literature review

S epsis is a serious condition that is a major cause of avoidable death (National Confidential Enquiry into Patient Outcome and Death (NCEPOD,) 2015). It is estimated that there are about 123 000 episodes of sepsis per year, with resulting mortality estimated

at 37 000 (NHS England, 2015), with an estimated total cost to the NHS of £1.5 billion per year (Daniels and Nutbeam, 2017). Improvements in addressing sepsis within hospital trusts has the potential to save £1.25 million annually (NHS England, 2015). Therefore, prompt identification and management are essential in reducing the sepsis-related morbidity, mortality and financial burden on the NHS.

Pathophysiology of sepsis Sepsis can be caused by any pathogenic microbe and may arise from pneumonia, urinary tract infection and infection in the skin and soft tissue (Brent, 2017). Pneumonia is the most common cause of sepsis, with bacter ia being the most common causative organism (Gaieski et al, 2010). Determining the causative microbe through blood cultures will help ensure that the patient receives targeted antibiotic therapy. Although sepsis can affect anyone, some individuals may be at higher risk, including those with chronic illness, the very young or old, people who have had recent surgery and those who are immunosuppressed (Table 1).

Understanding sepsis Karen Nagalingam

ABSTRACT This article provides information on sepsis, which can be life threatening and is often difficult to identify due to subtle signs and symptoms. It is the body’s response to infection resulting in injury to the tissues and organs. Assessment tools can be used to assess risk of sepsis and include considering a source of infection along with a NEWS 2 or qSOFA score. However, it is important to be aware of other subtle changes including cold or clammy skin and changes in the patient’s behaviour such as new confusion. Within 1 hour from diagnosis supportive treatments need to be administered, including the most appropriate antibiotic for the source of infection, fluid and oxygen. Blood cultures, bloods including lactate and urine measurement are all needed to support management of the patient.

Key words: Sepsis ■ Acute illness ■ National Early Warning Score 2 ■ Sepsis Six ■ quick Sepsis-related Organ Failure Assessment

Karen Nagalingam, Senior Lecturer in Adult Nursing, University of Hertfordshire, [email protected]

Accepted for publication: October 2018

Sepsis has been defined as follows:

‘A life-threatening condition that arises when the body’s response to an infection injures its own tissues and organs.’

Singer, 2016

This means that the signs and symptoms a patient may be presenting with are as a result of physiological responses to an infection.

When an infection occurs, an inflammatory response is initiated, which should lead to recovery from the infection. This involves a complex process that sets off a cascade of reactions involving the immune system and the coagulation cascade (Daniels and Nutbeam, 2017). Inflammation involves the release of mediator molecules, causing vasodilation and capillary permeability. This enables the infiltration of neutrophils and monocytes (white blood cells), fibrinogen and platelets into the area. The area will be red, hot and swollen as a result of this process. When the defensive responses are overwhelmed by infection or the inflammatory response is excessive, the patient is at an increased risk of death. Septic shock can occur as a result of this response. Therefore, identifying patients at risk or at an early stage of sepsis can improve the chances of survival.

Signs and symptoms A patient who is deteriorating, regardless of the cause, requires immediate interventions to support them. In clinical practice it can be difficult to determine whether sepsis is occurring because the signs and symptoms vary and can be subtle in certain patient groups (Brent, 2017).

In sepsis, a raised respiratory rate in a patient is a key indicator of deterioration. Decreased oxygen transfer across the alveoli occurs as a result of proteins and fluids leaking into the tissues of the lungs. This leads to an increased breathing rate to compensate for the reduced surface area available for oxygenation. The circulatory system is also affected in sepsis, with the release of nitric oxide and interleukins causing vasodilation (Daniels and Nutbeam, 2017). This results in hypotension in patients, leading to inadequate perfusion of tissues (Gauer, 2013). The body attempts to compensate for the low blood pressure by increasing the work of the heart, which is known as compensatory tachycardia. In early stages of sepsis, the patient may present with warm peripheries and normal capillary refill time (Daniels and Nutbeam, 2017). They may have non-specific symptoms and subtle changes in behaviour, such as withdrawal and agitation and therefore concerns raised by the patient, family or carer need to be considered. As sepsis progresses, the clinical signs and

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symptoms will include cold or clammy skin, reduced urine output, lactic acidosis and altered mental status.

