Malignant Hyperthermia Treatment Case Study

Malignant Hyperthermia Treatment Case StudyIn this scenario, in that location is a 35 year old young-bearing(prenominal) patient who develops tin cancerous hyperthermy during surgery. Malignant hyperthermia is an uncommon pharmacogeneric disorder that leads to the hypermetabolic reactions of the skeletal vigor. Ben Abraham, et al, 1998, Britt, 1985, Hopkins, 2008. Age, type of anesthetic, environmental temperature, mitigating drugs administered simultaneously and degree of stress play an Copernican role in triggering cancerous hyperthermia. Ording, 1985. Primarily, potent inhalation anesthetic agents and depolarizing ponderousness relaxants such as succinylcholine are the major triggering factor amongst all the triggering factors. Malignant hyperthermia can happen at any time during surgery in particular after the stimulus generalization of the anesthetic and in the early postoperative period. Besides that, there is a tendency of the recurrent of malignant hyperthermia as well.Even though hypermetabolic reaction of skeletal muscle builder will cause hyperthermia and rhabdomyolysis barely fever is not the earliest symptom of malignant hyperthermia. The earliest signs and symptoms of malignant hyperthermia are enlarge in the end-expired carbon dioxide concentration (EtCO2), tachycardia and muscle inflexibility ( oddly when succinylcholine is given). Britt, 1985. Furthermore, the late sign of malignant hyperthermia is elevation of the body temperature. Ali et al, 2003 Britt,1985.The other signs and symptoms are unstable blood pressure, tachypnea, hyperkalemia and arrhythmia.According to Hogan, 1998 the estimated incidence of malignant hyperthermia during anaesthesia in North America and Europe is 115000 anesthetics for children and adolescents and 150000- 1150000 anesthetics for adults. Hogan, 1998.All ethnic groups are affected with malignant hyperthermia and males are more habituated to be affected compared to female. Britt, 1976 Hopkins, 2008. The mortality was around 80% thirty years ago and has been reduced to less than 10% with the introduction of the muscle relaxant dantrolene sodium, far-flung education and clinical and research investigation. Ali, 2003 MacLennan, 1990Malignant hyperthermia is an inherited disorder where the calcium channel that mediates the excitation contraction coupling in skeletal muscle is mutated. As a result, the calcium channel is very sensitive to the anesthetic agents Hopkins, 2008. This will lead to the uncontrolled release of cytoplasmic calcium from the sarcroplasmic reticulum upon the induction of anesthetic agents Hopkins, 2008 Rosenberg et al. 2004. As a matter of fact, there is a continued interaction between actin and myosin with sustained muscle contraction Hopkins, 2008 Rosenberg et al. 2004. The manifestation of the signs and symptoms of malignant hyperthermia can be explained by the increased release of the calcium. At first, this mechanism is compensated by the resequestion of calcium, which has lead to the breakdown of the adenosine trisphosphate (ATP) Hopkins, 2008 Rosenberg et al. 2004. This will cause the stimulation of the metabolic process and results in increased oxygen consumption, agitate and carbon dioxide production. The breakdown of the ATP causes the release of the potassium into the extracellular fluid results in hyperkalemia and this will lead to the study of cardiac arrhythmias. Besides that, the continuous contraction of the skeletal muscle due to the breakdown of the ATP will lead to the further production of heat. As a result, there will be a further increase of oxygen consumption, carbon dioxide and lactic acid production, which, will lead to metabolic acidosis Britt, 1985 Hopkins, 2008 Rosenberg et al. 2004. In addition, the increase of the production of heat will also increase the contractility of the skeletal muscle hence further worsening the rhabdomyolysis process. If malignant hyperthermia is untreated, it might lead to snappy organ dysfunction, acute renal failure, disseminated intravascular coagulation, congestive heart failure and even close.In this scenario, since the patient developed malignant hyperthermia during surgery, thereby the management of malignant hyperthermia can be divided into emergency word