Clinical Pearls: Management of Sepsis and Septic shock - Updated Recommendations

September 26, 2022
By: Eric Katula

This article is part of a series appearing in Interactions, our biweekly newsletter, written and researched by CSHP's students. We've created this series as a valuable learning activity for pharmacy students undertaking rotations at CSHP. Crafting these pieces not only helps students gain in-depth knowledge of specific conditions, treatments, and resources, it also helps them hone their skills in research, critical appraisal, evaluation, synthesis, and writing – all of which will serve them well in clinical practice. The Professional Practice Team works with the students to select hot topics that are of interest and utility to both the students and to you, the reader. We hope you enjoy this piece by one of our future colleagues! Let us know what you think: If you would like to provide any comments or constructive feedback for our students, please email us at practice@cshp.ca.

Sepsis is a life-threatening medical condition that, when severe, can lead to acute organ dysfunction, tissue damage, septic shock, and even death20. It affects neonatal, pediatric, and adult patients worldwide20.  According to statistics Canada, one out of eighteen deaths in Canada is due to sepsis1, and it is among the leading cause of death in Intensive Care Unit (ICU) patients20. Most cases of sepsis are caused by bacterial infections, but it can also be caused by fungal infections, traumatic injuries, or viral infections such as COVID-1921.

The cost of sepsis is substantial as treatment often involves complex therapies and lengthy stays in the intensive care units22. Patients with sepsis are two to three times more likely to be readmitted into the hospital compared to patients with other medical conditions such as heart failure or COPD22. Additionally, the development of sepsis may be linked with other illnesses such as pneumonia22. Prevention and early management of sepsis saves healthcare costs as it reduces the number of patients readmitted into hospitals and intensive care units; This helps to increase beds for critically ill patients such as those with severe Covid-19. 

Pharmacists' Role in Sepsis Management

Pharmacists play a crucial role as members of multidisciplinary teams involved in the treatment of sepsis. Various studies have shown the impacts of pharmacists in sepsis management by decreasing the time to administration of antibiotics, ensuring the appropriate selection of antibiotics, improving adherence to medications, lowering health care costs, and decreasing patient mortality2-4.  Additionally, pharmacists are involved in preventing sepsis by monitoring patients, following up on sepsis survivors post-discharge, conducting medication reconciliation, developing guidelines for risk assessment, and educating healthcare providers, patients and the general public about sepsis prevention. These activities reduce health care costs by decreasing the number of sepsis survivors who get re-hospitalized for preventable diseases12. In some health care institutions, pharmacists are members of rapid response teams that assess patients who may require ICU care and prevent ICU admissions by identifying sepsis early and providing appropriate treatment24.   
     
An observational study conducted by Kayvan Moussavi et al. found that an emergency department found that pharmacists significantly decreased the time to antimicrobial administration to patients with sepsis, severe sepsis, or septic shock19. The presence of a pharmacist was also found to increase the number of patients who received appropriate antimicrobials within the timeline recommended by Surviving Sepsis Campaign (SSC) guidelines12,19. Decreasing time to antimicrobial administration is important as each hour of delay in antibiotic administration is associated with a 7.6% decrease in survival12,19. Patients who receive antimicrobials after shock recognition have a significant increase in mortality19. Therefore, incorporating a pharmacist on a multidisciplinary team provides additional value to treating patients with sepsis.  

Updated Surviving Sepsis Guidelines

To guide health care providers in making appropriate and evidence-based decisions when treating patients with sepsis, the international guideline, Surviving Sepsis Campaign, for treating sepsis was updated in 2021. This article aims to briefly highlight some recommendations and changes from the 2016 guidelines for managing infections and hemodynamic changes in adult patients with sepsis. Though all the changes and recommendations in the 2021 guideline are important, this article will highlight the changes most relevant to hospital pharmacists.

