Halothane

Chemical and Physical Properties

1. Halogenated compound chemically.
2. 2-bromo-2-chloro-1,1,1-trifluoroethane
3. Volatile, so kept in sealed bottles
4. Odorless
5. Colorless
6. Non-irritant
7. Non-explosive
8. Non-inflammable
9. Light-sensitive, so kept in amber coloured bottles
10. Corrosive
11. Interaction – rubber and plastic tubing

Pharmacokinetics

a. Potent general anesthetic

b. MAC – 0.75, thus lower MAC value, more drug potency

c. Blood Gas partition coefficient – 2.3

d. Induction & recovery is slower to cause change in partial pressure due to high lipid solubility

e. Metabolism – normally excreted in form of trifluoroacetic acid. 20-40% is metabolized in liver.

f. Clearance

Around 60-80% is cleared out unchanged by lungs

In some patients a toxic intermediate compound is formed, trifluoroacetylchloride. This:

1. Binds hepatic cellular proteins, responsible for hepatitis esp. on cell membrane, damaging hepatic cells

2. In a number of patients, against these trifluoroacetylated proteins (TFA proteins), body forms antibodies, leading to fulminant hepatic disease.

Pharmacological Effects

1.      CVS

Blood Pressure

Depressant effect on myocardial contractility, leading to decreased blood pressure.

But does not allow reflex tachycardia due to blood pressure lowering by suppressing baroreceptor reflex, instead causes bradycardia. Due to:

• Depressant effect on SA node
• Vagal stimulation
• It sensitizes myocardium to catecholamines so anxious patients or in pheochromocytoma or exogenous epinephrine, chances of cardiac arrhythmias.

Thus adrenaline is never used in patients anesthetized with halothane.

Treatment

For treatment of vagal stimulation:

I. Atropine

II. Beta-blockers to prevent cardiac arrhythmias

Redistribution of blood flow; also leads to redistribution of blood, increasing cerebral blood flow and blood flow to skin, it suppresses auto regulation in renal, splanchnic and cerebral vasculature.

When blood pressure is decreased, decreased flow to these areas occurs, with no auto regulation.

It does not affect coronary and pulmonary circulation.

2.      Respiratory system

a.      Pulmonary ventilation

Increases rate but tidal volume is decreased. Respiration becomes shallow.

b. CO₂ / O₂ response

Suppresses body response to carbon dioxide excess, by acting on chemoreceptor zone in medulla. Also suppresses hypoxic response by affecting peripheral chemoreceptor zone.

c.       Muco-ciliary function

Mucociliary functions are suppressed, sometimes stops -atelectasis

d.      Bronchodilator – status asthmatics

Bronchodilator effect so given in refractory cases of asthma.

3.      CNS

a.      Cerebral Blood Flow

Increases cerebral blood flow

b.      Metabolism

Decreases rate of metabolism in CNS.

c. Intra-cranial pressure

Increases intra-cranial pressure, so halothane is not given in patients of head injury, cerebral edema, space occupying lesion, and tumor

d.EEG

Has depressant effect on EEG.

4.      Kidneys

Decrease renal blood flow by suppressing auto regulation.

Concentrated urine is produced

The effect is transient and the patient goes back to normal.

5.  GIT

Suppresses auto regulation of splanchnic blood flow, decreasing it, which is of no significant clinical effect.

6.  Skeletal muscles

Relaxes skeletal muscles.

7.  Uterus

Relaxes uterus so can be used for manipulation of fetus, when positional changes are done perinatally. It is not given during delivery and can delay labor as may relax the uterus. It can be used after delivery for retained placenta as need to relax uterus.

Uses

Potent general anesthetic for:

1.  Maintenance anesthesia– 0.5-1%

2.  Induction – 2-4%

It has now been replaced by newer safer drugs. But are still used:

a. In children

b. And because of low cost

Adverse effects

1.      Halothane shake / Shivering

During recovery phase, patient complains of shivering known as halothane shake. The exact mechanism is not known.

2.      CVS / Respiration

Depressant effect on CVS and respiration.

Chronic toxicity studies have shown no carcinogenic or mutagenic property. Epidemiological studies show increased chances in patients working in theatres, but there is no official data.

3.  Hepatitis

Pathophysiology

Immune response of the body against trifluorated compounds. As a result of which hepatic cells are damaged, leading to severe hepatitis.

Predisposing factors

1. Elderly
2. Obese
3. Female
4. Electrolyte imbalance
5. Receiving enzyme agents or drugs

Clinical Signs/Symptoms

1. Nausea
2. Vomiting
3. Lethargy
4. Generalized weakness
5. Fever
6. Rash

Occurs several days after administration of halothane.

Those already exposed to halothane are at a higher risk of developing hepatitis.

Biochemical tests

1. Eosinophilia
2. Deranged LFTs
3. Autoantibodies
4. Trifluoroacetylated proteins in serum

Treatment

No specific treatment. In severe cases like liver failure, liver transplant is required.

4.  Malignant Hyperthermia

Also occurs with succinyl choline.

Pathophysiology

a.      Ryanodine Receptors (RyRI)

It is a autosomal genetic disease where there is gene mutation responsible for ryanodine receptors. Because of this increase release of calcium through these channels from sarcoplasmic reticulum occurs, leading to increased calcium levels in sarcoplasm of skeletal muscles.

b.      L-type Ca⁺² channels

In some cases, mutation is seen in genes for L-type of calcium channels. Result is the same.

Clinical Signs/Symptoms

Clinically patient shows:

1. Hyperthermia
2. Severe muscular rigidity
3. Hypertension
4. Increased heart rate
5. Signs and symptoms of hyperkalemia and acidosis

Biochemical tests

1. Acidosis
2. Hyperkalemia
3. Deranged electrolytes
4. Increased free calcium in skeletal muscles
5. Confirmed by tests on skeletal muscle biopsy
6. In vitro caffeine halothane contracture test

Treatment

1. Dantrolene, which decreases calcium release
2. Symptomatic treatment of fever

Restoration of electrolyte balance

Advantages	Disadvantages
Potent	Not an analgesic
Less irritant	Variable muscle relaxation
Induction smooth and rapid	Sensitizes heart to catecholamines
Quick recovery	Hypotension
Non – inflammable	Bradycardia
Compatible with soda lime	Hepatitis
Bronchodilator	Respiratory depression
Uterine relaxant	Shivering during recovery
Less incidence of post-operative nausea/ vomiting	Malignant hyperpyrexia
Does not cause laryngospasm	Enzyme inducer
Easier endotracheal intubation due to relaxation of masseter muscles	Corrodes metals
Cost-effective	Reacts with rubber equipment

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