Sepsis can be defined as a life-threatening organ dysfunction that is caused by a dysregulated host response to infection (Singer et al, 2016). Despite notable improvements in our understanding of the pathophysiology of sepsis, innovations in haemodynamic monitoring and methods of resuscitation, as well as pharmacological and surgical interventions, it remains one of the major causes of morbidity and mortality in critically ill patients. The global incidence of this clinical syndrome has been placed at 30 million patients each year with up to 6 million deaths. In the UK, this translates to 200 000 cases, 70% of which arise in the community and an estimated 52 000 deaths (Daniels and Nutbeam, 2019:9). The annual economic burden may be as high as £2 billion and this may rise to £15.6 billion if the long-term effects on survivors is taken into account (Daniels and Nutbeam, 2019:10). Despite the significant morbidity, mortality and economic costs associated with sepsis, 10 000 deaths are thought to be preventable and the care improved in 2 out of 3 patients (NHS England, 2015). It is generally agreed that the crux of improving outcomes associated with sepsis is its early identification, coupled with prompt diagnostic testing, antimicrobial therapy and haemodynamic resuscitation (Wentowski et al, 2018). In essence, it is vital to recognise and act before significant organ failure has occurred. Early appropriate management saves lives. Delay costs lives. Sepsis is life-threatening and time-critical (Daniels and Nutbeam, 2019:53).
Early appropriate management, however, is not without challenges. Sepsis recognition and management often takes place in busy healthcare settings and it can be difficult at first presentation to distinguish between sepsis and severe infection. Moreover, sepsis has a highly complex set of pathophysiological pathways. It is not so much an illness as a syndrome that can manifest itself through a number of nonspecific symptoms (Berg and Gerlach, 2018). A plethora of health professionals will come in contact with sepsis but it is nurses who take an inimitable position because of the constant interaction they have with patients.
The thrust of sepsis guidance is its proactive management. That is, ‘think sepsis’ if a patient presents with signs and symptoms that indicate possible infection. However, the Sepsis Manual (Daniels and Nutbeam, 2019) highlights the challenge in differentiating between ‘infection’ and ‘sepsis’. Infection is defined as:
‘The invasion of a normally sterile cavity by organisms, or inflammation caused by organisms in parts of the body which are not normally sterile.’
and sepsis as:
‘A deterioration in the Sequential Organ Failure Assessment score of 2 points.’
The quick Sequential Organ Failure Assessment (qSOFA) score is a prompt bedside assessment for patients with suspected infection; qSOFA is considered positive if the patient has at least two of the following clinical criteria (Daniels and Nutbeam, 2019:16):
This article will provide a brief overview of the pathophysiology of sepsis and septic shock. It will then outline high risk groups, the importance of early warning scores and red flags to aid a structured assessment and a prompt diagnosis. Finally, it will introduce the Sepsis six care bundle and highlight how it has been shown to improve patient mortality.
Pathophysiology of sepsis
Sepsis occurs when infective pathogens trigger a localised inflammatory reaction that stimulates a wider systemic inflammatory response (SIR). Physiologically, a bacterial pathogen enters the body and resident macrophages initiate a localised inflammatory response (Stearns-Kurosawa et al, 2011; Porth, 2015). Receptors in the lining of blood vessels detect infective agents on the cell wall of pathogens. The response from the host immune system is to infiltrate the local area with macrophages, leukocytes and neutrophils. Macrophages are specialised cells linked to the detection, phagocytosis and destruction of pathogens. Essentially, macrophage cells ingest (phagocytose) infective bacteria and create a series of pro-inflammatory cytokines which stimulate a SIR. In a similar way, leukocytes are white blood cells connected to pathogen recognition and destruction. Neutrophils are among the first specialist white blood cells to migrate to the site of infection and destroy invading micro-organisms (Gotts and Matthay, 2016). Interestingly, some forms of cancer treatments can suppress the ability of bone marrow to respond to infection. People receiving chemotherapy and health professionals providing care need to be aware of the risk of neutropenic sepsis. Neutropenic sepsis is an overwhelming infection that affects people with a low neutrophil count and is a potentially fatal complication of anticancer treatment (National Institute for Health and Care Excellence (NICE), 2012).
Infective agents can give rise to sepsis via a number of sources. These include: skin and joint infection, meningitis, respiratory tract (lungs), endocarditis, urinary tract infection (UTI) and healthcare device-related infection. Sometimes there may be a clinical suspicion of infection, but the source is unknown. Clinically, such patients may have a history of pyrexia (fever), diaphoresis or appear flushed. The Sepsis Manual reports that a ‘clinical suspicion of an infection is all that's needed’ to trigger further investigations to exclude sepsis (Daniels and Nutbeam, 2019:20).
