Caracterización del uso de emulsiones lipídicas como terapia antidotal en intoxicaciones diferentes a anestésicos locales en un centro de alta complejidad en Medellín / Characterization of the use of lipid emulsions as antidotal therapy in intoxications other than local anesthetics in a high complexity center in Medellin

Introducción. Las emulsiones lipídicas intravenosas (ELI) son unas emulsiones grasas no tóxicas con fosfolípidos, actualmente aprobadas para su uso en el tratamiento de intoxicaciones, específicamente en las producidas por anestésicos locales. El propósito de este estudio es la caracterización del uso de ELI en pacientes mayores de 18 años, que presentaron intoxicación por sustancias y medicamentos diferentes a anestésicos locales, en un hospital de alta complejidad de la ciudad de Medellín, durante el periodo comprendido entre 2015 y 2020. Metodología. Se realizó un estudio descriptivo, retrospectivo, de casos que recibieron ELI como tratamiento para su intoxicación. Se hizo revisión de las historias clínicas de la población objeto de estudio. Se recolectó información acerca de variables sociodemográficas, clínicas y paraclínicas, y de atención. Se hizo análisis univariado de las variables de interés. Resultados. Del total de 1.966 intoxicaciones, se incluyeron 51 (2,6 %) casos de intoxicación por sustancias y medicamentos diferentes a anestésicos locales, que recibieron la terapia con ELI entre 2015 y 2020. La mediana de edad de los participantes fue de 27 años. Un 74,5 % de los participantes presentó intoxicación por medicamentos. El promedio de la dosis de ELI recibida fue de 1.036 mL en 24 horas, dosis inferior a la calculada por kilo de peso que debían recibir, de 1.149 mL en promedio. Un 86,3 % (n=44) de los casos presentaron neurotoxicidad, y 76,5 % (n=39) presentaron cardiotoxicidad. La neurotoxicidad mejoró en el 34,7 % y la cardiotoxicidad en el 59,1 % de los individuos que recibieron terapia con ELI. Conclusión. La aplicación de las ELI se hizo en personas en su mayoría intoxicadas por antipsicóticos, hombres, jóvenes; menos de la mitad tenía compromiso de la ventilación, y hubo mejoría en la cardiotoxicidad y neurotoxicidad. Hubo una diferencia entre la dosis recibida y la que debían recibir ajustada por el peso

Introduction. Intravenous lipid emulsions (IVLE) are non-toxic fatty emulsions with phospholipids, currently approved for use in the treatment of poisoning, specifically those produced by local anesthetics. The purpose of this study is to characterize the use of IVLE in patients over 18 years of age, who presented intoxication by substances and medications other than local anesthetics, in a high complexity hospital in the city of Medellín, during the period between 2015 and 2020. Methodology. A retrospective descriptive study was carried out on cases that received IVLE as a treatment for their poisoning. The clinical records of the study population were reviewed. Information was collected about sociodemographic, clinical and paraclinical variables, and care. Univariate analysis of the variables of interest was performed. Results. Of the total of 1,966 poisonings, 51 (2.6%) cases caused by substances and medications other than local anesthetics, received ELI therapy between 2015 and 2020 and were included in the study. The median age of the participants was 27 years. 74.5% of the participants presented drug poisoning. The average IVLE dose received was 1,036 mL in 24 hours, a lower dose than the one calculated per kilo of weight, which had been on average 1,149 mL. 86.3% (n=44) of the cases presented neurotoxicity, and 76.5% (n=39) presented cardiotoxicity. Neurotoxicity improved in 34.7% and cardiotoxicity in 59.1% of individuals receiving ELI therapy. Conclusion. The application of IVLE was made in people mostly poisoned by antipsychotics, men, young people, less than half had compromised ventilation, and there was improvement in cardiotoxicity and neurotoxicity. There was a difference between the dose received and the one they should have received adjusted for weight

Uso de emulsiones lipídicas en el tratamiento exitoso de un caso de intoxicación por difenhidramina / Use of lipid emulsions in the successful treatment of a case of diphenhydramine poisoning / Uso de emulsões lipídicas no sucesso do tratamento de um caso de intoxicação por difenidramina

La difenhidramina tiene efectos antihistamínico anti-H1 específico y antimuscarínico que pueden ocasionar un desenlace fatal según la dosis total ingerida. Se reporta un caso de intoxicación por difenhidramina tratado de forma exitosa con emulsiones lipídicas a pesar de ingesta de dosis letal. Se presenta el caso de un paciente de 19 años que ingresó por intoxicación por difenhidramina a dosis de 25 mg/kg (1.5 g) después del tiempo de descontaminación, con toxidrome anticolinérgico, con neurotoxicidad, cardiotoxicidad (QRS y QT prolongados) y sin respuesta al enfoque inicial, se iniciaron emulsiones lipídicas y, a su vez, se logró alta temprana por evolución clínica favorable y resolución de la prolongación del intervalo QTc y del cuadro anticolinérgico. La emulsión lipídica es una opción terapéutica para disminuir la morbimortalidad y la estancia hospitalaria por contrarrestar la cardiotoxicidad y neurotoxicidad producidas por moléculas lipofílicas como la difenhidramina.

