Lactic Acidosis Research Articles

Twists in genetic mitochondria: Unraveling a case of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes overlapping with myoclonic epilepsy with ragged red fibers

This case report presents a 23-year-old female with a complex medical history, initially diagnosed with juvenile myoclonic epilepsy, later discovered to have the m.3243A>G variant associated with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). Despite a typical myoclonic epilepsy with ragged red fibers (MERRF) phenotype, genetic testing confirmed a singular MELAS mutation. The patient exhibited diverse symptoms, including seizures, chronic migraines, myoclonus, and visual disturbances. Diagnostic studies revealed basal ganglia calcifications and progressive brain MRI abnormalities consistent with mitochondrial dysfunction. Additionally, ophthalmologic exams identified features indicative of MELAS pigmentary retinopathy. The discussion highlights the clinical and genetic diversity of mitochondrial disorders, emphasizing the challenges in distinguishing overlapping phenotypes. The patient’s mitochondrial DNA heteroplasmy influenced the variable onset and severity of symptoms. The case underscores the importance of comprehensive genetic investigations, as the m.3243A>G variant is associated with both MELAS and MERRF, leading to diagnostic complexities. Management strategies, primarily symptom-focused due to the lack of a standardized treatment approach, include prophylactic arginine, taurine, and coenzyme Q10 supplementation. The patient’s response to various medications, including vagal nerve stimulator placement, Botox injections, and novel treatments like ASP0367, demonstrates the ongoing efforts to address symptoms and improve quality of life. This report contributes to the understanding of mitochondrial overlap syndromes, offering insights into the diagnostic challenges and management complexities associated with MELAS and MERRF. The case underscores the need for a multidisciplinary approach, combining clinical, genetic, and therapeutic considerations, to optimize care for individuals with mitochondrial encephalopathies.

Lactic Acidosis in a Neonate with Ventriculomegaly and Hypoplasia of the Corpus Callosum.

Lactic Acidosis in a Neonate with Ventriculomegaly and Hypoplasia of the Corpus Callosum.

381 - Profound lactic acidosis at birth, a marker to raise suspicion for mitochondrial disorders

381 - Profound lactic acidosis at birth, a marker to raise suspicion for mitochondrial disorders

Metformin exposure and the incidence of lactic acidosis in critically ill patients with T2DM: A retrospective cohort study.

The objective of this study was to investigate the correlation between metformin exposure and the incidence of lactic acidosis in critically ill patients. The patients with type 2 diabetes mellitus (T2DM) were included from Medical Information Mart for Intensive Care IV database (MIMIC-IV). The primary outcome was the incidence of lactic acidosis. The secondary outcomes were lactate level and in-hospital mortality. Propensity score matching (PSM) method was adopted to reduce bias of the confounders. The multivariate logistic regression was used to explore the correlation between metformin exposure and the incidence of lactic acidosis. Subgroup analysis and sensitivity analysis were used to test the stability of the conclusion. We included 4939 patients. There were 2070 patients in the metformin group, and 2869 patients in the nonmetformin group. The frequency of lactic acidosis was 5.7% (118/2070) in the metformin group and it was 4.3% (122/2869) in the nonmetformin group. There was a statistically significant difference between the two groups (P < 0.05). The lactate level in the metformin group was higher than in the nonmetformin group (2.78 ± 2.23 vs. 2.45 ± 2.24, P < 0.001). After PSM, the frequency of lactic acidosis (6.3% vs. 3.7%, P < 0.001) and lactate level (2.85 ± 2.38 vs. 2.40 ± 2.14, P < 0.001) were significantly higher in the metformin group compared with the nonmetformin group. In multivariate logistic models, the frequency of lactic acidosis was obviously increased in metformin group, and the adjusted odds ratio (OR) of metformin exposure was 1.852 (95% confidence interval (CI) = 1.298-2.643, P < 0.001). The results were consistent with subgroup analysis except for respiratory failure subgroup. Metformin exposure increased lactate level but did not affect the frequency of lactic acidosis in patients of respiratory failure with hypercapnia. However, the in-hospital mortality between metformin and nonmetformin group had no obvious difference (P = 0.215). In sensitivity analysis, metformin exposure showed similar effect as the original cohort. In critically ill patients with T2DM, metformin exposure elevated the incidence of lactic acidosis except for patients of respiratory failure with hypercapnia, but did not affect the in-hospital mortality.

