Topic: The Controversy of using Corticosteroid in septic shock patients
Ranya Bafail
University of Michigan School of Nursing
Introduction:
Severe sepsis and septic shock are major public health problems globally and are associated with substantial morbidity and mortality. The role of corticosteroid treatment in patients with severe sepsis and septic shock remains controversial despite the studies that have been using since decades.
The issue:
HPA axis and septic shock:
The complex pathophysiologic changes in severe sepsis and septic shock are known to have important impact on endocrine organs with reported alterations in thyroid, pancreas, and adrenal function (1). By far the most controversial endocrine topic in
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patients with severe sepsis and septic shock surrounds the optimum method to evaluate adrenal function in these critically ill patients and how to diagnose and subsequently treat those who have corticosteroid insufficiency (2). The HPA axis is composed of a complex set of positive and negative signals and feedback loops that regulate cortisol synthesis and release (3).
Corticotropin-releasing hormone initiates the synthesis of adrenal corticotropin hormone (ACTH) from the anterior pituitary gland, which stimulates the adrenal to produce cortisol (4). Sufficient levels of cortisol production inhibit further production via a negative feedback mechanism. In addition, vasopressin, a neurohormone synthesized in the supraoptic and paraventricular nucleus of the hypothalamus and stored in the posterior pituitary, has been shown to regulate cortisol production via V1a and V1b receptors (4,5). The majority of cortisol in the circulation is bound to proteins, corticosteroid-binding globulin (70%), and albumin (20%), but the circulating free cortisol is the active form (4 ,5). Critical illnesses, such as severe sepsis, are associated with a decrease in albumin and corticosteroid-binding proteins, which may result in a decreased total cortisol measurement but a relative increase in the free cortisol level (4, 6, …show more content…
7). The incidence of adrenal dysfunction during severe sepsis and septic shock has been estimated to be as high as 50% (8).
The dysfunction can be either inappropriately low production of glucocorticoids or an impaired response to cortisol in the systemic circulation. Molecular interactions, classified as either genomic or nongenomic pathways, may contribute to impaired cortisol response. The genomic pathways can affect the clinical interaction of cortisol with the glucocorticoid receptor (GR) via either transactivation or transrepression (4, 8). The GR plays an integral role in facilitating the activity of glucocorticoids, and GR-binding affinity has been demonstrated to be altered in severe sepsis and septic shock (4,8). The nongenomic effects include the interaction of glucocorticoids with vascular membranes, cellular junctions, and the various signaling pathways between cellular mediators
(4,8). Review of popular press/internet findings: Gibbison (2017) – Complete data from 22 studies and partial data from 1 study were included. There was no clear evidence that any one corticosteroid drug or treatment regimen is more likely to be effective in reducing mortality or reducing the incidence of gastrointestinal bleeding or superinfection in septic shock. Hydrocortisone delivered as a bolus or as an infusion was more likely than placebo and methylprednisolone to result in shock reversal Cochrane review (2015) – included a total of 33 RCTs, accounting for 4268 hospitalised patients with sepsis. Three trials included children, and the remaining 30 trials included only adults. Corticosteroids were compared with placebo in all except five trials, in which they were compared with standard therapy alone. Low-quality evidence indicates that steroids reduce mortality among patients with sepsis. Moderate-quality evidence suggests that a long course of low-dose steroids reduced 28-day mortality without inducing major complications. Review of Research Articles: One hundred seventy-four patients were potentially eligible of whom 101 patients met eligibility criteria. Fifty-seven patients were randomized, and 49 patients (23 and 26 patients in the hydrocortisone and placebo group, respectively) were included in the final analysis. The mean time from screening to randomization was 2.4±21 hours and from screening to first dose of study drug was 3.8± 2.6 hours. Forty-two percent of potentially eligible patient (73/174) received corticosteroids prior to randomization: 38.5% (67/174) were already on corticosteroids for shock at the time of screening, and in 3.4% (6/174) the treating physician wished to administer corticosteroids. Six of 49 randomized patients (12.2%) received open label steroid, three in each of the hydrocortisone and placebo group. Time on vasopressors days on mechanical ventilation, PICU and hospital length of stay and the rate of adverse events were not statistically different between the two groups (10). Studies that have examined low-dose corticosteroids in patients with septic shock found conflicting results. The landmark 2002 multicenter study by Annane et al demonstrated a significant increase in 28-day survival in 300 critically ill patients with vasopressor-refractory septic shock and multiorgan dysfunction randomized to low-dose IV hydrocortisone (50 mg every six hours) plus low-dose fludrocortisone for seven days. The mortality benefit was limited to patients with an impaired cortisol response to ACTH administration (hydrocortisone vs. placebo mortality, 53% vs. 63%; P=0.02) (11). Subsequent meta-analyses found that longer courses (at least five days) of low-dose corticosteroids (hydrocortisone 200-300 mg/day) decreased mortality without a significant increase in complication rates.
