Inspire Issue 6 Volume 2 Winter 2022

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ReviewMEDICINEChallenging the “golden hour” of sepsistreatment – is it contributing to the overadministrationof antibiotics?Mehnaz AabideenYear 2, Medicine, Plymouth University Peninsula School of MedicineEmail: mehnazaabideen@gmail.comAbstractThe first hour after recognising symptoms of sepsis in a patient isknown as the “golden hour”. Clinicians hold increased importanceto this hour and believe that many therapeutic interventions willbe most effective if administered within this time. One exampleis administering broad-spectrum antibiotics to septic patientsto help eliminate the pathological cause of sepsis. However,antibiotic resistance still needs to be considered as part of antibioticstewardship. It is important to balance the usefulness of the “goldenhour” principle whilst considering the negative implications thatoveruse of antibiotics has on antibiotic resistance.A literature search was conducted to explore this issue further.The key findings were that although antibiotics are paramount insepsis treatment, administering them within one hour of sepsisdiagnosis is not associated with an improvement in mortality. Onecould argue that giving broad-spectrum antibiotics is futile and willworsen antibiotic resistance. Other clinical interventions shouldbe considered when trying to reduce the occurrence of antibioticresistance, such as improved diagnosis of sepsis and de-escalationof antibiotic therapy.AbbreviationsNEWS2 – National Early Warning Score 2qSOFA – Quick Sequential Organ Failure AssessmentSOFA – Sequential Organ Failure AssessmentIntroductionMedical students, doctors and the general public hear the wordsepsis and a sense of panic begins to set in. This increased vigilanceis reflected in the hounding of emergency teams to administerantibiotics within the first hour of sepsis recognition, hailed as the“golden hour”. However, the practicality of this protocol has beenquestioned in a landmark study conducted by Kumar et al 1 Is it worthadministering antibiotics that could potentially save a septic patient’slife, whilst running the risk of unnecessarily contributing to antibioticresistance?What is sepsis?Sepsis is a life-threatening disorder that is characterised by adysregulated immune response to infection and can lead to organfailure and eventually death. 2 Septic shock is a more advancedversion of sepsis, whereby there are circulatory, cellular, or metabolicabnormalities. 3The diagnosis of sepsis is made based on symptoms that overlap withother non-infective pathologies. In addition, it takes a long time todetermine the causative pathogen from blood cultures; this makesit harder to ascertain that the condition is sepsis in the acute stagesof disease. 4 Some common symptoms are mottled or bluish skin;tachypnoea or hypotension. 5The exact incidence of sepsis is unknown – this is because there is alack of an agreed definition for it. However, according to NHS Englandin 2015, sepsis was a contributory cause to 23,135 deaths. The exactcontribution that sepsis plays in these deaths is currently unknown,as some of these patients had multiple comorbidities and frailty. 6 TheUK Sepsis Trust shares that in 2017 there were 200,000 admissionsto hospitals in England with one of the “definitely septic” diagnosticcodes. 7MethodsLiterature searchTo investigate the issue of the “golden hour” further, a literaturesearch was conducted primarily using PubMed, an online database.Inspire Student Health Sciences Research Journal | Winter 20224
Additionally, Google Scholar was used to search for further literature.The terms searched for included a combination of keywords from:“sepsis”, “septic shock”, “sepsis management”, “antibiotic resistance”,“antibiotic use”, “sepsis six” and “golden hour of sepsis”, using Booleanoperators where appropriate to refine the search. Citation chainingwas also used to find relevant articles.ResultsThe initial search yielded 20 journal articles. After manually screeningthe abstracts for relevance to this literature review, eight wereexcluded as they were not specific to antibiotic administration orsepsis treatment in adults.DiscussionHow is sepsis managed clinically?The Surviving Sepsis Campaign (SSC) is a collaborative initiativelaunched to reduce the risk of death from sepsis and septic shockworldwide, through developing and implementing protocols.These guidelines are evidence-based, which provides credibilityfor the widespread promulgation of said guidelines and is why theCampaign is commonly mentioned in the discourse surroundingsepsis. Participating in the Surviving Sepsis Campaign was associatedwith a 5.4% absolute survival rate for septic patients. 8One of the guidelines the Surviving Sepsis Campaign recommendsis the Sepsis Six care bundle, commonly remembered by the‘BUFALO’ acronym: bloods, urine, fluids, antibiotics, lactate, oxygen.In further detail, this involves taking two blood samples (to undergomicrobiological culturing), monitoring urine output, starting thepatient on fluids, administering intravenous antibiotics, measuringserum lactate and delivering high-flow oxygen. 9How are antibiotics used?The general medical community acknowledge that one of the mostimportant tenets of sepsis treatment is antibiotic administration. Thecommon goal of antibiotic therapy is to have a drug concentrationhigh enough to sufficiently kill as many bacteria as possible. 10 In anideal world, this could be done by administering as many antibioticsas possible without any repercussions. However, one major threat tothe value of these drugs is antibiotic resistance. Bacteria replicationover time will naturally give rise to genetic mutations that cause it tobecome resistant to the antibiotics used to treat bacterial infections,and therefore making the antibiotic futile. This is becoming anincreasingly worrying issue within healthcare as antibiotics are anessential part of treating serious infections. With the stagnation inantibiotic discovery someday antibiotics could be rendered uselessif bacteria continue to develop resistance. This makes the debatesurrounding the “golden hour” is so important. 