Effects And Priliminary Mechanism Of Intensive Insulin Therapy On Gastrointestinal Function And Clinical Outcomes In Patients Undergoing Cardiac Valve Replacement With Cardiopulmonary Bypass

The cardiopulmonary bypass operation is the most important method of surgicaltreatment for heart diseases as congenital heart disease, coronary artery disease,valvular heart disease. During CPB,because of the organs are exposed tounphysiological conditions, such as haemodilution, lower perfusion pressure,hypothermia; the artificial surface contact, surgical trauma, bleeding, drugs, etc.which will trigger severe inflammatory reaction and acute glucose metabolic disorder.The latter is characterized by hyperglycemia，acute insulin resistance, high lacticacidosis and cell energy disturbances. The gastrointestinal disorder is one of the mostcommon complications after cardiopulmonary bypass with a morbidity range of0.5-3%, and mortality was reported up to92-94%.How to prevent and treat the gastrointestinal complication in these patientsbecome more and more significant in our daily clinical care. Intensive insulin therapy has been extensively used to control the blood glucose levels during and after surgerywith the expectation to reduce severe hyperglycemia and inflammatory reaction. Butthe information about the effects of intensive insulin therapy on peri-operativegastrointestinal complication in these patients is rare. The hypothesis of this study isthat intensive insulin therapy can reduce the morbidity of gastrointestinal complication,improve the gastrointestinal function and the clinical outcomes are also improved inpatients undergoing cardiac valve replacement with cardiopulmonary bypass.OBJECTIVE：To investigate the effects and preliminary mechanism of intensive insulintherapy on gastrointestinal function and clinical outcome in patients undergoingcardiac valve replacement with cardiopulmonary bypass.METHODS:Part1One hundred of non-diabetic patients scheduled for valve replacementsurgery were randomly assigned to control group (CONTROL, N=50) and intensiveinsulin therapy group (IT, N=50). The blood glucose levels were maintained at6.1-10.0mmol/L during surgery and3.9-8.3mmol/L after surgery at in IT group,whereas patients in control group didn’t receive insulin therapy during and afteroperation. pH values, red blood cells counting of gastric juice, gastric mucosa pH,and serum gastrin concentrations in both groups were measured before anesthesia(T1), at the initiation of CPB(T2), and0h (T3),6h (T4),12h (T5),24h (T6) and48h (T7) after the termination of CPB.Part2Forty non-diabetic patients underwent valve replacement surgery wererandomly assigned to the control group (CONTROL,N=20) and the intensive insulintherapy group (IT,N=20). The blood glucose levels were maintained at3.9-10.0mmol/L (70-180MG/DL) during surgery and4.4-8.3mmol/L (80-150MG/DL) aftersurgery in IT group, whereas patients in control group didn’t receive insulin treatment. Levels of interleukin-1β, interleukin-10, interleukin-6, tumor necrosis factor-α andinsulin in both groups were measured before anesthesia (T1), at the initiation ofCPB(T2), and0h (T3),6h (T4),12h (T5),24h (T6) and48h (T7) after thetermination of CPB.RESULTS:Part1In control group, the levels of gastric fluid pH、gastric mucosal pHdeclined after the initiation of CPB and reached the lowest level at6h after thetermination of CPB (P <0.05or P<0.01vs baseline value), then increased to baselinevalue at48h after the termination of CPB. And at different time points during CPBand thereafter, they were significantly lower in the control group than in the IT group.In contrast, the red blood cells of gastric fluid and serum gastrin were increased afterthe initiation of CPB and reached the peak at6h after the termination of CPB (P <0.01vs baseline value), then decreased and reached the baseline level at48h after thetermination of CPB. During this process, they were significantly higher in the controlgroup than in the IT group. Part2The level of serum insulin increased after theinitiation of CPB (T2) and reached the peak at the termination of CPB (T3); at thetime point of T2, it was significantly higher in the IT group than in the control group(P<0.05,P<0.01).The levels of IL-6、IL-1β and TNF-α in both groups increased afterthe initiation of CPB and reached the peak at6h after the termination of CPB. At thetime points of T3, they were significantly lower in the IT group than in the controlgroup (P<0.05,P<0.01).In contrast the level of serum IL-10increased after thetermination of CPB (T3), and reached the peak at12h after the CPB (T5). After theinitiation of CPB, it was consistently higher in the IT group than in the control group(P<0.05, or P<0.01).It was pronounced that the postoperative mechanical ventilation time and ICUdays were significantly reduced in IT group. There are no significant differences innosocomial infections and the mortality between the two groups. CONCLUSIONS:1. Intensive insulin therapy can significantly restrain the levels of gastric fluidpH, gastric mucosal pH and the secretion of gastrin in patients undergoing cardiacvalve replacement.2. Intensive insulin therapy can attenuate the levels of IL-6、IL-1β and TNF-α inpatients undergoing cardiac valve replacement.3. Intensive insulin therapy canreduce the postoperative ventilation time and ICU stay, and improve thepostoperative recovery in patients undergoing cardiac valve replacement.