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Assessment and care of the patient with sepsis 

Assessment and care of the patient with sepsis
Chapter:
Assessment and care of the patient with sepsis
Author(s):

Kevin Barrett

DOI:
10.1093/med/9780198793458.003.0008
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date: 17 April 2021

Chapter contents

In order to understand how to assess and manage the patient with sepsis, it is essential to have an understanding of the pathophysiology of a dysregulated inflammatory response to an infective process. This chapter will examine:

  • definitions of sepsis and septic shock

  • physiological changes following widespread inflammation.

  • physiological changes to the cardiovascular system

  • nursing assessment of sepsis

  • nursing care of the patient with sepsis to include:

    • care bundles and their rationale

    • nursing management of the septic patient

Learning outcomes

This chapter will enable you to:

  • to appreciate the discussion surrounding the use of qSOFA and SOFA scoring systems

  • to consolidate your understanding of the normal inflammatory response

  • to develop an understanding of changes to this response during sepsis

  • to understand the significance of early and repeated assessment in patients with suspected sepsis

  • to discuss the management of patients with sepsis

  • to understand when the patient with worsening symptoms requires an escalation of support

  • to use the clinical assessment framework to guide your practice

Introduction

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection (Rhodes et al. 2017). In lay terms, sepsis is a life-threatening condition that arises when the body’s response to an infection injures its own tissues

and organs (Singer et al. 2016). Sepsis and its most serious consequence, septic shock, are very significant healthcare problems, affecting millions of people around the world every year. Although the mortality rate for sepsis varies globally, in England it is stated as 30% (NCEPOD 2015). However, assessing actual sepsis-related mortality is complicated, as the International Classification of Diseases, 10th Revision (ICD-10) is not clear in its coding for sepsis and sepsis-related conditions are not always used as the principle cause of death (McPherson et al. 2013). It is noted that sepsis is increasing in its occurrence (Sepsis Alliance 2015; APPG 2016) and that hospitalization for sepsis has more than doubled in the past decade (Nutbeam et al. 2016).

To date, much of the relevant research has focused on early identification and interventions for patients with sepsis in Accident & Emergency (A&E) departments and critical care areas. However, many patients actually acquire sepsis on the general wards (Bhattacharjee et al. 2017). Early sepsis recognition by ward nurses can both reduce progression of this lethal disease and improve survival for patients in hospital with sepsis (Torsvik et al. 2016). This is the focus of this chapter.

Infection is caused by microbes—most often bacteria—invading the tissues which results in a localized inflammatory response from the immune system. Sepsis is the body’s systemic, rather than localized, inflammatory reaction to infection (Mitchell and Whitehouse 2009). This is what is referred to as ‘dysregulated’; the locally mediated and contained immune system controls are lost and the response becomes disproportionate and global.

It is recognized that medical education about sepsis is variable (Health Education England 2016) and that training for registered staff varies significantly too, within the United Kingdom (APPG, 2016; Health Education England, 2016). Regrettably, instances of sepsis are still being misinterpreted by nurses and other healthcare staff with sometimes tragic consequences (Glasper 2016). It is also noted that the general public’s understanding of the condition is poor in the United Kingdom; 55% of the public had not heard of the term ‘sepsis’ and 25% were unaware that sepsis is a medical emergency (UK Sepsis Trust 2016). This widespread lack of awareness about sepsis alone constitutes a barrier in recognizing when these patients are becoming very unwell and require an escalation of interventions to try to avoid the very serious, often fatal, consequences of the condition, whether the patient begins to deteriorate at home or in hospital.

A recent systematic review (Smyth et al. 2016) identified some of the difficulties for identification of sepsis in the community and there is now a clinical toolkit provided for prehospital staff supported by NICE and the College of Paramedics (Nicholls et al. 2016)

Epidemiology: ‘The World’s Oldest Killer’

The epidemiology of sepsis, which is the study of the spread of the condition throughout populations, is helpful to look at because its incidence is so pervasive. Worldwide, there are over 18 million cases of sepsis each year, equivalent to the combined populations of Ireland, Norway, Denmark, and Finland. Although the focus of this chapter is on ward-based patients, it is worth realizing that once patients with sepsis are transferred to an intensive treatment unit (ITU) setting, where they can be best supported, even then a recent global assessment of the mortality rate of these patients, treated in ITU, found that more than one-third of these patients died before leaving hospital (Vincent et al. 2014). In fact, it is reported that within the ITU, patients with sepsis had a 70% relative higher mortality rate compared with patients without sepsis (Melville et al. 2015). This is an extremely high mortality rate and recent parliamentary reports highlight that a number of deaths from sepsis are preventable (PHSO 2013).

In the United Kingdom, the estimated annual figure for deaths from sepsis is in the region of 37,000. Sepsis is more common than myocardial infarction and has a higher mortality than any cancer (Global Sepsis Alliance 2015). The most recent figures for England show the number of deaths from sepsis is increasing; the escalating trend is thought to be due to an increasingly older population becoming ill with a greater comorbidity (NHS England 2015).

Additionally, the therapies used in hospitals are often invasive and any breach in a patient’s anatomical barriers to infection will increase their vulnerability to opportunistic infection (NICE 2016). Widespread use of antibiotics has resulted in many strains of micro-organisms developing resistance to antibiotic therapy and thus are becoming immune from the mainstay of treatment for infection (Sepsis Alliance 2017); consequently, the infection can become much more difficult to contain and suppress.

Sepsis also places a huge financial strain on the healthcare budget. The estimated cost of sepsis each year, including direct and indirect costs, in the United Kingdom is £7.76 billion, a sum that is likely to be a significant underestimation, given that sepsis is still under-reported (York Health Economics Consortium 2017). Much of the high expenditure results from this patient group requiring very intensive nursing care; the nurse-to-patient ratio for very dependent patient groups is high; often one to one (Intensive Care Society 2013). Sepsis is the leading cause for a need for intensive care.

The Surviving Sepsis Campaign

Appreciating the vast scale of sepsis worldwide, as well as the unacceptably high mortalities involved, an initiative to form the ‘Surviving Sepsis Campaign’, endorsed by many of the major critical care societies in North America and Europe, was put into effect in 2002. The initial mandate of the Campaign was to reduce mortality (Surviving Sepsis 2017). The means by which this is to be accomplished is through a seven-point strategy:

  • Building awareness of sepsis: increasing the awareness of healthcare workers and government agencies that fund healthcare as well as the general public of the dangers of sepsis

  • Improving diagnosis: improving early and accurate diagnosis of sepsis, partly by providing a consensus definition of sepsis that is relevant worldwide.

  • Increasing the use of appropriate treatment: disseminating a range of treatment options and urging their timely intervention. Since 2004 there have been internationally accepted guidelines for the bedside management of sepsis (Dellinger et al. 2004). These guidelines are periodically updated, with the most recent being in 2017 (Rhodes et al. 2017) and include the early stages of sepsis which nurses will be managing on the wards.

  • Educating healthcare professionals: providing support and information to all professionals who manage patients with sepsis, including interventions and standards of care.

  • Improving post-ICU (intensive care unit) care: providing a framework for improving and accelerating access to post-ITU care and counselling for patients who have had sepsis.

  • Developing guidelines of care: recognize the need for clear referral guidelines adopted by all countries through the development of global guidelines.

  • Implementing a performance improvement program

All of these points are relevant for nurses, and they are all addressed in this chapter.

New international guidelines have been published for the management of sepsis and septic shock (Rhodes et al. 2017). Within these new guidelines is the proposal that sepsis be identified or suspected through the use of a bedside assessment tool called ‘qSOFA’ or ‘quick SOFA’: SOFA standing for ‘Sequential (Sepsis-Related) Organ Failure Assessment’. The qSOFA score is intended to be an easy to implement tool to identify patients rapidly who are more likely to have poor outcomes typical of sepsis if they have at least two of the relevant clinical criteria, which are a systolic blood pressure of less than 100 mmHg, a Glasgow Coma Score (GCS) of less than 15/15, and a respiratory rate of more than 22 breaths per minute (Singer et al. 2016)

However—and of particular note to nurses practising in the United Kingdom—the qSOFA score has not been recommended by the National Institute for Health and Care Excellence (NICE), the UK Sepsis Trust, or the Royal College of Emergency Medicine to become the primary bedside test for sepsis in the United Kingdom (Nutbeam et al. 2016). One key reason for this is that it would require the introduction of an additional scoring system for patients who are likely to have already been identified as being at risk of sepsis using track-and-trigger systems already in use such as the National Early Warning Score (NEWS2). qSOFA has not been shown to be superior to NEWS in identifying patients with infection at risk of deterioration (Nutbeam et al. 2016).

