Malignant Hyperpyrexia & Scoline Apnoea

INTRODUCTION

Malignant hyperpyrexia and scoline apnoea and two problems that caused by certain anaesthetic agents and although they are rare, they do occur and it may be of interest to patients to know something about these problems. Malignant hyperpyrexia used to have a significant mortality when it occurred but fortunately there are drugs available to manage the problem and the mortality is significantly reduced with the appropriate treatment. Scoline apnoea is relatively more common however the drugs that cause this problem are less frequently used and when it does occur, the recognition and appropriate management of the problem should result in a zero mortality rate.

MALIGNANT HYPERPYREXIA

Malignant hyperpyrexia (MH) is an inherited problem of the skeletal muscle fibres. Individuals with this problem are predisposed to developing a potentially fatal reaction to certain anaesthetic agents.

The problem was first described in 1960 where a 21 year old patient had a history of 10 of his family members dying under anaesthesia. When he was exposed to the new anaesthetic halothane, within 10 minutes he started developing a fever, increased heart rate, low blood pressure and cyanosis. The anaesthetic was discontinued and fortunately he survived. Investigation of his family then revealed an inherited problem relating to anaesthetic agents.

Biopsy of muscle fibres from patients with MH reveals an abnormal reaction to exposure to caffeine, which induces a spasm in the muscle. This is due to excessive calcium release in the muscle fibres. Strangely susceptibility to MH is not confined to humans and certain strains of pigs, dogs and horses exhibit the same reaction when exposed to anaesthetic agents. In pigs it has been named the Porcine Stress Syndrome (PSS) and these animals have been used for invaluable research work on this problem.

The problem of MH is triggered by exposure to specific anaesthetic agents and this includes the inhaled agents halothane, enflurane, isoflurane, sevoflurane and desflurane and the muscle relaxant scoline (suxamthonium). With exposure to these agents patients develop an increased metabolic rate that manifests as increased output of carbon dioxide, rising body temperature, increased heart rate, cyanosis and mottling of the skin and muscle rigidity. Initially this presentation can be confused with other problems that involve the anaesthetic equipment, other caused of a rising output of carbon dioxide and fever. However, early recognition of the problem is essential for the successful management as the first intervention is to discontinue administration of the causative agent.

In the 1970’s as research was revealing the cause of the problem, a drug called dantrolene was found to be successful in treating pigs with PSS. In 1979, dantrolene was registered by the Food and Drug Administration in America for use in humans and it has dramatically reduced the mortality from the disease. Prior to use of the drug the mortality was in excess of 70% but this has been reduced to less than 10%.

The prevalence of MH susceptibility in the population is unknown and estimates of the frequency of fulminant episodes vary widely. one set of estimates predicts that if one includes all anaesthetics the incidence of MH is 1 in 250 000 and if you look at anaesthetics where the triggering agents are used, the incidence is 1 in 60 000. This means that not every anaesthetist will experience this problem during their career.

Patients who have a family history suspicious of malignant hyperpyrexia can be investigated at specific specialist centres. The tests that can be performed include muscle biopsy for contracture testing, molecular genetic testing, measurement of creatine kinase in the blood, nuclear magnetic resonance spectroscopy, microdialysis of skeletal muscle in vivo and calcium levels in Human B Cells. However none of these tests are entirely reliable.

If there is a strong suspicion of malignant hyperpyrexia or a specific diagnosis has been made, the approach to anaesthesia is to avoid the use of the triggering agents. Fortunately this is easy to do as there are numerous other anaesthetic drugs that are entirely safe and provide the same anaesthetic conditions as any of the triggering drugs.

Australia and New Zealand have a group that provide information and resources for the management of this problem and the link to the website is contained below.

http://www.malignanthyperthermia.com.au/RMH.htm

SCOLINE APNOEA/PSEUDOCHOLINESTERASE DEFICIENCY

Pseudocholinesterase is an enzyme found in the blood that has no known physiological function. However it is essential for the metabolism of suxamethonium/scoline. Scoline is a short acting muscle relaxant that is used to achieve rapid muscle paralysis after the induction of general anaesthesia. This is necessary in patients who are having emergency surgery and who have eaten recently. Rapid muscle paralysis is necessary so as to be able to place an endotracheal tube in the trachea so as to protect the lungs from the danger of inhaling regurgitated food.

Scoline is the best drug that anaesthetists have for this specific purpose. Normally the drug is metabolised very rapidly and it ceases to have any effect within 5 – 8 minutes. However this is dependent on the patient having normal levels of pseudochlinesterase in the blood. Patients with "Scoline Apnoea" can either have a partial or complete deficiency of this enzyme in the blood and in this instance the muscle paralysis will last for anything from 4 – 24 hours.

Key to the management of this problem is for the anaesthetist to recognise that the muscle relaxation is not reversing. The recognition of the problem is aided by the use of a nerve stimulator to test the level of response of the muscle fibres to specific electrical stimulation. Once the diagnosis has been made the problem can be reversed by the use of either Fresh Frozen Plasma or a concentrate of the enzyme supplied by the blood bank. This will speed the reversal of the drug. However despite the use of these interventions it would still be advisable for the patient to be taken to the Intensive Care Unit for a period of monitoring over the next 24 hours.

The incidence of this problem has been estimated at 1 in 1800. This means that if scoline were used frequently the problem would occur relatively regularly. Fortunately it is not usually necessary to use scoline and the problem is therefore avoided.

Blood tests can be performed that measure the activity of pseudocholinesterase and this will confirm the diagnosis. It is possible to avoid the use of scoline in the emergency situation if the diagnosis of scoline apnoea has been previously made. With the appropriate management the problem can be contained with no medium or long term complications.