Infection: the inflammatory response to micro-organisms or the presence of micro-organisms in normally sterile sites
Systemic inflammatory response syndrome (SIRS): systemic response to various insults including infection, trauma, surgery, burns; includes two or more of the following:
Respiratory rate (RR) >20 or PaCO2 <4.3 kPa
Heart rate (HR) >90
Temperature >38.3 oC or <36 oC
White cell count (WCC) >12 or <4 x 109/L
Acutely altered mental state
Glucose >8.3 mM (in the absence of diabetes mellitus)
Sepsis: systemic response to infection i.e. SIRS + source of infection e.g.
Focal crackles/bronchial breathing on chest auscultation
Consolidation on chest radiograph (CXR)
Positive urine dipstick and/or culture
Severe sepsis: sepsis + organ dysfunction or tissue hypoperfusion
Respiratory: new/increased oxygen requirements to maintain oxygen saturations (SpO2) >90%
Renal: creatinine >177 µM or urine output <0.5 ml/kg/hour for 2 hours
Hepatic: bilirubin >34 µM
Coagulation: platelets <100 x 109/L, INR >1.5 or APTT >60 s
Systolic blood pressure (SBP) <90 mmHg or mean arterial pressure (MAP) <65 mmHg
SBP >40 mmHg below normal despite adequate fluid resuscitation
Lactate >4 mM
Aetiology of sepsis
Sepsis can occur due to infection at any site in the body; bacteria are the usual culprit although viruses, fungi and parasites can all cause sepsis
Respiratory
Pneumonia
Lung abscess
Cardiac
Endocarditis
Myocarditis
Pericarditis
Genito-urinary
Cystitis
Pyelonephritis
Sexually-transmitted infections (STIs)
Gastrointestinal
Gastroenteritis
Cholecystitis
Ascending cholangitis
Appendicitis
Diverticulitis
Bowel perforation
Neurological
Meningitis
Encephalitis
Cerebral abscess
Dermatological
Cellulitis
Ulcers
Wound infection
Necrotising fasciitis
Orthopaedic
Osteomyelitis
Septic arthritis
Risk factors for sepsis
Immunocompromise
Extremes of age
Acquired immunodeficiency syndrome (AIDS)
Chemotherapy or underlying malignancy (especially haematological)
Steroids
Alcohol misuse
Malnutrition
Pregnancy
Genetic immune deficiencies – can present in adulthood (e.g. CVID)
In-dwelling devices
Peripheral venous cannula (PVC)
Central venous catheter (CVC)
Arterial line (ART)
Urethral catheter
Suprapubic catheter
Vascular lines
Urinary catheters
Drains
Recurrent antibiotic therapy
Pathophysiology of sepsis
Increased vascular permeability
Pro-inflammatory cytokines released as part of the systemic response to infection damage the vascular endothelium resulting in an inability to regular vascular permeability
As a result, the vascular endothelium becomes leaky, resulting in the migration of fluid and protein from the intravascular to extravascular space and a ‘capillary leak syndrome’
This leads to hypovolaemia, reduced preload, stroke volume (SV) and cardiac output (CO) via the Frank-Starling mechanism, as well as pulmonary oedema and hypoxia in the lungs
Myocardial dysfunction
The reduction in SV due to increased vascular permeability reduces CO via the Frank-Starling mechanism
In the early stages of sepsis, CO is maintain via an increase in HR and myocardial contractility and a ‘hyperdynamic circulation ‘is seen
However, further increases in HR reduce cardiac filling and coronary perfusion time, resulting in reduced CO and myocardial ischaemia, respectively
In the later stages of sepsis, pro-inflammatory cytokines, in addition to hypoxia and acidosis, directly impair myocardial contractility, reducing CO further
Disseminated intra-vascular coagulation (DIC)
Pro-inflammatory cytokines damage the vascular endothelium leading to widespread activation of the coagulation system and clot formation
This leads to thrombosis and multi-organ failure, but also thrombocytopenia and prolonged coagulation times from the consumption of platelets and clotting factors
History in sepsis
General symptoms
Fever
Chills
Malaise
Myalgia
Confusion
Constitutional symptoms indicative of underlying systemic disease (weight loss, fever, night sweats, lumps and bumps [nodes])
Symptoms of the source
Productive cough
Dyspnoea
Pleuritic chest pain
Respiratory
Cardiac
Chest pain
Valvular heart disease
Prosthetic valve replacement
Genito-urinary
Dysuria
Urinary frequency
Urinary urgency
Strangury
Cloudy, foul-smelling urine
Loin pain
Gastrointestinal
Abdominal pain
Nausea and vomiting
Diarrhoea
Jaundice
Neurological
Headache
Neck stiffness
Photophobia
Confusion
Drowsiness
Seizures
Dermatological
Hot, swollen, red, painful areas of skin
Orthopaedic
Hot, swollen, red, painful joints
Other considerations
Dates and destinations
Vaccinations
Chemoprophylaxis
Sexual partners in last three months (women, men, hetero/homosexual)
Last sexual intercourse
Use of protective contraception
Previous STIs
Current partner and their sexual history
Contacts, including non-human
