Literature Review Paper

Literature Review Paper

Literature Review Paper

A review of literature is an essential aspect of conducting a study on an observed patient practice problem that requires effective solution. The use of arthroplasty to manage osteoarthritis of the lower limbs continues to increase due to a rise in aging population and existence of lifestyle conditions like diabetes and obesity among other. As such, the purpose of this literature review is to critically evaluate existing evidence on the use of statins in pain management for arthroplasty post-operative patients and its association with increased prevalence of malignant hyperthermia.

Problem Statement

Osteoarthritis is a painful and disabling condition whose prevalence continues due to an aging population. Without known disease-limiting therapeutics, many individuals opt for arthroplasty of the knee and hip or the lower limbs as the most prevalent and effective treatment for lower limb osteoarthritis. Despite this remedy, arthroplasty of the lower limb has a limited life-span and a good number of patients go for revision arthroplasty. However, studies show that due to an increase in life expectancy and a rise in the number of people below 65 years going for arthroplasty, the demand for revision arthroplasty after failure of the implant will surge (Sarmanova et al., 2020). As stated, the conditions of patients before arthroplasty surgery is delicate and painful making it necessary for providers to prescribe statins. Statins are cholesterol- modulating medications used broadly to reduce the risk for cardiovascular disease. These drugs are effective in pain management before surgery, and have pleiotropic effects, including the increasing survival rates before one can go for a revision. Evidence also indicates that statins medications may improve bone growth at the bone-implant interface, leading to the enhancement of functional survival of the implants. However, concerns are now emerging over their role in increasing one’s susceptibility to malignant hyperthermia. In their study, Ward et al. (2019) note that statins reduce cholesterol and help mitigate cardiovascular related morbidity and mortality. The study observes that many discontinue using statin due to the development of statin-related muscle symptoms and other statin-induced side effects. The implication is that statin toxicity can result in malignant hyperthermia (MH) as a skeletal muscle condition.

A study by Oh et al. (2018) demonstrate that there is insufficient data to know if perioperative use of statin reduces or increases postoperative pain. The researchers conducted the study to investigate the link between perioperative statin use and pain outcomes after one has a knee arthroplasty carried out under spinal anesthesia. The retrospective observational study uses medical records from a tertiary healthcare facility to the link between perioperative statin use and a substantial rise in postoperative opioid utilization after arthroplasty surgery. The implication is that the use of statin postoperative situation in arthroplasty has increased leading to more concerns about its efficacy, especially in increasing the chances of one getting malignant hyperthermia.

The problem of malignant hyperthermia associated with the use of statins is a nursing practice issue because of the increased prevalence of surgical operations associated with lower limb osteoarthritis. Patients suffering from lower limb osteoarthritis are opting for arthroplasty surgeries to improve their conditions and live better lives. However, the increased use of statin in these procedures leads to susceptibility to malignant hyperthermia (Sarmanova et al., 2020). Nurses need to ensure that they offer the best pain management medications to patients under their care. However, the administration of statin medications may negate the need for quality care for patients due to the possibility of one developing malignancies in their knee areas leading to poor outcomes.

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Research Question/ PICOT Question

In their study, Gonzalez et al. (2020) assert that statin intake is linked to muscular side effects that include susceptibility to malignant hyperthermia. The study observes that the findings bases on limited experimental data prompts speculation that the use of statin may have negative effects on the performance of skeletal muscles and lower the thresholds in susceptible individuals with malignant hyperthermia or exacerbate its progression. Therefore, the research question is based on a PICOT question formulated to examine the link between statins medications for patients who have had knee arthroplasty and malignant hypothermia.

PICOT Question

In patients who have had knee arthroplasty (P), what is the effect of discontinuation of statin medications three weeks prior to surgery (I), in comparison to no discontinuation of statin medications (C), on incidence of malignant hyperthermia (O) over a six-month duration (T)?


Literature Review

The article by Gonzalez et al. (2020) explores the effects of statin intake on malignant hyperthermia based using in vitro and in vivo approaches. The authors assert that their findings using experimental data in small animals may lead to speculations that statin therapy may compromise the functioning of skeletal muscles in in vitro contracture tests (IVCT). The authors also focused on getting empirical data to determine if statins can lower the triggering thresholds in susceptible individuals (MHS) or increased progression of MH. In their conclusion, the researchers advance that statin treatment does not have any effects on muscle contracture to halothane. Instead, it enhances the muscles. The findings also show support to past studies and views that statin therapy may complicate clinical presentation of MH crises when similar outcomes extrapolate to individuals (Sarmanova et al., 2020). The implication is that use of statin has effects on incidence of malignant hyperthermia as it lowers its susceptibility and helps in pain management.

