11/14/24, 10\:44 AM Sepsis

Sepsis

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2 Oct 2024, 7\:56 p.m.
- Fix factual error - I think "deregulated"
was used a few times instead of "dysregulated"
.
Key points ⚡
Succinct notes to superpower your revision
Sepsis\: life-threatening organ dysfunction from a dysregulated host response to infection; incidence rising due to ageing
population, multimorbidity, antibiotic resistance; 200,000 admissions in England (2017/18), 20.3% mortality.
Risk factors\: age \<1 or >75, frailty, impaired immune system (immunosuppressants, long-term steroids, chemotherapy,
asplenia), indwelling lines/catheters, IV drug use, severe burns, recent invasive procedures, pregnancy, post-partum,
miscarriage within 6 weeks.
Aetiology\: can follow any infection, typically bacterial but can be viral or fungal; common sources include pneumonia
(50%), urinary tract (20%), abdomen (15%), skin/soft tissue/bone/joint (10%), device-related (1%), endocarditis (1%), meningitis
(1%).
Pathophysiology\: deregulated immune response, excessive cytokine release, vasodilation, increased vascular
permeability, inappropriate coagulation activation, leading to distributive shock, hypovolemia, small vessel occlusion, tissue
ischemia, multi-organ failure.
Symptoms\: non-speci
dyspnoea, dysuria, abdominal pain, erythema, neck sti
Signs\: pyrexia/hypothermia, tachypnoea, tachycardia, hypoxia, hypotension, altered mental status, mottling; speci
include respiratory crepitations, suprapubic tenderness, abdominal distension, erythema, nuchal rigidity.
Investigations\: venous blood gas (lactate), capillary blood glucose, ECG, urine dipstick; lab tests (FBC, U&Es, LFTs,
coagulation pro
puncture); imaging (CXR, abdominal ultrasound/CT, echocardiography).
Management\: assess using ABCDE approach; early recognition and antibiotics; NICE guidelines use ‘red

Lactate, Oxygen).
Sepsis six bundle\: ensure senior clinician attends, administer high-
broad-spectrum IV antibiotics, IV
Complications\: shock, ARDS, myocardial dysfunction, acute/chronic renal injury, acute liver failure, multi-organ failure,
disseminated intravascular coagulation, death, post-sepsis syndrome.
Article 🔍
A comprehensive topic overview

Introduction

Sepsis can be de
1
. It is a
rare but serious response to infection, in which the body’s immune system goes into overdrive, setting o
negative consequences.
The incidence of sepsis is increasing. This is thought to be due to the ageing population, increasing multimorbidity,
antibiotic resistance, and an increased emphasis on early recognition. 2
In England, there were 200,000 admissions with
sepsis in 2017/18. 3 4
The mortality rate in England due to sepsis stands at 20.3%.
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Sepsis vs septicaemia
Sepsis is often confused with septicaemia, which refers to microbiological invasion of the bloodstream. Sepsis is a
separate clinical entity that can occur in response to any infection, with or without septicaemia.

Aetiology

Sepsis can occur secondary to any form of infection. The source of infection is most commonly bacterial; however, it can
also be viral or fungal in origin.
Common sources of infection include\:
2,3
Pneumonia (50%)
Urinary tract (20%)
Abdomen (15%)
Skin, soft tissue, bone and joint (10%)
Device-related infection (1%)
Endocarditis (1%)
Meningitis (1%)

Pathophysiology

The pathophysiology of sepsis is complex. In certain circumstances, the physiological immune response to an infection
becomes deregulated for reasons that are not fully understood.
6
Excessive cytokine release leads to a cascade of cellular changes that cause\:
Vasodilation
Increased vascular (capillary) permeability
Inappropriate activation of the coagulation cascade.
Immune system impairment
Vasodilation leads to distributive shock, and the hypotension is worsened by hypovolemia secondary to excessive
capillary leakage.
Inappropriate coagulation cascade activation leads to micro-emboli formation, which causes small vessel occlusion.
These factors can rapidly lead to ischaemia of vital organ systems. If not quickly and appropriately managed, this can lead
to multi-organ failure and, ultimately, death.
Tissue hypoperfusion/ischaemia can lead to di
2,6,7
Central nervous system\: confusion/delirium.
Renal\: reduced urine output, acute kidney injury
Pulmonary\: ventilation-perfusion mismatch leading to hypoxaemia, acute respiratory distress syndrome (ARDS)
Cardiac\: impaired myocardial function
Gastrointestinal\: ischaemic hepatitis, translocation of gut microbes into the bloodstream
Septic shock
Septic shock is de
This will often be accompanied by the signs of organ dysfunction seen above, and serum markers of tissue ischemia
will be raised (e.g. serum lactate). Septic shock represents advanced immune dysregulation, which is associated
with increased mortality.
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Risk factors

