ABSTRACT
Background@#Lipid emulsion (LE) is effective in treating intractable cardiac depression induced by the toxicity of highly lipid-soluble drugs including local anesthetics. However, the effect of LE on chloroquine (CQ)-evoked cardiac toxicity remains unclear. This study aimed to examine the effect of Lipofundin MCT/LCT, an LE, on the cardiotoxicity caused by CQ in H9c2 rat cardiomyoblasts and elucidate the underlying cellular mechanism. @*Methods@#The effects of CQ (1 × 10-4 M), LE, and the reactive oxygen species (ROS) scavengers mitotempo and N-acetyl-L-cysteine (NAC), alone or combined, on cell viability and migration, apoptosis, ROS production, calcium levels, mitochondrial membrane potential, and adenosine triphosphate (ATP) were examined. Additionally, the effects of LE on the activities of catalase (CAT), malondialdehyde (MDA), and superoxide dismutase (SOD) induced by CQ were assessed. @*Results@#Pretreatment with LE, mitotempo, or NAC reversed the reduction in cell migration and viability, mitochondrial membrane potential, and ATP levels evoked by CQ, and inhibited the increase in cleaved caspase-3, ROS, and calcium concentration induced by CQ. LE inhibited the increase in Bax expression, terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells, MDA activity, and late apoptosis, and reversed the reduction in SOD and CAT activity induced by CQ. CQ did not significantly affect cleaved caspase-8 expression, and LE did not significantly affect CQ concentration. @*Conclusions@#Collectively, these results suggest that LE (Lipofundin MCT/LCT) inhibits the cardiotoxicity and late apoptosis induced by CQ toxicity via the intrinsic mitochondrial apoptotic pathway that is associated with direct inhibition of ROS production.
ABSTRACT
Currently, lipid emulsion (LE) is widely used to treat local anesthetic systemic toxicity (LAST). LE also ameliorates intractable cardiovascular collapse caused by lipid-soluble non-local anesthetic drug toxicity. This review aims to provide the underlying mechanism of LE resuscitation in drug toxicity (including LAST) and a detailed description of LE treatment and to discuss further research directions. We searched for relevant articles using the following keywords: “local anesthetic systemic toxicity or LAST or toxicity or intoxication or poisoning” and “Intralipid or lipid emulsion”. The underlying mechanisms of LE treatment can be classified into indirect and direct effects. One indirect effect known as the lipid shuttle is a commonly accepted mechanism of LE treatment. The lipid shuttle involves the absorption of highly lipid-soluble drugs (e.g., bupivacaine) from the heart and brain through the lipid phase, which are then delivered to the muscle, adipose tissue, and liver for storage and detoxification. The direct effects include inotropic effects, fatty acid supply, attenuation of mitochondrial dysfunction, glycogen synthase kinase-3β phosphorylation, and inhibition of nitric oxide. These mechanisms appear to act synergistically to treat drug toxicity. The recommended protocol for LE treatment of LAST is as follows: a bolus administration of 20% LE at 1.5 ml/kg over 2–3 min followed by 20% LE at 0.25 ml/kg/min. LAST most commonly occurs after intravenous administration of local anesthetics. However, non-local anesthetic drugs that cause drug toxicity are orally administered. Further studies are needed to determine the optimal dosing schedule of LE treatment for non-local anesthetic drug toxicity.
ABSTRACT
Background@#Prolotherapy is a proliferation therapy as an alternative medicine. A combination of dextrose solution and lidocaine is usually used in prolotherapy. The concentrations of dextrose and lidocaine used in the clinical field are very high (dextrose 10%-25%, lidocaine 0.075%-1%). Several studies show about 1% dextrose and more than 0.2% lidocaine induced cell death in various cell types. We investigated the effects of low concentrations of dextrose and lidocaine in fibroblasts and suggest the optimal range of concentrations of dextrose and lidocaine in prolotherapy. @*Methods@#Various concentrations of dextrose and lidocaine were treated in NIH-3T3. Viability was examined with trypan blue exclusion assay and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Migration assay was performed for measuring the motile activity. Extracellular signal-regulated kinase (Erk) activation and protein expression of collagen I and α-smooth muscle actin (α-SMA) were determined with western blot analysis. @*Results@#The cell viability was decreased in concentrations of more than 5% dextrose and 0.1% lidocaine. However, in the concentrations 1% dextrose (D1) and 0.01% lidocaine (L0.01), fibroblasts proliferated mildly. The ability of migration in fibroblast was increased in the D1, L0.01, and D1 + L0.01 groups sequentially. D1 and L0.01 increased Erk activation and the expression of collagen I and α-SMA and D1 + L0.01 further increased. The inhibition of Erk activation suppressed fibroblast proliferation and the synthesis of collagen I. @*Conclusions@#D1, L0.01, and the combination of D1 and L0.01 induced fibroblast proliferation and increased collagen I synthesis via Erk activation.
