Sat27November0445PM 15

A 63-year-old man develops hallucinations and agitation following anaesthesia for laparoscopic biliary surgery.

Central anticholinergic syndrome was diagnosed. Only after resolution of the clinical problems did a drug error origin of the syndrome become apparent. It was realised that hyoscine hydrobromide (scopolamine) had been inadvertently administered intraoperatively for biliary relaxation, instead of hyoscine butyl bromide.

Which of the following anticholinesterase drugs is the most suitable pharmacological therapy for central anticholinergic syndrome?

(Please select 1 option)

Neostigmine

Physostigmine This is the correct answer

Pyridostigmine Incorrect answer selected

Sarin

Edrophonium

Explanation

Central anticholinergic syndrome (CAS) is due to a decrease in the inhibitory acetylcholine activity in the brain. It occurs when central cholinergic sites are occupied by specific drugs and also as a result of an insufficient release of acetylcholine.

Central anticholinergic syndrome during recovery is essentially a diagnosis of exclusion and can be confirmed only after resolution of symptoms with physostigmine (0.03- 0.04 mg/kg). The incidence of CAS is as high as 8-10%.

The anticholinesterase of choice is physostigmine as this is the only anticholinergic agent used clinically that crosses the blood brain barrier because it is a tertiary amine (hydrophobic). Pyridostigmine, neostigmine and edrophonium are quaternary amines.

Symptoms include:

Agitation

Seizures

Restlessness

Hallucinations

Disorientation, or

Signs of depression such as stupor, coma and respiratory depression.

Such disturbances may be induced by:

Opiates

Benzodiazepines

Phenothiazines

Butyrophenones

Ketamine

Etomidate

Propofol

Nitrous oxide, and

Halogenated inhalation anesthetics

Disturbances may also be induced by H2-blocking agents such as cimetidine.

Differential diagnosis of the CAS includes:

Disorders of glucose and electrolyte metabolism

Severe hormonal imbalance

Respiratory disorders (hypoxia, hypercarbia)

Hypothermia

Hyperthermia and

Neuropsychiatric diseases (cerebral hypoxia, stroke, catatony, acute psychosis).

Sarin is a highly potent anticholinesterase and is used in chemical warfare as a "nerve agent". It produces almost irreversible inactivation of acetylcholinesterase by alkylphosphorylation. Recovery of acetylcholinesterase activity depends mainly on synthesis of new enzyme.

High lipid solubility, low molecular weight and volatility are features of this group of drugs facilitating rapid and effective absorption via inhalation and the transdermal route. They also readily penetrate the central nervous system.

Answer Statistics

1

15%

2

47%

3

32%

4

1%

5

7%

Times answered: 280