Evidence-based recommendations on the use of intravenous lipid emulsion therapy in poisoning.
BACKGROUND
Although intravenous lipid emulsion (ILE) was first used to treat life-threatening local anesthetic (LA) toxicity, its use has expanded to include both non-local anesthetic (non-LA) poisoning and less severe manifestations of toxicity. A collaborative workgroup appraised the literature and provides evidence-based recommendations for the use of ILE in poisoning.


METHODS
Following a systematic review of the literature, data were summarized in four publications: LA and non-LA poisoning efficacy, adverse effects, and analytical interferences. Twenty-two toxins or toxin categories and three clinical situations were selected for voting. Voting statements were proposed using a predetermined format. A two-round modified Delphi method was used to reach consensus on the voting statements. Disagreement was quantified using RAND/UCLA Appropriateness Method.


RESULTS
For the management of cardiac arrest, we recommend using ILE with bupivacaine toxicity, while our recommendations are neutral regarding its use for all other toxins. For the management of life-threatening toxicity, (1) as first line therapy, we suggest not to use ILE with toxicity from amitriptyline, non-lipid soluble beta receptor antagonists, bupropion, calcium channel blockers, cocaine, diphenhydramine, lamotrigine, malathion but are neutral for other toxins, (2) as part of treatment modalities, we suggest using ILE in bupivacaine toxicity if other therapies fail, but are neutral for other toxins, (3) if other therapies fail, we recommend ILE for bupivacaine toxicity and we suggest using ILE for toxicity due to other LAs, amitriptyline, and bupropion, but our recommendations are neutral for all other toxins. In the treatment of non-life-threatening toxicity, recommendations are variable according to the balance of expected risks and benefits for each toxin. For LA-toxicity we suggest the use of Intralipid®20% as it is the formulation the most often reported. There is no evidence to support a recommendation for the best formulation of ILE for non-LAs. The voting panel is neutral regarding ILE dosing and infusion duration due to insufficient data for non-LAs. All recommendations were based on very low quality of evidence.


CONCLUSIONS
Clinical recommendations regarding the use of ILE in poisoning were only possible in a small number of scenarios and were based mainly on very low quality of evidence, balance of expected risks and benefits, adverse effects, laboratory interferences as well as related costs and resources. The workgroup emphasizes that dose-finding and controlled studies reflecting human poisoning scenarios are required to advance knowledge of limitations, indications, adverse effects, effectiveness, and best regimen for ILE treatment.
a Department of Emergency Medicine , McGill University Health Centre , Montréal , Québec , Canada.|b Centre Antipoison du Québec , Montréal , Québec , Canada.|c Province of Alberta Drug Information Services , Calgary , Alberta , Canada.
Sophie
S
Gosselin
d Danish Poisons Information Centre, Anaesthesiology , Copenhagen University Hospital Bispebjerg , Copenhagen , Denmark.
Lotte C G
LC
Hoegberg
e Division of Medical Toxicology, Ronald O. Perelman Department of Emergency Medicine , New York University School of Medicine , New York , NY , USA.
Robert S
RS
Hoffman
f Monash Clinical Toxicology Service, Program of Emergency Medicine, Monash Health and School of Clinical Sciences at Monash Health, Faculty of Medicine, Nursing and Health Sciences , Monash University , Clayton , Victoria , Australia.
Andis
A
Graudins
g Upstate NY Poison Center , Syracuse , NY , USA.|h Department of Emergency Medicine , Upstate Medical University , Syracuse , New York , USA.
Christine M
CM
Stork
i National Poisons Information Service (Newcastle) and Medical Toxicology Centre , Institute of Cellular Medicine, Newcastle University , Newcastle , UK.
Simon H L
SH
Thomas
j Department of Emergency Medicine , Regions Hospital , Saint Paul , MN, USA.
Samuel J
SJ
Stellpflug
k Department of Pharmacy , University of Maryland Medical Center , Baltimore , MD , USA.|l Department of Emergency Medicine , University of Maryland School of Medicine , Baltimore , MD , USA.
Bryan D
BD
Hayes
m Department of Emergency Medicine, Section of Medical Toxicology , University of Southern California , Los Angeles , CA , USA.
Michael
M
Levine
n Schulich Library of Science and Engineering , McGill University , Montréal , Québec , Canada.
Martin
M
Morris
n Schulich Library of Science and Engineering , McGill University , Montréal , Québec , Canada.
Andrea
A
Nesbitt-Miller
o Division of Critical Care Medicine, Department of Anesthesiology and Critical Care Medicine, and CHU de Québec , Université Laval Research Center, Population Health and Optimal Health Practices Unit, Université Laval , Québec City , Québec , Canada.
Alexis F
AF
Turgeon
p Division of Emergency Medicine, Department of Pediatrics , CHU Sainte-Justine , Montréal , Québec , Canada.|q Centre Antipoison du Québec , Quebec , Canada.
Benoit
B
Bailey
r Medical Toxicology, Department of Emergency Medicine , Morristown Medical Center, Emergency Medical Associates , Morristown , NJ , USA.
Diane P
DP
Calello
s Department of Emergency Medicine, Division of Clinical Pharmacology and Toxicology, University of Calgary , Poison and Drug Information Service , Calgary , Alberta , Canada.
Ryan
R
Chuang
t St Luke's Roosevelt Hospital , New York , NY , USA.
Theodore C
TC
Bania
u Department of Medical and Toxicological Intensive Care , Lariboisière Hospital, Paris-Diderot University, INSERM UMRS1144 , Paris , France.
Bruno
B
Mégarbane
v Department of Internal Medicine , Post Graduate Institute of Medical Education and Research , Chandigarh , India.
Ashish
A
Bhalla
w Department of Medical Biology , Sacré-Coeur Hospital, University of Montréal , Montréal , Québec , Canada.
Valéry
V
Lavergne
D061605:Administration, Intravenous; D000777:Anesthetics / Q000506:poisoning; D000818:Animals; D002121:Calcium Channel Blockers / Q000506:poisoning; D003042:Cocaine / Q000506:poisoning; D004155:Diphenhydramine / Q000506:poisoning; D004195:Disease Models, Animal; D019317:Evidence-Based Medicine; D005217:Fat Emulsions, Intravenous / Q000627:therapeutic use*; D006801:Humans; D000077213:Lamotrigine; D011041:Poisoning / Q000628:therapy*; D016032:Randomized Controlled Trials as Topic; D014227:Triazines / Q000506:poisoning
D000777:Anesthetics; D002121:Calcium Channel Blockers; D005217:Fat Emulsions, Intravenous; D014227:Triazines; D004155:Diphenhydramine; D003042:Cocaine; D000077213:Lamotrigine
Fat emulsion; adverse effect; lipid interference; lipid resuscitation; recommendation