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Topic: Basic/Translational Science
Intralipid Resuscitation Confers Survival Advantage Compared to ClinOleic in Rats Overdosed with Propranolol
K. Macala, R. Khadaroo, S. Panahi, F. Gragasin, S. Bourque
Division of Critical Care Medicine, University of Alberta, Edmonton, Canada | Department of Surgery and Division of Critical Care Medicine, University of Alberta, Edmonton, Canada | Department of Anesthesiology and Pain Medicine, University of Alberta, Edmonton, Canada | Department of Anesthesiology and Pain Medicine, University of Alberta, Edmonton, Canada | Department of Anesthesiology and Pain Medicine, University of Alberta, Edmonton, Canada
Introduction:
Medication overdose is a prevalent issue across medical specialties. Most overdoses are treated with standard supportive therapies, but treatment with intravenous lipid emulsions (a component of parenteral nutrition1) is becoming popular for management of lipid soluble drug overdoses 2-7. The most widely used emulsion has been Intralipid4,5. However, Intralipid is being replaced with less pro-inflammatory emulsions such as ClinOleic for nutritional purposes8. We aimed to compare the resuscitation effectiveness of Intralipid (a soybean based emulsion) to that of ClinOleic (an olive-oil based emulsion).
Objectives: Specific Objective 1: Determine if Intralipid confers a survival advantage when used for resuscitation from propranolol overdose as compared to ClinOleic.
Specific Objective 2: Determine if rats surviving lipid resuscitation with either Intralipid or ClinOleic from propranolol overdose recovered blood pressure values to the same extent.
Methods:
Male Sprague-Dawley rats (3-5 months) were anesthetized with Isoflurane and instrumented for hemodynamic assessments with left-sided femoral arterial lines and left-sided femoral central venous catheters. In the first cohort, rats were randomly assigned to receive Intralipid (1mL/kg IV) or ClinOleic (1mL/kg IV) resuscitation following overdose with propranolol (15mg/kg IV). In the second cohort, rats received pre-treatment with either Intralipid (1mL/kg IV) or ClinOleic (1mL/kg IV) prior to propranolol (15mg/kg IV) administration. Endpoints included survival and time to recovery of 50%, 75%, and 90% of baseline hemodynamic parameters.
Results:
Figure 1 depicts a representative hemodynamic tracing through-out the experimental protocol. Baseline hemodynamic parameters were comparably similar in all groups of cohort 1 (table 1). Intralipid resuscitation conferred a survival advantage with 9/9 rats surviving whereas only 5/8 ClinOleic rats were resuscitated (100% versus 62.5% respectively, p = 0.0429). The number of rats achieving 50%, 75% and 90% of baseline mean arterial pressure was also improved in the Intralipid group (p = 0.043, p = 0.015, p = 0.027, respectively). Time to survival was similar in all surviving rats (table 2). Baseline hemodynamic parameters were also similar in the second cohort of rats (table 3). Intralipid pre-treatment resulted in prolonged survival compared to ClinOleic (p = 0.0427) (figure 2).
Conclusion: Intralipid improves survival in rats treated within minutes of propranolol overdose compared to ClinOleic. Intralipid pre-treatment improved survival time when compared to ClinOleic, suggesting alternative mechanisms of action other than ILEs acting as a lipid sink.
References:
1. Cave G, Harvey M. Intravenous lipid emulsion as antidote beyond local anesthetic toxicity: A systematic review. Acad Emerg Med. 2009;16:815-824.
2. American College of Medical Toxicology. ACMT position statement: Interim guidance for the use of lipid resuscitation therapy. J Med Toxicol. 2011;7:81-82.
3. Rosenblatt MA, Abel M, Fischer GW, Itzkovich CJ, Eisenkraft JB. Successful use of a 20% lipid emulsion to resuscitate a patient after a presumed bupivacaine-related cardiac arrest. Anesthesiology. 2006;105:217-218.
4. Weinberg GL. Lipid emulsion infusion: Resuscitation for local anesthetic and other drug overdose. Anesthesiology. 2012;117:180-187.
