The effects of intravenous lipid emulsion on hemodynamic recovery and myocardial cell mitochondrial function after bupivacaine toxicity in anesthetized pigs

Local anesthetic toxicity is thought to be mediated partly by inhibition of cardiac mitochondrial function. Intravenous (i.v.) lipid emulsion may overcome this energy depletion, but doses larger than currently recommended may be needed for rescue effect. In this randomized study with anesthetized pigs, we compared the effect of a large dose, 4 mL/kg, of i.v. 20% Intralipid (R) (n = 7) with Ringer's acetate (n = 6) on cardiovascular recovery after a cardiotoxic dose of bupivacaine. We also examined mitochondrial respiratory function in myocardial cell homogenates analyzed promptly after needle biopsies from the animals. Bupivacaine plasma concentrations were quantified from plasma samples. Arterial blood pressure recovered faster and systemic vascular resistance rose more rapidly after Intralipid than Ringer's acetate administration (p <0.0001), but Intralipid did not increase cardiac index or left ventricular ejection fraction. The lipid-based mitochondrial respiration was stimulated by approximately 30% after Intralipid (p <0.05) but unaffected by Ringer's acetate. The mean (standard deviation) area under the concentration-time curve (AUC) of total bupivacaine was greater after Intralipid (105.2 (13.6) mg.min/L) than after Ringer's acetate (88.1 (7.1) mg.min/L) (p = 0.019). After Intralipid, the AUC of the lipid-un-entrapped bupivacaine portion (97.0 (14.5) mg.min/L) was 8% lower than that of total bupivacaine (p <0.0001). To conclude, 4 mL/kg of Intralipid expedited cardiovascular recovery from bupivacaine cardiotoxicity mainly by increasing systemic vascular resistance. The increased myocardial mitochondrial respiration and bupivacaine entrapment after Intralipid did not improve cardiac function.Peer reviewe

Association of extracerebral organ failure with 1-year survival and healthcare-associated costs after cardiac arrest: an observational database study

BackgroundOrgan dysfunction is common after cardiac arrest and associated with worse short-term outcome, but its impact on long-term outcome and treatment costs is unknown.MethodsWe used nationwide registry data from the intensive care units (ICU) of the five Finnish university hospitals to evaluate the association of 24-h extracerebral Sequential Organ Failure Assessment (24h-EC-SOFA) score with 1-year survival and healthcare-associated costs after cardiac arrest. We included adult cardiac arrest patients treated in the participating ICUs between January 1, 2003, and December 31, 2013. We acquired the confirmed date of death from the Finnish Population Register Centre database and gross 1-year healthcare-associated costs from the hospital billing records and the database of the Finnish Social Insurance Institution.ResultsA total of 5814 patients were included in the study, and 2401 were alive 1year after cardiac arrest. Median (interquartile range (IQR)) 24h-EC-SOFA score was 6 (5-8) in 1-year survivors and 7 (5-10) in non-survivors. In multivariate regression analysis, adjusting for age and prior independency in self-care, the 24h-EC-SOFA score had an odds ratio (OR) of 1.16 (95% confidence interval (CI) 1.14-1.18) per point for 1-year mortality.Median (IQR) healthcare-associated costs in the year after cardiac arrest were Euro47,000 (Euro28,000-75,000) in 1-year survivors and Euro12,000 (Euro6600-25,000) in non-survivors. In a multivariate linear regression model adjusting for age and prior independency in self-care, an increase of one point in the 24h-EC-SOFA score was associated with an increase of Euro170 (95% CI Euro150-190) in the cost per day alive in the year after cardiac arrest. In the same model, an increase of one point in the 24h-EC-SOFA score was associated with an increase of Euro4400 (95% CI Euro3300-5500) in the total healthcare-associated costs in 1-year survivors.ConclusionsExtracerebral organ dysfunction is associated with long-term outcome and gross healthcare-associated costs of ICU-treated cardiac arrest patients. It should be considered when assessing interventions to improve outcomes and optimize the use of resources in these patients

Binding of local anaesthetics to the lipid emulsion Clinoleic™ 20%

Lipid emulsions have been used to treat cardiovascular collapse due to local anaesthetic toxicity. However, there are few data available on the comparative efficiency of the partitioning properties of available lipid emulsions in clinical use. This in vitro study compared the buffering properties of the lipid emulsions Clinoleic (TM) 20% (Baxter, Old Toongabbie, NSW) and Intralipid (R) 20% (Fresenius Kabi, Pymble, NSW) using both bupivacaine (Marcain (R) 0.5%, AstraZeneca, North Ryde, NSW) and ropivacaine (Naropin (R) 1%, AstraZeneca, North Ryde, NSW). The concentration of anaesthetic in buffer before and after mixing with lipid was quantified using chromatographic analysis. Bupivacaine was more effectively bound by the lipid agents, with a 40% reduction in initial concentration. Ropivacaine demonstrated a 20% reduction in concentration with the addition of lipid agents. Importantly, there was no significant difference between Intralipid and Clinoleic in terms of their buffering behaviour, suggesting equivalent binding efficacy

Association of extracerebral organ failure with 1-year survival and healthcare-associated costs after cardiac arrest:an observational database study

Abstract Background: Organ dysfunction is common after cardiac arrest and associated with worse short-term outcome, but its impact on long-term outcome and treatment costs is unknown. Methods: We used nationwide registry data from the intensive care units (ICU) of the five Finnish university hospitals to evaluate the association of 24-h extracerebral Sequential Organ Failure Assessment (24h-EC-SOFA) score with 1-year survival and healthcare-associated costs after cardiac arrest. We included adult cardiac arrest patients treated in the participating ICUs between January 1, 2003, and December 31, 2013. We acquired the confirmed date of death from the Finnish Population Register Centre database and gross 1-year healthcare-associated costs from the hospital billing records and the database of the Finnish Social Insurance Institution. Results: A total of 5814 patients were included in the study, and 2401 were alive 1 year after cardiac arrest. Median (interquartile range (IQR)) 24h-EC-SOFA score was 6 (5–8) in 1-year survivors and 7 (5–10) in non-survivors. In multivariate regression analysis, adjusting for age and prior independency in self-care, the 24h-EC-SOFA score had an odds ratio (OR) of 1.16 (95% confidence interval (CI) 1.14–1.18) per point for 1-year mortality. Median (IQR) healthcare-associated costs in the year after cardiac arrest were €47,000 (€28,000–75,000) in 1-year survivors and €12,000 (€6600–25,000) in non-survivors. In a multivariate linear regression model adjusting for age and prior independency in self-care, an increase of one point in the 24h-EC-SOFA score was associated with an increase of €170 (95% CI €150–190) in the cost per day alive in the year after cardiac arrest. In the same model, an increase of one point in the 24h-EC-SOFA score was associated with an increase of €4400 (95% CI €3300–5500) in the total healthcare-associated costs in 1-year survivors. Conclusions: Extracerebral organ dysfunction is associated with long-term outcome and gross healthcare-associated costs of ICU-treated cardiac arrest patients. It should be considered when assessing interventions to improve outcomes and optimize the use of resources in these patients