Does Glucocorticoid Therapy Decrease Mortality in Patients with Septic Shock?

Does Glucocorticoid Therapy Decrease Mortality in Patients with Septic Shock?

Abstract

Sepsis is identified as a global health issue and has proven to comprise of severe pharmacological problems. Septic shock, a derivative of sepsis, has a profound characteristic of hemodynamic alterations with the association to organ dysfunction. Primarily it has been associated with degrees of hypovolemia and a decrease in vascular tone in patients with septic shock. An in-depth understanding of septic shock has revealed that corticosteroid use can alleviate the problem and, thus, improve the survival rate of the patients. Diverse therapeutic mediations have been reported. Some address the microcirculatory function of the endocrine system, while others discuss the immunological aspects. Prevalent studies have dominated the immunosuppression mediations, including the use of Glucocorticoid therapy. In the 1900s, the first report of the use of the treatment showed improved survival rates of patients with septic shock. However, issues about consequential post-partum recovery reversed the incidence of mortality among patients with septic shock. As a result, abandonment or reduced use of the therapy was recommended. Despite the increased clinical conflict and adverse effects of Glucocorticoid therapy, research has intensified concerning the use of Glucocorticoid as a corticosteroid therapeutic medium for patients with septic shock. The following report delves into exploring Glucocorticoid therapy. The primary purpose of the paper is to determine if Glucocorticoid therapy can alleviate mortality rates in patients with septic shock. The qualitative review of six studies relating to Glucocorticoid therapy was used, including a wide range of peer-reviewed sources. The findings of the study are that Glucocorticoid therapy has no impact on altering the decrease in mortality rates in patients with septic shock.

Introduction

Septic shock is a global medical issue that has been identified by the World Health Organization as a complex illness that has no proven pharmacological treatment. Despite not having a universal recognition in its definition, reports indicate approximately 200 000 deaths occur each year¹. Sepsis is a clinical ailment that results from an invasion of the harmful or ineffective host response to infection². Sepsis emerges from an initial and necessary host response to an infection, which consequently becomes amplified then, dysregulated². The interest from a clinical and research arena has gained prominence over the years. The symptomology of the illness includes mental confusion, thrombocytopenia, reduced urine output, transient hypotension, and fever².  If left untreated, patients may suffer from respiratory and renal failure, aberrations of coagulation, and unresponsive hypotension². According to an epidemiological study conducted in the United States of America, the overall mortality rate of septic shock affects different age groups at different rates. For instance, the elderly are reported to be the most affected with those suffering from septic shock being also among the most susceptive to death². Septic shock is a form of sepsis that is associated with hypotension and perfusion aberrations³. This is despite the provision of adequate fluid. For the perfusion abnormalities, they include oliguria, acute alteration in mental status, and lactic acidosis³. Current clinical practice guidelines provide a myriad of therapeutic and medical interventions that can be used to treat patients suffering from sepsis, including septic shock. Primarily, the use of glucocorticoid therapy is among the most prominent methods. The rationale in the administration of Glucocorticoid in patients with septic shock is based upon profound studies that indicate that the critical illness induces a state of absolute or relative adrenal insufficiency, thus contributing to shock⁴. Hence, the purpose of administering glucocorticoid therapy is to restore the balance to the different hypothalamic-pituitary-adrenal axis to improve clinical outcomes, especially mortality⁴.  The present research aims to determine if the administration of glucocorticoid therapy in septic shock patients decreases mortality.

Background

1. Pathophysiology

Patients are suffering from septic shock experience extensive hemodynamic changes, which are often associated with organ dysfunction⁵. The hemodynamic changes are characterized by degrees of hypovolemia and reduction in vascular tones in addition to myocardial depression⁶. The pathophysiology of septic shock involves the imbalance between the supply and demand of oxygen. It consequently leads to the clinical syndrome, a septic shock that encompasses hypotension and hypoperfusion leading to cellular dysfunction⁶. In retrospect, sepsis is a response to infection in which septic shock is a type of sepsis that is caused by hypotension in addition to aberrations in perfusion. In this case, there are four types of septic shocks. They include: hypovolemic, cardiogenic, distributive, and obstructive⁶.  Septic shock, nonetheless, is primarily a vasodilatory shock or distributive shock. This means that there is an abnormal distribution of blood volume due to vasodilation. Therefore, it reflects at the continuum end, which is a progressive pathophysiological decline that culminates with hypotension that is poorly receptive to satisfactory fluid resuscitation⁶. As such, the hypotension is conveyed by hypoperfusion and organ dysfunction.

