Isoflurane


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Tyson Hawkley


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Phillip Hynes


Updated:
1/16/2019 9:55:49 AM

Indications

Isoflurane is a volatile anesthetic that is approved by the Federal Drug Administration (FDA) for the induction and maintenance of general anesthesia. Similar to most volatile anesthetics, isoflurane is a halogenated ether compound that is a structural isomer to its predecessor, enflurane, and has been approved for use in the United States since 1979. Unlike enflurane, isoflurane is a non-flammable volatile anesthetic, but carries a strong pungent odor that makes it difficult to use for inhalational induction of general anesthesia.

Mechanism of Action

Induction and maintenance of general anesthesia are achieved through various sites of action. The most likely of these sites include inhibition of neurotransmitter-gated ion channels such as GABA, glycine, and N-methyl-d-aspartate (NMDA) receptors in the central nervous system (CNS).[1] Inhibition of these receptors helps to produce the amnesia and sedation needed for adequate surgical conditions. Volatile anesthetics in general also have sites of action within the spinal cord that contribute to skeletal muscle relaxation through inhibition of NMDA-type glutamate and glycine receptors.

Other sites of action have organ system specific effects. With regards to cardiac function, isoflurane has minimal impact on left ventricular function but does cause a dose-dependent decrease in systemic vascular resistance due to mild beta-adrenergic stimulation. This would lead to decreased cardiac preload and in turn decreased cardiac output, but a rise in heart rate mitigates the decrease in cardiac output. In addition to decreasing systemic vascular resistance, it also causes coronary dilation. This could theoretically lead to a coronary steal phenomenon leading to diversion of blood away from a fixed stenotic lesion. This has largely been overshadowed by isoflurane's cardioprotective effect which occurs through ischemic preconditioning.[2]. This helps in reducing the degree of ischemia and reperfusion injury to the heart.

Isoflurane also affects the respiratory system by causing a large decrease in tidal volumes with minimal increase in respiratory rate leading to an overall decrease in minute ventilation. The decrease in minute ventilation causes an increased PaCO2.

At concentrations greater than 1 MAC, isoflurane causes an increase in cerebral blood flow and intracranial pressure. Although blood flow is increased, the cerebral metabolic rate is decreased, and concentrations of 2 MAC can produce an electrically silent electroencephalogram.

Isoflurane also produces a dose-dependent decrease in renal and hepatic blood flow with no clinical effect on renal or hepatic function.

Administration

Administration of volatile anesthetics, including isoflurane, is based on each agent’s individual minimum alveolar concentration (MAC), which is used as a surrogate for the partial pressure of each agent in the brain. MAC is then defined as the alveolar concentration needed to prevent movement in 50% of patients in response to surgical incision. MAC is based on the agent’s partial pressure relative to the atmospheric pressure. At sea level, the MAC of isoflurane is 1.2%, which can otherwise be stated as 1 MAC of isoflurane.

MAC is affected by several factors. Factors that increase MAC include young age, chronic alcohol abuse, and hypernatremia. Factors that decrease MAC include old age, hypothermia and hyperthermia, acute intoxication, and most intravenous anesthetics to include opioids, benzodiazepines, dexmedetomidine, and ketamine. The most impressive of all these factors is the effect of age, which cause a 6% decrease in MAC per decade of age above the age of 40 [3].

Isoflurane is administered via a specifically designed variable bypass vaporizer. This vaporizer has been calibrated to deliver a set percentage of gas based on the individual volatile’s vapor pressure over a broad range of flow rates and temperatures. Vapor pressure is defined as the pressure exerted by a vapor that is in thermodynamic equilibrium with its condensed phase, in the case of volatile anesthetics the liquid phase, at a given temperature in a closed system. It can also be thought of the pressure at which a liquid will boil. In the case of isoflurane, which has a vapor pressure of 240 mm Hg, at a normal atmospheric pressure of 760 mm Hg, the resting state is in its liquid form. If the atmospheric pressure were decreased to 240 mm Hg the resting state of isoflurane would be as a gas. This is important to recognize because each vaporizer is calibrated to a specific volatile anesthetic and filling of a vaporizer with a different volatile anesthetic will result in inappropriate delivery of the volatile anesthetic. It is worthy to note, that isoflurane has a similar vapor pressure to halothane (243 mm Hg). This means that if halothane were placed in the isoflurane vaporizer or vice versa the difference in amount delivered would be minimal.

Adverse Effects

Isoflurane should be carefully titrated to the patient’s hemodynamics as it can cause precipitous drops in blood pressure due to dose-dependent peripheral vasodilation. Patients who are hypovolemic may be especially sensitive to these effects. Otherwise, there are no specific adverse effects of isoflurane.

Contraindications

All halogenated volatile anesthetics, including isoflurane, are known triggers of malignant hyperthermia in susceptible patients. Any patient with a known or suspected personal or family history of malignant hyperthermia should be considered to be at increased risk of developing malignant hyperthermia. Appropriate precautions should be taken to include flushing out the anesthesia machine per manufacturer recommendations and using a total intravenous anesthetic to induce and maintain general anesthesia.