ABSTRACT
Background@#Prolotherapy is a proliferation therapy as an alternative medicine. A combination of dextrose solution and lidocaine is usually used in prolotherapy. The concentrations of dextrose and lidocaine used in the clinical field are very high (dextrose 10%-25%, lidocaine 0.075%-1%). Several studies show about 1% dextrose and more than 0.2% lidocaine induced cell death in various cell types. We investigated the effects of low concentrations of dextrose and lidocaine in fibroblasts and suggest the optimal range of concentrations of dextrose and lidocaine in prolotherapy. @*Methods@#Various concentrations of dextrose and lidocaine were treated in NIH-3T3. Viability was examined with trypan blue exclusion assay and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Migration assay was performed for measuring the motile activity. Extracellular signal-regulated kinase (Erk) activation and protein expression of collagen I and α-smooth muscle actin (α-SMA) were determined with western blot analysis. @*Results@#The cell viability was decreased in concentrations of more than 5% dextrose and 0.1% lidocaine. However, in the concentrations 1% dextrose (D1) and 0.01% lidocaine (L0.01), fibroblasts proliferated mildly. The ability of migration in fibroblast was increased in the D1, L0.01, and D1 + L0.01 groups sequentially. D1 and L0.01 increased Erk activation and the expression of collagen I and α-SMA and D1 + L0.01 further increased. The inhibition of Erk activation suppressed fibroblast proliferation and the synthesis of collagen I. @*Conclusions@#D1, L0.01, and the combination of D1 and L0.01 induced fibroblast proliferation and increased collagen I synthesis via Erk activation.
ABSTRACT
Potassium imbalances can be life-threatening and must be identified and corrected prior to surgery. Patients with hypokalemic periodic paralysis (hypoKPP) experience recurrent muscle weakness or paralysis due to hypokalemia. We present the management of a rare case of hypoKPP during surgery and discuss the general complications and perioperative management of the condition. A 70-year-old man with hypoKPP visited the emergency room with abdominal pain requiring a cholecystectomy. He had not experienced hypoKPP since 1993, 1 year after diagnosis. Preoperative examinations were normal, with a serum potassium level of 4.5 mEq/L. Surgery and recovery were uneventful, with potassium levels ≥ 3.3 mEq/L. The post-surgery serum potassium level was 4.3 mEq/L. The patient had no signs of hypokalemia until 1-week post-surgery. Thorough preoperative preparation, careful assessment of serum potassium levels, avoidance of triggering factors, and appropriate postoperative pain relief can help prevent a hypokalemic attack in patients with hypoKPP.
ABSTRACT
Potassium imbalances can be life-threatening and must be identified and corrected prior to surgery. Patients with hypokalemic periodic paralysis (hypoKPP) experience recurrent muscle weakness or paralysis due to hypokalemia. We present the management of a rare case of hypoKPP during surgery and discuss the general complications and perioperative management of the condition. A 70-year-old man with hypoKPP visited the emergency room with abdominal pain requiring a cholecystectomy. He had not experienced hypoKPP since 1993, 1 year after diagnosis. Preoperative examinations were normal, with a serum potassium level of 4.5 mEq/L. Surgery and recovery were uneventful, with potassium levels ≥ 3.3 mEq/L. The post-surgery serum potassium level was 4.3 mEq/L. The patient had no signs of hypokalemia until 1-week post-surgery. Thorough preoperative preparation, careful assessment of serum potassium levels, avoidance of triggering factors, and appropriate postoperative pain relief can help prevent a hypokalemic attack in patients with hypoKPP.
