Compound 347

Brand name:

Compound 347, Ethrane, Forane, Sojourn, Suprane, Terrell, Ultane, Ultane Amerinet, Ultane Novation.

General anesthetics (GAs) are the drugs which produce reversible loss of all sensation and consciousness. These agents fall into two types:

(A) Inhalational Anesthetics:

• Nitrous oxide (N2O)
• Ether (Diethyl ether)
• Halothane
• Isoflurane
• Desflurane
• Sevoflurane

(B)Intravenous Anesthetics:

• Thiopentone Sodium
• Methohexitone Sodium
• Propofol
• Etomidate
• Benzodiazepines (BZDs)
• Ketamine
• Fentanyl

General anesthesia is a reversible, drug-induced state of unresponsiveness to outside stimuli, characterized by non-awareness, analgesia and relaxation of striated muscle. The cardinal features of general anesthesia are given below for better understanding:

• Loss of all sensation, especially pain
• Sleep (unconsciousness) and amnesia
• Immobility and muscle relaxation
• Abolition of somatic and autonomic reflexes.

No single anesthetic drugs can fulfill the criteria mentioned above. Therefore, in modern practice of balanced anesthesia, these modalities are achieved by using combination of inhaled and intravenous drugs, each drug for a specific purpose. A common procedure involves the use of combination of drugs that would be:

• Thiopentone: to produce unconsciousness rapidly (with an intravenous induction agent)
• Nitrous oxide and halothane: to maintain unconsciousness and to produce analgesia (with one or more inhalational agent)
• Tubocurarine: to produce muscle paralysis (with a neuromuscular blocking drugs)

Here, most commonly used general anesthetics are described:

Nitrous oxide (N2O)

It is a general anesthetic agent of low potency. It is non-explosive, non-flammable, slightly sweetish odor gas. It produces light anesthesia without depressing the respiratory centers.

Halothane

It is a highly potent inhalational anesthetic agent. Surgical anesthesia is produced within 2-5 minutes. Further, it is considered as the best agent for pediatric patient and for patients with bronchial asthma.

Thiopentone

Onset of action is very rapid (within 20-30 seconds) due to rapid transfer across blood-brain-barrier; therefore, anesthesia is induced rapidly and pleasantly. This drug is used for induction of anesthesia prior to administration of inhalational and other anesthetics.

Propofol

Currently, propofol has superseded thiopentone as an intravenous anesthetic, both for induction as well as maintenance. It is an oily liquid employed as 1% emulsion. Unconsciousness after propofol injection occurs in 15-45 seconds and lasts for 5-10 minutes. Intermittent injection or continuous infusion of propofol is frequently used for total intravenous anesthesia when supplemented by fentanyl.

Fentanyl

This drug is a highly potent opioid analgesic. It can produce marked analgesia. This medicine is usually used in balanced anesthesia and conscious sedation.

Etomidate

This drug causes loss of consciousness within second. It has no analgesic effect. Rapid recovery occurs following an induction dose (within 3 minutes). Less cardiorespiratory depression has been observed (advantage over other intravenous anesthetic agents).

Ketamine

This unique anesthetic is pharmacologically related to the hallucinogen phencyclidine. It induces a so called “dissociative anesthesia” characterized by profound analgesia, immobility, and amnesia with light sleep.

If you are about to start this drug therapy, the risk-benefit ratio of taking the drug should be considered carefully. Besides, there are some important factors such as drug interactions, metabolic impairment, hypersensitivity reaction, pregnancy, lactation etc. which may alter the desired therapeutic effects of such medications.

Sometimes the presence of other health disorders affects the desired effects of this medicine and even may cause serious toxic effects. If you have had any allergic reactions to any medicine then you must inform your doctor about that. The use of different general anesthetics is contraindicated in different conditions such as following:

Contraindications of halothane:

• Unexplained jaundice following previous exposure to halothane
• Malignant hyperthermia
• Raised cerebrospinal fluid pressure

Contra of thiopentone:

• Barbiturates hypersensitivity
• Severe cardiovascular diseases or hypotension
• Obstructive pulmonary disease
• Severe acute bronchial asthma
• Addison’s disease
• Hepatic dysfunction
• Myxedema
• Acute intermittent porphyria

Contraindications of ketamine:

• Bronchial asthma
• Hypertension (moderate to severe)
• Congestive cardiac failure
• Raised intracranial pressure
• Pregnancy (before term) as ketamine has oxytocic action
• Schizophrenia and acute psychosis
• Eye injury and increased intraocular pressure

Certain drugs should not be used together when you are undergoing this diagnostic procedure. It is always recommended to consult with your doctor if you are in need of some other medications or even any over-the-counter medicine for another health problem in order to avoid unwanted toxic effects.