and postoperative treatment. When there is an acute development of malignant hyperthermia during surgery, all triggering agents have to be discontinued and the patient has to be hyperventilated with 100% oxygen to lower the end tidal CO2 immediately. This is followed by regime of 2.5mg/kg dantrolene sodium intravenously every 5 minute until the signs and symptoms of malignant hyperthermia are under controlled. Morgan et al. 2006. The dose of dantrolene can be titpaced up to 10mg/kg. Gronert et al., 1976 Harrison, 1988. The monitor of blood gases, all serum electrolytes, muscle enzyme such as cretine kinase, clotting profile, blood and urine for myoglobin, blood glucose, lactate and urea nitroge n must be carried out frequently during the surgery. Sodium bicarbonate should be given to correct the metabolic acidosis to the normal level. In addition, patient has to be closed monitored and anti-arrhythmic except calcium channel blocker can be given for arrhythmias. Cooling measures have to be initiated if there is the present of hyperthermia. Ice packs to groin, axilla, and neck, cooling blanket, and nasogastric lavage with iced answer can be used to cooling down the patient. The cooling measures have to be stop if the body temperature is at 38.5oC. In order to treat myoglobinaemia and thus acute prevent renal failure urine outfit and urine pH should be greater than 3ml/kg/h and pH7 respectively. Hopkins, 2008. This diuresis can be achieved by hydrating the patient with crystalloid solutions together with mannitol (0.3g/kg) and furosemide (0.5-1.0mg/kg). Hopkins, 2008 Mary, 1998. Hyperkalaemia which is life endanger can be treated with glucose, insulin, intravenous calciu m and intravenous potassium chloride. Britt, 1979 Hopkins, 2008.Once the surgery is finished, the patient has to be moved to intensive care whole or recovery room until malignant hyperthermia is under controlled and the patient should be monitored closely. Since it is possible for the recrudescence of malignant hyperthermia, dantrolene should be continued giving to patient for at least 48 hours. Flewellen, 1983 Rosenberg, 2004. Several laboratory tests such as blood gases, electrolytes, coagulation profile, muscle enzyme, blood and urine for myoglobin should be assessed more frequently. Hopkin, 2008.At first, anyhow dantrolene, procainamide/ procaine was recommended to treat malignant hyperthermia. The use of procainamide/ procaine was due to the successful studies carried out by Harrison, 1971, Denborough, 1972 and Noble, 1973. The study carried out by Harrison, 1971 showed a successful treatment of malignant hyperthermia with large dose of intravenous procaine in 2 out of 5 Landr ace pigs. However, the study from Gronert, 1976 showed that the recommendation dose of procaine/ procainamide was ineffective in preventing malignant hyperthermia of the 20 susceptible pigs. Study compared the effectiveness of dantrolene and procainamide conducted by Nelson, 1979 showed that procainamide did not block the contracture response to halothane and it is ineffective for therapeutic and as prophylaxis of malignant hyperthermia. Procainamide or procaine was not been used after all.Harrison, 1975 demonstrated that dantrolene can relax muscle rigor in pigs with malignant hyperthermia and ceased the excessive heat and acid production. The study showed 100% survival rate in the last seven of eight experiments. Besides that, based on Britt, 1984 that 79 patients who received dantrolene therapy showed a significant 16.56% reduction in mortally (pDantrolene is now the only known therapeutic agent used to treat malignant hyperthermia. Dantrolene is a diphenylhydantoin derived tha t is highly lipid soluble but scant(p)ly water soluble. PMJ GG Harrison. Dantrolene can be administered by oral route or intravenous route. Roughly, 70% of dantrolene is jailed with the peak plasma concentration reached in 6 hours following the ingestion of dantrolene by mouth. From the experiment performed by Harrison 1975, oral dantrolene was effective in treating procaine malignant hyperthermia. Nevertheless, there is a great variation in the plasma concentration for the oral dantrolene especially in children. Dantrolene is formulated as lyophilized orange powder, which comprises of dantrolene sodium, mannitol