Association between lactic acidosis and multiple organ dysfunction syndrome after cardiopulmonary bypass.

The relationship between hyperlactatemia and prognosis after cardiopulmonary bypass (CPB) is controversial, and some studies ignore the presence of lactic acidosis in patients with severe hyperlactacemia. This study explored the association between lactic acidosis (LA) and the occurrence of multiple organ dysfunction syndrome (MODS) after cardiopulmonary bypass. This study was a post hoc analysis of patients who underwent cardiac surgery between February 2017 and August 2018 and participated in a prospective study at Taizhou Hospital. The data were collected at: ICU admission (H0), and 4, 8, 12, 24, and 48 h after admission. Blood lactate levels gradually increased after CPB, peaking at H8 and then gradually decreasing. The patients were grouped as LA, hyperlactatemia (HL), and normal control (NC) based on blood test results 8 h after ICU admission. Basic preoperative, perioperative, and postoperative conditions were compared between the three groups, as well as postoperative perfusion and oxygen metabolism indexes. There were 22 (19%), 73 (64%), and 19 (17%) patients in the LA, HL, and NC groups, respectively. APACHE II (24h) and SOFA (24h) scores were the highest in the LA group (P<0.05). ICU stay duration was the longest for the LA group (48.5 (42.5, 50) h), compared with the HL (27 (22, 48) h) and NC (27 (25, 46) h) groups (P=0.012). The LA group had the highest incidence of MODS (36%), compared with the HL (14%) and NC (5%) groups (P=0.015). In the LA group, the oxygen extraction ratio (O2ER) was lower (21.5 (17.05, 32.8)%) than in the HL (31.3 (24.8, 37.6)%) and the NC group (31.3 (29.0, 35.4) %) (P=0.018). In the univariable analyses, patient age (OR = 1.054, 95% CI [1.003-1.109], P=0.038), the LA group (vs. the NC group, (OR = 10.286, 95% CI [1.148-92.185], P=0.037), and ΔPCO2 at H8 (OR = 1.197, 95% CI [1.022-1.401], P=0.025) were risk factor of MODS after CPB. We speculated that there was correlation between lactic acidosis and MODS after CPB. In addition, LA should be monitored intensively after CPB.

Renal manifestations of metformin-associated lactic acidosis; new findings

Renal manifestations of metformin-associated lactic acidosis; new findings

Prescription trend and lactic acidosis in patients prescribed metformin before and after the revision of package insert for allowing metformin administration to patients with moderately decreased kidney function based on real-world data from MID-NET® in Japan.

This study was conducted to understand the impact of package insert (PI) revision in Japan on 18 June 2019 to allow metformin use for patients with moderately decreased kidney function (30 ≤ estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2). A new user cohort design was employed to examine the prescription trend and the occurrence of lactic acidosis in patients prescribed metformin before and after PI revision using the Medical Information Database Network (MID-NET®). From 12 May 2016 to 31 March 2020, 5,874 patients (before, n = 4,702; after, n = 1,172) were identified as new metformin users, including 1,145 patients (before, n = 914; after, n = 231) with moderately decreased kidney function. Although no marked changes in metformin prescription were observed before and after PI revision, the daily metformin dose at the first prescription decreased after PI revision. For both before and after PI revision, less than 10 cases of lactic acidosis occurred in all patients prescribed metformin, and no lactic acidosis was observed in patients with moderately decreased kidney function. The results of this study are useful for understanding the safety of metformin use in patients with decreased kidney function and suggest no worse impacts of PI revision in Japan, indicating no further safety concerns on metformin use in patients with moderately decreased kidney function under the situation with careful use and safety monitoring of metformin.

Gastrointestinal Complications of Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-Like Episodes (MELAS) Syndrome Managed By Parenteral Nutrition.

Gastrointestinal complications of MELAS such as chronic intestinal pseudo-obstruction, pancreatitis and gastroparesis can lead to undernutrition.Superior mesenteric artery syndrome is a rare condition but should be considered in cases with significant weight loss and resistance to symptomatic treatment.Optimal caloric intake and energy support can improve the condition of patients with MELAS.