The findings from the article are related to the research problem as they demonstrate the efficacy of using statin medications to manage pain for individuals with arthroplasty surgical procedures. The article shows that the intervention is effective as it allows nurses to medicate events of pain for better patient outcomes. The authors demonstrate that while there is increased susceptibility to complications related to malignant hyperthermia, patients requiring knee arthroplasty should use these medications before surgery to lower their pain and manage the condition.

Despite its effective findings based on empirical data, the authors suggest the need for further studies to examine in detail the effects of cholesterol-reducing therapies on MH risk in susceptible individuals. The authors are categorical that the outcomes of their study should encourage the need for more research to ascertain the need for better interventions and a reduction of statin to help develop effective interventions. The study observes the need for better interventions and empirical data on the efficacy to deflate the current controversy about the use of statins due to their perceived effects on muscular function while reducing morbidity and mortality associated with the medications.

The second article by Lotteau et al. (2019) develops a mechanism for statin-induced susceptibility to myopathy. Using human and rat muscles, the authors examine the statin mechanism and its interactions with exercise for individuals and rats. The findings show that statin treatment lead to the loss of modulator protein from sarcoplasmic reticulum calcium release route. The authors assert that loss of the modulator protein(FKBP) is linked to reactive nitrogen species and oxygen species that rely on the leaking of species-reliant calcium leak and pro-apoptotic signaling. However, the study observes there are no effects on the functioning of muscles in the body. The study also observes that having moderate exercises like running can prevent the effects of statin treatment on the areas that it has effects on the body. The study shows that there are no detrimental or deleterious effects of statin on skeletal muscles. However, the study observes that statin treatment can induce a possible harmful leak which may trigger statin myopathy among susceptible individual. This effect can be mitigated and prevented using moderate exercise. Those taking statin treatment must use exercises to reduce its harmful effects and attain the positive benefits that the therapy provides.

The findings from the study shows the need for more research to establish the efficacy of statin treatment therapies, especially the harmful effects of the intervention for patients who require knee arthroplasty. The article shows the need for empirical data to support effective use of statin medications in all situations. For instance, among patients who have had knee arthroplasty, using statin medications may lower their risk for malignant hyperthermia in different situations, including the need to relieve and manage pain. The study is important to the research question as formulated by the PICOT framework as it shows that statin medication discontinuation may have mixed outcomes or results. The study demonstrates the need for an effective intervention for postoperative knee arthroplasty patients that may reduce their susceptibility to malignant hyperthermia.

The third article by Pothen et al. (2019) is a systematic review of literature to assess the genetic linkage between different components that include clozapine-induced agranulocytosis, malignant hyperthermia, neuroleptic malignant syndrome, and statin-induced myopathy. The implication is that the authors try to explore a potential common genetic features leading to the development of the adverse effects that include drug reactions. In exploration of a common genetic foundation between clozapine-induced agranulocytosis, malignant hyperthermia, NMS, and statin-induced myopathy, the authors found a gene, SCLO1B1 as prevalent in three of these situations.

The authors also assert that the systematic review shows that there could be another common gene among these conditions based on the overlap of clinical symptoms among the different conditions. The authors recommend the need for more research to help fill existing knowledge gaps in terms of any genetic association between these three conditions and the association mechanism. The article is emphatic that having a common linkage gene implies that statin induced myopathy may not have significant adverse effects on the muscles and lead to malignant hyperthermia among susceptible individuals. However, the suggestion by the authors about the need for more research means that using the intervention requires caution or needs mitigating features like having frequent body exercise for patients to manage pain after surgical operation.

The state of research in this article shows a link to the research problem as it illustrates that using statin medications three weeks before surgery leads to better outcomes for patients as it helps in pain management. The article also demonstrates that individuals susceptible to malignant hyperthermia may still use the intervention but not for an extended duration as this may increase their vulnerability and lead to low quality outcomes. The article emphasizes the need for more research studies to improve fill gaps in knowledge and provide clear evidence about the association between the intervention and adverse events for patients waiting for surgical procedures.