This point has been highlighted because although qSOFA and SOFA scoring will appear in any of the up-to-date literature you read regarding sepsis, they may well not be used in your Trust.

For your information, the more comprehensive SOFA assessment tool, which requires some invasive tests and laboratory results, is demonstrated in Table 8.1.

Table 8.1 Sequential Organ Failure Assessment (SOFA) Score

System

Score

0

1

2

3

4

Respiratory

Pa/FiO2

mHg (kPa)

≥ 400 (53.3)

< 400 (53.3)

< 300 (40)

< 200 (26.7) with respiratory support

< 100 (13.3) with respiratory support

Coagulation

Platelets, ×103/μ‎L

≥ 150

≥ 150

< 100

< 50

< 2 0

Liver

Bilirubin, mg/dL

< 1.2 (20)

1.2–1.9 (20–32)

2.0–5.9 (33–101)

6.0–11.9 (102–204))

> 12.0 (204)

Cardiovascular

MAP

MAP ≥ 70 mm Hg

MAP < 70 mm Hg

Dopamine* < 5 or Dobutamine* (any dose)

Dopamine*5.1–15

or epinephrine* ≤ 0.1

or norepinephrine* ≤ 0.1

Dopamine* > 15 or

Epinephrine* > 0.1

or norepinephrine* > 0.1

Central nervous system

Glasgow Coma Scale

15

13–14

10–12

6–9

< 6

Renal

Creatinine, mg/dL (μ‎mol/L)

< 1.2

(110)

1.2–1.9

(110–170)

2.0–3.4

(171–299)

3.5–4.9

(300–440)

> 5.0

(440)

Urine output, mL/day

<5 00

<2 00

* = Vasopressor doses are given as μ‎g/kg/min for at least 1 hour. Vasopressor drugs constrict the arterial vessels to help maintain blood pressure.

It should be noted that neither the qSOFA nor SOFA scores were intended to be definitive of sepsis. Sepsis is a broad term applied to a process that is still only partly understood. At present, there are no unequivocal clinical criteria that exclusively identify a patient with sepsis (Seymour, et al. 2016). For this reason, the emphasis is put very much on suspecting sepsis—and indeed suspecting infection—from the outset.

Adapted by permission from Springer Nature: Intensive Care Medicine, Vincent J-L., Moreno R., and Takala J. The SOFA (Sepsis.related Organ Failure Assessment) score to describe organ dysfunction/failure. 22:707–710. Copyright © 1996, SCCM and ESICM.

Abbreviations:

FiO2, fraction of inspired oxygen; MAP, mean arterial pressure; PaO2. partial pressure of oxygen.

Sepsis and septic shock

Because sepsis can manifest in varying degrees of severity leading, in the worst instances, to a state of shock and collapse of multiple organ systems, there are terms to define the progression of the illness that aim to define the scale of the damage that sepsis is causing to the patient. The terms used are sepsis and septic shock which we will consider; they are terms which have recently been reviewed in regard to their assessment criteria and their definitions (Seymour et al. 2016; Shankar-Hari et al. 2016) (see Table 8.2).

Table 8.2 Definition of key terms

Sepsis

Life-threatening organ dysfunction caused by a dysregulated host response to infection. (Rhodes, et al. 2017:1).

Septic shock

Septic shock is defined as a subset of sepsis in which underlying circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than sepsis alone. Adult patients with septic shock can be identified using the clinical criteria of hypotension requiring vasopressor therapy to maintain mean BP 65 mmHg or greater and having a serum lactate level greater than 2 mmol/L after adequate fluid resuscitation*. (Shankar-Hari, et al. 2016: 775)

* Lactate is considered later in the chapter.

Adapted by permission from Springer Nature: Intensive Care Medicine, Rhodes, A., et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock. 43(3): 304–377. Copyright © 2017, SCCM and ESICM. https://doi.org/10.1007/s00134-017-4683-6.

One of the difficulties in recognizing sepsis in its early stages is that the patient will complain of very general symptoms which might be attributable to any number of causes; the onset of the disease can be insidious (NCEPOD 2015). Also, although there are a variety of signs that the patient is developing sepsis, none of them alone are definitive of a septic patient; it is difficult to predict how poorly someone is becoming in early sepsis. Nurses need to be able to recognize that adults with any of the symptoms or signs in Table 8.3 can be at high risk of severe illness or death from sepsis.

Table 8.3 Signs and symptoms of early sepsis

Breathing

High respiratory rate, in excess of 25 per minute, possibly with shortness of breath. Purulent sputum if associated with a chest infection

Oxygen requirements

New need for 40% oxygen or more to maintain oxygen saturation more than 92% (or more than 88% in known chronic obstructive pulmonary disease)

Heart rate

Tachycardia of 130 or more beats per minute

Blood pressure

Systolic blood pressure of 90 mmHg or less, or systolic blood pressure more than 40 mmHg below normal.

Urine output

Low urine output (oliguria): not passed urine in previous 18 hours (or, for catheterized patients, passed less than 0.5 ml/kg/hour). May be painful to pass urine or the urine is foul smelling if associated with a urinary tract infection.

Central nervous system symptoms

Objective evidence of new altered mental state—a change in GCS. Headache if associated with CNS infection (e.g. meningitis)

Skin signs

Warm to touch and/or possible non-blanching skin rash

Abdominal symptoms

Pain if associated with abdominal infections or surgery.

Temperature

High—can be with rigours: this is especially associated with early sepsis but not always found OR can be

Low—especially in very young or elderly OR those patients who are immunosuppressed

General weakness

‘Fluey’ symptoms.

White cell count

Can be raised OR can be abnormally low

Microbiology report

Positive to bacteria or other organisms in biological fluids: blood, urine, sputum CSF, etc.

Adapted from © NICE (2016) Sepsis: recognition, diagnosis and early management. Available from www.nice.org.uk/guidance/ng51. All rights reserved. Subject to Notice of rights. NICE guidance is prepared for the National Health Service in England. All NICE guidance is subject to regular review and may be updated or withdrawn. NICE accepts no responsibility for the use of its content in this product/publication.

It is easy to see how the development of sepsis might remain unsuspected in a patient with one or two of the above signs or symptoms. What is needed is an enhanced ability to suspect sepsis earlier and provide an escalation of support for the patient as quickly as possible.

One term that has long been used in close association with sepsis is ‘SIRS’, which is worth explaining, even though the most recent definitions have recommended that the term is not used in relation to sepsis anymore as it does not necessarily indicate a dysregulated immune response (Singer et al. 2016). When a patient exhibits the systemic signs and symptoms of infection, but does not have a documented infection, the term ‘Systemic Inflammatory Response Syndrome’ (SIRS) is used. This could be caused by any event provoking inflammation in multiple sites throughout the body simultaneously, examples being burns, pancreatitis, or multiple trauma (Balk 2014). These patients can exhibit broadly similar clinical signs to sepsis but the response would not necessarily be a dysregulated one: what defines sepsis is organ failure (Singer et al. 2016).

One further, pre-emptive way of suspecting sepsis is to consider which patients might be at an increased risk of developing sepsis. When, for example, a change in temperature or an unexplained tachycardia is noted in such patients, it is imperative to monitor them closely and alert the shift leader or outreach team about their condition quickly. Patients that are at a high risk of developing sepsis are:

  • the very young (under 1 year) and older people (over 75 years) or people who are very frail

  • people who have impaired immune systems because of illness or drugs, including:

    • people being treated for cancer with chemotherapy

    • people who have impaired immune function (e.g. people with diabetes, people who have liver failure or who have had a splenectomy, or people with sickle cell disease)

    • people taking long-term steroids

    • people taking immunosuppressant drugs to treat non-malignant disorders such as rheumatoid arthritis or people who are already on antibiotics

    • people who have had surgery, or other invasive procedures, in the past six weeks

    • people with any breach of skin integrity (e.g. cuts, burns, blisters, or skin infections)

    • people who misuse drugs intravenously

    • people with indwelling lines or catheters

  • women who are pregnant, have given birth or had a termination of pregnancy or miscarriage in the past six weeks

  • people with complex comorbidities

Reproduced from National Institute for Health and Clinical Excellence (2016) Sepsis: recognition, diagnosis and early management. NICE. London. Available from https://www.nice.org.uk/guidance/ng51. All rights reserved. Subject to Notice of rights. NICE guidance is prepared for the National Health Service in England. All NICE guidance is subject to regular review and may be updated or withdrawn. NICE accepts no responsibility for the use of its content in this product/publication.

The first two groups are those with weak (or immature) immune systems and the next groups are those who have been made vulnerable or susceptible to invasion from micro-organisms. It is helpful to bear these two points in mind when caring for patients that cause concern in terms of changes in their routine observations or who begin to complain of feeling generally unwell.