Unfortunately, infection places people in the hospital and infection is developed in the hospital. Two ways to contract sepsis are through hospital-caused infection, like in Amy Widener’s case, and through an infection caused by outside sources, for example a urinary tract infection in an elderly person. Everyone is capable of getting sepsis however cases appear most often in children under one year of age and in elderly older than sixty-five years. This is due to the body’s immune system being weaker in these demographics than in a person that has a built-up and strong immune system (“Sepsis Questions and Answers”). Sepsis occurs because of infection so the immune system plays a large role in the body’s defense mechanism. When people with already compromised immune systems develop an infection or are in an environment that infection is likely to occur, for example an unsanitary procedure in a hospital, then the body’s chances of being able to fight the infection off are greatly
Sepsis is defined as an exaggerated, overwhelming and uncontrolled systemic inflammatory response to an initially localised infection or tissue injury, which may lead to severe sepsis and septic shock if left untreated (Daniels, 2009; Robson & Daniels, 2013; Dellinger et al, 2013; Perman, Goyal & Gaieski, 2012; Vanzant & Schmelzer, 2011). Septic shock can be classified by acute circulatory failure as a result of massive vasodilation, increased capillary permeability and decreased vascular resistance in the body, causing refractory hypotension despite adequate fluid resuscitation. This leads to irreversible tissue ischaemia, end organ failure and ultimately, death (McClelland & Moxon, 2014; Sagy, Al-Qaqaa & Kim, 2013, Dellinger et al, 2013).
The anterior pituitary is an endocrine gland controlled by the hypothalamus in several different fashions. Releasing and release-inhibiting hormones are synthesized in the paraventricular, periventricular, and the supraoptic nuclei of the hypothalamus. They control anterior pituitary hormone secretion. Paravocellular neurons in these nuclei send their axons into the tuberoinfundibular tract and terminate on a capillary bed of the superior hypophyseal arteries located around the base of the median eminence. A given paravocellular neuron may release one or more releasing factor into the capillaries that coalesce in six to ten small straight veins that form the hypophyseal-portal blood circulation which descends along the infundibular stalk and forms a second capillary plexus around the anterior pituitary. The releasing-hormones gain access to the five distinct types of target cells in the anterior pituitary back into the capillary bed that then drains into the systemic circulation and transports the hormones to peripheral target tissues. The target tissues are stimulated to produce final mediator-hormones that induce the physiologic...
