmias, or rising CK develops during prolonged infusion — discontinue propofol immediately and switch to alternative sedative (e.g., dexmedetomidine, midazolam)

• Lipid load calculation: 1 mL of 1% propofol provides 0.1 g lipid (1.1 kcal); account for this in total parenteral nutrition calculations during ICU sedation

• Recovery profile advantage: Propofol offers rapid, clear-headed recovery — ideal for day-case surgery and procedures requiring early neurological assessment

propofol; general anaesthesia; IV anaesthetic; ICU sedation; procedural sedation; PRIS; paediatric anaesthesia; lipid emulsion; rapid recovery; renal-safe

RxIndia v1.0 — 12 May 2025

• CDSCO approved prescribing information

• Indian Pharmacopoeia

• API Textbook of Medicine

• AIIMS Anaesthesiology Protocols

• Indian Society of Anaesthesiologists Guidelines

• WHO Model List of Essential Medicines (Anaesthesia section)

• ICMR/AIIMS Status Epilepticus Management Protocols (off-label use)

• Goodman & Gilman's The Pharmacological Basis of Therapeutics