In order to appreciate why a ‘systemic’ or ‘global’ response to infection is so problematical, it is important to review what the body’s normal or expected response would be.

The immune system: Layers of defence

For an infective agent, be it a bacteria, fungus, or virus, to establish itself within our tissues—or ‘colonize’ them—it must initially bypass the body’s many surface barriers. An infection occurs once our immune system cannot defend against colonizing micro-organisms and they begin to damage tissue (Chapel 2014). The surface barriers constitute the first in a series of defences against the outside world. An intact skin surface with a slightly acid pH provides an effective obstacle as there is no easy way through the skin and the pH is unsuitable for many organisms to inhabit. As the skin is keratinised and thus waterproofed, water-soluble organisms are kept at bay. A number of organisms do manage to colonize the skin surfaces but because the epidermal layers are constantly shedding, the colonies of micro-organisms are shed, too.

Generally, good personal hygiene means that the areas that are most likely to become colonized, such as the mouth, perineum, and hands, are kept clean and don’t allow colonization to develop. The body cavities that are exposed to the outside world such as the respiratory, digestive, and uro-genitary tracts secrete enzyme-laden fluids which are either directly antimicrobial or are lined with mucous that obstruct the pathogen from attaching to and colonizing those areas (Hall et al. 2016). The gastrointestinal tract uses extreme changes in pH to kill foreign bodies. As long as these first lines of defence stay undamaged and intact, patients are protected from most invading organisms. Later in the chapter, the frequently encountered breaks to the integrity of these surface barriers found in ward patients and the significance of these breaks in relation to sepsis will be considered.

However, once a foreign body does penetrate these defences, there are two further levels of protection: the innate responses and the acquired or adaptive reactions (Rote et al. 2014a). The innate system, although including the surface barriers, also consists of cellular and molecular components as well as the inflammatory response. Cells that employ phagocytosis—that is, they ingest other cells—circulate in the blood, lymph, and interstitial fluids as well as inhabit tissues: macrophages and neutrophils, for example. They engulf particles that are recognized as foreign and destroy them with powerful enzymes.

Macrophages are cells that can also release powerful inflammatory mediators which are responsible for much of the classical inflammatory reaction: localized production of heat, redness, swelling, and pain. The inflammatory response is central to and definitive of the second line of defence, and it is the inflammatory response—when it becomes widespread rather than locally contained—that causes many of the problems encountered in sepsis. This is examined in the next section.

The molecular element of the innate immune system is the collection of ‘chemical messengers’ that control the inflammatory and clotting responses and help contain them in the area that is affected. One of the key points here is that the inflammatory reaction is carefully controlled and manifests only in a limited area. These reactions occur in relation to any invading organism or breach in the first line of defence. They all form part of what is termed non-specific immunity; that is, they respond in the same way to any provoking agent and are not specific to that one agent only.

The third line of defence is the adaptive immune system, the behaviour of antigen-specific B- and T-cells which bind to antigen. Antigen is what the immune system interacts with and which helps it to recognize self- and non-self molecules (Male et al. 2013). B-cells secrete immunoglobulins; antibodies which are antigen-specific and which kill that particular antigen. T-cells assist B-cells in making these antibodies (Hall et al. 2016). A key point here is that these defences are specific to individually identified molecules and are thus called our specific immunity.

The inflammatory response and sepsis

It is the second line of our immune system—and in particular the inflammatory reaction—that is responsible for the exaggerated physiological response and the complications that we see in sepsis. Inflammation is a rapid and coordinated reply to cellular injury (Male 2014), characterized by the classic findings of redness, heat, swelling, and pain as well as loss of function. Blood tests will reveal an increased concentration of leucocytes—white blood cells (Blann 2013). Because much of the problem with sepsis is caused by inflammatory changes, this process is reviewed in-depth below.

When tissue is damaged or becomes contaminated with invading organisms, cells that are scouting for foreign bodies—mast cells and macrophages—are activated. Mast cells located in the interstitium around the affected area will ‘degranulate’—that is, release a number of chemical messengers—into the bloodstream. These chemicals will attract white blood cells—primarily neutrophils which are the most abundant white cell type—to the area to help fight the infection. They will also cause vasodilation, widening of the blood vessel, to increase blood flow to that localized area, increasing the supply of the oxygen, white cells, and nutrients needed to combat the infection. Additionally, the permeability the cells making up the lining of the capillary wall, the endothelium, is impacted upon, allowing plasma fluid and some white cells to migrate from within the capillaries to the area that has been injured or infected.

Macrophages will be also be amongst the first components of the innate response to encounter the invading organism. They will release numerous cellular messengers, collectively called cytokines, to alert other parts of the immune system of the invasion and they too, attract neutrophils to the site of infection. Cytokines will also instruct bone marrow cells to produce more neutrophils (Helbert 2017); they are sometimes referred to as the hormones of the immune system. Not all of the messengers involved are cytokines so the term inflammatory mediators can be used to address all of the different ‘families’ of chemicals released during inflammation.

The role of the endothelium

The inflammatory response is carefully orchestrated and something that plays a remarkable part in the coordination of events is the endothelium itself. As a single layer of cells, the capillary endothelium acts as a semi-permeable barrier between the bloodstream and the interstitium, the environment around the cells themselves (Aaronson 2013). Nevertheless, the endothelium is an extremely dynamic membrane.

  • It controls exchange of proteins, hormones, minerals, and immunoglobins between the blood and the tissues.

  • It secretes numerous substances that help control the degree of contraction of the muscle wall in the blood vessels, affecting blood flow and pressure

  • It secretes substances to encourage and also inhibit clotting processes and ensures that clotting is contained locally.

  • It responds to the mediators that are released in inflammation by becoming more permeable or ‘leaky’ (Pappano and Wier 2013).

It is not so important to remember the names of the various substances which are involved in the behaviour of the endothelial cells, but it is necessary to appreciate that once the endothelium is subject to widespread damage, as happens with sepsis, that all of the above controls are lost.

The role that the permeability of the endothelium plays in the normal inflammatory reaction is absolutely central (Levick 2010). For example, when neutrophils arrive at the site of inflammation, they will need to be allowed passage through the blood vessel wall to the affected tissue. The neutrophils are normally too large to squeeze through the tiny junctions between the individual cells of the capillary wall. This particular process, called diapedisis, is managed by cytokine influence on the integrity of the endothelium (Male 2014), making the endothelium ‘porous’ enough for the neutrophils to migrate out of the vascular space. Here the white cells can begin the process of ingesting and destroying foreign particles; it is the concentration of white cells and bacterial debris that is largely responsible for the colour of pus (Rote et al. 2014). This increase in permeability results in the collection of white cells found in inflamed tissue and also for the exudate of plasma fluid that results in inflammatory swelling.

This rather complex sounding series of events can be simplified through a flow chart representation shown in Figure 8.1.

The cardinal signs of inflammation are:

  • redness (erythema): caused by vasodilation and the increased blood flow to the affected area.

  • heat: also caused by vasodilation and increased blood flow as well as the increased metabolic activity at the area.

  • swelling: caused by the collection of plasma exudate.

  • pain: caused by some inflammatory mediators (noticeably one called bradykinin).

  • loss of function: caused by the localized swelling and the effects of pain.

  • leucocytosis (concentration of white cells): facilitated by the permeability of the endothelium.

These inflammatory processes are controlled in what is called a positive feedback loop. In the presence of an alien organism, an increase in macrophage activity and cytokine populations signal the need for a further increase of macrophage activity and release of even more cytokines which, in turn, results in an even further increase, and so on. These processes, by virtue of being influenced by positive feedback, are very powerful and fast acting; they need to be in order to respond to infection and contain it locally (Rote and McCance 2014). When the infection becomes spread throughout the body, as happens with sepsis, these same powerful responses are activated everywhere which results in a massive overreaction and the body’s response becomes uncontrolled and dysfunctional. The term ‘Systemic Inflammatory Response Syndrome’ is easier to appreciate in this light. The overwhelming inflammatory response acting globally on the epithelium actually damages it; it is not particularly the infection that is causing the damage but the patient’s response to it, their own inflammatory processes. Sometimes sepsis is therefore termed a type of hypersensitivity reaction (type V hypersensitivity) (Murphy and Weaver 2017). The widespread leakiness across the endothelium throughout the body results in significant losses of circulating plasma volume, causing hypovolaemia and hypotension, and also in widespread oedema. These are frequent findings in sepsis.

The increased presence of neutrophils (their production in the bone marrow having been stimulated by cytokines) contributes to a rise in the total number of white cells in the blood generally and this becomes a marker for infection. Generally, the white cell count (WCC) is between 3.7 and 9.5 × 109/L (Blann 2013). When the WCC rises above these limits it is indicative of an infective process.

