2nd August 2023

Sepsis

Shocked Patient

Definition

‘Shock’ can be defined as circulatory failure resulting in hypoperfusion of the tissues and an inadequate level of oxygen delivery to meet the metabolic requirements of tissues. Prolonged hypoperfusion can cause derangement in cell processes, ultimately leading to cell necrosis and end-organ failure. Early recognition and treatment of a shocked patient is essential.

Causes

Two main categories can lead to circulatory failure or ‘shock’. These can broadly be categorised as low flow volume or low arteriolar resistance (vasodilation). Based on the two categories, there are different conditions and causes that can lead to both (table 1).

Table 1: Two main categories of conditions that can lead to circulatory failure or ‘shock’ with examples of the main causes in each category respectively.

Clinical Features

Clinical features of shock are usually dependent on the primary pathophysiology or underlying cause. Patients who present due to low flow often have features such as cold peripheries, absent or weak peripheral pulses and evidence of low cardiac output. This can include features such as a narrowed pulse pressure.

Conversely, patients who present with shock from vasodilatation tend to have warm peripheries, bounding pulses and often features of high cardiac output. This can include features such as hypotension with wide pulse pressure, raised temperature and general distress.

Investigations and Management

The main features of ‘shock’ include hypotension, tachycardia, and evidence of end organ dysfunction. This can include poor kidney function, deranged coagulation, respiratory distress such as increasing oxygen requirements and liver derangement. The clinical presentation and observations will be dependent on the underlying causative factor.

Management of shock involves rapid identification of the underlying cause to be able to administer appropriate treatment.

Sepsis

Definition

Sepsis can be defined as a dysregulated response to severe infection resulting in life-threatening organ dysfunction. Sepsis starts from a local site of infection and results from the bacteria spreading into the bloodstream resulting in a systemic response. End organ dysfunction in sepsis can be defined using the Sequential (or Sepsis-related) Organ Failure Assessment (SOFA) criteria which scores patients on parameters of respiratory function, cardiovascular system, liver dysfunction, renal dysfunction, coagulation, and neurology (based on their GCS).

Septic shock is an important ‘not to be missed’ sequelae of sepsis and can be defined as the co-existence of persistent hypotension requiring vasopressors to maintain a mean arterial pressure ≥65mmHg and a serum lactate of >2mmol/L. Septic shock presents a much greater risk of mortality and is associated with the risk of circulatory, cellular, and metabolic deterioration.

Causes

Sepsis can be the result of both primary infection and because of secondary clinical interventions. Certain conditions and situations can put patients at higher risk of developing sepsis. Examples of these are:

• Patients <1 or >75 years of age
• Patients who have impaired immune systems
  • Chemotherapy for cancer patients
  • Impaired immune function (e.g. diabetes, sickle cell, splenectomy)
  • Long term steroids
  • Immunosuppressant drugs
• Surgery of invasive procedures in past 6 weeks
• Skin breaks
  • Cuts
  • Burns
  • Skin infections
• IV drug use
• Indwelling lines or catheters
• Women who are pregnant, have given birth or termination of pregnancy or miscarriage in the last 6 weeks. Higher risk for those who:
  • Have an impaired immune system
  • Gestational diabetes or diabetes
  • Needed invasive procedures (e.g. caesarean or forceps, removal of retained products)
  • Prolonged rupture of membranes
  • Have been in close contact with people with group A streptococcal infection
  • Continued vaginal bleeding or offensive discharge

When looking for the causes of sepsis, it is important to consider all body systems and to ensure the patient is fully examined and exposed to try and identify the source.

Common sites of infection include the lungs, for example, community acquired pneumonia, the urinary tract, and the abdomen, for example, abdominal abscesses or perforation.

Clinical Features

Sepsis is the result of bacteraemia and severe infection. There are several clinical features, and people can present in different ways. However, typically patients will have a high or low temperature, raised inflammatory markers, low BP, and high HR. In addition, patients often have a wide pulse pressure. Parameters such as hypothermia or neutropenia can indicate a more severe infection.

In addition to abnormal observations and systemic features causing sepsis, it is important to consider localising symptoms which can point to the source of the original infection.

Assessment

It is important to recognise sepsis early as it can lead to end organ damage, septic shock and death if not treated rapidly. History and examination remain key – make sure to obtain a collateral history if the patient cannot, e.g., altered mental state. Important questions include recent fevers, specific infective symptoms, such as dysuria or productive cough, clinical features suggesting dehydration, altered behaviour or mental state, sudden deterioration in functional ability and risk factors for sepsis.

Adopt an A-E approach utilising information from a patient’s National Early Warning Score (NEWS2) – this comprises 6 parameters: respiration rate, oxygen saturations, systolic blood pressure, pulse rate, level of consciousness or new-onset confusion and temperature. Each parameter is scored from 0-3. This score is then combined to give a total score indicating risk; low (1-4), low to medium (a score of 3 in any single parameter), medium (5-6) and high risk (≥8). This score can help provide an early indication that a patient is becoming unwell and possibly septic. It can identify parameters that may need urgent correction, such as hypoxia or hypotension, as well as thoroughly assessing and exposing the patient to look for an original source of infection to provide the correct antibiotic treatment.

As per recent NICE guidelines, patients should also be risk stratified according to their examination findings and assessed for the severity of their illness, risk of clinical deterioration and risk of death from sepsis (table 2).