The systemic immune response is characterised by the mobilising of white blood cells (neutrophils and monocytes) to the site of injured tissue to destroy pathogens. The proliferation of white blood cells due to the SIR is referred to as leukocytosis (Porth, 2015). Although increases in white cell count attempt to destroy the invasive pathogens, they can harm the cells that line blood vessels (endothelium). Critically, damage to the endothelium enhances vascular permeability causing capillaries to become ‘leaky’ (Daniels and Nutbeam, 2019:20). Damaged endothelial cells produce excesses of nitric oxide and other cytokines, which in turn, act as an effective vasodilator and key determinant in developing sepsis (Porth, 2015). Updated evidence from the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) suggests abandoning use of host inflammatory response syndrome criteria (systemic inflammatory response syndrome (SIRS)) in the identification of sepsis and, furthermore, eliminate the term ‘severe sepsis’ from existing terminology. This is particularly significant when discussing the progression of sepsis through to septic shock (Singer et al, 2016). Table 1 highlights the molecules and cytokines that are released during the SIRS phase.
Mediator molecules | Function |
---|---|
Nitric oxide | Nitric oxide causes and maintains vasodilation. This helps to make capillaries more permeable (‘leaky’) |
Bradykinin | Bradykinin is responsible for the pain at the site of inflammation and is also involved in vasodilatation, making capillaries more permeable. This permits white blood cells to pass through and fight infective agents |
Complement proteins | These act directly to neutralise pathogens, mobilise white blood cells and amplify the immune response |
Thrombin | Thrombin helps clot formation by turning fibrinogen into fibrin and is involved in nitric oxide production. During sepsis, activation of extrinsic coagulation pathways increases coagulation. The pro-coagulation state can lead to the formation of microvascular emboli and cause organ dysfunction |
Interleukins | These are a complex group of proteins that help white blood cells to function, attract them to the area and modulate inflammation—some cause inflammation, some damp it down |
Tumour necrosis | factor Tumour necrosis factor is a pro-inflammatory cytokine |
Septic shock
Septic shock is a life-threatening clinical emergency that occurs when the blood pressure drops to dangerously low level following an infection. This haemodynamic instability contributes to organ dysfunction due to decreased delivery of oxygen to cells (Thompson et al, 2019). Inflammatory mediators (cytokines) cause arterial and venous dilation. Consequently, venous return is impaired, which stimulates a state of septic cardiomyopathy and hypotension (Gyawali et al, 2019). Furthermore, septic shock has been described as:
‘The subset of sepsis in which underlying circulatory and cellular or metabolic abnormalities are profound enough to increase mortality substantially.’
First, intravascular fluid loss caused by endothelial cell damage results in the movement of fluid into interstitial spaces. Consequently, the intravascular fluid loss from increased vascular permeability causes decreased perfusion of cells and tissue. Second, this hypoperfused state restricts oxygen delivery to cells, thus evoking anaerobic respiration. Physiologically, anaerobic respiration produces increased levels of lactic acid. Increased serum lactate levels accelerate under hypotensive conditions and anaerobic glycolysis (breaking down glucose) (Lee and An, 2016). Lactate clearance normally occurs by the liver and kidneys but is inhibited during critical illness. Increasing levels of serum lactate causes lactic acidosis which, in turn, restricts cardiac function. At a cellular level, circulating cytokines cause depression of cardiac myocytes and affects their mitochondrial function (Gyawali et al, 2019). Essentially, septic shock happens when there is insufficient cardiac output to maintain metabolism because of sepsis (Lee and An, 2016).
Finally, the diagnosis of septic shock requires the presence of three elements:
Current guidelines and terminology | Sepsis | Septic shock |
---|---|---|
2015 clinical criteria | Suspected or documented infection and an acute increase of ≥2 sequential organ failure assessment (SOFA) score (a proxy for organ dysfunction) | Sepsis and vasopressor therapy needed to elevate Mean Arterial Pressure (MAP) ≥65 mmHg and lactate >2 mmol/L (18 mg/dL) despite adequate fluid resuscitation |
At-risk groups
Sepsis is a time-critical medical emergency that, unless treated quickly, can progress to severe sepsis, multi-organ failure, septic shock and ultimately death (NHS England, 2015). Successful management relies on the nurse to have a high index of suspicion when faced with a patient who is deteriorating or one that is failing to improve. ‘Think sepsis’ has entered healthcare language and the nurse should combine this approach with a knowledge of at-risk groups and their own clinical acumen, to achieve sound clinical outcomes (Daniels and Nutbeam, 2019:15).
NICE guidelines identify a number of at-risk groups who are at higher risk of acquiring sepsis. These include elderly frail people (aged over 75 years old), and the very young (under 1 years old). Individuals who have an impaired immune system due to illness, drugs or invasive devices, for example, those undergoing chemotherapy, people with diabetes, on long-term steroids, with breeches in skin and those with an indwelling device. Pregnant women who have any of the above, had a difficult labour, a termination of pregnancy, or miscarriage in the preceding 6 weeks; and neonates who are preterm, or where there has been a recent history of infection in mother or baby, are also at risk (NICE, 2016).
