C

Lipid resuscitation for local ane

sthetic toxicity: is it

really lifesaving?Ulana Leskiwa and Guy L. Weinberga,b

aUniversity of Illinois at Chicago College of Medicineand bJesse Brown VA Medical Center, Chicago, Illinois,USA

Correspondence to Ulana Leskiw, MD, University ofIllinois at Chicago College of Medicine, 1740 WestTaylor, Suite 3200W, M/C 515, Chicago, IL 60612,USATel: +1 312 996 4020; fax: +1 312 996 4019;e-mail: uleskiw@uic.edu

Current Opinion in Anaesthesiology 2009,22:667–671

Purpose of review

Laboratory studies and clinical reports have led to the acceptance of lipid emulsion

as an effective treatment of local anesthetic-induced cardiac arrest. This review

discusses subsequent clinical reports, relevant laboratory studies and topics for further

research.

Recent findings

Case reports have confirmed the efficacy of lipid resuscitation for local anesthetic

systemic toxicity. Furthermore, lipid emulsion has been used with apparent success

early in the spectrum of local anesthetic systemic toxicity to preempt cardiac arrest. The

role of lipid emulsion has expanded to treatment of cardiac toxicity due to other lipophilic

drugs. This appears to have an acceptable safety profile, although elevated amylase has

been reported. Laboratory investigations in animals suggest that concomitant

hypoxemia hinders resuscitation attempts, and that epinephrine and vasopressin are

more likely to be associated with poor outcomes than lipid.

Summary

Lipid emulsion infusion appears to be an effective treatment for cardiac toxicity induced

by lipophilic medications. Given the difficulties of performing clinical trials, further

laboratory investigation and clinical correlation are needed to better define its role in

resuscitation.

Keywords

lipid emulsion, local anesthetics, resuscitation, toxicity

Curr Opin Anaesthesiol 22:667–671� 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins0952-7907

IntroductionLocal anesthetic systemic toxicity (LAST) is a rare but

potentially catastrophic complication of regional anesthe-

sia [1]. Laboratory findings made over the last decade and

recent case reports suggest that lipid emulsion is a poten-

tial antidotal treatment and might reduce the morbidity

of this complication. Weinberg et al. [2] first reported in

1998 that lipid emulsion infused during resuscitation

increased the median lethal dose (LD50) of bupivacaine

in rats by 50%. In a subsequent study [3] of bupivacaine-

induced cardiac arrest in dogs, treatment with lipid

improved hemodynamics and survival compared with

isotonic saline-treated controls. This review will summar-

ize clinical experience with lipid emulsion, highlight

relevant laboratory studies and address the current status

of this therapy with respect to timing, dose, potential

adverse effects and its overall role in resuscitation.

Clinical experienceIn 2006, Rosenblatt et al. [4] and Litz et al. [5] reported

successful clinical use of lipid emulsion to reverse local

opyright © Lippincott Williams & Wilkins. Unauth

0952-7907 � 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins

anesthetic-induced cardiac arrest. In both cases, the

patients failed to respond to standard resuscitation

methods but regained normal hemodynamic parameters

shortly after lipid emulsion infusion. Further clinical

reports [6,7�–10�] have provided a growing body of sup-

port for use of this therapy. Lipid emulsion has been used

to treat LAST due to bupivacaine, levobupivacaine,

ropivacaine and mepivacaine, alone or in combination.

Lipid preparations other than Intralipid have also been

found to be effective; the successful use of 20% Liposyn

III (Hospira, Inc., Lake Forest, Illinois, USA) [10�] and

20% Medialipid (Braun, Kronberg, Germany) [8�] has

been reported. In addition to case reports published in

peer-reviewed journals, many cases have been posted at

the educational website www.lipidrescue.org.

Published guidelinesOn the basis of initial laboratory studies [2,3] and case

reports [4,5], the Association of Anaesthetists of Great

Britain and Ireland (AAGBI) published guidelines in

2007 for management of severe LAST, which stated that

lipid emulsion should be available in locations where

orized reproduction of this article is prohibited.

