Isoflurane: Biological Mechanisms, Surgical Applications, and Side Effects
Low angle view of Caucasian male surgeon wearing surgical gloves in operation theater of hospital

Isoflurane: Biological Mechanisms, Surgical Applications, and Side Effects

Isoflurane is a stable volatile anesthetic that is one of the most readily available inhalational anesthetic agents on the clinical market. While the exact mechanism of action is unknown, it is hypothesized that these inhalational anesthetics specifically target sites in the central nervous system. In particular, isoflurane targets the alpha subunits of the GABA(A) transmembrane receptor complex (1). Upon GABA binding to the receptor, a chloride channel opens and hyperpolarizes the cell membrane to increase the depolarization threshold (2). Through the action of these inhalational anesthetics, the sensitivity of receptors to GABA binding is increased, thus prolonging and augmenting inhibition of postsynaptic neuron excitability (1). Furthermore, isoflurane has also been shown to enhance the activity of two pore domain potassium channels, which also leads to hyperpolarization of the cell membrane (1). All of these effects contribute to the suppression of neuronal action potentials and explains the anesthetic effect of isoflurane as it relates to biological mechanisms.

Of all the volatile anesthetic agents commonly used, isoflurane allows for the fastest induction and recovery times. Clinically available in 1972, isoflurane has a lower blood solubility along with fast elimination times from the lungs. Thus, it retains highly favorable pharmacokinetics for a wide range of surgical applications. Due to these characteristics, isoflurane is seen as a good candidate for outpatient surgeries, as well as for patients with cardiovascular diseases, critically ill or unstable patients, and geriatric patients (3). Using a calibrated vaporizer, surgical anesthesia can be produced with a 1.5-3% concentration and maintained using 1-2.5% combined with nitrous oxide (4). If used with oxygen, an additional 0.5-1% may be needed to maintain anesthesia (4). Isoflurane then induces a reversible state of unconsciousness, and acts as a potent cerebral, coronary, and peripheral vasodilator (5). Patient respiration should be closely monitored, as isoflurane can produce marked decreases in minute respiration at deeper levels of anesthesia, which has also been reflected in animal models (6).

It is advised that anesthesiology professionals first check for hypersensitivity to isoflurane and other halogenated agents, as well as genetic susceptibilities to malignant hyperthermia before administering isoflurane as an anesthetic agent (4). Common side effects (1-10% of the patient population) include nausea, vomiting, and shivering. Less common side effects (less than 1% of the population) include hypotension, arrhythmias, hyperthermia, elevations in white blood count, decrease in creatinine, aggravation of renal dysfunction, and respiratory depression (4,7). Higher concentrations of isoflurane have shown to cause a mean decrease in blood pressure after intubation, although this can be recovered to no further negative effect to the patient (8). Furthermore, studies have shown that isoflurane and other volatile anesthetic agents can potentially attenuate detrimental inflammatory and immune-modulatory changes as it relates to sepsis or endotoxemia (7). However, isoflurane also reduces urine output, glomerular filtration, and renal blood flow, so the overall treatment advantage is marginal (7).

Isoflurane is seen as a strong candidate for general anesthesia during surgery, with limited side effects (primarily seen to be nausea and/or vomiting) and a significantly faster recovery time. Thus, understanding the mechanisms, applications, and side effects of isoflurane by anesthesiology professionals can be beneficial for patient care during surgery.

References

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2.         Campagna JA, Forman SA. Mechanisms of Actions of Inhaled Anesthetics. N Engl J Med. 2003;15.

3.         Dohoo SE. Isoflurane as an inhalational anesthetic agent in clinical practice. 1990;31:4.

4.         Isoflurane (Rx) [Internet]. Available from: https://reference.medscape.com/drug/forane-isoflurane-343097

5.         Constantinides C, Murphy K. Molecular and Integrative Physiological Effects of Isoflurane Anesthesia: The Paradigm of Cardiovascular Studies in Rodents using Magnetic Resonance Imaging. Front Cardiovasc Med [Internet]. 2016 Jul 29 [cited 2020 Jan 30];3. Available from: http://journal.frontiersin.org/Article/10.3389/fcvm.2016.00023/abstract

6.         Murat I, Chaussain M, Hamza J, Saint-Maurice Cl. The respiratory effects of isoflurane, enflurane and halothane in spontaneously breathing children. Anaesthesia. 1987 Jul;42(7):711–8.

7.         Frithiof R, Soehnlein O, Eriksson S, Fenhammar J, Hjelmqvist H, Lindbom L, et al. The effects of isoflurane anesthesia and mechanical ventilation on renal function during endotoxemia: Isoflurane and endotoxemic renal dysfunction. Acta Anaesthesiol Scand. 2011 Apr;55(4):401–10.

8.         Grood PMRM, Harbers JBM, Egmond J, Crul JF. Anaesthesia for laparoscopy.: A comparison of five techniques including propofol, etomidate, thiopentone and isoflurane. Anaesthesia. 1987 Aug;42(8):815–23.