and sodium chloride. These contents are dissolved in water to yield a solution with the pH of 9.5 for intravenous injection. Moreover, the additional of the mannitol is to improve the solubility since dantrolene is poorly water soluble and mannitol also acts as diuresis, which prevent the deleterious do of myoglobinaemia. The biological elimination half life of dantrol ene is 12 hours. As a result, after 12 hours the plasma concentration of dantrolene will be 4.2g/ml with the administration of 2.4mg/kg body weight of dantrolene intravenously. Allen et al, 1988 Muehlschlegel Sims, 2009. Dantrolene is mainly metabolized in the liver through oxidation and reduction reaction. Oxidation and reduction of the dantrolene result in the production 5-hydroxydantrolene and aminodantrolene respectively. Aminodantrolene will then undergo acetylation leads to the formation of reduced acetylated differential coefficient of dantrolene. The metabolites of the dantrolene are excreted in urine and bile with 79% of 5-hydroxydantrolene, 17% reduced acetylated derivative of dantrolene and 4% of the dose is excreted unchanged in the urine. Dykes, 1975 Lietman et al, 1974. Moreover, it has been stated that the metabolites of dantrolene especially 5-hydroxydantrolene has around muscle relaxant activity. Ellis Wessels, 1978 Ali et al, 2003.According to Malignant Hyperthe rmia Association (MHAUS) the recommended dosage of dantrolene is approximately 2-3mg/kg. Schulte-Sasse. It had been stated by Flewellen Nelson 1980 that, 95% of the skeletal muscle of swine was depressed with the administration of 3.5mg/kg dantrolene intravenously. In addition, clinical study showed that administration of 2.4mg/kg of dantrole intravenously was able to depress 75% of the skeletal muscle in human. Flewellen et al., 1983. The dose was turn out to be effective in the treatment of malignant hyperthermia. Hall et al, 1980 Kolb et al, 1982. Thus, for acute malignant hyperthermia crisis, 2.4mg/kg of intravenous dantrolene is effective in life-saving of treating malignant hyperthermia. Harrison 1988 Allen et al. 1988 Flewellen et al., 1983. The bingle dose of oral dantrolene that is currently given to patient is 1-2mg/kg four times a day. Pandit et al, 1979 Fitzgibbons, 1981. However, it was found that this recommended dose of oral dantrolene was not effective in preventin g malignant hyperthermia in human. Fitzgibbons, 1981 Flewellen et al, 1983. Administration of oral dantrolene has been recommended before the operation and after the malignant hyperthermia crisis to prevent the recrudescence. Besides administration oral dantrolene, dantrolene can also be given intravenously as a prophylaxis therapy after the crisis. Flewellen et al, 1983. The prophylactic continuous intravenous dose of dantrolene is approximately 2.4mg/kg. Flewellen et al, 1983.Dantrolene is a muscle relaxant, which, acts on skeletal muscle cell to inhibit the release of calcium from sarcoplasmic reticulum. This will reduce the contractility of the skeletal muscle cell. According to Ellis,1973, the relaxant action of dantrolene acted directly and specifically on skeletal muscle but did not act on cardiac and smooth muscle. Besides that, dantrolene did not have any action on central nervous system. Harrison,1988 Ellis, 1972. Harrison and Chapman 1982, stated that the reduction in th e amount and rate of calcium release by dantrolene is effective in preventing and reversing the pathophysiology of malignant hyperthermia in patient. In the experiment carried out by Harrison, 1975 has demonstrated that administration of dantrolene will cause a relaxation of the muscle rigor, cessation of the production of heat and acid.establish on the study carried out by Nelson, 1996 dantrolene is clinically effective in the treatment of malignant hyperthermia and showed a remarkable reduction in death and syndrome associated with malignant hyperthermia. When the syndrome of malignant hyperthermia was first noticed by the world during 60s, the rate of mortality was about 80%. The increasing awareness of syndrome with resultant in earlier diagnosis and treatment markedly reduced the mortality to 28% during 70s. With the introduction of the dantrolene, the rate of mortality reduced to 7%. Harrison, 1988. In addition, the