Sevoflurane Preconditioning and Total Knee Arthroplasty Bleeding: A Randomized Controled Trial

Background: Total knee arthroplasty (TKA) is a highly complex and effective surgery even though its perioperative bleeding may increase the need for blood transfusion and its associated infection risk, cardiovascular overload, increased costs, and mortality. As tourniquet reduces intraoperative bleeding it may be associated with postoperative bleeding, venous thrombosis, and distal ischemia. The reperfusion may trigger a local and systemic inflammatory response. Anesthetic preconditioning (APC) with sevoflurane minimizes ischemia-reperfusion syndrome (I/R). This study evaluated the effects of APC with sevoflurane on perioperative bleeding in TKA.Methods: We allocated 30 patients into two groups: a sevo group (sevoflurane 2% for 15 minutes before the tourniquet) and a control group (propofol infusion). Laboratory tests were collected right before the tourniquet (LAB PRE, in the operating room) and after its release at four moments: LAB POST (immediately after), LAB 2 (two hours after), LAB 12 (12 hours after), and LAB 24 (24 hours after). The volume of the suction drain was measured at one, two, 12, and 24 hours after the end of the surgery. Antifibrinolytics were not administered.Results: There was no statistically significant difference in bleeding-related variables, such as drained volume and hemoglobin and hematocrit measurements. Drainage volume was higher in the first two hours after the procedure, while hematocrit decreased pre- to post-operatively and between two- and 12-hours post-procedure.Conclusion: Sevoflurane as an anesthetic preconditioning did not reduce postoperative bleeding in TKA surgery.Trial Registration: ClinicalTrials.gov – NCT03379103; December 20, 2017.

Anesthetic Preconditioning of Traumatic Brain Injury is Ineffective in a Drosophila Model of Obesity

We tested the hypothesis that obesity influences the pharmacodynamics of volatile general anesthetics (VGAs) by comparing effects of anesthetic exposure on mortality from traumatic brain injury (TBI) in lean and obese Drosophila melanogaster. We induced TBI with a High-Impact Trauma device. Starvation-selection over multiple generations resulted in an obese phenotype (SS flies). Fed flies served as lean controls (FC flies). Adult (1-7 day old) SS and FC flies were exposed to equianesthetic doses of isoflurane or sevoflurane either before or after TBI. The principal outcome was percent mortality 24 hours after injury, expressed as the Mortality Index at 24 hours (MI24). TBI resulted in lower MI24 in FC than in SS flies (21 (2.35) and 57.8 (2.14), respectively n= 12, p=0.0001). Preexposure to isoflurane or sevoflurane preconditioned FC flies to TBI reducing the risk of death to 0.53 [0.25 to 1.13] and 0.82 [0.43 to 1.58], respectively, but had no preconditioning effect in SS flies. Postexposure to isoflurane or sevoflurane increased the risk of death in SS flies. Only postexposure to isoflurane increased the risk in FC flies (1.39 [0.81 to 2.38]). Thus, obesity affects the pharmacodynamics of VGAs, thwarting the preconditioning effect of isoflurane and sevoflurane in TBI.

Dynamics of chemiluminescence in the small intestine during anesthetic preconditioning in hemorrhagic hypotension