Monitoring

There are no specific monitoring parameters for those undergoing general anesthesia with isoflurane compared to other volatile anesthetics. All patients undergoing general anesthesia should have all basic monitoring devices placed before induction of general anesthesia to include:

  • Continuous pulse oximetry
  • Non-invasive blood pressure monitoring
  • Continuous electrocardiography
  • Inspired and expired oxygen, carbon dioxide, and volatile anesthetic monitoring
  • Airway pressure
  • Peripheral nerve stimulation (if neuromuscular blocking drugs are used)
  • Body temperature

Toxicity

Isoflurane is metabolized to trifluoroacetic acid, which increases concern for renal impairment. Although, it has been shown that fluoride fluid levels may rise as much as 50 micromol/L without evidence of postoperative renal dysfunction.

There has also been increased concern for neurotoxicity, especially in the developing brain. These effects have been seen in animal models, where it has been demonstrated that both intravenous and inhalational anesthesia promote neuronal apoptosis.[4] Animal studies have also found some evidence of learning deficiencies and behavioral changes after undergoing anesthesia with intravenous or inhalational agents. It is hard to translate these effects from animals to humans due to different biological systems and the higher doses needed by animal species to produce the same anesthetic effect in human subjects. This has led to further investigations between the known neuroprotective and neurotoxic effects of volatile anesthetics.

Enhancing Healthcare Team Outcomes

Isoflurane should only be administered by qualified health professionals who have been trained in managing a patient under general anesthesia. Communication between the surgeon and the anesthesia provider is essential to time the emergence of the patient from general anesthesia appropriately. This is due to isoflurane's increased blood solubility coefficient leading to increased times for both induction of and emergence from general anesthesia. Teamwork is a large part of patient safety in the operating room and good communication will not only improve operating room efficiency but will also help to increase patient safety.[5] (Level V)


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Isoflurane - Questions

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How soon is it safe to drive after anesthesia with isoflurane?



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What anesthetic agent is safest to use in cirrhotic patients?



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A patient developed fulminant hepatitis after a major surgery. What is the most likely cause of liver damage?



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Which of the following is a rare but serious adverse reaction to isoflurane?



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A 43-year-old male with no significant medical history is undergoing general anesthesia for a cholecystectomy. After induction with propofol muscle relaxation is induced with vecuronium. Maintenance of anesthesia is continued with isoflurane. What is the site of action for the muscle relaxation caused by isoflurane?



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Which of the following physiological effects are seen with isoflurane?



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A helpful medical student noticed that the isoflurane vaporizer was low and needed to be refilled. Unable to find more isoflurane and thinking all vaporizers were the same, he eagerly filled the isoflurane vaporizer with sevoflurane. How will this affect the dose of volatile anesthetic needed to achieve 1 MAC of volatile anesthetic?



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A 16-year-old male in good health with no significant medical history is undergoing general anesthesia for repair of a torn anterior cruciate ligament (ACL). The patient remained hemodynamically stable throughout induction of general anesthesia. 30 minutes into the surgery the patient’s temperature begins to rise along with his end-tidal carbon dioxide levels. Upon assessment of the patient, the endotracheal tube is patent. The surgeon then reports that the patient’s leg has become markedly rigid and asks for further paralysis. Use of what agent would lead to the above findings in this patient?



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A 37-year-old female who sustained 75% total body surface area burns two days prior is brought back to the operating room for initial burn debridement. What risks should be considered when deciding to use isoflurane for maintenance of general anesthesia?



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Isoflurane - References

References

Jones MV,Brooks PA,Harrison NL, Enhancement of gamma-aminobutyric acid-activated Cl- currents in cultured rat hippocampal neurones by three volatile anaesthetics. The Journal of physiology. 1992 Apr     [PubMed]
Van Allen NR,Krafft PR,Leitzke AS,Applegate RL 2nd,Tang J,Zhang JH, The role of Volatile Anesthetics in Cardioprotection: a systematic review. Medical gas research. 2012 Aug 28     [PubMed]
Nickalls RW,Mapleson WW, Age-related iso-MAC charts for isoflurane, sevoflurane and desflurane in man. British journal of anaesthesia. 2003 Aug     [PubMed]
Orser BA,Suresh S,Evers AS, SmartTots Update Regarding Anesthetic Neurotoxicity in the Developing Brain. Anesthesia and analgesia. 2018 Apr     [PubMed]
Sexton JB,Makary MA,Tersigni AR,Pryor D,Hendrich A,Thomas EJ,Holzmueller CG,Knight AP,Wu Y,Pronovost PJ, Teamwork in the operating room: frontline perspectives among hospitals and operating room personnel. Anesthesiology. 2006 Nov     [PubMed]

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