DOI:10.1097/ACO.0b013e32832eb93f

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668 Regional anaesthesia

potentially toxic doses of local anesthetics are adminis-

tered; recommended doses were provided (http://www.

aagbi.org/publications/guidelines/docs/latoxicity07.pdf).

In 2008, the American Society of Critical Care Anesthe-

siologists and the American Society of Anesthesiologists

Committee on Critical Care Medicine as well as the

Resuscitation Council of the UK also published protocols

for treatment of LAST, which incorporated the use of

lipid emulsion (http://www.asahq.org/clinical/Anesthe

siology-CentricACLS.pdf, http://www.resus.org.uk/pages/

caLocalA.htm). Of note, propofol is not a substitute for

lipid emulsion, given its lower lipid content and the known

myocardial depressant effects.

Application to other toxic eventsAnimal studies have demonstrated efficacy of lipid emul-

sion in treating verapamil toxicity [11,12], clomipramine

toxicity [13] and propranolol toxicity [14]. Furthermore,

lipid infusion has recently been used by physicians

treating patients for overdoses of other lipophilic toxins.

For instance, Sirianni et al. [15��] reported the dramatic

case of a 17-year-old girl with a severe overdose of

bupropion and lamotrigine. She subsequently suffered

a prolonged cardiac arrest refractory to standard advanced

cardiac life support (ACLS), including multiple defibril-

lations and bolus doses of epinephrine, NaHCO3, amio-

darone and ‘wide-open’ infusions of dopamine, norepi-

nephrine and epinephrine. One minute after an infusion

of 100 ml of 20% lipid emulsion, she regained normal

circulation and vital signs. Her hospital course was com-

plicated by acute lung injury (ALI) that was apparent

prior to the lipid infusion, and she was eventually dis-

charged with only minor memory deficits.

As the authors point out, bupivacaine and bupropion

share similar properties, including sodium channel block-

ing actions and nearly identical octanol : water partition

coefficients. Subsequent reports have described the suc-

cessful use of lipid rescue in the treatment of circulatory

and neurological symptoms of overdose with sertraline

and quetiapine (coma) [16�], sustained-release verapamil

(hypotension) [17�] and haldol (torsades de pointes) [18�].

An animal study [19�] of verapamil overdose indicates that

similar doses of lipid (in terms of total lipid mass) were

necessary as were used to treat bupivacaine-induced asys-

tole in rats.

Challenges in investigationThe infrequency of severe LAST cases and ethical

considerations preclude randomized clinical trials of lipid

resuscitation. We must, therefore, rely on case reports and

laboratory investigations to inform clinical practice. How-

ever, case reports suffer from positive reporting bias and

provide neither a precise numerator nor denominator of

opyright © Lippincott Williams & Wilkins. Unautho

cases. Although early clinical reports may have been

questioned because recovery might have resulted from

delayed response to conventional treatment rather than

lipid emulsion, the reliably rapid clinical improvement

after administration of lipid in dozens of cases appears to

support its efficacy. Taken together, the growing number

of cases and the highly consistent clinical descriptions of

return of spontaneous circulation strongly support the

usefulness of this therapy. This contrasts with classical

descriptions of refractory cardiac arrests in similar cir-

cumstances.

One current challenge is to define the role of lipid

emulsion in the treatment of toxicity induced by lipo-

philic agents. New information is inevitably followed by

new questions. Issues that remain to be determined

include optimal timing of administration and dose, poten-

tial adverse effects and the place of lipid in the scheme

of resuscitation.

Timing of administrationCurrent protocols from the AAGBI (and www.lipidres

cue.org) recommend lipid emulsion for cardiac arrest in

conjunction with standard basic life support (BLS) and

ACLS practices (http://www.lipidrescue.org, http://www.

aagbi.org/publications/guidelines/docs/latoxicity07.pdf).

However, as lipid therapy has become more accepted,

clinicians have chosen to administer lipid emulsion earlier

in the spectrum of adverse local anesthetic reactions,

preferring to act before refractory cardiac arrest occurs.

