Abstract
Sepsis is a common and dangerous condition. Early recognition and consequent initiation of appropriate management has significant impact on the morbidity and mortality of this condition. This article aims to help GPs to suspect sepsis and put into action an initial management plan in primary care. This article references all the latest guidance, helping GPs to manage sepsis effectively and safely.
Clinical case scenario
You are working in an urgent care clinic. You take a phone call from a father who is worried about his 4-year-old daughter, Jana who has ‘tummy pain’. He tells you they already consulted another GP colleague earlier today who diagnosed an upper respiratory tract infection with mesenteric adenitis. The father has a thermometer at home and reports that Jana’s temperature is now 39.6°C. He is worried because Jana has not recovered since her appointment earlier.
Background
Sepsis is defined as a life-threatening organ dysfunction due to a dysregulated host response to infection (National Institute for Health and Care Excellence (NICE), 2017). The danger of sepsis is not only due to infection, but also to the patient’s overwhelming immune response, which consequently results in collateral damage and death of host cells (Gyawali, 2019).
Sepsis is still a relatively modern and evolving definition. As a medical community, it is widely recognised that we still have a lot to understand about sepsis and severe infection. Research in recent years has identified the importance of early diagnosis and management of sepsis. If not treated immediately, sepsis can result in septic shock, multiple organ failure and death (World Health Organization, (WHO), 2020). GPs play a valuable role as they can initiate care early when sepsis is suspected, reducing morbidity and mortality rates. Recognising sepsis is notoriously difficult, due to the wide variety of patient presentations. This paper serves as a guide to primary care clinicians to aid in the recognition, risk stratification and initial management of patients with suspected sepsis. This is an update from our previous paper on sepsis (Allen, 2018).
Incidence and mortality
Sepsis is an extremely common and dangerous condition. Although advances have been made, the morbidity and mortality data are still shocking. Five people die with sepsis every hour in the UK (UK Sepsis Trust, 2023). Sepsis is a leading cause of avoidable death, and kills more people than breast, bowel and prostate cancer combined (National Confidential Enquiry into Patient Outcome and Death (NCEPOD), 2015; NICE, 2017; UK Parliamentary and Health Service Ombudsman, 2013). This picture is reflected by European mortality rates from sepsis as approximately 41% (Levy et al., 2012). Worldwide, sepsis kills between one-in-three and one-in-six of those who are diagnosed with the condition (Evans et al., 2021), which equates to almost 20% of all global deaths (Rudd, 2020). Of all sepsis cases worldwide, half occur among children (WHO, 2020). Sepsis is not only devastating due to the high mortality risk, but can also cause significant long-term morbidity, which requires high levels of support (WHO, 2020).
A factor that has potential to worsen these statistics in the future is the evidence that antimicrobial resistance (AMR) increases the likelihood of clinical unresponsiveness to treatment ( UK Sepsis Trust, 2023; WHO, 2020). There is evidence that AMR leads to the rapid escalation of infection to sepsis and septic shock (WHO, 2020). Unsurprisingly, patients who have sepsis due to resistant pathogens have been found to have a higher risk of hospital mortality. It is important to appreciate that hospital-acquired infections can be resistant to antibiotics, and patients who have recently been in hospital are vulnerable to sepsis (NCEPOD, 2015; WHO, 2020).
An early diagnosis of sepsis that leads to timely and appropriate management is imperative to increase the likelihood of survival (WHO, 2020). Studies cite an 8% increase in mortality rate per hour of delay in antimicrobial administration (Kumar et al., 2006; Tupchong et al., 2015). In another study, it was found that patients who received appropriate antibiotics less than an hour after triage had a 14% lower mortality than those who did not (Gaieski et al., 2010).
Diagnosis
The definition of sepsis is relatively modern, with a formal definition being formed in 1992 (American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference, 1992). At that time, sepsis was formally defined as the presence of a suspected infection and two of the four criteria of the systemic inflammatory response syndrome (SIRS):
Temperature over 38°C or below 36°C Heart rate of over 90 beats per minute Respiratory rate of over 20 breaths per minute or PaCO2 less than 32 mmHg White blood cell count of over 12,000/lL or under 4000/lL
The SIRS criteria are now outdated, and this definition is no longer used; another out-of-favour term is ‘severe sepsis’ (NICE, 2017). Sepsis is defined as ‘life-threatening organ dysfunction due to a dysregulated host response to infection’ (NICE, 2017). Septic shock is defined as ‘persistent hypotension requiring vasopressors and a lactate of over 2 mmol/l despite adequate volume resuscitation’ (NICE, 2017). This evolution in the definition and terminology of sepsis over the last three decades is partly due to the advances made in our understanding of its pathophysiology.
