Malignant Hyperthermia Treatment Case Study

Malignant Hyperthermia Treatment Case StudyIn this scenario, at that place is a 35 year old female longanimous who develops cancerous hyperthermy during surgery. Malignant hyperthermy is an uncommon pharmacogeneric dis tell apart that leads to the hypermetabolic reactions of the atrophied brawninessman. Ben Abraham, et al, 1998, Britt, 1985, Hopkins, 2008. Age, fount of anesthetic agent, environmental temperature, mitigating drugs administered simultaneously and degree of stress play an important affair in triggering malignant hyperthermia. Ording, 1985. Primarily, potent inhalation anesthetic agents and depolarizing bodybuilder depressants such as succinylcholine are the major triggering factor amongst each(prenominal) the triggering factors. Malignant hyperthermia can happen at any time during surgery curiously after the induction of the anesthetic and in the early postoperative period. likewise that, there is a tendency of the recurrent of malignant hyperthermia as well.Even though hypermetabolic reaction of skeletal muscle result obtain hyperthermia and rhabdomyolysis but fever is not the earliest symptom of malignant hyperthermia. The earliest signs and symptoms of malignant hyperthermia are increase in the end-expired degree Celsius dioxide compactness (EtCO2), tachycardia and muscle rigidity (especi anyy when succinylcholine is presumption). Britt, 1985. Furthermore, the late sign of malignant hyperthermia is elevation of the clay temperature. Ali et al, 2003 Britt,1985.The other signs and symptoms are unst adequate to(p) broth pressure, tachypnea, hyperkalemia and arrhythmia. tally to Hogan, 1998 the estimated incidence of malignant hyperthermia during anesthesia in North the States and Europe is 115000 anesthetics for children and adolescents and 150000- 1150000 anesthetics for adults. Hogan, 1998.All ethnic groups are travel(p) with malignant hyperthermia and males are more prone to be affected compared to female. Britt, 197 6 Hopkins, 2008. The mortality was around 80% thirty years ago and has been trim back to less than 10% with the introduction of the muscle relaxant dantrolene sodium, widespread pedagogy and clinical and research investigation. Ali, 2003 MacLennan, 1990Malignant hyperthermia is an hereditary disorder where the atomic number 20 channel that mediates the excitation contraction coupling in skeletal muscle is mutated. As a result, the atomic number 20 channel is very sensitive to the anesthetic agents Hopkins, 2008. This get out lead to the uncontrolled boot out 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 reflectivity of the signs and symptoms of malignant hyperthermia can be explained by the increased release of the calcium. At first, thi s 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 get out establish the stimulation of the metabolism and results in increased atomic number 8 consumption, modify and carbon dioxide payoff. The breakdown of the ATP causes the release of the potassium into the extra cellular legato results in hyperkalemia and this go outing lead to the development of cardiac arrhythmias. likewise that, the endless contraction of the skeletal muscle due to the breakdown of the ATP leave alone lead to the further production of heating system. 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 and therefore further worsening the rhabdomyolysis process. If malignant hyperthermia is un dole outed, it might lead to merry organ dysfunction, crafty renal failure, disseminated intravascular coagulation, congestive heart failure and steady death.In this scenario, since the patient developed malignant hyperthermia during surgery, thereby the way of malignant hyperthermia can be divided into emergency word and postoperative crossment. When there is an acuate 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 administration of 2.5mg/kg dantrolene sodium endovenously every 5 minute until the signs and symptoms of malignant hyperthermia are under controlled. Morgan et al. 2006. The pane of dantrolene can be tit assessd up to 10mg/kg. Gronert et al., 1976 Harrison, 1988. The observe of blood gases, all serum electrolytes, muscle en zyme such as cretine kinase, change state profile, blood and pissing for myoglobin, blood glucose, lactate and urea nitrogen must(prenominal) be carried out frequently during the surgery. Sodium bicarbonate should be given over to correct the metabolic acidosis to the normal level. In addition, patient has to be unopen 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, modify blanket, and nasogastric lavage with iced solution can be used to cooling system 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 discerning prevent renal failure piss output 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 (0.3 g/kg) and furosemide (0.5-1.0mg/kg). Hopkins, 2008 Mary, 1998. Hyperkalaemia which is life-time threatening can be treated with glucose, insulin, intravenous calcium and intravenous potassium chloride. Britt, 1979 Hopkins, 2008.Once the surgery is finished, the patient has to be moved to intensive care unit 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(prenominal) 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, besides 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, 1 972 and Noble, 1973. The study carried out by Harrison, 1971 showed a successful treatment of malignant hyperthermia with large window pane of intravenous procaine in 2 out of 5 Landrace pigs. However, the study from Gronert, 1976 showed that the recommendation dose of procaine/ procainamide was unproductive in preventing malignant hyperthermia of the 20 susceptible pigs. Study compared the potency of dantrolene and procainamide conducted by Nelson, 1979 showed that procainamide did not block the contracture response to halothane and it is in impressive for therapeutic and as prophylaxis of malignant hyperthermia. Procainamide or procaine was not been used after all.Harrison, 1975 show that dantrolene can relax muscle rigor in pigs with malignant hyperthermia and ceased the excessive heat and acid production. The study showed 100% endurance rate in the last seven of eight examines. also that, based on Britt, 1984 that 79 patients who received dantrolene therapy showed a signif icant 16.56% reducing in mortally (pDantrolene is now the only known therapeutic agent used to treat malignant hyperthermia. Dantrolene is a diphenylhydantoin derivative that is highly lipid oil-soluble but poorly water soluble. PMJ GG Harrison. Dantrolene can be administered by verbal route or intravenous route. Roughly, 70% of dantrolene is absorbed with the peak plasma concentration reached in 6 hours following the ingestion of dantrolene by mouth. From the experiment performed by Harrison 1975, viva voce dantrolene was effective in treating procaine malignant hyperthermia. Nevertheless, there is a great variation in the plasma concentration for the verbal dantrolene especially in children. Dantrolene is explicate as lyophilized orange powder, which comprises of dantrolene sodium, mannitol and sodium chloride. These contents are dissolved in water to progeny a solution with the pH of 9.5 for intravenous injection. Moreover, the additional of the mannitol is to im sustain the solubility since dantrolene is poorly water soluble and mannitol also acts as diuresis, which prevent the deleterious effects of myoglobinaemia. The biological elimination half life of dantrolene 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 drop-off 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 cut down acetylated derivative 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 most muscle relaxant activity. Ellis Wessels, 1978 Ali et al, 2003.According to Malignant Hyperthermia 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 prove 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 single 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 preventing 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 undisturbed muscle. Besides that, dantrolene did not have any action on aboriginal nervous system. Harrison,1988 Ellis, 1972. Harrison and Chapman 1982, stated that the reduction in the 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.Based 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 notice by the world during 60s, the rate of mortality was about 80%. The increase knowingness 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 done by Harrison, 1988 showed that 100% survival 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 baffle the mineral vein which will lead to phlebitis and tissue necrosis. in that locationfore, 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 barrier 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, wea kness, 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 hyperkalaemia 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. incomplete 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 costly drug, for in travenous dantrolene, it costs 15.08 per 20mg vial. As it is a huge amount of dantrolene are demand for immediate use, this has became an issue for some hospitals when purchase the dantrolene as dantrolene 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 separate 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 crisi s 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 the awareness of patient who is malignant hyperthermia susceptible. With appropriate counseling, pre-operative screening and intraoperative monitoring the decisive signs and symptoms of malignant hyperthermia can prevent the potential lethal complications arise.