Введение. Ведущим патогенетическим фактором массивной кровопотери является гипоксия, инициирующая активацию процессов свободнорадикального окисления (СРО) в органах и тканях и системный воспалительный ответ. Показано, что одним из универсальных звеньев формирования множественной органной дисфункции при кровопотере является изменение проницаемости кишечной стенки с транслокацией микрофлоры и токсинов в системный кровоток на фоне реперфузии. В последнее время внимание исследователей привлекает эффект анестетического прекондиционирования, в том числе при операциях, сопровождающихся геморрагической гипотензией (ГГ). Цель исследования - оценка в эксперименте динамики процессов СРО в тонкой кишке при геморрагической гипотензии на фоне применения анестетика севофлурана, обладающего эффектом анестетического прекондиционирования. Методика. Эксперименты проведены на 105 белых крысах-самцах. ГГ моделировали, используя в 1-й группе в качестве анестетика эфир во 2-й - анестетик севофлуран. Контролем служили 2 группы интактных животных: одна - с эфиром, другая - с севофлураном. Для оценки процессов СРО через 15 мин, 30 мин, 1 ч, 2 ч ГГ забирали фрагменты тонкой кишки. Исследование хемилюминесценции (ХЛ) гомогенатов тонкой кишки проводили по методу Р.Р. Фархутдинова, используя хемилюминомер “Флюорат АБЛФ-2Т”. Регистрировались показатели СРО: спонтанная светимость (СС), вспышка (В), светосумма (С∑). Результаты. Через 15 мин ГГ (2-я группа,. севофлуран) обнаружено повышение показателя СС в тощей кишке на 33%; снижение показателя В в 12-пк в 2 раза, в тощей и подвздошной кишке - на 24 и 36% соответственно. Показатель С∑ снижался в 12-пк на 36%, в тощей и подвздошной кишке - на 45% и 52% соответственно по сравнению с 1-й группой (эфир). На 30-й мин показатель СС в тощей кишке повышался на 80%. На фоне ГГ при применении севофлурана отмечено снижение показателя В в 12-пк на 38%, в тощей кишке на 22%, а в подвздошной в 3 раза. Через 1 ч ГГ при использовании севофлурана наблюдалось повышение СС в в тощей кишке в 2 раза, в 12-пк и подвздошной - на на 38% и 15% соответственно. Показатель В снижался в 12-пк на 67, в тощей - на 43%; Показатель С∑ в 12-пк и тощей кишке снижался в 2,6 и 2,5 раза, в подвздошной - на 70% по сравнению с группой «эфир». Через 2 ч ГГ в группе «севофлуран» обнаружено увеличение СС в тощей и подвздошной кишках на 80% и в 3 раза, соответственно, по сравнению с эфирным наркозом. При этом наблюдалось уменьшение С∑ в 12-п и тощей кишке - на на 24% и 15% соответственно. Заключение. На фоне ГГ наблюдается активация процессов СРО в тонкой кишке при использовании эфира; прекондиционирование анестетиком севофлураном способствовало значительному ограничению окислительного стресса в тонкой кишке крыс возможно за счет активации антиоксидантной системы. Introduction. The major pathogenetic factor of massive blood loss is hypoxia, which triggers activation of free-radical oxidation (FRO) processes in organs and tissues and the systemic inflammatory response. A universal factor of multiple organ dysfunction in blood loss is altered intestinal wall permeability with translocation of microflora and toxins into the systemic circulation during reperfusion. Recently, much of the attention has been focused on effects of anesthetic preconditioning, including during operations associated with hemorrhagic hypotension (HH). The aim of this study was to evaluate in experiment the dynamics of small intestinal FRO in HH during the use of the anesthetic sevoflurane, which has an effect of anesthetic preconditioning. Methods. Experiments were performed on 105 white male rats divided into two groups; groups 1 and 2 were exposed to HH with ether or sevoflurane as the anesthetic, respectively. Two groups of intact animals treated with ether or sevoflurane were used as the controls. Five animals died during the experiment. To evaluate FRO processes, samples of the duodenum, jejunum, and ileum were taken at 15 min, 30 min, 1 h, and 2 h of HH. The chemiluminescence (CL) study of small intestine homogenates was performed according to the Farukhutdinov method on a Fluorate ABLF-2T chemiluninometer. The following FRO indexes were recorded: spontaneous luminosity (SL), flash (F), and light sum (L∑). Significance of differences was determined with the Mann-Whitney test. Results. In the sevoflurane group 2 compared to the ether group after 15 min of HH, SL was increased in the jejunum by 33%; F was decreased in the duodenum by 50%, in the jejunum by 24%, and in the ileum by 36%; L∑ was decreased in the duodenum by 36%, in the jejunum by 45%, and in the ileum by 52%. At 30 min, SL in the jejunum was increased by 80%. In the HH+sevoflurane group, F was decreased in the duodenum by 38%, in the jejunum by 22%, and in the ileum by 27%; L∑ in the duodenum was decreased by 44%, in the jejunum by 45%, and in the ileum by 67%. After 1 h of HH+sevofluran, SL was increased in the jejunum twofold, in the duodenum by 38% and in the ileum by 15%; F was decreased in the duodenum by 67% and in the jejunum by 43%; L∑ in the duodenum was decreased by 62%, in the jejunum by 60%, and in the ileum by 70% compared to the ether group. After 2 h of HH+sevofluran, SL was increased in the jejunum and ileum by 80% and 67%, respectively, compared to the ether group. In this process, L∑ in the duodenum was decreased by 24% and in the jejunum by 15%. Conclusion. The HH+diethyl ether exposure was associated with activation of FRO processes in the small intestine. The sevoflurane preconditioning provided a significant restriction of oxidative stress in the rat small intestine due to activation of the antioxidant system in the duodenum, jejunum, and ileum at 1 h, 15 min, and 30 min of HH, respectively.