5. Cao D, Heard K, Foran M, Koyfman A. Intravenous lipid emulsion in the emergency department: A systematic review of recent literature. J Emerg Med. 2015;48:387-397.
6. Weinberg GL, VadeBoncouer T, Ramaraju GA, Garcia-Amaro MF, Cwik MJ. Pretreatment or resuscitation with a lipid infusion shifts the dose-response to bupivacaine-induced asystole in rats. Anesthesiology. 1998;88:1071-1075.
7. Macala K, Tabrizchi R. The effect of fat emulsion on hemodynamics following treatment with propranolol and clonidine in anesthetized rats. Acad Emerg Med. 2014;21:1220-1225.
8. Siqueira J, Smiley D, Newton C, Le NA, Gosmanov AR, Spiegelman R, Peng L, Osteen SJ, Jones DP, Quyyumi AA, Ziegler TR, Umpierrez GE. Substitution of standard soybean oil with olive oil-based lipid emulsion in parenteral nutrition: Comparison of vascular, metabolic, and inflammatory effects. J Clin Endocrinol Metab. 2011;96:3207-3216.Topic: Basic/Translational Science
Intralipid Resuscitation Confers Survival Advantage Compared to ClinOleic in Rats Overdosed with Propranolol
K. Macala, R. Khadaroo, S. Panahi, F. Gragasin, S. Bourque
Division of Critical Care Medicine, University of Alberta, Edmonton, Canada | Department of Surgery and Division of Critical Care Medicine, University of Alberta, Edmonton, Canada | Department of Anesthesiology and Pain Medicine, University of Alberta, Edmonton, Canada | Department of Anesthesiology and Pain Medicine, University of Alberta, Edmonton, Canada | Department of Anesthesiology and Pain Medicine, University of Alberta, Edmonton, Canada
Introduction:
Medication overdose is a prevalent issue across medical specialties. Most overdoses are treated with standard supportive therapies, but treatment with intravenous lipid emulsions (a component of parenteral nutrition1) is becoming popular for management of lipid soluble drug overdoses 2-7. The most widely used emulsion has been Intralipid4,5. However, Intralipid is being replaced with less pro-inflammatory emulsions such as ClinOleic for nutritional purposes8. We aimed to compare the resuscitation effectiveness of Intralipid (a soybean based emulsion) to that of ClinOleic (an olive-oil based emulsion).
Objectives: Specific Objective 1: Determine if Intralipid confers a survival advantage when used for resuscitation from propranolol overdose as compared to ClinOleic.
Specific Objective 2: Determine if rats surviving lipid resuscitation with either Intralipid or ClinOleic from propranolol overdose recovered blood pressure values to the same extent.
Methods:
Male Sprague-Dawley rats (3-5 months) were anesthetized with Isoflurane and instrumented for hemodynamic assessments with left-sided femoral arterial lines and left-sided femoral central venous catheters. In the first cohort, rats were randomly assigned to receive Intralipid (1mL/kg IV) or ClinOleic (1mL/kg IV) resuscitation following overdose with propranolol (15mg/kg IV). In the second cohort, rats received pre-treatment with either Intralipid (1mL/kg IV) or ClinOleic (1mL/kg IV) prior to propranolol (15mg/kg IV) administration. Endpoints included survival and time to recovery of 50%, 75%, and 90% of baseline hemodynamic parameters.
Results:
Figure 1 depicts a representative hemodynamic tracing through-out the experimental protocol. Baseline hemodynamic parameters were comparably similar in all groups of cohort 1 (table 1). Intralipid resuscitation conferred a survival advantage with 9/9 rats surviving whereas only 5/8 ClinOleic rats were resuscitated (100% versus 62.5% respectively, p = 0.0429). The number of rats achieving 50%, 75% and 90% of baseline mean arterial pressure was also improved in the Intralipid group (p = 0.043, p = 0.015, p = 0.027, respectively). Time to survival was similar in all surviving rats (table 2). Baseline hemodynamic parameters were also similar in the second cohort of rats (table 3). Intralipid pre-treatment resulted in prolonged survival compared to ClinOleic (p = 0.0427) (figure 2).