Diphenhydramine has specific anti-H1 antihistamine and antimuscarinic effects that can be fatal depending on the total dose ingested. A case of diphenhydramine poisoning successfully treated with lipid emulsions despite ingesting a lethal dose is presented. We present the case of a 19-year-old patient who was admitted for diphenhydramine intoxication at a dose of 25 mg/kg (1.5 g) after the decontamination time, with anticholinergic toxidrome, with neurotoxicity, cardiotoxicity (prolonged QRS and QT) and without response to initial approach. Lipid emulsions were started and, in turn, early discharge was achieved due to favorable clinical evolution and resolution of the prolongation of the QTc interval and the anticholinergic symptoms. Lipid emulsion is a therapeutic option to reduce morbidity and mortality and hospital stay by counteracting cardiotoxicity and neurotoxicity produced by lipophilic molecules such as diphenhydramine.

A difenidramina tem efeitos anti-histamínicos e antimuscarínicos anti-H1 específicos que podem ser fatais dependendo da dose total ingerida. Relata-se um caso de intoxicação por difenidramina tratada com sucesso com emulsões lipídicas apesar da ingestão de uma dose letal. Apresentamos o caso de uma paciente de 19 anos que foi internada por intoxicação por difenidramina na dose de 25 mg/kg (1,5 g) após o tempo de des-contaminação, com toxina anticolinérgica, neurotoxicidade, cardiotoxicidade (QS e QT prolongados) e sem resposta na abordagem inicial, iniciaram-se emulsões lipídicas e, por sua vez, obteve-se alta precoce devido à evolução clínica favorável e resolução do prolongamento do intervalo QTc e dos sintomas anticolinérgicos. A emulsão lipídica é uma opção terapêutica para reduzir a morbimortalidade e o tempo de internação por neutralizar a cardiotoxicidade e a neurotoxicidade produzidas por moléculas lipofílicas como a difenidramina.

Effect of long-chain fat emulsion on perioperative nutritional status of patients with low rectal cancer / 肿瘤研究与临床

Objective:To explore the effect of long-chain fat emulsion in parenteral nutrition therapy on the perioperative nutritional status of patients with low rectal cancer.Methods:A total of 204 patients who underwent rectal cancer surgery in the Third Hospital of Shanxi Medical University from January 2017 to June 2020 were retrospectively analyzed. The patients were divided into two groups according to the specific nutritional treatment methods, 100 cases in the study group used long-chain fat emulsion for parenteral nutrition support, and 104 cases in the control group used medium- and long-chain fat emulsion injection. After admission, the nutritional status of patients were evaluated according to the results of Scored Patient-Generated Subjective Global Assessment (PG-SGA) and related laboratory tests. At 7th day before the operation, the patients were treated with nutrition and electrolyte support. Parenteral nutrition and enteral nutrition combined treatment and early enteral nutrition were given after the operation. The albumin, prealbumin, retinol-binding protein, total cholesterol and body mass index (BMI) at 7th day before the operation, 1st day after the operation and 7th day after the operation and the patient's first exhaust time after surgery, occurrence of postoperative complications, postoperative fever and total hospital stay were recorded and compared between the two groups.Results:Postoperative first exhaust time [(42±11) h vs. (54±10) h], fever time [(48±8) h vs. (57±7) h], total hospital stay [(16.0±0.7) d vs. (18.0±0.9) d)], resting energy expenditure at the 7th day after surgery [(5 326±589) kJ/d vs. (5 840±599) kJ/d] and total cholesterol at the 7th day after surgery [(4.8±0.3) mmol/L vs. (5.0± 0.4) mmol/L] in the study group were lower than those in the control group, and albumin [(33±3) g/L vs. (28± 3) g/L], prealbumin [(0.189±0.041) g/L vs. (0.164±0.037) g/L] and retinol-binding protein [(0.039±0.016) g/L vs. (0.032±0.013) g/L] at the 7th day after surgery in the study group were higher than those in the control group, and the differences between the two groups were statistically significant (all P < 0.05). There was no statistical difference in other detection indexes between the two groups (all P > 0.05). Conclusion:The use of long-chain fat emulsion in low rectal cancer patients with malnutrition during the perioperative period may be more conducive to the recovery of the body.

Effect of SMOF lipid on parenteral nutrition-associated cholestasis and other complications in premature infants / 中国小儿急救医学

Objective:To compare the effect of SMOF lipids composed of soybean oil, medium chain triglycerides, olive oil, and fish oil with medium-long chain mixed fat emulsions(Lipofundin) on parenteral nutrition-associated cholestasis(PNAC) in premature infants.Methods:Clinical data were collected from premature infants hospitalized in the neonatal intensive care unit of Shanghai Children′s Hospital from January 2018 to December 2019 with gestational age ≤34 weeks, birth weight ≤2 000 g, and duration of parenteral nutrition ≥14 days.They were devided into SMOF lipid group and Lipofundin group, and the incidence of PNAC, neonatal necrotizing enterocolitis(NEC), bronchopulmonary dysplasia(BPD), retinopathy of prematurity(ROP), periventricular-intraventricular hemorrhage(PVH-IVH), late-onset sepsis and liver function were compared between two groups.Results:The incidence of PNAC in the SMOF lipid group was significantly lower than that in Lipofundin group( P=0.042). The average level of ALT and AST in SMOF lipid group were markedly lower than those in Lipofundin group( P<0.05). The time to reach full enteral feeding of SMOF lipid group was shorter than that of Lipofundin group( P=0.005). There was no significant difference in the incidence of NEC, BPD, ROP, PVH-IVH, and late-onset sepsis between two groups( P>0.05). Conclusion:Compared with lipofundin, SMOF lipid can reduce the incidence of PNAC in premature infants, and has no significant effect on the incidence of NEC, BPD, ROP, PVH-IVH and late-onset sepsis.