Total Intravenous Anesthesia for Myocardial Protection and Preconditioning

Perioperative myocardial injury is common after any major surgical procedure even with best possible anesthesia and surgical management. Organ preservation during surgical procedure prevents morbidity and mortality. The effect of ischemic preconditioning on myocardial as well as other organ protection is well known. A variety of other agents also shown to have preconditioning thus protective effect on myocardium during anesthesia and surgery. The beneficial effect of volatile anesthetic preconditioning is well studied. However, the effect of intravenous anesthetic agents on this context is still way to go. This review is an attempt to look into the latest available research regarding the preconditioning and myocardial protective effect of intravenous anesthetic agents.

Endogenous intoxication associated with anesthetic preconditioning in hemorrhagic hypotension

Актуальность. Интерес к возможности уменьшения эндогенной интоксикации при острой массивной кровопотере, сопровождающей обширные сочетанные травмы и оперативные вмешательства, растёт. Феномен анестезиологического прекондиционирования обсуждается активно, так как появилась возможность дополнительной протекции различных органов и систем организма. Цель исследования: оценка параметров эндогенной интоксикации на фоне анестезиологического прекондиционирования севофлюраном при геморрагической гипотензии. Материалы и методы. Эксперимент выполнен на 100 белых беспородных крысах-самцах: 2 группы контроля (по 10 интактных животных, получавших наркоз эфиром или севофлюраном), 2 опытные группы (по 40 крыс в условиях геморрагической гипотензии на фоне наркоза эфиром или севофлюраном). Далее исследовали содержание веществ низкой и средней молекулярной массы в крови общей сонной артерии у интактных крыс и в опытных группах через 15, 30, 60 и 120 мин геморрагической гипотензии. Рассчитывали пептидно-нуклеотидный коэффициент и коэффициент ароматичности для качественной оценки пула веществ. Статистическую значимость полученных показателей определяли с использованием непараметрического критерия Манна-Уитни. Результаты. Выявлено снижение показателей эндогенной интоксикации анаболического и катаболического пулов в группах животных, получавших севофлюран. Величина пептидно-нуклеотидного коэффициента в крови была ниже только на 15-й мин геморрагической гипотензии в условиях наркоза севофлюраном, по сравнению с опытной группой крыс, получавших эфир. Заключение. У интактных животных при применении севофлюрана для анестезии эндогенная интоксикация выражена слабее, чем при использовании диэтилового эфира. В условиях геморрагической гипотензии показатели эндогенной интоксикации ниже на фоне наркоза севофлюраном, что позволяет констатировать факт системной цитопротекции, а, значит, реализацию эффекта анестезиологического прекондиционирования. Background. Interest in the possibility of reducing endogenous intoxication in acute massive blood loss is growing. The phenomenon of anesthetic preconditioning has been actively discussed since a possibility of additional protection of various organs and systems has appeared. The aim of this study was to assess parameters of endogenous intoxication associated with anesthetic preconditioning with sevoflurane in hemorrhagic hypotension. Materials and methods. Experiments were carried out on 100 white outbred male rats divided into two control groups (10 intact rats in each group anesthetized with ether or sevoflurane) and two experimental groups (40 rats in each group with hemorrhagic hypotension induced during anesthesia with ether or sevoflurane). After 15, 30, 60, and 120 min of hemorrhagic hypotension, the blood content of low and medium molecular weight substances was measured in the blood from the common carotid artery of control and experimental rats. The peptide-nucleotide coefficient and the aromaticity coefficient were calculated for qualitative assessment of the substance pool. Statistical analysis was performed with the nonparametric Mann-Whitney test. Results. Indices of endogenous intoxication of anabolic and catabolic pools were decreased in the groups receiving sevoflurane. The blood peptide-nucleotide coefficient was decreased only at 15 min of hemorrhagic hypotension during sevoflurane anesthesia compared to the experimental group receiving ether. Conclusions. In control animals anesthetized with sevoflurane for anesthesia, systemic endotoxemia was less pronounced than in the diethyl ether group. In hemorrhagic hypotension, indexes of endogenous intoxication were lower for sevoflurane anesthesia, which evidenced systemic cytoprotection, and, thus, occurrence of the effect of anesthetic preconditioning.