Recognising sepsis is notoriously difficult, as patients can present with a range of signs and symptoms. Some patients present with a normal temperature, which leads clinicians away from a diagnosis of infection or sepsis. NICE (NICE, 2017) encourages clinicians to recognise subtle signs such a change in behaviour, which can be particularly important in patients who have carers or have communication difficulties. This range of non-specific presentations has led to GPs being encouraged to suspect sepsis, asking themselves ‘could this be sepsis?’ (NICE, 2017). By suspecting sepsis in this way, the hope is that we reduce the risk of misdiagnosis, delay in treatment and any associated increase the in the rates of morbidity and mortality from sepsis.
When taking a history, it is extremely important to determine if the patient is likely to have an infection and where that infection most likely occurred. This can include subtle signs, such as change in behaviour or decreased frequency of urination. It is important to specifically ask about these topics. Physical examination should be used to screen for any abnormal observations and to help identify a source of infection. NICE (2017) recommends completing and documenting a structured set of observations using NEWS2 if sepsis is suspected, including heart rate, respiratory rate, blood pressure, level of alertness and oxygen saturation (Fig. 1). NICE (2017) warns that there have been reports of oxygen saturation being overestimated by saturation probes when used with patients who have darker skin tones, so to be aware that there may be some inaccuracy in the recording. It is also important to assess the skin to identify presence of mottling, cyanosis, rash (including non-blanching rash), or breach of skin integrity. Vital sign derangements may be absent early on and in elderly patients.
The NEWS scoring system.
Stratifying risk
Due to the difficulty diagnosing sepsis, especially in primary care without access to many investigations, we need to focus on assessing the risk that a patient may have sepsis. If a patient is at an increased risk of having sepsis, you may consider managing them more conservatively. Examples of patients at an increased risk of sepsis include:
Under 1 year, over 75 years in age, or very frail Impaired immune system - chemotherapy, diabetes, splenectomy, sickle cell, long term steroids, immunosuppressant drugs Surgery or invasive procedure in last 6 weeks Breach of skin integrity Intravenous drug user Indwelling lines or catheters Pregnant, given birth, termination, miscarriage in past 6 weeks (especially prolonged rupture of membranes, vaginal bleeding or offensive discharge, have, or been in contact with someone with group A strep)
Once you have determined if a patient is at an increased risk of sepsis or not, it is important to stratify their risk of severe illness or death from sepsis. BMJ Best Practice (2023) recommend taking a cautious approach, keeping in mind if the patient lives alone with poor access to communication and/or transport, or if a carer or parent expresses serious concern about the patient (for example ‘they’re just not right’). NICE (2017) has developed high, moderate-to-high, and low-risk criteria, which the UK Sepsis Trust has formulated into a decision aid for clinicians (Fig. 2) (Nutbeam and Daniels, 2023). The presence of these criteria therefore determines the appropriate management plan.
Screening and action tool for adults, children and young people 12 years and over.
Management
The management of sepsis is a developing area. Before 2001, there was no standard for early management of severe sepsis and septic shock in the emergency department (Nguyen et al., 2016). Since then, management bundles have been developed such as the Surviving Sepsis Campaign 6-h sepsis resuscitation bundle, which was then streamlined into a single 1-hour bundle in the 2018 Surviving Sepsis Campaign guidelines (Gyawali et al., 2019; Levy et al., 2018; Robson and Daniels, 2008). This reiterates the importance of prompt recognition by primary care providers in the initial hours to improve outcomes.
Referring to secondary care
If a patient has any of the high- risk criteria according to NICE (2017), they should be transferred to secondary care via a 999 ambulance. The GP should pre-alert secondary care of the incoming patient with a verbal handover. If the patient is having anticancer treatment, neutropenic sepsis should be suspected, and they should be referred immediately to secondary care. Many oncology units have a specific emergency assessment unit, thus reducing the infection risk for immunocompromised patients in the usual emergency department. Please check your local protocols to find your nearest oncology emergency assessment unit. If meningococcal disease is suspected, the GP should give an intramuscular injection of benzylpenicillin if this is available, and transfer as an emergency. If a patient is under 17 years old, is immunocompromised, and has any moderate to high-risk criteria, they should similarly be transferred by a 999 ambulance. With all transfers, if the transfer time will take over an hour, antibiotics should be given by the GP or paramedics on route (BMJ Best Practice, 2023).
