Influence of Anesthetics on Clinical Outcome During Cardiac Surgery in Adults
Condition: CHD - Coronary Heart Disease
MeSH terms: Heart Diseases; Coronary Disease; Coronary Artery Disease; Myocardial Ischemia
Study type: Interventional

Summary: 
      Abstract Cardiac surgery in adults is associated with the occurrence of post-operative
      complications. Even minor complications can increase the cost of their treatment. Given the
      potentially preventable nature of a number of these postoperative complications, preventive
      methods should be used to improve outcomes after cardiac surgery. One of them, is the choice
      of anaesthetic technique.

      Objectives: To evaluate the effects of sevoflurane, isoflurane and propofol on blood oxygen
      transport function and body energy expenditure during cardiac surgery in adults.

      Materials and methods. A total of 90 patients were included in the study. All patients were
      divided into 3 groups: 1- (n=30) included patients who were anesthetized with propofol. The
      second group (n=30) consisted of patients who underwent sevoflurane inhalation anaesthesia.
      Group 3 (n=30) was treated with isoflurane. All patients underwent coronary artery bypass
      grafting under cardiopulmonary bypass.
    

Detailed description: 
      Introduction Anaesthetic support for various types of cardiac surgery, such as coronary
      artery bypass grafting (CABG), heart valve repair or replacement, ascending aorta surgery,
      heart transplantation and surgical treatment of congenital heart disease, share many
      principles. Indirect calorimetry can be an indicator of homeostatic changes during surgery.
      Stress increases oxygen consumption (VO2) and during anaesthesia there is a decrease in VO2.

      Cardiac surgery in adults is associated with the occurrence of postoperative complications
      [1]. Even minor complications, can increase the cost of their treatment. Given the
      potentially preventable nature of a number of these postoperative complications, preventive
      methods should be used to improve outcomes after cardiac surgery. One of them, is the choice
      of anaesthetic technique [2].

      Tissues vary considerably in their sensitivity to hypoxia. Neurons tolerate hypoxia for only
      a few minutes, whereas the smooth muscles of the bladder go several days without oxygen. This
      has important implications for oxygen transport and monitoring of tissue hypoxia in patients.
      The mechanisms controlling the distribution of oxygen in the body are not fully understood
      (3). Increased oxygen extraction, the ratio of consumption to transport, has been associated
      with poor outcome after surgery. The authors note [4] a -65 ml decrease in oxygen consumption
      after general anaesthesia. Researchers [5,6] found that surgery and anaesthesia did not
      significantly affect oxygen consumption and energy expenditure during anaesthesia. However,
      Julia Jakobsson et al (2021) state that general anaesthesia reduced VO2 by approximately one
      third in elderly patients undergoing major abdominal surgery. These changes require further
      evaluation in relation to outcomes and surgery (7). Cerebral blood flow was reduced by 27.6%
      and cerebral vascular resistance by 51% at moderate propofol concentrations. Brain oxygen
      consumption was reduced by 18.2% [8]. Oxygen delivery (DO2) is an important marker of O2
      transport than arterial blood oxygen saturation (SaO2). Anaesthetics (propofol or
      sevoflurane) had no significant effect on DO2 . In addition, no correlation was found between
      SaO2 and DO2. DO2 data may provide useful additional information about the patient's
      condition, especially with low SaO2 [9]. A decrease in metabolic rate during anaesthesia has
      been noted in patients with hypothermia, but this did not alter DO2. A significant decrease
      in O2ER might be partly due to a shift to the left of the oxyhemoglobin dissociation curve,
      as indicated by a decrease in P50 [10]. Oxygen consumption during general anaesthesia was
      independent of the type of anaesthetics. General anaesthesia leads to a marked decrease in
      oxygen consumption, but during recovery the O2 uptake can increase dramatically. Meperidine
      can suppress and reduce postoperative VO2 to the level observed after TIA [11]. Indirect
      calorimetry can be an indicator of homeostatic changes during surgery. Stress increases
      oxygen consumption and during anaesthesia there is a decrease in VO2 due to lack of kinetic
      energy as a cellular metabolic response to surgical trauma and anaesthesia. More research is
      needed to find out which oxygen consumption measurement system is the most appropriate for
      anaesthesia and what the VO2 limit values might be [12].

      In view of the above opinion of the authors and the lack of studies that have shown the
      effects of sevoflurane, isoflurane and propofol on energy expenditure, blood oxygen and
      oxygen transport function, this needs to be further investigated.

      Objectives: To evaluate the effects of sevoflurane, isoflurane and propofol on blood oxygen
      transport function and body energy expenditure during cardiac surgery in adults.

      Methods Study type: single-centre prospective randomised clinical trial. The study includes
      data from 90 patients operated on at the Cardiosurgery Department of the RSE Medical Centre
      Hospital of the President's Affairs Administration of the Republic of Kazakhstan. All
      patients underwent coronary artery bypass grafting under cardiopulmonary bypass (CPB). This
      research work was conducted between 2021 and 2022. To calculate the sample size, we used the
      formula n=t2*D*N/confidence interval*N+t2*α, which will allow to identify the static
      significance of the study.

      This research was approved by the Local bioethical committee of Non-commercial joint-stock
      company AMU №3 and written informed consent was obtained from all subjects.