Sevoflurane protects cardiomyocytes against hypoxia/reperfusion injury via LINC01133/miR-30a-5p axis

Previous studies failed to elucidate the detailed mechanisms of anesthetic preconditioning as a protective approach against ischemic/reperfusion (I/R) injury in cells. The present study mainly centered on discovering the mechanisms of Sevoflurane (Sev) in preventing cardiomyocytes against I/R injury. Human cardiomyocyte AC16 cell line was used to simulate I/R injury based on a hypoxia/reperfusion (H/R) model. After Sev treatment, cell viability and apoptosis were detected by MTT assay and flow cytometry, respectively. Lactate dehydrogenase (LDH) content was measured using an LDH Detection Kit. Relative mRNA and protein expressions of LINC01133, miR-30a-5p and apoptosis-related proteins were detected using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot as needed. Target gene of miR-30a-5p and their potential binding sites were predicted using Starbase and confirmed by dual-luciferase reporter assay. Cell behaviors were assessed again after miR-30a-5p and LINC01133 transfection. Sev could improve cell viability, reduce LDH leakage, and down-regulate the expressions of apoptosis-related proteins (Bax, cleaved caspase-3 and cleaved caspase-9) and LINC01133 as well as up-regulate miR-30a-5p and Bcl-2 expressions in H/R cells. MiR-30a-5p was the target of LINC01133, and up-regulating miR-30a-5p enhanced the effects of Sev in H/R cells, with a suppression on H/R-induced activation of the p53 signaling pathway. However, up-regulating LINC01133 reversed the enhancing effects of miR-30a-5p on Sev pretreatment in H/R cells. Sev could protect cardiomyocytes against H/R injury through the miR-30a-5p/LINC01133 axis, which may provide a possible therapeutic method for curing cardiovascular I/R injury.

Opioids Preconditioning Upon Renal Function and Ischemia-Reperfusion Injury: A Narrative Review

Kidneys have an important role in regulating water volume, blood pressure, secretion of hormones and acid-base and electrolyte balance. Kidney dysfunction derived from acute injury can, under certain conditions, progress to chronic kidney disease. In the late stages of kidney disease, treatment is limited to replacement therapy: Dialysis and transplantation. After renal transplant, grafts suffer from activation of immune cells and generation of oxidant molecules. Anesthetic preconditioning has emerged as a promising strategy to ameliorate ischemia reperfusion injury. This review compiles some significant aspects of renal physiology and discusses current understanding of the effects of anesthetic preconditioning upon renal function and ischemia reperfusion injury, focusing on opioids and its properties ameliorating renal injury. According to the available evidence, opioid preconditioning appears to reduce inflammation and reactive oxygen species generation after ischemia reperfusion. Therefore, opioid preconditioning represents a promising strategy to reduce renal ischemia reperfusion injury and, its application on current clinical practice could be beneficial in events such as acute renal injury and kidney transplantation.