Isoflurane (Forane) - Uses, Dose, Side effects, MOA, Brands

An inhaled general anaesthetic called isoflurane (Forane) is used to induce and maintain general 

anaesthesia.

Isoflurane (Forane) Uses:

  • Anesthesia:

    • Inhaled Isoflurane is used in the maintenance of general anesthesia.
    • Data regarding its use in obstetrical anesthesia is limited.

Isoflurane dose in Adults:

Note:

When patients are put to sleep for a procedure, they might start coughing, holding their breath, or having a spasm in their throat.

To prevent these issues, a very quick-acting barbiturate can be used.

In kids, the amount of anesthetic needed is more, but in older people, it's less.

Before the procedure, the doctor will decide on the right pre-medication. It's important to know that the drug used might slightly increase fluids in the body and make the heart beat faster.

Whether to use drugs that affect the nervous system along with isoflurane is a choice the doctor will make based on the situation.

Isoflurane (Forane) Dose in the Anesthesia: Inhalation:

  • Induction:

    • 1.5% to 3% of isoflurane in oxygen, or an oxygen-nitrous oxide combination.
  • Maintenance:

    • Along with 1% to 2.5% nitrous oxide
    • Add 0.5% to 1% with oxygen only

Use in Children:

 

For information on the use of isoflurane in children, please refer to the "Dose in Adults."

Isoflurane (Forane) Pregnancy Risk Category: C

  • Regarding pregnancy, isoflurane (Forane) falls under Pregnancy Risk Category C.

  • This means the medication can pass through the placental barrier to the baby.

  • Studies on animals suggest that prolonged use of general anesthesia and certain drugs during pregnancy may affect the development of the baby's brain.
  • If a surgery is planned to last more than three hours, it's important for the healthcare team to carefully consider the potential risks and benefits of using isoflurane.
  • Using isoflurane during obstetrical sedation can lead to fetal depression or relaxation of the uterus.
  • The American College of Obstetricians and Gynecologists (ACOG) suggests that pregnant women can undergo life-saving surgeries at any trimester, but elective procedures should be postponed until after delivery.

Use of isoflurane while breastfeeding

  • We don't know if the drug will pass into breast milk. Even though it's not the first choice for breastfeeding moms, it can be used if needed.
  • If a surgery is planned, it's suggested to pump and store breast milk before the procedure.
  • The mom can start breastfeeding again once she's awake.
  • If there's a concern that the baby might have low blood pressure or stop breathing, saving some milk before and after the surgery might be a good idea.

Dose in Kidney Disease:

The information from the manufacturer doesn't include details on changing the dose for people with kidney problems.

Dose in Liver disease:

According to the manufacturer's instructions, there is no information on changing the dose for individuals with liver disease.

Isoflurane (Forane) Side effects.

  • Cardiovascular:

    • Tachycardia (Transient)
    • Cardiac Insufficiency
    • Hypotension
    • Cardiac Arrhythmia
  • Central Nervous System:

    • Shivering
    • Malignant Hyperthermia
    • Cognitive Dysfunction (May Persist For ≤3 Days After Administration)
    • Mood Changes (May Persist For ≤6 Days After Administration)
  • Endocrine & Metabolic:

    • Hyperkalemia (Perioperative)
    • Decreased Serum Cholesterol
    • Hyperglycemia
    • Decreased Blood Urea Nitrogen
  • Gastrointestinal:

    • Nausea
    • Intestinal Obstruction
    • Vomiting
  • Hematologic & Oncologic:

    • Leukocytosis (Transient)
  • Hepatic:

    • Decreased Alkaline Phosphatase
  • Neuromuscular & Skeletal:

    • Laryngospasm (Related To Induction)
  • Renal:

    • Increased Serum Creatinine
  • Respiratory:

    • Respiratory Depression
    • Cough (Related To Induction)

Contraindications to Isoflurane (Forane):

  • Allergy to any of the components, other halogenated substances, or the drug.