      All patients were divided into 3 groups: 1 (control group) (n=30) consisted of patients who
      underwent anaesthesia with propofol (P). The second group (n=30) were patients who received
      sevoflurane inhalation anaesthesia (S). Group 3 (n=30) with isoflurane (I).

      The study was conducted in 5 stages:

        1. determined the patient's baseline values before anaesthesia;

        2. after tracheal intubation;

        3. Before the CPB;

        4. after the CPB;

        5. The post-operative period. Before induction into anaesthesia, haemodynamic monitoring
           with Nihon Kohden monitors (Japan) was initiated on admission to the operating theatre.
           The right radial artery was catheterised for invasive systemic pressure monitoring and
           arterial blood sampling, then a catheter was inserted into the central jugular vein
           (under ultrasound machine control) and guided into the right atrium for mixed venous
           blood sampling.

      Cardiac stroke volume was determined by transthoracic echocardiography (CS=end diastolic
      volume - end systolic volume). Cardiac output (CO=CS x heart rate), cardiac index (CI=CB/body
      surface area) were determined. Blood oxygen content was determined using the formula CaO2
      (arterial blood gas ABG) and CvO2 (central mixed venous BG) = [(1.34 × Hb × SO2) + (PO2 ×
      0.031)] / 100, arteriovenous difference = CaO2-CvO2. Oxygen delivery was determined using the
      formula (DO2 = CI* CaO2), oxygen consumption (VO2 = Cardiac index (CI)*AVR or VO2 = CB ×
      (CaO2 - CvO2) ~ CB × Hb × 1.34 × (SaO2 - SvO2) / 100).

      In the second stage, after tracheal intubation, indirect calorimetry was used to determine
      VO2, energy expenditure during anaesthesia, using a "Spirometry" (Oxford, UK), which was
      connected to an endotracheal tube and continuously showed oxygen demand and energy
      expenditure. Additionally, cardiac output was determined using Fick's formula. In the third
      and fourth stages of anaesthesia the same tests (cardiac output, cardiac index, consumption,
      oxygen delivery and energy expenditure) were determined. In the last stage to assess the
      pharmaco-efficiency of anaesthetics, the consumption of muscle relaxants and opioid
      analgesics was calculated. The time of extubation and the time of transfer of the patient to
      the specialist department were determined.

      All patients were given the same type of premedication: 30-40 minutes before surgery, 0.3
      mg/kg promedol was administered intramuscularly. Patients continued to take their usual
      baseline drugs both before and on the day of surgery to prevent withdrawal syndrome and to
      reduce the risk of myocardial ischaemia in the perioperative period.

      All patients in both groups were given fentanyl in a dose of 5-7 µg/kg, ketamine 1.5-2 mg/kg,
      and propofol 1-1.5 mg/kg intravenously fractionally. Pipecuronium bromide 0.04-0.07 mg/kg was
      used as muscle relaxant in all patients. To maintain anaesthesia in Group 1 P, propofol was
      used as an anaesthetic in a dose of 5-6 mg/kg/h intravenously on a perfusor (BBRAUN). In
      Group 2, sevoflurane was used as an anaesthetic in a dose of - 1.7-1.9 MAC. In Group 3
      isoflurane was used as anaesthetic. In all groups fentanyl 100 µg intravenously was
      administered fractionally to increase heart rate and blood pressure, also pipecuronium
      bromide 2 mg intravenously for muscle relaxation. During CPB in all patients in all groups,
      propofol was used at a dose of 6 mg/kg/h intravenously via perfusion, analgesic regimen:
      fentanyl 100 µg intravenously every 30 min; myorelaxant piperonium bromide 2 mg every 40-60
      min. Norepinephrine solution was administered at a dose of 0.05 µg/kg/min intravenously on
      perfusor after CPB in all patients at the same dosages in all groups.

      Aim to use cardiotonic drugs:

        1. in order to maintain mean arterial perfusion pressure (CPB causes cytokine storm and
           vasodilation).

        2. for inotropic support (for reperfusion syndrome, resulting in a lower ejection
           fraction).

      The depth of anaesthesia was monitored with a processed electroencephalogram, such as a BIS.

      Statistical analysis was performed using IBM SPSS Statistics 20 package using one-factor
      analysis of variance for independent samples and nonparametric Kraskel Wallis test. The
      Kraskel-Wallis test was applied only to myorelaxant consumption, as the distribution was
      non-normal on this parameter. A Pearson and Spearman correlation analysis was also performed
      to determine the significance of the association between cardiac index and oxygen
      consumption, as well as energy expenditure.
    

Intervention name(s): Propofol; Isoflurane; Sevoflurane
Intervention type(s): Drug; Drug; Drug
Intervention description(s): To maintain anaesthesia in Group 1 P, propofol was used as an anaesthetic in a dose of 5-6 mg/kg/h intravenously on a perfusor.; isoflurane was used as anaesthetice of - 1.1-1.2 MAC.; sevoflurane was used as an anaesthetic in a dose of - 1.7-1.9 MAC
Other intervention name(s): Propofol;
Intervention MeSH terms: Propofol; Sevoflurane; Isoflurane
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: Single (Participant)
Primary purpose: Supportive Care
Keywords: sevoflurane; isoflurane; propofol; Oxygen consumption; energy expenditure; oxygen transport; metabolic status