Ethanol injection is used as an antiseptic, for tissue ablation, nerve block, and as an antidote for methanol toxicity.

Ethanol indications: 

• Replenishment of fluid and carbohydrate calories:

  • It is used for the Replenishment of fluid and carbohydrate calories

• Septal ablation for hypertrophic obstructive cardiomyopathy (HOCM) (Ablysinol only):

  • It is useful in inducing controlled cardiac septal infarction and improvement of exercise capacity in patients with symptomatic hypertrophic obstructive cardiomyopathy who are not suitable for surgical myectomy.

• Therapeutic nerve or ganglion block:

  • In order to control intractable chronic pain, therapeutic neurolysis of nerves or ganglia is indicated in certain conditions.

• Ethanol Topical use:

• Antiseptic:

  • It is used as a topical anti-microbicidal agent

• Off Label Use of Ethanol in Adults:

  • Antidote for Ethylene glycol overdose
  • Antidote for Methanol overdose

Ethanol Dose in Adults

Ethanol as an Antiseptic:

• Denatured alcohol (liquid form):
  • Apply topically 1 to 3 times daily as required

Ethanol injection for Therapeutic nerve or ganglion block:

• Dehydrated alcohol injection 98%:

  • Intraneural:

    • The dosage depends upon the site of injection (eg, trigeminal neuralgia: 0.05 to 0.5 mL as a single dose per interspace)

  • subarachnoid injection:

    • 0.5 to 1 mL as a single injection per interspace); single doses >1.5 mL are not usually required.
  • Note: Only indicated when pain is from the malignant origin.

Replenishment of fluid and carbohydrate calories:

• Dehydrated alcohol infusion:

  • Alcohol 5% and dextrose 5%:

    • 1 to 2 L/day by slow infusion

Ethanol injection for Septal ablation for HOCM:

Intracoronary injection:

• The dosage depends on septal anatomy and the rate of contrast wash-out.
• Single-injection administered as 1 to 3 mL of at least 95% concentration infused slowly into septal arterial branches;
• The maximum dose is 5 mL/procedure.

• Note:

  • The minimum possible dose should be used to achieve the required reduction in peak left ventricular outflow tract pressure gradient;
  • The smaller dose is safer as it can reduce the size of the septal infarct with a lesser incidence of complications (eg, complete heart block).

Ethanol injection for Methanol or ethylene glycol overdose:

Note:

• Intravenous route of administration is preferred.
• Therapy should be continued until ethylene glycol and/or methanol can no longer be  detected or levels are <20 mg/dL and the patient is asymptomatic and metabolic acidosis has been resolved If ethylene glycol and/or methanol levels are not available in a timely manner, treatment should be continued until the estimated time of removal of ethylene glycol or methanol has elapsed and the patient has no symptoms and a normal pH is achieved.
• Depending upon the physical condition of the patient and their endogenous metabolism of ethanol, it is vital to test serum ethanol concentrations more frequently to determine the exact dose for each patient.
• Titrating above or below the stated doses may be necessary.
• If the patient has accidentally swallowed ethanol, measurement of baseline serum ethanol concentration and adjustment of the loading dose of ethyl alcohol-based on results to attain a serum ethanol level of ~100 mg/dL.

Absolute ethyl alcohol [98% (196 proof) = 77.4 g EtOH/dL]:

• Note: Contact the Poison Control Center for management related to compounding Intravenous ethanol.

  • Loading dose:

    • 600 to 700 mg/kg [equivalent to 7.6 to 8.9 mL/kg using a 10% solution]

  • Maintenance dose:

    • Goal of therapy is to maintain serum ethanol levels >100 mg/dL.

  • Non-drinker:

    • 66 mg/kg/hour [equivalent to 0.83 mL/kg/hour using a 10% solution]

  • Chronic drinker:

    • 154 mg/kg/hour [equivalent to 1.96 mL/kg/hour using a 10% solution]

Ethanol injection Dose adjustment for patients on hemodialysis:

Maintenance dose:

• Nondrinker:

  • 169 mg/kg/hour [equivalent to 2.13 mL/kg/hour using a 10% solution]

• Chronic drinker:

  • 257 mg/kg/hour [equivalent to 3.26 mL/kg/hour using a 10% solution]

Note:

An oral diluted solution to a ≤ 20% concentration (to prevent gastritis) with water or juice and given per oral or via nasogastric tube. Due to the pharmacokinetics of alcohol (ethyl), it is important that oral ethanol is administered strictly at an interval of one hour.