Although it has been stated that identification of sepsis can be difficult, an awareness of the physiological processes that occur and the presenting features will help aid diagnosis. In a study by Gaieski et al (2010) it was found that delays in treatment directly influenced mortality in patients with sepsis. Various methods for determining sepsis have been used in the past, with track and trigger systems, such as the National Early Warning Score (NEWS) 2 (Royal College of Physicians, 2017), being more accurate at identifying sepsis than tools such as the quick Sepsis-related Organ Failure Assessment (qSOFA) (Churpek et al, 2017). However, where infection is suspected, qSOFA is a quick, easy and valid way to identify a patient at risk of sepsis (Lamontagne et al, 2017), which can be easily used in settings where a track and trigger system has not been introduced (Table 2).

Management Rapid clinical assessment and prompt management is required if a deteriorating patient presents with a risk factor for sepsis, a NEWS 2 score of 5 or more (or local equivalent), and a clinical suspicion of infection (Daniels and Nutbeam, 2017). The Sepsis Six is a care bundle designed to be delivered within the first hour of diagnosis (Brent, 2017) (Box 1). This includes supplementing oxygen to improve oxygenation to maintain saturations between 94% and 98%. If the patient is critically ill, this can be given as high-flow oxygen using a mask with a reservoir at 15 L (Resuscitation Council, 2014).

It has been found that patients in septic shock had improved outcome if antibiotics were administered within the first hour of diagnosis (Sherwin et al, 2017). Although there is disputed evidence around the precise time from diagnosis to treatment, there is consensus that this should be as soon as possible (Gotts and Matthay, 2016). Antibiotic choice should be guided by local hospital guidelines and the suspected focus of infection. To aid correct and targeted administration of antibiotics, it is essential to take blood cultures peripherally and from any intravenous devices such as lines and cannulas. Blood cultures should be taken before antibiotics are administered where possible, so that the organism causing sepsis can be identified and the most appropriate antibiotic prescribed.

Supportive management of a patients with sepsis includes administration of fluid. This improves the delivery of oxygen and nutrients to tissues by improving circulation. Initial fluid resuscitation is 500 ml of saline over less than 15 minutes, and this is repeated if there is no improvement (National Institute for Health and Care Excellence (NICE), 2017a). The need for further fluids will be determined by the patient’s response to fluids and escalation may be required. NICE (2017b) recommends that, if within 1 hour the patient has not responded to either the antibiotics or fluid resuscitation, a consultant review is required. Failure to respond is indicated in Table 3.

Although evidence is sketchy surrounding the amount of fluid required, expert consensus is that fluid resuscitation has reduced mortality from septic shock (Gotts and Matthay, 2016). Any delay in receiving fluid can lead to prolonged tissue

Table 1. Risk factors for sepsis

Age ■ Younger than 1 year ■ Older than 75 years

Impaired immune system

■ Drugs: chemotherapy, immunosuppressant medication or steroids

■ Illness: diabetes, sickle cell or patients who have had a splenectomy

Invasive procedures ■ Surgery ■ Indwelling lines or catheters ■ Misuse of intravenous drugs

Breach of skin integrity ■ Burns, blisters, cuts or skin infections

Pregnancy ■ Miscarriage, given birth, pregnant or termination in the past 6 weeks

Source: National Institute for Health and Care Excellence, 2017b

Table 3. Indication for escalation after initial resuscitation (fluid and antibiotics)