11Deciding which antibiotics to start patients on in the acute settingmay be difficult, as there is often a lack of more definitive bloodculture data on the species and sensitivities of the infective microorganisms.Sometimes clinicians get it wrong – studies have shownthat 10-40% of the antibiotic regimens that are administered initiallyare inadequate or inappropriate. 12 The Surviving Sepsis Campaignrecommends that the patient is started with broad-spectrumantibiotics intravenously, and then after the causative agent isdetermined, the therapy is to be de-escalated to be more targetedto the pathogen. 13During the initial stages of treatment, an antibiotic that targets awide range of pathogens is needed. Piperacillin and Tazobactam areantibiotics that can be combined and used to treat gram-negative orPseudomonas spp. bacterial infections, whereas Vancomycin can beused for gram-positive or Methicillin-resistant Staphylococcus aureusbacteria. Broad-spectrum carbapenems are also commonly used insepsis treatment. 14 It may seem counter-intuitive to start a patienton antibiotics when you do not know what the bacteria causing theinfection is. However, sepsis is a condition that is too unpredictable towait for microbiological blood culture results as this can sometimestake several days. 15 During this time, the patient’s health canpotentially deteriorate and this could lead to death.After considering both sides of the scale, it seems understandablethat clinicians would rather take the risk of increased antibioticresistance from administering broad-spectrum antibiotics, ratherthan the patient’s deterioration and death.Why is the timing of antibiotic administration important?The timing of antibiotic administration is thought to be a major tenetof sepsis management since patients can rapidly deteriorate. There iscommon agreement that once sepsis is recognised, timely antibioticadministration will benefit the patient more and lead to betteroutcomes. However, the 60-minute time constraint of the “goldenhour” is increasingly being called into question. 6Professor Mervyn Singer is very vocal about his discontent with‘timely’ being misinterpreted as ‘early’. In his letter to the Lancet, hehighlights that a reason for inappropriate antibiotic administrationis that clinicians will often administer antibiotics straight away, justfor the sake of taking action against suspected sepsis. He argues thatthey do not realise that ‘timely’ means avoiding unnecessary delays,and not just administering them straight away. 16 Spiegel et al alsoaddress the one-hour time constraint in an editorial for the Annalsof Emergency Medicine. They explain that although treatmentwith no delay is paramount in sepsis management, condensingthe six treatment directives into a one-hour time limit may causeoperational problems for emergency departments that are alreadystruggling with three- and six-hour time limits previously used forsepsis treatment. 17 This may cause clinicians to be more rushed andcould cause harm to patients.The problem with misdiagnosing sepsisA big issue with adhering to the golden hour protocol is that tomeet the one-hour goal, clinicians in a rush may misdiagnose apatient with sepsis, and then start them on this treatment bundle.Essentially, the patient is being given high doses of broad-spectrumantibiotics for no clinical reason, which goes against a major dogmain antibiotic stewardship – broad-spectrum antibiotics should onlybe used when necessary due to the potential they have to increaseantibiotic resistance.A way to prevent this is by increasing the accuracy of sepsis diagnosis.SOFA (Sequential Organ Failure Assessment score) and qSOFA (quickSOFA) are two tools commonly used in determining prognosisin critical illness however, they are not recommended for sepsisidentification. Instead, NEWS (National Early Warning Score) is morecommonly used as it has better sensitivity and specificity comparedto qSOFA, which only includes three of the seven NEWS2 criteria. Inclinical practice it is recommended that if the patient has a qSOFAscore above two, then the full SOFA score is obtained. However, thisincludes taking arterial blood gases, which is not routinely done inseptic patients, and could jeopardise the small time window in sepsismanagement. 18 This further stresses the need for other measurementstaken urgently such as serum lactate, in addition to NEWS2 to detectsepsis and diagnose it accurately.Accurate diagnosis is important because many cases are diagnosedas sepsis but are not in reality. A retrospective cohort study lookedat patients with acutely decompensated heart failure between 2015and 2018 and found that sepsis was misdiagnosed in 25% of thepatients. 19 This possibly taints the results yielded from the study,which puts the usefulness of the “golden hour” protocol into jeopardy.However, as 75% of the patients were accurately diagnosed, thereneeds to be a way to reduce misdiagnosis without eliminating the“golden hour” approach.Inspire Student Health Sciences Research Journal | Winter 2022 5
Page 2 and 3: Welcome to the Winter 2022 issue of
Page 6 and 7: The evidence behind the “golden h
Page 8 and 9: ReviewDENTISTRYThe mechanistic acti
Page 10 and 11: chromogenic compounds converting th
Page 12 and 13: ReviewDENTISTRYErgonomic interventi
Page 14 and 15: pain. 9-10 The findings of this pap
Page 16 and 17: ReviewMEDICINEWhy do allergies occu
Page 18 and 19: A.W. Rook in 2003, 25 which blames
Page 20 and 21: ReviewMEDICINENovel target-specific
Page 22 and 23: PETPET scan uses an injected radioa
Page 24 and 25: Figure 1. Illustration of plaquepro
Page 26 and 27: ResearchDENTISTRYA dental volunteer
Page 28 and 29: The exception to this being a small
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Page 32 and 33: Conference ReportOne Health Showcas
Page 34 and 35: InterviewVETERINARYEcologist Dr Reb
Page 36 and 37: InterviewMEDICINEConsultant paediat
Page 38 and 39: CareersMEDICINESenior medical write
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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