ABSTRACT
Carotid artery rupture during head and neck surgery is a catastrophic, life-threatening emergency. Although recent incidence has declined, it still occurs in many patients. Hemorrhage from the carotid artery is usually massive and uncontrollable. Fast, aggressive treatment to prevent hemodynamic instability is required. Even if patients survive this event, they may experience severe neurological sequelae. A ruptured carotid artery is usually controlled by direct compression and arterial ligation. However, apart from the inherent difficulty of operation, these traditional surgical treatments are associated with high morbidity and mortality. In the past two decades, endovascular management has become a mainstay of carotid rupture treatment. We report a case of successful recovery without any sequelae after cardiovascular collapse due to an unintentional common carotid artery (CCA) rupture during neck surgery. The exposed CCA was treated with a covered stent. In such a case, multidisciplinary cooperation is crucial.
Subject(s)
Humans , Anesthesia , Carotid Arteries , Carotid Artery, Common , Emergencies , Head , Hemodynamics , Hemorrhage , Incidence , Ligation , Mortality , Neck , Radiology, Interventional , Rupture , StentsABSTRACT
BACKGROUND: The goal of this in vitro study was to investigate the effect of lipid emulsion on vasodilation caused by toxic doses of bupivacaine and mepivacaine during contraction induced by a protein kinase C (PKC) activator, phorbol 12,13-dibutyrate (PDBu), in an isolated endothelium-denuded rat aorta. METHODS: The effects of lipid emulsion on the dose-response curves induced by bupivacaine or mepivacaine in an isolated aorta precontracted with PDBu were assessed. In addition, the effects of bupivacaine on the increased intracellular calcium concentration ([Ca²⁺]ᵢ) and contraction induced by PDBu were investigated using fura-2 loaded aortic strips. Further, the effects of bupivacaine, the PKC inhibitor GF109203X and lipid emulsion, alone or in combination, on PDBu-induced PKC and phosphorylation-dependent inhibitory protein of myosin phosphatase (CPI-17) phosphorylation in rat aortic vascular smooth muscle cells (VSMCs) was examined by western blotting. RESULTS: Lipid emulsion attenuated the vasodilation induced by bupivacaine, whereas it had no effect on that induced by mepivacaine. Lipid emulsion had no effect on PDBu-induced contraction. The magnitude of bupivacaine-induced vasodilation was higher than that of the bupivacaine-induced decrease in [Ca²⁺]ᵢ. PDBu promoted PKC and CPI-17 phosphorylation in aortic VSMCs. Bupivacaine and GF109203X attenuated PDBu-induced PKC and CPI-17 phosphorylation, whereas lipid emulsion attenuated bupivacaine-mediated inhibition of PDBu-induced PKC and CPI-17 phosphorylation. CONCLUSIONS: These results suggest that lipid emulsion attenuates the vasodilation induced by a toxic dose of bupivacaine via inhibition of bupivacaine-induced PKC and CPI-17 dephosphorylation. This lipid emulsion-mediated inhibition of vasodilation may be partly associated with the lipid solubility of local anesthetics.
Subject(s)
Animals , Rats , Anesthetics, Local , Aorta , Blotting, Western , Bupivacaine , Calcium , Fura-2 , In Vitro Techniques , Mepivacaine , Muscle, Smooth, Vascular , Myosin-Light-Chain Phosphatase , Phorbol 12,13-Dibutyrate , Phosphorylation , Protein Kinase C , Solubility , VasodilationABSTRACT
BACKGROUND: The goal of this in vitro study was to investigate the effect of lipid emulsion on vasodilation caused by toxic doses of bupivacaine and mepivacaine during contraction induced by a protein kinase C (PKC) activator, phorbol 12,13-dibutyrate (PDBu), in an isolated endothelium-denuded rat aorta. METHODS: The effects of lipid emulsion on the dose-response curves induced by bupivacaine or mepivacaine in an isolated aorta precontracted with PDBu were assessed. In addition, the effects of bupivacaine on the increased intracellular calcium concentration ([Ca²⁺]ᵢ) and contraction induced by PDBu were investigated using fura-2 loaded aortic strips. Further, the effects of bupivacaine, the PKC inhibitor GF109203X and lipid emulsion, alone or in combination, on PDBu-induced PKC and phosphorylation-dependent inhibitory protein of myosin phosphatase (CPI-17) phosphorylation in rat aortic vascular smooth muscle cells (VSMCs) was examined by western blotting. RESULTS: Lipid emulsion attenuated the vasodilation induced by bupivacaine, whereas it had no effect on that induced by mepivacaine. Lipid emulsion had no effect on PDBu-induced contraction. The magnitude of bupivacaine-induced vasodilation was higher than that of the bupivacaine-induced decrease in [Ca²⁺]ᵢ. PDBu promoted PKC and CPI-17 phosphorylation in aortic VSMCs. Bupivacaine and GF109203X attenuated PDBu-induced PKC and CPI-17 phosphorylation, whereas lipid emulsion attenuated bupivacaine-mediated inhibition of PDBu-induced PKC and CPI-17 phosphorylation. CONCLUSIONS: These results suggest that lipid emulsion attenuates the vasodilation induced by a toxic dose of bupivacaine via inhibition of bupivacaine-induced PKC and CPI-17 dephosphorylation. This lipid emulsion-mediated inhibition of vasodilation may be partly associated with the lipid solubility of local anesthetics.