Risk factors for sepsis include\:
2,5
Age \<1 and > 75
Frailty
Impaired immune system\: people on immunosuppressants, long-term steroids, chemotherapy, asplenia and other
causes of immunosuppression
Indwelling lines and catheters
Intravenous drug users
Severe burns
History of invasive procedures in the last 6 weeks
Women who are pregnant, have given birth or have had a termination of pregnancy or miscarriage in the past 6 weeks

Clinical features

History

Due to its non-speci
Symptoms may initially relate to the source of the infection (e.g. dysuria in a urinary tract infection, productive cough in
pneumonia). However, symptoms of sepsis tend to be extremely vague (e.g. increased confusion, feeling lethargic or
generally unwell).
As such, sepsis should be considered a potential diagnosis in any unwell patient. A thorough clinical assessment should
be undertaken to ascertain a patient's risk/likelihood of sepsis.
Non-speci
Fever symptoms (e.g. chills, rigors)
Malaise and lethargy
Confusion
Myalgias
Skin changes (mottling)
Symptoms speci
Respiratory\: dyspnoea, productive cough
Urinary\: dysuria, urinary frequency and urgency, cloudy or foul-smelling urine
Gastrointestinal\: diarrhoea, abdominal pain
Skin/soft tissue\: skin redness (erythema) or heat (calor), joint pain/swelling
Central nervous system\: neck sti

Clinical examination

Clinical signs on examination may be generalised (secondary to the pathophysiology of sepsis) or related to the
underlying infection.
General signs
General clinical signs of sepsis may include\:
Pyrexia (or hypothermia)
Tachypnoea
Tachycardia
Hypoxia
Hypotension, poor capillary re
Altered mental status
Mottling of skin or ashen appearance
Speci
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Clinical signs related to underlying infection may include\:
Respiratory\: coarse respiratory crepitations, bronchial breathing
Urinary\: suprapubic tenderness,
Gastrointestinal\: abdominal distension, abdominal guarding/rigidity
Skin / soft tissue\: skin redness (erythema) / heat (calor)
Central nervous system\: reduced GCS, nuchal rigidity, papilloedema, positive Kernig’s sign
Cardiovascular\: new murmur, splinter haemorrhages

Investigations

Bedside investigations

Relevant bedside investigations include\:
Venous blood gas\: assess lactate level (a key marker of tissue hypoperfusion)
Capillary blood glucose\: rule out hypoglycaemia, hyperglycaemia
Electrocardiogram\: rule out arrhythmias
Urine dipstick\: assess for the presence of a urinary tract infection (in certain populations)

Laboratory investigations

Relevant laboratory investigations include\:
Full blood count\: assess for neutrophilia or neutropenia (note neutropenic sepsis is a medical emergency)
Urea and electrolytes\: assess renal function
Liver function tests\: assess for liver dysfunction
Coagulation pro\: rule out coagulopathy and disseminated intravascular coagulation (DIC)
CRP\: a non-speci
Microbiological investigations
Relevant microbiological investigations include\:
Blood cultures\: two peripheral sets, plus cultures from invasive lines if present
Urine culture\: to identify UTI and establish antibiotic sensitivities
Viral swabs\: including COVID-19
Sputum culture\: if productive cough is present
Stool culture\: if diarrhoea is present
Lumbar puncture\: if suspecting meningitis

Imaging investigations

Relevant imaging investigations include\:
Chest X-ray\: to assess for pneumonia
Ultrasound / CT abdomen\: if suspecting intra-abdominal infection
Echocardiography\: if suspecting endocarditis

Management

All acutely unwell patients should be assessed using an ABCDE approach.
The key to managing sepsis is early recognition and early administration of antibiotics, alongside e
Any acutely unwell patient should be considered a potential case of sepsis.