Sammy is rating his pain as a 10 out of 10 on a scale where 10 is the highest level of pain and 1 is the lowest. It is evident that some of the choices Sammy made prior to ending up in the emergency room were not beneficial to his health. Sammy has been discarding lunches and drinks as school, is feeling nauseas, having diarrhea, and was playing in 21 degrees Fahrenheit weather without a jacket. Sammy’s diarrhea may be explained by his electrolyte imbalance as a high potassium (K+) level can cause diarrhea. Due to the fact that sickled RBCs are blocking blood flow, oxygen cannot be delivered to the cells. As the cells produce lactic acid, the pH is lowered creating an acidotic environment. With an increase in hydrogen (H+) ions, K+ moves out of the cell into extracellular fluid (ECF) to maintain ionic balance, explaining a K+ level of 6.2 mEq/L (citation). Sammy’s arterial blood gas (ABG) results also play a role in determining Sammy’s condition. With a low pH of 7.28, PCO2 of 32, a PO2 of 64, and a HCO3 21 these results are indicative of metabolic acidosis. Sammy’s increased respiratory rate of 32 breaths per minute is the body’s was of compensating for increased levels of acid. The body increases respirations in order to excrete CO2 at a higher rate and increase the pH level. Unfortunately, the body can only keep this up for so long as this type of buffering system is physically
When a receptor is activated and the stimulus is taken to the hypothalamus and then relayed out to the “limbic system and neocortical areas…impulses stimulate the neuroendocrine and autonomic nervous system,” which can cause an array of issues if not careful and if the stress signal is prolonged. (3)
Many great historical figures of the scientific community have written on the subject of the same perplexing disease over the centuries (Angus, van der Poll, Finfer, Vincent 2013). Sepsis has been given many names, origins, and etiologies. In the 4th century, Hippocrates declared the disease the cause of organic decomposition, wound festering, and swamp gas (Angus et al. 2013). During the 19th century, Louis Pasteur theorized the disease was the outcome of a pathogenic microorganism in the bloodstream, which resulted in a body-wide infection (Angus et al. 2013). In the 21st century, the medical community made a breakthrough with the discovery of the disease’s link to the inflammatory response system and devised a plan of action to combat the high mortality rates among those infected (Angus et al. 2013). According to Hotchkiss, Monneret, & Payen (2013) the effects of sepsis are well documented, while the molecular processes it utilizes are still being explored; however, new studies are helping to expand our understanding of the centuries old disease.
Cortisol is in the class of hormones called glucocorticoids and affects almost every organ in the body. One of the most important functions of cortisol is to help regulate the body’s response to stress. Cortisol is also responsible for other necessary functions including: helping to maintain blood pressure and cardiovascular functions, helping to slow the immune system’s inflammatory response, helping to balance the effects of insulin in breaking down sugars for energy, helping to regulate the metabolism of proteins, carbohydrates, and fats, and helping to maintain proper arousal of sense of well being. The amount of cortisol is precisely balanced and regulated by the brain’s hypothalamus.
Sepsis is a life threating health condition and if not treated early can lead to shock, multiple organ failure and death (Ho, 2012). The main study of which practice has been based world-wide is the Surviving Sepsis Campaign. The Surviving Sepsis Campaign was developed to create evidence-based management guidelines. The Surviving Sepsis Campaign completed this by using an educational program to implement the guidelines by integrating their recommendations into resuscitation and management bundles (Marik, 2011). The first Surviving Sepsis Campaign Guidelines were published in Critical Care Medicine in 2004 with an updated version published in 2008 with the core of the recommendation's remained largely unchanged (Ahrens, 2011).
Maglione-Garves, Christine A, Len Kravitz and Suzzane Schneider. Cortisol Connection: Tips on Managing Stress and Weight. n.d. Web. 22 Oct. 2013.
The AFSP has been funding research to better understand suicidal risk, for example work done by Yair Ben-Efaim Ph.D. who focus is in psychiatry, genetic epidemiology, and biostatics form the Weizmann Institute of Science found, “The cortisol response to psychosocial stress may become dysregulated in stress-related disorders. It is potentiated by pituitary secretion of adrenocorticotropic hormone (ACTH), which is, in part, regulated by arginine vasopressin receptor-1B (AVPR1B)… were previously reported to associate with mood and anxiety disorders”, which those people who suffer from mood and anxiety disorders are at higher risk of committing suicide (Efraim et al.). The AFSP has also done extens...