Subject(s)
Animals , Rats , Anesthetics, Local , Aorta , Blotting, Western , Bupivacaine , Calcium , Fura-2 , In Vitro Techniques , Mepivacaine , Muscle, Smooth, Vascular , Myosin-Light-Chain Phosphatase , Phorbol 12,13-Dibutyrate , Phosphorylation , Protein Kinase C , Solubility , VasodilationABSTRACT
BACKGROUND: Lipid emulsions have been used to treat various drug toxicities and for total parenteral nutrition therapy. Their usefulness has also been confirmed in patients with local anesthetic-induced cardiac toxicity. The purpose of this study was to measure the hemodynamic and composition effects of lipid emulsions and to elucidate the mechanism associated with changes in intracellular calcium levels in myocardiocytes. METHODS: We measured hemodynamic effects using a digital analysis system after Intralipid(R) and Lipofundin(R) MCT/LCT were infused into hearts hanging in a Langendorff perfusion system. We measured the effects of the lipid emulsions on intracellular calcium levels in H9c2 cells by confocal microscopy. RESULTS: Infusion of Lipofundin(R) MCT/LCT 20% (1 ml/kg) resulted in a significant increase in left ventricular systolic pressure compared to that after infusing modified Krebs-Henseleit solution (1 ml/kg) (P = 0.003, 95% confidence interval [CI], 2.4-12.5). Lipofundin(R) MCT/LCT 20% had a more positive inotropic effect than that of Intralipid(R) 20% (P = 0.009, 95% CI, 1.4-11.6). Both lipid emulsion treatments increased intracellular calcium levels. Lipofundin(R) MCT/LCT (0.01%) increased intracellular calcium level more than that of 0.01% Intralipid(R) (P < 0.05, 95% CI, 0.0-1.9). CONCLUSIONS: These two lipid emulsions had different inotropic effects depending on their triglyceride component. The inotropic effect of lipid emulsions could be related with intracellular calcium level.
Subject(s)
Animals , Humans , Rats , Blood Pressure , Calcium , Drug-Related Side Effects and Adverse Reactions , Emulsions , Heart , Hemodynamics , Microscopy, Confocal , Myocardial Contraction , Parenteral Nutrition, Total , Perfusion , TriglyceridesABSTRACT
A reninoma is an uncommon, benign, renin-secreting juxtaglomerular cell tumor that causes secondary hypertension in young patients. This hypertension is treated by tumor resection. Except for increased levels of plasma renin and angiotensin I and II, the other physical and laboratory examinations and electrocardiographs were within normal limits upon admission of a 19-year-old woman with a reninoma. For percutaneous computed tomography-guided radiofrequency ablation, general anesthesia was induced by thiopental sodium and rocuronium bromide and maintained with servoflurane (2-4 vol%) and oxygen. The operation ended uneventfully in hemodynamic stability. However, the patient complained of dizziness while sitting 5 hours after the operation, and hypotension was diagnosed. After aggressive normal saline (1 L) infusion over 30 min, the hypotension was corrected and the patient recovered without any other surgical complications. Here, we report the anesthetic management of a patient who underwent percutaneous computed tomography-guided radiofrequency ablation for reninoma destruction, particularly focusing on postoperative hypotension.