A Successful Single Early Hemodialysis Treatment for a Late-Onset Lactic Acidosis After Metformin Poisoning in a Type 2 Diabetes Patient with Advanced Diabetic Nephropathy

A Successful Single Early Hemodialysis Treatment for a Late-Onset Lactic Acidosis After Metformin Poisoning in a Type 2 Diabetes Patient with Advanced Diabetic Nephropathy

P-29 Metformin poisoning without lactic acidosis: Case report

Abstract Introduction Metformin is the most widely used oral antidiabetic, which belongs to the biguanide pharmacological group. Metformin-associated lactic acidosis (MALA) is a rare event with an incidence of approximately 19 cases per 100,000 patient-years. The risk of developing lactic acidosis, when taking metformin is enhanced by several factors such as: age &amp;gt; 65 years; concomitant diseases that have the ability to induce hypoxemia (chronic renal failure, congestive heart failure, cardiogenic shock, severe lung disease, sepsis, advanced liver disease, history of lactic acidosis); an excessive alcohol consumption; an administration of iodinated contrast agents. Clinical Case A 46-year-old man was urgently admitted with the following symptoms: drowsiness, repeated vomiting, lethargy, dizziness. The symptoms started after he administered outpatient and at own initiative 50 tablets of metformin, each tablet contains a dose of 500 mg (total dose 25g). Concomitant pathologies: diagnosed with Type 2 Diabetes for 8 years; Toxic liver cirrhosis, compensated Child-Pugh A (recently diagnosed); hypertension; CKD G3aA2 KDIGO. The patient's condition at admission was assessed as extremely serious, Glasgow scale - 11 points, mild hypertension, tachycardia, tachypnea. The paraclinical investigations revealed the presence of metabolic acidosis, but with lactate &amp;lt;5 mmol/l; the progressive renal dysfunction with creatinine values in the first 24 hours up to 1184 µmol/l, urea – 24.5 mmol/l; a severe hypoglycemia - 1.68 mmol/l; a moderate cytolytic syndrome; a cholestatic syndrome, an inflammatory and hepatoprive syndrome; coagulation disorders; a pancreatic dysfunction. In the context of the evident increase of urea and creatinine, the decision was made to initiate the intermittent hemodialysis, a total of 14 sessions were required during hospitalization. The particularity of this case is represented by the absence of lactic acidosis, despite metformin intoxication with altered neurological status, acute renal failure, developed due to chronic kidney disease, liver cirrhosis of toxic etiology and severe hypoglycemia. Conclusion Metformin should be administered with caution in patients with multiple comorbidities. Metformin intoxication can induce lactic acidosis with an increased risk of serious, potentially fatal adverse events. It is essential to identify metformin intoxication as early as possible, with prompt initiation of renal replacement measures and dynamic monitoring of biochemical parameters.

P-33 A rare form of diabetes: MELAS

Abstract Introduction MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes) is a fatal multisystemic condition caused by a mitochondrial DNA mutation, the most prevalent is m.3243AAG. Diagnosis is common at a young age,and individuals with late diagnosis due to comorbidities have a shorter life expectancy. It causes dementia, epilepsy, myopathy, hearing loss, diabetes, and growth retardation. We present a patient with MELAS who was diagnosed late since it is a rare manifestation of diabetes with a different treatment than regular diabetes. Clinical Case A fifty-year-old female patient requested regulation of her blood sugar. She had type 2 diabetes for 20 years and hypertension, hyperlipidemia; she had a coronary bypass surgery three years ago and had been using a hearing implant for one year. She is under insulin treatment since 2018. Her 13-year-old daughter was just diagnosed with MELAS due to growth and development delays, and the m.3243AG mutation was discovered. She also screened for MELAS and found heteroplasmic m.3243A&amp;lt;G mutation. Her height was 143 cm, weight was 38 kg and BMI was 18.5 kg/m2. The patient was oriented and cooperative, but reluctant to answer questions. Her speech was slow, she was partial numbness, and she was not open to communication due to hearing loss, questions were always answered by her daughter. She exhibited a poor memory and calculation functions. She had muscle weakness in both extremities with a proximal muscles strength level of 3 and also described exercise intolerance. The patient did not have any seizures. She described a loss of hearing in the left ear and very poor hearing in the right ear. She had attacks of a migraine-like headache in left side of head and palpitation. Her medications included insulin glargine 1×22 units, insulin glulisine 3×8 units, coenzyme Q10 2×100 mg, arginine 3×2.5 grams, ranolazine 375 mg, perindopril 5 mg, sprinolactone 25 mg, metoprolol 50 mg, and rosuvastatin 20 mg. While Hba1c was 10.4 µg/dl, there were postprandial hyperglycemias with the highest 372 mg/dl and fasting hypoglycemias with the lowest 55 mg/dl in blood sugar follow-ups. The patient's treatment was arranged as 2×15 units of insulin degludec aspart and 1×8 units of insulin glulisine before lunch. Linagliptin was preferred instead of the weight-loss GLP-1 agonist to reduce mitochondrial stress in the patient with low BMI. Diabetic oral nutrition therapy was recommended to the malnourished patient. For cardiac evaluation, echocardiography and rhythm holter were requested. The patient was referred to the dementia outpatient clinic for memory and poor higher neurological function. Our patient had late diagnosis of MELAS with multiple complications including sensorineural deafness, a short stature and neurologic manifestations. Considering MELAS in diabetic patients with hearing loss, neurodegenerative findings, low body mass index and intolerant of metformin will significantly reduce the morbidity of the disease by enabling early diagnosis and treatment.

The synergism of cytosolic acidosis and reduced NAD+/NADH ratio is responsible for lactic acidosis-induced vascular smooth muscle cell impairment in sepsis

BackgroundDuring sepsis, serve vascular dysfunctions lead to life-threatening multiple organ failure, due to vascular smooth muscle cells (VSMC) impairments, resulting in vasoplegia, hypotension and hypoperfusion. In addition, septic patients have an altered cell metabolism that leads to lactic acidosis. Septic patients suffering from lactic acidosis have a high risk of mortality. In addition, septic survivors are at risk of secondary vascular disease. The underlying mechanisms of whether and how lactic acidosis leads to the changes in VSMCs is not well understood. The aim of this study was to comprehensively investigate the effect of lactic acidosis on VSMCs and additionally compare the effects with those induced by pure acidosis and sodium lactate.MethodsPrimary human aortic smooth muscle cells (HAoSMCs) were treated for 48 h with lactic acidosis (LA_pH 6.8), hydrochloric acid (HCl_pH 6.8), sodium lactate (Na+-lactate_pH 7.4) and the respective controls (ctrl._pH 7.4; hyperosmolarity control: mannitol_pH 7.4) and comparatively analyzed for changes in (i) transcriptome, (ii) energy metabolism, and (iii) phenotype.ResultsBoth types of acidosis led to comparable and sustained intracellular acidification without affecting cell viability. RNA sequencing and detailed transcriptome analysis revealed more significant changes for lactic acidosis than for hydrochloric acidosis, with lactate being almost ineffective, suggesting qualitative and quantitative synergism of acidosis and lactate. Bioinformatic predictions in energy metabolism and phenotype were confirmed experimentally. Lactic acidosis resulted in strong inhibition of glycolysis, glutaminolysis, and altered mitochondrial respiration which reduced cellular ATP content, likely due to increased TXNIP expression and altered NAD+/NADH ratio. Hydrochloric acidosis induced significantly smaller effects without changing the NAD+/NADH ratio, with the ATP content remaining constant. These metabolic changes led to osteo-/chondrogenic/senescent transdifferentiation of VSMCs, with the effect being more pronounced in lactic acidosis than in pure acidosis.ConclusionsOverall, lactic acidosis exerted a much stronger effect on energy metabolism than pure acidosis, whereas lactate had almost no effect, reflecting the qualitative and quantitative synergism of acidosis and lactate. As a consequence, lactic acidosis may lead to acute functional impairments of VSMC, sustained perturbations of the transcriptome and cellular dedifferentiation. Moreover, these effects may contribute to the acute and prolonged vascular pathomechanisms in septic patients.

Carbon dioxide production index (VCO2i) predicts hyperlactatemia during cardiopulmonary bypass in pediatric carDiac surGery (pGDP- VCO2i): Study protocol for a nested case-control trial.