The flooding of inflammatory mediators into the bloodstream typifies the ‘acute-phase response’ to infection in which core temperature is increased and certain proteins in the plasma become activated (Helbert 2017). These are key findings in most patients who have sepsis; the development of a temperature is an especially important one to be vigilant about. The increase in temperature—pyrexia—is caused by the hypothalamus’ reaction to the presence of specific cytokines. The autonomic nervous system (ANS) then ‘resets’ the body’s core temperature in an attempt to make the body’s internal environment hostile to the replication of invading organisms. The acute-phase proteins will be monitored by the medical team in patients suspected of having a systemic infection; the most commonly measured of these proteins is called C-reactive protein (CRP).

One further blood test may be the erythrocyte sedimentation rate (ESR). This test is also suggestive of infection if the value is prolonged. The ESR indicates that cells are taking longer to ‘settle’ or ‘sediment’ in a sample of blood than expected. This, in turn, indicates that the blood has become more viscous or sticky. The viscosity is the result of an increased presence of released cytokines and activated plasma proteins secondary to infection. CRP is a more sensitive test for infection and inflammatory processes than ESR and more likely to be done (Higgins 2013).

The infective agents that are associated with sepsis can be bacteria, viruses, fungi, and some parasites. Predominantly, it is bacteria that are the causative agents and particularly the ‘Gram-negative’ bacteria. Gram-negative simply describes the fact that these bacteria don’t retain a stain—called the ‘Gram stain’—which is applied in the laboratory to differentiate bacteria. Gram-negative bacteria contain molecules called ‘endotoxins’ which are responsible for much of the cardiovascular dysfunction seen in septic patients. Endotoxins are a component of the Gram-negative bacterial cell wall and directly injure the endothelial lining of capillary vessels; endotoxin will cause vasodilatation, inappropriately activate the coagulation cascade, and depress the myocardium (Cilliers et al. 2009). Gram-positive bacteria can also result in similar compromises.

One group of patients that require particular vigilance in terms of the development of sepsis and shock are neutropenic patients (Dunkley and McLeod 2015). Neutropenic patients are unable to mount a normal response to infection because their white cell population is very low. By definition the WCC will be less than 4 × 109/L (Gargani 2012), but it can be much lower even than this. Neutropenia may be congenital or, more likely, acquired due to infections, autoimmune disorders, or due to chemotherapeutic regimens in cancer treatment, for example (Barrett and Dikken 2010). Neutrophils have a very short life span and the stem cells that produce them in bone marrow must divide very rapidly to maintain circulating levels in the bloodstream (Coico and Sunshine 2015); for this reason, chemotherapy agents that target rapidly reproducing cells (such as tumour cells) will affect neutrophils levels too.

Neutrophils help contain infection and without them infection can spread unhindered and become systemic quickly (Nairn and Helbert 2017). An infection in the lungs, for example, will not result in localized symptoms and pus formation but can spread rapidly into the blood. The macrophage activity is still intact, however, so cytokine release will still produce a temperature and shivering responses. Sometimes this is the only warning sign in neutropenic patients that an infection is present and in these patients sepsis may develop quickly. It may be that patients simply report feeling generally poorly, which is not uncommon in chemo- or radiation therapy patients. If a temperature rise is noted in a neutropenic patient, intravenous antibiotics are indicated and should be given immediately (NICE 2012), within one hour of the pyrexia being noted, in order to combat the bacteria and the effects of its endotoxin. If a tachycardia and hypotension are noted in the patient, it signifies that sepsis and shock are already developing and these patients need an urgent medical review.

Review point 1

  • Sepsis is the result of a dysregulated immune response to an infection.

  • Sepsis can lead to shock states with a very high mortality.

  • The inflammatory response is influenced and moderated by the endothelium. When the endothelium is damaged in a widespread fashion, this moderation is lost and inflammation becomes inappropriate.

  • Neutropenic patients cannot mount a normal white cell response. These patients may only show a temperature or complain of feeling vaguely unwell. Time is of the essence in these patients, particularly in terms of having a medical review and intravenous antibiotics being administered.

  • The prevalence of sepsis is very high but this is underestimated by healthcare professionals. The Surviving Sepsis Campaign aims to raise awareness of sepsis and provides treatment guidelines.

Pathophysiology: The cardiovascular system

Sepsis will affect every system in the body to some degree, partly because the infective agent is blood-borne and thus can spread everywhere, but also because the effects upon the cardiovascular system, responsible for blood pressure and oxygen delivery to all cells, is so profoundly and immediately affected. The cardiovascular manifestations of sepsis are essentially vasodilatation, the resultant maldistribution of blood flow, and myocardial depression (Guarracino et al. 2016) The main cardiovascular response to sepsis is widespread vasodilation: the relaxing of the smooth muscle wall inside the blood vessels which leads to looser, wider blood vessels. This global vasodilation is caused in part by the release of a substance called nitric oxide which the endothelial cells release in response either to changes in blood flow or in response to cytokines (Levick 2010).

The main consequence of such widespread vasodilatation is that of hypotension, inadequate blood pressure to supply the tissues and cells with nutrients and, in particular, oxygen. Hypotension, if it is left unnoticed and untreated, will affect every body system simply because they all rely upon the cardiovascular system to deliver oxygen and remove waste products. The worst case scenario in terms of hypotension is shock. Shock can be defined as circulatory insufficiency (Levick 2010): the cardiovascular system cannot meet the metabolic demands of the cells and the cells begin to dysfunction. This leads, if unsuccessfully treated, to multiple organ failure, because all cells are affected, and ultimately to death.

In order to appreciate exactly why hypotension occurs in these patients it is helpful to quickly review how blood pressure is maintained in health (see also Chapter 3). The cardiac cycle is the sequence of events that the heart undergoes throughout one heart beat (McCance 2014). The heart pumps blood through the pulmonary and systemic vasculature by generating enough pressure to propel the blood that has drained into the ventricles—the ‘stroke volume’—forward. This is called the systolic pressure and is produced by forceful contraction. The heart then relaxes and allows the next stroke volume to drain into the ventricles; this stage of the cycle is termed diastole. Clearly, the previous stroke volume will stop its forward movement as the propelling force from the heart comes to rest, as in diastole. There must be some other influences that support both the forward movement of blood and also maintenance of the pressure that the blood is under in order for it to reach the tissues far from the heart and at a pressure high enough to perfuse those tissues. These other influences are the behaviour of the blood vessels; there are cardiac and vascular components to blood pressure, hence the term ‘cardiovascular’.

When the arterial vessels receive the stroke volume under high systolic pressure, they distend in order to accommodate the bolus of blood. They are able to do this because of the elastic nature of their walls; they have a layer of smooth muscle and elastic tissue, called the ‘tunica media’, which provides the ability to stretch. Whilst the heart stops contracting, the vessel wall can recoil from their stretched position, further squeezing the blood onward, and this provides some continuity of forward propulsion for the blood. The most important factor, however, in preserving the blood pressure throughout the cardiac cycle is the tension that the blood vessel wall is kept under. This accounts for the pressure of blood in the vessels during the period that the heart is resting and filling: the diastolic pressure. This is the pressure that the heart has to overcome in order to provide the next stroke volume and is termed the ‘systemic vascular resistance’ (SVR) (Pappano and Wier 2013). SVR is maintained by a number of factors, though primarily through the sympathetic nervous system (SNS). The SNS innervates the smooth muscle wall of the vessels and sustains a level of contraction, or muscular tone, to ensure that the lumen, or internal diameter of the vessel, is within a range of functional limits. The timing of the cardiac cycle is approximately two-thirds diastole and only one-third systole, and thus the vessel wall tone contribution to maintaining blood pressure is very significant.

With a wider lumen in the blood vessels, it is increasingly harder for the heart to maintain the blood pressure at its normal value. An analogy here would be of a hose pipe with a narrow lumen—perhaps because a thumb has been partly placed over the opening—providing a good pressure of water. Compare that with the pressure of water from the hose when the thumb is removed; the pressure drops because the lumen is wider. When the blood vessel lumen widens, the diastolic component or SVR is reduced. In response to the decreased SVR, the heart rate increases to compensate for this loss in diastolic pressure, and tachycardia is a classic finding in patients in early stages of sepsis. The bounding, fast heartbeat is indicative of the cardiovascular system adjusting for vasodilation and the patient is said to be in a ‘hyperdynamic’ state. At this stage of sepsis the patient has a high cardiac output but only a normal or adequate blood pressure. This hyperdynamism can only be maintained for a limited amount of time. After further vasodilation, the ability to compensate with a tachycardia alone becomes exhausted and the blood pressure becomes ‘de-compensated’ and falls to inadequate levels. At this point the pulse will feel ‘thready’ or weak. This is when shock is likely to develop very quickly. One of the reasons that patients with sepsis will be moved to a critical care unit is that their blood pressure and cardiac output can be monitored very closely and supported with powerful drugs, such as vasopressors, which are considered in Chapter 3.

