Intralipid/Lipid Emulsion in Beta-blocker overdose

Date First Published:
February 3, 2010
Last Updated:
October 23, 2011
Report by:
Dianne Tabone, ST6 Emergency Medicine (Royal Bolton Hospital)
Search checked by:
Craig Ferguson, Royal Bolton Hospital
Three-Part Question:
In [an adult with beta-blocker overdose] is [intralipid/intravenous lipid emulsion] beneficial in [treating resistant hypotension and refractory arrhythmias]?
Clinical Scenario:
A 30-year-old man attends your emergency department after a deliberate overdose of his father's atenolol tablets. He is bradycardic, hypotensive and has had seizures. Despite fluids, atropine and a glucagon infusion, he remains hypotensive and you start treatment with inotropes. He remains unresponsive to treatment and very hypotensive and you wonder if an intravenous lipid infusion would help.
Search Strategy:
MEDLINE 1950 to August 2011
EMBASE 1980 to August 2011
Google Scholar Cochrane Database.
Lipid rescue website (http://www.lipidrescue.org)

Lipid registry website (http://www.lipidregistry.org/)
Search Details:
{intralipid.af} OR {lipid AND emulsion.af} OR {intravenous AND fat AND emulsion.af} OR {intravenous AND lipid AND emulsion.af} OR {fat AND emulsion.af} OR {intravenous AND lipid AND therapy.af} OR {liposyn*.af}) AND ({β AND blocker*.af} OR {atenolol.af} OR {carvedilol.af} OR {labetolol.af} OR {metoprolol.af} OR {oxprenolol.af} OR {pindolol.af} OR {propranolol.af} OR {sotalol.af} OR {bisoprolol.af} OR {esmolol.af})
Outcome:
Medline and Embase found 225 papers, of which 13 were relevant. Four systematic reviews, one of which related to the history and mechanism of intravenous lipid emulsion, seven case reports, one case series. The systematic reviews quoted the individual case report and series.

No further articles in Google Scholar. No related articles in the Cochrane Database. The Lipid rescue website mentions one case report.
Relevant Paper(s):
Study Title Patient Group Study type (level of evidence) Outcomes Key results Study Weaknesses
Intravenous fat emulsion for refractory verapamil and atenolol-induced shock: a human case report. Dolcourt BA, Aaron CK 2008 USA 52 yr old male with overdose of atenolol and verapamil, presented unconscious with HR 49, SBP 40, anuric, cold extremities. Case report ILE 20% given as 1.5 ml/kg bolus followed by an infusion of 0.25 ml/kg/min for 30 min. Patient conscious within minutes, BP 109/60 mm Hg within 3 h. Further shock 8 h after infusion. ILE given for 1 h improved BP. 4 h after end of infusion, shock recurred. A balloon pump. Patient died 12 h later ILE 20% given as 1.5 ml/kg Mixed overdose.
One case.
Efficacy and safety of intravenous lipid therapy in a beta-blocker overdose Harchelroad FP, Palma A 2008 USA 46yr old female, overdose with atenolol, paracetamol and ethyl alcohol. Case report 6 h After ingestion: HR 32, SBP 62. Treatment with 2 mg atropine, 5 mg glucagon, 2 L N saline improved HR 43, BP 96/53 mm Hg Treated with 1 l 20% ILE over 2 h—HR 70, BP 110/72 Mixed overdose
One case.
Beta Blocker toxicity successfully treated with intravenous fat emulsion: a case series. Meehan TJ, Gummin DD, Kostic MA et al. 2009 USA Case 1: 53yr old male, overdose of carvedilol.

Case 2: 22 yr old female, overdose of propranolol.		 Case series. Case 1: Treated with glucagon, insulin, maximal doses of dopamine and norepinephrine but remained hypotensive (60/30). Case 2: Asystole while in ICU. Treated with glucagon, atropine, epinephrine, sodium bicarbonate. Case 1: ILE given as bolus and infusion, with improvement of HR 93, BP 108/62 and survival to discharge. Case 2: ROSC within minutes of treatment with ILE (HR 90, SBP 110) and survived to discharge. Individual cases, time-span not given, dose of ILE not specified.