Effects of structured fat emulsion and medium / long chain fat emulsion on patients after hepatectomy / 中华肝胆外科杂志

Objective To analyze the effects of structured fat emulsion and medium/long chain fat emulsion on blood lipids,immune cells and acute inflammation after hepatectomy for hepatocellular carcinoma.Methods Total of 60 patients with hepatocellular carcinoma who underwent hepatectomy in Henan People's Hospital (Zhengzhou University People's Hospital) from January 2013 to March 2017 were divided into experimental group (using structured fat emulsion) and control group (using medium/long chain fat emulsion),30 cases in each group.Triglyceride (TG),high density lipoprotein cholesterol (HDL-C),low density lipoprotein cholesterol (LDL-C),total cholesterol (TC),T lymphocyte level,fibrinogen (FIB),C-reactive protein (CRP),prostaglandin E2 (PGE2) were detected before and 2,4,6 and 8 days after infusion.Results There were no significant differences in LDL-C,HDL-C,TG and TC between the two groups before infusion (P＞0.05).On the 2nd day of parenteral nutrition infusion,the level of blood lipids in both groups was higher than experimental group before infusion;on the 4th,6th and 8th day of infusion,LDL-C,HDL-C,TG and TC in the control group were higher than those in the experimental group (P＜0.05).After parenteral nutrition infusion,the levels of CD3+,CD4+,CD8+,CD4+/CD8+ in both groups were higher than experimental group before infusion,and the experimental group was higher than the control group,the differences were statistically significant (P＜0.05).Compared with before infusion,level of FIB,CRP and PGE2 began to increase on the 2nd day of infusion,and the differences were statistically significant (P＜0.05).On the 2nd,4th,6th and 8th day,CRP in the control group was higher than experimental group.And resepeatively (19.12±5.84) mg/ml vs.(13.76±2.36) mg/ml,(31.67±8.68) mg/ml vs.(17.21±2.66) mg/ml,(22.15±8.33) mg/ml vs.(12.48±0.63) mg/ml,(9.65±4.66) mg/ml vs.(7.52±0.99) mg/ml,and PGE2 were also higher than that in the experimental group (P＜0.05).Conclusion Structured fat emulsion is superior to medium/long chain fat emulsion in improving blood lipid,immune cells and inflammatory reaction in patients after hepatectomy.

Effect of enteral nutritional emulsion on nutritional status and immune function in patients with gastrointestinal tumor / 中国基层医药

Objective To observe the effect of enteral nutritional emulsion on nutritional status and immune function in patients with gastrointestinal cancer. Methods From January 2014 to January 2017,100 patients with gastrointestinal cancer in Yuncheng Central Hospital were selected in the research and randomly divided into two groups according to the digital table, with 50 cases in each group. All the patients underwent chemotherapy, the observation group was given enteral nutritional emulsion during chemotherapy. The indicators of nutritional status, immune function, the effect of chemotherapy, the incidence of adverse reactions were compared between the two groups. Results After treatment,the prealbumin,albumin,transferrin and hemoglobin levels in the observation group were (0. 30 ± 0. 07)g/ L,(32. 93 ± 1. 67)g/ L,(2. 61 ± 0. 15)g/ L,(109. 94 ± 2. 31)g/ L,respectively,which in the control group were (0. 19 ± 0. 09)g/ L,(30. 89 ± 1. 49)g/ L,(2. 49 ± 0. 14)g/ L,(108. 07 ± 2. 04)g/ L,respectively, there were statistically significant differences between the two groups(t = 6. 822,6. 445,4. 135,4. 291,all P < 0. 05). After treatment,the CD +3 ,CD4 / CD8,NK cells in the observation group were (43. 84 ± 7. 65)％ ,(1. 70 ± 0. 18) and (37. 78 ± 7. 51)％ ,respectively,which in the control group were (36. 12 ± 6. 57)％ ,(1. 52 ± 0. 19) and (31. 07 ± 4. 20)％ ,respectively,there were statistically significant differences between the two groups ( t = 5. 413,4. 863, 6. 124,all P < 0. 05). The objective response rate of the observation group (64％ ) was significantly higher than that of the control group(44％ )(χ2 = 4. 026,P < 0. 05). The incidence rate of adverse reaction of the observation group (18％ ) was significantly lower than that of the control group(36％ )(χ2 = 4. 110,P < 0. 05). Conclusion Enteral nutritional emulsion can effectively improve the nutritional status and immune function of patients with gastrointestinal cancer during chemotherapy,but also can effectively enhance sensitivity to chemotherapy,improve the effect of chemo-therapy,and the safety is reliable.

