Cause of death: In surgeries

The government of Nepal must intervene to motivate a manufacturer or importer to develop or import an orphan drug through variety of means such as tax incentives, exclusivity, and financial research subsidies

The likelihood of adverse effects of anesthesia always exists, when the surgery is done under general anesthesia. Malignant Hyperthermia (MH) is a life-threatening clinical syndrome of hyper metabolism involving the skeletal muscle. It is triggered in susceptible individuals primarily by the volatile inhalational anesthetic agents and the muscle relaxant succinylcholine, though other drugs have also been involved as potential triggers. This adverse effect of the general anesthesia may occur in one in five thousands or fifty thousand patients who undergo surgical procedure under general anesthesia. Severe muscle spasms, dangerously high body temperature and a fast heart rate are the signs and symptoms of malignant hyperthermia reaction. Malignant Hyperthermia (MH) may occur either in the operating room (OR) or in the early postoperative period.

The morality rate of Malignant Hyperthermia is 70-80%. This happens because in persons susceptible to Malignant Hyperthermia, the ryanodine receptor in skeletal muscle is abnormal, and this abnormality interferes with regulation of calcium in the muscle.

An abnormal ryanodine receptor that controls calcium release causes a buildup of calcium in skeletal muscle, resulting in a massive metabolic reaction. This hypermetabolism causes increased carbon dioxide production, metabolic and respiratory acidosis, accelerated oxygen consumption, heat production, activation of the sympathetic nervous system, hyperkalemia, disseminated intravascular coagulation (DIC), and multiple organ dysfunction and failure. In most cases, the genetic defect, mutation of ryanodine receptor that causes Malignant Hyperthermia, is inherited. That means if one has a parent, sibling or child with Malignant Hyperthermia, there is a 50 percent chance that he/she has the condition as well. Other close relatives, such as aunts, uncles and grandchildren, have a 25 percent chance.

It is called a pharmacogenetic disorder because the reaction is caused by specific drugs and a genetic testing can reveal whether one has these mutations. In contrary, it is possible that Malignant Hyperthermia may not trigger a reaction during a person’s first surgery. However, the risk of a crisis remains for future surgeries.

Following the induction of general anesthesia in patient, if MH is suspected then a drug called “Dantrolene” must be given. Dantrolene (Dantrium) is a drug used to treat the reaction. Dantrolene, the antidote, decreases the loss of calcium from the sarcoplasmic reticulum in the skeletal muscle and restores normal metabolism. The mortality rates of MH after an introduction of dantrolene sodium for the treatment of MH is estimated to be less than 5%. Other remedies could include, ice packs, cooling blankets and fans may also be used to help reduce body temperature.

One of the reasons might be that the importer or pharmaceutical companies may be reluctant to import or develop them under usual marketing conditions. Dantrolene falls under the category of orphan drugs which are intended to treat rare diseases or conditions. For importers or pharmaceutical companies this area of marketing may not be creditworthy due to limited application scope.

The government of Nepal must intervene to motivate a manufacturer or importer to develop or import an orphan drug through variety of means such as tax incentives, exclusivity (enhanced patent protection and marketing rights), and financial research subsidies or by creating a government-run enterprise to engage in research and development. In the context of United States, the Orphan Drug Act is meant to encourage pharmaceutical companies to develop drugs for diseases that have a small market.

Incidents like these also identify for the role of a clinical pharmacist. Clinical pharmacists work directly with physicians, other health professionals, and patients to ensure that the medications prescribed for patients contribute to the best possible health outcome. In the aforesaid case the clinical pharmacist’s role would be in drug selection and preparation, drug procurement, reporting of adverse drug reactions, updating allergy list and other supportive therapies. The process also involves addition of dantrolene sodium in formulary list, preparation of Malignant Hyperthermia emergency box and reviewing it on timely fashion, calculating dose of dantrolene and reconstituting it on the bed side of the patient, alerting the health care team regarding the Malignant Hyperthermia crisis and supporting the research in such areas.

The trends of clinical pharmacy practice in hospitals by clinical pharmacist started from Europe and US during the early 1970s. In our context the role of clinical pharmacist, except in a few hospitals, is not well justified. The clinical pharmacist should come forward to take up on their role. The health care team should also be willing to accept them as one of their members of health care. Questioning the medical team expertise without proper investigation, bargaining on the dead body for the sake of money and facilitating all this process only create fear towards use of modern medicine.

Rather, every case of death in the hospitals should be discussed and well evaluated so that appropriate measures can be taken to prevent such events in the future. Demotivated health care team is never an answer.

Dr. Upreti is doctor of Pharmacy and a Clinical Pharmacist