Infections
Bacterial infections are the most common causes of sepsis4. Sepsis can also be caused by fungal, parasitic, or viral infections. Hospital pharmacists are valuable members of sepsis response teams and improve adherence to early goal-oriented therapy such as administration of appropriate antimicrobials. Numerous studies have concluded that the presence of a pharmacist on a trained team of health care professionals who are educated in early recognition, diagnosis, and treatment of sepsis, has a significant impact on the time to antimicrobial administration3-7.  Also, clinical pharmacists monitor and adjust dosage regimens based on pharmacologic responses and biological fluid and tissue drug concentrations in conjunction with clinical signs and symptoms or other biochemical variables. They recommend measurements of drug concentrations in bodily fluids or tissues to facilitate the evaluation of dosage regimens14,15, 23, 25

Refer to Table 1 for changes and recommendations made in the 2021 Surviving Sepsis Campaign8 deemed most relevant to hospital pharmacist:

Table 1

It is crucial to rapidly assess patients at risk of developing sepsis. If antimicrobials are indicated, administer them within 3 hours; If the patient is at high risk of MRSA, administer antibiotics with MRSA coverage; and if the patient is at high risk of fungal infection, use empiric antifungal therapy.

Hemodynamic Management and Additional Therapies
Cardiovascular alterations resulting from sepsis and septic shock include myocardial depression, hypovolemia, and systemic vasodilation. These alterations lead to tissue hypoperfusion, which in turn lead to organ failures16. Early interventions to improve oxygen delivery body organs and tissues improve outcome, but continuing hemodynamic support is often required12,16. Table 2 highlights some changes and recommendations most relevant to hospital pharmacists. 

Table 2



Rather than delaying initiation of vasopressors until a central venous access is secured, the guideline suggests starting vasopressors peripherally to restore mean arterial pressure. Additionally, the guidelines recommend administering IV corticosteroids in patients requiring vasopressors. Lastly, do not administer IV vitamin C to patients with sepsis or septic shock. 

Summary

As crucial members of the multidisciplinary teams involved in treating sepsis, pharmacists reduce the time to administration of antibiotics, ensure appropriate selection of antimicrobial or antifungals, and improve patient adherence to medications; these activities contribute to decreasing health care costs, and patient mortality2-4.  Pharmacists can play a crucial role in facilitating early diagnosis of sepsis by recognizing the signs and symptoms of sepsis and by ensuring rapid treatment of patients at risk of developing sepsis or septic shock2,3,6,12. The highlighted changes and recommendations in this article are aimed at improving the care of adult patients with sepsis and septic shock. For a complete list of changes and recommendations, please review the Surviving Sepsis guidelines.  

