Effect of Selenium on Succinylcholine-Induced POM

Summary

For more than 60 years, succinylcholine is still being administered as the selective relaxant for rapid sequence intubation by anesthesiologists in many countries. It has been shown to possess unique features such as low cost, fast-acting, short half-life, safe metabolites, and causing excellent muscle relaxation for intubation. However, it has many side effects as well.

Postoperative myalgia (POM), with an incidence rate of about 41%-92%, is one of the most common side effects of this drug and can take several days to cause significant discomfort in patients. However, its effect is felt more in the throat, neck, shoulder, and abdominal muscles and is common among patients with outpatient surgery. Due to its unknown real context of pathogenesis and in an effort to reduce the incidence and severity of succinylcholine-induced myalgia, various medications including non-depolarizing muscle relaxants, benzodiazepines, magnesium sulfate, opioids, gabapentin, pregabalin and nonsteroidal anti-inflammatory drugs have been tested, with varying degrees of success.

Free radicals are created as a consequence of ATP (adenosine triphosphate) production by the mitochondria. These by-products are generally reactive oxygen species (ROS) as well as reactive nitrogen species (RNS) that result from the cellular redox process. These species play a dual role as both toxic and beneficial compounds. The delicate balance between their two antagonistic effects is clearly an important aspect of life. At low or moderate levels, ROS and RNS exert beneficial effects on cellular responses and immune function. At high concentrations, they generate oxidative stress, a deleterious process that can damage all cell structures. Muscle injuries might lead to the production of free radicals and further cellular damage, triggered by lipid peroxidation and protein oxidation. Peroxidation of membrane lipids leads to loss of membrane fluidity and elasticity, impaired cellular functioning, and even cell rupture. The various direct products of lipid peroxidation, such as malondialdehyde (MDA), isoprostanes, and 4-hydroxynonenal are considered among the most important biomarkers of oxidative stress in tissues. Malondialdehyde is a reactive carbonyl compound and is both mutagenic and carcinogenic. It reacts with DNA to form DNA adducts that are believed to contribute significantly to cancers linked to lifestyle and dietary factors. Protein oxidation can cause fragmentation at amino acid residues, formation of protein-protein cross-linkages, and oxidation of the protein backbone which ultimately leads to loss of function. Damaged proteins affect intracellular pathways and are contributing factors to different disorders and diseases. Protein carbonyl (CO) groups are produced on protein side chains during oxidation. High levels of protein CO groups have been observed in rheumatoid arthritis, Alzheimer's disease, diabetes, sepsis and chronic renal failure.

Selenium is a well-recognized antioxidant which act s as a cofactor of antioxidant enzymes. This essential element helps protect the body against free radicals causing damage to the cells. Substantial evidence suggests that free radical production leads to increased oxygen uptake over time. The indirect though significant impact of selenium supplements is to protect the cells against oxidative stress and free radical production. Nature-made selenium contains 200 mg of this element with a natural origin, high absorption capacity, and prolonged retention. Selenium exerts its antioxidant effects through glutathione peroxidase. Glutathione peroxidase is an enzyme containing four selenium-cofactors that catalyze the breakdown of hydrogen peroxide and organic hydroperoxides. There are at least four different glutathione peroxidase isozymes in animals. Glutathione peroxidase 1 is the most abundant and is a very efficient scavenger of hydrogen peroxide, while glutathione peroxidase 4 is most active with lipid hydroperoxides. The glutathione S-transferases show high activity with lipid peroxides. These enzymes are at particularly high levels in the liver and serve in detoxification metabolism.

Conditions

• Postoperative Myalgia

Interventions

DRUG

Placebo

40 patients will receive starch capsules orally with sips of water 2 hours before induction of anesthesia

DRUG

Selenium

40 patients will receive Selenium (selenium NATURE'S BOUNTY, INC. Bohemia) 200 mcg orally with sips of water 2 hours before induction of general anesthesia

Sponsors & Collaborators

• Assiut University

  lead OTHER

Principal Investigators

• Ekram A Osman, MD · Assiut University, Faculty of Medicine

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

20 Years

Max Age

40 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-06-01

Primary Completion

2020-03-31

Completion

2020-03-31

Countries

• Egypt

Study Locations