Hyperlactacidemia in Major Abdominal Surgery and Monocarboxylate Receptors
- Conditions
- Abdomen DiseaseHyperlactatemiaSurgical Procedure, UnspecifiedPostoperative Complications
- Interventions
- Genetic: Genetic analysis of polymorphism of membrane receptors involved in lactate transport
- Registration Number
- NCT06222021
- Brief Summary
The goal of this clinical trial is to identify those situations in which the increase of lactate levels is not clinically relevant since it is associated with altered genetic polymorphism of the genes involved in the membrane proteins acting as carriers for lactate (mainly monocarboxylate transporters, MCTs) patients undergoing major abdominal surgery.
The main questions it aims to answer are:
1. Is there a relationship between the lactate levels in the immediate post-operative period and the presence of some lactate receptor polymorphisms?
2. Can hyperlactacidemia related to lactate receptor polymorphisms affect length of stay in the recovery room and/or in intensive care unit, postoperative hospital stay, postoperative complications? - Which are the risk factors for hyperlactacidemia in the immediate post-operative period in addition to the presence of lactate receptors polymorphisms?
Participants will undergo pre-operative genomic assay testing.
- Detailed Description
Lactic acidosis is traditionally attributed to cellular hypoxia, to an imbalance between the body's demand for oxygen and its availability. Lactate is produced by the muscles, skin, brain, red blood cells and intestine and eliminated by the liver and kidneys. Lactate is produced by the following biochemical reaction: Pyruvate + reduced nicotinamide adenine dinucleotide (NADH) + H+ ↔ Lactate + nicotinamide-adenine dinucleotide (NAD+). Under normal conditions, this reaction produces lactate from pyruvate in a ratio of 10 to 1. Pyruvate comes from glycolysis and is used by mitochondria. When glycolysis is increased or mitochondrial oxidative phosphorylation is blocked, pyruvate accumulates and is converted into lactate generating hyperlactacidemia and acidosis. Normal lactate levels are 0-2 mmol/L. Hyperlactacidemia, usually defined as values above 2.2 mmol/L, is divided into two types: A (associated with hypoxia) and B (related to increased stress-induced aerobic metabolism, mitochondrial diseases and the use of drugs such as metformin and beta2 agonists). The lactate/pyruvate ratio allows us to distinguish the two types of hyperlactacidemia. In hyperlactacidemia type A, this ratio is \>10 while in type B it remains constant (L/P=10). In case of liver dysfunction, hyperlactacidemia may be associated with a variable L/P ratio based on the determining cause reduction in lactate clearance. In fact, lactate extraction may depend on the hepatic blood flow, the polymorphism of some genes involved in the lactate transport (mainly MCT1) and the potential of hydrogen (pH) which inhibits gluconeogenesis when lower than 7.10. Since lactic acid is an hydrophilic weak acid, its transport across membranes requires transporters that belong to the transporter family monocarboxylates (MCTs) encoded by the solute carrier family 16 (SLC16) gene family. It has been demonstrated that the MCT1 (rs1049434) T1470A polymorphism is associated with a deficit in the transmembrane transport of lactate: in fact, the T allele is correlated with an approximately 50% reduction in the lactate transport rate compared to the A6 allele. MCT4, which has a very low affinity for pyruvate and a greater affinity for lactate, ensures that pyruvate is converted into lactate before transmembrane transport. Polymorphisms affecting these receptors can influence the different speed of transmembrane lactate flow and therefore correlate with lesser or greater accumulation of serum lactate. Another membrane receptor involved in lactate transport has recently been described: G-coupled protein receptor 81 (GPR81), present in adipocytes. Polymorphisms affecting the gene encoding this receptor could correlate with a different accumulation of lactate. An increase in the level of lactates is often correlated with increased morbidity and mortality in critical situations critical such as sepsis, trauma, major cardiac and abdominal surgery. Measurement of perioperative biomarkers such as lactate is often used in clinical practice as an outcome predictor. However, there are no studies aimed to identify those situations in which the increase of lactates is not clinically relevant since it is associated with altered genetic polymorphism.
The investigators hypothesized that lactate levels at 3 hours after the end of major abdominal surgery will be higher in the patients carrying the T allele versus the A allele for MCT1 gene.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 109
- Age ≥ 18 years
- Indication for elective major abdominal surgery
- Age <18 years
- Liver cirrhosis
- Liver surgery
- Intraoperative chemotherapy
- Previous gastric bypass surgery (thiamine deficiency)
- Severe cardiovascular/respiratory impairment
- Mitochondrial diseases
- Pheochromocytoma
- Chronic renal failure ≥ stage III
- Refusal to sign the informed consent
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Genetic analysis of polymorphisms of membrane receptors involved in lactate transport Genetic analysis of polymorphism of membrane receptors involved in lactate transport Before the start of surgery, after arterial line cannulation, a blood sample will be collected in an ethylenediaminetetraacetic acid (EDTA) test tube for genetic analysis of polymorphisms of membrane receptors involved in lactate transport including transporter family monocarboxylates 1 (MTC1), transporter family monocarboxylates 4 (MTC4) and Gi-coupled protein receptor 81 (GPR81).
- Primary Outcome Measures
Name Time Method Lactate levels 3 hours after the end of surgery Lactate levels (mmol/L) in the patients carrying the T allele versus the A allele for MCT1 gene.
- Secondary Outcome Measures
Name Time Method Polymorphisms of lactate receptors (presence of MCT4 and GPR8) Minutes and an average of 30 minutes before the start of surgery Prevalence of the lactate receptors MCT4 and GPR8 polymorphisms throughout the genetic analysis of a blood sample.
Lactate clearance 24 hours after the end of surgery Evaluation of the association between lactate clearance (lactate levels at the end of surgery - lactate levels at 24 hours after the end of surgery)x100/lactate levels at the end of surgery and the presence of lactate receptor polymorphisms (MCT4 and GPR8).
Postoperative recovery Hours (RR) or days (ICU) and average of three hours for RR and one day in ICU Length of stay in recovery room (RR) or in intensive care (ICU)
In-hospital stay Days until discharge, an average of 7 day Hospital stay duration
Hyperlactacidemia 3 hours after the end of surgery Analysis of potential risk factors for hyperlactacidemia (lactate levels \>2.2 mmol/L) as well as the presence of lactate receptor polymorphisms including age (years), comorbidities, American Society of Anesthesiologists (ASA) physical status classification system, Body Mass Index (kg/m2), type and duration of surgery (hours), surgical approach (open, laparoscopic, robotic), total of liquids administered (ml), total diuresis (ml), blood losses (ml), intraoperative blood components transfusions (units), blood gas analyses parameters, number of hypotensive episodes during surgery (MAP\<65 mmHg) requiring the administration of norepinephrine or its dosage increase.
Trial Locations
- Locations (1)
UOC Anestesia delle Chirurgie Generali e dei Trapianti, Fondazione Policlinico Universitario A. Gemelli IRCCS
🇮🇹Rome, Italy/Lazio, Italy