Septic shock is accompanied by three significant pathophysiologic effects that are cardiovascular oriented. They include maldistribution of blood flow, vasodilation, and myocardial depression⁶. The intravascular volume (absolute) may be standards; nonetheless, due to acute vasodilation, there is relative hypovolemia, which occurs as a result. Contrary to this, the other types of septic shocks occur that are characterized by reduced cardiac output or obstructive. It is a defining aspect of septic shock, which is the maldistribution of blood flow in the microcirculation⁶. The resulting issue is that myocardial depression may occur. With relative hypovolemia, myocardial depression, and maldistribution, there is a resultant decrease in oxygen delivery, which subsequently affects tissue hypoxia⁶.

• Vasodilation: with septic shock, the pro-inflammatory cytokines, in addition to other metabolites, increasing endothelial-derived nitric oxide. Nitric oxide is associated with alterations in the cell wall transport mechanism in addition to intracellular factors. The effect is the reduction in intracellular calcium, which subsequently leads to vasodilation⁶. The development of resistance from vasopressor agents is also consequential. In this case, the resistance to the agents leads to the activation of adenosine triphosphate-sensitive potassium channels. This, as a result, leads to the reduction in intracellular levels (hypoxia) and amplified intracellular hydrogen concentration as well as lactate. The activation of the potassium channel results in hyperpolarization, which inhibits calcium influx into the cells. The countermeasure is the activation of potassium channels, which result in hyperpolarization, which is the gateway to septic shock development.
• Maldistribution of blood flow: it is reported that some vessels within the circulatory system remain vasoconctricted. The reason is based on septic shock pathology, which is associated with vasodilation. As a result, it leads to the phenomenon of maldistribution of blood flow. Epidemiological studies on vasoconstriction indicate that it results from the various inflammatory mediators. These could include tumor necrosis factor⁶.
• Myocardial depression: inadequate fluid resuscitation within the body alongside septic shock results in a hyperdynamic state, which entails amplified cardiac output and decreased systemic vascular resistance⁶. They altered beta-adrenergic signal transduction results in reduced leaves of cell membrane protein, which is paramount for beta-adrenergic binding in addition to signal transduction⁶. For patients who suffer from acute cardiovascular alterations, may experience the symptoms for more than four days. For those who survive the episode, they return to normal for ten days. Interestingly, it is reported that those who persevere through the cardiac episode are more likely to suffer from myocardial depression compared to those who do not⁶.

1. Diagnostic Criteria of Septic Shock

The general variables with septic shock include fever, hypothermia, heart rates (> 90/min), tachypnea, altered mental state, and significant edema or positive balance in fluid (> 20 ml over 24 hours). Additionally, variable on hyperglycemia is also measured. The variations include plasma glucose should be > 120 g/dl⁶.

For the inflammatory variables, leukocytes should comprise white blood cells count above 12 000 per microliter, leukopenia, which ought to contain white blood cell count below 4000 microliters, and normal white blood cell count should be more than 10% immature forms⁶.

For the hemodynamic variables: the arterial hypotension should comprise of SBP < 90 mm Hg and cardiac index of less than 3.5 L/min/m².

For the organ dysfunction variables: arterial hypoxemia, acute oliguria, creatinine increase, coagulation abnormalities, thrombocytopenia, hyperbilirubinemia, and ileus are determined⁶.

For the tissue perfusion variables: the hyperlactatemia and decreased capillary refill are monitored⁶.

