CHAPTER THREE

SEPSIS

What is sepsis?

Unlike an infection like meningitis or pneumonia, sepsis is not a stand-alone illness or disease. It is rather the body’s overactive inflammatory response to severe infection and is a medical emergency, which can lead to tissue damage, multi-organ failure, and death. It is not the same thing as septicaemia,¹ which is blood poisoning caused by large numbers of bacteria in the bloodstream, although the two are often conflated or confused with one another (as septicaemia will lead to a state of sepsis). As of 2016, the technical internationally recognised definition is “life-threatening organ dysfunction caused by a dysregulated host response to infection.”²

As described above, when there is a significant bacterial infection, the immune response causes systemic inflammation (SIRS). This inflammation will damage the lining of all the vessels in the body causing them to become leaky. Water and proteins from the blood will leak into the tissues of the body and reduce the circulating blood volume. The pumping of the heart is also affected by toxins produced by the bacteria. The body will compensate for reduced blood volume by making the heart pump faster to maintain the blood pressure. Blood is diverted away from the peripheries (hands and feet) and the kidneys. The aim of this ‘cardiac compensation’ is to maintain perfusion of the heart and brain as long as possible. The coagulation system is deranged making the blood less coagulable and the platelets also fall. A state of septic shock occurs when the circulation is inadequate to meet the body’s needs.

When sepsis is severe, the blood pressure may drop due to loss of fluid from the circulating volume. Organ failure may then arise from decreased flow of blood and oxygen. Septic shock in adults is characterised by low blood pressure despite adequate fluid replacement, and organ dysfunction or failure. In children, septic shock usually occurs with a normal blood pressure, and a fall in blood pressure is a late and very ominous sign.

The diagnosis of sepsis is clinical (i.e. a diagnosis made on the basis of signs and symptoms rather than diagnostic tests) with a few simple laboratory tests such as lactate.

However, there is new and ongoing research into developing a laboratory diagnosis. A very recent paper published in February 2019,³ and widely reported in the national press,⁴ published the details of research into a test which measures a protein biomarker of sepsis (interleukin-6, which is a cytokine), using a microelectrode integrated into a needle shaped substrate, which it is claimed could provide results within two-and-a-half minutes. It will be interesting to see how this research develops, and whether this device becomes a part of NHS care.

The NICE Guideline has a stated aim of raising awareness within the medical profession such that when a patient presents with infection, the treating professional should ask themselves the question ‘could this be sepsis?’.

Septic shock

Septic shock in adults is defined as persisting hypotension requiring vasopressors (medicines that cause blood vessels to contract and raise blood pressure) to maintain a mean arterial pressure of 65mmHg or more and having a serum lactate (a marker detected in a blood gas, which becomes raised when a patient is severely septic) level of greater than 2 mmol/l despite adequate volume resuscitation.

In essence that means a low blood pressure and a raised lactate level, not improving with intravenous fluids.

Clinical features of septic shock are:

• Fever with severe shaking (rigors)

• Muscle aches and severe discomfort

• Dizziness

• Fast pulse rate (tachycardia)

• Shortness of breath / fast breathing/ tachypnoea

• Cold or mottled skin

• Poor urine output

• Low blood pressure

• Confusion

Treatment will normally require ICU admission with fluids, intravenous antibiotics, vasopressors, and respiratory support.

Septic shock in children differs in that hypotension is not required to make the diagnosis. The particulars of paediatric septic shock are covered in Chapter 4 under the section on meningococcal sepsis.

Loss of peripheral tissues through gangrene can develop in some infections (particularly meningococcal infection or group A streptococcal sepsis) as a result of lack of blood flow and disturbance of the coagulation system. This is known as purpura fulminans.

If a bacterial infection originating in gangrenous tissue spreads, that can cause septic shock.

Spotting sepsis

There are several risk factors for developing sepsis, which any doctor should be aware of. These are not new within the NHS. Even before the new Sepsis Guideline was published in July 2016, these factors were taught as part of compulsory life support and paediatric life support training.⁵

However, since that Guideline was published, any doctor in a primary (i.e. GP) or secondary care (i.e. hospital) setting ought to be acutely aware of the relevant factors, and at the very least, ought to have the Guideline in mind (and use it as a point of reference) when assessing an acutely ill patient.

The following groups are at higher risk of developing sepsis:⁶

• The very young and the very old (i.e. under 1 or over 75), or the very frail

• Those with impaired immune systems due to illness (e.g. those with diabetes) or medications (e.g. whilst undergoing chemotherapy)

• Anyone who has undergone a recent surgery, or other invasive procedure

• People with cuts, burns, blisters or skin infections

• Intravenous drug users

• People with indwelling lines or catheters

• Women who have recently given birth, had a termination of pregnancy or miscarriage in the previous six weeks

The Guideline is very helpful in that it sets out algorithms in both written and tabular form for different age groups, and differentiates between patients in a hospital setting and those outside a hospital setting.

