Continuous Sedation With Low-dose Propofol In Severe Burns

Objective:Propofol can effectively prevent and regulate dyserethism, excessive inflammatory response, immunologic imbalance, metabolic disturbance and improve the survival rate of critical patients through multiple links after severe burns or trauma. However, in recent years it was reported in some literatures that high-dose (> 4mg·kg-1·h-1) and long-term (> 48h) propofol infusion may induce "propofol infusion syndrome (PRIS)" with low incidence but high mortality, so its safety for sedation of critical patients was challenged. It was found that rhabdomyolysis (RM) played an important role in the occurrence and development of PRIS and the ubiquitin-proteasome pathway played a key role in skeletal muscle damage and dysbolism. This study adopted animal model and in vitro cell culture, and used the low-dose propofol as continuous sedation for burns to observe:1. the impact on releases of stress hormones and inflammatory mediators; 2. the impact on blood gas, blood biochemistry and histopathology of major organ; 3. the impact on the skeletal muscle structure and gene expression of ubiquitin system. This study also systematically evaluated the safety and effectiveness of continuous sedation by low-dose propofol for severe burns, and studied the influence on ubiquitin system of skeletal muscle from the level of gene, providing the theory basis of sedation for severely burned patients using propofol.Material and Methods:1. Experiments on Animals(1) Twenty four healthy oryctolagus cuniculuses were randomly divided into scalding sedation group, scalding control group, sham injury sedation group and sham injury control group. Scalding groups were suffered from 30%TBSA full thickness injury with boiling water after anesthesia, sham injury groups were immerged in warm water (37℃) after anesthesia and then were treated same as scalding groups.3h after scalding/sham injury, sedation groups were constantly infused with 6.2 mg·kg-1·h-1 (2 mg·kg-1·h-1 equivalent of human)1% propofol for 48h, control groups were constantly infused with normal saline of same volume and rate for 48h. Blood samples were taken and preserved before scalding,3h after scalding,6h after scalding (3h after sedation),9h after scalding (6h after sedation) and 51h after scalding (48h after sedation); anesthetized the animals after 48h, the heart, lung, liver, kidney, intestine and skeletal muscle tissue samples and urine sample were preserved. (2) determined concentrations of major stress hormone in blood plasma, inflammatory mediators in blood serum and blood glucose; (3) determined blood gas, blood biochemistry and concentrations of muscle hemoglobin in blood serum and urine; (4) observed the pathological changes of major organ tissue by optical microscope and the ultramicroscopic structure changes of skeletal muscle tissue by transmission electron microscope; (5) determined the gene expression changes of relevant component genes in ubiquitin-proteasome pathway of skeletal muscle tissue.2. In Vitro Cell Experiments(1) Established stable method on separation, culturing, purifying and fusion of satellite cells of rabbit skeletal muscle. (2) Co-cultured the mature myotube with propofol (2μg/ml), dexamethasone (DXM,100μmol/ml) and norepinephrine (NE,10-'mmol/L) for 48h respectively or together, and determined the gene expression changes of relevant component genes in ubiquitin-proteasome pathway of myotube.Results:1. Epnephrine, adrenocorticotropic hormone (ACTH) and insulin in blood plasma were reduced (p<0.05), cortisol was constantly increased (p<0.05) after severe scalding injury; cortisol of scalding sedation group was higher than that of scalding control group after propofol sedation (p< 0.05), and ACTH of sham injury sedation group was reduced compared with sham injury control group (p<0.05) after sedation; 2. TNF-a, IL-1 and IL-10 in blood serum were all increased after severe scalding injury (p<0.05), and propofol sedation may reduce the increasing (p< 0.05); 3. Compared with control group, propofol sedation had no significant influence on PCO2 and PO2 of sedation group(p> 0.05), lactic acid and glucose level in blood of scalding sedation group were decreased compare with scalding control group(p< 0.05); 4. Propofol sedation relieved the increasing of contents of ALT, AST, CK, CK-MB and muscle hemoglobin in blood serum and urine after severe scalding injury (p< 0.05 or p <0.01), and had no significant influence on sham injury group (p> 0.05), but blood cholesterol and triglyceride increased after continuous propofol sedation (p<0.05).5. Heart, lung, liver, kidney, intestine and skeletal muscle were all damaged in varying degrees after severe scalding injury, propofol may attenuate the damage and had no notable influence on sham injury animals; 6. Gene expressions of E2-14KDa enzyme, E3a enzyme and C2 subunit were enhanced in skeletal muscle after severe scalding injury, propofol sedation reduced its high gene expressions effectively (p<0.05 or p<0.01) and had no influence on gene expressions of sham group (p>0.05); 7. Propofol had no influence on gene expression of myotube ubiquitin system when it cultured with myotube alone(p >0.05), but propofol restrained the high gene expression of various component gene of ubiquitin system induced by NE and DXM (p<0.05 or p<0.01).Conclusion:The effects of continuous sedation by low-dose propofol are as following:1. Continuous sedation by low-dose propofol may improve dyserethism after severe scalding injury; may restrain the releasing of main inflammatory factors after severe scalding injury, and regulate the balance of pro-inflammatory factors and anti-inflammatory factors; may attenuate organ injuries after severe scalding injury and improve liver function; may restrain the high gene expressions of skeletal muscle ubiquitin system caused by severe scalding injury and high level of catecholamine and cortisol, and this may be one of its main functions to decrease skeletal muscle injuries.It is a safe and effective treatment to take low-dose propofol for continuous sedation for severe burns, and has no risk to induce PRIS.