Canadian labeling: Additional contraindications not in US labeling

Zavzpret may not be suitable for:

  • Individuals with a history of liver problems or those who had issues with anesthesia medications in the past.
  • People who experienced liver problems, jaundice (yellowing of the skin), unexplained fever, high white blood cell count, or increased eosinophils after using a similar type of anesthesia.
  • Those who cannot undergo general anesthesia due to specific reasons.

Warnings and precautions

  • Cardiovascular effects

    • Using this drug can lead to the blood vessels in the periphery widening, causing a drop in blood pressure that depends on the dose.

      It's important to note that this drop in blood pressure can be problematic for individuals with coronary artery disease, as it might contribute to a heart attack.

      People who already have low blood pressure, low blood volume, or are not in a stable hemodynamic condition should avoid using this medication.

      There's a potential risk of prolonging the QT interval, especially for patients already at high risk. Those considering the drug should be cautious.

      Even though this drug doesn't directly cause issues with the heart's electrical conduction and doesn't make the heart more sensitive to certain types of arrhythmias, like some other anesthetics, it can lead to an increase in heart rate and widen the coronary blood vessels.

  • Reduced blood flow

    • It is thought that this drug may decrease the blood flow to the liver, kidneys, and spleen.
  • Hepatic effects

    • The use of this drug has been associated with liver problems, including potentially fatal hepatitis. People who have been sensitive to similar halogenated drugs in the past are at a higher risk of developing hepatitis, a condition related to liver sensitivity.
  • Hyperkalemia

    • Inhaled anesthetics can bring about high levels of potassium during surgery, which could lead to irregular heartbeats.

    • In many cases, patients also received succinylcholine at the same time, as noted in case reports.

    • Children with certain neuromuscular conditions, like Duchenne muscular dystrophy, are more prone to experiencing high potassium levels.

    • This can result in increased potassium and myoglobin (a muscle protein) in the blood.

    • If there are signs of irregular heartbeats or high potassium levels, it's crucial to check and treat them right away.

 

  • Increased intracranial pressure

    • As the drug leads to the widening of blood vessels in the brain, it can potentially cause an increase in intracranial pressure.
  • Malignant hyperthermia

    • This drug has the potential to trigger malignant hyperthermia, a severe reaction that raises body temperature dangerously. Individuals at a high risk for malignant hyperthermia should avoid using this medication.

  • Anesthesia for obstetrical purposes:

    • The use of isoflurane during abortions has been linked to greater blood loss compared to the use of halothane.
  • Respiratory depression

    • The drug can lead to a reduction in breathing, and this effect becomes stronger with higher doses.

    • It also dampens the body's natural response to low oxygen levels and high carbon dioxide levels.

  • Heart Failure:

    • The American Heart Association has pointed out that isoflurane is a substance that can worsen heart function, according to their scientific statement.

Isoflurane: Drug Interaction

Risk Factor C (Monitor therapy)

Alcohol (Ethyl)

Alcohol's CNS depressing effect may be amplified by CNS depressants (Ethyl).

Alfuzosin:

The hypotensive effects of blood pressure-lowering medications  may be strengthened.

Alizapride

CNS depressants may have an enhanced CNS depressant impact.

Antipsychotic Agents (Second Generation [Atypical])

Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]).

Barbiturates

May enhance the hypotensive effect of Blood Pressure Lowering Agents.

Benperidol

May enhance the hypotensive effect of Blood Pressure Lowering Agents.

Blood Pressure Lowering Agents

May enhance the hypotensive effect of HypotensionAssociated Agents.

Brexanolone

CNS Depressants may enhance the CNS depressant effect of Brexanolone.

Brimonidine (Topical)

May enhance the CNS depressant effect of CNS Depressants.

Brimonidine (Topical)

May enhance the hypotensive effect of Blood Pressure Lowering Agents.

Bromopride

May enhance the CNS depressant effect of CNS Depressants.

Cannabidiol

May enhance the CNS depressant effect of CNS Depressants.

Cannabis

May enhance the CNS depressant effect of CNS Depressants.