Role of mitochondrion-dependent apoptosis in reduction of bupivacaine-induced cardiotoxicity by lipid emulsion in rats / 中华麻醉学杂志

Objective To evaluate the role of mitochondrion-dependent apoptosis in reduction of bupivacaine-induced cardiotoxicity by lipid emulsion in rats.Methods Forty-five healthy adult male Sprague-Dawley rats,weighing 300-350 g,were divided into 3 groups by a random number table method:sham operation group (Sham group,n =5),bupivacaine group (B group,n =20),and lipid emulsion group (L group,n =20).Cardiac arrest was induced by intravenously injecting 0.4％ bupivacaine 30mg/kg over 20 s to establish the cardiotoxicity model.Twenty percent lipid emulsion was intravenously injected in a dose of 5 ml/kg during resuscitation in group L,and normal saline was intravenously injected in a loading dose of 5 ml/kg during resuscitation in group B,followed by a 3-min infusion of 1 ml · kg-1 · min-1 in two groups.The successful resuscitation and survival rate at 120 min of return of spontaneous circulation (ROSC) were recorded.Systolic blood pressure,heart rate,mean arterial pressure,rate-pressure product (RPP) and ratio of RPP at each time point after recovery of spontaneous heart beat to baseline value (RPPh) were recorded every 10 min after ROSC.The time from administration to cardiac arrest (T0),time from beginning of cardiopulmonary resuscitation to appearance of the first spontaneous heart beat (Ts) and time from beginning of cardiopulmonary resuscitation to appearance of ROSC (Tr) were recorded.Rats were sacrificed at 120 min of ROSC,and left ventricular tissues were obtained for determination of the expression of Bax,Bcl-2,cleaved caspase-9,cleaved caspase-3,cytochrome C (Cyt c) in cytoplasm and mitochondria (by Western blot) and expression of Bax and Bcl-2 mRNA (by real-time polymerase chain reaction) and for examination of myocardial ultrastructure.Results Compared with Sham group,the expression of Bcl-2 protein and mRNA and mitochondrial Cyt c was significantly down-regulated,and the expression of Bax protein and mRNA,cleaved caspase-9,cleaved caspase-3 and cytoplasmic Cyt c was up-regulated in B group (P＜0.05).Compared with B group,the rate of successful resuscitation and survival rate were signif-icantly increased,Tr was shortened,systolic blood pressure,heart rate,RPP and RPPh were increased after ROSC,the expression of Bcl-2 protein and mRNA and mitochondrial Cyt c was up-regulated,the expression of Bax protein and mRNA,cleaved caspase-9,cleaved caspase-3 and cytoplasmic Cyt c was downregulated (P＜0.05),no significant change was found in To or Ts (P＞0.05),and the pathological changes of myocardium were significantly attenuated in L group.Conclusion The mechanism by which lipid emulsion reduces bupivacaine-induced cardiotoxicity may be related to inhibiting mitochondrion-dependent apoptosis in rats.

Intravenous lipid emulsion therapy for cardiac arrest and refractory ventricular tachycardia due to multiple herb intoxication

Herbal products have been used for therapeutic purposes for a long time. However, many herbs can be toxic and even life-threatening. If refractory ventricular tachycardia (VT) is caused by herbal products and shows no response to conventional therapy, intravenous lipid emulsion (ILE) therapy can be considered. We report a case of herbal intoxication leading to refractory VT, which was successfully treated with ILE therapy. A 36-year-old woman with aplastic anemia presented with mental changes. She had taken an unknown herbal decoction three days before visiting the hospital. Soon after coming to the hospital, she went into cardiac arrest. Cardiopulmonary resuscitation was performed, and return of spontaneous circulation with VT was achieved. Synchronized cardioversion was then performed and amiodarone was administered. However, VT with pulse continued, so ILE therapy was attempted, which led to the resolution of VT.

Role of mitochondrion-dependent apoptosis in reduction of bupivacaine-induced cardiotoxicity by lipid emulsion in rats / 中华麻醉学杂志