If a patient has any moderate to high-risk criteria, the GP should try to decide whether they can be treated safely outside hospital. If this cannot be done, again, the patient should be referred urgently for emergency care.
If a patient has no moderate or high-risk features, the GP should educate the patient about which symptoms they need to monitor. The patient should also be educated on how to access appropriate medical care if they are concerned.
BMJ Best Practice (2023) recommends using the patient’s NEWS2 score to determine the appropriate referral pathway (Fig. 1). If the patient scores 7 or more, make an emergency referral to hospital. If the patient scores 5–6 in total, or 3 or more in any one area, urgently refer them to acute care setting for an acute care physician to review them within an hour.
Fluids
Patients with sepsis are often hypovolaemic; however, most GP practices do not have the resources to correct hypovolaemia. If available, consider obtaining more than one point of Intravenous (IV) access. If the ambulance crew has IV fluids, discuss giving a fluid bolus. NICE (2017) recommend a 500 ml fluid bolus of 0.9% sodium chloride or Hartmann’s solution in under 15 minutes. If the patient is under 16 years of age, 0.9% sodium chloride 10–20 ml/kg is recommended, to be given over less than 10 minutes. In all patients who do not show an improvement, a second bolus of the same volume is recommended. Patients often need large volumes of fluid; in one trial, patients received an average of 4.3 ± 3.9 L of intravenous fluid from hours 6 to 72.
Oxygen
If you have decided to refer the patient as an emergency, BMJ Best Practice (2023) recommends giving oxygen while you wait for the ambulance to arrive. Oxygen should be given to maintain an oxygen saturation of 94–98%. If the patient has chronic obstructive pulmonary disease, or is at risk of hypercapnic respiratory failure, aim for 88–92%. The oxygen saturation aim for children is above 92%, though NICE (2017) acknowledges that oxygen can be given if clinically indicated, even when the child’s oxygen saturations are over 92%.
Information giving
Care should be taken to give information to the patient, their family or carer. If the patient has an infection, but they are low risk and you deem that they can be treated in the community, it is important you provide verbal and written safety netting information. BMJ Best Practice (2023) advise not to say, ‘come back if you get worse’, but rather you should provide key symptoms to watch out for (for example a non-blanching rash, change in behaviour or mental state, mottled skin, or ashen appearance). Check the patient knows where and how to access immediate medical care (in and out of hours). BMJ Best Practice (2023) also states that it is good practice to consider arranging a next-day review either by appointment or telephone call. The UK Sepsis Trust (Nutbeam and Daniels, 2023) and BMJ Best Practice (2023) advise educating the patient on the SEPSIS acronym, and to call an ambulance if any of these symptoms develop:
‘
If you suspect sepsis, you should explain that the person may have sepsis and what sepsis means. They should be told what investigations they may need, as well as the expected management plan at the time. No medical jargon should be used, and you should give opportunities for questions, with repetition of information if necessary.
Summary
Sepsis is an extremely dangerous condition. Diagnosis and management of sepsis is still an evolving field. Early recognition is important, so GPs are encouraged to think ‘could this be sepsis?’ Consider if a patient is at risk of developing sepsis due to their demographics and past medical history. Consider if the patient is at risk of becoming severely unwell or dying due to sepsis, using the NICE (2017) criteria. Take a structured set of observations using NEWS2 (Fig. 1). With this information, determine whether the patient needs to be treated in secondary care or in the community. If you call an ambulance, consider giving oxygen and consider giving a fluid bolus with the paramedics. Always make sure to give the patient, their family or carer information, safety netting appropriately.
Key points
Sepsis can present with subtle signs and symptoms - ask yourself: ‘Could this be sepsis?’ Identify if the patient is at risk of developing sepsis Identify if the patient is likely to develop severe illness or death from sepsis using the high, moderate to high, and low-risk criteria from NICE Take a structured set of observations using NEWS2
○ score of 7 or more, emergency transfer to hospital ○ scores 5–6 in total, or three or more in any one area, urgently refer them to hospital
If a patient has any NICE high-risk criteria they need to be emergency transferred to secondary care via a 999 ambulance (give benzylpenicillin if meningococcal disease is suspected) Give the patient, their family or carer sufficient information including clear safety netting instructions