For instance, lipid emulsion was used to treat central

nervous system (CNS) toxicity and ventricular ectopy in

an attempt to prevent progression to cardiac arrest [6].

Other examples include a 13-year-old girl who developed

ventricular tachycardia after lumbar plexus block with

a ropivacaine–lidocaine mixture. Lipid emulsion was

administered at the onset of arrhythmia; the electrocardio-

gram reverted to normal, and surgery was performed

uneventfully [8�]. A 91-year-old man became unrespon-

sive with extrasystoles after upper extremity regional

anesthesia with mepivacaine and prilocaine. He received

lipid emulsion, with subsequent restoration of conscious-

ness and resolution of ectopy [9�]. Similarly, lipid reversed

CNS symptoms and ventricular tachycardia in an 82-year-

old woman after lower extremity nerve block [7�]. A

parturient who developed agitation and inability to follow

commands after epidural with bupivacaine was success-

fully treated with lipid emulsion [20].

Effective doseCase reports indicate that currently proposed dose

regimens are efficacious, although it is certainly possible

that there are treatment failures that have not been

reported. For local anesthetic-induced cardiac arrest,

rized reproduction of this article is prohibited.

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Lipid resuscitation Leskiw and Weinberg 669

recommendations include a bolus of 20% lipid, 1.5 ml/kg

(http://www.lipidrescue.org, http://www.aagbi.org/publi

cations/guidelines/docs/latoxicity07.pdf, http://www.

resus.org.uk/pages/caLocalA.htm) followed by an infu-

sion of 0.25 ml/kg/min for 20 min (http://www.aagbi.org/

publications/guidelines/docs/latoxicity07.pdf), 30–60 min

(http://www.lipidrescue.org) or until stable rhythm is

restored (http://www.resus.org.uk/pages/caLocalA.htm).

If adequate circulation is not restored, various regimens

have been suggested: bolus doses may be repeated up to

two times (http://www.lipidrescue.org), up to two times at

5 min intervals (http://www.aagbi.org/publications/guide

lines/docs/latoxicity07.pdf) or at 5 min intervals until

stable rhythm is restored (http://www.resus.org.uk/

pages/caLocalA.htm), and the infusion rate may be

increased (http://www.lipidrescue.org) or increased to

0.5 ml/kg/min for 10 min (http://www.aagbi.org/publi

cations/guidelines/docs/latoxicity07.pdf). Marwick et al.[21��] reported recurrence of ventricular ectopy in a

72 kg man who was successfully treated with Intralipid

for bupivacaine-induced cardiac arrest. A 150 ml bolus was

initially administered, followed by 350 ml over the next

30 min. Sinus rhythm and hemodynamic stability were

restored, and surgery proceeded, but 40 min later, ventri-

cular ectopy recurred. They point out that a full 1000 ml of

lipid may be required. On the contrary, in a study [8�]

describing lipid treatment of ventricular tachycardia after

nerve block, the bolus dose alone was adequate and infu-

sion was unnecessary.

Adverse effectsThere are concerns regarding possible adverse effects of

lipid therapy. The risk–benefit ratio becomes parti-

cularly important when lipid emulsion is used in patients

prior to the onset of overt hemodynamic instability and

cardiac arrest. The most serious adverse effect that has

been associated with the use of lipid emulsion for par-

enteral nutrition is pulmonary injury.

Recently, a single elevated amylase level was reported in

the patient described by Marwick et al. [21��] above; the

patient had received a total of 500 ml of Intralipid. No

clinical signs of pancreatitis were noted, and no specific

treatment was needed. Whether other cases of hypera-

mylasemia have occurred or are underreported is not

known. Notably, no other adverse effects have been

reported with the use of lipid for the treatment of

drug-related toxicity. Again, this may reflect underreport-

ing or positive bias; long-term follow-up may reveal

problems that are not currently apparent.