1. Management of Septic Shock

The management of septic shock relies on a variety of clinically approved therapeutic and medical oriented interventions. Among them include initial resuscitation and infection issues, hemodynamic support, and adjunctive therapy, and supportive treatment of severe septic shock or sepsis. With respect to the current report, Glucocorticoid therapy is of interest. Previously, the use of hydrocortisone in patients suffering from septic shock was recommended¹. This was only recommended if fluid adequate for resuscitation and treatment use of vasopressors was not adequately restored for hemodynamic stability. Concurrent use of hydrocortisone therapy is an alternative therapeutic approach clinically suggested. The downside to all the treatments mentioned above is that limited success in the survival of septic shock patients is reported ^{7, 8}. Therefore, the increased popularity use of Glucocorticoid therapy has emerged¹. Glucocorticoids play a significant role in the regulation of the activity of nuclear aspects, which is crucial to the induction of cytokine gene expression⁸. However, different glucocorticoids play a differential effect on gene transcription, which have differing pharmacodynamics effects⁸. Evidence-studies have indicated that glucocorticoids have been associated with high-level incidences of deficiency, which significantly affects mortality rates in patients.

Nonetheless, the dilemma remains on whether the efficacy of Glucocorticoids in reducing mortality among patients is achievable. The inquiry is based on emergent issues such as side effects regarding the use of Glucocorticoid therapy among septic shock patients. These include superinfection and metabolic as well as neuromuscular effects¹. Nevertheless, the intact hypothalamic-pituitary-adrenal axis is regarded as the most effective intracellular glucocorticoid activity for host survival during septic shock⁷. Exploration of this from a scientific perspective may determine how this happens and whether it affects death rates.

Methodology

The present report aimed to investigate if the use of glucocorticoid therapy affected the rate of mortality in patients with septic shock. To achieve this, the researcher embarked on determining the best keywords to use for the search. The keywords for this report were: septic shock, sepsis, glucocorticoid therapy, mortality rates, and pathophysiology. After determining the keywords, the appropriate search engines were determined. Based on the recommendation from the learning institution, the researcher used the following search engines: NCBI, PubMed, MEDLINE, Google Scholar, EMBASE, and CINAHL. The search criterion was based on inclusion and exclusion criteria as follows. The inclusion/exclusion criteria included a timeline of publication, area of study, journal, study design, language, and proximity (geographical). American-based publications were used for the project. Besides, the inclusion criteria required the studies to either be epidemiological, pathological, meta-analysis, and experimental. Also, reviews of previous studies were accepted in this research. The exclusion criteria did not include paper published before 2000 with the inclusion criteria giving lee-way to papers published after 2000 to improve on information gathering on glucocorticoid therapy and its achievements and setbacks. Additionally, the exclusion criteria disqualified articles or publications that did not expound on septic shock patients. The initial search provided 100 documents; however, with improved keyword search, the resulting number of journals was six. They are:

1. Meduri, G. Umberto. “A historical review of glucocorticoid treatment in sepsis. Disease pathophysiology and the design of treatment investigation.” Sepsis3, no. 1 (1999): 21-38.
2. Sprung, Charles L., Serge Goodman, and Yoram G. Weiss. “Steroid therapy of septic shock.” Critical Care Nursing Clinics, 23, no. 1 (2011): 171-180.
3. Prigent, Hélène, Virginie Maxime, and Djillali Annane. “Science review: mechanisms of impaired adrenal function in sepsis and molecular actions of glucocorticoids.” Critical Care8, no. 4 (2004): 243.
4. Marik, Paul E. “Glucocorticoids in sepsis: dissecting facts from fiction.” Critical Care, 15, no. 3 (2011): 158.
5. Annane, Djillali, Alain Cariou, Virginie Maxime, Elie Azoulay, Gilles D’honneur, Jean François Timsit, Yves Cohen et al. “Corticosteroid treatment and intensive insulin therapy for septic shock in adults: a randomized controlled trial.” Jama303, no. 4 (2010): 341-348.
6. Bornstein, Stefan R., and Josef Briegel. “A new role for glucocorticoids in septic shock: balancing the immune response.” (2003): 485-486.