Conclusion: Intralipid improves survival in rats treated within minutes of propranolol overdose compared to ClinOleic. Intralipid pre-treatment improved survival time when compared to ClinOleic, suggesting alternative mechanisms of action other than ILEs acting as a lipid sink.
References:
1. Cave G, Harvey M. Intravenous lipid emulsion as antidote beyond local anesthetic toxicity: A systematic review. Acad Emerg Med. 2009;16:815-824.
2. American College of Medical Toxicology. ACMT position statement: Interim guidance for the use of lipid resuscitation therapy. J Med Toxicol. 2011;7:81-82.
3. Rosenblatt MA, Abel M, Fischer GW, Itzkovich CJ, Eisenkraft JB. Successful use of a 20% lipid emulsion to resuscitate a patient after a presumed bupivacaine-related cardiac arrest. Anesthesiology. 2006;105:217-218.
4. Weinberg GL. Lipid emulsion infusion: Resuscitation for local anesthetic and other drug overdose. Anesthesiology. 2012;117:180-187.
5. Cao D, Heard K, Foran M, Koyfman A. Intravenous lipid emulsion in the emergency department: A systematic review of recent literature. J Emerg Med. 2015;48:387-397.
6. Weinberg GL, VadeBoncouer T, Ramaraju GA, Garcia-Amaro MF, Cwik MJ. Pretreatment or resuscitation with a lipid infusion shifts the dose-response to bupivacaine-induced asystole in rats. Anesthesiology. 1998;88:1071-1075.
7. Macala K, Tabrizchi R. The effect of fat emulsion on hemodynamics following treatment with propranolol and clonidine in anesthetized rats. Acad Emerg Med. 2014;21:1220-1225.
8. Siqueira J, Smiley D, Newton C, Le NA, Gosmanov AR, Spiegelman R, Peng L, Osteen SJ, Jones DP, Quyyumi AA, Ziegler TR, Umpierrez GE. Substitution of standard soybean oil with olive oil-based lipid emulsion in parenteral nutrition: Comparison of vascular, metabolic, and inflammatory effects. J Clin Endocrinol Metab. 2011;96:3207-3216.
Topic: Basic/Translational Science
Intralipid Resuscitation Confers Survival Advantage Compared to ClinOleic in Rats Overdosed with Propranolol
K. Macala, R. Khadaroo, S. Panahi, F. Gragasin, S. Bourque
Division of Critical Care Medicine, University of Alberta, Edmonton, Canada | Department of Surgery and Division of Critical Care Medicine, University of Alberta, Edmonton, Canada | Department of Anesthesiology and Pain Medicine, University of Alberta, Edmonton, Canada | Department of Anesthesiology and Pain Medicine, University of Alberta, Edmonton, Canada | Department of Anesthesiology and Pain Medicine, University of Alberta, Edmonton, Canada
Introduction:
Medication overdose is a prevalent issue across medical specialties. Most overdoses are treated with standard supportive therapies, but treatment with intravenous lipid emulsions (a component of parenteral nutrition1) is becoming popular for management of lipid soluble drug overdoses 2-7. The most widely used emulsion has been Intralipid4,5. However, Intralipid is being replaced with less pro-inflammatory emulsions such as ClinOleic for nutritional purposes8. We aimed to compare the resuscitation effectiveness of Intralipid (a soybean based emulsion) to that of ClinOleic (an olive-oil based emulsion).
Objectives: Specific Objective 1: Determine if Intralipid confers a survival advantage when used for resuscitation from propranolol overdose as compared to ClinOleic.
Specific Objective 2: Determine if rats surviving lipid resuscitation with either Intralipid or ClinOleic from propranolol overdose recovered blood pressure values to the same extent.
Methods:
Male Sprague-Dawley rats (3-5 months) were anesthetized with Isoflurane and instrumented for hemodynamic assessments with left-sided femoral arterial lines and left-sided femoral central venous catheters. In the first cohort, rats were randomly assigned to receive Intralipid (1mL/kg IV) or ClinOleic (1mL/kg IV) resuscitation following overdose with propranolol (15mg/kg IV). In the second cohort, rats received pre-treatment with either Intralipid (1mL/kg IV) or ClinOleic (1mL/kg IV) prior to propranolol (15mg/kg IV) administration. Endpoints included survival and time to recovery of 50%, 75%, and 90% of baseline hemodynamic parameters.
