Background. There have been some discussions that using swine or rabbits in a resuscitation model to study lipid emulsion infusions may be inappropriate because of a consistent “pseudoallergic” reaction that has been found in lipid-based nanoparticle liposome drug carrier systems. Assertions have been made that the lipid emulsions may contain a certain amount of liposomes; therefore swine may not be an appropriate model for study. Methods. This study was prospective, crossover design within subjects, and research design with each Yorkshire swine receiving a 20% lipid bolus infusion followed by a lipid infusion for 10 min. Each swine had a total of four blood draws and each draw had complete blood gas analysis with three different types of inflammatory markers examined. Cardio vascular monitoring was performed every 2 minutes. Results. Using data reported in similar studies, a large effect size of 0.6 was calculated. Using the effect size of 0.6, a power of 0.8 and an alpha of 0.05 it was determined that a sample size of five swine was needed. There were no significant changes in any CV parameter both before and after lipid emulsion. Likewise there were no significant changes in any of the blood tests, nor any inflammatory markers. Conclusions. There were no significant changes in the examined parameters with swine before and after lipid emulsion infusions. It is suggested that due to the close size of swine to humans, similar physiology, and ease of using these animals, they may be utilized for lipid emulsion studies. 1. Introduction There have been many antidotal letters indicating that an accidental overdose of local anesthetics (or other lipid drugs) has been treated effectively with a 20% lipid emulsion infusion [1–6]. These patients were not responding effectively to standard ACLS resuscitation protocols but recovered shortly after a last ditch effort with a lipid emulsion infusion [7]. However, a comparison of different resuscitation techniques with and without lipid emulsion infusion has never been performed to determine if lipid emulsion or ACLS protocol or possibly a combination of the two is the most effective treatment [8]. The model that may be the easiest to determine effectiveness of lipid emulsion in the face of drug overdose is swine. Swine (specifically Sus scrofa) physiology, size, and ease of use seem to make these animals very compatible models for this type of research [9]. Rats are not the best model due to more anatomical and physiological variance with humans and the inherent variability in using humans for CPR compressions
References
[1]
H. Ludot, J. Y. Tharin, M. Belouadah, J. X. Mazoit, and J. M. Malinovsky, “Successful resuscitation after ropivacaine and lidocaine-induced ventricular arrhythmia following posterior lumbar plexus block in a child,” Anesthesia and Analgesia, vol. 106, no. 5, pp. 1572–1574, 2008.
[2]
S. D. H. Finn, D. R. Uncles, J. Willers, and N. Sable, “Early treatment of a quetiapine and sertraline overdose with Intralipid？,” Anaesthesia, vol. 64, no. 2, pp. 191–194, 2009.
[3]
A. J. Sirianni, K. C. Osterhoudt, D. P. Calello et al., “Use of lipid emulsion in the resuscitation of a patient with prolonged cardiovascular collapse after overdose of bupropion and lamotrigine,” Annals of Emergency Medicine, vol. 51, no. 4, pp. 412–415.e1, 2008.
[4]
G. Foxall, R. Mccahon, J. Lamb, J. G. Hardman, and N. M. Bedforth, “Levobupivacaine-induced seizures and cardiovascular collapse treated with Intralipid,” Anaesthesia, vol. 62, no. 5, pp. 516–518, 2007.
[5]
M. Harvey, G. Cave, and A. Kazemi, “Intralipid infusion diminishes return of spontaneous circulation after hypoxic cardiac arrest in rabbits,” Anesthesia and Analgesia, vol. 108, no. 4, pp. 1163–1168, 2009.
[6]
S. Markowitz and J. M. Neal, “Immediate lipid emulsion therapy in the successful treatment of bupivacaine systemic toxicity,” Regional Anesthesia and Pain Medicine, vol. 34, no. 3, p. 276, 2009.
[7]
G. Weinberg, “Lipid rescue resuscitation from local anaesthetic cardiac toxicity,” Toxicological Reviews, vol. 25, no. 3, pp. 139–145, 2006.
[8]
L. Rothschild, S. Bern, S. Oswald, and G. Weinberg, “Intravenous lipid emulsion in clinical toxicology,” Scandinavian Journal of Trauma, Resuscitation, and Emergency Medicine, vol. 18, article 51, 2010.
[9]
F. Dorandeu, J. R. Mikler, H. Thiermann et al., “Swine models in the design of more effective medical countermeasures against organophosphorus poisoning,” Toxicology, vol. 233, no. 1–3, pp. 128–144, 2007.
[10]
J. Szebeni, “Complement activation-related pseudoallergy caused by liposomes, micellar carriers of intravenous drugs, and radiocontrast agents,” Critical Reviews in Therapeutic Drug Carrier Systems, vol. 18, no. 6, pp. 567–606, 2001.
[11]
J. Szebeni, “Complement activation-related pseudoallergy: a new class of drug-induced acute immune toxicity,” Toxicology, vol. 216, no. 2-3, pp. 106–121, 2005.
[12]
J. Szebeni, C. R. Alving, L. Rosivall et al., “Animal models of complement-mediated hypersensitivity reactions to liposomes and other lipid-based nanoparticles,” Journal of Liposome Research, vol. 17, no. 2, pp. 107–117, 2007.
[13]
J. Szebeni, L. Baranyi, S. Sávay et al., “Complement activation-related cardiac anaphylaxis in pigs: role of C5a anaphylatoxin and adenosine in liposome-induced abnormalities in ECG and heart function,” American Journal of Physiology, vol. 290, no. 3, pp. H1050–H1058, 2006.
[14]
B. Zider and G. Weinberg, “Are pigs the right model for lipid resuscitation?” AANA Journal, vol. 79, no. 6, pp. 453–454, e453.
[15]
The Association of Anaesthetists of Great Britain and Ireland 2010, Guidelines for the Management of Sever Local Anaesthetic Toxcity, 2012, http://www.aagbi.org/sites/default/files/la_toxicity_2010_0.pdf.
[16]
G. Weinberg, “Lipid rescue: caveats and recommendations for the ‘Silver Bullet’,” Regional Anesthesia and Pain Medicine, vol. 29, pp. 74–75, 2004.
[17]
R. J. Litz, M. Popp, S. N. Stehr, and T. Koch, “Successful resuscitation of a patient with ropivacaine-induced asystole after axillary plexus block using lipid infusion,” Anaesthesia, vol. 61, no. 8, pp. 800–801, 2006.
[18]
M. A. Rosenblatt, M. Abel, G. W. Fischer, C. J. Itzkovich, and J. B. Eisenkraft, “Successful use of a 20% lipid emulsion to resuscitate a patient after a presumed bupivacaine-related cardiac arrest,” Anesthesiology, vol. 105, no. 1, pp. 217–218, 2006.
[19]
X. Caide, Z. Liu, Q. Gao, Q. Zhou, and S. F. Sui, “Specific interaction of rabbit C-reactive protein with phospholipid membranes,” Thin Solid Films, vol. 284-285, pp. 793–796, 1996.
[20]
D. B. Hiller, G. Di Gregorio, K. Kelly et al., “Safety of high volume lipid emulsion infusion: a first approximation of LD50 in rats,” Regional Anesthesia and Pain Medicine, vol. 35, no. 2, pp. 140–144, 2010.
[21]
M. Buhl, J. Gjedsted, A. Granfeldt et al., “Circulating free fatty acids do not contribute to the acute systemic inflammatory response. An experimental study in porcine endotoxaemia,” Basic and Clinical Pharmacology and Toxicology, vol. 105, no. 5, pp. 319–326, 2009.