• Loading dose:

  • 600 to 700 mg/kg [equivalent to 0.78 to 0.9 mL/kg using a 98% solution]

• Maintenance dose:

  • Goal of therapy is to maintain serum ethanol levels >100 mg/dL

  • Nondrinker:

    • 66 mg/kg/hour [equivalent to 0.09 mL/kg/hour using a 98% solution]

  • Chronic drinker:

    • 154 mg/kg/hour [equivalent to 0.20 mL/kg/hour using a 98% solution]

Ethanol injection Dosage adjustment for patients on hemodialysis:

Maintenance dose:

• Nondrinker:

  • 169 mg/kg/hour [equivalent to 0.22 mL/kg/hour using a 98% solution]

• Chronic drinker:

  • 257 mg/kg/hour [equivalent to 0.33 mL/kg/hour using a 98% solution]

Ethanol injection Dose in Children:

• See institution-based protocol: Intravenous dehydrated alcohol injection is indicated

Catheter-related bloodstream infection (CRBSI):

• Prophylaxis:

  • Note:
  • It is indicated for patients with long term catheterization and high risk or history of catheter-related bloodstream infection.

  • Variable dosage:

    • 70% ethanol.
    • Instill a volume equal to the internal volume of the catheter once every 24 hours with a dwell time of 2 to 14 hours.
    • Withdraw ethanol at the end of the dwell time.
    • Less frequent dosing (3 times per week) for a minimum 4 hour dwell time and once every 7 days dosing with 2-hour dwell time have shown to produce a remarkable reduction in the rate of infection and catheter loss;
    • Most study subjects were receiving long-term outpatient cyclic parenteral nutrition.
    • However, a small number of subjects showed an increase in infection rate when the ethanol locks frequency was decreased to less than daily during an ethanol shortage;
    • all patients in this study had tunneled Silastic catheters.

• Treatment:

  • Variable dosage:
  • 70% ethanol, instill a volume equal to the internal volume of the catheter with a dwell time 4 to 25 hours;
  • some protocols use single-dose and others repeated the dose once every 24 hours for 3 to 5 days;
  • The dosing should be repeated for each lumen and used in combination with systemic antibiotics.
  • For fungal bloodstream infection, case-reports showed success using single daily with dwell times of 2 to 24 hours for two weeks following the patient's first negative blood culture.

• Fat occlusion of central venous catheters:

  • Dehydrated alcohol injection:
    • Up to 3 mL of 70% ethanol (maximum: 0.55 mL/kg).
    • Instill a volume equal to the internal volume of the catheter.
    • It can be repeated if patency is not restored after 30 minutes to 1 hour dwell time.
    • Reassess after 4-hour dwell time in case of repeated doses.

Pregnancy Risk Factor: C

• Ethanol crosses the placenta and enters the fetal circulation. It also has teratogenic properties in humans.
• Neonatals often experience withdrawal symptoms like crying, hyperactivity and irritability as well as tremors, seizures and poor sleeping patterns.
• Fetal alcohol syndrome (FAS), is a condition where there are a variety of cognitive, behavioral and physical abnormalities that result from ethanol exposure during fetal growth.
• Pregnant women or those who plan to become pregnant should limit their intake of ethanol. There is no safe amount of ethanol for pregnancy.
• Fetal Alcohol Syndrome is rarely reported in the last two trimesters due to its short treatment period. However, it is possible that it is used during the first trimester.
• It is unlikely that the fetus will be exposed to ethanol if the medication is administered through the septal artery during percutaneous septal septal myocardial ablation.
• However, it should be stopped until after birth if possible.

Use of ethanol during breastfeeding

• Breast milk contains a similar amount of ethanol to that found in maternal blood.
• Ethanol may cause reduced milk production, which can lead to adverse events for the nursing infant (such as sleep disturbances or impaired motor development and postnatal growth).
• The weight of the mother, as well as the amount of ethanol consumed, will determine the actual level of ethanol in breast milk.
• Guidelines suggest that you avoid drinking or reduce your intake to ethanol 0.5g/kg/day. Wait 90 to 120 minutes before starting to breastfeed.
• The infant is not exposed to significant amounts of alcohol after ethanol has been administered to the septal artery as part of percutaneous transluminal Septal Myocardial Ablation.

Dose adjustment in Renal disease:

There are no dosage adjustments provided in the manufacturer's labeling

Dose adjustment in liver disease:

There are no dosage adjustments provided in the manufacturer's labeling.

Side effects of Ethanol injection:

• Cardiovascular:

  • Cardiac failure
  • Heart block
  • Myocardial necrosis (excessive)
  • Ventricular fibrillation
  • Ventricular tachycardia

• Central nervous system:

  • Hyperesthesia
  • Neuritis
  • Pain
  • Paresthesia

Contraindications to Ethanol injection:

• Hypersensitivity to ethyl Alcohol or any component of this formulation
• Diabetic coma and seizure disorder;
• Alcohol injection in subarachnoid space in patients on anticoagulants.