Objective@#To evaluate the role of mitochondrion-dependent apoptosis in reduction of bupivacaine-induced cardiotoxicity by lipid emulsion in rats.@*Methods@#Forty-five healthy adult male Sprague-Dawley rats, weighing 300-350 g, were divided into 3 groups by a random number table method: sham operation group (Sham group, n=5), bupivacaine group (B group, n=20), and lipid emulsion group (L group, n=20). Cardiac arrest was induced by intravenously injecting 0.4% bupivacaine 30 mg/kg over 20 s to establish the cardiotoxicity model.Twenty percent lipid emulsion was intravenously injected in a dose of 5 ml/kg during resuscitation in group L, and normal saline was intravenously injected in a loading dose of 5 ml/kg during resuscitation in group B, followed by a 3-min infusion of 1 ml·kg-1·min-1in two groups.The successful resuscitation and survival rate at 120 min of return of spontaneous circulation (ROSC) were recorded.Systolic blood pressure, heart rate, mean arterial pressure, rate-pressure product (RPP) and ratio of RPP at each time point after recovery of spontaneous heart beat to baseline value (RPPh) were recorded every 10 min after ROSC.The time from administration to cardiac arrest (T0), time from beginning of cardiopulmonary resuscitation to appearance of the first spontaneous heart beat (Ts) and time from beginning of cardiopulmonary resuscitation to appearance of ROSC (Tr) were recorded.Rats were sacrificed at 120 min of ROSC, and left ventricular tissues were obtained for determination of the expression of Bax, Bcl-2, cleaved caspase-9, cleaved caspase-3, cytochrome C (Cyt c) in cytoplasm and mitochondria (by Western blot) and expression of Bax and Bcl-2 mRNA (by real-time polymerase chain reaction) and for examination of myocardial ultrastructure.@*Results@#Compared with Sham group, the expression of Bcl-2 protein and mRNA and mitochondrial Cyt c was significantly down-regulated, and the expression of Bax protein and mRNA, cleaved caspase-9, cleaved caspase-3 and cytoplasmic Cyt c was up-regulated in B group (P<0.05). Compared with B group, the rate of successful resuscitation and survival rate were significantly increased, Tr was shortened, systolic blood pressure, heart rate, RPP and RPPh were increased after ROSC, the expression of Bcl-2 protein and mRNA and mitochondrial Cyt c was up-regulated, the expression of Bax protein and mRNA, cleaved caspase-9, cleaved caspase-3 and cytoplasmic Cyt c was down-regulated (P<0.05), no significant change was found in To or Ts (P>0.05), and the pathological changes of myocardium were significantly attenuated in L group.@*Conclusion@#The mechanism by which lipid emulsion reduces bupivacaine-induced cardiotoxicity may be related to inhibiting mitochondrion-dependent apoptosis in rats.

Sudden Deaths of Neonates Receiving Intravenous Infusion of Lipid Emulsion Contaminated with Citrobacter freundii

At an intensive care unit, four neonates died consecutively within 80 minutes. Citrobacter freundii was isolated from blood samples of the 4 patients. It was also cultured from the leftover SMOFlipid that had been infused intravenously into the patients. In this in vitro study, we evaluated the bacterial growth kinetics and change in size of fat globules in SMOFlipid contaminated with C. freundii. Following the growth of bacteria, pH of SMOFlipid decreased to < 6, and the number of fat globules larger than 5 µm increased. Pulmonary fat embolism is proposed as a possible cause of the sudden deaths as well as fulminant sepsis.

Role of GSK-3β in lipid emulsion-induced inhibition of bupivacaine-induced apoptosis in cardiomyocytes of rats: evaluation using RNA interference adenovirus infection method / 中华麻醉学杂志

Objective To evaluate the role of glycogen synthase kinase 3 beta (GSK-3β) in lipid emulsion-induced inhibition of bupivacaine-induced apoptosis in cardiomyocytes of rats using RNA interference (RNAi) adenovirus infection method.Methods H9C2 cells were transferred into 96-well cell plates at a density of 1× 105 cells/ml after culture and then divided into 8 groups (n =10 each) using a random number table:control group (group C),bupivacaine group (group B),lipid emulsion group (group LE),bupivacaine plus lipid emulsion group (group B+LE),control plus GSK-3βRNAi adenovirus (GSK-3βi) group (group C+GSK-3βi),bupivacaine plus GSK-3βi group (group B+GSK-3βi),lipid emulsion plus GSK-3βi group (group LE+GSK-3βi) and bupivacaine plus lipid emulsion plus GSK-3βi group (group B+LE+GSK-3βi).ln B,LE and B+LE groups,the cells were incubated with culture medium containing 1 mmol/L bupivacaine,1％ lipid emulsion and 1 mmol/L bupivacaine plus 1％ lipid emulsion,respectively.In C+GSK-3βi,B+GSK-3βi,LE+GSK-3βi and B+LE+GSK-3βi groups,the cells were incubated with the drugs mentioned above on 2nd day after being infected by adenovirus.At 24 h after incubation with drugs,the expression of Bax and Bcl-2 was determined by Western blot,and the apoptosis rate was calculated using DAPI staining.Results Compared with group C,the expression of Bax was significantly upregulated,the expression of Bcl-2 was down-regulated,and the apoptosis rate was increased in group B (P＜0.05).Compared with group B,the expression of Bax was significantly down-regulated,the expression of Bcl-2 was up-regulated,and the apoptosis rate was decreased in group B+LE (P＜0.05).Compared with group B+LE,the expression of Bax was significantly up-regulated,the expression of Bcl-2 was downregulated and the apoptosis rate was increased in group B+LE+GSK-3βi (P＜0.05).Conclusion The mechanism by which lipid emulsion inhibits bupivacaine-induced apoptosis in cardiomyocytes of rats is associated with GSK-33.

