Propofol
CLASS
- IV hypnotic agent
MECHANISM OF ACTION
- potentiates the inhibitory transmitters glycine & GABA which enhance spinal inhibition.
PHARMACEUTICS
- white
- oil-in-water emulsion
- 1% or 2%
- soybean oil
- purified egg phosphatide
- sodium hydroxide
- lecithin
DOSE
- onset: 30-60 seconds
- induction Bolus – 1.5 – 2.0mg/kg -> maintenance 4 – 12mg/kg/hr
- children: induction dose : increase dose by 50% -> maintenance: increase by 25 to 50%
- plasma concentrations: sedation: 0.5 – 1.5 mcg/mL, hypnosis: 2 – 6 mcg/mL
INDICATIONS
- Induction + maintenance of General Anaesthesia
- Sedation
- Status epilepticus
- N+V treatment in chemotherapy
ADVERSE EVENTS
- hypotension
- negative inotropy
- bradycardia
- propofol infusion syndrome -> see below
- apnoea
- pain on injection
- hypertriglyceridemia
PHARMACOKINETICS
- Absorption – IV
- Distribution – 97% protein bound, Vd large
- Metabolism – hepatic
- Elimination – urine, t1/2 = 10-70 min
PROS AND CONS
Advantages in ICU
- characteristically white emulsion mixture (decreased risk of drug errors with multiple infusion in ICU)
- rapid onset
- rapid offset (short context-sensitive half time) -> good for waking up quickly and neurologically +/- extubation
- used for toleration of ventilation, procedures, sedation for transport
- causes bronchodilation
- anti-emetic
- safe in porphyria
- safe in MH patients
- maintenance of cerebral metabolism and blood flow (unlike volatile agents that have been occasionally used in ICU for sedation +/- bronchodilation)
- decrease in ICP
- anticonvulsant (good agent in cerebral oedema and seizures)
- no active metabolites (unlike midazolam and morphine)
- cheap (compared to dexmedetomidine)
Disadvantages in ICU
- painful in injection
- no provision of analgesia (unlike clonidine or dexmetidtomidine, need to infuse opioid for analgesia)
- causes vasodilation and negative inotropy -> hypotension (may not be tolerated in patient with severe cardiovascular compromise ie. severe sepsis with multiorgan failure, midazolam and opioid more sensible in this context)
- can cause apnoea and decreased response to PaCO2 and PaO2 -> have to provide controlled ventilation if using boluses.
- decrease renal blood flow and GFR from hypotension
- metabolised by liver (unlike remifentanil which has organ independent metabolism and inactivation)
- doses of >4mg/kg/hr for >48 hours associated with propofol infusion syndrome -> severe metabolic acidosis, bradycardia, multiorgan failure and treatment resistant cardiac arrest (described mainly in children)
- expensive (compared to midazolam and morphine)
- may support bacterial growth if infused over long period of time (>8 hours) although does now have EDTA and sodium metabisulphide which are anti-bacterial agents in its formulation
References and Links
CCC Pharmacology Series
Respiratory: Bosentan, Delivery of B2 Agonists in Intubated Patients, Nitric Oxide, Oxygen, Prostacyclin, Sildenafil
Cardiovascular: Adenosine, Adrenaline (Epinephrine), Amiodarone, Classification of Vasoactive drugs, Clevidipine, Digoxin, Dobutamine, Dopamine, Levosimendan, Levosimendan vs Dobutamine, Milrinone, Noradrenaline, Phenylephrine, Sodium Nitroprusside (SNiP), Sotalol, Vasopressin
Neurological: Dexmedetomidine, Ketamine, Levetiracetam, Lignocaine, Lithium, Midazolam, Physostigmine, Propofol, Sodium Valproate, Sugammadex, Thiopentone
Endocrine: Desmopressin, Glucagon Therapy, Medications and Thyroid Function
Gastrointestinal: Octreotide, Omeprazole, Ranitidine, Sucralfate, Terlipressin
Genitourinary: Furosemide, Mannitol, Spironolactone
Haematological: Activated Protein C, Alteplase, Aprotinin, Aspirin, Clopidogrel, Dipyridamole, DOACs, Factor VIIa, Heparin, LMW Heparin, Protamine, Prothrombinex, Tenecteplase, Tirofiban, Tranexamic Acid (TXA), Warfarin
Antimicrobial: Antimicrobial Dosing and Kill Characteristics, Benzylpenicillin, Ceftriaxone, Ciprofloxacin, Co-trimoxazole / Bactrim, Fluconazole, Gentamicin, Imipenem, Linezolid, Meropenem, Piperacillin-Tazobactam, Rifampicin, Vancomycin
Analgesic: Alfentanil, Celecoxib, COX II Inhibitors, Ketamine, Lignocaine, Morphine, NSAIDs, Opioids, Paracetamol (Acetaminophen), Paracetamol in Critical Illness, Tramadol
Miscellaneous: Activated Charcoal, Adverse Drug Reactions, Alkali Therapies, Drug Absorption in Critical Illness, Drug Infusion Doses, Epidural Complications, Epidural vs Opioids in Rib Fractures, Magnesium, Methylene Blue, Pharmacology and Critical Illness, PK and Obesity, PK and ECMO, Sodium Bicarbonate Use, Statins in Critical Illness, Therapeutic Drug Monitoring, Weights in Pharmacology
Toxicology: Digibind, Flumazenil, Glucagon Therapy, Intralipid, N-Acetylcysteine, Naloxone, Propofol Infusion Syndrome
Critical Care
Compendium
Chris is an Intensivist and ECMO specialist at The Alfred ICU, where he is Deputy Director (Education). He is a Clinical Adjunct Associate Professor at Monash University, the Lead for the Clinician Educator Incubator programme, and a CICM First Part Examiner.
He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives. He was one of the founders of the FOAM movement (Free Open-Access Medical education) has been recognised for his contributions to education with awards from ANZICS, ANZAHPE, and ACEM.
His one great achievement is being the father of three amazing children.
On Bluesky, he is @precordialthump.bsky.social and on the site that Elon has screwed up, he is @precordialthump.
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