The following are high risk warning signs that apply generally, albeit that each factor is generally dependent on the age of the patient:⁷

1. History:

• • Objective evidence of altered behaviour or mental state

  • Appears ill to a healthcare professional (particularly in children)

  • Does not wake, or if roused, does not stay awake

2. Respiratory:

• • Raised respiratory rate or tachypnoea (e.g. for a person over 12 years a respiratory rate (RR) of more than 25 breaths per minute, for a child aged 5 an RR of more than 29, for a child aged 1 to 2 an RR of more than 50)

  • Decreased oxygen saturations (generally less than 90% in air)

3. Circulation and hydration

• • Low heartrate or bradycardia (a heartrate of less than 60 beats per minute (bpm) in a child of 11 or under)

  • Rapid heartrate tachycardia (for a person aged 12 years or more 130 beats per minute (bpm), for a child aged 6-7 years 120 bpm or more, for a baby under 1 a heartrate of 160 bpm or more))

4. Skin

• • Mottled (irregular appearance caused by blood vessel changes) or ashen appearance (skin looking grey or pale, due to lack of oxygenation)

  • Cyanosis of skin, lips or tongue (bluish discolouration, also caused by hypoxia, or lack of oxygenation)

  • Non-blanching rash (i.e. a skin rash that does not fade under pressure)

Perhaps surprisingly, body temperature is not a high-risk factor except:

1. in children under 5 years, in which case a temperature of less than 36ºC is a high-risk factor

2. in children under 3 months in which case a temperature of over 38ºC is a high-risk factor.

Treatment

According to the Guideline all people with suspected sepsis outside an acute hospital setting should be referred for emergency medical care by the most appropriate means of transport if they meet any of the above high-risk criteria.

The treatment the patient would then receive in a hospital setting depends on their age.

For example, for a child aged 5-11, with any high-risk criteria (or with two or more moderate to high risk criteria under the Guideline), the protocol is:

• to arrange for immediate review by the senior clinical decision maker to assess the child and think about alternative diagnoses to sepsis

• to carry out a venous blood test

• to give broad spectrum antibiotics (what antibiotic is to be given will often depend on local trust-based protocols or guidelines)

• discuss with a consultant (noting that if the admission takes place at night, for instance, the most senior paediatrician in the hospital is likely to be a registrar)

• where lactate is raised, give an intravenous fluid bolus (a means of rapid rehydration)

While sepsis is suspected (and indeed for any patient in a hospital setting undergoing treatment for acute infection), monitoring should be in place at least every 30 minutes.

Tools like the national early warning score (NEWS) or paediatric early warning score (PEWS) should be in place, and will be an indication after the event of how ill the patient was considered to be. However, these tools are not always consistently applied, such that there is limited weight that can be attached to these scores.

Outcomes

Many people who suffer sepsis, including those who become critically ill, make a full recovery. The extent of recovery, and how long it takes, will usually depend on the severity of the sepsis, the overall state of the patient’s health, the duration of hospital admission, and whether the patient required treatment in an intensive care unit.

Many of the cases that involve sepsis will be fatal cases. Precise statistics about the number of deaths from sepsis are hard to come by, as, because sepsis will arise in the context of an underlying illness or infection, it is not always recorded. The Office of National Statistics (ONS) mortality data for 2017 records only 2,705 deaths as being from sepsis. Based on research, and other data, that figure is probably a gross under-reflection of the true number.

One paper,⁸ published following a systematic review of 15 international citation databases for population-level estimates of sepsis incidence and fatality data, gave figures of hospital mortality of 17% for sepsis and 26% for severe sepsis in the period 2005 to 2015.

The Sepsis Trust estimates that 52,000 people in the UK die every year from sepsis. In August 2018, the BBC reported that following an analysis of NHS mortality data at 133 NHS trusts, recorded deaths from sepsis had increased by 38% between April 2015 and April 2017.⁹

In a 2016 paper,¹⁰ it was said that in the first year following an episode of sepsis, 60% of patients will have at least one rehospitalisation episode, and at least one in six will die. Survivors also have a higher risk of cognitive impairment and cardiovascular disease, resulting in a reduced life expectation.

In an American study of patients of over 65 years admitted to hospital with sepsis, it was suggested that mortality following the episode may be as high as one in five, and that the mortality remained higher for at least two years relative to adults not in hospital.¹¹

Due to the increased risk of readmission and death, if following a septic episode, there is readmission or death, even where it is not immediately apparent that such was caused by the septic episode, a claimant will need to ask their experts to comment on causation (which may involve a literature review).

Some patients will experience lethargy, muscle weakness, rheumatic swelling and pain, chest pain or breathlessness, which may fall within what is described as ‘Post Sepsis Syndrome’ (PSS). Relatively little has been written on this diagnosis, although the NHS webpage on sepsis¹² now recognises the possibility of a patient developing PSS, and links to the Sepsis Trust’s information page on the subject.¹³ There is not a single reported case (including quantum report on Lawtel) which refers to this diagnosis. This may be because the diagnosis is relatively new. I could locate only one paper (from June 2018)¹⁴ which examined the diagnosis.

It is likely that PSS will become a more common feature in litigation. This is because the sort of symptoms which can be attributed to it may have been diagnosed as separate conditions not directly linked to the sepsis. For example, in the case of Welsh v Walsall Healthcare NHS Trust [2018] EWHC 1917 (QB), the claimant, who had suffered from sepsis following negligent management after a bowel perforation during surgery, went on to be diagnosed with fibromyalgia and chronic pain. In a post-septic patient, it is suggested that a diagnosis of PSS could probably be made in the alternative.

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