Hyperlactatemia (HL) during cardiopulmonary bypass (CPB) is relatively frequent in infants and associates with increased morbidity and mortality. Studies on adults have shown that carbon dioxide production index (VCO2i) during CPB is linked to the occurrence of HL, with 'critical thresholds' for VCO2i reported to be 60mL/min/m2. However, considering infants have a higher metabolic rate and lower tolerance to hypoxia, the critical threshold of VCO2i in infants cannot be replied to the existing adults' standards. The objective of this study is to investigate the association of VCO2i during CPB and HL, and explore the critical VCO2i threshold during CPB in infants. VCO2i predicts hyperlactatemia during cardiopulmonary bypass in pediatric cardiac surgery (pGDP-VCO2i) is a nested case-control study. A cohort of consecutive pediatric patients of less than 3years of age, undergoing congenital cardiac surgeries between May 2021 and December 2023 in West China Hospital will be enrolled. The VCO2i levels of each patient will be recorded every 5min during CPB. The primary outcome is the rate of HL. The infants will be divided into two groups based on the presence or not of HL. Pre- and intraoperative factors will be tested for independent association with HL. Then, we will make an analysis, and the critical value of VCO2i will be obtained. The postoperative outcome of patients with or without HL will be compared. This will be the first trial to investigate the association of VCO2i during CPB and HL, and explore the critical VCO2i threshold during CPB in pediatrics. The results of this study are expected to lay a foundation for clinical application of goal-directed perfusion (GDP) management strategy, and optimize the perfusion strategy and improve the prognosis of pediatric patients undergoing cardiac surgery. Chictr.org.cn, ChiCTR2100044296 on 16 March 2021.

High Levels of Blood Lactate Associated with the Use of Low Dose Aspirin: A Case-Control Study

High Levels of Blood Lactate Associated with the Use of Low Dose Aspirin: A Case-Control Study

Chapter 4 - Primary mitochondrial diseases

Primary mitochondrial diseases (PMDs) are a heterogeneous group of hereditary disorders characterized by an impairment of the mitochondrial respiratory chain. They are the most common group of genetic metabolic disorders, with a prevalence of 1 in 4,300 people. The presence of leukoencephalopathy is recognized as an important feature in many PMDs and can be a manifestation of mutations in both mitochondrial DNA (classic syndromes such as mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes; myoclonic epilepsy with ragged-red fibers [RRFs]; Leigh syndrome; and Kearns-Sayre syndrome) and nuclear DNA (mutations in maintenance genes such as POLG, MPV17, and TYMP; Leigh syndrome; and mitochondrial aminoacyl-tRNA synthetase disorders). In this chapter, PMDs associated with white matter involvement are outlined, including details of clinical presentations, brain MRI features, and elements of differential diagnoses. The current approach to the diagnosis of PMDs and management strategies are also discussed. A PMD diagnosis in a subject with leukoencephalopathy should be considered in the presence of specific brain MRI features (for example, cyst-like lesions, bilateral basal ganglia lesions, and involvement of both cerebral hemispheres and cerebellum), in addition to a complex neurologic or multisystem disorder. Establishing a genetic diagnosis is crucial to ensure appropriate genetic counseling, multidisciplinary team input, and eligibility for clinical trials.

Anesthetic management of glycogen storage disease type 1b during liver transplantation: a case report

The glycogen storage disease type 1b is a rare metabolic disease caused by the glucose 6-phosphate transporter disorder. This study presents a 10-year-old female patient with growth retardation, neutropenia and inflammatory bowel disease, severe hypoglycemia attacks before and during the surgery, and hepatocellular carcinoma who underwent liver transplantation. A multidisciplinary approach from the preoperative preparation stage is essential in addition to intraoperative intervention for hypoglycemia and lactic acidosis in the anesthetic management of these patients.

The New Nano-Resuscitation Solution (TPP-MR) Attenuated Myocardial Injury in Hemorrhagic Shock Rats by Inhibiting Ferroptosis.