Laboratory investigationsIn order to better define the place of lipid emulsion in

resuscitation, Weinberg et al. [22��] studied lipid versus

opyright © Lippincott Williams & Wilkins. Unauth

epinephrine in a rat model of cardiac arrest. Anesthetized

rats received bupivacaine, 20 mg/kg, to induce asystole,

then immediately received cardiopulmonary resuscita-

tion (CPR) with 100% oxygen and either 30% lipid,

5 ml/kg bolus and 0.5 ml/kg/min infusion, epinephrine,

30 mg/kg bolus or normal saline. Bolus doses of medi-

cations were repeated at 2.5 and 5 min until the rate

pressure product was above 20% of baseline. At 10 min,

resuscitation rates were 5/5, 4/5 and 0/5 in the lipid group,

epinephrine group and saline group, respectively; pH,

paO2 and saturated venous oxygen (SvO2) were higher

and lactate lower in the lipid group. Notably, an early

increase in blood pressure (BP) with epinephrine was

followed by subsequent decline and pulmonary edema,

not seen in the lipid group. In a similar follow-up study

[23��], lipid emulsion was superior to vasopressin and

vasopressin/epinephrine with respect to rate pressure

product, pH, SvO2 and lactate. Results with vasopressin

alone were particularly unfavorable. In a rat model of

bupivacaine-induced asystole, concomitantly adminis-

tered epinephrine above 10 mg/kg hindered resuscitation

[24��]. These data suggest that use of lipid emulsion

earlier in the resuscitative effort and avoidance of press-

ors may result in better outcomes in this setting. These

are preliminary findings in animals, however, which need

to be investigated further and confirmed prior to extra-

polating to the clinical setting.

Of interest, the patient described by Sirianni et al.[15��] above, who received multiple doses of epinephrine

(18 mg total), had postresuscitation pulmonary edema/

ALI. Although pulmonary edema may occur after resus-

citation from cardiac arrest treated with standard ACLS

protocols, the consistent pattern of postvasopressor pul-

monary edema and worsened recovery in the pressor-

treated animals in the above-mentioned investigations is

notable. Whether this phenomenon is particular to the rat

model, whether bupivacaine somehow predisposes to

ALI or whether this results from significant myocardial

poisoning by local anesthetic and the vasoconstriction

caused by vasopressin and epinephrine which then over-

whelms the weakened ventricle leading to severe failure

remains to be elucidated in further studies.

Despite an apparent general enthusiasm for lipid resus-

citation, several reports question its efficacy with respect

to vasopressor treatment. Mayr et al. [25��], working with

a porcine model of bupivacaine overdose, reported that

vasopressin combined with epinephrine resulted in higher

coronary perfusion pressure during CPR and better short-

term survival rates than lipid emulsion. In this model,

mechanical ventilation was stopped after anesthetized

animals received 0.5% bupivacaine, 5 ml/kg, then not

resumed until 1 min after asystole occurred, at which time

CPR was initiated and mechanical ventilation resumed.

Animals received either 20% Intralipid (4 ml/kg, followed

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670 Regional anaesthesia

by infusion of 0.5 ml/kg/min) or vasopressin/epinephrine

(every 5 min in escalating doses, 0.4/45, 0.4/45 and

0.8/200 units/kg and mg/kg). Return of spontaneous circula-

tion, defined as SBP of at least 80 mmHg for at least 5 min,

was obtained in 5/5 of the pressor group but 0/5 of the lipid

group. The authors note that, in this short-term study,

they might have missed survival at a later time among

the lipid group. The design of the study, however, raises

the question of whether the cardiac arrest was bupivacaine-

induced or hypoxemia-induced in the context of

bupivacaine toxicity.

In contrast to perioperative occurrences in which the cause

is known, emergency rooms receive patients presenting

with cardiopulmonary and neurologic compromise of

unknown cause. Physicians need to decide whether to

administer lipid without knowing definitively whether the

patient had ingested a lipophilic toxin. It is, therefore,

important to know whether lipid itself interferes with

standard resuscitation. Harvey et al. [26��] addressed this

question in a rabbit model of asphyxial cardiac arrest. The

endotracheal tube was cross-clamped to cardiac arrest.