Review of Literature

The interest in the use of glucocorticoid therapy in patients diagnosed with sepsis or septic shock has gained both positive and negative reviews. Based on a review study on the evaluation of prolonged glucocorticoid therapy in patients with septic shock, it was revealed that the treatment led to reduced mortality rates among the patients. The review study analyzed four small-sample sizes, double-blind, randomized trials⁹. In the end, the results perpetuated that the use of glucocorticoid therapy resulted in a significant reduction in mortality rate, meaning the beneficial component of treatment was noticeable. However, the downside to these studies is the sample size⁹. From a clinical perspective, it is elucidated that such as small epicenter study cannot be extrapolated to highlight a massive investigation of the possible outcomes of glucocorticoid therapy for septic shock patients⁹. A closer look at the review study suggests that the positive results obtained from the four studies were as a result of the individual parameters utilized within the groups. Parameters, including dosage, administration time, and duration of administration, contributed immensely to the positive results. For example, it was noted that high dosages of Glucocorticoid resulted in lower mortality rates among the patients diagnosed with septic shock⁹. It was observed that if dosages were employed at rates five to sixty times higher than the standard dosage, then the rates of mortality significantly decreased. However, one concerning factor was that despite the strides made within the trials, the mortality rate was still experienced. The hypothesis within these studies was that underlying secondary infections might have contributed to the high mortality rates. To this end, therefore, a different look at how glucocorticoid therapy could be deduced for reduced mortality rates was necessary.

With respect to glucocorticoid therapy, clinical and medical research has focused on understanding how glucocorticoid therapy in sepsis redefined the concept of immunology, adrenal physiology, cellular mechanisms, and infectious diseases⁹. In the beginning, that is in the 1970s and 1980s, the use of a high dosage of Glucocorticoid as a form of corticosteroids was utilized. However, the detrimental effects of the high dosages included the inability of the patients to withdraw safely from the high clinical addiction to medicine. Concurrently, the rates of deaths subsequently increased over the years¹⁰.  There have been numerous reports devising explanations as to why they use of glucocorticoid therapy leads to increase mortality rather than the intended reduction in mortality.

The current issue is on the glucocorticoid insufficiency. Glucocorticoid insufficiency is described as the inability of corticosteroid therapy to properly induce the intended effects, which is to reduce septic shock in patients ¹⁰. The mechanisms of glucocorticoid insufficiency have been widely studied in patients with septic shock from a molecular level. With patients with severe sepsis, for instance, it is reported that numerous tenets, including drugs, coagulation abnormalities, and inflammatory mediators, contribute to the ineffectiveness of Glucocorticoid therapy¹¹. These factors, according to a meta-analysis study, concluded that they affect the HPA, including the secondary adrenal failure and the inability of the Glucocorticoid to access the target cells¹¹. Glucocorticoids interact with specific glucocorticoid cytosolic receptors allowing them to undergo specific conformational alterations, including shedding heat in septic shock patients. As a result, it relocates to the nucleus. Worse still is that Glucocorticoid may interact with membrane binding sites on the cell surfaces. This results in genomic and non-genomic effects, indirect and direct transcriptional effects relating to the glucocorticoid receptors.

Ideally, to keep the HPA intact, the combination of HPA alongside the use of glucocorticoid therapy is recommended for anti-inflammatory activity, which is necessary for patients with severe exposure to infectious agents such as those with septic shock. The primary role that Glucocorticoid has played through extensive study resolution is in the regulation of the activity in the nucleus. The nuclear factor kappa-beta has a critical role in inducing cytokine gene transcription after exposure to an infectious agent¹². Nevertheless, patients with severe sepsis, for instance, have been reported to show complex alterations of the HPA axis¹². A meta-analysis research study involving more than ten reports indicated that most of the patients subjected to Glucocorticoid had varied reactions. One study suggested that patients who received Glucocorticoid went into severe shock alterations, and only 24% recovered after administration of etomidate while those who did not receive glucocorticoid therapy, 19% only survived¹². The selection criteria of the study revealed biasness. The participants were only chosen if they exhibited refractory septic shock. As such, the results from these studies might not be pertinent to the overall outcome of determining glucocorticoid therapy on the effects on mortality rates among patients with septic shock.