Systolic blood pressure <90 mmHg

Consciousness level ■ Reduced consciousness level (<15 Glasgow Coma Scale)

■ VPU the AVPU [Alert, Voice, Pain, Unresponsive] scale

Respiratory rate >25 breaths per minute

Lactate Reduced by 20% in first hour

Source: National Institute for Health and Care Excellence, 2017b

Box 1. Sepsis Six care bundle

■ Deliver oxygen to achieve saturations of 94–98% or 88–92% in patients who retain CO2

■ Take blood cultures and other cultures

■ Administer intravenous (IV) antibiotics within 1 hour of diagnosis

■ Commence crystalloid IV infusion 500 ml in 15 minutes and reassess

■ Measure venous bloods: glucose, lactate and full blood count. Urea and electrolytes, creatinine, C-reactive protein and clotting screen

■ Measure urine output

Source: National Institute for Health and Care Excellence, 2017b; Daniels and Nutbeam, 2017

Table 2. quick Sepsis Related Organ Failure Assessment (qSOFA)

Fast respiratory rate

Low blood pressure

Altered mental state

≥ 22 breaths per minute

≤100 mmHg <15 Glasgow Coma Scale

Source: University of Pittsburgh, 2018

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hypoxia, resulting in multiple organ failure (Gauer, 2013), so it is important that patients with sepsis receive timely intervention to prevent further deterioration. Evidence has indicated that fluid overload leads to worse outcome (Kelm et al, 2015), and this means that a robust approach to assessment and management of fluid is required to optimise patient outcomes.

Lactate is a marker of anaerobic respiration, and this is produced when tissue hypoxia occurs. Oxygen is required for the production of energy in the form of adenosine triphosphate (ATP), but when there is a lack of oxygen, lactate is produced. Lactate represents ischaemia and therefore its measurement helps to identify whether treatment is working. An elevated lactate of greater than 2 mmol/l predicts mortality, while a fall in lactate from the previous measurement may indicate that fluid resuscitation is working (Daniels and Nutbeam, 2017).

Measurement of urine output and any fluids administered provides a clear record of fluid status. Prolonged poor perfusion of the kidneys as a result of hypotension can lead to a reduction in urine output, which is an indicator of acute kidney injury (AKI). Sepsis and AKI frequently occur together and this is associated with worse outcomes, including increased length of hospital stay and mortality (Godin et al, 2015). Robust measurement of fluid input and output should ensure clearer patient management.

Conclusion Sepsis can be difficult to identify because the signs and symptoms can be variable and subtle. Assessment tools, such as NEWS 2 and qSOFA, can aid health practitioners in determining a patient’s risk of sepsis with the management of sepsis guided by NICE (2017b) and the Sepsis Trust (Daniels and Nutbeam, 2017). Oxygen, fluid and antibiotics are aimed to be delivered within the first hour of diagnosis, with blood cultures, measurement of lactate and urine output all guiding management. BJN

Declaration of interest: none

Brent A. Sepsis. Medicine. 2017; 45(10): 649-653. https://doi.org/10.1016/j. mpmed.2017.07.010

Churpek M, Snyder A, Han X et al. Quick Sepsis-related Organ Failure Assessment, systemic inflammatory response syndrome, and early warning scores for detecting clinical deterioration in infected patients outside the intensive care unit. Am J Respir Crit Care Med. 2017; 195(7): 906-911. https://doi.org/10.1164/rccm.201604-0854OC

Daniels R, Nutbeam T, eds. The sepsis manual: responsible management of sepsis, severe infection and antimicrobial stewardship. 4th edn. Birmingham: The UK Sepsis Trust; 2017. https://tinyurl.com/ya7wplm6 (accessed 16 October 2018)

Gaieski D, Mikkelsen M, Band R et al. Impact of time to antibiotics on survival in patients with severe sepsis or septic shock in whom early goal-directed therapy was initiated in the emergency department. Crit Care Med 2010; 38(4): 1045-1053. https://doi.org/10.1097/ CCM.0b013e3181cc4824