References

1. Navaneelan, T., Peters, P., Alam, S. and Phillips, O., 2016. Deaths involving sepsis in Canada. [online] Www150.statcan.gc.ca. Available at: <https://www150.statcan.gc.ca/n1/pub/82-624-x/2016001/article/14308-eng.htm> [Accessed 8 September 2022].
2. Cavanaugh JB Jr, Sullivan JB, East N, Nodzon JN. Importance of Pharmacy Involvement in the Treatment of Sepsis. Hosp Pharm. 2017;52(3):191-197. doi:10.1310/hpj5203-191
3. Moussavi K, Nikitenko V. Pharmacist impact on time to antibiotic administration in patients with sepsis in an ED. Am J Emerg Med. 2016;34(11):2117-2121. doi:10.1016/j.ajem.2016.07.031
4. Sarani B, Brenner SR, Gabel B, et al. Improving sepsis care through systems change: the impact of a medical emergency team. Jt Comm J Qual Patient Saf. 2008;34(3):179-125. doi:10.1016/s1553-7250(08)34021-5
5. Tarabichi Y, Cheng A, Bar-Shain D, et al. Improving Timeliness of Antibiotic Administration Using a Provider and Pharmacist Facing Sepsis Early Warning System in the Emergency Department Setting: A Randomized Controlled Quality Improvement Initiative. Crit Care Med. 2022;50(3):418-427. doi:10.1097/CCM.0000000000005267
6. Gawrys GW, Tun K, Jackson CB, et al. The impact of rapid diagnostic testing, surveillance software, and clinical pharmacist staffing at a large community hospital in the management of Gram-negative bloodstream infections. Diagn Microbiol Infect Dis. 2020;98(1):115084. doi:10.1016/j.diagmicrobio.2020.115084
7. MacLaren R, Bond CA, Martin SJ, Fike D. Clinical and economic outcomes of involving pharmacists in the direct care of critically ill patients with infections. Crit Care Med. 2008;36(12):3184-3189. doi:10.1097/CCM.0b013e31818f2269
8. Gaieski DF, Edwards JM, Kallan MJ, Carr BG. Benchmarking the incidence and mortality of severe sepsis in the United States. Crit Care Med. 2013;41(5):1167-1174. doi:10.1097/CCM.0b013e31827c09f8
9. Peltan ID, Brown SM, Bledsoe JR, et al. ED Door-to-Antibiotic Time and Long-term Mortality in Sepsis. Chest. 2019;155(5):938-946. doi:10.1016/j.chest.2019.02.008
10. Alam N, Oskam E, Stassen PM, et al. Prehospital antibiotics in the ambulance for sepsis: a multicentre, open label, randomised trial. Lancet Respir Med. 2018;6(1):40-50. doi:10.1016/S2213-2600(17)30469-1
11. Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Intensive Care Med. 2017;43(3):304-377. doi:10.1007/s00134-017-4683-6
12. Evans L, Rhodes A, Alhazzani W, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med. 2021;47(11):1181-1247. doi:10.1007/s00134-021-06506-y
13. Seymour CW, Gesten F, Prescott HC, et al. Time to Treatment and Mortality during Mandated Emergency Care for Sepsis. N Engl J Med. 2017;376(23):2235-2244. doi:10.1056/NEJMoa1703058
14. Callejo-Torre F, Eiros Bouza JM, Olaechea Astigarraga P, et al. Risk factors for methicillin-resistant Staphylococcus aureus colonisation or infection in intensive care units and their reliability for predicting MRSA on ICU admission. Infez Med. 2016;24(3):201-209.
15. Timsit JF, Azoulay E, Schwebel C, et al. Empirical Micafungin Treatment and Survival Without Invasive Fungal Infection in Adults With ICU-Acquired Sepsis, Candida Colonization, and Multiple Organ Failure: The EMPIRICUS Randomized Clinical Trial. JAMA. 2016;316(15):1555-1564. doi:10.1001/jama.2016.14655
16. De Backer, D. Hemodynamic management of septic shock. Curr Infect Dis Rep 8, 366–372 (2006). https://doi.org/10.1007/s11908-006-0047-z
17. Rochwerg B, Alhazzani W, Sindi A, et al. Fluid resuscitation in sepsis: a systematic review and network meta-analysis. Ann Intern Med. 2014;161(5):347-355. doi:10.7326/M14-0178
18. Rygård SL, Butler E, Granholm A, et al. Low-dose corticosteroids for adult patients with septic shock: a systematic review with meta-analysis and trial sequential analysis. Intensive Care Med. 2018;44(7):1003-1016. doi:10.1007/s00134-018-5197-6
19. Moussavi K, Nikitenko V. Pharmacist impact on time to antibiotic administration in patients with sepsis in an ED. Am J Emerg Med. 2016;34(11):2117-2121. doi:10.1016/j.ajem.2016.07.031
20. Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016; 315(8): 801-10.
21. Centers for Disease Control and Prevention [Internet]. Atlanta (GA): U.S. Department of Health and Human Services. Sepsis: clinical information; 2020. Available from: https://www.cdc.gov/sepsis/clinicaltools/index.html
22. Hajj J, Blaine N, Salavaci J, Jacoby D. The “centrality of sepsis”: a review on incidence, mortality, and cost of care. Healthcare (Basel) [Internet]. Available from: https://www.mdpi.com/2227-9032/6/3/90/htm
23. Garau J, Bassetti M. Role of pharmacists in antimicrobial stewardship programmes. Int J Clin Pharm. 2018;40(5):948-52.
24. Sarani B, Brenner SR, Gabel B, et al. Improving sepsis care through systems change: the impact of a medical emergency team. Jt Comm J Qual Patient Saf. 2008;34(3):179-125. doi:10.1016/s1553-7250(08)34021-5
25. ASHP statement on the pharmacist's role in antimicrobial stewardship and infection prevention and control. Am J Health Syst Pharm. 2010;67(7):575-577. doi:10.2146/sp100001

 

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