Therefore, you should know about the following drug interactions:

• Patients on antihypertensives given general anesthetics –BP may fall markedly.
• Neuroleptics, opioids, clonidine and monoamine oxidase inhibitors potentiate anesthetics.
• Halothane sensitizes the heart to adrenaline.
• If a patient on corticosteroids is to be anesthetized, give 100mg hydrocortisone intraoperatively because anesthesia is a stressful state –can precipitate adrenal insufficiency and cardiovascular collapse.
• Insulin need of a diabetic is increased during general anesthesia; thus, it is recommended to switch over to plain insulin even if the patient is on an oral hypoglycemic.

However, it is not well-known whether these drugs can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Thus, this medicine can be used during pregnancy only if clearly needed.

The dosage schedule and the duration of drug therapy depend on the particular medical problem for which you are using this medicine. The therapeutic dose may also vary with patient’s condition or requirement and the strength of the medicine as well. Such medicines are always given to the patients by an anesthesiologist and he/she will decide the right amount for you.

In addition, the dose of a general anesthetic will vary depending upon the following criteria.

• Age,
• General physical condition,
• The kind of surgery or other procedure you are having; and
• Other medicines you are taking or will receive before and during surgery.

Firstly, assessment of the patient prior to the induction of general anesthesia must be done by an anesthesiologist. This assessment is of greater importance to do a safe anesthesia.

It prevents per-operative complications as well as post-operative hazards. Proper assessment comprises the following appliances:

1) History should be obtained about any allergy, bronchial asthma, chest pain, and cough.

2) Medical check-list:

• Cardiovascular –hypertension, angina, arrhythmias, failure
• Respiratory –infection, asthma
• Gastrointestinal –regurgitation, bowel obstruction, jaundice
• Metabolic –porphyria, hyperpyrexia, diabetes, steroids
• Coagulation –hereditary and acquired
• Neurological –consciousness level, cervical instability

3) Investigations:

• Blood:
  • Total & differential count of white blood cells
  • Hemoglobin percentage estimation and ESR
  • Fasting/random/post-prandial blood sugar level
  • Blood urea and serum creatinine
• Urine for routine examination (R/E) for protein, sugar, casts, and pus cell. Culture sensitivity is required if there is urinary tract infection.
• Chest X-ray
• ECG (if age 40 years or more)

Besides, the following guidelines should be followed after receiving a general anesthetic:

• General anesthetics may cause you to feel drowsy, tired, or weak for up to a few days after they have been administered. These drugs may also cause problems with coordination and the ability to think. Therefore, you should not drive, or use machines for at least 24 hours (or longer if necessary) after receiving a general anesthetic.

• Further, you should avoid drinking alcoholic beverages or taking other CNS depressants (e.g. sedatives, tranquilizers, antihistamines, etc.) for about 24 hours after you have received a general anesthetic. To do so may add to the effects of the anesthetic.

There are some unwanted side-effects associated with each drug that usually do not need medical attention. These side-effects usually go away during the treatment episode as your body adjusts to the medicine. In addition, your doctor may advise you about the ways how to prevent or reduce those unwanted side-effects. Further, the following problems may take place and warrant immediate medical help –

A) During anesthesia:

• Respiratory depression and hypercarbia (presence of an abnormally high level of carbon dioxide in the circulating blood)
• Salivation, respiratory secretions. This is less problematic now as nonirritant anesthetics are mostly used.
• Cardiac arrhythmias, asystole.
• Fall in blood pressure
• Aspiration of gastric contents: acid pneumonitis.
• Laryngospasm and asphyxia
• Awareness: dreadful perception and recall of events during surgery. This may occur due to use of light anesthesia+analgesics and muscle relaxants.
• Delirium, convulsions and other excitatory effects are generally seen with intravenous anesthetics; especially if phenothiazines or hyoscine have been given in premedication. These are suppressed by opioids.
• Fire and explosion. This is rare now due to use of non-inflammable anesthetics.

B) After anesthesia:

• Nausea and vomiting
• Persisting sedation: impaired psychomotor function
• Pneumonia, atelectasis
• Organ toxicities: liver, kidney damage
• Nerve palsies –due to faulty positioning
• Emergency delirium
• Cognitive defects: prolonged excess cognitive decline has been observed in some patients, especially the elderly, who have undergone general anesthesia, particularly of long duration.