Hemorrhagic shock was a leading cause of death worldwide, with myocardial injury being a primary affected organ. As commonly used solutions in fluid resuscitation, acetated Ringer's (AR) and Lactate Ringer's solution (LR) were far from perfect for their adverse reactions such as lactic acidosis and electrolyte imbalances. In previous studies, TPP@PAMAM-MR (TPP-MR), a novel nanocrystal resuscitation fluid has been found to protect against myocardial injury in septic rats. However, its role in myocardial injury in rats with hemorrhagic shock and underlying mechanism is unclear. The hemorrhagic shock rats and hypoxia-treated cardiomyocytes (H9C2) were utilized to investigate the impact of TPP-MR on cardiac function, mitochondrial function, and lipid peroxidation. The expressions of ferritin-related proteins glutathione peroxidase 4 (GPX4), Acyl CoA Synthase Long Chain Family Member 4 (ACSL4), and Cyclooxygenase-2(COX2) were analyzed through Western blotting to explore the mechanism of TPP-MR on hemorrhagic myocardial injury. TPP-MR, a novel nanocrystalline resuscitation fluid, was synthesized using TPP@PAMAM@MA as a substitute for L-malic acid. We found that TPP-MR resuscitation significantly reduced myocardial injury reflected by enhancing cardiac output, elevating mean arterial pressure (MAP), and improving perfusion. Moreover, TPP-MR substantially prolonged hemorrhagic shock rats' survival time and survival rate. Further investigations indicated that TPP-MR improved the mitochondrial function of myocardial cells, mitigated the production of oxidative stress agents (ROS) and increased the glutathione (GSH) content. Additionally, TPP-MR inhibited the expression of the ferroptosis-associated GPX4 protein, ACSL4 and COX2, thereby enhancing the antioxidant capacity. The results showed that TPP-MR had a protective effect on myocardial injury in rats with hemorrhagic shock, and its mechanism might be related to improving the mitochondrial function of myocardial cells and inhibiting the process of ferroptosis.

Metformin Associated Lactic Acidosis (MALA Syndrome): A Case Report

Metformin Associated Lactic Acidosis (MALA Syndrome): A Case Report

Approach to poisoned patients with high anion gap metabolic acidosis in the emergency department - a case series

Toxicology cases are frequent presentations in the emergency department (ED) and often their presentation can vary from a straightforward manner to a complex manner. In this case series we will discuss three cases that presented to the ED with a known, suspected, and unknown toxicological substance ingestion with the common denominator being high anion gap metabolic acidosis (HAGMA). HAGMA is a subcategory of metabolic acidosis. Categorizing metabolic acidosis as a high anion gap aids in identifying the underlying disease process and subsequently initiating appropriate treatment. There have been many broadly inclusive mnemonics used to list the common causes of High anion gap acidosis such as CAT MUDPILES which correspond to Carbon monoxide, Cyanide, Congenital heart disease, Aminoglycosides, Theophylline, Toluene, Methanol, Uremia, Diabetic ketoacidosis, Alcoholic ketoacidosis, Starvation, Acetaminophen, Phenformin, Paraldehyde, Iron, Isoniazid, Inborn errors of metabolism, Lactic acidosis, Ethanol, Ethylene glycol, and Salicylates, respectively. It is not uncommon to be faced with patients with an unclear clinical picture and a lack of clear toxicological ingestion. In such circumstances, the presence of a high anion gap acidosis is an important clue that should prompt investigating for uncommon toxicological causes not listed in the forementioned mnemonics, such as metformin, beta blockers, and CCBs.

Sudden Death Associated with Propofol Infusion Syndrome

In forensic practice, PRIS is considered as the comorbid disease. The project was devoted to the study of PRIS signs in 38 cases of sudden death after surgical interventions. Archival forensic material of “medical cases” for the period from 2011 to 2020 was studied. The clinical and laboratory features of PRIS are summarized. It was found that the most common symptoms were lactic acidosis, hyperkalemia, and progressive heart failure. Optimization of standard forensic chemical study was carried out, in which it was established that the hydrolysis stage must be included in the urine sample preparation procedure for the determination of propofol. When conducting forensic chemical study of biological objects for the content of propofol, the analytical technologies used must have the sensitivity for detecting propofol in the blood at the level of 0.01 μg/ml or lower. Solid-phase extraction method on cartridges with mixed hydrophobic-anion exchange properties with sorbent such as Oasis MAX Cartridge 3cc, /60 mg/60μm companies Waters (USA) is 17% more effective than the routine liquid-liquid extraction method of propofol from blood. The preparation of TMS derivatives of propofol, increases the efficiency of chromatographic separation and provides the possibility for the analytical study of extracts from blood over a longer period of time (up to 24 hours).