Endocrine Hormones Are Involved In the Homeostasis of Blood Pressure Human body is probably as scientific as it could get with a whole network of controls and balances well in place. We have the nervous systems and immune systems and these systems are there to stay and more importantly they evolve and change with the passage of time. They keep upgrading themselves and this what keeps the man up to par with everything else and the change as and when they do come about. The hormone is like a messenger or a communicator in the case of out body. Once released, it carries the message through and forth and it travels through the main blood stream until it reaches and finds a cell with a receptor that it fits. This has to be a perfect fit and that is why it is sale that it must attach itself to the molecule like a key made for a certain lock. Then, like a key in a lock, the molecule attaches to the receptor and sends a signal inside the cell, which is relayed from here onwards. It is the content of the message which implies as to whether produce, release, take in or reduce the supply of p...
“ Sepsis” according to the International Surviving Sepsis Campaign, is defined as the presence of infection together with systemic manifestations of infection (Dellinger et al., 2013) In todays modern society sepsis still accounts for 15% of maternal deaths a year worldwide (Dolea & Stein, 2003). Despite medical advances, aseptic technique, and antibiotic use, sepsis is the most common cause of direct maternal death in the UK. According to the CMACE report the maternal mortality rate increased from 0.85 deaths per 100,000 maternities in 2003–05 to 1.13 deaths in 2006–08 (Harper, 2011). Puerperal sepsis has a long history within obstetrics and midwifery, and yet despite this knowledge it has become, yet again, the leading cause of direct maternal death. Therefore due to the increased maternal mortality, I have chosen to focus on the care of a woman within ...
Endocrinology can be defined as the study of the structure and function of the endocrine system (Tortora & Grabowski 1996). The endocrine system is composed cells, known as endocrine cells, which are distributed around the body and produce the chemical messengers known as hormones. Following secretion by endocrine cells, hormones travel in the blood where they affect tissues outside of their tissue of origin - and are therefore a form of cellular communication. In multicellular organisms, such as humans, cellular communication is essential for a number of body processes and the maintenance of homeostasis (Campbell, N.A. et al. 2015). In this essay, I am going to outline some of a number of body
The endocrine system is a group of glands distributed throughout the human body. This group of glands secretes substances called hormones. These hormones discharge into the bloodstream (Shier, Butler & Lewis, 2009). The endocrine system does not have a single anatomic location. It is dispersed throughout the human body. The final purpose of this system is to control, regulate, and coördinate the functioning of the human body (p.291). Some body functions can be activated or inhibited by hormones, which are secreted in very small quantities. Hormone related diseases may be due to hyper secretion or hypo secretion. The hormones secreted by the endocrine glands regulate the growth, development and function of many tissues, and coördinate the body's metabolic processes (pp. 294-296). An inadequate secretion of hormones may cause disorders in the body, which on occasion may result in serious health consequences. The major endocrine glands are the pituitary gland, thyroid gland, parathyroid glands, adrenal glands, pancreas, pineal gland, thymus gland, and reproductive glands (Shier et al., 2009). The pituitary gland is situated at the base of the brain and it secretes hormones that control the operation of the major endocrine glands (pp. 295-299). In reaction to excess or deficiency of pituitary hormones, the glands affected by these hormones can cause an excess or a deficiency of their own hormones. On the other hand the pituitary gland acts on the stimulation of the thyroid gland to secrete hormones that regulate the body's metabolism, energy, and nervous system activity (p. 295).The thyroid is a small gland in the neck, in front of the trachea and below the larynx. Thyroid hormones control metabolism, which is the body's ability to br...
Stress as we know it, is a mental or physical tension brought about by internal or external pressures. With our understanding through research we have found significant biochemical changes that take place in the body during stress. For instance, the body will at time increase cortisol production to aid with managing the amount of stress. As explained by Selye in his stress model, when an individual’s well-being is disrupt from being stress it activates the bodily response--general adaptation syndrome which includes the three ordinal stages; alarm, resistance and exhaustion. Prolong long experience of the three stage syndrome can lead to posttraumatic stress disorder(PTSD)