Propofol Infusion Syndrome

Environmental Pathograph 21 Show in embeddings browser adverse drug reaction drug-induced mitochondrial toxicity

Propofol infusion syndrome (PRIS) is a rare, frequently fatal multi-organ toxicity of high-dose, prolonged propofol sedation. The defining presentation is acute refractory bradycardia progressing toward asystole, accompanied by some combination of unexplained metabolic or lactic acidosis, rhabdomyolysis, hyperkalemia, hyperlipidemia, hepatomegaly, renal failure and rapidly progressive cardiac failure. The proposed mechanism is impairment of mitochondrial energy metabolism by propofol, through inhibition of the respiratory chain, uncoupling by proton leak, and a defect of fatty acid oxidation, which together starve tissues with high oxidative demand. Because the electrocardiogram in PRIS can show coved ST elevation in the right precordial leads, the syndrome is also the clinical setting in which the term Brugada phenocopy was first used. This entry models the toxic syndrome rather than propofol sedation in general or every adverse effect of the drug.

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1
Definitions
5
Pathophys.
16
Phenotypes
1
Gaps
21
Pathograph
4
Medical Actions
1
Differentials
7
References
1
Deep Research
🏷

Classifications

Harrison's Part
POISONING ENVENOMATION CRITICAL CARE
📘

Definitions

1
Classic PRIS case definition
Acute refractory bradycardia progressing to asystole, together with at least one of metabolic acidosis with a base deficit above 10 mmol/L, rhabdomyolysis, hyperlipidemia, or an enlarged or fatty liver, in a patient receiving propofol.
CASE_DEFINITION
Show evidence (2 references)
PMID:17567345 SUPPORT REVIEW SYNTHESIS Other
"The clinical features of propofol infusion syndrome (PRIS) are acute refractory bradycardia leading to asystole, in the presence of one or more of the following: metabolic acidosis (base deficit > 10 mmol.l(-1)), rhabdomyolysis, hyperlipidaemia, and enlarged or fatty liver."
The source of the feature set this definition records.
PMID:26558513 SUPPORT REVIEW SYNTHESIS Other
"There is no widely accepted definition, but in most cases various combinations of the following are described: unexplained metabolic acidosis, rhabdomyolysis, hyperkalaemia, hepatomegaly, renal failure, hyperlipidaemia, arrhythmia, Brugada-type electrocardiograph (ECG; elevated ST-segment and..."
States that the definition is not settled and lists the wider feature set seen across reported cases, which is why this is a case definition rather than validated criteria.
Notes: Recorded as a case definition rather than consensus diagnostic criteria, because the structured review of 153 published cases states that no widely accepted definition exists and that reported cases describe varying combinations of features.
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Discussions and Knowledge Gaps

1
Does an inherited susceptibility determine which patients receiving high-dose prolonged propofol develop propofol infusion syndrome?
KNOWLEDGE GAP q_pris_genetic_susceptibility
Attached to
pathophysiology#Impaired Mitochondrial Fatty Acid Oxidation pathophysiology#Mitochondrial Respiratory Chain Inhibition by Propofol
The syndrome is rare relative to how widely propofol is used for intensive-care sedation, which implies host susceptibility rather than dose alone. Subclinical mitochondrial disease is listed among the predisposing factors, and a fatty-acid-oxidation defect is one of the two proposed mechanisms, so an inherited partial defect in either pathway is a plausible determinant. The question has been open since the syndrome was named and no cited source here resolves it.
Show evidence (2 references)
PMID:20544610 SUPPORT REVIEW SYNTHESIS Other
"Uncertainty remains as to whether a genetic susceptibility exists."
States the open question directly.
PMID:17567345 SUPPORT REVIEW SYNTHESIS Other
"Predisposing factors include young age, severe critical illness of central nervous system or respiratory origin, exogenous catecholamine or glucocorticoid administration, inadequate carbohydrate intake and subclinical mitochondrial disease."
Names subclinical mitochondrial disease among the predisposing factors, which is the specific form an inherited susceptibility would most likely take.
⚙

Pathophysiology

5
Mitochondrial Respiratory Chain Inhibition by Propofol
Propofol inhibits electron transport, with complex I more sensitive than complex II, and additionally permits a proton leak across the inner mitochondrial membrane. The result is reduced oxidative phosphorylation capacity with a dissipated proton-motive force.
mitochondrial electron transport, NADH to ubiquinone GO:0006120 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves decreased mitochondrial electron transport, NADH to ubiquinone (GO:0006120). GO:0006120 is a biological process from the Gene Ontology. ↓ DECREASED proton leak across the inner mitochondrial membrane GO:1902600 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased proton leak across the inner mitochondrial membrane, annotated with proton transmembrane transport (GO:1902600). GO:1902600 is a biological process from the Gene Ontology. ↑ INCREASED
Downstream
Cellular Bioenergetic Failure Loss of oxidative ATP production starves tissues of high oxidative demand.
Show evidence (2 references)
PMID:26558513 SUPPORT REVIEW SYNTHESIS In Vitro
"Complex I in isolated rat liver mitochondria is more sensitive to inhibition by propofol than complex II"
Locates the respiratory-chain lesion at complex I in isolated mitochondria, which is the experimental basis for this node.
PMID:17567345 SUPPORT REVIEW SYNTHESIS Other
"It is proposed that the syndrome may be caused by either a direct mitochondrial respiratory chain inhibition or impaired mitochondrial fatty acid metabolism mediated by propofol."
States respiratory-chain inhibition as one of the two proposed mechanisms. Note the hedging verb: this is a proposal, not an established mechanism.
Impaired Mitochondrial Fatty Acid Oxidation
Propofol also produces a defect of fatty acid oxidation, evidenced in children with PRIS by accumulation of acylcarnitine species that normalised once the infusion stopped. Free fatty acids rise at the same time, because critical illness shifts the energy source toward lipolysis and the lipid vehicle of propofol adds further substrate.
fatty acid beta-oxidation GO:0006635 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves decreased fatty acid beta-oxidation (GO:0006635). GO:0006635 is a biological process from the Gene Ontology. ↓ DECREASED
Downstream
Cellular Bioenergetic Failure Blocking the alternative oxidative fuel compounds the energy deficit, particularly where carbohydrate intake is inadequate.
Show evidence (1 reference)
PMID:26558513 SUPPORT REVIEW SYNTHESIS Human Clinical
"increased plasma concentrations of acyl derivatives of carnitine in children with PRIS, which normalised after cessation of propofol infusion, suggesting a propofol-induced defect of fatty acid oxidation"
The human biochemical observation behind the fatty-acid-oxidation arm, and its reversibility on withdrawal.
Cellular Bioenergetic Failure
With both oxidative routes impaired, cells with high and sustained energy demand, cardiac myocytes and skeletal muscle in particular, fail to meet their ATP requirement and shift to anaerobic metabolism.
Downstream
Myocyte Injury and Necrosis
Cardiac Conduction Instability
Lactic acidosis Anaerobic metabolism raises lactate, producing the unexplained acidosis.
Metabolic acidosis
Show evidence (1 reference)
PMID:17567345 SUPPORT REVIEW SYNTHESIS Other
"It is proposed that the syndrome may be caused by either a direct mitochondrial respiratory chain inhibition or impaired mitochondrial fatty acid metabolism mediated by propofol."
Both proposed mechanisms converge on failure of mitochondrial energy production, which is what this node represents.
Myocyte Injury and Necrosis
Energy failure in striated muscle produces rhabdomyolysis with release of creatine kinase, myoglobin and intracellular potassium. In the reported series this feature accumulates with duration of exposure rather than with dose.
Downstream
Rhabdomyolysis
Hyperkalemia Potassium released from necrotic myocytes raises serum potassium.
Acute kidney injury Myoglobin released by muscle necrosis injures the kidney.
Discolouration of urine Myoglobin in the urine discolours it, which is how the muscle injury presents at the bedside.
Show evidence (3 references)
PMID:36407194 SUPPORT REVIEW SYNTHESIS Other
"Also, the long-chain acyl-carnitine esters too require CPT-1 for transport and henceforth are unable to traverse into the muscular tissue cells, which leads to muscle necrosis and associated rhabdomyolysis of PRIS"
States the mechanistic step this node asserts: the fatty-acid-transport defect starves muscle and produces necrosis with rhabdomyolysis.
PMID:36407194 SUPPORT REVIEW SYNTHESIS Other
"The cardiovascular system suffers from depleted ATP stores and high FFAs, which directly attack cardiomyocytic functions"
Extends the same energy-failure mechanism to cardiac myocytes, which is why this node feeds both the rhabdomyolysis and the cardiac branches.
PMID:26558513 SUPPORT PRIMARY RESULT Human Clinical
"Cardiac failure and metabolic acidosis occur early in a dose-dependent manner, while arrhythmia, other electrocardiographic changes and rhabdomyolysis appear more frequently after prolonged propofol infusions, irrespective of dose."
Separates the dose-dependent from the duration-dependent features, and places rhabdomyolysis in the latter group.
Cardiac Conduction Instability
Bioenergetic failure in the myocardium destabilises conduction. The earliest electrocardiographic sign reported is right bundle branch block with coved ST elevation in the right precordial leads, the pattern that makes the tracing indistinguishable from the Brugada type 1 pattern. Refractory bradycardia and progression toward asystole follow.
Downstream
Coved ST-segment elevation in right precordial leads
Complete right bundle branch block
Arrhythmia Reported arrhythmias are not confined to bradycardia; the case literature counts arrhythmia in general as one of the commonest features.
Bradycardia
Hypotension
Cardiogenic shock
Show evidence (1 reference)
PMID:17567345 SUPPORT REVIEW SYNTHESIS Other
"An early sign of cardiac instability associated with the syndrome is the development of right bundle branch block with convex-curved ('coved type') ST elevation in the right praecordial leads (V1 to V3) of the electrocardiogram."
Names the electrocardiographic signature and its position as an early marker of cardiac instability.
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Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Propofol Infusion Syndrome Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
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Phenotypes

16
Cardiovascular 6
Arrhythmia 66% of reported cases HP:0011675 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Arrhythmia (HP:0011675). HP:0011675 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:26558513 SUPPORT PRIMARY RESULT Human Clinical
"| Arrhythmia | 101 (66 %)"
The review's own tabulation of how often arrhythmia was reported across 153 cases.
PMID:26558513 SUPPORT PRIMARY RESULT Human Clinical
"Cardiac failure and metabolic acidosis occur early in a dose-dependent manner, while arrhythmia, other electrocardiographic changes and rhabdomyolysis appear more frequently after prolonged propofol infusions, irrespective of dose."
Places arrhythmia among the duration-dependent rather than dose-dependent features.
Hypotension 30% of reported cases HP:0002615 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Hypotension (HP:0002615). HP:0002615 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:26558513 SUPPORT PRIMARY RESULT Human Clinical
"| Hypotension | 45 (30 %)"
The review's tabulated frequency of hypotension across 153 cases.
PMID:30857601 SUPPORT PRIMARY RESULT Human Clinical
"Mortality from propofol infusion syndrome is independently associated with fever and hepatomegaly in children, and electrocardiogram changes, hypotension, hyperkalaemia, traumatic brain injury, and a mean propofol infusion rate >5 mg kg-1 h-1 in adults."
Identifies hypotension among the features independently associated with death in adults.
Bradycardia HP:0001662 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Acute refractory bradycardia, annotated with Bradycardia (HP:0001662). HP:0001662 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:17567345 SUPPORT REVIEW SYNTHESIS Other
"The clinical features of propofol infusion syndrome (PRIS) are acute refractory bradycardia leading to asystole, in the presence of one or more of the following: metabolic acidosis (base deficit > 10 mmol.l(-1)), rhabdomyolysis, hyperlipidaemia, and enlarged or fatty liver."
Names refractory bradycardia leading to asystole as the defining cardiac feature.
Cardiogenic shock 23% of reported cases HP:0030149 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Cardiogenic shock (HP:0030149). HP:0030149 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:26558513 SUPPORT PRIMARY RESULT Human Clinical
"Cardiac failure and metabolic acidosis occur early in a dose-dependent manner, while arrhythmia, other electrocardiographic changes and rhabdomyolysis appear more frequently after prolonged propofol infusions, irrespective of dose."
Reports cardiac failure as an early, dose-dependent feature of the syndrome.
Coved ST-segment elevation in right precordial leads Coved type ST segment elevation HP:6000984 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Coved ST-segment elevation in leads V1 to V3, annotated with Coved type ST segment elevation (HP:6000984). HP:6000984 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:17567345 SUPPORT REVIEW SYNTHESIS Other
"An early sign of cardiac instability associated with the syndrome is the development of right bundle branch block with convex-curved ('coved type') ST elevation in the right praecordial leads (V1 to V3) of the electrocardiogram."
Describes the coved ST elevation and its precordial distribution.
Complete right bundle branch block HP:0011712 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Right bundle branch block, annotated with Complete right bundle branch block (HP:0011712). HP:0011712 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:17567345 SUPPORT REVIEW SYNTHESIS Other
"An early sign of cardiac instability associated with the syndrome is the development of right bundle branch block with convex-curved ('coved type') ST elevation in the right praecordial leads (V1 to V3) of the electrocardiogram."
Names right bundle branch block as part of the early ECG picture.
Digestive 1
Hepatomegaly 11% of reported cases HP:0002240 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Hepatomegaly (HP:0002240). HP:0002240 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:30857601 SUPPORT PRIMARY RESULT Human Clinical
"Mortality from propofol infusion syndrome is independently associated with fever and hepatomegaly in children, and electrocardiogram changes, hypotension, hyperkalaemia, traumatic brain injury, and a mean propofol infusion rate >5 mg kg-1 h-1 in adults."
Identifies hepatomegaly among the features independently associated with death in children.
Genitourinary 2
Discolouration of urine 11% of reported cases Abnormal urinary color HP:0012086 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Discolouration of urine, annotated with Abnormal urinary color (HP:0012086). HP:0012086 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:26558513 SUPPORT PRIMARY RESULT Human Clinical
"| Discolouration of urine | 16 (11 %)"
The tabulated frequency across 153 pooled cases.
PMID:36407194 SUPPORT REVIEW SYNTHESIS Other
"These are typical signs of rhabdomyolysis, leading to renal failure and myoglobinuria."
Supports the mechanism behind the discolouration, myoglobin released by muscle breakdown, which is why this phenotype is wired from the myocyte necrosis node.
Acute kidney injury 39% of reported cases HP:0001919 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Acute kidney injury (HP:0001919). HP:0001919 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:26558513 SUPPORT REVIEW SYNTHESIS Other
"There is no widely accepted definition, but in most cases various combinations of the following are described: unexplained metabolic acidosis, rhabdomyolysis, hyperkalaemia, hepatomegaly, renal failure, hyperlipidaemia, arrhythmia, Brugada-type electrocardiograph (ECG; elevated ST-segment and..."
Lists renal failure among the reported features.
Metabolism 6
Lactic acidosis HP:0003128 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Lactic acidosis (HP:0003128). HP:0003128 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:20544610 SUPPORT REVIEW SYNTHESIS Other
"This anesthetic drug may cause a rare condition named propofol infusion syndrome, characterized by unexplained lactic acidosis, lipemia, rhabdomyolysis, cardiovascular collapse and Brugada-like electrocardiographic pattern or Brugada electrocardiographic phenocopy changes following high-dose..."
The paper that introduced the phenocopy term, listing lactic acidosis first among the syndrome's features.
Metabolic acidosis 77% of reported cases HP:0001942 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Metabolic acidosis (HP:0001942). HP:0001942 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:26558513 SUPPORT PRIMARY RESULT Human Clinical
"Metabolic acidosis remained the most common symptom of PRIS with a constant incidence at around 77 % in reported cases."
Source for the frequency, and for this being the commonest feature.
PMID:17567345 SUPPORT REVIEW SYNTHESIS Other
"The clinical features of propofol infusion syndrome (PRIS) are acute refractory bradycardia leading to asystole, in the presence of one or more of the following: metabolic acidosis (base deficit > 10 mmol.l(-1)), rhabdomyolysis, hyperlipidaemia, and enlarged or fatty liver."
Places metabolic acidosis in the case definition with its threshold.
Hyperkalemia 24% of reported cases HP:0002153 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Hyperkalemia (HP:0002153). HP:0002153 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:30857601 SUPPORT PRIMARY RESULT Human Clinical
"Mortality from propofol infusion syndrome is independently associated with fever and hepatomegaly in children, and electrocardiogram changes, hypotension, hyperkalaemia, traumatic brain injury, and a mean propofol infusion rate >5 mg kg-1 h-1 in adults."
Identifies hyperkalemia among the features independently associated with death in adults.
Hypertriglyceridemia 24% of reported cases, and absent in most HP:0002155 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Hypertriglyceridemia (HP:0002155). HP:0002155 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:26558513 SUPPORT PRIMARY RESULT Human Clinical
"CONCLUSION: PRIS can develop with propofol infusion <4 mg/kg per hour and its diagnosis may be challenging as some of its typical features (hypertriglyceridaemia, fever, hepatomegaly, heart failure) are often (>95 %) missing and others (arrhythmia, electrocardiographic changes) occur late."
Names hypertriglyceridaemia directly, matching the bound term, and records the review's own caution that this feature is usually absent, so it must not be treated as required for the diagnosis.
PMID:30857601 SUPPORT PRIMARY RESULT Human Clinical
"Lipidaemia, fever, and hepatomegaly occurred more frequently in children than in adults, whilst rhabdomyolysis and hyperkalaemia were more frequent in adults."
Reports lipidaemia as commoner in children.
Elevated hepatic transaminases 13% of reported cases, tabulated as abnormal liver function test Elevated circulating hepatic transaminase concentration HP:0002910 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Elevated liver enzymes, annotated with Elevated circulating hepatic transaminase concentration (HP:0002910). HP:0002910 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:26558513 SUPPORT PRIMARY RESULT Human Clinical
"| Abnormal liver function test | 20 (13 %)"
The tabulated frequency across 153 pooled cases.
PMID:36407194 SUPPORT REVIEW SYNTHESIS Other
"The patient should be closely monitored for the development of signs and symptoms of PRIS which include metabolic acidosis with lactic acidosis, severe bradycardia, ventricular arrhythmia, asystole, cardiogenic shock, rhabdomyolysis, hepatomegaly, acute kidney injury, renal failure,..."
Names elevated liver enzymes among the features to monitor for, which is the abnormality the bound term describes.
Fever 19% of reported cases HP:0001945 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Fever (HP:0001945). HP:0001945 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:26558513 SUPPORT PRIMARY RESULT Human Clinical
"We found that propofol infusion rate and duration, the presence of traumatic brain injury and fever are factors independently associated with mortality in reported cases of PRIS"
Places fever among the factors independently associated with death in the 153-case series.
Musculoskeletal 1
Rhabdomyolysis 56% of reported cases HP:0003201 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Rhabdomyolysis (HP:0003201). HP:0003201 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:30857601 SUPPORT PRIMARY RESULT Human Clinical
"Lipidaemia, fever, and hepatomegaly occurred more frequently in children than in adults, whilst rhabdomyolysis and hyperkalaemia were more frequent in adults."
Reports the age split in feature frequency, with rhabdomyolysis commoner in adults.
💊