Successful resuscitation of a carvedilol overdose using intravenous fat emulsion. Carr D, Boone A, Hoffman RS et al. 2009 Canada 31yr old female presenting to ED 4 -5 hours post ingestion of 875mg carvedilol (12mg/kg). Case report. HR 73, BP 78/22, RR16, Sat02 97%. Treated with N saline, 5mg glucagon, calcium chloride and dopamine infusion. Hypotension persisted despite max dose of dopamine, epinephrine and high dose insulin. 100ml bolus of 20% ILE, followed by 150ml over 15minutes. Within 80minutes BP 132/70, later weaned off vasopressors and insulin and extubated. One case.
Time spans not given.
Intravenous lipid emulsion in propranolol overdose. Dean P, Ruddy JP, Marshall S. 2010 UK 27yr old female presenting to ED 1 hour after ingestion of 7gr propranolol. Case report as correspondence. On arrival in ED: GCS 3, generalized tonic clonic seizure, BP 60/30, PR 25. ECG: broad complex bradycardia. Treated with crystalloids, 3mg atropine, glucagon 5mg boluses and infusion (5mg/hr), insulin infusion (70U/hr) with 50% dextrose, lorazepam boluses (8mg) and phenytion infusion (which stopped seizures), isoprenaline infusion, and external cardiac pacing. Patient’s condition deteriorated into cardiac arrest (PEA) with ROSC after 2 cycles of CPR. Adrenaline infusion started. SBP 40, PR 25- 30. Intralipid 20% started as 100ml bolus followed by 400ml infusion over 20min. Adrenaline requirements decreased 5minutes after starting intralipid, and stopped after 7 hours. ECG reverted to NSR. One case.
Intentional overdose with cardiac arrest treated with intravenous fat emulsion and high-dose insulin. Stellpflug SJ, Harris CR, Engebretsen KM et al(a). 2010 USA 48yr old male, ingested nebivolol, ethanol and possibly diazepam and cocaine. Case report. HR 71, BP 98/61, ECG: SR, QTc 483 ms, QRS 112 ms. Within 4 h, bradycardic, hypotensive and asystolic cardiac arrest. Standard resuscitation ROSC 30 s after a 100 ml bolus of 20% ILE. HR 123, BP 251/162. ILE infusion and high-dose insulin. Survived to discharge Mixed overdose? Effect of high-dose insulin. Duration of cardiac arrest and standard resuscitation drugs before ILE not stated
Overdose of diltiazem, metoprolol and amiodarone treated with intravenous fat emulsion and high dose insulin in an awake patient. Stellpflug SJ, Cole JB, Fritzlar SJ et al. (b). 2010 USA 30yr old female with h/o HOCM, CHF and an AICD presenting with abdominal pain. Case report. HR 73, BP 89/46, but over 3 h HR 70, BP 64/41 and patient became confused. Treated with 2 l N saline. Admitted taking diltiazem, metoprolol and amiodarone 6 h before arrival in ED. Given 2 l N saline, 27 mEq calcium, high-dose insulin bolus of 0.5 U/kg followed by infusion up to 10 U/kg/h. Remained hypotensive, confused, anuric. CVP 20, ejection fraction ‘low’ 100 ml bolus of 20% ILE, followed by infusion 1.5 l over 1 h. Within 15 min of bolus, BP 110/60 and confusion improved. Patient discharged from ICU 5 days later Mixed overdose? Effect of high-dose insulin. (Authors argue against inotropic and vasodilatory effect of insulin as patient had HOCM).
Intralipid for combined propranolol/clonidine overdose. Smith A. 2010 48yr old female with GCS 10 after overdose including propranolol and clonidine. Case report on lipid rescue website. Patient intubated and ventilated. HR dropped to 60 and SBP 70. No response to fluids. Glucagon improved HR but not BP. No response to naloxone, maximum epinephrine and vasopressin, high-dose insulin at 120 U/h and 50% dextrose. More acidotic over next 90 min Patient given intralipid and moved to ICU. Within 1 h patient had BP 120/80 and became more rousable. Survived to discharge Mixed overdose. Case described in a website, not formally published.