Chlorphenesin Carbamate

May enhance the adverse/toxic effect of CNS Depressants.

CNS Depressants

Other CNS depressants' harmful or toxic effects might be exacerbated.

Diazoxide

May enhance the hypotensive effect of Blood Pressure Lowering Agents.

Dimethindene (Topical)

May enhance the CNS depressant effect of CNS Depressants.

Doxylamine

May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended.

Dronabinol

May enhance the CNS depressant effect of CNS Depressants.

DULoxetine

Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine.

EPINEPHrine (Nasal)

The arrhythmogenic effects of inhaled anaesthetics may be increased (Nasal).

EPINEPHrine (Oral Inhalation)

The arrhythmogenic effects of inhaled anaesthetics may be increased  (Oral Inhalation).

Esketamine

CNS depressants may have an enhanced CNS depressant impact.

Fenoterol

Inhalational Anesthetics may enhance the arrhythmogenic effect of Fenoterol.

Formoterol

The arrhythmogenic impact of formoterol may be enhanced by inhalational  anaesthetics.

Haloperidol

QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTcprolonging effect of Haloperidol.

Herbs (Hypotensive Properties)

May enhance the hypotensive effect of Blood Pressure Lowering Agents.

HydrOXYzine

May enhance the CNS depressant effect of CNS Depressants.

Hypotension-Associated Agents

Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents.

Isoniazid

may lower the serum level of CYP2E1 substrates (High risk with Inhibitors).  In particular, it may lower serum concentrations of CYP2E1 substrate below  baseline following isoniazid cessation.  The serum concentration of CYP2E1 Substrates may rise when isoniazid  is used (High risk with Inhibitors).

Kava Kava

CNS depressants' harmful or toxic effects could be increased.

Levodopa-Containing Products

Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products.

Lofexidine

CNS depressants may have an enhanced CNS depressant impact.  Management: Separate drug interaction monographs go into further detail about the  medications indicated as exceptions to this book.

Lormetazepam

May enhance the hypotensive effect of Blood Pressure Lowering Agents.

Magnesium Sulfate

May enhance the CNS depressant effect of CNS Depressants.

MetyroSINE

The sedative effects of metyroSINE may be strengthened by CNS depressants.

Minocycline (Systemic)

CNS depressants may have an enhanced CNS depressant impact.

Molsidomine

May enhance the hypotensive effect of Blood Pressure Lowering Agents.

Nabilone

May enhance the CNS depressant effect of CNS Depressants.

Naftopidil

The hypotensive effects of blood pressure-lowering medications  may be  strengthened.

Neuromuscular-Blocking Agents (Nondepolarizing)

The neuromuscular-blocking impact of neuromuscular-blocking agents  may be  enhanced by inhaled anaesthetics (Nondepolarizing).

Nicergoline

The hypotensive effects of blood pressure-lowering medications  may be  strengthened.

Nicorandil

The hypotensive effects of blood pressure-lowering medications may be  strengthened.

Nitroprusside

Nitroprusside's hypotensive impact may be strengthened by blood pressure-lowering medications.

Pentoxifylline

The hypotensive effects of blood pressure-lowering medications may be  strengthened.

Pholcodine

Pholcodine's hypotensive impact may be strengthened by blood pressure lowering  medications.

Phosphodiesterase 5 Inhibitors

The hypotensive effects of blood pressure-lowering medications may be  strengthened.

Piribedil

Piribedil's CNS depressing effects may be enhanced by other CNS depressants.

Pramipexole

The sedative effects of pramipexole might be enhanced by CNS depressants.

Prostacyclin Analogues

The hypotensive effects of blood pressure-lowering medications may be  strengthened.

QT-prolonging Agents (Highest Risk)

QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk).

Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.

Quinagolide

May enhance the hypotensive effect of Blood Pressure Lowering Agents.

Ritodrine

May enhance the adverse/toxic effect of Inhalational Anesthetics.

ROPINIRole

CNS Depressants may enhance the sedative effect of ROPINIRole.

