Clinical trial NCT06222021: Hyperlactacidemia in Major Abdominal Surgery and Monocarboxylate Receptors
Official title: Hyperlactacidemia in Major Abdominal Surgery: Role of Variation in the Monocarboxylate Receptors
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Surgical Procedure, Unspecified
Postoperative Complications
Hyperlactatemia
Abdomen Disease
Lead sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Sponsor class: OTHER
First posted: 2024-01-24
Enrollment: 109
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Participants will undergo preoperative genomic assay testing
Primary purpose: SCREENING

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.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years
* Indication for elective major abdominal surgery

Exclusion Criteria:

* 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

Primary outcomes:
measure: Lactate levels
timeFrame: 3 hours after the end of surgery
Secondary outcomes:
measure: Polymorphisms of lactate receptors (presence of MCT4 and GPR8)
timeFrame: Minutes and an average of 30 minutes before the start of surgery
measure: Lactate clearance
timeFrame: 3 hours after the end of surgery
measure: Lactate clearance
timeFrame: 24 hours after the end of surgery
measure: Postoperative recovery
timeFrame: Hours (RR) or days (ICU) and average of three hours for RR and one day in ICU
measure: In-hospital stay
timeFrame: Days until discharge, an average of 7 day
measure: Hyperlactacidemia
timeFrame: 3 hours after the end of surgery
Other outcomes:
Locations:
city: Rome
country: Italy
facility: UOC Anestesia delle Chirurgie Generali e dei Trapianti, Fondazione Policlinico Universitario A. Gemelli IRCCS
state: Italy/Lazio
Study officials:
References: