Inspire Issue 6 Volume 2 Winter 2022

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The evidence behind the “golden hour” protocolA retrospective cohort study done by Kumar et al between 1989 and2004 is the main piece of long-standing evidence used to back the“golden hour”. This was the first landmark study done to examine therelationship between antibiotic administration and sepsis survival.The main finding was that patients who received antibiotics withinthe first hour of sepsis recognition had a 79.9% chance of survival.It was also found that with every additional hour, the chance ofsurvival decreased by 7.6%. 1 Through critically appraising this study,a strength of it is that it is a large cohort study that used data from 14ICUs and 10 hospitals in Canada and the USA. However, a weaknessof this study is because of its retrospective design and the timespan of 15 years, there is the potential for an absence of data on theconfounding factors of this study, leading to confounding bias anddiminish the quality of the study.On the other hand, another study published in 2016 opposes therecommendations of the Surviving Sepsis Campaign. This is asystematic review and meta-analysis of 11 publications and soughtto find evidence for the SSC guidelines. 20 In total, 11,017 patients’data was used. The results of this conflicted with those of the previousstudy and provided evidence against the Surviving Sepsis Campaign’srecommendations. It was found that antibiotic administration withinone hour of sepsis recognition in septic patients was not associatedwith an improvement in mortality.A strength of this meta-analysis is that the selection process of thepapers was very refined and ensured that only high-quality papers,all of which were multi-centre and had a large sample size, andclosely related to the aim of the meta-analysis. Each study was scored,with eight being the highest, based on how sepsis was recognised,the study design, population sampling and data on the timing ofantibiotics. The studies that yielded a score above four were included.However, a downside to this study is the potential for informationbias. Some studies were not included in this meta-analysis due to alack of response after contacting the author, therefore it is possiblethat not all potential data had been collected, which could alter theresults.No other studies have been done to directly compare the timing ofantibiotic administration and sepsis survival. A randomised clinicaltrial comparing immediate and delayed antibiotic administrationwould be a very useful study to refer to, however this is difficult toorganise and conduct due to ethical and patient safety concerns. 20There is not enough data available to make a clear and direct claim.De-escalation of antibiotic therapyAfter the results of the blood cultures have been received, theemergency team will know the pathogen that is causing the patient’ssepsis. Naturally, the antibiotic regimen could be adapted at this pointto follow a more individualised approach. The antibiotic therapy canbe changed from broad-spectrum antibiotics to a more narrowspectrumantibiotic. This is called the de-escalation of antibiotictherapy. The main purpose of this is to prevent the unnecessarydevelopment of antibiotic resistance, which would happen if broadspectrumantibiotics were used for the whole treatment plan. 21A meta-analysis of published studies sought to determine if deescalationwas a useful programme in septic patients – and the resultssupport it to be. It was found that there is no difference in the lengthof hospital stay, and also there was significantly lower mortality inthe de-escalation group when compared to the non-de-escalationgroup. 22 This forms the evidence that is backing the implementationof de-escalation protocols in hospitals. In the NHS, the “Start Smartthen Focus” strategy is being implemented to back de-escalation oftherapy after reviewing the regimen at 48–72 hours. 23Aside from data from academic studies, de-escalation as aprogramme ingrained into sepsis treatment is logical. We are in theage where antibiotics cannot be used freely – resistance plaguestheir massive potential, and we need to implement programmesto reduce it wherever possible. Antibiotic stewardship needs tounderpin every single avenue of antibiotic therapy, including sepsistreatment. Switching to a narrow spectrum antibiotic as soon as theopportunity presents itself will help to reduce the unnecessary use ofbroad-spectrum antibiotics, which contribute to antibiotic resistance.ConclusionWe can see that the current evidence for the “golden hour” of sepsistreatment is underwhelming. Setting a stringent time limit of onehour may be practically unfeasible and could inadvertently leadto the overtreatment of patients who are not septic. Antibioticresistance will only continue to increase unless reasonable, logicbasedprogrammes are implemented to combat it, for example deescalationprogrammes and accurate sepsis diagnosis which is veryimportant.However, this does not mean that antibiotic administration isunimportant, in fact it is the cornerstone of sepsis treatment. Instead,this highlights the importance of evidence-based and operationallyfeasible guidelines. Nonetheless, the principle that the “golden hour”seeks to uphold is important. Timely antibiotic administration isparamount in such a time-dependent condition like sepsis. However,to back the stringent time limit of one hour, more studies need to beconducted.Copyright