Animals were randomized to normal saline versus 20%

Intralipid, 3 ml/kg. Resuscitation included BLS/ACLS

with defibrillation and epinephrine, 100 mg/kg, repeated

if needed. Lipid emulsion/ACLS resulted in lower coron-

ary perfusion pressure and lower rates of return of spon-

taneous circulation (1/12 versus 7/11) compared with

ACLS alone. Of interest, however, at 50 min, there was

no difference in survival between groups.

What can we conclude from these conflicting studies?

First of all, the critical importance of prompt airway

management and maintenance of adequate oxygenation

cannot be overstated. The abysmal outcomes in the study

by Harvey et al. [26��] reinforce the importance of the ‘A’

and ‘B’ of the ‘ABC’s’ – airway, breathing and circulation.

The reports of successful use of lipid rescue are likely at

least partly predicated on these being ‘witnessed’ events

and the resulting absence of significant hypoxemia as a

contributing factor. These reports generally describe

appropriate airway management at the first sign of CNS

irritability, ventricular ectopy or hemodynamic instability,

with supplemental oxygen, ventilation and intubation

when necessary. The study of Mayr et al. [25��] describes

a somewhat different scenario. On the contrary, if docu-

mentation of lipophilic toxin ingestion is lacking and

hypoxemia is present, the data by Harvey et al. [26��]

would argue against lipid use. Finally, in cases of known

LAST complicated by significant hypoxemia, the data by

Harvey et al. [26��] might caution against earlier use of

lipid; however, the poor 50 min survival in both groups

suggests there is still much room for research as the

hypoxemia is likely more damaging than the lipid. The

poor overall survival is consistent with that noted in studies

of out-of-hospital cardiac arrest [27�].

opyright © Lippincott Williams & Wilkins. Unautho

MechanismInsights into the mechanism of action of lipid emulsion

will aid in optimizing its use. At present, the most likely

theory appears to be that of the lipid ‘sink’ binding the

lipophilic drugs and thereby reducing tissue content of

the toxin. Plasma levels are difficult to obtain during

resuscitation, however, and results so far are inconsistent.

An in-vitro study did indeed demonstrate high solubility

of local anesthetics in lipid emulsions and high binding

capacity of these emulsions; interestingly, Intralipid

appeared about 2.5 times more efficacious than Media-

lipid and binding was reduced at lower pH [28�].

ConclusionLipid emulsion has an apparently acceptable safety pro-

file in currently recommended doses and appears to be

effective in the treatment of cardiac arrest resulting

from lipophilic toxins. Clinicians report successful, early

administration of lipid emulsion to preempt cardiac

arrest. Continued diligent observation and reporting by

clinicians as well as appropriate laboratory investigation

will lead to better information and understanding of the

precise role of lipid emulsion in resuscitation.

AcknowledgementsDr Weinberg has Veterans’ Affairs Merit Funding. Dr Weinberg wasawarded U.S. patent 7 261 903 B1 ‘Lipid emulsion in the treatment ofsystemic poisoning’. He does not have equity interest or agreementswith any company or commercial entity related to this method. He hasnever received salary or support from any company. He does notintend to prohibit or restrict the practice of this method on any patientrequiring this treatment. Dr Weinberg also created and maintainswww.lipidrescue.org, an educational, noncommercial website provid-ing information and a forum for discussing the use of lipid emulsion intreating cardiac toxicity. He derives no salary or support related tothis website.

References and recommended readingPapers of particular interest, published within the annual period of review, havebeen highlighted as:� of special interest�� of outstanding interest

Additional references related to this topic can also be found in the CurrentWorld Literature section in this issue (p. 696).

1 Albright G. Cardiac arrest following regional anesthesia with etidocaine orbupivacaine. Anesthesiology 1979; 51:285–287.

2 Weinberg G, VadeBoncouer T, Ramaraju G, et al. Pretreatment or resuscita-tion with a lipid infusion shifts the dose-response to bupivacaine-inducedasystole in rats. Anesthesiology 1998; 88:1071–1075.