Adjunctive therapeutic interventions using glucocorticoid therapy have been suggested as a mediatory mechanism for reducing the counter-effects noted in septic shock patients. Primarily, the use of hydrocortisone has been recommended. According to the study done by Annane et al. ¹³ discovered that patients with severe septic shock might have a prolonged immune dysregulation. In their view, they suggest that the more extended use of corticosteroids, including Glucocorticoid, was necessary. But, previous results involving more than 3 000 patients resulted in severe mortality rates in durations within 90 days and 24 days after administration of the therapeutic intervention¹³. Therefore, the researcher recommended the use of hydrocortisone alongside glucocorticoid therapy to expedite the recovery process. It was discovered that the continuous use of hydrocortisone resulted in better glycemic control with less variability in glucose concentrations in the blood system¹³. Similar reports on the same indicate that differential concentration levels of glucose in patients may be an independent factor to how well they handle the shock¹³. Nonetheless, the reports agree that the continuous use of Glucocorticoid may result in impairment of the HPA axis. Alongside this, Glucocorticoid has been documented to alter the gene transcription; thus, it has differential pharmacodynamics effects¹³. In retrospect, alterations in the HPA axis, the difference in pharmacodynamics effects, and glucocorticoid insufficiency warrant the impaired use of the therapy for septic shock patients.

Nonetheless, with increased interest in glucocorticoid therapy, alternative use of the Glucocorticoid has emerged. This, in the end, may result in reduced mortality rates of the Glucocorticoid in septic shock patients¹⁴. According to a review study on the new role of Glucocorticoid, it has emerged that it can play a more immune-based role than the initial intent on inflammatory concern¹⁴. Glucocorticoids have been known to have an essential role in the immunosuppressive agent in medicine for patients with inflammatory diseases, including septic shock. However, due to the uncertainty surrounding the use of the therapy, abandonment of the treatment altogether has always been the recommended ideology.

Other than that, it has been recommended by the extensive study done by Annane et al. ¹³ to understand individual patient needs and adjust dosages in the required amounts for effective treatment. Previous reports on corticosteroid use, including hydrocortisone, have revealed reduced inflammatory cytokines, including interleukin-6 and 8¹⁴. Interleukin-6 and -8 are necessary anti-inflammatory mediators in patients. The receptors are reported to work well with hydrocortisone but not with Glucocorticoid. The reason is that, based on a pathological study on Glucocorticoid, it was determined that the therapeutic medium acts antagonistically with the interleukin-receptors¹⁴. The Glucocorticoid induce Fc receptors on monocyte cells and peritoneal macrophages. As a result, the high-affinity for Glucocorticoid in patients results in increased phagocytosis¹⁴.

A counter study done on Glucocorticoid showed an increased immune-enhancing effect on the innate immune system profiling through the use of a micro-array technology¹⁴. It is reported that within the human cells, the T-cells receptor cross-links with Glucocorticoid then downregulated through the expression of specific genes that are previously in the resting stage. In this, the researchers determine that it provides synergistic effects in the glucocorticoid therapy. Of particular interest was the discovery of the interleukin-12 which is reported to increase during hydrocortisone treatment in patients with septic shock. Similarly, it was observed that the interleukin-12 was suppressed during non-septic conditions¹⁴. The revelation, according to the study, is that this has changed the view in which Glucocorticoid plays in immunosuppressive mechanisms during an immune system recovery. Therefore, it appears that the dosage, time of administration, and withdrawal from glucocorticoid therapy may be the key to redefining the use of Glucocorticoid in reduced mortality rates for patients with septic shock. Nonetheless, issues surrounding corticosteroid insufficiency has been reported to induce exaggerated pro-inflammatory response¹³. However, there remain extraordinarily controversial and conflicting recommendations when it comes to the use of Glucocorticoid, given the increase or predominant issues surrounding mortality rates among patients with septic shock¹⁵. Therefore, there is a lot in question regarding the effects that Glucocorticoid has on patients, including immunological, organ –adrenal and HPA, and molecular and genomic effects¹⁵.

