Propofol-related Infusion Syndrome
Reviewed and revised 4 August 2015
OVERVIEW
Propofol-related Infusion Syndrome (PRIS) is a life-threatening condition characterised by acute refractory bradycardia progressing to asystole and one or more of:
- metabolic acidosis
- rhabdomyolysis
- hyperlipidaemia
- enlarged or fatty liver
MECHANISM
Poorly understood — even the central role of propofol has been questioned
- ? direct mitochondrial respiratory chain inhibition
- ? impaired mitochondrial fatty acid metabolism
CLINICAL FEATURES
- high dose, long duration proprofol infusion (maximum dose should be 28mL/hr (70kg adult, 1% propofol at maximum of 4mg/kg/hr)
- on propofol!
- increasing inotrope support
- green urine (some sources say no correlation with PRIS)
- cardiovascular collapse (reflected in PICCO, PAC, ECHO)
RISK FACTORS
- >4mg/kg/hr for 48 hours (large dose, long time); but can occur at lower doses
- younger age
- acute neurological injury
- low carbohydrate intake
- catecholamine infusion
- corticosteroids infusion
INVESTIGATIONS
Bedside
- ECG: Brugada like pattern (coved type = convex-curved ST elevation in V1-V3), RBBB, arrhythmia, heart block
- blood gas: unexplained lactic acidosis; hyperkalaemia (if rhabdomyolysis or renal failure)
Laboratory
- lipids (lipaemic serum)
- UEC (renal failure)
- CK (rhabdomyolysis)
- propofol levels or chromatography (if available)
MANAGEMENT
- high index of suspicion
- monitor for early warning signs (lactate, CK, urinary myoglobin, ECG)
- discontinue propofol immediately
- supportive care and monitoring
- consider pacing
- adequate carbohydrate intake (6-8mg/kg/min)
- carnitine supplementation (theoretical benefit)
- haemodialysis and haemoperfusion (used with success in case reports)
- ECMO (at least 2 cases reported, reasonable strategy given readily reversible pathology)
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
CCC Toxicology Series
General
Approach to acute poisoning, ECGs in Tox, Evidenced-based Tox, Toxicology literature summaries, Does anti-venom work?
Toxins / Overdose
Amphetamines, Barbituates, Benzylpiperazine, Beta Blockers, Calcium Channel Blocker, Carbamazepine, Carbon Monoxide, Ciguatera, Citrate, Clenbuterol, Cocaine, Corrosive ingestion, Cyanide, Digoxin, Ethanol, Ethylene Glycol, Iron, Isoniazid, Lithium, Local anaesthetic, Methanol, Monoamine oxidase inhibitor (MAOI), Mushrooms (non-hallucinogenic), Opioids, Organophosphate, Paracetamol, Paraquat, Plants, Polonium, Salicylate, Scombroid, Sodium channel blockers, Sodium valproate, Theophylline, Toxic alcohols, Tricyclic antidepressants (TCA)
Envenomation
Marine, Snakebite, Spider, Tick paralysis
Syndromes
Alcohol withdrawal, Anticholinergic syndrome, Cholinergic syndrome, Drug withdrawals in ICU, Hyperthermia associated toxidromes, Malignant hyperthermia (MH), Neuroleptic malignant syndrome (NMS), Opioid withdrawal, Propofol Infusion Syndrome (PrIS) Sedative toxidrome, Serotonin syndrome, Sympatholytic toxidrome, Sympathomimetic toxidrome
Decontamination
Activated Charcoal, Gastric lavage, GI Decontamination
Enhanced Elimination
Enhanced elimination, Hyperbaric therapy for CO
Antidotes
Antidote summary, Digibind, Glucagon, Flumazenil, HIET – High dose euglycaemic therapy, Intralipid, Methylene Blue, N-Acetylcysteine (NAC), Naloxone
Miscellaneous
Cocaine chest pain, Digoxin and stone heart theory, Hyperbaric oxygen, Hypoxaemia in tox, Liver failure in tox, Liver transplant for paracetamol, Methaemoglobinaemia, Urine drug screen
Journal articles
- Fudickar A, Bein B. Propofol infusion syndrome: update of clinical manifestation and pathophysiology. Minerva Anestesiol. 2009 May;75(5):339-44
- Loh N, Nair P. Propofol infusion syndrome, Continuing Education in Anaesthesia Critical Care & Pain, 2013; 13(6): 200–202
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.
| INTENSIVE | RAGE | Resuscitology | SMACC