Table 2: Risk stratification tool for patients with sepsis

National Institute for Clinical Excellence (2017) Sepsis: recognition, diagnosis, and early management. Available at: https://www.nice.org.uk/guidance/ng51 (Accessed: 16 March 2022).

Investigation and Management

The UK Sepsis Trust ‘Sepsis Six’ bundle, which should be given within the first hour of identifying sepsis.

• ‘3 in’ –intravenous fluids, broad spectrum antibiotics and oxygen therapy (if required)
• ‘3 out’ –blood cultures (2 sets), serum lactate measurement and urine output

If patients are critically unwell, a discussion with intensive care may be required to consider central venous access, inotropes, or vasopressors.

• Inotropes: medications which can increase cardiac output by increasing cardiac contractility
• Vasopressors: increase blood pressure by increasing peripheral vascular resistance

These may be required to maintain perfusion pressure in patients with severely deranged observations and parameters, those in the high-risk criteria (table 2), and those not responding to initial treatments.

Fever of Unknown Origin (FUO)

Note that roughly 75% of patients with pyrexia will not receive a diagnosis. Therefore, a risk stratified approach is the best method in standing any chance of finding an underlying cause.

Differential Diagnoses

Whilst infection is responsible for most pyrexial scenarios, other strong contributors include malignancy (especially lymphomas) and connective tissue diseases such as rheumatoid arthritis and Kawasaki disease (see table 3). Be astute to not be caught out by the occult pulmonary embolism or drug induced fever – ironically, antimicrobials and anti-epileptics are chief culprits here.

Table 3: A broad overview of non-infective causes of FUO

Focusing on Infection

The list of potential infectious diseases is exhaustive. Therefore, marrying the pattern of pyrexia with associated symptoms and clinical history will help guide your diagnosis.

For example, abscesses and TB may result in a daily temperature spike, as can Schistosomiasis. Additionally, the recently returned traveller with a high enteric fever is far more likely to have Salmonella typhi infection than cytomegalovirus colitis in the absence of immunosuppressive predisposition.

Of the 25% of fevers with an established diagnosis in the UK, the most important identifiable imported cause is Malaria. Malaria classically presents with intermittent fevers and should resolve after a course of appropriate treatment. If a patient complains of recurrent feverish episodes years after initial malaria diagnosis and supposed treatment – be sure to rule out Plasmodium ovale or Plasmodium vivax as their hypnozoites may have been stirred into acute infective action.

Work Up

Investigations, such as full blood count (leucocytosis vs eosinophilia), blood films, rapid molecular testing and CXR, will guide your diagnosis. Dental abscesses and infective endocarditis are uncommon causes of FUO but warrant further investigations, such as via an orthopantomogram and echocardiogram, respectively, if suspected.

Whilst blood cultures are useful in identifying bacterial septicaemia, they may miss the underlying cause. Note that it is important to exclude infective causes in a pyrexial and unwell patient despite negative blood cultures –consider Q fever, caused by the obligate intracellular bacterial pathogen Coxiella burnetii –a favoured question in exams!

Evaluation of the Unwell Returning Traveller

Introduction

The increase in international travel over recent decades has led to higher numbers of travellers developing a febrile illness during or soon upon returning to the UK. There is an extensive list of differential diagnoses to consider, and therefore a systematic approach to patient management will enable timely and suitable treatment.

As discussed earlier, most patients with febrile illnesses presenting to a UK hospital with a travel history do not end up with a clear-cut pathogenic diagnosis. Of those that do, malaria is the most common and prudent to consider, given the possibility of severe disease progression. All patients with a travel history in countries with known malaria transmission should have multiple sets of blood cultures & malaria screens. Other diagnoses, inclusive of dengue, enteric fever (typhoid & paratyphoid), HIV seroconversion and rickettsia infections, are also important considerations due to their common importation into the UK. The more esoteric pathogens may require serological or molecular testing at specialist reference laboratories.

In all cases of a returned febrile traveller, a detailed and structured history should include the following:

• Geographical locations visited
• Dates of travel and onset of illness
• Pre-travel preparation (including malaria prophylaxis)
• Activities during travel/type of travel
• Risk assessment of viral haemorrhagic fever (due to the very serious nature of these infections)
• Patient immune status
• Bites and wounds

Disease Presentations

A ‘Fever Plus’ approach, whereby recognising a fever in addition to an acute key symptom such as diarrhoea or rash, can be extremely useful in narrowing down differentials to inform further investigation and management.

Table 4: A ‘Fever Plus’ approach by key symptom(s)

Diagnostics

Not all disease presentations follow a predetermined diagnostic sieve, so additional investigations are needed. A thick and thin blood film for malarial parasites from at least two separately timed samples is required to exclude malaria.

Serology tests are available to identify the viral antigen when suspecting ‘FAR Syndrome’ viral infections – presenting with Fever, Arthralgia and Rash – such as Dengue and Zika Virus. Molecular testing, such as PCR, may be available and is ultimately more specific to rule out certain viral pathogens.

Remember that Tuberculosis (TB) is particularly unreliable to culture. If suspecting TB, a ‘GeneXpert’ test is often available and more reliable for diagnosis; this uses PCR to identify conserved regions of the mycobacterial genome alongside genes encoding resistance to anti-TB regimen drugs.