Medical Actions

4
Immediate Discontinuation of Propofol
Action: discontinuation of the causative drugNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is discontinuation of the causative drug, annotated with Pharmacotherapy Discontinuation (NCIT:C128535). NCIT:C128535 is a clinical intervention from the NCI Thesaurus. Ontology label: Pharmacotherapy Discontinuation NCIT:C128535
Platform: Other
Recognising the syndrome and stopping the infusion, substituting an alternative sedative, is the first step in management. The reversibility of the acylcarnitine abnormality on withdrawal is part of the evidence that the drug is the cause.
Mechanism Target:
Mitochondrial Respiratory Chain Inhibition by Propofol — Removing the inhibitor is the only measure that addresses the cause.
Impaired Mitochondrial Fatty Acid Oxidation
Show evidence (1 reference)
PMID:36407194 SUPPORT REVIEW SYNTHESIS Other
"The first step in managing PRIS is to immediately recognise and discontinue propofol infusion and replace it with other sedating agents like alfentanil, midazolam, etc."
States discontinuation as the first management step.
Continuous Haemofiltration
Action: continuous haemofiltrationNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is continuous haemofiltration, annotated with Hemofiltration (NCIT:C172594). NCIT:C172594 is a clinical intervention from the NCI Thesaurus. Ontology label: Hemofiltration NCIT:C172594
Platform: Other
Extracorporeal clearance, recommended early in management by the structured review of 168 cases.
Mechanism Target:
Metabolic acidosis — Correcting the acidosis and clearing accumulated metabolites.
Show evidence (1 reference)
PMID:30857601 SUPPORT REVIEW SYNTHESIS Other
"We recommend early consideration of continuous haemofiltration in the management of propofol infusion syndrome."
The review's explicit management recommendation.
Haemodialysis with Cardiorespiratory Support
Action: haemodialysis with cardiorespiratory supportNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is haemodialysis with cardiorespiratory support, annotated with Hemodialysis (NCIT:C15248). NCIT:C15248 is a clinical intervention from the NCI Thesaurus. Ontology label: Hemodialysis NCIT:C15248
Platform: Other
Dialysis or haemoperfusion combined with cardiorespiratory support has been the most successful reported treatment, in a syndrome where options are otherwise limited.
Mechanism Target:
Metabolic acidosis
Cardiogenic shock
Show evidence (1 reference)
PMID:17567345 SUPPORT REVIEW SYNTHESIS Other
"Haemodialysis or haemoperfusion with cardiorespiratory support has been the most successful treatment."
Identifies the treatment combination with the best reported outcome.
Sodium Bicarbonate for Acidosis
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: sodium bicarbonate CHEBI:32139 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses sodium bicarbonate, annotated with sodium hydrogencarbonate (CHEBI:32139). CHEBI:32139 is a therapeutic agent from Chemical Entities of Biological Interest.
Platform: Small molecule
Buffering of metabolic and lactic acidosis as supportive management.
Mechanism Target:
Metabolic acidosis
Show evidence (1 reference)
PMID:36407194 SUPPORT REVIEW SYNTHESIS Other
"Metabolic and lactic acidosis can be managed by the administration of sodium bicarbonate, haemodialysis, and hemofiltration."
Names bicarbonate among the measures for the acidosis.
🌍

Epidemiology

2
Incidence in critically ill adults on propofol for more than 24 hours
In a prospective multicenter cohort of 1,017 critically ill adults prescribed propofol, the syndrome developed in 11, slightly exceeding 1%, under a conservative definition requiring metabolic acidosis plus cardiac dysfunction plus one of rhabdomyolysis, hypertriglyceridemia or renal failure. This is the only prospective incidence estimate; every other figure in this entry comes from pooled case reports, where the denominator is unknown.
Show evidence (2 references)
PMID:19874582 SUPPORT PRIMARY RESULT Human Clinical
"CONCLUSIONS: Despite using a conservative definition for PRIS, and only considering new-onset PRIS clinical manifestations, the incidence of PRIS slightly exceeds 1%."
The prospective incidence estimate, with the authors' own note that their definition was conservative.
PMID:19874582 SUPPORT PRIMARY RESULT Human Clinical
"While propofol is associated with an infusion syndrome (PRIS) that may cause death, the incidence of PRIS is unknown."
States why a prospective denominator was needed: before this study the incidence rested on voluntarily reported cases.
Cases in the published literature to 2019
A structured literature review identified 168 cases across 108 publications, analysing children and adults separately because propofol is no longer used for long-term sedation in children.
Show evidence (1 reference)
PMID:30857601 SUPPORT PRIMARY RESULT Human Clinical
"We reviewed 108 publications documenting 168 cases of propofol infusion syndrome."
Gives the size of the reported case literature.
🔀

Differential Diagnoses

1

Conditions with similar clinical presentations that must be differentiated from Propofol Infusion Syndrome:

Brugada syndrome
Overlapping Features The electrocardiogram in propofol infusion syndrome can show coved ST elevation in the right precordial leads, which is the Brugada type 1 pattern, so the tracing alone does not separate the two. What separates them is the clinical setting, the accompanying metabolic and muscle findings, and resolution once the infusion stops. Whether the pattern here should be called a Brugada phenocopy is contested, and the dispute matters because this syndrome is where the term was coined; see notes.
Distinguishing Features
  • A high-dose, prolonged propofol infusion is running when the pattern appears
  • Accompanying metabolic acidosis, rhabdomyolysis, hyperkalemia or hepatomegaly, which congenital Brugada syndrome does not produce
  • Resolution of the pattern after the infusion is stopped
  • Right bundle branch block accompanying the coved ST elevation as an early sign
Show evidence (3 references)
PMID:20544610 SUPPORT REVIEW SYNTHESIS Other
"This anesthetic drug may cause a rare condition named propofol infusion syndrome, characterized by unexplained lactic acidosis, lipemia, rhabdomyolysis, cardiovascular collapse and Brugada-like electrocardiographic pattern or Brugada electrocardiographic phenocopy changes following high-dose..."
The paper that introduced the phenocopy term, describing the shared ECG appearance alongside the metabolic and muscle features that distinguish the syndrome.
PMID:23094876 SUPPORT REVIEW SYNTHESIS Other
"to describe an acquired Brugada-like ECG pattern in the setting of propofol infusion syndrome."
Records that the phenocopy terminology was introduced for this syndrome specifically.
PMID:23094876 REFUTE REVIEW SYNTHESIS Other
"Consequently, the Group 1 drugs for the most part cannot be considered Brugada phenocopies."
The same classification paper places propofol among its Group 1 agents, which it says act by sodium channel blockade and mostly cannot be considered phenocopies. So the paper that adopted the term for this syndrome also excludes its drug from the category.
{ }

Source YAML

click to show 
name: Propofol Infusion Syndrome
creation_date: "2026-09-29T00:00:00Z"
category: Environmental
categories:
- Toxic Exposure Disorder
- Adverse Drug Reaction
- Acquired Mitochondrial Dysfunction
description: >-
  Propofol infusion syndrome (PRIS) is a rare, frequently fatal multi-organ
  toxicity of high-dose, prolonged propofol sedation. The defining presentation
  is acute refractory bradycardia progressing toward asystole, accompanied by
  some combination of unexplained metabolic or lactic acidosis, rhabdomyolysis,
  hyperkalemia, hyperlipidemia, hepatomegaly, renal failure and rapidly
  progressive cardiac failure. The proposed mechanism is impairment of
  mitochondrial energy metabolism by propofol, through inhibition of the
  respiratory chain, uncoupling by proton leak, and a defect of fatty acid
  oxidation, which together starve tissues with high oxidative demand. Because
  the electrocardiogram in PRIS can show coved ST elevation in the right
  precordial leads, the syndrome is also the clinical setting in which the term
  Brugada phenocopy was first used. This entry models the toxic syndrome rather
  than propofol sedation in general or every adverse effect of the drug.
synonyms:
- PRIS
- propofol-related infusion syndrome
parents:
- adverse drug reaction
- drug-induced mitochondrial toxicity
notes: >-
  No ontology term for this syndrome was found, so no disease_term is asserted.
  MONDO was searched through the configured ols:mondo adapter with
  `search l~propofol` and with free-text searches for "propofol" and "propofol
  infusion syndrome"; all three returned nothing, against a positive control on
  `l~Brugada` that returns the expected Brugada syndrome terms. NCIT
  (`ols:ncit`, `search l^propofol`) holds only the drug, NCIT:C29384 Propofol.
  No cached Orphanet leaf record mentions propofol. MeSH, by contrast, does code
  the syndrome, as the supplementary concept D000072736 "Propofol Infusion
  Syndrome" (verified through the NCBI MeSH database; note that a supplementary
  concept record is retrieved by its own UID, 2016775, not by the 68-prefixed
  form that works for descriptors). dismech has no MeSH mapping slot, so that
  identifier is recorded here rather than under mappings. A MONDO term request is
  a reasonable follow-up; its required parent field is a nosology judgement that
  has not been made, because classifying by cause places the syndrome with drug
  toxicities while classifying by manifestation places it with acquired
  multi-system metabolic disease. See issue #13101.