experiment through by Harrison, 1988 showed that 100% surviva l rate was achieved with the administration of dantrolene.Long term administration of dantrolene orally is associated with some side effects such as hepatotoxicity and vomiting, which sometimes may be accompanied by diarrhea. Faling et al, 1980 Wilkinson et al, 1979. However, the occurrence of hepatotoxicity is rare and several studies have been failed to prove whether hepatotoxicity is due to ingestion of dantrolene orally alone. Flewellen et al, 1983 Dykes 1975 Durham et al, 1984. As the reconstitution solution that is formulated for intravenous injection is highly alkaline, if extravasation occur it may irritate the vena which will lead to phlebitis and tissue necrosis. Therefore, dantrolene is recommended that to be injected into the large vein via a central venous catherter.Ward et al, 1986 Muehlschlegel Sims, 2009. Besides that, the mannitol that added to the dantrolene powder will cause osmotic diuresis with the loss of fluids and electrolytes. This will increase the risk of the patient who has poor renal function. Bastron,1983. In addition, in the experiment that carried out by Flewellen and Nelson, chronic administered of dantrolene intravenously will result in difficulty in walking especially down stair. Muscle weakness lasting up to 48hours in 12 malignant hyperthermia subjects and associated with difficulty in walking, especially down stairs. Flewellen Nelson,1983. In the clinical studies that performed by Flewellen and Nelson and Oikkonen and his colleagues, patients were experienced fatigue and difficulty in swallowing accompanied to the long term administration of continuous intravenous dantrolene. Flewellen Nelson, 1983 Oikkonen et al, 1987. The other common side effects of administered of dantrolene are dizziness, light-headedness, drowsiness, weakness, malaise and nausea. Ward et al, 1986 Dkyes, 1975.There is an adverse interaction of dantrolene when co-administration with verapamil. Co-administration of dantrolene and verapamil will cause h yperkalaemia and depression of the cardiac contractility. Rubin Zablocki,1987 Saltzman et al, 1984. The studies carried out by Lynch and colleagues and Saltzman and colleagues stated that administered dantrolene and verapamil concomitantly will cause remarkable hyperkaelemia and cardiac depression in dogs and swine. Saltzman et al, 1984 Lynch et al, 1986. However, not all the calcium channel blockers will cause hyperkaleamia and the depression of cardiac contractility. Neither nifedipine nor amlodipine has significant of hyperkalaemia and depression of cardiac contractility when given together with dantrolene. Freysz, 1996 Saltzman et al, 1984.Besides having adverse effects and adverse interaction, another disadvantage of dantrolene is its cost. Dantrolene is an expensive drug, for intravenous dantrolene, it costs 15.08 per 20mg vial. As it is a huge amount of dantrolene are needed for immediate use, this has became an issue for some hospitals when purchase the dantrolene as dantro lene is very expensive especially intravenous dantrolene and dantrolene has a limited shelf life of 18 months to 2 years. Allen et al, 1988 Hall, 1980.In conclusion, malignant hyperthermia is uncommon life-threatening inherited disorder of the muscle cells. A sudden hypermetabolic reaction of the skeletal muscle when exposed to potent volatile anaesthetics and depolarizing muscle relaxants such as succinylcholine will endanger the patient by causing hyperthermia and massive rhabdomyolysis. Studies showed that appropriate dose intravenous dose of dantrolene is effective in treating patient during acute malignant hyperthermia crisis. Thus, 2.4mg/kg of dantrolene should be given intravenously during acute malignant hyperthermia crisis and continue giving 2.4mg/kg dantrolene after the crisis for 48 hours to avoid recrudescence of malignant hyperthermia. Besides, hypermetabolic reaction and the mortality rate of malignant hyperthermia can be reduced by taking precautions and increasing t he awareness of patient who is malignant hyperthermia susceptible. With appropriate counseling, pre-operative screening and intraoperative monitoring the vital signs and symptoms of malignant hyperthermia can prevent the potential lethal complications arise.