Subject(s)
Female , Humans , Young Adult , Anesthesia, General , Angiotensin I , Catheter Ablation , Dizziness , Electrocardiography , Hemodynamics , Hypertension , Hypotension , Oxygen , Plasma , Renin , ThiopentalABSTRACT
Although intravenous lipid emulsion (LE) is used mainly for parenteral nutrition, recently it has been used to treat patients with cardiopulmonary resuscitation (CPR)-resistant cardiovascular collapse induced by a toxic dose of local anesthetics or other drugs. Intravenous LE resolves symptoms of local anesthetic systemic toxicity, including convulsion, myoclonus, loss of consciousness, cardiac arrest, supraventricular tachycardia, and ventricular fibrillation. The main underlying mechanisms suggested to be responsible for LE-induced reversal of cardiac arrest due to drug toxicity are the lipid sink effect and the metabolic effect. The lipid sink theory posits that LE extracts a lipid-soluble toxic drug from the tissue. When a patient with cardiovascular collapse induced by a local anesthetic or another lipid-soluble drug is unresponsive to supportive treatments, including CPR and vasopressor therapy, LE administration can be considered. The suggested dosing regimen is as follows: 1) an initial intravenous bolus administration of 20% LE (1.5 mL/kg) is followed by a continuous infusion of 20% LE (0.25 mL/kg/min); and 2) when hemodynamic functions are unstable after the initial LE infusion, an intravenous administration of 20% LE (1.5 mL/kg) is repeated and followed by an increased continuous infusion of 20% LE (0.5 mL/kg/min). Further research is warranted regarding other possible mechanisms of LE's effect, the timing of LE administration, and the effect of various fatty acids on the LE-mediated reversal of cardiac arrest. This article reviews case reports and experimental evidence concerning the LE-mediated reversal of intractable cardiac arrest induced by drug toxicity, the underlying mechanism, and the dosing regimen.
Subject(s)
Humans , Administration, Intravenous , Anesthetics, Local , Cardiopulmonary Resuscitation , Drug-Related Side Effects and Adverse Reactions , Fatty Acids , Heart Arrest , Hemodynamics , Myoclonus , Parenteral Nutrition , Seizures , Tachycardia, Supraventricular , Unconsciousness , Ventricular FibrillationABSTRACT
BACKGROUND: A toxic dose of bupivacaine produces vasodilation in isolated aortas. The goal of this in vitro study was to investigate the cellular mechanism associated with bupivacaine-induced vasodilation in isolated endotheliumdenuded rat aortas precontracted with phenylephrine. METHODS: Isolated endothelium-denuded rat aortas were suspended for isometric tension recordings. The effects of nifedipine, verapamil, iberiotoxin, 4-aminopyridine, barium chloride, and glibenclamide on bupivacaine concentration-response curves were assessed in endothelium-denuded aortas precontracted with phenylephrine. The effect of phenylephrine and KCl used for precontraction on bupivacaine-induced concentration-response curves was assessed. The effects of verapamil on phenylephrine concentration-response curves were assessed. The effects of bupivacaine on the intracellular calcium concentration ([Ca2+]i) and tension in aortas precontracted with phenylephrine were measured simultaneously with the acetoxymethyl ester of a fura-2-loaded aortic strip. RESULTS: Pretreatment with potassium channel inhibitors had no effect on bupivacaine-induced relaxation in the endothelium-denuded aortas precontracted with phenylephrine, whereas verapamil or nifedipine attenuated bupivacaine-induced relaxation. The magnitude of the bupivacaine-induced relaxation was enhanced in the 100 mM KCl-induced precontracted aortas compared with the phenylephrine-induced precontracted aortas. Verapamil attenuated the phenylephrine-induced contraction. The magnitude of the bupivacaine-induced relaxation was higher than that of the bupivacaine-induced [Ca2+]i decrease in the aortas precontracted with phenylephrine. CONCLUSIONS: Taken together, these results suggest that toxic-dose bupivacaine-induced vasodilation appears to be mediated by decreased calcium sensitization in endothelium-denuded aortas precontracted with phenylephrine. In addition, potassium channel inhibitors had no effect on bupivacaine-induced relaxation. Toxic-dose bupivacaine- induced vasodilation may be partially associated with the inhibitory effect of voltage-operated calcium channels.