Rotigotine

CNS Depressants may enhance the sedative effect of Rotigotine.

Rufinamide

May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced.

Selective Serotonin Reuptake Inhibitors

CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced.

Tetrahydrocannabinol

May enhance the CNS depressant effect of CNS Depressants.

Tetrahydrocannabinol and Cannabidiol

May enhance the CNS depressant effect of CNS Depressants.

Trimeprazine

May enhance the CNS depressant effect of CNS Depressants.

Risk Factor D (Consider therapy modification)

Amifostine

Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine.

Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered.

Bambuterol

May enhance the arrhythmogenic effect of Inhalational Anesthetics.

Management: Some labels recommend specifically avoiding halothane; others recommend separating administration by at least 6 hours; other bambuterol labels do not mention this possible interaction.

Blonanserin

CNS Depressants may enhance the CNS depressant effect of Blonanserin.

Buprenorphine

CNS Depressants may enhance the CNS depressant effect of Buprenorphine.

Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants.

Chlormethiazole

May enhance the CNS depressant effect of CNS Depressants.

Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used.

CYP2E1 Inhibitors (Strong)

May decrease the metabolism of CYP2E1 Substrates (High risk with Inhibitors).

Droperidol

CNS depressants may have an enhanced CNS depressant impact.  Consider lowering the dosage of droperidol or other CNS drugs (such as opioids or barbiturates)  when they are used concurrently.  In separate drug interaction monographs, exceptions  to this monograph are covered in more detail.

EPINEPHrine (Systemic)

The arrhythmogenic effects of inhaled anaesthetics may be increased (Systemic).  Treatment: When treating patients who are now receiving or have just had inhalational  anaesthetics, provide epinephrine with extra caution.  Use epinephrine at lower dosages than usual and keep an eye out  for the emergence of cardiac arrhythmias.

Flunitrazepam

Flunitrazepam's CNS depressing effects may be enhanced by other CNS depressants.

HYDROcodone

The CNS depressive action of HYDROcodone may be enhanced by CNS depressants.  Management: Whenever feasible, refrain from using hydrocodone and benzodiazepines  or other CNS depressants concurrently. Only in the event that other treatment choices are  insufficient should these medications be combined. Limit the duration and dosage of each  medicine  when used together

Lemborexant

CNS depressants may have an enhanced CNS depressant impact.  Management: Due to the possibility of additive CNS depressant effects when lemborexant and  concurrent CNS depressants are administered concurrently, dosage modifications may be required.  Effects of CNS depressants must be closely monitored.

Methotrimeprazine

CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants.

Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after a clinically effective methotrimeprazine dose is established.

Obinutuzumab

The hypotensive effects of blood pressure-lowering medications may be strengthened.  Management: Take into account temporarily stopping blood pressure-lowering drugs 12 hours before the start of the obinutuzumab infusion and  keeping them off until 1 hour after the infusion is finished.

Opioid Agonists

Opioid agonists' CNS depressing effects may be amplified by CNS depressants.  Management: When at all possible, refrain from using benzodiazepines or other CNS depressants  concurrently with opioid agonists. Only in the event that other treatment choices are insufficient  should these medications be combined. Limit the duration and dosage of each medicine  when used together.

OxyCODONE

CNS Depressants may enhance the CNS depressant effect of OxyCODONE.

Management: Avoid concomitant use of oxycodone and benzodiazepines or  other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.

Perampanel

May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination until they have experience using the combination.

Sodium Oxybate

CNS depressants may have an enhanced CNS depressant impact.  Management: Take into account substitutes for combined use.  Reduce the doses of one or more medications when simultaneous use is necessary.  It is not advised to use sodium oxybate with alcoholic beverages or hypnotic sedatives.

Suvorexant

Suvorexant's CNS depressing effects may be amplified by other CNS depressants.  Treatment: Suvorexant and/or any other CNS depressant dosage reduction may be required.  Suvorexant shouldn't be taken with alcohol, and it shouldn't be taken for sleeplessness  with any other medication either.