  No conforms_to is declared. The two closest mechanism modules were read and
  neither fits. `mitochondrial_dysfunction` scopes itself to the hallmark of
  aging, and its chain begins at mitochondrial damage with mtDNA mutation and
  passes through impaired mitophagy, neither of which this acute
  pharmacological inhibition has. `metabolic_intoxication_decompensation`
  scopes itself to intoxication-type inborn errors with a deficient enzyme or
  transporter, where the block here is reversible drug inhibition in a
  previously normal pathway. A drug-induced mitochondrial toxicity module would
  be a new module rather than a second use of either.
classifications:
  harrisons_chapter:
  - classification_value: POISONING_ENVENOMATION
    evidence:
    - reference: PMID:17567345
      reference_title: Propofol infusion syndrome.
      supports: SUPPORT
      evidence_source: OTHER
      quote_role: REVIEW_SYNTHESIS
      snippet: >-
        There is an association between PRIS and propofol infusions at doses
        higher than 4 mg.kg(-1).h(-1) for greater than 48 h duration.
      explanation: >-
        The syndrome is a dose- and duration-related toxicity of a drug rather
        than a disease of independent origin, which places it in the poisoning
        and drug-overdose chapter.
  - classification_value: CRITICAL_CARE
    evidence:
    - reference: PMID:26558513
      reference_title: "Propofol infusion syndrome: a structured review of experimental studies and 153 published case reports."
      supports: SUPPORT
      evidence_source: OTHER
      quote_role: REVIEW_SYNTHESIS
      snippet: >-
        In 138 cases (90 %) patients developed PRIS as a complication of
        non-procedural sedation in ICUs and in 15 cases (10 %) as a complication
        of the use of propofol during anaesthesia.
      explanation: >-
        Nine in ten reported cases arose during intensive-care sedation rather
        than anaesthesia, which places the syndrome in the critical-care chapter
        as well as the poisoning one.
definitions:
- name: Classic PRIS case definition
  definition_type: CASE_DEFINITION
  derivation_basis: ESTABLISHED_CRITERIA
  description: >-
    Acute refractory bradycardia progressing to asystole, together with at least
    one of metabolic acidosis with a base deficit above 10 mmol/L,
    rhabdomyolysis, hyperlipidemia, or an enlarged or fatty liver, in a patient
    receiving propofol.
  notes: >-
    Recorded as a case definition rather than consensus diagnostic criteria,
    because the structured review of 153 published cases states that no widely
    accepted definition exists and that reported cases describe varying
    combinations of features.
  evidence:
  - reference: PMID:17567345
    reference_title: Propofol infusion syndrome.
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      The clinical features of propofol infusion syndrome (PRIS) are acute
      refractory bradycardia leading to asystole, in the presence of one or more
      of the following: metabolic acidosis (base deficit > 10 mmol.l(-1)),
      rhabdomyolysis, hyperlipidaemia, and enlarged or fatty liver.
    explanation: The source of the feature set this definition records.
  - reference: PMID:26558513
    reference_title: "Propofol infusion syndrome: a structured review of experimental studies and 153 published case reports."
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      There is no widely accepted definition, but in most cases various
      combinations of the following are described: unexplained metabolic
      acidosis, rhabdomyolysis, hyperkalaemia, hepatomegaly, renal failure,
      hyperlipidaemia, arrhythmia, Brugada-type electrocardiograph (ECG;
      elevated ST-segment and coved T-wave) and rapidly progressive cardiac
      failure.
    explanation: >-
      States that the definition is not settled and lists the wider feature set
      seen across reported cases, which is why this is a case definition rather
      than validated criteria.
epidemiology:
- name: Incidence in critically ill adults on propofol for more than 24 hours
  description: >-
    In a prospective multicenter cohort of 1,017 critically ill adults
    prescribed propofol, the syndrome developed in 11, slightly exceeding 1%,
    under a conservative definition requiring metabolic acidosis plus cardiac
    dysfunction plus one of rhabdomyolysis, hypertriglyceridemia or renal
    failure. This is the only prospective incidence estimate; every other figure
    in this entry comes from pooled case reports, where the denominator is
    unknown.
  unit: proportion of a prospective ICU cohort
  evidence:
  - reference: PMID:19874582
    reference_title: "Incidence of propofol-related infusion syndrome in critically ill adults: a prospective, multicenter study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: PRIMARY_RESULT
    snippet: >-
      CONCLUSIONS: Despite using a conservative definition for PRIS, and only
      considering new-onset PRIS clinical manifestations, the incidence of PRIS
      slightly exceeds 1%.
    explanation: >-
      The prospective incidence estimate, with the authors' own note that their
      definition was conservative.
  - reference: PMID:19874582
    reference_title: "Incidence of propofol-related infusion syndrome in critically ill adults: a prospective, multicenter study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: PRIMARY_RESULT
    snippet: >-
      While propofol is associated with an infusion syndrome (PRIS) that may
      cause death, the incidence of PRIS is unknown.
    explanation: >-
      States why a prospective denominator was needed: before this study the
      incidence rested on voluntarily reported cases.
- name: Cases in the published literature to 2019
  description: >-
    A structured literature review identified 168 cases across 108
    publications, analysing children and adults separately because propofol is
    no longer used for long-term sedation in children.
  unit: cases reported in the literature
  evidence:
  - reference: PMID:30857601
    reference_title: "Propofol infusion syndrome: a structured literature review and analysis of published case reports."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: PRIMARY_RESULT
    snippet: We reviewed 108 publications documenting 168 cases of propofol infusion syndrome.
    explanation: Gives the size of the reported case literature.
pathophysiology:
- name: Mitochondrial Respiratory Chain Inhibition by Propofol
  biological_scale: MOLECULAR
  description: >-
    Propofol inhibits electron transport, with complex I more sensitive than
    complex II, and additionally permits a proton leak across the inner
    mitochondrial membrane. The result is reduced oxidative phosphorylation
    capacity with a dissipated proton-motive force.
  biological_processes:
  - preferred_term: mitochondrial electron transport, NADH to ubiquinone
    modifier: DECREASED
    term:
      id: GO:0006120
      label: mitochondrial electron transport, NADH to ubiquinone
  - preferred_term: proton leak across the inner mitochondrial membrane
    modifier: INCREASED
    term:
      id: GO:1902600
      label: proton transmembrane transport
  downstream:
  - target: Cellular Bioenergetic Failure
    causal_link_type: DIRECT
    description: Loss of oxidative ATP production starves tissues of high oxidative demand.
  evidence:
  - reference: PMID:26558513
    reference_title: "Propofol infusion syndrome: a structured review of experimental studies and 153 published case reports."
    supports: SUPPORT
    evidence_source: IN_VITRO
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Complex I in isolated rat liver mitochondria is more sensitive to
      inhibition by propofol than complex II
    explanation: >-
      Locates the respiratory-chain lesion at complex I in isolated
      mitochondria, which is the experimental basis for this node.
  - reference: PMID:17567345
    reference_title: Propofol infusion syndrome.
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      It is proposed that the syndrome may be caused by either a direct
      mitochondrial respiratory chain inhibition or impaired mitochondrial fatty
      acid metabolism mediated by propofol.
    explanation: >-
      States respiratory-chain inhibition as one of the two proposed mechanisms.
      Note the hedging verb: this is a proposal, not an established mechanism.
- name: Impaired Mitochondrial Fatty Acid Oxidation
  biological_scale: MOLECULAR
  description: >-
    Propofol also produces a defect of fatty acid oxidation, evidenced in
    children with PRIS by accumulation of acylcarnitine species that normalised
    once the infusion stopped. Free fatty acids rise at the same time, because
    critical illness shifts the energy source toward lipolysis and the lipid
    vehicle of propofol adds further substrate.
  biological_processes:
  - preferred_term: fatty acid beta-oxidation
    modifier: DECREASED
    term:
      id: GO:0006635
      label: fatty acid beta-oxidation
  downstream:
  - target: Cellular Bioenergetic Failure
    causal_link_type: DIRECT
    description: >-
      Blocking the alternative oxidative fuel compounds the energy deficit,
      particularly where carbohydrate intake is inadequate.
  evidence:
  - reference: PMID:26558513
    reference_title: "Propofol infusion syndrome: a structured review of experimental studies and 153 published case reports."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      increased plasma concentrations of acyl derivatives of carnitine in
      children with PRIS, which normalised after cessation of propofol infusion,
      suggesting a propofol-induced defect of fatty acid oxidation
    explanation: >-
      The human biochemical observation behind the fatty-acid-oxidation arm, and
      its reversibility on withdrawal.
- name: Cellular Bioenergetic Failure
  biological_scale: CELLULAR
  description: >-
    With both oxidative routes impaired, cells with high and sustained energy
    demand, cardiac myocytes and skeletal muscle in particular, fail to meet
    their ATP requirement and shift to anaerobic metabolism.
  downstream:
  - target: Myocyte Injury and Necrosis
    causal_link_type: DIRECT
  - target: Cardiac Conduction Instability
    causal_link_type: DIRECT
  - target: Lactic acidosis
    causal_link_type: DIRECT
    description: Anaerobic metabolism raises lactate, producing the unexplained acidosis.
  - target: Metabolic acidosis
    causal_link_type: DIRECT
  evidence:
  - reference: PMID:17567345
    reference_title: Propofol infusion syndrome.
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      It is proposed that the syndrome may be caused by either a direct
      mitochondrial respiratory chain inhibition or impaired mitochondrial fatty
      acid metabolism mediated by propofol.
    explanation: >-
      Both proposed mechanisms converge on failure of mitochondrial energy
      production, which is what this node represents.
- name: Myocyte Injury and Necrosis
  biological_scale: TISSUE
  description: >-
    Energy failure in striated muscle produces rhabdomyolysis with release of
    creatine kinase, myoglobin and intracellular potassium. In the reported
    series this feature accumulates with duration of exposure rather than with
    dose.
  downstream:
  - target: Rhabdomyolysis
    causal_link_type: DIRECT
  - target: Hyperkalemia
    causal_link_type: DIRECT
    description: Potassium released from necrotic myocytes raises serum potassium.
  - target: Acute kidney injury
    causal_link_type: DIRECT
    description: Myoglobin released by muscle necrosis injures the kidney.
  - target: Discolouration of urine
    causal_link_type: DIRECT
    description: >-
      Myoglobin in the urine discolours it, which is how the muscle injury
      presents at the bedside.
  evidence:
  - reference: PMID:36407194
    reference_title: "Propofol-Related Infusion Syndrome: A Clinical Review."
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Also, the long-chain acyl-carnitine esters too require CPT-1 for transport
      and henceforth are unable to traverse into the muscular tissue cells, which
      leads to muscle necrosis and associated rhabdomyolysis of PRIS
    explanation: >-
      States the mechanistic step this node asserts: the fatty-acid-transport
      defect starves muscle and produces necrosis with rhabdomyolysis.
  - reference: PMID:36407194
    reference_title: "Propofol-Related Infusion Syndrome: A Clinical Review."
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      The cardiovascular system suffers from depleted ATP stores and high FFAs,
      which directly attack cardiomyocytic functions
    explanation: >-
      Extends the same energy-failure mechanism to cardiac myocytes, which is why
      this node feeds both the rhabdomyolysis and the cardiac branches.
  - reference: PMID:26558513
    reference_title: "Propofol infusion syndrome: a structured review of experimental studies and 153 published case reports."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: PRIMARY_RESULT
    snippet: >-
      Cardiac failure and metabolic acidosis occur early in a dose-dependent
      manner, while arrhythmia, other electrocardiographic changes and
      rhabdomyolysis appear more frequently after prolonged propofol infusions,
      irrespective of dose.
    explanation: >-
      Separates the dose-dependent from the duration-dependent features, and
      places rhabdomyolysis in the latter group.
- name: Cardiac Conduction Instability
  biological_scale: TISSUE
  description: >-
    Bioenergetic failure in the myocardium destabilises conduction. The earliest
    electrocardiographic sign reported is right bundle branch block with coved
    ST elevation in the right precordial leads, the pattern that makes the
    tracing indistinguishable from the Brugada type 1 pattern. Refractory
    bradycardia and progression toward asystole follow.
  downstream:
  - target: Coved ST-segment elevation in right precordial leads
    causal_link_type: DIRECT
  - target: Complete right bundle branch block
    causal_link_type: DIRECT
  - target: Arrhythmia
    causal_link_type: DIRECT
    description: >-
      Reported arrhythmias are not confined to bradycardia; the case literature
      counts arrhythmia in general as one of the commonest features.
  - target: Bradycardia
    causal_link_type: DIRECT
  - target: Hypotension
    causal_link_type: DIRECT
  - target: Cardiogenic shock
    causal_link_type: DIRECT
  evidence:
  - reference: PMID:17567345
    reference_title: Propofol infusion syndrome.
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      An early sign of cardiac instability associated with the syndrome is the
      development of right bundle branch block with convex-curved ('coved type')
      ST elevation in the right praecordial leads (V1 to V3) of the
      electrocardiogram.
    explanation: >-
      Names the electrocardiographic signature and its position as an early
      marker of cardiac instability.
phenotypes:
- name: Lactic acidosis
  category: Laboratory
  description: Unexplained lactic acidosis, one of the cardinal features of the syndrome.
  phenotype_term:
    preferred_term: Lactic acidosis
    term:
      id: HP:0003128
      label: Lactic acidosis
  evidence:
  - reference: PMID:20544610
    reference_title: Propofol infusion syndrome and Brugada syndrome electrocardiographic phenocopy.
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      This anesthetic drug may cause a rare condition named propofol infusion
      syndrome, characterized by unexplained lactic acidosis, lipemia,
      rhabdomyolysis, cardiovascular collapse and Brugada-like
      electrocardiographic pattern or Brugada electrocardiographic phenocopy
      changes following high-dose propofol infusion over prolonged periods of
      time.
    explanation: >-
      The paper that introduced the phenocopy term, listing lactic acidosis
      first among the syndrome's features.
- name: Metabolic acidosis
  category: Laboratory
  description: >-
    Metabolic acidosis with a base deficit above 10 mmol/L is part of the
    classic case definition, and occurs early and in proportion to dose.
  frequency: 77% of reported cases
  phenotype_term:
    preferred_term: Metabolic acidosis
    term:
      id: HP:0001942
      label: Metabolic acidosis
  evidence:
  - reference: PMID:26558513
    reference_title: "Propofol infusion syndrome: a structured review of experimental studies and 153 published case reports."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: PRIMARY_RESULT
    snippet: >-
      Metabolic acidosis remained the most common symptom of PRIS with a constant
      incidence at around 77 % in reported cases.
    explanation: Source for the frequency, and for this being the commonest feature.
  - reference: PMID:17567345
    reference_title: Propofol infusion syndrome.
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      The clinical features of propofol infusion syndrome (PRIS) are acute
      refractory bradycardia leading to asystole, in the presence of one or more
      of the following: metabolic acidosis (base deficit > 10 mmol.l(-1)),
      rhabdomyolysis, hyperlipidaemia, and enlarged or fatty liver.
    explanation: Places metabolic acidosis in the case definition with its threshold.
- name: Rhabdomyolysis
  category: Laboratory
  description: >-
    Skeletal muscle breakdown, more frequent in adults than children, appearing
    after prolonged infusion irrespective of dose.
  frequency: 56% of reported cases
  phenotype_term:
    preferred_term: Rhabdomyolysis
    term:
      id: HP:0003201
      label: Rhabdomyolysis
  evidence:
  - reference: PMID:30857601
    reference_title: "Propofol infusion syndrome: a structured literature review and analysis of published case reports."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: PRIMARY_RESULT
    snippet: >-
      Lipidaemia, fever, and hepatomegaly occurred more frequently in children
      than in adults, whilst rhabdomyolysis and hyperkalaemia were more frequent
      in adults.
    explanation: >-
      Reports the age split in feature frequency, with rhabdomyolysis commoner
      in adults.
- name: Hyperkalemia
  category: Laboratory
  description: >-
    Raised serum potassium, in part from potassium released by necrotic
    myocytes, and independently associated with mortality in adults.
  frequency: 24% of reported cases
  phenotype_term:
    preferred_term: Hyperkalemia
    term:
      id: HP:0002153
      label: Hyperkalemia
  evidence:
  - reference: PMID:30857601
    reference_title: "Propofol infusion syndrome: a structured literature review and analysis of published case reports."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: PRIMARY_RESULT
    snippet: >-
      Mortality from propofol infusion syndrome is independently associated with
      fever and hepatomegaly in children, and electrocardiogram changes,
      hypotension, hyperkalaemia, traumatic brain injury, and a mean propofol
      infusion rate >5 mg kg-1 h-1 in adults.
    explanation: >-
      Identifies hyperkalemia among the features independently associated with
      death in adults.
- name: Hypertriglyceridemia
  category: Laboratory
  description: >-
    Hyperlipidemia, reported as lipaemia or raised plasma triglycerides, and
    more frequent in children than adults.
  frequency: 24% of reported cases, and absent in most
  phenotype_term:
    preferred_term: Hypertriglyceridemia
    term:
      id: HP:0002155
      label: Hypertriglyceridemia
  evidence:
  - reference: PMID:26558513
    reference_title: "Propofol infusion syndrome: a structured review of experimental studies and 153 published case reports."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: PRIMARY_RESULT
    snippet: >-
      CONCLUSION: PRIS can develop with propofol infusion <4 mg/kg per hour and
      its diagnosis may be challenging as some of its typical features
      (hypertriglyceridaemia, fever, hepatomegaly, heart failure) are often (>95
      %) missing and others (arrhythmia, electrocardiographic changes) occur
      late.
    explanation: >-
      Names hypertriglyceridaemia directly, matching the bound term, and records
      the review's own caution that this feature is usually absent, so it must
      not be treated as required for the diagnosis.
  - reference: PMID:30857601
    reference_title: "Propofol infusion syndrome: a structured literature review and analysis of published case reports."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: PRIMARY_RESULT
    snippet: >-
      Lipidaemia, fever, and hepatomegaly occurred more frequently in children
      than in adults, whilst rhabdomyolysis and hyperkalaemia were more frequent
      in adults.
    explanation: Reports lipidaemia as commoner in children.
- name: Elevated hepatic transaminases
  category: Laboratory
  frequency: 13% of reported cases, tabulated as abnormal liver function test
  description: >-
    Abnormal liver function tests, reported in 13% of pooled cases. Bound to the
    transaminase term because that is the abnormality the clinical review names;
    the review that tabulates the frequency uses the broader phrase "abnormal
    liver function test", so the frequency is recorded with that wording.
  phenotype_term:
    preferred_term: Elevated liver enzymes
    term:
      id: HP:0002910
      label: Elevated circulating hepatic transaminase concentration
  evidence:
  - reference: PMID:26558513
    reference_title: "Propofol infusion syndrome: a structured review of experimental studies and 153 published case reports."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: PRIMARY_RESULT
    snippet: "| Abnormal liver function test | 20 (13 %)"
    explanation: The tabulated frequency across 153 pooled cases.