Toxicidad sistémica por anestésicos locales: consideraciones generales, prevención y manejo / Systemic toxicity by local anesthetics: general considerations, prevention and management

La administración de anestésicos locales se lleva a cabo en distintos escenarios clínicos y por diferentes profesionales de la salud, principalmente, médicos y odontólogos. Su uso está asociado a complicaciones de baja frecuencia como edema, urticaria y dermatitis, pero la intoxicación por anestésicos locales puede ser fatal. La presentación clínica de esta complicación es muy variable y abarca un gran espectro de síntomas relacionados principalmente con la toxicidad neurológica y cardiovascular, incluyendo presentaciones atípicas. La prevención de la toxicidad sistémica se basa en considerar los factores de riesgo para su presentación, elegir cuidadosamente el anestésico local y la dosis a administrar, aspirar antes de inyectar, fraccionar la dosis y el uso de marcadores de inyección intravascular. El manejo de la intoxicación por anestésicos locales incluye un manejo de la vía aérea, control de las convulsiones, mantención de la circulación sistémica y el uso de terapia intravenosa con emulsión lipídica.(AU)

The administration of local anesthetics is carried out in different clinical settings and by different health professionals, mainly physicians and dentists. Its use is associated with low frequency complications such as edema, urticaria and dermatitis, but poisoning by local anesthetics can be fatal. The clinical presentation of this complication is highly variable and encompasses a large spectrum of symptoms mainly related to neurological and cardiovascular toxicity, including atypical presentations. The prevention of systemic toxicity is based on considering the risk factors for its presentation, carefully choosing the local anesthetic and the dose to be administered, aspirating before injecting, fractionating the dose and the use of intravascular injection markers. Management of local anesthetic poisoning includes airway management, seizure control, systemic circulation maintenance, and intravenous lipid emulsion therapy.(AU)

A bioequivalence evaluation of long-chain triacylglycerol/medium-chain triacylglycerol emulsion in beagle dogs / 中华临床营养杂志

Objective Long-chain triacylglycerol (LCT) by three producers,each mixed with the same medium-chain triacylglycerol (MCT),were compared with the brand MCT/LCT in causing focal necrosis of hepatocytes in beagle dogs (a bioequivalence evaluation).Methods 21 beagle dogs (male,0.7-1.5 years old,10-15 kg) were used in this study.According to the sources of the LCT,the animals were divided into Group A (LCT made in China),Group B (LCT made in Japan),Group C (LCT made in Germany),and the control group (the brand 10％ MCT/LCT).Central venous port was placed via the lumber vein of the animals under general anesthesia.After 2 weeks of rehabilitation,MCT/LCT was administered through this port for 28 days at 9 g/ (kg · d) [while the routine dose used clinically was 1 g/ (kg · d)].The laboratory indexes and the pathomorphism of the liver and kidney were studied single blindly.Results Laboratory tests,including liver and kidney function,blood coagulation function and lipid metabolism,did not identify differences among emulsions with different sources of LCT.Liver biopsy at day 28 showed no focal necrosis in Group C and the control group;there was minor damage in Group B;and Group A had obvious liver necrosis.and the pathological findings of other organs are similar.No significant difference was observed in biopsies of other organs.Conclusions Emulsions with different sources of LCT varied in their damage to the liver.Generics with LCT of higher quality were equivalent to the brand MCT/LCT in terms of safety.

Influence of Fish Oil-Containing Lipid Emulsions on Parenteral Nutrition-Associated Liver Disease in Neonates

PURPOSE: This study is a comparative evaluation of the incidence of parenteral nutrition-associated liver disease (PNALD) when administering intravenous fat emulsions containing fish oil. METHODS: The medical records of patients who were in the neonatal intensive care unit at Severance Hospital from January, 2012 to December 2015, were reviewed retrospectively. Patients who were administered either soybean oil (SO) or SMOF (containing soybean oil, medium chain triglycerides, olive oil, and fish oil) more than 14 days were included. The patients were excluded if they were administered both agents or had underlying hepatic disease. An increase in bilirubin to 2 mg/dL was defined as PNALD. RESULTS: PNALD occurred in only 8 out of a total of 77 patients: 6 out of 31 (19.4%) in the SO group and 2 out of 46 (4.3%) in the SMOF group (P=0.055). The number of patients, whose lab values, such as direct bilirubin, total bilirubin, asparate aminotransferase (AST), alanine amino-transferase, gamma-glutamyl transpeptidase, C-reactive protein, serum triglyceride, and alkaline phosphate, exceeded the normal range, were similar in both groups. The gestational age, birth body weight, and APGAR score at 1 min and 5 min were significantly higher in the SO group and the PN duration was significantly long in the SMOF group. Considering only term infants, there were no significant differences in baseline characteristics and incidence of PNALD. The number of patients whose AST exceeded the normal range was significantly higher in the SO group (P=0.034). CONCLUSION: The incidence of PNALD was similar in both groups. On the other hand, considering the tendency, there was a high correlation between the type of lipid emulsion and an increased direct bilirubin level in the SO group.