Discussion

The main discussion point for this project is to determine whether glucocorticoid therapy reduces mortality rates in patients with septic shock. Thorough analyses of the peer-reviewed journal have given profound information with this regard. Primarily, the results have indicated that there are factors that influence the probability of using glucocorticoid therapy in the reduction of mortality rates among patients with septic shock. From a historical view, studies focused on understanding how the proposed treatment, Glucocorticoid, could aid patients with septic shock or sepsis were conducted. The results of the literature review indicate that initially, there were positive results pertaining to the alleviation of mortality rates in patients. To effectively connote this, the double-blind studies placed the selected patients into two groups: one provided with the corticosteroid and another with placebo. Those under glucocorticoid therapy were reported to have reduced septic shock meaning that mortality rates were significantly reduced.

Nonetheless, a further look at the studies reveals that differential treatments were put into account. One factor on dosage was determined to alleviate the stress. High dosage, for instance, was shown to have a higher impact outcome compared to low dosages. The recommended dosage was five times to sixty times the minimum amount of dosage required for the patients. The downside to this is that, consecutive studies on dosage have shown that withdrawal from glucocorticoid therapy by patients with septic shock has more detrimental effects than positive effects. Therefore, an articulation that Glucocorticoid may not alleviate mortality rates became a reality.

Further, the results of the literature review indicated that clinical and experimental results focused on a different factor. The factor of focus was the molecular and immunological concept regarding how efficiently glucocorticoid therapy would improve on survival rates among patients with septic shock. The revelation within the studies was that mechanisms that underlie within the therapeutic mechanism showed insufficiency in glucocorticoid effectiveness. The survey conducted by Prigent et al. on mechanisms impairing adrenal function in sepsis and molecular actions of Glucocorticoid showed that there were severe organ failures concerning the use of Glucocorticoid therapy¹¹. The review article indicates that several factors predispose the glucocorticoid insufficiency which in turn limits its potential in intended survival rates among patients. Factors such as coagulation, inflammatory mediators and drug use were chief among the issues that reduce efficiency of the medication. Primarily, the factors affect the functionality of the hypothalamic-pituitary axis, the adrenal glands and impair the glucocorticoid access to target cells. Similar reports have been provided by Marik ¹²on glucocorticoid and sepsis and the meta-analysis research by Annane et al. ¹³ The studies explicitly indicate that the continuous use of glucocorticoid therapy has resulted in reverse anatomical alterations. As a result, there are irreversible connotations with the hypothalamus, adrenal glands and the pituitary glands. The consequence to this is that, the survival rate of patients with septic shock drastically reduces. Therefore, comprehension of how Glucocorticoid works alongside the patient has been deduced to be individual based, which according to the study conducted by Annane et al., has shown to be more effective in drug dosage alterations¹³.

Another factor that was noticed during the analysis of the results is that glucocorticoid therapy results in adrenal gland failure. The initial perspective about glucocorticoid therapy is that it formulates on being an immunosuppressive agent. Therefore, its primary intent is to alleviate chronic inflammatory diseases, particularly in patients with septic shock. But, with consistent clinical trials, negative results have been obtained with the continuous use of glucocorticoid therapy. Among them is the irreversible function of the adrenal glands. A randomized study determining the effect of glucocorticoid therapy on patients with septic shock revealed that anatomical damage to the adrenal glands was present. According to the study¹¹spetic shock often results in decreased synthesis of CRH and ACTH through the induction of irreversible anatomical damage in the pituitary gland and hypothalamus.

In most cases reported in the study, patients’ arterial supply to the pars distalis was reduced or was absent. This means that pituitary necrosis was well established due to the dramatic cardiovascular collapse or Sheehan syndrome during the post-exposure period of Glucocorticoid therapy¹⁵. Therefore, the conclusion to this study was that glucocorticoid insufficiency is often associated with a deficiency in the thyroid in addition to the growth hormones, including vasopressin. This is a result of necrosis of the hypothalamus or the pituitary gland, which has been reported in patients with prolonged hypotension and coagulation disorders.