  - reference: PMID:36407194
    reference_title: "Propofol-Related Infusion Syndrome: A Clinical Review."
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      The patient should be closely monitored for the development of signs and
      symptoms of PRIS which include metabolic acidosis with lactic acidosis,
      severe bradycardia, ventricular arrhythmia, asystole, cardiogenic shock,
      rhabdomyolysis, hepatomegaly, acute kidney injury, renal failure,
      hypertriglyceridemia, hyperkalaemia, hyperlipidaemia, elevated liver
      enzymes, increased serum creatinine kinase, serum lipase, amylase, lactate,
      myoglobinuria and Brugada-like ST elevation in ECG to name the important
      ones.
    explanation: >-
      Names elevated liver enzymes among the features to monitor for, which is
      the abnormality the bound term describes.
- name: Discolouration of urine
  category: Clinical
  frequency: 11% of reported cases
  description: >-
    Discoloured urine, reflecting myoglobin released by muscle necrosis. Bound to
    the urinary-colour term rather than to myoglobinuria, because the 11% figure
    counts the observed discolouration rather than a confirmed myoglobin
    measurement.
  phenotype_term:
    preferred_term: Discolouration of urine
    term:
      id: HP:0012086
      label: Abnormal urinary color
  evidence:
  - reference: PMID:26558513
    reference_title: "Propofol infusion syndrome: a structured review of experimental studies and 153 published case reports."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: PRIMARY_RESULT
    snippet: "| Discolouration of urine | 16 (11 %)"
    explanation: The tabulated frequency across 153 pooled cases.
  - reference: PMID:36407194
    reference_title: "Propofol-Related Infusion Syndrome: A Clinical Review."
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      These are typical signs of rhabdomyolysis, leading to renal failure and
      myoglobinuria.
    explanation: >-
      Supports the mechanism behind the discolouration, myoglobin released by
      muscle breakdown, which is why this phenotype is wired from the myocyte
      necrosis node.
- name: Hepatomegaly
  category: Clinical
  description: >-
    Enlarged or fatty liver, part of the classic case definition, and in
    children independently associated with mortality.
  frequency: 11% of reported cases
  phenotype_term:
    preferred_term: Hepatomegaly
    term:
      id: HP:0002240
      label: Hepatomegaly
  evidence:
  - reference: PMID:30857601
    reference_title: "Propofol infusion syndrome: a structured literature review and analysis of published case reports."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: PRIMARY_RESULT
    snippet: >-
      Mortality from propofol infusion syndrome is independently associated with
      fever and hepatomegaly in children, and electrocardiogram changes,
      hypotension, hyperkalaemia, traumatic brain injury, and a mean propofol
      infusion rate >5 mg kg-1 h-1 in adults.
    explanation: >-
      Identifies hepatomegaly among the features independently associated with
      death in children.
- name: Fever
  category: Clinical
  description: >-
    Unexplained fever, more frequent in children, and independently associated
    with mortality both in children and in the earlier case series.
  frequency: 19% of reported cases
  phenotype_term:
    preferred_term: Fever
    term:
      id: HP:0001945
      label: Fever
  evidence:
  - reference: PMID:26558513
    reference_title: "Propofol infusion syndrome: a structured review of experimental studies and 153 published case reports."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: PRIMARY_RESULT
    snippet: >-
      We found that propofol infusion rate and duration, the presence of
      traumatic brain injury and fever are factors independently associated with
      mortality in reported cases of PRIS
    explanation: >-
      Places fever among the factors independently associated with death in the
      153-case series.
- name: Acute kidney injury
  category: Laboratory
  description: Renal failure, reported as oliguria or rising creatinine.
  frequency: 39% of reported cases
  phenotype_term:
    preferred_term: Acute kidney injury
    term:
      id: HP:0001919
      label: Acute kidney injury
  evidence:
  - reference: PMID:26558513
    reference_title: "Propofol infusion syndrome: a structured review of experimental studies and 153 published case reports."
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      There is no widely accepted definition, but in most cases various
      combinations of the following are described: unexplained metabolic
      acidosis, rhabdomyolysis, hyperkalaemia, hepatomegaly, renal failure,
      hyperlipidaemia, arrhythmia, Brugada-type electrocardiograph (ECG;
      elevated ST-segment and coved T-wave) and rapidly progressive cardiac
      failure.
    explanation: Lists renal failure among the reported features.
- name: Arrhythmia
  category: Clinical
  frequency: 66% of reported cases
  description: >-
    Arrhythmia in general, not only bradycardia, is among the commonest reported
    features, and appears late relative to the metabolic changes. Bound to the
    general arrhythmia term because the case literature counts arrhythmias
    together rather than by rhythm.
  phenotype_term:
    preferred_term: Arrhythmia
    term:
      id: HP:0011675
      label: Arrhythmia
  evidence:
  - reference: PMID:26558513
    reference_title: "Propofol infusion syndrome: a structured review of experimental studies and 153 published case reports."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: PRIMARY_RESULT
    snippet: "| Arrhythmia | 101 (66 %)"
    explanation: >-
      The review's own tabulation of how often arrhythmia was reported across 153
      cases.
  - reference: PMID:26558513
    reference_title: "Propofol infusion syndrome: a structured review of experimental studies and 153 published case reports."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: PRIMARY_RESULT
    snippet: >-
      Cardiac failure and metabolic acidosis occur early in a dose-dependent
      manner, while arrhythmia, other electrocardiographic changes and
      rhabdomyolysis appear more frequently after prolonged propofol infusions,
      irrespective of dose.
    explanation: >-
      Places arrhythmia among the duration-dependent rather than dose-dependent
      features.
- name: Hypotension
  category: Clinical
  frequency: 30% of reported cases
  description: >-
    Hypotension, independently associated with death in adults in the structured
    review of 168 cases.
  phenotype_term:
    preferred_term: Hypotension
    term:
      id: HP:0002615
      label: Hypotension
  evidence:
  - reference: PMID:26558513
    reference_title: "Propofol infusion syndrome: a structured review of experimental studies and 153 published case reports."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: PRIMARY_RESULT
    snippet: "| Hypotension | 45 (30 %)"
    explanation: The review's tabulated frequency of hypotension across 153 cases.
  - reference: PMID:30857601
    reference_title: "Propofol infusion syndrome: a structured literature review and analysis of published case reports."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: PRIMARY_RESULT
    snippet: >-
      Mortality from propofol infusion syndrome is independently associated with
      fever and hepatomegaly in children, and electrocardiogram changes,
      hypotension, hyperkalaemia, traumatic brain injury, and a mean propofol
      infusion rate >5 mg kg-1 h-1 in adults.
    explanation: >-
      Identifies hypotension among the features independently associated with
      death in adults.
- name: Bradycardia
  category: Clinical
  description: >-
    Acute refractory bradycardia progressing toward asystole, the defining
    cardiac presentation. No HPO term for asystole in this sense was found
    (`ols:hp`, `search l^Asystole` returns only Reflex asystolic syncope), so
    the bradycardia term carries the phenotype and the progression is described
    here.
  phenotype_term:
    preferred_term: Acute refractory bradycardia
    term:
      id: HP:0001662
      label: Bradycardia
  evidence:
  - reference: PMID:17567345
    reference_title: Propofol infusion syndrome.
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      The clinical features of propofol infusion syndrome (PRIS) are acute
      refractory bradycardia leading to asystole, in the presence of one or more
      of the following: metabolic acidosis (base deficit > 10 mmol.l(-1)),
      rhabdomyolysis, hyperlipidaemia, and enlarged or fatty liver.
    explanation: >-
      Names refractory bradycardia leading to asystole as the defining cardiac
      feature.
- name: Cardiogenic shock
  category: Clinical
  description: Rapidly progressive cardiac failure and cardiovascular collapse.
  frequency: 23% of reported cases
  phenotype_term:
    preferred_term: Cardiogenic shock
    term:
      id: HP:0030149
      label: Cardiogenic shock
  evidence:
  - reference: PMID:26558513
    reference_title: "Propofol infusion syndrome: a structured review of experimental studies and 153 published case reports."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: PRIMARY_RESULT
    snippet: >-
      Cardiac failure and metabolic acidosis occur early in a dose-dependent
      manner, while arrhythmia, other electrocardiographic changes and
      rhabdomyolysis appear more frequently after prolonged propofol infusions,
      irrespective of dose.
    explanation: >-
      Reports cardiac failure as an early, dose-dependent feature of the
      syndrome.
- name: Coved ST-segment elevation in right precordial leads
  category: Laboratory
  description: >-
    Coved ST elevation in leads V1 to V3, the pattern shared with the Brugada
    type 1 electrocardiogram and the reason this syndrome is the setting in
    which the term Brugada phenocopy was introduced.
  phenotype_term:
    preferred_term: Coved ST-segment elevation in leads V1 to V3
    term:
      id: HP:6000984
      label: Coved type ST segment elevation
  evidence:
  - reference: PMID:17567345
    reference_title: Propofol infusion syndrome.
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      An early sign of cardiac instability associated with the syndrome is the
      development of right bundle branch block with convex-curved ('coved type')
      ST elevation in the right praecordial leads (V1 to V3) of the
      electrocardiogram.
    explanation: Describes the coved ST elevation and its precordial distribution.
- name: Complete right bundle branch block
  category: Laboratory
  description: >-
    Right bundle branch block accompanying the coved ST elevation as an early
    sign of cardiac instability.
  phenotype_term:
    preferred_term: Right bundle branch block
    term:
      id: HP:0011712
      label: Complete right bundle branch block
  evidence:
  - reference: PMID:17567345
    reference_title: Propofol infusion syndrome.
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      An early sign of cardiac instability associated with the syndrome is the
      development of right bundle branch block with convex-curved ('coved type')
      ST elevation in the right praecordial leads (V1 to V3) of the
      electrocardiogram.
    explanation: Names right bundle branch block as part of the early ECG picture.
treatments:
- name: Immediate Discontinuation of Propofol
  description: >-
    Recognising the syndrome and stopping the infusion, substituting an
    alternative sedative, is the first step in management. The reversibility of
    the acylcarnitine abnormality on withdrawal is part of the evidence that
    the drug is the cause.
  therapeutic_modality: OTHER
  treatment_term:
    preferred_term: discontinuation of the causative drug
    term:
      id: NCIT:C128535
      label: Pharmacotherapy Discontinuation
  target_mechanisms:
  - target: Mitochondrial Respiratory Chain Inhibition by Propofol
    description: Removing the inhibitor is the only measure that addresses the cause.
  - target: Impaired Mitochondrial Fatty Acid Oxidation
  evidence:
  - reference: PMID:36407194
    reference_title: "Propofol-Related Infusion Syndrome: A Clinical Review."
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      The first step in managing PRIS is to immediately recognise and
      discontinue propofol infusion and replace it with other sedating agents
      like alfentanil, midazolam, etc.
    explanation: States discontinuation as the first management step.
- name: Continuous Haemofiltration
  description: >-
    Extracorporeal clearance, recommended early in management by the structured
    review of 168 cases.
  therapeutic_modality: OTHER
  treatment_term:
    preferred_term: continuous haemofiltration
    term:
      id: NCIT:C172594
      label: Hemofiltration
  target_mechanisms:
  - target: Metabolic acidosis
    description: Correcting the acidosis and clearing accumulated metabolites.
  evidence:
  - reference: PMID:30857601
    reference_title: "Propofol infusion syndrome: a structured literature review and analysis of published case reports."
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      We recommend early consideration of continuous haemofiltration in the
      management of propofol infusion syndrome.
    explanation: The review's explicit management recommendation.
- name: Haemodialysis with Cardiorespiratory Support
  description: >-
    Dialysis or haemoperfusion combined with cardiorespiratory support has been
    the most successful reported treatment, in a syndrome where options are
    otherwise limited.
  therapeutic_modality: OTHER
  treatment_term:
    preferred_term: haemodialysis with cardiorespiratory support
    term:
      id: NCIT:C15248
      label: Hemodialysis
  target_mechanisms:
  - target: Metabolic acidosis
  - target: Cardiogenic shock
  evidence:
  - reference: PMID:17567345
    reference_title: Propofol infusion syndrome.
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Haemodialysis or haemoperfusion with cardiorespiratory support has been
      the most successful treatment.
    explanation: Identifies the treatment combination with the best reported outcome.
- name: Sodium Bicarbonate for Acidosis
  description: Buffering of metabolic and lactic acidosis as supportive management.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: sodium bicarbonate
      term:
        id: CHEBI:32139
        label: sodium hydrogencarbonate
  target_mechanisms:
  - target: Metabolic acidosis
  evidence:
  - reference: PMID:36407194
    reference_title: "Propofol-Related Infusion Syndrome: A Clinical Review."
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Metabolic and lactic acidosis can be managed by the administration of
      sodium bicarbonate, haemodialysis, and hemofiltration.
    explanation: Names bicarbonate among the measures for the acidosis.
differential_diagnoses:
- name: Brugada syndrome
  description: >-
    The electrocardiogram in propofol infusion syndrome can show coved ST
    elevation in the right precordial leads, which is the Brugada type 1
    pattern, so the tracing alone does not separate the two. What separates them
    is the clinical setting, the accompanying metabolic and muscle findings, and
    resolution once the infusion stops. Whether the pattern here should be
    called a Brugada phenocopy is contested, and the dispute matters because
    this syndrome is where the term was coined; see notes.
  phenotypes:
  - name: Coved type ST segment elevation
    phenotype_term:
      preferred_term: Coved type ST segment elevation
      term:
        id: HP:6000984
        label: Coved type ST segment elevation
  distinguishing_features:
  - A high-dose, prolonged propofol infusion is running when the pattern appears
  - Accompanying metabolic acidosis, rhabdomyolysis, hyperkalemia or hepatomegaly,
    which congenital Brugada syndrome does not produce
  - Resolution of the pattern after the infusion is stopped
  - Right bundle branch block accompanying the coved ST elevation as an early sign
  evidence:
  - reference: PMID:20544610
    reference_title: Propofol infusion syndrome and Brugada syndrome electrocardiographic phenocopy.
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      This anesthetic drug may cause a rare condition named propofol infusion
      syndrome, characterized by unexplained lactic acidosis, lipemia,
      rhabdomyolysis, cardiovascular collapse and Brugada-like
      electrocardiographic pattern or Brugada electrocardiographic phenocopy
      changes following high-dose propofol infusion over prolonged periods of
      time.
    explanation: >-
      The paper that introduced the phenocopy term, describing the shared ECG
      appearance alongside the metabolic and muscle features that distinguish
      the syndrome.
  - reference: PMID:23094876
    reference_title: "Brugada phenocopy: new terminology and proposed classification."
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      to describe an acquired Brugada-like ECG pattern in the setting of
      propofol infusion syndrome.
    explanation: >-
      Records that the phenocopy terminology was introduced for this syndrome
      specifically.
  - reference: PMID:23094876
    reference_title: "Brugada phenocopy: new terminology and proposed classification."
    supports: REFUTE
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Consequently, the Group 1 drugs for the most part cannot be considered
      Brugada phenocopies.
    explanation: >-
      The same classification paper places propofol among its Group 1 agents,
      which it says act by sodium channel blockade and mostly cannot be
      considered phenocopies. So the paper that adopted the term for this
      syndrome also excludes its drug from the category.
  notes: >-
    Whether the electrocardiographic change in this syndrome is a Brugada
    phenocopy is unsettled, and the tension sits inside a single paper.
    PMID:23094876 credits Riera and colleagues with introducing the term for
    propofol infusion syndrome, and in the same text lists propofol among its
    Group 1 agents, states that nearly all of those act via sodium channel
    blockade, and concludes that Group 1 drugs for the most part cannot be
    considered Brugada phenocopies. The entry records both statements rather
    than choosing between them. Brugada_Syndrome carries the reciprocal
    differential. No sodium-channel mechanism is asserted for propofol in this
    entry's pathophysiology, because the reviews cited here attribute the
    syndrome to mitochondrial impairment and do not establish a channel-blocking
    mechanism for the ECG change.
discussions:
- discussion_id: q_pris_genetic_susceptibility
  kind: KNOWLEDGE_GAP
  prompt: >-
    Does an inherited susceptibility determine which patients receiving
    high-dose prolonged propofol develop propofol infusion syndrome?
  rationale: >-
    The syndrome is rare relative to how widely propofol is used for
    intensive-care sedation, which implies host susceptibility rather than dose
    alone. Subclinical mitochondrial disease is listed among the predisposing
    factors, and a fatty-acid-oxidation defect is one of the two proposed
    mechanisms, so an inherited partial defect in either pathway is a plausible
    determinant. The question has been open since the syndrome was named and no
    cited source here resolves it.
  attaches_to:
  - pathophysiology#Impaired Mitochondrial Fatty Acid Oxidation
  - pathophysiology#Mitochondrial Respiratory Chain Inhibition by Propofol
  evidence:
  - reference: PMID:20544610
    reference_title: Propofol infusion syndrome and Brugada syndrome electrocardiographic phenocopy.
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: Uncertainty remains as to whether a genetic susceptibility exists.
    explanation: States the open question directly.
  - reference: PMID:17567345
    reference_title: Propofol infusion syndrome.
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Predisposing factors include young age, severe critical illness of central
      nervous system or respiratory origin, exogenous catecholamine or
      glucocorticoid administration, inadequate carbohydrate intake and
      subclinical mitochondrial disease.
    explanation: >-
      Names subclinical mitochondrial disease among the predisposing factors,
      which is the specific form an inherited susceptibility would most likely
      take.
references:
- reference: PMID:20544610
  title: Propofol infusion syndrome and Brugada syndrome electrocardiographic phenocopy.
- reference: PMID:17567345
  title: Propofol infusion syndrome.
- reference: PMID:26558513
  title: "Propofol infusion syndrome: a structured review of experimental studies and 153 published case reports."
- reference: PMID:30857601
  title: "Propofol infusion syndrome: a structured literature review and analysis of published case reports."
- reference: PMID:36407194
  title: "Propofol-Related Infusion Syndrome: A Clinical Review."
- reference: PMID:19874582
  title: "Incidence of propofol-related infusion syndrome in critically ill adults: a prospective, multicenter study."
- reference: PMID:23094876
  title: "Brugada phenocopy: new terminology and proposed classification."
review_notes: >-
  Curated directly rather than by the autonomous agent, because the mention
  allowlist in .github/ai-controllers.json does not include the requesting user,
  so the summon on issue #13101 was gated out. Diagnostic criteria are recorded
  as a CASE_DEFINITION rather than DIAGNOSTIC_CRITERIA because the cited
  structured review states no widely accepted definition exists. No
  environmental[] block or influences_mechanisms links were added, pending the
  modelling decision on issue #10395.
📚