3 Weinberg G, Ripper R, Feinstein D, Hoffman W. Lipid emulsion infusionrescues dogs from bupivacaine-induced cardiac toxicity. Reg Anesth PainMed 2003; 28:198–202.

4 Rosenblatt MA, Abel M, Fischer GW, et al. Successful use of a 20% lipidemulsion to resuscitate a patient after a presumed bupivacaine-relatedcardiac arrest. Anesthesiology 2006; 105:217–218.

5 Litz RJ, Popp M, Stehr SN, Koch T. Successful resuscitation of a patient withropivacaine-induced asystole after axillary plexus block using lipid infusion.Anaesthesia 2006; 61:800–801.

6 Foxall G, McMahon R, Lamb J, et al. Levobupivacaine-induced seizures andcardiovascular collapse treated with Intralipid. Anaesthesia 2007; 62:516–518.

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Lipid resuscitation Leskiw and Weinberg 671

7

�McCutchen T, Gerancher JC. Early Intralipid therapy may have preventedbupivacaine-associated cardiac arrest. Reg Anesth Pain Med 2008; 33:178–180.

This study describes use of lipid emulsion to successfully treat CNS signs andventricular tachycardia with a pulse in a patient after nerve block.

8

�Ludot H, Tharin JY, Belouadah M, et al. Successful resuscitation afterropivacaine and lidocaine-induced ventricular arrhythmia following posteriorlumbar plexus block in a child. Anesth Analg 2008; 106:1572–1574.

This study describes the successful use of Medialipid to treat a 13-year-old girlwho developed ventricular tachycardia after lumbar plexus block with ropivacaine.

9

�Litz RJ, Roessel T, Heller AR, Stehr S. Reversal of central nervous system andcardiac toxicity after local anesthetic intoxication by lipid emulsion injection.Anesth Analg 2008; 106:1575–1577.

This study describes the successful use of lipid emulsion to reverse CNS signs andtreat ventricular ectopy in a patient who received brachial plexus block.

10

�Warren J, Thoma RB, Georgescu A, Saurin S. Intravenous lipid infusion in thesuccessful resuscitation of local anesthetic-induced cardiovascular collapseafter supraclavicular brachial plexus block. Anesth Analg 2008; 106:1578–1580.

This study describes the successful use of Liposyn III to treat cardiac arrest afterbrachial plexus block.

11 Tebbutt S, Harvey M, Nicholson T, Cave G. Intralipid prolongs survival in a ratmodel of verapamil toxicity. Acad Emerg Med 2006; 13:134–139.

12 Bania TC. Hemodynamic effects of intravenous fat emulsion in an animalmodel of severe verapamil toxicity resuscitated with atropine, calcium andnormal saline. Acad Emerg Med 2007; 14:105–111.

13 Harvey M, Cave G. Intralipid outperforms sodium bicarbonate in a rabbitmodel of clomipramine toxicity. Ann Emerg Med 2007; 49:178–185.

14 Harvey MG, Cave GR. Intralipid infusion ameliorates propranolol-inducedhypotension in rabbits. J Med Toxicol 2008; 4:71–76.

15

��Sirianni AJ, Osterhoudt KC, Callelo DP, et al. Use of lipid emulsion in theresuscitation of a patient with prolonged cardiovascular collapse afteroverdose of bupropion and lamotrigine. Ann Emerg Med 2008; 51:412–415.

This study describes the first clinical use of lipid emulsion to treat a patient withtoxicity due to lipophilic medications other than local anesthetics.

16

�Finn SDH, Uncles DR, Willers J, Sable N. Early treatment of quetiapine andsertraline overdose with Intralipid. Anaesthesia 2009; 64:191–194.

This study describes the use of lipid emulsion to reverse coma in a patient withdrug overdose.

17

�Young AC, Velez LI, Kleinschmidt KC. Intravenous fat emulsion therapyfor intentional sustained-release verapamil overdose. Resuscitation 2009;80:591–593.