Vasodilatation is also responsible for, or contributes to, some of the other frequently encountered assessment findings in the patient with sepsis. These include the heat of their skin—surface temperature, their flushed appearance, and widespread peripheral oedema—although this is most markedly noticeable in patients in the latter stages of sepsis; hopefully these patients have already been relocated to the high-dependency unit (HDU) or ITU by this point. The flushed appearance and, in part, increased skin temperature are due to the inappropriate dilation of peripheral vessels close to the skin, bringing an increased flow of blood close to the skin surface. Physiologically, the formation of oedema is more complex.

Oedema formation

In health, a constant balance of the ‘escape’ and return of plasma from the intravascular space into the interstitial space and back to the intravascular space is maintained. Fresh plasma fluid bathes the cells and so helps to deliver dissolved oxygen, electrolytes, and nutrients directly to respiring cells. The homeostatic mechanisms that regulate this circulation prevent any build-up of fluid in the interstitium which would interrupt the supply, for example, of fresh oxygen and the removal of waste gas. Because oedema can be global and very exaggerated in septic patients and because it can cause a number of secondary complications requiring nursing care, it is helpful to review how oedema occurs in sepsis.

Typically, blood arrives at the capillary beds from arterioles at a perfusing pressure of approximately 32 mmHg. This perfusing pressure is enough to push a small yet constant volume of the plasma, complete with all of its dissolved contents, through the microscopic junctions that exist between the single cell layer of the capillary vessels. The volume able to leave the vascular space is regulated by the perfusing pressure and the size of the cell junctions and the integrity of the vessel wall; there are only a certain number of tiny outlets for the fluid. It is also regulated by a force exerted by molecules in the capillary blood called colloid molecules; these are large molecules that are too big to squeeze through the cell junctions—red and white blood cells and proteins, for example—and create what is known as colloid or oncotic pressure. Oncotic pressure, approximately 20 mmHg in the capillaries, serves to retain most of the plasma fluid in the vascular space; it exercises a holding force on the fluid which can only escape its influence if the perfusing pressure is greater. At the arteriolar end of the capillary bed, the perfusing pressure (32 mmHg) is greater and plasma leaves the vascular space and becomes part of the interstitial fluid.

Once the fresh plasma has bathed the cells it will be depleted of fresh oxygen and nutrients, etc., and also will have picked up the waste products of the cells’ metabolism—noticeably, carbon dioxide gas. This exchange will be due to concentration gradients of the various substances between the cell and the interstitial fluid. Unless the interstitial fluid is able to ‘drain’ itself back into the vascular space, there will be an accumulation of waste products and an interruption of the concentration gradients. This drainage happens because of the constant oncotic pressure in the capillary vessels provided by the presence of the large molecules: in a healthy, intact capillary vessel the large colloid molecules cannot escape through the vessel wall and this guarantees a consistent oncotic pressure along the length of the vessel. The perfusing pressure however, decreases along the length of the capillary from the arterioles (32 mmHg) to venules (12 mmHg) (Figure 8.2).

Figure 8.2 Normal tissue perfusion and drainage.

Figure 8.2 Normal tissue perfusion and drainage.

Note now that the colloid pressure (20 mmHg) exceeds the perfusing pressure at the venous end (12 mmHg). At this point the interstitial fluid can be drawn back into the vascular space, through the same epithelial wall junctions, because the ‘pulling’ colloid influence of all of the large molecules now exerts a stronger influence than the ‘pushing’ perfusing pressure. In this way there is a constant flow of fluid into and out of the interstitium. Any residual fluid that might collect in the interstitium is collected by lymphatic vessels and then drained back into the bloodstream.

Sepsis disrupts this mechanism predominantly through compromising the integrity of the vessel walls. Endotoxin injures the endothelium directly and excessive cytokine activity causes the capillary junctions to become inappropriately permeable: sepsis has ‘over-induced’ the inflammatory response, causing it to ‘overreact’ (Figure 8.3).

The combined effect is to let not only far too much fluid into the interstitium but also to allow some of the colloid molecules, especially the smaller proteins, to enter the interstitial space and thus ruin the oncotic pressure balance responsible for draining fluid back into the circulation. Too much fluid in to the interstitium and not enough back out results in the oedema that develops in more advanced cases of sepsis and also in the patients who have returned from ITU settings after having survived sepsis. Oedema can be incapacitating for patients because it may lead to blisters and rashes and cause restrictive, swollen joints and swelling of, or effusions around, vital organs (Levick 2010). The oedema experienced by patients who have had sepsis will have been profound and, as well as its debilitating physical effects on the patient themselves, it may have had a disturbing effect on relatives as the swelling of the soft facial tissue such as eyelids and lips can render people unrecognizable.

Secondary to hypotension and poor perfusion will be hypoxia of the tissues. When cells are in an ‘oxygen-poor’ environment, they begin to respire anaerobically, a byproduct of which is lactate. Lactate is acidic and when it builds up in the tissues it has a toxic effect on cells. Lactate levels in health are low—normal values being 0.5–2 mmol/L (Higgins 2013) and raised levels signify that tissues are being under-perfused, hence lactate has become a frequently monitored blood value at the bedside. Other clinical signs of poor perfusion are acutely diminished mental status, a slow capillary refill time when a nail bed is pressed, cool and/or pale skin (Vaughan and Parry 2016).

Another of the key features of cardiovascular compromise in sepsis is the effect upon the body’s clotting mechanisms. In sepsis the epithelium has a prominent role in the derangement of clotting controls; coagulopathy (Levick 2010). Damage to the epithelium will activate the clotting cascade (Levi and Schmaier 2016); this can occur in sepsis from excessive cytokine activity or endotoxin from Gram-negative bacteria, for example. Because of the extensive nature of the injury to the endothelium in sepsis, the clotting cascade will be activated in numerous sites resulting in microthrombi which occlude vessels supplying vital organs and tissue beds. Because the clotting processes are widespread rather than locally contained and because the thrombus is formed inside blood vessels, the condition is termed disseminated intravascular coagulopathy (DIC) and is seen in up to 35% of cases of sepsis and septic shock (Okamoto et al. 2016). The indiscriminate nature of thrombus formation throughout the body results in the profound depletion of clotting factors and this leads, in turn, to uncontrolled bleeding or ‘oozing’ of blood from any puncture sites such as intravenous access or the patient’s gums or invisibly as internal bleeds from ulceration points, for instance. When the occlusion of vessels is combined with poor perfusing pressure due to vasodilation and loss of circulating fluid due to oedema formation, the effects are catastrophic and patients develop refractory shock; that is, shock which is unresponsive to fluid resuscitation and the powerful drugs that constrict blood vessels to support the blood pressure. This combination of pathologies contributes to the organ failure that results in such high mortality for sepsis.

The last of the three main cardiovascular compromises is myocardial depression which is commonly met in sepsis (Lu and Wang 2016). This is caused directly by some inflammatory mediators; in fact, one is named myocardial depressant factor. The result upon the heart is a reduced contractility so that even when fluid is given to resuscitate the blood pressure, the heart fails to respond adequately (Kakihana et al. 2016). This reduced contractility affects the ability to generate sufficient systolic pressure. This is dangerous for the septic patient as they also have a loss of circulating volume in the form of oedema and a reduced diastolic pressure due to vasodilation. All three situations together wreak havoc with the body’s ability to supply enough oxygen to cells, this is why shock states develop so frequently in sepsis and why mortality is so high. The important point is to suspect its development and act quickly with the other multidisciplinary team (MDT) members to support the patient early, and this is how septic patients are most likely to survive.

Review point 2

  • Global endothelial dysfunction results in profound cardiovascular compromise which, in turn, will affect all body systems.

  • Sepsis causes vasodilation due to endothelial damage and massive inflammatory mediator release, resulting in hypotension from compromise of the diastolic function.

  • At a time when increased oxygen delivery is needed, the myocardium becomes ‘depressed’ resulting in hypotension from compromise of the systolic function.

  • Widespread oedema, caused by global endothelial permeability changes, is a common finding in sepsis which effectively renders the patient hypotensive.

  • Sepsis, through damaging the endothelium, can initiate the clotting cascade globally. This can result in multiple microthrombi that occlude vessels, resulting in poor perfusion of vital organs which can lead to organ failure.

  • Lactate is an indicator of tissue hypoxia and shock.