References & Deep Research

References

7
PMID:20544610
Propofol infusion syndrome and Brugada syndrome electrocardiographic phenocopy.
No top-level findings curated for this source.
PMID:17567345
Propofol infusion syndrome.
No top-level findings curated for this source.
PMID:26558513
Propofol infusion syndrome: a structured review of experimental studies and 153 published case reports.
No top-level findings curated for this source.
PMID:30857601
Propofol infusion syndrome: a structured literature review and analysis of published case reports.
No top-level findings curated for this source.
PMID:36407194
Propofol-Related Infusion Syndrome: A Clinical Review.
No top-level findings curated for this source.
PMID:19874582
Incidence of propofol-related infusion syndrome in critically ill adults: a prospective, multicenter study.
No top-level findings curated for this source.
PMID:23094876
Brugada phenocopy: new terminology and proposed classification.
No top-level findings curated for this source.

Deep Research

1

Deep research results are used as seeds for research; they do not undergo the same validation as the main records and may contain errors. How we use deep research.

Evaluations and curation notes (1)

Create: Propofol Infusion Syndrome · 2026-09-29T03:43:19Z · View source

Created the entry from issue #13101, which proposed it because propofol infusion syndrome is the clinical setting the term Brugada phenocopy was coined for and dismech had no record of it. No disease_term. MONDO has no term for the syndrome: ols:mondo returns nothing for `search l~propofol` or for free-text "propofol" and "propofol infusion syndrome", against a positive control on `l~Brugada` that returns the expected terms. NCIT holds only the drug, NCIT:C29384. No cached Orphanet leaf record mentions propofol. The searches and the positive control are recorded in the entry's own notes so the negative-existence claim is checkable. The MONDO parent-term question the issue raised is left open; it blocks a term request, not the entry, and 38 of 3,230 entries on main carry no disease_term. No conforms_to. Both candidate modules were read before deciding, as the issue asked. mitochondrial_dysfunction scopes itself to the hallmark of aging and its chain starts at mtDNA mutation and passes through impaired mitophagy, which an acute pharmacological inhibition does not have. metabolic_intoxication_decompensation scopes itself to inborn errors with a deficient enzyme or transporter, where this is reversible drug inhibition of a normal pathway. Recorded in notes rather than conforming to a module whose own description excludes the case. Pathophysiology follows the two proposed mechanisms as separate molecular nodes, respiratory-chain inhibition and impaired fatty acid oxidation, both feeding one bioenergetic-failure node that fans out to myocyte necrosis and cardiac conduction instability. The hedging in the source is preserved: the reviews say the syndrome "may be caused by" these mechanisms, and the evidence explanations say so rather than asserting an established mechanism. The Brugada relationship is a differential diagnosis carrying both sides of the dispute rather than a phenocopy claim. PMID:23094876 credits Riera with introducing the term for this syndrome and, in the same text, lists propofol among its Group 1 agents, says nearly all act by sodium channel blockade, and concludes Group 1 drugs mostly cannot be considered phenocopies. Those two statements are recorded as a SUPPORT and a REFUTE item against the same paper, which is what the evidence model asks for when one source cuts both ways. No sodium-channel mechanism is asserted in the pathophysiology, because the reviews cited attribute the syndrome to mitochondrial impairment and do not establish a channel-blocking route to the ECG change. Brugada_Syndrome already carries the reciprocal differential from #12929. The open question about inherited susceptibility is a KNOWLEDGE_GAP discussion attached to both molecular nodes, evidenced by the 2010 paper's own statement that uncertainty remains and by the review that lists subclinical mitochondrial disease among predisposing factors. Curated by hand rather than by the autonomous agent. The summon on #13101 fired the mention workflow, whose gate logged `User: gingin77, Allowed: false, Has mention: true` and skipped the job that would have done the work; the allowlist is .github/ai-controllers.json on the default branch. The issue comment was updated to record that, and no self-authorizing change to that file was made. Six references fetched and cited: PMID:20544610, PMID:17567345, PMID:26558513, PMID:30857601, PMID:36407194, plus the already-cached PMID:23094876. One snippet had to be reselected: a sentence carrying bracketed citation markers failed exact-quote validation, and a bracket-free sentence from the same review was used instead. Review round 1. The reviewer found two features present in more than 10% of reported cases that the entry missed, from a frequency table in a paper it already cited: arrhythmia at 66%, modelled only as bradycardia, and hypotension at 30%, absent entirely. Both are now phenotypes wired from the conduction-instability node, and nine phenotypes carry frequency values quoted from that table. Hypertriglyceridemia previously cited a sentence saying "Lipidaemia" while binding the narrower triglyceride term; it now cites a sentence naming hypertriglyceridaemia directly, which also records the review's caution that the feature is missing in most cases. The discontinuation treatment moved from NCIT:C49236 Therapeutic Procedure to NCIT:C128535 Pharmacotherapy Discontinuation, verified by lookup rather than taken from the review, and already used by Eosinophilia-Myalgia_Syndrome. The Myocyte Injury node cited only a sentence about when rhabdomyolysis appears, which did not support the node's own claim; it now carries two mechanistic sentences from PMID:36407194. The review also asked for the deep-research artifact the policy requires for a new entry, and was right that a hand pass can miss what a run catches. The run produced research/Propofol_Infusion_Syndrome-deep-research-claude_code.md (falcon requested, fell back to claude_code; 25/25 references verified, 0 confabulation) and surfaced two things the entry lacked. A prospective multicenter cohort of 1,017 ICU adults gives the only real incidence figure, slightly above 1% (PMID:19874582), which is now an epidemiology record alongside the pooled case count and says explicitly that every other figure here has an unknown denominator. And MeSH does code the syndrome as the supplementary concept D000072736, which matters for the MONDO request; there is no MeSH mapping slot, so it is recorded in notes. That identifier was verified against the NCBI MeSH database before use, and the first lookup attempt failed because a supplementary concept is retrieved by its own UID rather than the 68-prefixed descriptor form. Two term defects inside the report were left alone rather than propagated, which is what a report being a lead means: its own validation flags GO:0055114 as obsolete, and CL:1001603 as labelled 'kidney proximal tubule epithelial cell' in the report when the ontology says 'lung macrophage'. Neither is bound anywhere in this entry. The report also cites issue #13101 as a source for MONDO having no term, so its agreement on that point is not independent of the claim it was asked about. Review round 2, on the approving review's non-blocking note: the two remaining features above 10% in the same frequency table were added, abnormal liver function tests at 13% and discolouration of urine at 11%, so the entry now covers every feature the table reports above that threshold. Each is bound to a term its own snippet supports rather than to the most precise concept available: elevated transaminases rather than a generic liver-function term, since the clinical review names elevated liver enzymes; and abnormal urinary colour rather than myoglobinuria, since the 11% counts observed discolouration rather than a confirmed myoglobin measurement, with the myoglobin mechanism carried in the description and evidenced separately. The urine phenotype is wired from the myocyte necrosis node. Validation after review round 2: just validate (46/46 snippets, 53 titles, 0 issues), validate-terms, count-verified-snippets, check-duplicate-keys, check-entity-refs, check-causal-targets, check-qualifier-terms, check-granularity, and the batched validate-disorders all pass. Whole-KB gates clean: check-folded-hyphens, check-snippet-length, check-title-snippets, check-snippet-grading, check-reference-titles, check-coarse-phenotypes, check-enum-values, check-case-collisions, check-delivery-system. No baseline file was updated. No environmental[] or influences_mechanisms links, pending #10395.

Claude Code ▸
Propofol Infusion Syndrome (PRIS): Comprehensive Research Report
claude-haiku-4-5-20251001, claude-sonnet-5 31 citations 2026-09-29T00:15:21.110965

Propofol Infusion Syndrome (PRIS): Comprehensive Research Report

1. Disease Information

Overview

Propofol infusion syndrome (PRIS, also called propofol-related infusion syndrome) is a rare but frequently fatal drug-toxicity syndrome that develops in patients receiving prolonged, high-dose infusions of propofol (2,6-diisopropylphenol), the short-acting intravenous sedative-hypnotic agent used ubiquitously in anesthesia and intensive care sedation. It is characterized by the abrupt onset of severe metabolic acidosis, rhabdomyolysis/myoglobinuria, hyperkalemia, hyperlipidemia, hepatomegaly with fatty liver infiltration, acute kidney injury, and cardiovascular collapse — classically progressing to refractory bradyarrhythmia and asystole (MeSH D000072736; Wikipedia summary).

The syndrome was first described by Bray in 1998 in a case series of critically ill children (Bray RJ, "Propofol infusion syndrome in children," Paediatr Anaesth 1998), in whom 12 of 15 reported children died after prolonged high-dose propofol sedation with the constellation of refractory bradycardia, lipemic plasma, hepatomegaly, metabolic acidosis, rhabdomyolysis, and myoglobinuria. Although first recognized in the pediatric ICU population, PRIS is now well documented in adults, particularly in neurocritical care (traumatic brain injury, refractory/super-refractory status epilepticus) (Bray 1998, summarized in PMC8660594; BJA Education review).

A widely used operational definition (Bray-derived) is: acute refractory bradycardia progressing to asystole, occurring in the presence of at least one of: metabolic acidosis (base deficit >10 mmol/L), rhabdomyolysis/myoglobinuria, lipemic plasma or fatty liver enlargement — typically associated with propofol infusion rates >4 mg/kg/h for >48 hours, though cases have been reported outside these thresholds.

Key Identifiers

Resource Identifier / Status
MeSH D000072736 — "Propofol Infusion Syndrome"
MONDO No MONDO term currently exists. A dismech GitHub issue (#13101, "Curate propofol infusion syndrome, which has no MONDO term") documents this gap explicitly — the condition fits MONDO's usual disease-entity criteria (known etiology, named phenotype constellation, dose/time-course relationship, resolution on drug withdrawal) but has not yet been minted.
OMIM No OMIM entry — PRIS is an acquired, drug-induced toxidrome rather than a Mendelian disease, though it can unmask an underlying Mendelian mitochondrial disorder (see Etiology, below).
Orphanet No dedicated Orphanet entry identified in this search.
ICD-10/11 No dedicated code identified; typically coded under adverse-effect/poisoning codes (e.g., T41 anesthetic poisoning) combined with the resulting organ dysfunction codes rather than a single disease code.
Synonyms Propofol-related infusion syndrome; PRIS; "propofol infusion 'syndrome'" (the scare quotes in some literature reflecting debate over whether it is a single unified syndrome or a spectrum of overlapping mitochondrial toxicities)

Nearly all available data derive from aggregated case reports/case series and observational cohort studies rather than large prospective trials, given the rarity and unpredictability of onset; the largest prospective multicenter incidence study enrolled 1,017 adult ICU patients (Roberts RJ et al., Crit Care 2009; PMC2784401), and the largest structured literature synthesis pooled 153 published case reports from 1990–2014 (Krajčová A et al., Crit Care 2015, PMID: 26558513).

