Malignant Hyperthermia Treatment Case Study

Malignant Hyperthermia Treatment Case Study In this scenario, there is a 35 year old female patient who develops malignant hyperthermia during surgery. Malignant hyperthermia is an uncommon pharmacogeneric disorder that leads to the hypermetabolic reactions of the skeletal muscle. [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 important role in triggering malignant hyperthermia. [Ording, 1985]. Primarily, potent inhalation anesthetic agents and depolarizing muscle relaxants such as succinylcholine are the major triggering factor amongst all the triggering factors. Malignant hyperthermia can happen at any time during surgery especially after the induction 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 will cause 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 carbon dioxide concentration (EtCO2), tachycardia and muscle rigidity (especially 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 anesthesia in North America and Europe is 1:15000 anesthetics for children and adolescents and 1:50000- 1:150000 anesthetics for adults. [Hogan, 1998].All ethnic groups are affected with malignant hyperthermia and males are more prone 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, widespread education and clinical and research investigation. [Ali, 2003; MacLennan, 1990] Malignant 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 metabolism and results in increased oxygen consumption, heat and carbo n 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 development 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 vital organ dysfunction, acute renal failure, disseminated intravascular coagulation, congestive heart failure and even death. In this scenario, since the patient developed malignant hyperthermia during surgery, thereby the management of malignant hyperthermia can be divided into emergency treatment 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 administration 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 titrated up to 10mg/kg. [Gronert et al., 1976; Harrison, 1988]. The monitoring of blood gases, all serum electrolytes, muscle enzyme such as cretine kinase, clotting profile, blood and urine for myoglobin, blood glucose, lactate and urea nitrogen must be carried out frequently during the surgery. Sodium bicarbonate should be given to correct the me tabolic 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 solution 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 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 (0.3g/kg) and furosemide (0.5-1.0mg/kg). [Hopkins, 2008; Mary, 1998]. Hyperkalaemia which is life 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 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, 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 Landrace 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 (p Dantrolene is now the only known therapeutic agent used to treat malignant hyperthermia. Dantrolene is a diphenylhydantoin derivative that is highly lipid soluble but poorly water soluble. [PMJ GG Harrison]. Dantrolene can be administered by oral 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, 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 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 4.2ÂÂÂ µg/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 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 dantr olene especially 5-hydroxydantrolene has some 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 proved 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 d antrolene 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 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 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 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 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 irritate the vein 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. [Bastro n,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 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. 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 ÂÂ £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 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 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 the awareness of patient who is malignant hyperthermia susceptible. With appropriate counseling, pre-operative screening and intraoperative monitoring th e vital signs and symptoms of malignant hyperthermia can prevent the potential lethal complications arise.

Immigration Reform Essay

Immigration reform is a widely debated topic that affects the lives of every citizen whether they are for, against or indifferent to the issue. The United States needs a new immigration policy that is based less on wishful thinking and more on realism. Spending vast sums of money trying to enforce arbitrary numerical limits on immigration that bear no relationship to economic reality is a fool’s errand. We need flexible limits on immigration that rise and fall with U.S. labor demand, coupled with strict enforcement of tough wage and labor laws that protect all workers, regardless of where they were born. We need to respect the natural human desire for family reunification, while recognizing that even family-based immigrants are unlikely to come here if jobs are not available. And we need to create a pathway to legal status for unauthorized immigrants who are already here so that they can no longer be exploited by unscrupulous employers who hang the threat of deportation over t heir heads. The impact on ethics regarding immigration reform is that there are many Americans who object to providing health care to those who are in this country illegally and they make the principled point that people who violate the immigration laws of this country have forfeited any moral claim to assistance and should not benefit from their illegal behavior. They also argue that providing those here illegally with access to regular health care will as a practical matter have the undesirable effect of increasing illegal immigration. On the other hand the principled argument in favor of including illegal immigrants in health reform is that decent health coverage is a basic human right. A just nation should support that right for everyone, regardless of why or how a person is in the country. There are also practical reasons to support including undocumented immigrants in health reform. Ethics aside, there is no pragmatic way to deny emergency care to illegal immigrants The impact on morals regarding immigration reform would be how does the issue of immigration reform sits with your mores and values. Should the Christian Values of treating others how you would like to be treated be used? Many Liberals would like to change the laws on immigration to strengthen border security and be fair to taxpayers but also include a pathway to citizenship for immigrants who are in the country illegally. Conservatives would like  to strengthen the existing laws and see that the immigrants that entered the country illegally are deported even though in most cases it would cause the break-up of families as some members may be here illegally and some may be either naturalized or citizens by birth. The things to consider when reviewing how Immigration Reforms would impact our lives is: What are the costs of securing our borders? The current estimate in the costs of securing the borders is $40, 000 per illegal immigrant and the impact it would have on the families and economy of those that live in the border cities would be devastating in terms of loss jobs and revenue. This does not take into account the amount of money spent to hire and train new Border Patrol Agents and drug dogs; using the National Guard and their equipment, and building a fence which places the cost at about 90 billion dollars a year. What are the costs of detaining immigrants? According to the American Civil Liberties Union the cost of detaining an illegal immigrant is between $122 -$164 a day. Should illegal immigrants receive help with medical and food? This is an ethics and moral issue concerning decent human treatment. Though it would place a heavy strain on resources and the economy some type of system should be set up with a limit on how often an illegal immigrant could use the services until citizenship is granted and a repayment plan is instituted.

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Hitlers Rise to Power Essay - 1443 Words

The 1900s marked was one of the most consequential periods of time as it marked the onset of Nazi ideology, an ideology that would be advocated by radical leaders such as Adolf Hitler to maintain power of Germany. Hitler would use National Socialism, which renounced Marxist ideals, as a basis to formulate his own basic views of a philosophy which he would bolster for the rest of his life. As a strong anti-Semite, and an ardent German nationalist, Hitler recognized the importance in the need for struggle and emphasized a crude Social Darwinism; the world was a brutal place filled with constant struggle in which only the fit survived (Spielvogel 794). In order to implement his ideals, Hitler legally came to power in Germany and became†¦show more content†¦Truth was irrelevant. Physical terror was a useful persuader. The way to deliver the message, whatever it was, was through public speaking (Flaherty 10). This is strongly supported by Hitler himself, who commented in Mein Kampf on the magic power of the spoken word and that along. The broad masses of people can be moved only by the power of speech (Hitler 12). Besides speech, Hitler used clever wit to get parliament to pass the Enabling Act, which freed Hitler from the last remaining constraints of constraints of constitutional law and cleared the way for him to seize virtually unlimited power (Fest 28). Thus, because of this, the left was too divided and demoralized to mount effective resistance to the new regime (Stackelberg 103). The militaristic methods used by Hitler are key in assessing why there was so little resistance to his rule. Fest offers an excellent argument in reference to why most people accepted the SA, stating that demoralization had occurred and that people had grown accustomed over the years to unruliness and violence in the streets and were not overly shocked by the activities of the SA gangs...Many people construed Nazi violence as the last means of achieving the sort of profound change in which the only hope of salvation lay (Fest 16). This isShow MoreRelatedHitlers Rise to Power715 Words   |  3 PagesHitlers Rise to Power Following their dramatic loss in the First World War, the people of Germany were suffering greatly, both emotionally and physically during the period of the 1920s and into the 1930s. The harsh stipulations of the Treaty of Paris forced the German government into a fragile and fragmented institution which was ripe for the abuse of power-hungry would-be tyrants. 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