Sepsis thus affects the cardiovascular system in a profound way, but all systems are affected. The respiratory system is a major indicator of physiological changes in sepsis. The increased metabolic demand for oxygen and increase in production of carbon dioxide, will result in a higher respiratory rate (tachypnoea). Tachypnoea is viewed as being a reliable marker of patient deterioration (Resuscitation Council (UK) 2017). Other signs of the patient struggling with respiratory function are use of accessory muscles which include the abdomen, shoulder girdle, and facial muscles. If the infection has come from the respiratory system, which is likely as a reported 68% of sepsis cases are from pneumonia (Royal College of Nursing 2016), there may be other signs of respiratory distress such as coughing, painful breathing, low saturation levels, or purulent sputum. Sputum samples should be sent for microbiological culture and sensitivity testing (MC&S).

The renal system relies on a perfusing pressure to filter blood plasma at the glomerulus in order to begin to form urine (Doig and Huether 2014). Without this pressure, urine production falls or ceases altogether. Urine output is a good indicator of the perfusion of the kidneys (and thus all other vital organs) and so it is important for us to have a clear indication of the patient’s renal function. The minimum that a normal urine output amounts to is 0.5mL/kg, so in a person weighing 80kg, 40mL per hour is expected; anything less is termed oliguria. The complete absence of urine output, which is a serious indication of renal failure, is called anuria.

It is important to recognize if a patient is becoming oliguric before they become anuric; once organ failure is evidenced, the patient is in sepsis and beginning the decline into the awful morbidity and mortality associated with it. To this end an hourly urine output is helpful as it alerts to possibly small but consistent changes in kidney function and a catheter can facilitate these observations. However, catheters are also a frequent source of hospital-acquired infection (NICE 2015) and, thus, sepsis. Needless to say, strict asepsis is always imperative in catheter insertion (NICE 2015).

If the original infection has come from the urinary tract, the patient may complain of discomfort when passing urine and the urine itself may well be cloudy, discoloured, and foul smelling. A urine-analysis dip stick test can identify the presence of leucocytes or nitrites—both indicators of bacterial presence. Any abnormal findings from this simple and quick test need to be followed up or referred on to the senior nurses or medical team. In the case of a positive result for bacterial presence a urine sample needs to be sent for MC&S; urinary tract infections (UTI) make up 14% of infective sources for sepsis (Royal College of Nursing 2016). Other markers of renal function will be gleaned from biochemistry results such as urea and creatinine levels and are discussed in Chapter 5.

The other significant source of infection in sepsis is the gastrointestinal (GI) tract; 22% are from abdominal sources (Royal College of Nursing 2016). Abdominal pain would be an obvious cause for concern as would a distended abdomen; this may be caused by collections of gas or fluid. These collections, in turn, are due to poor perfusion of the gut causing an ‘ileus’ or immobile intestine, which allows fluids to collect rather than be absorbed or transported. One interesting point in relation to the GI tract is that it will allow much of its own blood supply to be diverted to the other vital organs in hypovolaemic or shock states. If the shock state is not resolved quickly, the GI tract begins to suffer the consequences of poor perfusion.

Immediate response—the ‘Sepsis Six’

It is known that delayed identification and response to serious illness like sepsis results in poorer care for the patient, which will impact on their morbidity and mortality (NCEPOD 2015). It is also well known that recognition and therapeutic support given early—in the ‘golden hours’ of illness—provide the most benefit for patients. There are elements of evidence-based care that all patients should receive, but which are subject to variability; sometimes they are not put into effect in the same way (Williamson et al. 2014). To standardize care into best practice everywhere, these elements are sometimes grouped into ‘care bundles’, and there are two care bundles for sepsis, one for the first three hours and one for the first six hours. Both bundles have recently been refined (Surviving Sepsis Campaign 2015). Implementation of the bundles has been shown to improve survival (Levy et al. 2015), although in order to have their positive impact on patient care, all components of the bundle must be carried out.

In order to improve awareness of sepsis and the implementation of these two sepsis care bundles, the UK Sepsis Trust, a registered charity (see Resources section) has developed a number of educational resources for healthcare professionals. It has specific sections for acute hospital ward staff, recognizing that initiation of early management steps outside of designated critical care areas is an essential part of providing the best care for patients who are ill with sepsis. Some elements of the six-hour bundle do require specialist environments with specially trained staff and equipment, highlighting the need for responses to sepsis to be multidisciplinary in nature (Vaughan and Parry 2016a). Nonetheless, there are six points of care that can be initiated or requested quickly by ward nurses within the first hour of recognizing deterioration from sepsis, which have a major impact on whether the patient survives or not. These are called the ‘Sepsis Six’ and are outlined below as per the guidelines produced in collaboration with NICE by the UK Sepsis Trust (2016a). The Sepsis Six is one of many toolkits that are published by the Sepsis Trust; there are protocols for A&E departments and other specific areas.

  1. 1. Oxygen

    Metabolic demand for oxygen throughout the body is hugely increased by sepsis and it is essential to at least ensure the supply of oxygen is maximized; as discussed earlier in the chapter, delivery and uptake at cellular level may be impaired. The British Thoracic Society’s Guideline for Oxygen Use in Adults in Healthcare and Emergency Settings (2017) stipulates the following:

    In critical illness, including major trauma, sepsis, shock and anaphylaxis, initiate treatment with a reservoir mask at 15 L/min and aim at a saturation range of 94–98%. This advice also applies to patients with critical illness who have risk factors for hypercapnia pending the results of blood gas measurements and expert assessment. In patients with spontaneous circulation and a reliable oximetry reading, it may be possible to maintain a saturation of 94–98% using lower concentrations of oxygen. (The British Thoracic Society’s Guideline for Oxygen Use in Adults in Healthcare and Emergency Settings, 2017:49)

    The patient will also benefit from an arterial blood gas sample being taken, so a member of the medical team will need to be involved for this. High-flow oxygen will be drying to the patient’s upper respiratory tract mucosa so a humidified delivery system and frequent oral hygiene should be offered. The patient should not be left alone at this stage; reassurance is particularly important and their observations may need repeating frequently. It is also important for the mask to be kept on; if a patient is becoming hypoxic and confused they will often try and remove the mask.

  2. 2. Blood cultures

    It is imperative to identify the infecting organism and blood cultures must be taken prior to administration of antibiotics. At least two sets should be drawn: one percutaneously, from a peripheral vein, and one from each intravascular device if in for more than 24 hours. Consideration should be given to other samples, including sputum, urine, cerebrospinal fluid, and pus. Strict asepsis whilst obtaining the samples is vital (NICE 2012a). Contamination of blood results can lead to ‘false positive’ results suggesting infection where there is none. Typically results are ready within 48 hours and all members of the team should be involved in actively seeking the results.

  3. 3. IV antibiotics

    The early administration of broad-spectrum antibiotics is associated with significant reductions in mortality (Ferrer et al. 2014). Prescriptions should be reviewed once positive blood cultures are obtained to ensure that the identified organism is being targeted in as specific a fashion as possible. Most Trusts have strict protocols addressing this.

  4. 4. IV Fluids

    Patients with sepsis often require early, rapid fluid resuscitation to optimize tissue perfusion and limit subsequent shock and multi-organ dysfunction (see also Chapter 7). Fluid resuscitation is replacing some of the circulating volume that has been ‘lost’ because of capillary leak and oedema. Crystalloids are favoured over colloids in recent international guidelines (Rhodes et al. 2017) and a bolus of 500 mL is recommended and is repeatable, although must not exceed 30 mL/Kg in total (UK Sepsis Trust, 2016a). A successful response would be indicated by a rise in blood pressure and central venous pressure, where that is being measured, and these improvements would be maintained without the need for further fluid. Patients that we must observe especially closely here are those with a history of heart failure, left ventricular failure in particular, because of the ease with which they can become fluid-overloaded and begin to develop pulmonary oedema. Elderly patients and those in renal failure must also be cautiously monitored during fluid resuscitation.

  5. 5. Serial lactate levels

    Tissue perfusion is compromised in sepsis and when cells are in a hypoxic environment they respire anaerobically resulting in lactate production. Lactate therefore provides an indication of the adequacy of tissue perfusion. Normal values are 0.5–2 mmol/L (Higgins 2013) and values above 4 mmol/L are diagnostic of shock. Lactate is important in the recognition of sepsis and is prognostic of mortality (Nutbeam et al. 2016), although as an isolated value is not definitive of sepsis per se (Fenwick 2016). Serial measurements may demonstrate a response or a lack of response to resuscitation. If the fluid resuscitation is raising blood pressure and improving perfusion, the cells can begin to respire aerobically once again and stop producing the lactate. Lactate can be measured using a blood gas analyser or hand-held device.

