Effect Of Continuous Infusion Of Esmolel On Stress And Hemodynamics In Radical Esophagectomy

Stress can be defined as a "reaction by living beings to any relevant impairment". The sympathetic-adrenomedullary system is activated during the fight-flight reaction, thus representing an active role of the organism. The pituitary-adrenocortical system is activated during loss of control, submission and depression. Main valid parameters of this endocrine stress response are adrenaline, noradrenaline, ADH, ACTH and cortisol. In the per operative period, both pathways are "stressed". Human beings have developed an array of integrated stress-response axes that work in concert to return the host to a sustainable homeostatic plateau when they face the surgical stress. Surgical stress activates the higher cortical center of the brain and the spinal and baroreceptor reflexes that stimulate the hypothalamus to secrete CRH. CRH stimulates the release of ACTH from the pituitary gland, which causes the release of Glucocorticoids from the adrenal cortex. Simultaneously, in a parallel fashion, surgical stress activates the sympathetic system to release catecholamines. Glucocorticoids and catecholamines are the major effectors of stress adaptation and interact at multiple levels in a synergistic fashion. They bind to specific receptors that are present in virtually every organ, although the number and affinity of a given tissue's receptor vary dramatically for individual ligands. Receptor occupancy results in short-term and long-term effects that ultimately improve the host's prospects of tolerating the stressful event. The short-term effects result in rapid actions, such as cardiovascular and metabolic responses that benefit the host in a stress reaction. The long-term effects generally occur through alterations in gene transcription that prepare the host for, or adapt the host to, repetitive or chronic stress. Changes in the phosphorylation state of intracellular proteins are a common mode of action for both the short-term and long-term responses. These stress-responsive proteins have an enormous functional capacity: they alter enzymatic pathways, modulate hormone levels, and act as transcription factors to modify the expression of stress-responsive genes.The development of anesthesia has reached a stage where the evaluation of the usefulness of metabolic and endocrine responses is highly important. At present, these responses are commonly modulated in patients known to benefit most (e.g. patients with ischemic cardiovascular disease and patients undergoing major abdominal surgery), but no methods of totally response-free anesthesia and surgery are available, nor are there methods for the modulation of the responses on a wide clinical scale. Fortunately, in most patients undergoing conventional elective operations good anesthetic care is sufficient for blunting of the responses.Esmolol is ultra-short-acting intravenous beta-blocker without intrinsic sympathomimetic activity. It have high cardioselectivity (beta1/beta2 selectivity of esmolol(1:33) and short elimination half time(9min). Since the duration of beta-adrenergic blockade is short and cardioselectivity is high compared with traditional intravenous beta-blocker propranolol, it is titrated easily. It's use is particularly suited to critically ill patient and for perioperative period. In clinical settings, it has been used for prevention of perioperative tachycardia after endotracheal intubation or surgical incision and treatment of supuraventricular arrhythmias. Esmolol also has been used for treatment of perioperative hypertension and for reducing cardiac work in patients with ischemic heart disease. Recently, it was reported that prophylactic administration of esmolol may prevent perioperative myocardial ischemia in high risk group. This study was designed to provide a theoretical basis of rational use of esmolol perioperatively through observing the effect of esmolol continuous infusion on stress and hemodynamics in Radical Esophagectomy. Materials and MethodsSxty ASA I and II patients, ages 42～70 either sex undergoing Radical Esophagectomy under general anaesthesia were studied. All Patients' heart rate must be higher than 70 beats/min and the systolic pressure must higher than 110 mmHg. All patients were randomly divided into there groups(A,B,C) with 20 patients each. group B received esmolol with infusion rate 30μg·kg^-1·min^-1 , group C received esmolol with infusion rate 50μg·kg^-1·min^-1 and group A received normal saline after they enter the operation room. All tatients received iv esmolol 0.5mg/kg