Subject(s)
Animals , Rats , 4-Aminopyridine , Aorta , Barium , Bupivacaine , Calcium Channels , Calcium , Glyburide , Nifedipine , Phenylephrine , Potassium Channels , Relaxation , Vasodilation , VerapamilABSTRACT
BACKGROUND: Mepivacaine induces contraction or decreased blood flow both in vivo and in vitro. Vasoconstriction is associated with an increase in the intracellular calcium concentration ([Ca2+]i). However, the mechanism responsible for the mepivacaine-evoked [Ca2+]i increase remains to be determined. Therefore, the objective of this in vitro study was to examine the mechanism responsible for the mepivacaine-evoked [Ca2+]i increment in isolated rat aorta. METHODS: Isometric tension was measured in isolated rat aorta without endothelium. In addition, fura-2 loaded aortic muscle strips were illuminated alternately (48 Hz) at two excitation wavelengths (340 and 380 nm). The ratio of F340 to F380 (F340/F380) was regarded as an amount of [Ca2+]i. We investigated the effects of nifedipine, 2-aminoethoxydiphenylborate (2-APB), gadolinium chloride hexahydrate (Gd3+), low calcium level and Krebs solution without calcium on the mepivacaine-evoked contraction in isolated rat aorta and on the mepivacaine-evoked [Ca2+]i increment in fura-2 loaded aortic strips. We assessed the effect of verapamil on the mepivacaine-evoked [Ca2+]i increment. RESULTS: Mepivacaine produced vasoconstriction and increased [Ca2+]i. Nifedipine, 2-APB and low calcium attenuated vasoconstriction and the [Ca2+]i increase evoked by mepivacaine. Verapamil attenuated the mepivacaine-induced [Ca2+]i increment. Calcium-free solution almost abolished mepivacaine-induced contraction and strongly attenuated the mepivacaineinduced [Ca2+]i increase. Gd3+ had no effect on either vasoconstriction or the [Ca2+]i increment evoked by mepivacaine. CONCLUSIONS: The mepivacaine-evoked [Ca2+]i increment, which contributes to mepivacaine-evoked contraction, appears to be mediated mainly by calcium influx and partially by calcium released from the sarcoplasmic reticulum.
Subject(s)
Animals , Rats , Aorta , Calcium , Endothelium , Fura-2 , Gadolinium , Mepivacaine , Nifedipine , Sarcoplasmic Reticulum , Vasoconstriction , VerapamilABSTRACT
BACKGROUND: Intravenous lipid emulsion has been used to treat systemic toxicity of local anesthetics. The goals of this in vitro study were to determine the ability of two lipid emulsions (Intralipid(R) and Lipofundin(R) MCT/LCT) to reverse toxic dose local anesthetic-induced vasodilation in isolated rat aortas. METHODS: Isolated endothelium-denuded aortas were suspended for isometric tension recording. Vasodilation was induced by bupivacaine (3 x 10(-4) M), ropivacaine (10(-3) M), lidocaine (3 x 10(-3) M), or mepivacaine (7 x 10(-3) M) after precontraction with 60 mM KCl. Intralipid(R) and Lipofundin(R) MCT/LCT were then added to generate concentration-response curves. We also assessed vasoconstriction induced by 60 mM KCl, 60 mM KCl with 3 x 10(-4) M bupivacaine, and 60 mM KCl with 3 x 10(-4) M bupivacaine plus 1.39% lipid emulsion (Intralipid(R) or Lipofundin(R) MCT/LCT). RESULTS: The two lipid emulsions reversed vasodilation induced by bupivacaine, ropivacaine, and lidocaine but had no effect on vasodilation induced by mepivacaine. Lipofundin(R) MCT/LCT was more effective than Intralipid(R) in reversing bupivacaine-induced vasodilation. The magnitude of lipid emulsion-mediated reversal of vasodilation induced by high-dose local anesthetics was as follows (from highest to lowest): 3 x 10(-4) M bupivacaine-induced vasodilation, 10(-3) M ropivacaine-induced vasodilation, and 3 x 10(-3) M lidocaine-induced vasodilation. CONCLUSIONS: Lipofundin(R) MCT/LCT-mediated reversal of bupivacaine-induced vasodilation was greater than that of Intralipid(R); however, the two lipid emulsions equally reversed vasodilation induced by ropivacaine and lidocaine. The magnitude of lipid emulsion-mediated reversal of vasodilation appears to be correlated with the lipid solubility of the local anesthetic.