Concerning secondary adrenal failure, there has been an association with hypothalamic or pituitary necrosis. Concurrently, it has been reported that with drug therapy, adrenal insufficiency is reported. Studies regarding the performance of the adrenal glands during glucocorticoid therapy have reported that prolonged use of the therapeutic measure has induced prolonged suppression of CRH and ACTH synthesis. Worse still, is that the reports have shown delayed HPA performance with a single use of Glucocorticoid depending on the inflammation and duration of glucocorticoid administration¹⁶. For example, the topical administration of Glucocorticoid has resulted in immediate adrenal failure and subsequent suppression of the pituitary gland and hypothalamus functionalities. In summary, it can be concluded that from a pathological point of view, the use of glucocorticoid therapy has shown higher adrenal insufficiency in patients with septic shock.

The increased failure but corresponding effectiveness of glucocorticoid therapy has resulted in reviewing the dogma regarding the use of the medication. The proposed use of hydrocortisone alongside Glucocorticoid has been revered as an excellent method for improving the effects of Glucocorticoid. A review study by Bornstein et al. on the role of Glucocorticoid has shown that diverse blinded experiments led to improved performance of patients with septic shock¹⁴. The placebo-controlled study by Keh et al. ¹⁷showed that low-dose hydrocortisone could restore the hemodynamic stability in patients with septic shock or sepsis. The definition to this is that hydrocortisone infusion lead to hypertension and systemic vascular resistance alongside reduced heart rates. The relief to these studies is that the use of hydrocortisone is associated with reduced inflammatory incidences with respect to interleukin-6 and -8. Coincidentally, with increased use of v therapy alongside hydrocortisone has led to improved inflammation reduction in patients with septic shock¹⁸. The explanation is that with glucocorticoid hormones there is a synergistic relationship with the interleukin-6 and -8. Glucocorticoid hormones have a high affinity for the interferons and to induce Fc receptor expression in monocytes. It suggests that the effect of Glucocorticoid may have a more provisional role in boosting the immune system when working alongside other corticosteroid therapies.

In summary, the results of the research have shown that when Glucocorticoid is used singularly, there are detrimental effects on the human body. Primarily, it has been observed that the facts are on the immune system, adrenal, and other organ structures, as well as mortality rates as a consequential effect. As a result, the use of the therapy has always been riddled with negativity, including conflict on the recommendation of use as well as clinical use. However, with the recent adjunctive studies regarding the therapy¹⁸, it has been noted that glucocorticoid therapy can be used alongside other treatments under corticosteroids to impart a more positive effect and outcome. Consequently, it has been reported that glucocorticoid therapy can be used to boost immune systems, rather than the original intent of alleviating inflammations in patients with septic shock.

Conclusion

The research overall has provided in-depth knowledge of the ups and downs of the use of glucocorticoid therapy concerning patients with septic shock. In particular, the treatment has been noted to have more negative effects than positive ones concerning reducing inflammations. Effects include reduced pituitary and hypothalamus, reduced adrenal gland functionality, and immunosuppression¹⁹. As a result, the therapy has faced negative reviews of use from clinical to experimental. Therefore, the effects of Glucocorticoid have shown diverse responses in different patients based on whether they have acute or severe septic shock. Inherently, reduced or abandonment of the use of the glucocorticoid therapy has been adopted. However, the present research has shown some hope concerning how the Glucocorticoid is used. This pertains to the continuous use and appreciation of the therapy given that clinical trials and experiments have reported different results, unlike similar results in the medical arena. Among the perceived applications is for immune-boosting treatments rather than the original intent for inflammation therapy. Previous studies have shown extreme adverse effects regarding the use of glucocorticoid therapy. With this in perception, it is necessary to take into account the recommendation of understanding the use of glucocorticoid therapy from an immunological standpoint alongside the use of other corticosteroids. Studies explored in this project have revealed that the use of glucocorticoid therapy has provided more positive results than those which have used the treatment alone. Therefore, addressing the effects of the treatment in the immune system alone may provide more improvements in the use of the corticosteroid to improve the survival rates of a patient with septic shock.

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