infused five minutes before intubation and extubition. Exclusion criteria included: (1)second or third-degree atrial and ventricular block; (2)congestive heart failure; (3)bronchospasm; (4)ischemia heart disease; (5)liver or renal insufficient; (6) moderate or heavy obstructive disease of the airways; (7)diabetes; (8)hypertension treated with beta-adrenergic blocker preoperatively; (9) Patients who had recently taken corticosteroids or nonsteroidal antiinflammatory medications.All patients were premedication with Atropine 0.5 mg/kg and Midazolam 0.04 mg/kg intramuscularly half an hour before surgery. An IV cannula was placed for fluid administration. Anesthesia was induced with Midazolam 0.1 mg/kg, fentanyl 3ug/kg, Propofol 2mg/kg, and Succinylcholine 1 mg/kg, Vecuronium 0.1 mg/kg was given after intubation. All patients used left bronchi Robershaw double-lumen endobronchial tube (DLT). Anesthesia was maintained with continuous infusion of Propofol 100μg·kg^-1·min^-1, fentanyl 1～2μg·kg^-1·h^-1 and Vecuronium was given interruptedly when necessary. Application of ephedrine 5 mg intravenous when Intraoperative systolic blood pressure below 80 mmHg or lower than the 80% of preoperative value ; application of atropine 0.2-0.3 mg when HR<55 bpm. Maintenance of end-tidal carbon dioxide partial pressure (PetCO₂) 35～45mmHg.All patients underwent routine ECG and noninvasive blood pressure monitor after entering the operation room. Intraopertive monitoring included measurement of noninvasive and invasive arterial blood pressure, ECG monitoring, measurement of pulse oximetry and end-tidal carbon dioxide level. HR, SBP and RPP were recorded at the following time points: 10mintues after patients into the operation room (T₀), Just intubation time(T₁), Just before incision(T₂), 30 minutes after incision (T₃), 60 minutes after incision (T₄), Just extubation time (T₅). Venous blood samples were collected at T₀, T₂, T₄ and T₅ to measure the plasm level of ACTH, Cor and Ang II concentration by radioimmunoassay(RIA), and the blood glucose concentration. Duration of the surgery, the volume of blood loss and fluid replacement, urinary production, ST-segment display cases of myocardial ischemia (ST-segment depression more than 0.1 mV or ST-segment elevation more than 0.2mV and sustained over 1 minutes can be thought myocardial ischemia), the case of ephedrine and atropine application were recorded. Statistical Analysis: all measurement data were expressed as means±Standard Deviation. Statistical analysis performed with statistical programs (SPSS 11.0 FOR WINDOWS). Data such as age, weight and duration of surgery using one-way variance analysis. Date of the haemodynamics and endocrine levels were analyzed using analysis of variance for repeated measurement date and the least significant difference(LSD).Numeration data was evaluated using a Chi-Square test. Differences were considered significant at P<0.05.Results1. Patients age, gender, weight, duration of surgery, urinary production, the volume of blood loss and fluid replacement were similar among the groups. None patient in there groups had intraoperative awareness.2. Hemodynamic response: at T₁ and T₅, HR, Systolic Blood Pressure and Heart Rate-Systolic Blood Pressure Product were significantly increased than preoperative values in group A (P<0.05). At the same time, HR, Systolic Blood Pressureand and Heart Rate-Systolic Blood Pressure Product in group A were significant increased in comparison with group C(P<0.05). At T₂, T₃ and T₄, HR and Heart Rate-Systolic Blood Pressure Product in group A were significant increased in comparison with group C(P<0.05).There was two patient (2/20) in group A suffer the acute myocardial ischemia. There were two patients (2/20) in group C and one patient (1/20) in group A and group B used ephedrine for hypopiesia. No one who's HR was less than 55 beats per minute in there groups.3. In compared with preoperative levels, the plasma level of ACTH, cortisol and glucose were significant increased at after the surgery began in there groups.(P<0.05).The plasma level of AngII in group A increased significantly after the surgery began, and increased significantly in compared with group B and group C(P<0.05).ConclusionContinuous infusion of esmolol with the rate of 50μg·kg^-1·min^-1 introperationly conbined with iv esmolol 0.5 mg/kg before intubation and extubition can restrain the effects of tracheal intubation or extubation on Heart Rate, Systolic Blood Pressure, Heart Rate-Systolic Blood Pressure Product and the plasma concentration of AngII in patients undergoing Radical Esophagectomy.