Subject(s)
Animals , Rats , Amides , Anesthetics, Local , Aorta , Bupivacaine , Emulsions , Lidocaine , Mepivacaine , Solubility , Vasoconstriction , VasodilationABSTRACT
PURPOSE: Intravenous lipid emulsions have been used to treat the systemic toxicity of local anesthetics. The goal of this in vitro study was to examine the effects of lipid emulsions on the norepinephrine-mediated reversal of vasodilation induced by high doses of levobupivacaine, ropivacaine, and mepivacaine in isolated endothelium-denuded rat aorta, and to determine whether such effects are associated with the lipid solubility of local anesthetics. MATERIALS AND METHODS: The effects of lipid emulsions (0.30, 0.49, 1.40, and 2.61%) on norepinephrine concentration-responses in high-dose local anesthetic (6x10-4 M levobupivacaine, 2x10-3 M ropivacaine, and 7x10-3 M mepivacaine)-induced vasodilation of isolated aorta precontracted with 60 mM KCl were assessed. The effects of lipid emulsions on local anesthetic- and diltiazem-induced vasodilation in isolated aorta precontracted with phenylephrine were also assessed. RESULTS: Lipid emulsions (0.30%) enhanced norepinephrine-induced contraction in levobupivacaine-induced vasodilation, whereas 1.40 and 2.61% lipid emulsions enhanced norepinephrine-induced contraction in both ropivacaine- and mepivacaine-induced vasodilation, respectively. Lipid emulsions (0.20, 0.49 and 1.40%) inhibited vasodilation induced by levobupivacaine and ropivacaine, whereas 1.40 and 2.61% lipid emulsions slightly attenuated mepivacaine (3x10-3 M)-induced vasodilation. In addition, lipid emulsions attenuated diltiazem-induced vasodilation. Lipid emulsions enhanced norepinephrine-induced contraction in endothelium-denuded aorta without pretreatment with local anesthetics. CONCLUSION: Taken together, these results suggest that lipid emulsions enhance the norepinephrine-mediated reversal of local anesthetic-induced vasodilation at toxic anesthetic doses and inhibit local anesthetic-induced vasodilation in a manner correlated with the lipid solubility of a particular local anesthetic.
Subject(s)
Animals , Male , Rats , Amides/adverse effects , Anesthetics, Local/adverse effects , Bupivacaine/adverse effects , Emulsions/chemistry , Lipids/chemistry , Mepivacaine/adverse effects , Norepinephrine/therapeutic use , Rats, Sprague-Dawley , Vasodilation/drug effectsABSTRACT
The common predisposing risk factors for perioperative stroke include: previous stroke, atrial fibrillation, old age (> 75 years), carotid stenosis, and diabetes mellitus. An endoscopic sinus surgery was performed in a 49-year-old male with chronic paranasal sinusitis and nasal polyps. The vital signs, physical and laboratory examinations, and electrocardiography on admission were within the normal limit. Anesthesia was maintained with nitrous oxide in oxygen and 6% desflurane. The operation and anesthesia were uneventful with the exception of transient intraoperative hypotension. The patient recovered fully from the anesthesia (modified Aldrete score: 10) in the recovery room. However, he developed right arm weakness and dysarthria in the general ward 7 hours after the operation. We report a rare case of multifocal acute cerebral infarctions found on the postoperative magnetic resonance imaging in a noncardiac surgical patient.
Subject(s)
Humans , Male , Middle Aged , Anesthesia , Anesthesia, General , Arm , Atrial Fibrillation , Carotid Stenosis , Cerebral Infarction , Diabetes Mellitus , Dysarthria , Electrocardiography , Foramen Ovale, Patent , Hypotension , Isoflurane , Magnetic Resonance Imaging , Nasal Polyps , Nitrous Oxide , Oxygen , Patients' Rooms , Recovery Room , Risk Factors , Sinusitis , Stroke , Vital SignsABSTRACT
No abstract available.