  6. 6. Measure and improve urine output

    This often requires insertion of a urinary catheter where not already in place; some patients are still able to urinate spontaneously but ideally urine output should be measured hourly to notice when it begins to fall. Urine output is a direct measure of blood flow to the kidneys and therefore an easily observable measure of cardiac output, for most people. A low cardiac output will mean poor blood supply to all organs, not just the kidneys. Early recognition of a low urine output, and taking steps to improve it, will help to reduce the likelihood of an acute kidney injury developing (NICE 2013). Fluid balance charts should be precisely maintained and certainly should be commenced for patients if they are not already on one.

A helpful, preliminary step may be to ensure that the patient has a patent intravenous access for the IV therapies mentioned above. It may be prudent to ensure two cannulae are in place so that antibiotics and fluid can run concurrently. Check if existing cannulae are patent. Check if the lumen is wide enough to run fluid in quickly, if needed. Check for signs of phlebitis at any existing cannula site and the need to change it as this can be a precursor to infection and even sepsis in itself. These checks for phlebitis can be extended to other catheters; central venous lines, for instance. A check on how long they have been in situ is also valuable. If a central line is in place and asymptomatic then ensuring that the ports are all patent and available for infusions, in keeping with local policy, is sensible.

The term ‘Red Flag Sepsis’ was introduced by the UK Sepsis Trust (2014) and a series of screening tools have been developed to support clinicians in a range of settings (UK Sepsis Trust 2016a, 2014b) to highlight the significance of some key individual physiological findings in relation to suspected sepsis. The ‘red flag’ indicators are:

  • Systolic BP ≤ 90 mmHg

  • Heart rate > 130 per minute

  • Respiratory rate ≥ 25 per minute

  • Oxygen saturations < 91% (it may be appropriate to accept SpO2 < 91% in patients with known chronic obstructive pulmonary disease (COPD))

  • Responds only to voice or painful stimuli or is unresponsive

  • Has a purpuric rash

Adapted with permission from The UK Sepsis Trust. Sepsis Red Flags. https://sepsistrust.org/.

Any of these findings alone in a patient with suspected sepsis needs to be escalated to senior staff’s attention.

The other essential point is that specialist help is available to commence any additional interventions or therapies. Certainly the Trust’s support team such as the Critical Care Outreach team or Patient at Risk Team (PART) will be involved in the care of this patient group, and a referral to the HDU will need to have been made. This is because the continuing care for these patients does generally require specialist facilities. One area of support that can be provided for ward-based patients is blood glucose monitoring: in sepsis, the cells’ ability to take up the glucose they need is impaired and there is a resultant hyperglycaemia. It may be that an intravenous insulin regime needs to be initiated to control high glucose levels because poor glycaemic control is associated with worse survival levels (NICE 2014).

Referral

It has been acknowledged that some acutely ill patients have received suboptimal care in hospitals, leading to their condition worsening unnecessarily (PHSO 2013). Errors in the early management of these patients include failure of the organization, but issues within the MDT have also been identified. There was a failure to take a timely history and make a timely patient examination, the source of infection was not identified quickly enough, and the key treatments were not initiated soon enough. Some of the organizational issues included inadequate staff education and training about sepsis and appropriate, timely senior input was not ensured (PHSO 2013).

Government documents have extolled the need for track-and-trigger systems to be in place for patients who are deteriorating in hospitals, culminating in the Royal College of Physicians’ recommendations of the use of the National Early Warning Score (NEWS2) (Royal College of Physicians 2017). This scoring system is now used across NHS Trusts within the United Kingdom to identify acute deterioration in patients such as those with sepsis. Staff are encouraged to review for sepsis if the NEWS2 is greater than 5 (RCP 2017). Early escalation of concern and initiation of therapeutic support for patients suspected of developing sepsis is emphasized (Nutbeam et al. 2016) and these issues relate directly to the nurse’s role in the management of sepsis (McClelland and Moxon 2014).

Critical Care Outreach Services are now understood as an integral aspect of the critical care specialty (Quinton and Gonzalez 2019). Essentially, the outreach team is a central means of supporting patients who are deteriorating and also of referring them on to critical care if required and the team has become a key resource for ward staff concerned about a deteriorating patient. Being willing to contact the outreach team as early as possible with concerns about suspected sepsis helps to speed up referral to definitive care.

There are issues, however, involved in what is seemingly a simple process of referral. Studies to date in the utilization of care bundles and early recognition of sepsis outside of critical care, for instance, have shown that there is a need for improvement (Levy et al. 2010). Some of the obstacles recorded to successful referral have been incomplete recordings of the observation charts and hesitation in escalating concerns, leading to adverse incidents that are deemed avoidable; these nursing issues are global in their occurrence (Massey et al. 2017). The cause for these situations was considered to be complex, a combination of confidence and communication skills amongst other factors. These issues cannot be viewed in too simplistic a manner, however. Reports from ward nurses looking after critically ill patients identify that there are not only educational issues that still need to be met but that assertiveness in professional relationships appears to be a key skill—and one that often comes with experience—in terms of ensuring that a patient is reviewed (Massey et al. 2017). Concerns about calling the medical team inappropriately have been voiced, as well as a need for emotional support in terms of dealing with unstable patients in a ward setting and anxieties with inter-professional issues such as appearing foolish for misinterpreting a degree of deterioration (Massey et al. 2014).

However, it is known that basic physiological observations are delegated to healthcare assistants in many instances and that a reliance on automated machinery to take blood pressures, for example, is commonplace. This removes nurses from core physical assessment findings that we would be exposed to if we were undertaking them; noticing that a pulse was weak by feeling it rather than reading it from a display or feeling that an arm was very cool whilst taking a blood pressure, for example. As more patients being cared for on the wards are especially unwell or prone to deterioration, the role of nurses’ physical assessment abilities is vital and will have an impact on detection of abnormalities and patient well-being (Zambas et al. 2016).

Counselling and support

A critical illness, in its entirety, can be viewed as a continuum and ward nurses are in a position to be with the patient at the start and the end of their stay in hospital whilst having sepsis. Care needs for those patients who have survived sepsis needs further consideration.

Typically, patients with sepsis will be cared for in an ITU. For many patients and their families, leaving the perceived security of a critical care unit to anywhere else in the hospital can be anxiety provoking and it is important that counselling and support is provided for patients who survived an episode of sepsis as it is a component of the Surviving Sepsis Campaign. Patients and their loved ones begin to try and make sense of what will have been a near-death experience. Patients and families will need to construct a ‘story’ of what has happened to make sense of events and nurses have a key role in facilitating this (Stayt et al. 2016)

It is well recognized that patients experience an enduring impact after having survived sepsis (Gallop et al. 2015) and follow-up care afterwards is now a recognized component of critical care (NICE 2009, 2015a). NICE quality standards (2017) address the need for short- and medium-term rehabilitation goals to be agreed before discharge from critical care and for those patients transferring to a general ward to have a formal handover of their individualized rehabilitation programme, ideally. Patients discharged from hospital should be given information about what to expect afterwards and those with ongoing rehabilitation needs should have a review two to three months after their discharge from critical care (NICE 2017), and the fact that patients may need a variety of types of help for several months after discharge from critical care units should be impressed upon family members (Svenningsen et al. 2015). It is also noted that patients who have had sepsis are likely to be readmitted to critical care areas (Bateson and Patton 2015).

Problems encountered after a critical illness, such as sepsis, include physical, psychological, emotional, and cognitive dysfunction (NICE 2015a). Post-Intensive Care Syndrome is a term referring to new or worsening impairments in physical, cognitive, and/or mental health in patients that have required intensive care (Wolpaw et al. 2016). These morbidities persist beyond patients’ stay in critical care areas and may be present in their stay on general wards. Patients report profound disorientation (Parker et al. 2013). Strahan and Brown (2005) have compiled some practical recommendations for care for patients at this phase of their recovery, which are still very relevant:

  • Nursing interventions should aim at maximizing patient control and help towards reducing anxiety levels. This will entail inclusion of the patient in possible choices available for medical or nursing care and explanations of all that is being done.

  • Patients should be encouraged to re-adopt their ‘normal’ sleep pattern.

  • Education regarding rehabilitation and diet is essential—physiotherapy and dietician input is important here.

  • Families should be involved in care and the rehabilitation process.

  • Opportunity should be offered to discuss memories and nightmares, both real and hallucinatory. This is potentially time-consuming for nurses on a busy ward but needs to be accommodated. It may also be that specially trained personnel such as hospital counsellors are best suited to this.

  • The need for patient information, explanation, and reassurance is real. One significant difference between critical care environments and wards is the staffing ratio and patients and relatives should be assured that although staff may not be constantly at the bedside, they are available and approachable.