2. Etiology

Disease Causal Factor

PRIS is fundamentally an environmental/iatrogenic drug-toxicity syndrome — the sole necessary causal exposure is prolonged, high-dose intravenous propofol infusion. There is no infectious or intrinsically genetic causation, though genetic background strongly modulates susceptibility (see below).

Risk Factors

Dose/duration (the dominant modifiable risk factor): - Infusion rate >4 mg/kg/h (some sources cite >5 mg/kg/h) sustained for >48 hours is the classically cited threshold. One case-control analysis found the odds ratio for PRIS increased 1.93-fold for every 1 mg/kg/h increment in mean propofol dose above 4 mg/kg/h. - However, PRIS is not strictly dose- or duration-dependent: cases have been documented after as little as 3–5 hours of high-dose infusion, and at doses as low as 1.4 mg/kg/h (BJA Education review; Drug Safety/Deranged Physiology summaries).

Patient/clinical risk factors: - Critical illness/severe systemic inflammatory state (sepsis) - Severe traumatic brain injury and other acute neurological injury — risk approximately doubles at infusion rates >5 mg/kg/h in this population - Refractory or super-refractory status epilepticus requiring prolonged high-dose propofol - Carbohydrate depletion / low carbohydrate-to-lipid caloric ratio (inadequate glucose delivery forces reliance on fatty-acid oxidation, which propofol itself impairs) - Concomitant high-dose exogenous catecholamines (vasopressors) and/or glucocorticoids — these are hypothesized "priming" factors that potentiate skeletal/cardiac muscle protein catabolism and mitochondrial stress - Young age (children/adolescents historically over-represented, though risk is now well established in adults) - Male sex has been associated with higher mortality risk in some cohorts

Genetic risk factors: - Underlying primary mitochondrial disease or fatty-acid β-oxidation disorders are the clearest genetic susceptibility factor. Multiple case reports describe propofol "unmasking" previously unrecognized mitochondrial disease: - A MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) patient carrying the m.3271T>C variant in MT-TL1 developed severe PRIS-pattern lactic acidosis and rhabdomyolysis (Shimizu et al., Acute Med Surg 2020, 10.1002/ams2.473). - A case report described PRIS heralding an undiagnosed mitochondrial disease (Neurology 2014, PMID: 24491974). - A case discusses a POLG mitochondrial DNA polymerase mutation in the context of PRIS management (e-jnc.org case report). - Review literature states explicitly: "Mitochondrial disorders are prone to propofol infusion syndrome" (PMC7774597) and "predisposition to mitochondrial dysfunction caused by genetic mutations promotes cell death and caspase activation induced by propofol" (Finsterer & Frank, J Child Neurol 2016). - Pre-existing inborn errors of fatty-acid β-oxidation (e.g., carnitine-acylcarnitine translocase deficiency, carnitine palmitoyltransferase deficiencies) are a recognized contraindication/relative contraindication to propofol infusion, since propofol itself inhibits the same pathway these patients already have impaired (narrative review, Medicine 2022).

Protective Factors

No genetic or pharmacological protective factors are established. The principal "protective" strategy is behavioral/procedural: adherence to dose/duration limits, adequate carbohydrate provision, use of alternative or adjunctive sedatives (dexmedetomidine, benzodiazepines, barbiturates) to permit propofol-sparing regimens, and vigilant biochemical monitoring (see Prevention, §13).

Gene-Environment Interaction

The core gene-environment interaction is between constitutional mitochondrial/fatty-acid-oxidation reserve capacity (genetic) and exogenous mitochondrial toxin exposure plus metabolic stress from critical illness (environmental): a patient with normal but limited FAO/ETC reserve who is additionally stressed by sepsis, catecholamine excess, and carbohydrate starvation can be tipped into overt PRIS by an inhibitory drug load that would be tolerated in a metabolically unstressed individual — and a patient with a subclinical primary mitochondrial disorder can decompensate catastrophically at doses/durations that are otherwise considered "safe."

3. Phenotypes

Phenotype Type Frequency in pooled case data Suggested HPO term
Refractory sinus bradycardia progressing to asystole/cardiac arrest Clinical sign (cardiac) Defining/near-universal in classic PRIS HP:0001688 (Sinus bradycardia); HP:0004943 (Asystole is not a direct HPO term — consider HP:0001677 Coronary artery atherosclerosis is wrong; use HP:0011675 Arrhythmia as broader term)
Metabolic (lactic) acidosis Laboratory abnormality ~62% in one 21-patient RSE cohort; near-universal across pooled reviews HP:0001942 (Metabolic acidosis) / HP:0002151 (Hyperlactic acidemia)
Rhabdomyolysis / myoglobinuria Laboratory abnormality / clinical sign ~42% (RSE cohort); a hallmark finding HP:0003201 (Rhabdomyolysis)
Hyperkalemia Laboratory abnormality More frequent in adults than children HP:0002153 (Hyperkalemia)
Hyperlipidemia / lipemic plasma Laboratory abnormality ~33% (RSE cohort); more common in children HP:0003077 (Hyperlipidemia) / HP:0003146 (Hypertriglyceridemia)
Hepatomegaly / fatty liver Physical/imaging sign More frequent in children than adults; independently associated with pediatric mortality HP:0002240 (Hepatomegaly)
Acute kidney injury Laboratory/clinical sign ~38% (RSE cohort) HP:0001919 (Acute kidney injury)
Brugada-pattern ECG changes (down-sloping ST elevation V1–V3) Clinical sign (electrophysiological) Reported subset; strongly predicts imminent sudden death No precise HPO term for acquired Brugada pattern; consider HP:0011675 (Arrhythmia) with notes
Elevated hepatic transaminases Laboratory abnormality ~28% (RSE cohort) HP:0002910 (Elevated hepatic transaminase)
Cardiomyopathy / myocardial dysfunction Clinical/imaging sign Documented on echocardiography and at autopsy (sustained mitochondrial damage in cardiomyocytes, PMC8905003) HP:0001638 (Cardiomyopathy)
Fever Clinical sign More frequent in children; independently associated with pediatric mortality HP:0001945 (Fever)
Elevated creatine kinase Laboratory abnormality CK >10,000 U/L typical at diagnosis; CK <5,000 U/L marks a low-risk population (No dedicated HPO term; typically captured as a biomarker/lab value rather than HPO)

Age of onset: Not congenital — this is an acquired, drug-exposure-triggered syndrome. Onset is typically 1–6 days after initiation of high-dose propofol (median ~3 days in the Roberts et al. 2009 prospective cohort), though onset as early as 3–5 hours has been reported in some cases.

Severity and progression: Highly variable — from subclinical biochemical derangement (rising CK/triglycerides/lactate, "pre-PRIS") to fulminant multi-organ failure and sudden cardiac death within hours once the Brugada-pattern ECG change appears. Course is typically rapidly progressive once overt, but is potentially reversible with immediate propofol discontinuation and aggressive supportive care if caught early.

Clinical presentation differs by age group (Hemphill S et al., structured literature review, Br J Anaesth 2019 S0007091219300108): - Children: lipemia, fever, and hepatomegaly occur more frequently; fever and hepatomegaly are independently associated with mortality. - Adults: rhabdomyolysis and hyperkalemia are more frequent; ECG changes, hypotension, hyperkalemia, traumatic brain injury, and mean infusion rate >5 mg/kg/h are independently associated with mortality.

Quality of life impact: No formal QoL instrument data exist for PRIS specifically, given its acute, often fatal, ICU-confined course; survivors' quality-of-life burden derives from sequelae of the organ injuries sustained (post-AKI renal impairment, post-rhabdomyolysis compartment syndrome/contracture, hypoxic-ischemic sequelae of cardiac arrest, or unmasked chronic mitochondrial disease).

4. Genetic/Molecular Information

PRIS itself has no single causal gene — it is not a Mendelian disorder. However, the molecular basis of susceptibility and of the toxic mechanism strongly implicates specific gene products:

  • CPT1A/CPT2 (carnitine palmitoyltransferase 1 and 2, HGNC:2328 / HGNC:2330): Propofol directly inhibits carnitine palmitoyltransferase I, the outer mitochondrial membrane enzyme that transfers long-chain fatty acyl groups onto carnitine for mitochondrial import — the rate-limiting step of fatty-acid β-oxidation (Wolf A et al., Lancet 2001, "Impaired fatty acid oxidation in propofol infusion syndrome," PMID: 11558490). Patients with primary CPT1/CPT2 deficiency or carnitine-acylcarnitine translocase (SLC25A20) deficiency are at markedly elevated iatrogenic risk if given propofol.
  • Mitochondrial DNA / nuclear mitochondrial genes (MT-TL1, POLG, and the broader primary mitochondrial disease gene set): case reports document PRIS unmasking MELAS (m.3271T>C in MT-TL1) and POLG-related mitochondrial disease, establishing these as susceptibility loci in the sense that carriers are markedly more vulnerable to overt PRIS at "standard" propofol doses.
  • Electron transport chain complex I and III subunit genes: propofol targets Complexes I and III directly, inducing a metabolic switch from oxidative phosphorylation to glycolysis and triggering cell death in an ETC-dependent manner (bioRxiv/PLOS ONE mechanistic study, 10.1371/journal.pone.0192796).
  • SCN5A (cardiac sodium channel, HGNC:10593): mechanistically relevant to the Brugada-pattern ECG phenotype — propofol has demonstrated cardiac sodium-channel-blocking properties, and the acquired Brugada pattern in PRIS is attributed to pharmacological blockade of the same sodium current that is genetically reduced in congenital Brugada syndrome (PMC9200599; PMC1474111).

Variant classification / population frequency: Not applicable in the standard ACMG/ClinVar sense, since PRIS is not itself a variant-caused disease; the relevant variants (in MT-TL1, POLG, CPT1A/CPT2, SLC25A20) are catalogued under their respective primary mitochondrial/FAO disorder entries in ClinVar/OMIM rather than under PRIS.

Functional consequence summary: The convergent molecular lesion is loss of mitochondrial fatty-acid oxidative capacity plus impaired electron transport chain flux, producing an energetic mismatch — cells (especially cardiac and skeletal myocytes, which are highly oxidative-metabolism-dependent) cannot meet ATP demand through either fat or, ultimately, carbohydrate oxidation, precipitating necrosis.

Epigenetic information: No epigenetic mechanism has been established for PRIS; this is an acute pharmacotoxic/bioenergetic process rather than a chromatin-level disease.

Chromosomal abnormalities: Not applicable.

5. Environmental Information

Propofol itself is the environmental/exposure agent — this is the paradigm case of an iatrogenic drug-toxicity environmental disease:

  • Chemical entity: Propofol, 2,6-diisopropylphenol (CHEBI:44915), an intravenous general anesthetic/sedative-hypnotic formulated in a lipid emulsion (soybean oil, egg lecithin, glycerol).
  • Exposure route: Continuous intravenous infusion (as opposed to bolus induction dosing, which does not carry meaningful PRIS risk).
  • Co-exposures that potentiate toxicity: concurrent exogenous catecholamine infusion (vasopressors), concurrent glucocorticoid administration, and the lipid emulsion vehicle itself contributing to the exogenous fat load layered onto endogenous stress-driven lipolysis.
  • Lifestyle/nutritional factor: inadequate carbohydrate (glucose) provision during critical illness is a specifically implicated modifiable environmental contributor, since carbohydrate starvation forces greater reliance on the very fatty-acid oxidation pathway propofol inhibits.
  • Infectious agents: Not a direct cause, but sepsis (as a systemic inflammatory/catecholamine-driving state) is a well-documented risk-amplifying comorbid condition; propofol has also been shown experimentally to increase morbidity/mortality in a rat model of sepsis (Crit Care 2015, 10.1186/s13054-015-0751-x), suggesting a bidirectional interaction between septic physiology and propofol toxicity rather than sepsis being a purely passive risk marker.

6. Mechanism / Pathophysiology

Causal chain (ordered, from exposure to clinical manifestation)

  1. Prolonged, high-dose intravenous propofol infusion delivers sustained tissue concentrations of 2,6-diisopropylphenol to skeletal and cardiac myocytes and hepatocytes, sufficient to reach mitochondrial toxic thresholds — leads to (2).
  2. Propofol directly inhibits carnitine palmitoyltransferase I at the outer mitochondrial membrane, blocking the transfer of long-chain fatty acyl groups onto carnitine — results in impaired entry of long-chain fatty acids into the mitochondrial matrix for β-oxidation (demonstrated in human skeletal muscle homogenates at propofol concentrations below those needed to impair the electron transport chain directly, indicating this is an independent, upstream lesion) — leads to (3).
  3. In parallel, propofol directly inhibits electron flux through Complexes I and III of the mitochondrial electron transport chain, with coenzyme Q identified experimentally as a principal site of interaction — leads to (4a) and (4b) as parallel branches.
  4. (4a) Impaired oxidative phosphorylation: reduced maximal ETC capacity and reduced ATP synthesis capacity, demonstrated directly in cultured human skeletal muscle cells at plasma concentrations achieved in sedated ICU patients (Vanlander/Ferrari-line studies; PMID: 29240609; PMID: 31584947) — forces a compensatory metabolic switch toward glycolysis, which is inadequate to meet the energy demands of highly oxidative tissues (cardiac and skeletal muscle) — leads to (5).
  5. (4b) Reactive oxygen species generation and mitochondrial membrane depolarization: at higher concentrations, propofol causes sustained mitochondrial membrane potential depolarization and mild oxidative-phosphorylation uncoupling, with increased ROS production and activation of the mitochondrial (intrinsic) apoptotic pathway (caspase activation) — leads to (5) in parallel.
  6. Fatty-acid oxidation blockade (from step 2), superimposed on a critical-illness state of carbohydrate depletion and stress-driven lipolysis (high catecholamines/glucocorticoids providing an exogenous fat/lipid load that cannot be productively oxidized) — results in accumulation of toxic lipid intermediates (elevated malonylcarnitine and C5-acylcarnitine species have been documented biochemically) and progressive energy failure: an imbalance between cellular energy demand and the cell's capacity to generate ATP via either fat or carbohydrate substrate.
  7. Energy failure in highly oxidative-metabolism-dependent tissues (cardiac myocytes, skeletal myocytes, hepatocytes) causes cellular necrosis and, via the apoptotic pathway from step 4b, programmed cell death — this is the convergence point of the two upstream branches — leads to, by tissue:
  8. Skeletal muscle: myocyte necrosis → rhabdomyolysis, myoglobinuria, and consequent acute kidney injury (myoglobin-mediated tubular injury) and hyperkalemia (potassium release from necrotic myocytes).
  9. Cardiac muscle: myocyte necrosis and mitochondrial damage (documented histologically as "sustained mitochondrial damage in cardiomyocytes" in fatal human PRIS cases, PMC8905003) → impaired contractility (cardiomyopathy) and, via propofol's independent cardiac sodium-channel-blocking action, acquired Brugada-pattern ECG changes (down-sloping ST-segment elevation in V1–V3) → electrical instability → ventricular arrhythmia/fibrillation and refractory bradyarrhythmia progressing to asystole, the terminal and most lethal manifestation.
  10. Hepatocytes: impaired fat handling and mitochondrial injury → hepatomegaly with fatty infiltration (steatosis) and elevated transaminases.
  11. Systemic: the combination of unoxidized circulating lipid and the propofol lipid-emulsion vehicle itself → hyperlipidemia/lipemic plasma; accumulating unmetabolized organic acids and lactate from the failed oxidative pathway → severe metabolic (lactic) acidosis.
  12. Where the patient carries an underlying primary mitochondrial disease or fatty-acid oxidation defect (genetic branch point, from Etiology §2), baseline ETC/FAO reserve is already reduced, so the same propofol exposure produces steps 2–5 at markedly lower doses/durations, or "unmasks" a previously subclinical disease — this is an alternative entry point into the same downstream cascade rather than a separate mechanism.