Gauer R. Early recognition and management of sepsis in adults: the first six hours. Am Fam Physician 2013; 88(1): 44-53. https://tinyurl.com/ y9mow8m6 (accessed 16 October 2018)

Godin M, Murray P, Mehta RL. Clinical approach to the patient with AKI and sepsis. Semin Nephrol. 2015; 35(1), 12-22. https://doi.org/10.1016/j. semnephrol.2015.01.003

Gotts J E, Matthay MA. Sepsis: pathophysiology and clinical management. BMJ 2016;353:i1585. https://doi.org/10.1136/bmj.i1585

Kelm DJ, Perrin JT, Cartin-Ceba R, Gajic O, Schenck L, Kennedy CC. Fluid overload in patients with severe sepsis and septic shock treated with early- goal directed therapy is associated with increased acute need for fluid- related medical interventions and hospital death. Shock 2015; 43(1): 68-73. https://doi.org/10.1097/shk.0000000000000268

Lamontagne F, Harrison DA, Rowan KM. qSOFA for identifying sepsis among patients with infection. JAMA 2017; 317(3): 267-268. https://doi. org/10.1001/jama.2016.19684

National Confidential Enquiry into Patient Outcome and Death. Just say sepsis! A review of the process of care received by patients with sepsis. London: NCEPOD; 2015. https://tinyurl.com/y8bfer88 (accessed 16 October 2018)

NHS England. Improving outcomes for patients with sepsis. A cross-system action plan. London: NHS England; 2015. https://tinyurl.com/gm4zkps (accessed 16 October 2018)

National Institute for Health and Care Excellence. Intravenous fluid therapy in adults in hospital. Clinical guideline 174. 2017a (updated guideline, first published 2013). https://tinyurl.com/mach6kv (accessed 16 October 2018)

National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. NICE guideline 51. 2017b (updated guideline, first published 2016). https://tinyurl.com/zss9cg4 (accessed 16 October 2018)

Resuscitation Council (UK). Guidelines and guidance. The ABCDE approach. Underlying principles. London: Resuscitation Council (UK); 2014. https://tinyurl.com/hoaesdh (accessed 19 October 2018)

Royal College of Physicians. National Early Warning Score (NEWS) 2: standardising the assessment of acute-illness severity in the NHS. 2017. https://tinyurl.com/ycodbu85 (accessed 19 October 2018)

Sherwin R, Winters ME, Vilke GM, Wardi G. Does early and appropriate antibiotic administration improve mortality in emergency department patients with severe sepsis or septic shock? J Emerg Med 2017; 53(4): 588- 595. https://doi.org/10.1016/j.jemermed.2016.12.009

Singer M. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016; 315(8): 801-810. https://doi.org/10.1001/ jama.2016.0287

University of Pittsburgh. Quick Sepsis-related Organ Failure Assessment. (qSOFA). https://www.qsofa.org/ (accessed 19 October 2018)

Vincent J, Sakr Y, Sprung C et al. Sepsis in European intensive care units: results of the SOAP study. Crit Care Med 2006; 34(2): 344-353. https:// doi./org/10.1097/01.CCM.0000194725.48928.3A

CPD reflective questions ■ Consider how you could improve recognition of sepsis in your clinical area

■ What support would you need to ensure that the 1-hour target of management is met in the septic patient?

■ Consider in which patient groups it may be harder to identify sepsis. How could this be improved?

■ Which patients are at a higher risk of sepsis and what can be done to improve this?

LEARNING OUTCOMES ■ Understand how to identify whether a patient is at a high risk of sepsis

■ Understand the signs and symptoms of sepsis

■ Identify the management strategy for a patient with a high risk of sepsis

■ Be aware of the importance of subtle signs of sepsis, such as new confusion and changes in behaviour

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