The fourth article by Sangkuhl et al. (2021) explores important pharmacogene information for CACNA1S, as a gene whose variants are related to malignant hyperthermia susceptibility (MHS) as a pharmacogenetic disorder. The article shows different variants of the gene that are linked to an array of muscle disorders with clinical symptoms and manifestations including myopathies, episodic paralysis and even life-endangering responses to those under anesthesia. The article is emphatic that CACNA1S is a gene that affects the overall need to protect MH susceptible individuals from adverse effects of their surgical processes. The article postulates that different variants of the CACNA1S cause adverse effects like MHS while other variants lead to statin-induced myopathy. The article asserts that substantial advances have been made to elucidate the molecular approaches through which mutations from CACNA1S lead to MHS, there is still more to be done in determining the pathomechanisms through which the different variants cause muscle disorders alongside MHS. The authors also recommend the use of their findings among patients and clinicians to understand routine genetic screening and up-to-date information concerning the possible pathogenic nature of any of these variants.

The article is important as it highlights potential negative effects of certain genes and their contribution to increasing one’s susceptibility to malignant hyperthermia. The article shows that calcium variants may be effective in reducing different aspects of pain during surgical process for knee arthroplasty. However, providers and patients must be aware of the causative aspect and reduce their susceptibility to such situations. The implication is that the article contributes to the PICOT question or research question by giving another perspective about the efficacy of the intervention. The article is also important as it illustrates the need for providers to possess knowledge about different aspects of care provision.  The article shows that malignant hyperthermia susceptibility arises from genetic mutations which may interfere with the overall functioning of body muscles among vulnerable individuals. Therefore, using the intervention in patients who may require surgical procedures can be challenging yet have positive outcomes.

The fifth article by Litman et al. (2018) focuses on malignant hyperthermia susceptibility and associated diseases. The authors assert that malignant hyperthermia is an inherited condition of skeletal muscle that presents clinically as a hyper-metabolic crisis when susceptible persons get a halogenated inhalation anesthetic agent before surgical procedures. The authors show that a host of clinical signs present when susceptible individuals are exposed to such agents. These signs may include hypercapnia, masseter muscle and general rigidity of muscles and hyperthermia. The article provides the mechanism of malignant hyperthermia susceptibility that include the unregulated entry of myoplasmic calcium. Through this route, the resulting outcomes include a hyper-metabolic cascade that entails sustained muscular contractures, loss of adenosine triphosphate and the death of muscle cells.


The authors also observe that gene inheritance of pathogenic variants or mutations are linked to MH susceptibility and account for the genetic foundation of close to 70% of patients investigated. Further, using a systemic literature review, the article observes that conditions or diseases caused by variants are mainly linked to MH and these are found in the RYR1 gene that encodes the skeletal muscle ryanodine receptor type 1 protein. Accordingly, it is the protein that is charged with regulation of calcium movement from sarcoplasmic reticulum to the intracellular space within the muscle cells. The implication is that the article demonstrates that MH susceptibility is genetic and may not be associated with the use of statin-induced substances.

The article shows the need for effective information and understanding of the MH susceptibility mechanism among providers to examine the effects of any interventions before one goes for knee arthroplasty procedures. The article is essential for the research question as it shows the need to have an effective understanding of the mechanism underlying malignant hyperthermia susceptibility to help make decisions on whether to use statin medications. The article shows that while statin medications can induce MH susceptibility, most of the causative aspects of the MH susceptibility arise from individuals genetic and inherited factors.

The sixth article by Biesecker et al. (2020) explores genomic screening for malignant hyperthermia susceptibility. The article poses a critical question about the need to end deaths associated with malignant hyperthermia. By reviewing the latest advances and proposing a scientific and clinical pathway, the article offers an in-depth analysis of the need to understand different components of malignant hyperthermia, especially those associated with deaths of individuals in such situations. The article observes that malignant hyperthermia is a prevalent syndrome of acutely disordered skeletal muscle excitation-contraction leading to fever and other symptoms like muscle rigidity. These symptoms arise from triggers like inhalation of anesthetics and depolarizing neuromuscular blocking agents. The implication is that such reactions are challenging to manage and require interventions focused on discontinuation of the trigger agents and administration of correct interventions.

The article offers an analytical approach to the issue and implores one to consider the effects of malignant hyperthermia susceptibility before giving any statin medications to patients requiring knee arthroplasty surgeries. Mortality from a malignant hyperthermia situation accounts for between 4 and 10% of diagnosed cases. Therefore, using any intervention that may be a trigger to the condition may prove challenging for providers. The implication is that malignant hyperthermia is a delicate condition that results from trigger situations where nurse practitioners must have sufficient knowledge before they can provide any medications that they act as trigger factors. The article illustrates increased level of evidence to show that trigger factors may necessitate change of interventions for patients requiring knee arthroplasty where statin medications are considered as the most appropriate yet they can lead to increased susceptibility to the condition.