NICE guidelines

NICE now recommend using speci
patients with potential sepsis.
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Patients with suspected sepsis should be assessed to see if any ‘red
are markers of severe disease needing urgent management.
High risk criteria (‘red
Red
Behaviour\: objective evidence of new alteration in mental state
Heart rate\: >130 beats per minute
Respiratory rate\: >25 breaths per minute or new oxygen requirement to maintain saturations
Systolic blood pressure\: \<90 mmHg or more than 40 mmHg below baseline.
Urine output\: not passed urine in the previous 18 hours, or less than 0.5 ml/kg of urine per hour in catheterised patients.
Skin\: mottled appearance or Cyanosis or Non-blanching rash.
Moderate risk criteria (‘amber
Amber
Behaviour\: new onset altered behaviour or acute deterioration in function
Heart rate\: 91-130 beats per minute or new onset arrhythmia
Respiratory rate\: 21-25 breaths per minute
Systolic blood pressure\: 91-100 mmHg
Urine output\: not passed urine in the past 12–18 hours, or for catheterised patients passed 0.5–1 ml/kg of urine per hour.
Temperature\: tympanic temperature \<36°C
High-risk patients\: immunosuppressed, recent (\<6 weeks) trauma or surgery
Figure 1. NICE (2016) algorithm on the management of suspected sepsis.
5

Sepsis six bundle

(within one hour)\:
In the acute setting, any patients with suspected sepsis should be started on the sepsis six bundle as soon as possible
Ensure senior clinician attends
Administer high-2
\<92%
IV access & blood tests (blood cultures, lactate, FBC, U&E, CRP)
Administer broad-spectrum intravenous antibiotics and consider source control
Administer intravenous
Monitor urine output and lactate
Sepsis six mnemonic
You can remember the sepsis six using the acronym BUFALO\:
Blood Cultures
Urine output
Fluids
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Antibiotics
Lactate
Oxygen
Or, you can remember it by thinking of the steps as ‘taking 3 and giving 3’
\:
Taking 3\: blood cultures, lactate and urine output
Giving 3\: antibiotics, oxygen (to maintain SpO 2
>94%),
Figure 2. The sepsis six. The UK Sepsis Trust
Once stabilised, infection source control is the next priority (e.g. chest physiotherapy in pneumonia, surgical referral if
suspected intra-abdominal sepsis etc).
For patients with septic shock, vasopressor medications may be required to overcome severe vasodilation and
hypotension. These patients should be admitted to a critical care environment and closely monitored.

Complications

Complications of sepsis include\:
Shock
ARDS
Myocardial dysfunction
Acute/chronic renal injury
Acute liver failure
Multi-organ failure
Disseminated intravascular coagulation
Death
Post-sepsis syndrome

References

Singer, M., Deutschman, C. S., Seymour, C. W., Shankar-Hari, M., Annane, D., Bauer, M., ... & Angus, D. C. (2016). The third
international consensus de
Gotts, J. E., & Matthay, M. A. (2016). Sepsis\: pathophysiology and clinical management. B M J , 3 5 3 .
UK Sepsis Trust. Sepsis Manual. 2022. Available from\: [LINK]
Burki, T. K. (2018). Sharp rise in sepsis deaths in the UK. T h e L a n c e t R e s p i r a t o r y M e d i c i n e , 6 (11), 826.
NICE. Sepsis\: recognition, diagnosis and early management. 2016. Available from\: [LINK]
https\://app.geekymedics.com/notebook/2787/ 6/711/14/24, 10\:44 AM Sepsis
Jarczak, D., Kluge, S., & Nierhaus, A. (2021). Sepsis—pathophysiology and therapeutic concepts. F r o n t i e r s i n m e d i c i n e , 8 ,
609.
Hosein, S., A Udy, A., & Lipman, J. (2011). Physiological changes in the critically ill patient with sepsis. C u r r e n t p h a r m a c e u t i c a l
b i o t e c h n o l o g y , 1 2 (12), 1991-1995.

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Test yourself

Contents

Introduction
Aetiology
Risk factors
Clinical features
Investigations
Management
Complications
Source\: geekymedics.com
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