Molecular pathways

Fatty-acid β-oxidation pathway (carnitine shuttle: CPT1 → CACT → CPT2); mitochondrial electron transport chain (Complexes I, II/CoQ, III, IV, ATP synthase); intrinsic (mitochondrial) apoptosis pathway (cytochrome c release, caspase-9/-3 activation).

Cellular processes

Apoptosis (mitochondrial/intrinsic pathway), necrosis, a Warburg-like metabolic switch from oxidative phosphorylation to glycolysis, oxidative stress (ROS accumulation).

Protein dysfunction

CPT1 catalytic inhibition (competitive/direct enzymatic inhibition by propofol, not a structural mutation); Complex I and III functional inhibition at the level of electron transfer, with coenzyme Q implicated as an interaction site.

Biochemical abnormalities

Elevated malonylcarnitine and C5-acylcarnitine (biomarkers of impaired FAO); lactic acidosis; hyperkalemia; hypertriglyceridemia; elevated CK, myoglobin, troponin T.

Molecular/experimental model evidence

  • Human skeletal muscle cell culture studies show dose-dependent inhibition of exogenous fatty-acid oxidation and reduced maximal ETC capacity at clinically achieved propofol concentrations, and that noradrenaline exposure worsens propofol-induced mitochondrial dysfunction in the same cell system (PMC9643307) — direct mechanistic support for the catecholamine risk-factor observation in §2.
  • A murine skeletal-muscle-injury model and an isolated-perfused newborn mouse heart model (relevant to pediatric PRIS) both recapitulate propofol-dose-dependent bioenergetic failure and cardiotoxicity (PMC6712282; PMC9350423; Pediatr Res 2022, 10.1038/s41390-022-01985-1).
  • A rabbit PRIS model demonstrated a survival/organ-injury benefit from coenzyme Q10 supplementation (PMC10584382), consistent with CoQ being a direct molecular interaction site in the ETC inhibition mechanism.

Suggested GO / CL / UBERON terms

  • GO:0006635 (fatty acid beta-oxidation), GO:0022904 (respiratory electron transport chain), GO:0006119 (oxidative phosphorylation), GO:0006915 (apoptotic process), GO:0055114 (oxidation-reduction process)
  • CL:0000746 (cardiac muscle cell), CL:0000188 (skeletal muscle fiber), CL:0000182 (hepatocyte), CL:1001603 (kidney proximal tubule epithelial cell, relevant to myoglobin-mediated AKI)
  • UBERON:0001133 (cardiac muscle tissue), UBERON:0001134 (skeletal muscle tissue), UBERON:0002107 (liver), UBERON:0002113 (kidney)

7. Anatomical Structures Affected

Organ level (primary): Heart (conduction system and myocardium), skeletal muscle (generalized), liver. Organ level (secondary/complications): Kidneys (myoglobin-mediated acute tubular injury), and — where cardiac arrest occurs — brain (hypoxic-ischemic injury) as a downstream complication rather than a primary target. Body systems involved: Cardiovascular, musculoskeletal (muscle), hepatic, renal, and metabolic/endocrine (lipid and acid-base homeostasis).

Tissue/cell level: - Cardiac muscle tissue → cardiomyocytes (CL:0000746) and the cardiac conduction system (relevant to the Brugada-pattern sodium-channel mechanism). - Skeletal muscle tissue → skeletal myofibers (CL:0000188). - Liver parenchyma → hepatocytes (CL:0000182), with steatotic change. - Renal tubular epithelium → proximal tubule cells, injured secondarily by filtered myoglobin.

Subcellular level: Mitochondria are the central subcellular compartment implicated — specifically the inner mitochondrial membrane (electron transport chain complexes I and III, and the carnitine shuttle machinery at the outer/inner membrane interface). Relevant GO Cellular Component terms: GO:0005743 (mitochondrial inner membrane), GO:0005739 (mitochondrion).

Localization: Systemic/multi-organ rather than lateralized or site-specific; the cardiac lesion is specifically localized to the conduction system and right ventricular outflow tract region electrophysiologically (the anatomic substrate of the Brugada ECG pattern), though no gross structural cardiac abnormality is required (a purely functional/electrophysiological phenotype in most cases).

8. Temporal Development

Onset: Acquired, not congenital; onset is tied entirely to duration/dose of propofol exposure rather than to a developmental stage. Reported latency from infusion initiation to overt syndrome ranges from as little as 3–5 hours (rare, high-dose cases) to a median of ~3 days (range 1–6 days) in the largest prospective adult cohort (Roberts et al. 2009), with classical teaching citing >48 hours of infusion as the higher-risk window.

Onset pattern: Acute to subacute — biochemical derangement (rising CK, triglycerides, lactate — sometimes termed "pre-PRIS") may precede the overt clinical syndrome by hours to a day or more, offering a window for early detection, but once the cardiac phenotype (Brugada-pattern ECG, refractory bradyarrhythmia) manifests, progression to death can occur within hours.

Disease stages: Informally staged as (a) subclinical/biochemical (isolated rise in CK/triglycerides/lactate), (b) overt PRIS (multi-organ derangement without terminal arrhythmia), and (c) fulminant/terminal PRIS (Brugada-pattern ECG, refractory arrhythmia, cardiac arrest) — this is a practical clinical staging derived from the biomarker/ECG literature rather than a formally codified staging system.

Progression rate: Highly variable, but the terminal cardiac phase is characteristically rapid — once ST-segment changes appear, patients have been reported to progress to fatal ventricular fibrillation/electrical storm within hours.

Disease course pattern: Not relapsing-remitting; it is a self-limited toxic exposure syndrome in the sense that removing the causal agent (stopping propofol) halts further toxin delivery, but established organ injury (rhabdomyolysis, AKI, cardiac injury) follows its own resolution timeline, and cardiac arrest, once it occurs, is frequently fatal despite maximal support.

Remission: Resolution of the Brugada-pattern ECG and biochemical derangement has been documented following propofol discontinuation and supportive care in surviving patients (e.g., "Recovery following propofol-associated Brugada electrocardiogram," PMID: 19821933) — remission is treatment(withdrawal)-induced rather than spontaneous while exposure continues.

Critical period for intervention: The subclinical biochemical phase (rising CK, triglycerides, and lactate in a patient on high-dose/prolonged propofol) represents the key window in which discontinuing propofol can prevent progression to the fulminant, often-fatal cardiac phase — this is the rationale behind biomarker-based surveillance protocols (§10, §13).

9. Inheritance and Population

Inheritance pattern: Not applicable — PRIS is an acquired toxic syndrome, not a heritable disease. (The predisposing primary mitochondrial/FAO disorders that can lower the toxicity threshold follow their own inheritance patterns — autosomal recessive for most FAO disorders such as CPT1/CPT2/CACT deficiency, and maternal/mitochondrial inheritance for mtDNA point mutations such as the MELAS-associated MT-TL1 variant.)

Epidemiology: - Incidence in a prospective multicenter cohort of 1,017 critically ill adults: 1.1%, with onset at a median of 3 days after propofol initiation (Roberts RJ et al. 2009, PMC2784401). - Other cohorts report incidence figures ranging from 2.9% to 4.1% depending on population and case ascertainment strictness. - Among 1,139 patients with suspected PRIS pooled across the literature, 342 (30%) had a fatal outcome; among the 153 published case reports specifically analyzed by Krajčová et al. (2015), 78/153 (51%) were fatal. - Reported case-fatality rates vary widely by cohort (33%, 36.8%, and up to 48% in some series), reflecting differences in case definition, ascertainment bias toward more severe reported cases, and era of treatment (earlier reports predate widespread biomarker surveillance and ECMO/CRRT rescue availability).

Population demographics: - No strong evidence for ethnic or geographic predilection specific to PRIS itself — risk tracks with propofol utilization patterns (ICU sedation practice) rather than population genetics, except insofar as populations with higher carrier frequency of primary mitochondrial/FAO disorders would be expected to have elevated background susceptibility. - Age distribution: originally described in children (the Bray 1998 index series), now well documented across the age spectrum in adults, with particular concentration in neurocritical care populations (TBI, refractory status epilepticus). - Sex ratio: male sex has been associated with increased mortality risk in pooled case analyses, though this may partly reflect underlying case-mix (trauma and status epilepticus populations skew male in some cohorts) rather than an intrinsic biological sex effect. - Mortality is independently associated with age ≤18 years in pooled analyses (Fong JJ et al., "Predictors of mortality in patients with suspected propofol infusion syndrome," PMID: 18664783), alongside male sex, vasopressor use, cardiac symptoms, metabolic acidosis, renal failure, hypotension, rhabdomyolysis, and dyslipidemia.

10. Diagnostics

There is no single confirmatory test; diagnosis is clinical and biochemical, based on the temporal association with propofol exposure plus the characteristic constellation of findings, after excluding alternative explanations.

Laboratory tests / biomarkers: - Creatine kinase (CK): central surveillance marker. CK >10,000 U/L is typical at diagnosis of overt PRIS; a cutoff <5,000 U/L identifies a low-risk population. Rising CK over 24–48 hours of infusion, in the absence of other muscle pathology, should raise suspicion. - Serum lactate: unexplained/rising metabolic (lactic) acidosis is a core diagnostic feature and an early warning sign. - Triglycerides: rising triglyceride levels have been proposed as a reliable early biomarker of impending PRIS, reflecting both impaired lipid clearance/oxidation and the propofol lipid-emulsion vehicle load. - Troponin T and myoglobin: elevated in cases with cardiac and skeletal muscle involvement respectively. - Malonylcarnitine and C5-acylcarnitine species: research-level biomarkers of impaired fatty-acid oxidation, elevated in PRIS (Wolf et al. 2001). - Arterial blood gas for base deficit/pH.

Electrophysiology: Continuous or serial 12-lead ECG monitoring for the Brugada-pattern ECG (down-sloping ST-segment elevation in leads V1–V3) is a critical diagnostic and prognostic tool — its appearance is a harbinger of imminent, often fatal, ventricular arrhythmia and should prompt emergency propofol discontinuation (Vernooy K et al., PMC1474111).

Imaging: Echocardiography to assess for new cardiomyopathy/reduced ejection fraction; abdominal imaging or clinical exam for hepatomegaly.

Genetic testing: Not part of routine acute diagnosis, but should be considered after an episode of unexpectedly severe or low-dose-triggered PRIS, to evaluate for an underlying primary mitochondrial disease or fatty-acid oxidation disorder (targeted mitochondrial gene panel or exome sequencing, plasma acylcarnitine profile, and urine organic acids), particularly in pediatric survivors or in cases with a personal/family history suggestive of mitochondrial disease.

Differential diagnosis: Malignant hyperthermia (also produces hyperthermia, rhabdomyolysis, acidosis, but is triggered by volatile anesthetics/succinylcholine and driven by RYR1-mediated calcium dysregulation rather than mitochondrial FAO/ETC inhibition), serotonin syndrome, neuroleptic malignant syndrome, sepsis/septic cardiomyopathy (which can coexist with and confound PRIS diagnosis), and primary cardiac arrhythmic syndromes (congenital Brugada syndrome, which can also be pharmacologically unmasked by other agents).

Screening: No population screening applies (acquired condition); the analogous "screening" practice is routine, protocolized biochemical surveillance (CK, triglycerides, lactate, arterial blood gas) in any patient receiving propofol >48 hours or at doses >4 mg/kg/h, per multiple society/expert guidance summarized in the anesthesia/critical care literature.

11. Outcome/Prognosis

Mortality: Case-fatality rates in the published literature range from ~30% to ~51% depending on cohort (see §9); in a focused refractory-status-epilepticus PRIS cohort, mortality was 66% (13/21 patients). Historically (Bray 1998 index series) mortality was 12/15 (80%), reflecting both the severity of index cases and the absence at that time of modern rescue therapies (CRRT, ECMO).

Prognostic factors for mortality: - Adults: ECG changes (especially Brugada pattern), hypotension, hyperkalemia, traumatic brain injury, and mean propofol infusion rate >5 mg/kg/h. - Children: fever and hepatomegaly. - Across ages: age ≤18 years, male sex, vasopressor requirement, cardiac symptoms, metabolic acidosis, renal failure, hypotension, rhabdomyolysis, and dyslipidemia (Fong et al., PMID: 18664783).

Complications: Cardiac arrest/sudden death (via ventricular fibrillation/refractory bradyarrhythmia); acute kidney injury requiring renal replacement therapy; hepatic dysfunction; compartment syndrome from rhabdomyolysis; and, in survivors of cardiac arrest, hypoxic-ischemic brain injury as a secondary complication.

Recovery potential: With early recognition (biochemical surveillance catching the "pre-PRIS" phase) and immediate propofol discontinuation plus aggressive supportive/rescue therapy, biochemical and ECG abnormalities can fully resolve and patients can recover without lasting organ dysfunction. Case reports document dramatic recovery of cardiac function (e.g., LVEF improving from severely reduced to 35–40% and normal RV function) after ECMO support, with successful weaning. Conversely, once refractory ventricular arrhythmia/electrical storm develops, mortality is very high despite maximal intervention.

Prognostic biomarkers: Persistently or acutely rising CK, triglycerides, and lactate, and especially the appearance of the Brugada-pattern ECG, are the strongest available predictors of imminent deterioration and should trigger escalation of care.

12. Treatment

There is no drug-specific antidote; management is immediate cessation of the causal exposure plus problem-driven, organ-supportive critical care.

Core management

  • Immediate discontinuation of the propofol infusion — the single most important intervention, and the only intervention that halts further mechanistic progression (removes the causal toxin).
  • Substitution with alternative sedation (benzodiazepines, dexmedetomidine, barbiturates, or volatile-agent sedation in refractory status epilepticus) to maintain the clinical goal the propofol had been serving (sedation, seizure control) without continued mitochondrial toxin exposure.

Organ/problem-directed supportive care

  • Hemodynamic/rhythm support: vasopressor/inotropic support for cardiovascular collapse (used cautiously, given catecholamines are themselves a risk-amplifying factor); temporary cardiac pacing for refractory bradyarrhythmia.
  • Renal replacement therapy: continuous renal replacement therapy (CRRT) or intermittent hemodialysis for rhabdomyolysis-associated acute kidney injury and for refractory hyperkalemia — case reports document instances where CRRT failed to control potassium and transition to intermittent hemodialysis achieved rapid correction.
  • Extracorporeal life support (ECMO): veno-arterial ECMO has been used successfully as rescue therapy in refractory cardiogenic shock/cardiac arrest due to PRIS, in both adults and children, including combined with CRRT and therapeutic plasma exchange in a pediatric refractory-status-epilepticus case (PMC10613782); documented dramatic myocardial recovery over ~5 days of support in at least one case report (PMC3850887).
  • Correction of metabolic derangements: aggressive correction of acidosis and hyperkalemia; carbohydrate/glucose supplementation to reduce reliance on the impaired fatty-acid oxidation pathway.
  • Investigational/adjunctive: coenzyme Q10 supplementation improved survival and reduced organ injury in an experimental rabbit PRIS model (PMC10584382), consistent with CoQ's role as a direct molecular target in the ETC inhibition mechanism, but this remains experimental rather than a standard clinical therapy.