Adapted from Intensive and Critical Care Nursing, 21, 3, Strahan, E.H.E., and Brown, R.J., A qualitative study of the experiences of patients following transfer from intensive care, pp. 160–71. Copyright © 2004 Elsevier Ltd. All rights reserved. https://doi.org/10.1016/j.iccn.2004.10.005.

The multidisciplinary approach is an important overview to keep when patients return to the ward. Relevant referrals are essential; perhaps to the Occupational Therapy department or to the chaplaincy service or other forms of spiritual support. It is possible that the mental health team might be an appropriate resource or a hospital counsellor would be able to offer practical input for the patient or family members. These referrals are within the remit of nurses to consider and put forward as practical, helpful options. Because they can entail the addressing of sensitive issues, it is advisable to broach matters privately with the patient first, if possible. Some resources for patients or relatives which can be particularly meaningful are those that share the experiences of other patients—one online example being healthtalk.org (see Resources section); there may be support groups active locally, too.

It is also appreciated that the turmoil that relatives experience during a family member’s critical illness can leave them very drained physically and psychologically (O’Gara and Pattison 2015). It is also highly likely that the care of the patient at home will involve family members, and to this end it may be appropriate to engage with social services to offer them support. As before, this referral needs to be done, ideally after consultation with the family members themselves.

An important reality check for relatives to be aware of is that psycho-social recovery from this kind of extreme illness is often complex, alongside a slow recovery of physical functioning (McPeake and Quasim 2016). This point is now becoming the focus of intensive care follow-up, and guidelines to support physical and non-physical rehabilitation have recently been published (NICE 2015a). The community nursing team will benefit from a very thorough handover of the history of the patient’s stay in hospital and of any referrals that have been put in place.

Review of assessment practice

Below is a list of the main factors to consider in assessing a patient with sepsis or suspected sepsis. You can use this as a revision of the points discussed throughout the chapter and to prepare for the Skills Assessment. The assumption here is that you have only a sphygmomanometer and watch as equipment, even though you may well have access to other tools such as pulse oximetry, and are therefore employing a ‘look, listen and feel’ approach to your assessment.

Risk factors

  • Is the patient very elderly?

  • Do they have an already compromised immune system from taking immune suppressant drugs for auto-immune disorders or chemotherapy for cancer?

  • Do they have addictions to drugs or alcohol?

  • Do they have deep tissue wounds: for example, from burns or trauma, or have had invasive surgery?

  • Do they have indwelling IV lines or catheters?

Patient history

  • Do they have an identified infection (or have they had a recent infection)? Do they have a past medical history that includes sepsis?

Patient complaining of …

  • coughing phlegm, which is new for them.

  • discomfort passing urine, or discoloured, malodorous urine.

  • dizziness.

  • vague responses when interacted with.

  • feels unwell—non-specific or ‘fluey’ symptoms.

Skin

  • Hot to touch due to:

    • vasodilatation carrying blood (and therefore) metabolic heat to peripheries

    • viral/ bacterial pathogens increasing metabolic/inflammatory response from cells

    • hypothalamus ‘re-setting’ the internal thermostat

Blood pressure

  • Hypotensive due to:

    • vasodilatation—this is seen in the diastolic pressure

    • myocardial depressant effect of sepsis—this is seen in the systolic pressure

Pulse

  • Fast—tachycardic

  • In early sepsis this will feel to be a ‘bounding’ pulse

  • Compensation for relative hypovolaemia/distributive shock

  • In later or decompensated sepsis and shock the pulse will be felt to be thready (due to hypovolaemia)

  • Possibly difficult to find, due to oedema, and ‘thready’ in quality.

Pallor

  • Flushed (more noticeable in Caucasians), due to

    • vasodilatation –more blood at periphery

  • OR mottled, due to

    • patchy maldistribution of blood and poorly perfused capillary beds.

  • OR pale, due to poor perfusion globally secondary to low cardiac output/oxygen delivery

  • Also, impeded oxygen delivery due to oedema

  • Poor capillary refill

Central nervous system

  • Acutely altered/low GCS due to:

    • hypoperfusion

    • endotoxin

  • Pupils—constricted—shock state

  • Dull, responses obtunded—shock state

Kidneys

  • Oliguric (poor urine output): less than 0.5 mL/kg/h

Abdomen

  • Possibly distended, hard, uncomfortable/ painful

  • Bowel sounds possibly absent due to:

    • ischaemia—poor GI tract perfusion—‘auto transfusion’ of gut blood supply to other vital organs

    • ileus—poor motility secondary to hypoperfusion

End of chapter assessment

The following assessment will enable you to evaluate your theoretical knowledge of sepsis and its management as well as your ability to apply this theory to clinical practice.

Knowledge assessment

With the support of your mentor/supervisor from practice, work through the following prompts to explore your knowledge level about sepsis and its management.

  • Demonstrates an understanding of the difference between sepsis and septic shock.

  • Broadly discusses the role of the inflammatory reaction and sepsis.

  • Is able to identify common origins of sepsis, including those that are hospital acquired.

  • Can explain the broad differences in patient presentation between ‘early’ and ‘late’ sepsis.

  • The rationale behind lactate readings can be explained.

  • Can demonstrate awareness of essential management responses of the ‘Sepsis Six’ and their underpinning rationale.

  • Can discuss the notion of ‘care bundles’.

  • Discuss the nurse’s role with microbiology samples for septic patients.

  • Describe the clinical syndrome D and why it is related to septicaemia.

  • Understands the local Trust’s policy for taking blood cultures.

  • Can identify local, national, and international strategies to address sepsis.

  • Is aware of support resources available to relatives.

  • Is aware of support resources and research available to nurses.

Skills assessment

Under the guidance of your mentor/supervisor, undertake a full assessment of a patient for signs and symptoms of sepsis followed by appropriate interventions for any significant abnormality. Your mentor/supervisor will be able to assess your ability and provide feedback based on the following skills:

  • All universal precautions are adhered to whilst clinically interacting with the patient.

  • Conduct a full patient history with a systems review considering key points that are relevant for a patient with sepsis or suspected sepsis.

  • Demonstrate a comprehensive physical assessment and explain the physiological underpinnings normal/abnormal findings from the respiratory, cardiovascular, renal, gastrointestinal, skin, and neurological systems.

  • Findings are related to the data already charted and trends in potential deterioration or compensation identified.

  • The likely source and cause of sepsis for the patient are discussed.

  • Microbiological and biochemical laboratory results are related to the patient’s condition.

  • Intravenous access and all invasive lines are checked for date and necessity. Line sites are assessed for signs of inflammation or infection.

  • Demonstrate an ability to follow infection control guidelines while undertaking intravenous therapy including the management of the intravenous access and intravenous fluids.

  • Any potentially diagnostic samples are taken and documented.

  • Any outstanding and relevant laboratory results are pursued and relevant personnel informed.

  • Any vulnerability to further infection is identified, in terms of threats of infection and the patient’s own physiological reserve.

  • If an early warning observations chart is in use, score the patient.

  • Any indication from the observations gathered that member of the MDT or the Medical Emergency Team/Patient at Risk/Outreach teams need to be informed is acted upon. The shift leader for the ward is also notified.

  • Ensure an estimation of when these personnel are able to review the patient is provided and follow this up if necessary.

  • Document all interventions and referrals, including times as per Trust policy.

  • Care for that shift is prioritized on the basis of the clinical picture gathered.

Resources

The UK Sepsis Trust: http://sepsistrust.org/

The UK Sepsis Trust seeks to save lives and improve outcomes for survivors of sepsis by instigating political change, educating healthcare professionals, raising public awareness, and providing support for those affected by this devastating condition. The website has information for healthcare professionals and for the public.

Surviving Sepsis: http://www.survivingsepsis.org/

The Surviving Sepsis Campaign is a joint collaboration of the Society of Critical Care Medicine and the European Society of Intensive Care Medicine committed to reducing mortality from severe sepsis and septic shock worldwide.

Global Sepsis Alliance

The Global Sepsis Alliance is a non-profit charity organization with the aim to raise awareness of sepsis worldwide and reduce sepsis deaths by 20% by 2020. It organizes and manages World Sepsis Day: http://www.world-sepsis-day.org/

Healthtalk: http://www.healthtalk.org/

Its mission is to help and inform patients, carers, and healthcare professionals by sharing trustworthy, personal health experiences.

Its aims are:

  • To support patients and their loved ones, who may feel alone or ill-prepared for challenges ahead.

  • To support healthcare professionals in providing patient-focused care.

  • To promote better communication between patients and health professionals.

ICUsteps: http://www.icusteps.org/

ICUsteps is the UK’s only support group for people who have been affected by critical illness and has helped many former patients, their relatives, and medical staff from organizations around the world.

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