Tapentadol

CNS depressants may have an enhanced CNS depressant impact.  Treatment: When feasible, refrain from using tapentadol and benzodiazepines or  other CNS depressants simultaneously. Only in the event that other treatment choices are  insufficient  should  these medications  be combined.  Limit the duration and dosage of each medicine when used together.

Zolpidem

CNS Depressants may enhance the CNS depressant effect of Zolpidem.

Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol.

Risk Factor X (Avoid combination)

Azelastine (Nasal)

CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal).

Bromperidol

Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Bromperidol may diminish the hypotensive effect of Blood Pressure Lowering Agents.

Bromperidol

May enhance the CNS depressant effect of CNS Depressants.

Dexmethylphenidate

May enhance the hypertensive effect of Inhalational Anesthetics.

DOPamine

DOPamine's ability to induce arrhythmias may be enhanced by inhalational anaesthetics.  Management: Patients receiving halogenated hydrocarbon anaesthetics should not be  given dopamine. Watch for arrhythmia if concurrent treatment cannot be avoided.  Based on studies from animals, propranolol may be able to reverse ventricular arrhythmia  brought on by dopamine.

Ephedra

Can make inhalational anaesthetics more arrhythmogenic.

EPHEDrine (Nasal)

Can make inhalational anaesthetics more arrhythmogenic.

EPHEDrine (Systemic)

Can make inhalational anaesthetics more arrhythmogenic.

Isoproterenol

Isoproterenol's ability to cause heart arrhythmias may be increased by inhalational anaesthetics.

Metaraminol

Isoproterenol's ability to cause heart arrhythmias may be increased by inhalational anaesthetics.

Methylphenidate

Inhalational anaesthetics' tendency to cause hypertension may be enhanced.

Norepinephrine

Norepinephrine's ability to induce arrhythmias may be enhanced by inhalational anaesthetics.

Orphenadrine

The CNS depressing action of orphenadrine may be enhanced by CNS depressants.

Oxomemazine

CNS depressants may have an enhanced CNS depressant impact.

Paraldehyde

The CNS depressing effects of paraldehyde may be enhanced by CNS depressants.

Thalidomide

The CNS depressing effect of thalidomide may be enhanced by CNS depressants.

 

Monitoring parameters:

  • Isoflurane concentrations before and throughout anesthesia
  • Blood pressure
  • Oxygen saturation
  • Heart rate and rhythm
  • End-tidal CO2 
  • Serum potassium

How to administer Isoflurane (Forane)?

It is given using a vaporizer specially designed for isoflurane or a vaporizer that ensures the right amount of gas is delivered.

Mechanism of action of Isoflurane (Forane):

Isoflurane is an inhaled anesthetic utilized for general anesthesia.

It has the potential to induce significant respiratory depression. The drug influences neuronal activity, particularly in receptors that respond quickly to neurotransmitters like nicotinic acid, gamma-aminobutyric acids, and glutamate.

Additionally, it can reduce the strength of contractions in the heart muscle, decrease blood pressure by dilating blood vessels (lowering systemic resistance), and dampen the activity of the sympathetic nervous system.

Metabolism:

  • Metabolized minimally in the liver (<0.2%), predominantly CYP2E1.

Excretion:

  • Exhaled gases

International Brand Names of Isoflurane:

  • Forane
  • Terrell
  • Aerane
  • Aerrane
  • AErrane
  • Anahal
  • Floran
  • Florane
  • Flurane
  • Fluren
  • Forane
  • Forene
  • Forthane
  • Isocane
  • Isofluran
  • Isofluran Pharmacia
  • Isoflurane
  • Isoflurano
  • Isofor
  • Isoplan
  • Isorane
  • Isotan
  • Sofloran
  • Terrell
  • Terrell Soln
  • Zuflax

Isoflurane Brand Names in Pakistan:

Isoflurane Liquid 2 %w/v in Pakistan

Isoflurane Akhai Pharmaceuticals.