This work is licensed under the Creative CommonsAttribution-NonCommercial-NoDerivatives 4.0 International License.To view a copy of the license, visit https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode. The copyright of all articles belongsto the author(s), and a citation should be made when any article isquoted, used or referred to in another work. All articles included inthe INSPIRE Student Health Sciences Research Journal are writtenand reviewed by students, and the Editorial Board is composed ofstudents. Thus, this journal has been created for educational purposesand all content is available for reuse by the authors in other formats,including peer-reviewed journals.References1.2.3.4.5.6.7.8.9.10.11.12.13.Kumar A, Roberts D, Wood KE, Light B, Parrillo JE, Sharma S, et al. Durationof hypotension before initiation of effective antimicrobial therapy is thecritical determinant of survival in human septic shock. Crit Care Med.2006;34:1589-96.Sepsis Alliance. What is Sepsis.https://www.sepsis.org/sepsis-basics/what-issepsis/.Accessed: 1 March 2022Esposito S, De Simone G, Boccia G, De Caro F, Pagliano P. Sepsis and septicshock: New definitions, new diagnostic and therapeutic approaches. J GlobAntimicrob Resist. 2017;10:204-12.Case-based learning: recognising sepsis.https://pharmaceutical-journal.com/article/ld/case-based-learning-recognising-sepsis. Accessed: 28February 2022NHS Inform. Sepsis.https://www.nhsinform.scot/illnesses-and-conditions/blood-and-lymph/sepsis. Accessed: 1 March 2022BMJ Best Practice. Sepsis in adults.https://bestpractice-bmj-com.plymouth.idm.oclc.org/topics/en-gb/3000098/epidemiology Accessed: 28 February2022UK Sepsis Trust. References and Sources.https://sepsistrust.org/about/about-sepsis/references-and-sources/. Accessed: 25 October 2022Marshall JC, Dellinger RP, Levy M. The Surviving Sepsis Campaign: a historyand a perspective. Surg Infect (Larchmt). 2010;11:275-81.Daniels R, Nutbeam T, McNamara G, Galvin C. The sepsis six and the severesepsis resuscitation bundle: a prospective observational cohort study.Emerg Med J. 2011;28:507-12.van Zanten AR. The golden hour of antibiotic administration in severe sepsis:avoid a false start striving for gold*. Crit Care Med. 2014;42:1931-2.Ventola CL. The antibiotic resistance crisis: part 1: causes and threats. P T.2015;40:277-83.Garnacho-Montero J, Gutierrez-Pizarraya A, Escoresca-Ortega A, Fernandez-DelgadoE, Lopez-Sanchez JM. Adequate antibiotic therapy prior to ICUadmission in patients with severe sepsis and septic shock reduces hospitalmortality. Crit Care. 2015;19:302.Battula V, Krupanandan RK, Nambi PS, Ramachandran B. Safety and Feasibilityof Antibiotic De-escalation in Critically Ill Children With Sepsis - A ProspectiveAnalytical Study From a Pediatric ICU. Front Pediatr. 2021;9:640857.Inspire Student Health Sciences Research Journal | Winter 20226
14.15.16.17.18.19.20.21.22.23.Allison MG, Heil EL, Hayes BD. Appropriate Antibiotic Therapy. Emerg MedClin North Am. 2017;35:25-42.Sepsis Alliance. Testing for Sepsis.https://www.sepsis.org/sepsis-basics/testing-for-sepsis/.Accessed: 28 February 2022Singer M, Inada-Kim M, Shankar-Hari M. Sepsis hysteria: excess hype andunrealistic expectations. Lancet. 2019;394:1513-4.Spiegel R, Farkas JD, Rola P, Kenny JE, Olusanya S, Marik PE, et al. The 2018Surviving Sepsis Campaign's Treatment Bundle: When Guidelines Outpacethe Evidence Supporting Their Use. Ann Emerg Med. 2019;73:356-8.Norse AB, Guirgis F, Black LP, DeVos EL. Updates and controversies in theearly management of sepsis and septic shock. Emerg Med Pract. 2021;23:1-24.Pino E, Ramos Tuarez F, Saona J, Chen K, Ceka E, Gradeja Chavex J, et al. Misdiagnosisof Sepsis in Patients with Acutely Decompensated Heart Failure.Real World Outcomes. Journal of Cardiac Failure. 2019;25.Sterling SA, Miller WR, Pryor J, Puskarich MA, Jones AE. The Impact of Timingof Antibiotics on Outcomes in Severe Sepsis and Septic Shock: A SystematicReview and Meta-Analysis. Crit Care Med. 2015;43:1907-15.Martinez ML, Plata-Menchaca EP, Ruiz-Rodriguez JC, Ferrer R. An approachto antibiotic treatment in patients with sepsis. J Thorac Dis. 2020;12:1007-21.Gutierrez-Pizarraya A, Leone M, Garnacho-Montero J, Martin C, Martin-LoechesI. Collaborative approach of individual participant data ofprospective studies of de-escalation in non-immunosuppressed critically illpatients with sepsis. Expert Rev Clin Pharmacol. 2017;10:457-65.Hamilton WL, Pires SM, Lippett S, Gudka V, Cross ELA, Llewelyn MJ. The impactof diagnostic microbiology on de-escalation of antimicrobial therapyin hospitalised adults. BMC Infect Dis. 2020;20:102.Mehnaz AabideenHi! I am Mehnaz and I’m a second-year medicalstudent studying at Peninsula Medical School,Plymouth University. My interest in medicinestems from my love of interacting with peopleof all different backgrounds. Writing has alwaysbeen a way for me to delve deeper into topicsthat fascinate me, such as the protocols thatsurround sepsis management, and I really enjoy it! My passionsoutside medicine are reading, art and playing the piano. I am excitedto be more involved in research and academic medicine as I continuemy studies!Inspire Student Health Sciences Research Journal | Winter 20227
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Page 40 and 41: Senior Editors,Winter 2022Anoushka
Page 42 and 43: Advisory board,Winter 2022Sam Deuts

Inspire Issue 6 Volume 2 Winter 2022

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