Warnings and precautions

• Heart block (septal Ablation):

  • A septal artery injector of alcohol causes transient heart block.
  • After percutaneous transluminal myocardial ablation, about 10% of complete heart blocks become permanent.
  • Permanent pacemaker risk factors include a baseline PQ interval of >160 msec and a baseline minimum pulse 50bpm. The baseline left ventricular output gradient is >70 mmHg. Maximum QRS within the first 48 hours is >155 msec. Third-degree atrioventricular blocks can occur during the procedure. There is no clinical recovery period between 12 and 48 hours.

• Myocardial Infarction

  • It is used to treat myocardial infarction.
  • However, there have been reports of excessive myocardial necrosis (and subsequent heart failure).
  • There are two factors that increase the risk of excessive tissue destruction: a higher alcohol consumption and a greater number of septal branches injected to lower the gradient of left ventricular outflow tract.

• Ventricular arrhythmia (septal Ablation):

  • The frequency of ventricular fibrillation requiring electrocardiversion and Ventricular Tachycardia was approximately 1%.
  • Two days should be allowed for continuous electrocardiographic monitoring.

• Diabetes:

  • Patients with diabetes mellitus should use it with caution.
  • Hypoglycemia may be caused by ether alcohol

• Gout

  • Patients with gout should be cautious.

• Hepatic impairment

  • Patients with hepatic impairment need to be cautious when using the device.

• Surprise!

  • Patients in shock should exercise caution.

Ethanol (topical and injection): Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring Parameters:

• Septal ablation for hypertrophic obstructive cardiomyopathy:

  • Continuous electrocardiogram monitoring for 2 days after the procedure.
  • note the signs/symptoms of heart failure, chest pain, and arrhythmias several days after the treatment.

• Antidote therapy:

  • Blood ethanol levels should be checked every 1 to 2 hours until steady-state, then tested every 2 to 4 hours.
  • Monitor Blood glucose,
  • Serum  electrolytes (including serum magnesium),
  • Arterial pH,
  • Blood gases,
  • Methanol or ethylene glycol concentration in the blood
  • Heart rate and blood pressure should be monitored

Administration of Ethanol injection?

• Ethylene glycol or methanol overdose:

  • Diluted oral ethyl alcohol to ≤20% solution (to prevent gastritis) with water or juice and administer hourly by mouth or via nasogastric tube.
  • Oral administration of ethanol is not recommended outside the hospital but has been demonstrated to be efficacious.
  • Due to the pharmacokinetics of alcohol, it is important that oral ethanol is given precisely at one-hour intervals.

• Ethylene glycol or methanol overdose (off-label use):

  • Intravenous administration via a central vein is the preferred route.
  • Administer as a 10% solution in 5%dextrose.
  • Initial dose should be given over 60 minutes.

• Treatment of occluded central venous catheter:

  • Instill a 70% solution with a volume equal to the internal volume of the catheter.
  • Check for patency at 30 minutes to 1 hour (or per institutional protocol).

• Intraneural administration:

  • Separate needles should be used for each of multiple injections or sites to avoid residual alcohol deposition at sites not targeted for tissue destruction.
  • Slow injection after determining proper placement of needle should be given.
  • Since dehydrated alcohol is hypobaric in nature as compared to the spinal fluid, the proper position of the patient is important to control the localization of injections into the subarachnoid region.

• Intracoronary administration:

  • Inject small volumes over 1 to 2 minutes percutaneously into septal arterial branches with regards to assessment of the gradient.

Mechanism of action of Ethanol injection:

• Overdose of ethylene glycol (or methanol):
  • The competitive inhibitor of alcohol dehydrogenase, an enzyme that catalyzes methyl and ethylene glycol metabolism to toxic metabolites, is ethanol.
• Neurolysis:
  • The injection site can be destroyed by alcohol.
• Septal ablation
  • Tissue toxin causes a myocardial injury when it is injected via an intra-arterial catheter to a target septal vessel. This causes the hypertrophied septum's narrowing to occur.

Absorption:

• Oral route has rapid absorption.

Metabolism:

• Hepatic (90% to 98%) to acetaldehyde or acetate

Half-life elimination:

• Rate: 15 to 20 mg/dL/hour (range: 10 to 34 mg/dL/hour); increased in alcoholics

Excretion:

• Kidneys and lungs (~2% unchanged)

Ethanol Injection and Gel Brand Names (International):

• Ablysinol
• Epi-Clenz
• GelRite
• Isagel
• Lavacol
• Prevacare
• ProtecTeaV
• Purell Advanced
• Purell
• Biobase
• Biobase-G
• Aogel

Ethanol injection and Gel Brand Names in Pakistan:

No Brands Available in Pakistan.