Results:
Figure 1 depicts a representative hemodynamic tracing through-out the experimental protocol. Baseline hemodynamic parameters were comparably similar in all groups of cohort 1 (table 1). Intralipid resuscitation conferred a survival advantage with 9/9 rats surviving whereas only 5/8 ClinOleic rats were resuscitated (100% versus 62.5% respectively, p = 0.0429). The number of rats achieving 50%, 75% and 90% of baseline mean arterial pressure was also improved in the Intralipid group (p = 0.043, p = 0.015, p = 0.027, respectively). Time to survival was similar in all surviving rats (table 2). Baseline hemodynamic parameters were also similar in the second cohort of rats (table 3). Intralipid pre-treatment resulted in prolonged survival compared to ClinOleic (p = 0.0427) (figure 2).
Conclusion: Intralipid improves survival in rats treated within minutes of propranolol overdose compared to ClinOleic. Intralipid pre-treatment improved survival time when compared to ClinOleic, suggesting alternative mechanisms of action other than ILEs acting as a lipid sink.
References:
1. Cave G, Harvey M. Intravenous lipid emulsion as antidote beyond local anesthetic toxicity: A systematic review. Acad Emerg Med. 2009;16:815-824.
2. American College of Medical Toxicology. ACMT position statement: Interim guidance for the use of lipid resuscitation therapy. J Med Toxicol. 2011;7:81-82.
3. Rosenblatt MA, Abel M, Fischer GW, Itzkovich CJ, Eisenkraft JB. Successful use of a 20% lipid emulsion to resuscitate a patient after a presumed bupivacaine-related cardiac arrest. Anesthesiology. 2006;105:217-218.
4. Weinberg GL. Lipid emulsion infusion: Resuscitation for local anesthetic and other drug overdose. Anesthesiology. 2012;117:180-187.
5. Cao D, Heard K, Foran M, Koyfman A. Intravenous lipid emulsion in the emergency department: A systematic review of recent literature. J Emerg Med. 2015;48:387-397.
6. Weinberg GL, VadeBoncouer T, Ramaraju GA, Garcia-Amaro MF, Cwik MJ. Pretreatment or resuscitation with a lipid infusion shifts the dose-response to bupivacaine-induced asystole in rats. Anesthesiology. 1998;88:1071-1075.
7. Macala K, Tabrizchi R. The effect of fat emulsion on hemodynamics following treatment with propranolol and clonidine in anesthetized rats. Acad Emerg Med. 2014;21:1220-1225.
8. Siqueira J, Smiley D, Newton C, Le NA, Gosmanov AR, Spiegelman R, Peng L, Osteen SJ, Jones DP, Quyyumi AA, Ziegler TR, Umpierrez GE. Substitution of standard soybean oil with olive oil-based lipid emulsion in parenteral nutrition: Comparison of vascular, metabolic, and inflammatory effects. J Clin Endocrinol Metab. 2011;96:3207-3216.Topic: Basic/Translational Science
Intralipid Resuscitation Confers Survival Advantage Compared to ClinOleic in Rats Overdosed with Propranolol
K. Macala, R. Khadaroo, S. Panahi, F. Gragasin, S. Bourque
Division of Critical Care Medicine, University of Alberta, Edmonton, Canada | Department of Surgery and Division of Critical Care Medicine, University of Alberta, Edmonton, Canada | Department of Anesthesiology and Pain Medicine, University of Alberta, Edmonton, Canada | Department of Anesthesiology and Pain Medicine, University of Alberta, Edmonton, Canada | Department of Anesthesiology and Pain Medicine, University of Alberta, Edmonton, Canada
Introduction:
Medication overdose is a prevalent issue across medical specialties. Most overdoses are treated with standard supportive therapies, but treatment with intravenous lipid emulsions (a component of parenteral nutrition1) is becoming popular for management of lipid soluble drug overdoses 2-7. The most widely used emulsion has been Intralipid4,5. However, Intralipid is being replaced with less pro-inflammatory emulsions such as ClinOleic for nutritional purposes8. We aimed to compare the resuscitation effectiveness of Intralipid (a soybean based emulsion) to that of ClinOleic (an olive-oil based emulsion).