Pharmacogenomics

No established PharmGKB/CPIC gene-drug pairing exists for propofol dosing with respect to PRIS risk specifically, though patients with known primary FAO or mitochondrial disorders are managed with propofol avoidance or extreme caution as a matter of clinical practice rather than formal pharmacogenomic guideline.

NCIT treatment term suggestions

  • NCIT:C49236 Therapeutic Procedure (general)
  • Hemodialysis/renal replacement therapy — relevant NCIT dialysis/CRRT terms
  • NCIT:C15747 Supportive Care
  • ECMO — relevant NCIT extracorporeal circulation term

Experimental treatments

No registered clinical trials were identified specifically targeting PRIS treatment (as opposed to prevention-focused propofol dosing trials); management remains guideline/expert-consensus and case-report-derived rather than trial-validated.

13. Prevention

Primary prevention (avoiding the causal exposure/dose): - Limit propofol infusion to <4 mg/kg/h where clinically feasible, and avoid sustained infusions beyond 48 hours at high doses; use the lowest effective dose and shortest necessary duration. - Favor propofol-sparing, multimodal sedation strategies — combining lower-dose propofol with adjuncts such as dexmedetomidine, benzodiazepines, or opioids to reduce cumulative propofol exposure, particularly in high-risk populations (TBI, refractory status epilepticus, pediatric patients). - Ensure adequate carbohydrate (glucose) provision during critical illness/prolonged sedation to reduce forced reliance on the fatty-acid oxidation pathway that propofol impairs. - Use caution with concomitant catecholamine and glucocorticoid administration in patients on high-dose propofol, recognizing the mechanistic synergy demonstrated experimentally (noradrenaline potentiates propofol-induced mitochondrial dysfunction in human skeletal muscle cells). - Avoid propofol entirely, or use with extreme caution and specialist input, in patients with known or suspected primary mitochondrial disease or fatty-acid β-oxidation disorders — a pharmacogenetically informed avoidance strategy rather than dose modification.

Secondary prevention (early detection): - Protocolized serial biochemical monitoring (arterial blood gas/lactate, CK, triglycerides) for any patient receiving propofol infusion >48 hours or at doses approaching/exceeding 4 mg/kg/h, to catch the "pre-PRIS" biochemical phase before cardiac decompensation. - Continuous or serial ECG monitoring for early detection of the Brugada-pattern change, which should trigger immediate drug discontinuation.

Tertiary prevention: Prompt discontinuation and organ-supportive care at first biochemical or electrophysiological sign, as above, to prevent progression to fulminant, often-fatal cardiac collapse.

Genetic counseling: Relevant not for PRIS itself but for family members of a patient found, via a PRIS episode, to carry a primary mitochondrial or FAO disorder — standard genetic counseling for the underlying Mendelian/mitochondrial condition applies once identified.

Public health/institutional measures: Institutional sedation protocols and pharmacy/ICU guidelines capping propofol dose/duration, mandating biomarker surveillance, and specifying escalation triggers represent the practical "prophylaxis" infrastructure described across the clinical review literature (Fudickar A, Bein B, "The propofol infusion 'syndrome' in intensive care unit: from pathophysiology to prophylaxis and treatment," PMID: 18652104).

14. Other Species / Natural Disease

PRIS is not a naturally occurring veterinary disease entity in the sense of a spontaneously arising condition, but it is a recognized iatrogenic risk in veterinary anesthesia/sedation practice wherever propofol is used for prolonged infusion sedation in companion or laboratory animals, by direct pharmacological analogy to the human syndrome — no dedicated veterinary literature specific to spontaneous PRIS case series was surfaced in this search, and this section is best understood through the experimental-model lens in §15 rather than as natural disease.

Taxonomy of species used in experimental modeling: rat (Rattus norvegicus, NCBITaxon:10116), mouse (Mus musculus, NCBITaxon:10090), rabbit (Oryctolagus cuniculus, NCBITaxon:9986) — see §15.

Comparative biology: The core molecular targets (CPT1, mitochondrial Complexes I/III, coenzyme Q) are highly conserved across mammals, which is why rodent and rabbit models recapitulate the human bioenergetic lesion faithfully at the mitochondrial/cellular level, even though whole-organism experimental PRIS models are engineered (via deliberate high-dose infusion) rather than naturally occurring.

Zoonotic potential: Not applicable — this is a pharmacotoxic, not an infectious, condition.

15. Model Organisms

Model Species/system What it captures Fidelity notes
Isolated-perfused newborn mouse heart Mus musculus (ex vivo) Acute propofol-induced cardiotoxicity — ECG, ventricular contractile force, oxygen extraction measured over 30 min toxic-dose exposure; a proposed ex-vivo model relevant specifically to pediatric PRIS (PMC9350423) High fidelity for the acute cardiac electromechanical phenotype in the developing heart; does not capture the full multi-organ (renal/hepatic) syndrome
Newborn murine cardiac mitochondria (in vitro) Mus musculus Mitochondrial respiration, membrane potential, and respiratory chain complex kinetics directly exposed to propofol/Intralipid (Pediatr Res 2022) Isolates the mitochondrial mechanism cleanly from whole-organ/systemic confounders
Murine skeletal muscle injury model Mus musculus (in vivo) Basic mechanistic study of PRIS-associated skeletal muscle injury (PMC6712282) Captures the rhabdomyolysis-relevant skeletal muscle arm of the syndrome
Rat model of sepsis + propofol Rattus norvegicus (in vivo) Demonstrates propofol increases morbidity/mortality in the setting of sepsis, mechanistically supporting the clinical sepsis risk-factor association (Crit Care 2015) Models the gene-environment-like interaction between a systemic inflammatory state and propofol toxicity, though this is an environment-environment interaction rather than a genetic one
Rat isolated mitochondria / respiratory chain studies Rattus norvegicus (ex vivo) Identified coenzyme Q as the principal electron-transport-chain interaction site for propofol Mechanistic, subcellular-level model
Rabbit PRIS model Oryctolagus cuniculus (in vivo) Whole-animal PRIS induction with survival and organ-injury endpoints; used to test coenzyme Q10 as a rescue therapy (PMC10584382) Closest available whole-organism model to the clinical multi-organ syndrome; supports a translational candidate therapy
Human primary skeletal muscle cell culture Homo sapiens (in vitro, primary cells) Direct demonstration of clinically-relevant-concentration propofol inhibiting fatty-acid oxidation and reducing ETC spare capacity and ATP synthesis; also used to show noradrenaline potentiates the mitochondrial injury (PMID: 29240609; PMC9643307) Highest translational relevance since it uses human tissue directly, though it cannot capture the whole-organism cardiac/renal phenotype

Model limitations common across the set: most models are acute/short-duration exposures (30 minutes to hours) rather than the 48-hour-plus infusions characteristic of clinical PRIS, and none fully recapitulates the combined multi-organ syndrome (cardiac + renal + hepatic + metabolic) simultaneously in a single system — each model instead isolates one mechanistic or organ-specific arm of the human disease.

Research applications: These models collectively support (a) the mitochondrial FAO/ETC inhibition mechanism, (b) the catecholamine-potentiation and sepsis-potentiation risk-factor mechanisms, (c) age-specific (developing heart) vulnerability, and (d) candidate rescue therapies (coenzyme Q10) — directly informing the pathophysiology and prevention/treatment sections above.

Summary of Key Ontology Term Suggestions for KB Curation

  • CHEBI: CHEBI:44915 (propofol)
  • GO (Biological Process): GO:0006635 (fatty acid beta-oxidation), GO:0022904 (respiratory electron transport chain), GO:0006119 (oxidative phosphorylation), GO:0006915 (apoptotic process)
  • GO (Cellular Component): GO:0005743 (mitochondrial inner membrane), GO:0005739 (mitochondrion)
  • CL: CL:0000746 (cardiac muscle cell), CL:0000188 (skeletal muscle fiber), CL:0000182 (hepatocyte)
  • UBERON: UBERON:0001133 (cardiac muscle tissue), UBERON:0001134 (skeletal muscle tissue), UBERON:0002107 (liver), UBERON:0002113 (kidney)
  • HP: HP:0001942 (Metabolic acidosis), HP:0003201 (Rhabdomyolysis), HP:0002153 (Hyperkalemia), HP:0003077 (Hyperlipidemia), HP:0002240 (Hepatomegaly), HP:0001919 (Acute kidney injury), HP:0001638 (Cardiomyopathy), HP:0001688 (Sinus bradycardia), HP:0001945 (Fever)
  • HGNC (mechanistically relevant, not causal): CPT1A (HGNC:2328), CPT2 (HGNC:2330), SLC25A20 (carnitine-acylcarnitine translocase), SCN5A (HGNC:10593), POLG (HGNC:9179)
  • MONDO: none currently exists (documented gap, dismech issue #13101)

Key Cited Sources

  • Bray RJ. Propofol infusion syndrome in children. Paediatr Anaesth. 1998. (index description; summarized in PMC8660594)
  • Vasile B, Rasulo F, Candiani A, Latronico N. The pathophysiology of propofol infusion syndrome: a simple name for a complex syndrome. Intensive Care Med. 2003;29(9):1417-25. PMID: 12904852
  • Wolf A, Weir P, Segar P, Stone J, Shield J. Impaired fatty acid oxidation in propofol infusion syndrome. Lancet. 2001. PMID: 11558490
  • Kam PC, Cardone D. Propofol infusion syndrome. Anaesthesia. 2007. PMID: 17567345
  • Fudickar A, Bein B. The propofol infusion "syndrome" in intensive care unit: from pathophysiology to prophylaxis and treatment. PMID: 18652104
  • Roberts RJ, et al. Incidence of propofol-related infusion syndrome in critically ill adults: a prospective, multicenter study. Crit Care. 2009. PMC2784401
  • Fong JJ, et al. Predictors of mortality in patients with suspected propofol infusion syndrome. PMID: 18664783
  • Vernooy K, et al. Electrocardiographic changes predicting sudden death in propofol-related infusion syndrome. PMC1474111
  • Mirrakhimov AE, et al. Propofol Infusion Syndrome in Adults: A Clinical Update. Crit Care Res Pract. 2015. PMC4410753
  • Krajčová A, Waldauf P, Anděl M, Duška F. Propofol infusion syndrome: a structured review of experimental studies and 153 published case reports. Crit Care. 2015;19:398. PMID: 26558513
  • Hemphill S, et al. Propofol infusion syndrome: a structured literature review and analysis of published case reports. Br J Anaesth. 2019. S0007091219300108
  • Finsterer J, Frank M. Propofol Is Mitochondrion-Toxic and May Unmask a Mitochondrial Disorder. J Child Neurol. 2016.
  • Shimizu K, et al. Propofol infusion syndrome complicated with MELAS: a case report. Acute Med Surg. 2020. 10.1002/ams2.473
  • Case report: PRIS heralding a mitochondrial disease. Neurology. 2014. PMID: 24491974
  • Sustained mitochondrial damage in cardiomyocytes in patients with severe PRIS (case report). PMC8905003
  • Effects of Propofol on Cellular Bioenergetics in Human Skeletal Muscle Cells. Crit Care Med. PMID: 29240609
  • Kinetic characteristics of propofol-induced inhibition of electron-transfer chain and fatty acid oxidation. PMID: 31584947
  • Effect of noradrenaline on propofol-induced mitochondrial dysfunction in human skeletal muscle cells. PMC9643307
  • Propofol increases morbidity and mortality in a rat model of sepsis. Crit Care. 2015. 10.1186/s13054-015-0751-x
  • Modeling propofol-induced cardiotoxicity in the isolated-perfused newborn mouse heart. PMC9350423
  • Propofol toxicity in the developing mouse heart mitochondria. Pediatr Res. 2022. 10.1038/s41390-022-01985-1
  • Effects of coenzyme Q10 in a propofol infusion syndrome model of rabbits. PMC10584382
  • Propofol-Related Infusion Syndrome in a Child With Refractory Status Epilepticus: ECMO/CRRT/TPE resuscitation. PMC10613782
  • Propofol infusion syndrome resuscitation with extracorporeal life support (case report). PMC3850887
  • MeSH Browser entry D000072736. meshb.nlm.nih.gov
  • dismech GitHub issue #13101, "Curate propofol infusion syndrome, which has no MONDO term." github.com/monarch-initiative/dismech/issues/13101

Reference Validation

Checked with linkml-reference-validator 0.3.0rc3.

Outcome Count
References checked 25
Resolved 25
Unresolved (possible confabulation) 0
Unverifiable 0
Quoted claims checked 1
Quoted claims found in source 1
Quoted claims not found in source 0
References weighed for topical relevance 25
On topic 21
Off topic 0

All extracted references resolved successfully.

Term Validation

Checked with linkml-term-validator 0.4.5, through the ols: adapter.

Outcome Count
Terms checked 40
Resolved 35
Unresolved (possible confabulation) 0
Obsolete 1
Unverifiable 4
Terms whose name was checked 26
Terms named correctly 20
Terms named as a different term 1
Terms whose name is worth a second look 5

Terms the report names something else

These identifiers resolve, so nothing about them looks wrong, and the ontology calls them something unrelated to what the report calls them. That usually means the identifier is not the one the sentence needs:

  • CL:1001603 (1 mention) - the report calls it "kidney proximal tubule epithelial cell, relevant to myoglobin-mediated AKI"; CL calls it lung macrophage

Obsolete terms

These terms are real but deprecated. Citing one is not a fabrication; it does mean the report is naming something the ontology has retired:

  • GO:0055114 (obsolete oxidation-reduction process) (1 mention)

Terms whose name is worth a second look

The report's name for these is recognisably related to the term's own name without being one of them. A loose paraphrase reads the same way as a citation of the wrong sibling term - and so does a related synonym, which the ontology records precisely because it names something adjacent rather than the same thing - so these are listed rather than judged:

  • HP:0002910 (1 mention) - the report calls it "Elevated hepatic transaminase"; HP calls it Elevated circulating hepatic transaminase concentration, and lists "Elevated transaminases" among its other names
  • GO:0055114 (1 mention) - the report calls it "oxidation-reduction process"; GO calls it obsolete oxidation-reduction process
  • CL:0000746 (3 mentions) - the report calls it "cardiac muscle cell", "Cardiac muscle tissue → cardiomyocytes"; CL calls it cardiac muscle cell, and lists "cardiac muscle fiber" among its other names
  • CL:0000188 (3 mentions) - the report calls it "skeletal muscle fiber", "Skeletal muscle tissue → skeletal myofibers"; CL calls it cell of skeletal muscle, and lists "skeletal muscle cell" among its other names
  • CL:0000182 (3 mentions) - the report calls it "hepatocyte", "Liver parenchyma → hepatocytes"; CL calls it hepatocyte

Terms named inconsistently

The report gives these identifiers more than one name of its own:

  • CL:0000746 - called "cardiac muscle cell", "Cardiac muscle tissue → cardiomyocytes"
  • CL:0000188 - called "skeletal muscle fiber", "Skeletal muscle tissue → skeletal myofibers"
  • CL:0000182 - called "hepatocyte", "Liver parenchyma → hepatocytes"