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Can the infusion of remifentanil ensure hemodynamic stability in diabetic patients with CAN?Temel Va, Arkan Ma, Temel Ga, Erkln Ab, Gzelmeri Fba Department of Anesthesiology and Reanimation, Karabk State Hospital, Karabk, Turkey.b Department of Cardiovascular Surgery, Kouyolu Heart and Research Hospital, Istanbul, Turkey.Key words: anesthesia, diabetes mellitus, cardiac autonomic neuropathy, remifentanil.Running Head: Cardiac Autonomic Neuropathy and Anesthesia.Corresponding Author:Mge Arkan, M.D.Department of Anesthesiology and Reanimation, Karabk State Hospital, Karabk, Turkey. Tel : +90 505 3969097 Fax: +90 312 310 31 00E-mail: .trCan the infusion of remifentanil ensure hemodynamic stability in diabetic patients with CAN?ABSTRACT:Background: Remifentanil is an extremely rapid and short-acting opioid analgesic which is effective in controlling acute stress responses during surgery. This prospective study was designed to investigate the effects of remifentanil with respect to hemodynamics in diabetics with Cardiac Autonomic Neuropathy (CAN).Methods: We studied 43 patients (ASA I-III) scheduled for elective abdominal laparoscopic surgery. Cardiovascular autonomic function was examined preoperatively by a combination of tests. The patients were then divided into the following groups: Group I (n=12) diabetics with CAN, Group II (n=12) diabetics without CAN, Group III (n=19) non-diabetics. For all patients, anesthesia was induced with propofol (1.5 mg/kg), remifentanil (1 g/kg), rocuronium (0.6 mg/kg), and it was then maintained with a infusion of remifentanil (0.25-0.5 g/kg/min) and sevoflurane. Mean Arterial Pressure (MAP) and Heart Rate (HR) were recorded at baseline (T0), 1 min after anesthesia induction (T1), 1 min after tracheal intubation (T2), thereafter at 10, 20, 30 min after intubation (respectively; T3, T4, T5) and 1 min after tracheal extubation (T6). Perioperative complications, mean infusion rate of remifentanil and extubation time were recorded. Results: The variability of MAP was significantly higher in Group I than in the other two groups (p0.05). HR variability was similar as well as within in the groups themselves and compared to the other groups. In Group I, the median extubation time was longer and the mean infusion rate of remifentanil significant reduced compared to Group II and III (p30 or 20, with history of severe cardiopulmonary diseases, psychiatric illness, and the patients using medications like -2 adrenergic agonists, blocker, methyldopa, MAO inhibitors, tricyclic antidepressant, and benzodiazepines.On the preoperative day, glycosylated hemoglobin (HbA1c) levels were obtained and a standardized test combination (variability in heart rate during deep breathing, valsalva ratio (30:15 ratio), change in blood pressure from lying to standing, sustained handgrip test) was used to study the patients cardiovascular reflectory reactions. (Table 1). The patients were then divided into the following groups: Group I (n=12) diabetics with CAN, Group II (n=12) diabetics without CAN, Group III (n=19) non-diabetics.Patients were given 1 mg midazolam (iv) as premedication. Perioperative monitoring included electrocardiogram (EKG) and heart rate (HR), invasive (radial artery) arterial blood pressure (MAP), and peripheral oxygen saturation (SpO2).Anesthesia was induced with propofol (1.5 mg/kg) followed by rocuronium (0.6 mg/kg) to facilitate orotracheal intubation. Two minutes after the propofol injection, 1 g/kg initial dose of remifentanil was given for 60 seconds. After tracheal intubation, the patients were ventilated to normocapnia in 50 % O2 in air. Anesthesia was maintained with sevoflurane (at minimum alveolar anesthetic concentration 1) and the infusion of remifentanil throughout surgery in all patients. The infusion was started at 0.25 g/kg/min and subsequently increased stepwise by 0.5 g/kg/min increments if insufficient anesthesia was suspected. Insufficient anesthesia was defined as a heart rate that exceeded preinduction values by 15 % or a systolic arterial blood pressure that exceeded baseline values by 20 % for at least 1 min. Hypotension, defined by a systolic arterial blood pressure 80 mmHg or a MAP 10 breaths/min, ETCO2 40 mmHg). Extubation time (from end of anesthesia to extubation of the trachea), perioperative complications and mean infsion rate of remifentanil were recorded. After extubation, the patients remained in the recovery room for 1 hour. Hemodynamic parameters (HR, MAP, SpO2) were recorded at baseline (T0), 1 min after anesthesia induction (T1), 1 min after tracheal intubation (T2), thereafter at 10, 20, 30 min after intubation (respectively; T3, T4, T5) ,and at 1 min after tracheal extubation (T6). In statistical analyses we used General Linear Model for repeated measurements, t-test, Chi-square and Mann-Whitney U-test when appropriate. A p-value 0.05 was considered significant.RESULTS:The demographic data, history of hypertension, HbA1c levels and the operation time for all groups are given in Table 2. No significant differences were observed between the groups in terms of gender, BMI and operation time. The history of hypertension, age and HbA1c levels were significantly higher in Group I in comparison to Group II and III (p0.05).The baseline HR was similar in all three groups. Baseline MAP, however, was higher in Group I than in Group II and III (p0.05).After induction of anesthesia, MAP significantly decreased below the baseline values in all three groups (p0.05). However, only MAP in Group I was significantly lower than Group II and III (p0.05). With tracheal intubation, MAP significantly increased over the after induction of anesthesia values in all three groups (p0.05). Within 10 min after tracheal intubation, MAP gradually decreased to the baseline levels in all three groups. No significant changes in HR values were observed between the groups (Table 3).The mean infusion rate of remifentanil in Group I was significant lower than Group II and III (p0.01). The median extubation time in Group I was significantly higher than in the two other groups (p1.21 1.11-1.2015 beat/min.11-14 beat/min1.041.01-1.031.00Blood pressure response to standingMeasure blood