Effect of emulsified isoflurane post-conditioning on mitochondrial function during lung ischemia-reperfusion in rats: an in vitro experiment / 中华麻醉学杂志

Objective To evaluate the effect of emulsified isoflurane post-conditioning on the mitochondrial function during lung ischemia-reperfusion (I/R) in rats in an in vitro experiment.Methods Twenty-four SPF healthy male Sprague-Dawley rats,weighing 250-300 g,were used in the study.After the animals were anesthetized,the lungs were removed,connected to the perfusion system and then divided into 4 groups (n=6 each) using a random number table:control group (group C),group I/R,emulsified isoflurane post-conditioning group (group EI) and intralipid post-conditioning group (group IL).After 20 min of equilibration,the lungs were continuously perfused for 105 min in group C,and the lungs were subjected to 45 min ischemia followed by 60 min reperfusion to establish the model of lung I/R injury in the other three groups.During the reperfusion period,the common perfusate was used in group I/R,the perfusate containing 1.68 mmol/L emulsified isoflurane was used in group EI,and the equal volume of perfusate containing 30％ intralipid was used in group IL.At the end of the equilibration (T0),immediately after beginning of reperfusion (T1) and at 30 and 60 min of reperfusion (T2.3),the arterial oxygen partial pressure (PaO2),airway resistance,pulmonary compliance and tidal volume (VT) were recorded.The right upper lobe of the lung was removed at T3 for determination of wet to dry weight ratio (W/D ratio).The right middle lobe of the lung was removed at T3 for pathologic examination with light microscope.The contents of reactive oxygen species (ROS),NAD+ and ATP in lung tissues were detected.Results Compared with group C,the PaO2,pulmonary compliance and Vr were significantly decreased,and the airway resistance was increased at T1-3,and the W/D ratio and ROS content were increased,and NAD+ and ATP contents were decreased at T3 in I/R,EI and IL groups (P＜0.05).Compared with I/R and IL groups,the PaO2,pulmonary compliance and VT were significantly increased,and the airway resistance was decreased at T2.3,and the W/D ratio and ROS content were decreased,and NAD+ and ATP contents were increased at T3 in group EI (P＜0.05).The pathologic changes of lungs were significantly attenuated in group EI as compared with group I/R.Conclusion The mechanism by which emulsified isoflurane post-conditioning attenuates lung I/R injury is related to decrease in mitochondrial dysfunction in rats in an in vitro experiment.

Stability assessment of neonatal parenteral nutrition solutions with various amino acid concentrations / 中华临床营养杂志

Objective To explore the influence of various concentrations of amino acid on the stability of neonatal parenteral nutrition solutions .Methods Five formulations were designed with 5 different amino acid concentrations containing the same components .The final amino acid concentrations of admixtures were 0%, 1%, 2%, 3%, and 3.5%, respectively .The appearance , pH, and osmolality were observed or meas-ured after preparation (0 hour) and at 12, 24, 48 and 72 hours after preparation.The average size and the size distribution of the lipid globules were also evaluated by laser nanometer particle size analyzer .Results There was no observable alteration in color , phase separation , precipitate , and flocculation in any admixture at any of the observation time points.The mean pH values for all groups were between (5.49 ±0.01) to (6.19 ±0.01) within 72 hours.The mean osmolalities for all groups were between (774 ±3) to (1106 ±13) mOsm/kg.The mean diameters of lipid globules for all groups were between (280.6 ±0.7 ) mm to (332.2 ±2.0 ) nm.The mean polydispersity for all groups were between (0.200 ±0.011) to (0.245 ±0.012).The enrichment of ami-no acid concentration was linked to lower pH ( P=0.000 ) , higher osmolality ( P=0.000 ) and larger average lipid globules size ( P=0.000 ) .However , there was no distinct linear dependence between amino acid concen -tration and polydispersity value ( P=0.628 ) .Conclusion After 72 hours of storage at room temperature , the appearance, pH, osmolality, and the average lipid globules diameter of the parenteral nutrition solutions are within the safe range when the amino acid is not contained or the concentrations are no more than 3.5%.

Effect of emulsified isofluraue postconditioning on mitophagy during myocardial ischemia-reperfusion in rats / 中华麻醉学杂志

Objective To evaluate the effect of emulsified isoflurane postconditioning on mitophagy during myocardial ischemia-reperfusion (I/R) in rats.Methods Forty-eight pathogen-free healthy male Sprague-Dawley rats,aged 4-5 months,weighing 250-300 g,were divided into 4 groups (n=12 each) using a random number table:sham operation group (group S),group I/R,fat emulsion group (group F) and emulsified isoflurane postconditioning group (group EIP).Myocardial I/R was induced by occlusion of the anterior descending branch of the left coronary artery for 30 min followed by 120 min of reperfusion in pentobarbital sodium-anesthetized rats.Starting from 3 min before reperfusion,8％ emulsified isoflurane 2 ml/kg was intravenously infused over 8 min in group EIP,while 30％ fat emulsion 2 ml/kg was intravenously infused over 8 min in group F.Rats were sacrificed at the end of reperfusion,and hearts were removed for measurement of the myocardial infarct size (by 2,3,5-triphenyltetrazolium chloride staining),cell apoptosis (by TUNEL),mitochondrial membrane potential and expression of microtubule-associated protein 1 light chain 3 (LC3),Beclinl,P62,PINK1 and Parkin in cardiomyocytes (by using Western blot).Apoptosis index (AI) was calculated.Results Compared with group S,the myocardial infarct size and AI were significantly increased,the mitochondrial membrane potential was decreased,the expression of LC3,Beclinl,PINK1 and Parkin was up-regulated,and the expression of P62 was down-regulated in I/R,F and EIP groups (P＜0.05).Compared with group I/R,the myocardial infarct size and AI were significantly decreased,the mitochondrial membrane potential was increased,the expression of LC3,Beclinl,PINK1 and Parkin was down-regulated,and the expression of P62 was up-regulated in group EIP (P＜0.05).Compared with group F,the myocardial infarct size and AI were significantly decreased,the mitochondrial membrane potential was increased,the expression of LC3,Beclin1,PINK1 and Parkin was down-regulated,and the expression of P62 was up-regulated in group EIP (P＜0.05).Conclusion The mechanisin by which emulsified isoflurane postconditioning reduces myocardial I/R injury is related to inhibition of mitophagy in rats.