This study describes the use of lipid emulsion to treat hypotension due to overdoseof sustained-release verapamil.

18

�Weinberg G, Di Gregorio G, Hiller G, et al. Lipid emulsion reversal ofhaloperidol-induced cardiac arrest. Ann Intern Med 2009; 150:737–738.

This study describes the successful use of lipid emulsion to treat pulselessmultiform ventricular tachycardia resulting from administration of haldol.

opyright © Lippincott Williams & Wilkins. Unauth

19

�Perez E, Bania TC, Medlej K, Chu J. Determining the optimal dose ofintravenous fat emulsion for the treatment of severe verapamil toxicity in arodent model. Acad Emerg Med 2008; 15:1284–1289.

In this animal study of treatment of verapamil toxicity, the optimal dose of lipid wasapproximately 18 ml/kg.

20 Spence A. Lipid reversal of central nervous system symptoms of bupivacainetoxicity (letter). Anesthesiology 2007; 107:516–517.

21

��Marwick PC, Levin AI, Coetzee AR. Recurrence of bupivacaine toxicity afterlipid rescue from bupivacaine-induced cardiac arrest. Anesth Analg 2009;108:1344–1346.

This study describes a patient who developed recurrence of ventricular ectopy40 min after successful resuscitation from cardiac arrest with lipid. Amylase waselevated postoperatively, but no signs of pancreatitis were noted.

22

��Weinberg G, DiGregorio G, Ripper R, et al. Resuscitation with lipid versusepinephrine in a rat model of bupivacaine overdose. Anesthesiology 2008;108:907–913.

This study of bupivacaine-induced cardiac arrest in a rat model found that lipid wassuperior to epinephrine with respect to resuscitation rates and metabolic parameters.

23

��Di Gregorio G, Schwartz D, Ripper R, et al. Lipid emulsion is superior tovasopressin in a rodent model of resuscitation from toxin-induced cardiacarrest. Crit Care Med 2009; 37:993–999.

This study in a rat model found that lipid was superior to vasopressin andvasopressin/epinephrine for resuscitation of bupivacaine-induced cardiac arrest.

24

��Hiller D, Di Gregorio G, Ripper R, et al. Epinephrine impairs lipid resuscitationfrom bupivacaine overdose: a threshold effect. Anesthesiology (in press).

In this study of bupivacaine-induced cardiac arrest in a rat model, epinephrine morethan 10 mg/kg hindered resuscitation.

25

��Mayr VD, Mitterschiftthaler L, Neurater A, et al. Comparison of the combinationof epinephrine and vasopressin with lipid emulsion in a porcine model ofasphyxial cardiac arrest after intravenous injection of bupivacaine. AnesthAnalg 2008; 106:1566–1571.

In this study of bupivacaine toxicity in a porcine asphyxial model, vasopressin/epinephrine resulted in a better short-term survival than lipid emulsion.

26

��Harvey M, Cave G, Kazemi A. Intralipid infusion diminishes return of sponta-neous circulation after hypoxic cardiac arrest in rabbits. Anesth Analg 2009;108:1163–1168.

In this study, in a rabbit asphyxial model of cardiac arrest without lipophilic toxins,ACLS alone resulted in better return of spontaneous circulation than ACLS/lipidemulsion.

27

�Gueugniaud PY, David JS, Chanzy E, et al. Vasopressin and epinephrine vs.epinephrine alone in cardiopulmonary resuscitation. N Engl J Med 2008;359:21–30.

In this large study of epinephrine/vasopressin versus epinephrine alone for out-of-hospital cardiac arrest, there were no significant differences between groups insurvival to hospital admission (approximately 21%) or survival to hospital discharge(approximately 2%).

28

�Mazoit JX, Le Guen R, Beloeil H, Benhamou D. Binding of long-lasting localanesthetics to lipid emulsions. Anesthesiology 2008; 106:1333–1336.

This in-vitro study demonstrated high solubility of local anesthetics in lipid emulsionand high binding capacity of lipid emulsions.

orized reproduction of this article is prohibited.