The need to manage pain associated with osteoarthritis in the lower limbs implores nurse practitioners and other healthcare providers to use different interventions to improve care delivery. The review of the articles on the intervention for patients with pain shows the need for more research to elucidate evidence and demonstrate the efficacy of the suggested interventions. The literature review also demonstrates an increased body of knowledge and evidence to ensure that the intervention works best for patients requiring knee arthroplasty surgical procedures with the view that they will have a revision in the short term. Having more research evidence and empirical data will be key to enhancing overall care provision for individuals with susceptibility.


Biesecker, L. G., Dirksen, R. T., Girard, T., Hopkins, P. M., Riazi, S., Rosenberg, H., … &

Weber, J. (2020). Genomic screening for malignant hyperthermia susceptibility. Anesthesiology, 133(6), 1277-1282.

Gonzalez, A., Iles, T. L., Iaizzo, P. A., & Bandschapp, O. (2020). Impact of statin intake on

malignant hyperthermia: an in vitro and in vivo swine study. BMC anesthesiology, 20(1), 1-8. DOI:

Litman, R. S., Griggs, S. M., Dowling, J. J., & Riazi, S. (2018). Malignant hyperthermia

susceptibility and related diseases. Anesthesiology, 128(1), 159-167.

Lotteau, S., Ivarsson, N., Yang, Z., Restagno, D., Colyer, J., Hopkins, P., … & Calaghan, S.

(2019). A mechanism for statin-induced susceptibility to myopathy. JACC: Basic to translational science, 4(4), 509-523.

Oh, T. K., Chang, C. B., Shin, H. J., Han, S., Do, S. H., Lee, H. J., & Hwang, J. W. (2019).

Association between perioperative statin use and postoperative pain after total knee arthroplasty. Regional Anesthesia & Pain Medicine, 44(2), 221-226. DOI: 10.1136/rapm-2018-000018

Pothen, N., Kansal, S., Rais, T., Doumas, S., & Solhkhah, R. (2019). A look at genetic linkage

between clozapine-induced agranulocytosis, malignant hyperthermia, neuroleptic malignant syndrome, and statin-induced myopathy. Innovations in Clinical Neuroscience, 16(11-12), 28-31.

Sangkuhl, K., Dirksen, R. T., Alvarellos, M. L., Altman, R. B., & Klein, T. E. (2020).

PharmGKB summary: very important pharmacogene information for CACNA1S. Pharmacogenetics and genomics, 30(2), 34. DOI: 10.1097/FPC.0000000000000393

Sarmanova, A., Doherty, M., Kuo, C., Wei, J., Abhishek, A., Mallen, C., … & Zhang, W. (2020).

Statin use and risk of joint replacement due to osteoarthritis and rheumatoid arthritis: a propensity-score matched longitudinal cohort study. Rheumatology, 59(10), 2898-2907.

Ward, N. C., Watts, G. F., & Eckel, R. H. (2019). Statin toxicity: mechanistic insights and

clinical implications. Circulation Research, 124(2), 328-350.


1. Review of the Literature Paper (30% of total grade)
Identify a problem that you have encountered in your nursing practice as a student. The problem could be a procedural practice, a communication problem, or a decision-making problem. Create a problem statement and a research question relevant to the problem. You may use your PICOT question.

Conduct a literature review to identify peer-reviewed articles that relate to the research question. Select a minimum of six (6) peer-reviewed articles (quantitative and qualitative). Write a reflective paper using APA format summarizing each of the six articles, pointing out what the state of the research is related to your research problem. Be sure to include the potential areas for further study.

Paper must be in Word and in APA format, and submitted in Blackboard.


Rubric for Review of the Literature Paper = 30 points

Category 10 5 2 0
Identification of the problem
area in nursing practice Identifies a problem area in nursing practice, providing background and significance of the problem Identifies a problem area with little documentation of background and significance of problem. Does not identify a problem area, and does not include background and significance of problem
Research question Submits a research question using PICOT format Submits a research question but not in PICOT format Omits research question and PICOT format
Review of the literature Submits a literature review describing study findings of six (6) articles (quantitative and qualitative) related to the research question Submits a literature review of three to five (3-5) articles related to the research question with little description of study findings Submits a literature of less than three (3) peer-reviewed articles
Reflective writing Submits reflective writings on 6 articles, mixture of quantitative and qualitative research, summarizing the major tenets of research in each article Submits reflective writings on three articles Submits reflective writings on two articles Submits reflective writing on one article

Uses correct grammar, spelling and APA format Utilizes APA format with minimal errors (1-2) in citation, grammar and spelling Utilizes APA format with moderate errors (3-5) in citation, grammar and Utilizes APA format with significant errors (greater than 5) in citation, grammar and spelling




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