Objectives: Specific Objective 1: Determine if Intralipid confers a survival advantage when used for resuscitation from propranolol overdose as compared to ClinOleic.
Specific Objective 2: Determine if rats surviving lipid resuscitation with either Intralipid or ClinOleic from propranolol overdose recovered blood pressure values to the same extent.
Methods:
Male Sprague-Dawley rats (3-5 months) were anesthetized with Isoflurane and instrumented for hemodynamic assessments with left-sided femoral arterial lines and left-sided femoral central venous catheters. In the first cohort, rats were randomly assigned to receive Intralipid (1mL/kg IV) or ClinOleic (1mL/kg IV) resuscitation following overdose with propranolol (15mg/kg IV). In the second cohort, rats received pre-treatment with either Intralipid (1mL/kg IV) or ClinOleic (1mL/kg IV) prior to propranolol (15mg/kg IV) administration. Endpoints included survival and time to recovery of 50%, 75%, and 90% of baseline hemodynamic parameters.
Results:
Figure 1 depicts a representative hemodynamic tracing through-out the experimental protocol. Baseline hemodynamic parameters were comparably similar in all groups of cohort 1 (table 1). Intralipid resuscitation conferred a survival advantage with 9/9 rats surviving whereas only 5/8 ClinOleic rats were resuscitated (100% versus 62.5% respectively, p = 0.0429). The number of rats achieving 50%, 75% and 90% of baseline mean arterial pressure was also improved in the Intralipid group (p = 0.043, p = 0.015, p = 0.027, respectively). Time to survival was similar in all surviving rats (table 2). Baseline hemodynamic parameters were also similar in the second cohort of rats (table 3). Intralipid pre-treatment resulted in prolonged survival compared to ClinOleic (p = 0.0427) (figure 2).
Conclusion: Intralipid improves survival in rats treated within minutes of propranolol overdose compared to ClinOleic. Intralipid pre-treatment improved survival time when compared to ClinOleic, suggesting alternative mechanisms of action other than ILEs acting as a lipid sink.
References:
1. Cave G, Harvey M. Intravenous lipid emulsion as antidote beyond local anesthetic toxicity: A systematic review. Acad Emerg Med. 2009;16:815-824.
2. American College of Medical Toxicology. ACMT position statement: Interim guidance for the use of lipid resuscitation therapy. J Med Toxicol. 2011;7:81-82.
3. Rosenblatt MA, Abel M, Fischer GW, Itzkovich CJ, Eisenkraft JB. Successful use of a 20% lipid emulsion to resuscitate a patient after a presumed bupivacaine-related cardiac arrest. Anesthesiology. 2006;105:217-218.
4. Weinberg GL. Lipid emulsion infusion: Resuscitation for local anesthetic and other drug overdose. Anesthesiology. 2012;117:180-187.
5. Cao D, Heard K, Foran M, Koyfman A. Intravenous lipid emulsion in the emergency department: A systematic review of recent literature. J Emerg Med. 2015;48:387-397.
6. Weinberg GL, VadeBoncouer T, Ramaraju GA, Garcia-Amaro MF, Cwik MJ. Pretreatment or resuscitation with a lipid infusion shifts the dose-response to bupivacaine-induced asystole in rats. Anesthesiology. 1998;88:1071-1075.
7. Macala K, Tabrizchi R. The effect of fat emulsion on hemodynamics following treatment with propranolol and clonidine in anesthetized rats. Acad Emerg Med. 2014;21:1220-1225.
8. Siqueira J, Smiley D, Newton C, Le NA, Gosmanov AR, Spiegelman R, Peng L, Osteen SJ, Jones DP, Quyyumi AA, Ziegler TR, Umpierrez GE. Substitution of standard soybean oil with olive oil-based lipid emulsion in parenteral nutrition: Comparison of vascular, metabolic, and inflammatory effects. J Clin Endocrinol Metab. 2011;96:3207-3216.