Early warning scores
If an understanding of at-risk groups is the first stage, the second is for nurses to use a structured set of observations to help quantify potential acute illness. Moreover, in the context of infection, they should use a tool that prompts them to actively look for organ dysfunction and facilitate a prompt and appropriate clinical response (Daniels and Nutbeam, 2019:15). In an observational study Churpek et al (2017) found that the National Early Warning Score (NEWS) was the most accurate tool for predicting in-hospital mortality, and intensive care unit (ICU) transfer in non-ICU patients, where there was a suspicion of infection. NEWS is an early warning score that was first produced in 2012 and updated in 2017 to NEWS 2 (Royal College of Physicians (RCP), 2017). It calculates a score from a series of physiological observations (Table 3), the higher the score the more severe a patient's condition.
Respiration rate | Pulse rate |
Oxygen saturation | Level of consciousness or new confusion |
Systolic blood pressure | Temperature |
A score of 5 or more reflects medium clinical risk, and a score of 7 or more high clinical risk, and key thresholds for potential, acute serious clinical deterioration, and the need for an urgent clinical response (RCP, 2017). This is echoed by the UK Sepsis Trust, which states that a screen for sepsis should be triggered when a patient has a combined NEW score of 5 or more, when one of the aforementioned risk factors is present, or when the nurse is unduly worried. This should also include an immediate check for any red flags (Daniels and Nutbeam, 2019:23).
‘Red flag’ sepsis (Table 4) was a term first used by the UK Sepsis Trust, NHS England and several of the royal colleges. It was developed in 2015 as part of a pragmatic operational solution, for use at the bedside, in patients who do not fulfil the criteria for severe sepsis on physiological or near-patient assessment alone. It is not seen as a formal ‘diagnosis’, but a set of criteria that can be measured rapidly. If a patient identifies one or more red flags the nurse should assume the patient has sepsis and has a degree of organ dysfunction (Daniels and Nutbeam, 2019:22).
Responds only to voice or pain/unresponsive | Needs oxygen to keep SpO2 ≥ 92% |
Acute confusional state | Non-blanching rash, mottled/ashen/cyanotic |
Systolic BP ≤ 90 mmHg (or drop >40 from normal) | Not passed urine in last 18 hours/UO <0.5 ml/kg/hour |
Heart rate >130 per minute | Lactate ≥ 2mmol / l |
Respiratory rate ≥25 per minute | Recent chemotherapy |
BP=blood pressure; SpO2=oxygen saturation; UO=urinary output
The sepsis six
Once sepsis is suspected the key immediate interventions that increase survival are described in a care bundle termed the sepsis six (Table 5). Care bundles were introduced by the Institute for Healthcare Improvement and were founded on the idea that if you group together a small number of evidence-informed practices, and then perform these collectively, reliably and continuously, it will improve patient outcomes (Lavallée et al, 2017). The sepsis six was specifically designed to facilitate early intervention in a busy hospital and pre-hospital setting (Kumar et al, 2015). Developed in 2015 by The UK Sepsis Trust and revised in 2019, it consists of three diagnostic and three therapeutic steps (UK Sepsis Trust, 2020). The crucial point is that these need to be delivered within 1 hour to control the source of infection, restore circulation and promote oxygen delivery. In one study, the effective delivery of the sepsis six reduced the relative risk of death by 46.6% (Daniels et al, 2011). If these figures were extrapolated to the NHS as a whole, 80% compliance would save an estimated 15 000 lives each year.
Give oxygen to keep SATS above 94% | Give a fluid challenge |
Take blood cultures | Measure lactate |
Give IV antibiotics | Measure urine output |
It is important to note that primary care settings have a different pre-hospital sepsis screening tool and action tool. If the NEWS score is above 3 and/or the patient looks sick then sepsis should be considered. Significantly, the prehospital sepsis screening tool advises practitioners to arrange immediate transfer of the patient to a ‘designated destination’ and ‘communicate likelihood of sepsis at handover’ (Daniels and Nutbeam, 2019: 29).
Conclusion
Sepsis remains a significant healthcare challenge and economic burden. This article has explained how a sound understanding of the pathophysiology of sepsis can equip the nurse with the knowledge needed to ensure prompt action and save lives. Nurses are the health professional that has greatest contact with high-risk patients. As such, they are uniquely placed to use clinical guidelines and make a rapid detection of the syndrome and then activate appropriate interventions. In particular, the integration of early warning scores is a proven template that can ‘track and trigger’ clinical deterioration and ensure patient safety and timely intervention.