RT Book, Section
A1 Kearney, Thomas E.
A2 Olson, Kent R.
A2 Anderson, Ilene B.
A2 Benowitz, Neal L.
A2 Blanc, Paul D.
A2 Clark, Richard F.
A2 Kearney, Thomas E.
A2 Kim-Katz, Susan Y.
A2 Wu, Alan H. B.
SR Print(0)
ID 1179992988
T1 LIPID EMULSION
T2 Poisoning & Drug Overdose, 7e
YR 2018
FD 2018
PB McGraw-Hill Education
PP New York, NY
SN 9780071839792
LK accessmedicine.mhmedical.com/content.aspx?aid=1179992988
RD 2024/04/19
AB Pharmacology.  Intravenous  lipid  emulsion  (ILE)  therapy  is  one  of  the  newest  treatments  touted  for  cardiovascular  toxicity  from  fat-soluble  drugs.  It  was  first  used  in  resuscitations  from  local  anesthetic  toxicity,  particularly  bupivacaine.  Some  animal  studies  have  demonstrated  dramatic  benefits,  including  resuscitation  from  cardiac  arrest,  severe  hypotension,  and  bradycardia  induced  by  cardiotoxic  drugs,  but  others  had  variable  results.  Anecdotal  human  case  reports  suggest  that  ILE  might  be  effective  for  reversal  of  cardiovascular  or  neurological  toxicity  in  some  cases  of  local  anesthetic  and  other  poisonings  but  is  less  or  not  effective  in  others  and  may  be  subject  to  reporting  bias  in  favor  of  positive  results.  Effectiveness  in  controlled  studies  with  animal  models  has  been  inconsistent  with  human  case  experiences.The  mechanisms  for  the  efficacy  of  ILE  are  uncertain  and  several  of  the  following  have  been  proposed:The  "lipid  sink"  theory—ILE  may  sequester  lipid-soluble  drugs  within  the  intravascular  compartment,  making  less  of  the  drug  available  for  tissue  toxicity.ILE  may  provide  extra  fatty  acids  to  cardiac  myocyte  mitochondria  for  a  heart  unable  to  use  its  usual  energy  supply  when  stressed.Long-chain  fatty  acids  may  activate  calcium  channels  in  myocytes,  augmenting  further  release  of  intracellular  calcium  and  resulting  in  improved  contractility.Medium-  and  long-chain  fatty  acids  stimulate  a  rise  of  cytosolic  calcium  in  pancreatic  cells,  causing  release  of  insulin,  which  in  turn  may  improve  cardiac  performance  in  shock.ILE  may  reverse  nitric  oxide-induced  vasodilation  by  inhibition  of  endothelial  nitric  oxide  synthase.The  infused  fat  particles  behave  like  natural  chylomicrons.  Circulating  triglycerides  are  quickly  hydrolyzed  by  intravascular  lipoprotein  lipase,  releasing  free  fatty  acids.  These  fatty  acids  are  taken  up  by  Kupfer  cells  in  the  liver  as  well  as  the  reticuloendothelial  system.  With  large  infusions,  free  fatty  acids  are  also  taken  up  by  skeletal  muscle  and  subcutaneous  tissue.  Any  free  fatty  acids  that  enter  tissues  can  be  stored  or  transported  into  the  mitochondria,  where  they  undergo  beta-oxidation.IndicationsThe  initial  use  of  ILE  for  overdose  was  based  on  case  reports  of  return  of  spontaneous  circulation  in  patients  with  overdose  of  local  anesthetic  drugs,  including  bupivacaine  and  mepivacaine.Human  case  reports  of  a  variety  of  other  poisonings  (tricyclic  antidepressants,  calcium  channel  blockers,  beta-blockers,  GABA  agonists,  antiarrhythmics,  anticonvulsants,  pesticides,  diphenhydramine,  sedative  hypnotics,  cocaine,  and  others)  have  demonstrated  mixed  results.In  patients  who  are  hemodynamically  unstable  from  overdoses  with  fat-soluble  xenobiotics,  when  more  conventional  resuscitative  interventions  have  failed,  consider  ILE  as  adjunctive  therapy  for  refractory  hypotension.  This  should  be  reserved  for  life-threatening  situations  and  not  considered  a  standard  of  care.ContraindicationsAllergy  to  soy  or  egg  products.Black  box  warning.  Neonates:  Deaths  have  occurred  in  preterm  infants  owing  to  intravenous  lipid  accumulation  in  the  lungs  as  a  result  of  impaired  clearance  and  elimination  of  the  drug.Relative  contraindications  include  pulmonary  disease,  pancreatitis,  and  fat  metabolism  disorders.ILE  given  too  quickly  in  large  amounts  to  patients  with  lung  disease,  particularly  ARDS,  can  temporarily  impair  proper  oxygenation.Pancreatitis  has  resulted  after  repeated  doses,  and  ILE  infusion  may  exacerbate  existing  pancreatitis.The  manufacturer  states  that  abnormal  fat  metabolism,  hyperlipidemia,  and  lipid  nephrosis  are  all  contraindications  to  the  administration  of  ILE.Adverse  effectsFat  emboli  syndrome.  Excessive  infusion  of  lipid  emulsion  may  transiently  increase  pulmonary  vascular  ...