The obtained data of our study focused on qualitative aspects. The results of our study in evaluation of anesthesia parameters in treatments, which associated with fat emulsion have shown faster induction, longer anesthesia, more immobilization and longer recovery time. Additionally, the survey of anesthesia depth percentages shown that emulsified isoflurane entered the anesthesia depth earlier and was removed immediately after discontinuation of administration and also, it remained longer time in deep (surgical) anesthesia during the infusion. There were no significant differences among treatments in hemodynamical variables following the administration of emulsified isoflurane, and stability in (T) and situational indicators, was observed.
In a study that examined postconditioning of emulsified isoflurane against myocardial infarction, it showed rapid recovery for emulsified isoflurane in comparison with propofol, and expressed a remarkable hemodynamic stability. Furthermore, IV administration of emulsified isoflurane required significantly less isoflurane to obtain comparable anesthetic (Yan et al., 2012).
In another study that applied 15% isoflurane lipid nanoemulsion IV for general anesthesia in dogs, the induction time of anesthesia was reduced and more stable and faster anesthesia was observed than inhalation exposure (Natalini et al,. 2017).
In the emulsification of other volatile anesthetics, such as halothane and isoflurane in pigs and dogs respectively, faster induction, faster recovery and more stable dynamic status than the inhalation treatment were reported (Musser et al., 1999; Natalini et al., 2016).
The safe concentrations of anesthetic compounds and dose-response relationship of emulsified isoflurane in rats were also investigated. Compared to propofol, the time to return from anesthesia (forepaw righting reflex) was significantly shorter. It also created a faster recovery. It had a comparable safety index compared to propofol. Moreover, the administration of emulsified isoflurane required less isoflurane to reach anesthesia and the effects of organic protection that mentioned (Zhou et al., 2006).
The formulation of fat emulsion significantly affects the kinetics and dynamics of the drug. A two-part model, in the administration of bolus and fat emulsion infusions, has been seen in these compounds. Rapid induction can be due to the rapid release of isoflurane from the fat emulsion and rapid recovery can be due to the redistribution to the fat emulsion and its removal through the lungs. The depth of anesthesia changes with the speed of infusion. The fat emulsion reduces the volume of the central compartment ten times and reduces the total volume of distribution three times and also increases the safety of the drug compared with lipid-free compounds. These compounds have lower MAC than inhaled ones and create more desirable hemodynamic profile. No significant histopathological or Hemodynamical changes were observed. (Musser et al., 1999; Yang et al., 2013; Natalini et al., 2017).
A study by Yang et al., which examined the minimum alveolar concentrations of emulsified isoflurane and inhaled isoflurane in dogs expressed that, the primary route of elimination of emulsified isoflurane was through the lungs. In the inhalation method, for inducing and maintaining of anesthesia, the difference between the alveolar gases and the arterial blood should be a positive value while in the IV emulsified isoflurane method is a negative value. However, in order to maintain the anesthesia, the partial arterial pressure of isoflurane (indicating the partial pressure in central nervous system) must be the same between the IV and inhalation methods. It is also important to balance the isoflurane concentration between the alveoli and the arterial partial pressure, which is longer in the inhalation method, so it is expected to take a longer time for induction of anesthesia and more consumption than the IV method. The infusion of fat emulsion increases the blood/gas partition coefficient, indicating that isoflurane dissolves more easily in blood and it is difficult to remove from the blood into the lungs. Also, the minimum venous concentration and the minimum arterial concentration in IV group were higher than the inhalation group (Yang et al., 2006).
In a study, the effects of IV emulsified halogenated anesthetics were examined on acute and delayed preconditioning against myocardial infarction in rabbits. It was described that the lipid vehicles increased the amount of isoflurane in the myocardium; in other words, increase the release of active anesthetic in the site of action into the cardiac myocytes (Chiari et al., 2004).
The increase of tissue solubility and the decrease of drug availability about isoflurane pulmonary elimination may explain the differences between the alveolar concentration mean in the inhalation route and the IV route. It would also decrease the amounts of required anesthetics to produce general anesthesia. On the other hand, emulsified halogenated anesthetics may increase the solubility and uptake in body tissues and both raising the volume of its distribution and potency. This may concentrate the halogenated anesthetic in body tissues including the brain, and it can be potentially harmful to patients. Besides, the blood/gas partition coefficient of IV isoflurane with inhalation showed a significant increase. It can decrease the clearance of isoflurane and reduce the pulmonary excretion (Li et al., 2014; Natalini et al., 2017).
Lipid emulsion (LE) delayed the maximum effect and prolonged the duration of epinephrine efficacy on mean arterial pressure (MAP), but did not change the maximum increase in MAP or the heart rate response. This could be interference at the level of receptor binding. LE may delay the initial release due to sequestration of epinephrine into a lipid compartment or binding of epinephrine to its receptors and/or delay its dissociation (Carreiro et al., 2013).
After IV administration, the concentration of isoflurane in pulmonary blood and then in pulmonary alveoli increases, which may cause temporary hypoxia in the animals. In this study, SpO2 values were not significantly distinct in different groups. Hemodynamic and respiratory stability were also observed despite the use of painful stimuli. No significant changes were observed in heart rate and respiration between groups. There was adequate muscle relaxation in the study. Isoflurane has been reported to exert the potential effects on the center of thermotaxis and reduce the animal's temperature. To deal with this issue, appropriate pads were used during anesthesia in all treatments (Qin et al., 2014).
Jiang et al. evaluated the preanesthetic effects of ketamine-xylazine on hemodynamical changes in anesthetized pigs with emulsified isoflurane and showed that emulsified isoflurane could produce stable hemodynamic and temperature conditions. In another study on the pig model hemodynamic and respiratory stability was reported (Jiang et al., 2014).
Limitations of this study include non-calculation of volume consumption, dose optimization, measurement of blood concentration, the minimum alveolar concentration of isoflurane, and kinetic indices of composition. However, 14 days after the study, the pigeons were monitored for mortality, biochemical and hematological parameters for evaluation of safety were not measured.