Severe Propanolol and ethanol overdose with wide complex tachycardia treated with intravenous lipid emulsion: A case report. Jovic-Stosic J, Gligic B, Putic V, et al. Serbia 2011 31-Year-old woman who had presented 2 h after an overdose of propranolol plus ethanol Case report Presented in a coma with BP of 65/35. Treated with diazepam for repeated seizures, intubated and ventilated. Conventional treatment with atropine, glucagon, HDI and sodium bicarbonate and dopamine infusion Intralipid 100 ml bolus and 400 ml infusion were administered. The seizure activity stopped and the BP improved. The BP deteriorated again and a further intralipid infusion was given over 50 min. Patient regained consciousness and was extubated after a few hours Single case report
Author Commentary:
There are no human studies about the use of intravenous lipid emulsion in β-blocker overdose. Studies on rodents and rabbits have shown that intralipid reduces QRS duration and improves bradycardia and hypotension in propranolol toxicity. Similar studies with metoprolol failed to show a significant improvement in blood pressure. Intravenous lipid emulsion is thought to act as a lipid sink, attracting the drugs away from tissues, and thus may be more effective with more lipophilic drugs such as propranolol compared with metoprolol. Several case reports provide anecdotal suggestions of benefit but no firm evidence is available and it is likely that there is publication bias. Intravenous lipid emulsion has recently been recommended by Toxbase as worth consideration in patients with a history of overdose of β blockers, who have cardiotoxic symptoms that are not responsive to standard treatment.(Toxbase)
Bottom Line:
There is no clear evidence about the effectiveness of intravenous lipid emulsion in beta blocker overdose.
References:
  1. Dolcourt BA, Aaron CK. Intravenous fat emulsion for refractory verapamil and atenolol-induced shock: a human case report.
  2. Harchelroad FP, Palma A. Efficacy and safety of intravenous lipid therapy in a beta-blocker overdose
  3. Meehan TJ, Gummin DD, Kostic MA et al.. Beta Blocker toxicity successfully treated with intravenous fat emulsion: a case series.
  4. Carr D, Boone A, Hoffman RS et al.. Successful resuscitation of a carvedilol overdose using intravenous fat emulsion.
  5. Dean P, Ruddy JP, Marshall S.. Intravenous lipid emulsion in propranolol overdose.
  6. Stellpflug SJ, Harris CR, Engebretsen KM et al(a).. Intentional overdose with cardiac arrest treated with intravenous fat emulsion and high-dose insulin.
  7. Stellpflug SJ, Cole JB, Fritzlar SJ et al. (b). . Overdose of diltiazem, metoprolol and amiodarone treated with intravenous fat emulsion and high dose insulin in an awake patient.
  8. Smith A.. Intralipid for combined propranolol/clonidine overdose.
  9. Brent J.. A systematic review of the use of intravenous lipid therapy in the management of poisoned patients.
  10. Cave G, Harvey M.. Intravenous lipid emulsion as antidote beyond local anaesthetic toxicity: a systematic review.
  11. Cave G, Harvey M, Graudins A. . Intravenous lipid emulsion as antidote: a summary of published human experience.
  12. Jamaty C, Bailey B, Laroque A, Notebaert E, Sanogo K, Chauny JM. . Lipid emulsions in the treatment of acute poisoning: a systematic review of human and animal studies.
  13. National Poisons Information Service (UK).. TOXBASE Database [Online]
  14. Jovic-Stosic J, Gligic B, Putic V, et al. . Severe Propanolol and ethanol overdose with wide complex tachycardia treated with intravenous lipid emulsion: A case report.
  15. Rothschild L, Bern S, Oswald S, et al.. Intravenous lipid emulsion in clinical toxicology.