A Case of Aconite Poisoning Successfully Recovered after Intravenous Fat Emulsion Therapy

Aconitum is a genus of various species of flowering plants that belongs to the Family Ranunculaceae. Most Aconitum sp. have extremely toxic alkaloid substances such as aconitine, mesaconitine and hypaconitine. Among these substances, aconitine can cause fatal cardiotoxicity by activating sodium channels followed by calcium channels in myocardial cells. Even though there have been various therapeutic plans suggested comprising antidotes based on diverse case reports and studies, there is no confirmatory treatment protocol for aconite poisoning. Here, we report an aconite poisoning patient who had refractory ventricular tachyarrhythmia that did not respond to intravenous amiodarone therapies even though they were sustained for over 2 hours, but showed successful recovery following intravenous fat emulsions (IFE) therapy.

A Case of Aconite Poisoning Successfully Recovered after Intravenous Fat Emulsion Therapy

Aconitum is a genus of various species of flowering plants that belongs to the Family Ranunculaceae. Most Aconitum sp. have extremely toxic alkaloid substances such as aconitine, mesaconitine and hypaconitine. Among these substances, aconitine can cause fatal cardiotoxicity by activating sodium channels followed by calcium channels in myocardial cells. Even though there have been various therapeutic plans suggested comprising antidotes based on diverse case reports and studies, there is no confirmatory treatment protocol for aconite poisoning. Here, we report an aconite poisoning patient who had refractory ventricular tachyarrhythmia that did not respond to intravenous amiodarone therapies even though they were sustained for over 2 hours, but showed successful recovery following intravenous fat emulsions (IFE) therapy.

Effects of emulsified isoflurane on apoptosis in human neuroblastoma cells : the role of c-Jun N-terminal kinase / 中华麻醉学杂志

Objective To investigate the effects of emulsified isoflurane on apoptosis in human neuroblastoma cells and the role of c-Jun N-terminal kinase (JNK) in it.Methods The human neuroblastoma SHSY-5Y cells were seeded in 96-well plates or dishes and then randomly divided into 8 groups using a random number table:control group(group C,n=24),different concentrations of lipid emulsion groups(LE1 groups [n =24],LE2 group [n =24] and LE3 group [n =72]),different concentrations of emulsified isoflurane groups (EI1 group [n=24],El2 group [n=24] and EI3 group [n=72]),and emulsified isoflurane + JNK inhibitor SP600125 group (group EI-SP,n =24).At 24 h after the cells were plated,in LE1-3 groups,30％ lipid emulsion was added to the culture medium with the final concentrations of 0.395 6,0.791 2 and 1.582 4 μl/ml,respectively;in EI1-3 groups,8％ emulsified isoflurane was added with the final concentrations of 0.56,1.12 and 2.24 mmol/L,respectively;in group EI-SP,emulsified isoflurane was added with the final concentration of 1.12 mmol/L,and SP600125 was added at 1 h before addition of emulsified isoflurane with the final concentration of 10 μmol/L;the cells were cultured normally in group C.At 6,12 and 24 h of incubation in EI3 and LE3 groups,and at 24 h of incubation or culture in the other groups,the morphology of cells was detected,the cell viability was measured using methyl thiazolyl tetrazolium assay,and the expression of JNK,phosphorylated JNK (p-JNK) and cytochrome c (Cyt c) was detected by Western blot.Results Compared with group C,the cell viability was significantly decreased,and the expression of p-JNK and Cyt c was significantly up-regulated at 24 h of incubation in group EI2 and at 12 and 24 h of incubation in group EI3,the cell viability was significantly decreased (P＜0.05),and no significant change was found in the expression of p-JNK and Cyt c in group EI-SP,and no significant change was found in the cell viability and expression of p-JNK and Cyt c in LE1-3 and EI1 groups (P＞0.05).Compared with group EI1,the cell viability was significantly decreased,and the expression of p-JNK and Cyt c was significantly up-regulated at 24 h of incubation in EI2.3 groups (P＜0.05).Compared with group EI2,the cell viability was significantly decreased,and the expression of p-JNK and Cyt c was significantly up-regulated at 24 h of incubation in group EI3,and the cell viability was significantly increased,and the expression of p-JNK and Cyt c was significantly down-regulated in group EI-SP (P＜0.05).There was no significant difference in JNK expression between the eight groups (P＞0.05).Conclusion High concentrations of emulsified isoflurane can induce apoptosis in neurons only when applied for a long time,while low concentrations do not have the effect when applied for a short time.The mechanism by which emulsified isoflurane induces neuronal apoptosis is related to activation of JNK pathway.