Travel history
Sexual history
Vaccination history
Examination in sepsis
General signs
Pyrexia
Rigors
Tachypnoea
Tachycardia
Acutely altered mental state
Signs of the source
Ipsilateral reduced air entry
Ipsilateral dullness to percussion
Ipsilateral crackles/bronchial breathing
Respiratory
Cardiac
Splinter haemorrhages
Osler nodes
Janeway lesions
New regurgitant murmur
Roth spots
Genito-urinary
Suprapubic tenderness
Loin tenderness
Gastrointestinal
Abdominal distension
Abdominal tenderness
Guarding
Rigidity
Jaundice
Neurological
Nuchal rigidity
Kernig’s sign positive
Brudzinski’s sign positive
Photophobia
Confusion
Reduced/fluctuating consciousness level
Focal neurological signs
Papilloedema
Dermatological
Warm, erythematous, tender, oedematous areas of skin
Pupuric rash
Orthopaedic
Warm, erythematous, tender, oedematous joints
Other
Nodes
Signs of septic shock
May be compromised by reduced consciousness level
Hypoxia
Tachypnoea
Warm, flushed peripheries
In early stages of sepsis
Cold, pale peripheries
In later stages of sepsis
Airway
Breathing
Circulation
Tachycardia
Hypotension
Disability
Confusion
Reduced consciousness level
Initial investigation of sepsis
Venous blood gas (VBG) looking for lactic acidosis suggestive of severe sepsis (>2 mM) or septic shock (>4 mM)
Full blood count (FBC) looking for raised WCC, neutrophilia or neutropenia, as well as haemoglobin (Hb) level for its oxygen-carrying capacity
Urea & electrolytes (U&Es) looking for impaired renal function
Liver function tests (LFTs) looking for derangement that may suggest a heptatobiliary source or hepatic failure as a complication
Clotting and fibrinogen looking for DIC
C-reactive protein (CRP)
Blood cultures
Peripheral cultures
Lines cultures if vascular lines present
Urine dipstick +/- culture looking for leucocytes, nitrites and bacteria that would suggest a genito-urinary source
Electrocardiogram (ECG)
CXR looking for focal consolidation that would suggest a respiratory source or pulmonary oedema that would suggest acute respiratory distress syndrome (ARDS)
Sputum culture if productive cough present
Stool culture if diarrhoea present
Further investigation of sepsis
Echocardiography (echo) if endocarditis suspected
Lumbar puncture (LP) if meningitis suspected
CT chest and/or abdomen if source remains occult
Initial management of sepsis
Assess the patient from an ABCDE perspective
Maintain a patent airway: use manoeuvres, adjuncts, supraglottic or definitive airways as indicated and suction any sputum or secretions
Deliver high flow oxygen 15L/min via reservoir mask and titrate to achieve SpO2 94-98% or 88-92% if known to have chronic obstructive pulmonary disease (COPD)
Attach monitoring
Pulse oximetry
Non-invasive blood pressure
Three-lead cardiac monitoring
Request 12 lead ECG and portable CXR
Obtain intravenous (IV) access and take bloods
Anti-pyretics
Give paracetamol 1 g orally (PO) +/- ibuprofen 400 mg PO if no contraindications
If temperature remains high consider removal of excess clothing +/- bathing with tepid water
Sepsis six
Should be given as soon as possible and within an hour of recognising severe sepsis or septic shock
If the source is known, give the appropriate empirical IV antibiotic(s) as per local guidelines
For sepsis of unknown origin, give the appropriate broad-spectrum IV antibiotic(s) as per local guidelines e.g. piperacillin + tazobactam (tazocin) + gentamicin; once the source has been identified, switch to the appropriate empirical IV antibiotic(s) as per local guidelines
Give dexamethasone 10 mg IV if bacterial meningitis suspected
Guided by clinical context
Give boluses of crystalloid 500-1000 ml IV and re-assess after each
Patients with severe sepsis should receive a minimum of 20 ml/kg
Patients with septic shock often require up to 60 ml/kg
Oxygen titrated to achieve SpO2 94-98% or 88-92% if known to have COPD
Check lactate
Take blood cultures
Give IV antibiotics
Commence IV fluid resuscitation
Monitor urine output, aiming for >0.5 ml/kg/hour; this may require urinary catheter insertion
Source control
Removal of infected line eg urinary catheter, arterial line, central line
Abscess drainage
Tissue debridement
Early goal-directed therapy (EGDT)
Patients who remain hypotensive (SBP <90 mmHg) despite 20 ml/kg of crystalloid IV by definition have septic shock
These patients should ideally have a CVC inserted and their CVP monitored; fluid resuscitation should continue with boluses of crystalloid 500-1000 ml IV, aiming to maintain CVP >8 mmHg
Once CVP >8 mmHg, patients can be considered to have adequate preload to maintain CO
If they remain hypotensive (MAP <65 mmHg and/or SBP <90 mmHg) in spite of this, a vasopressor should be commenced to maintain these target BPs
First line vasopressor is noradrenaline
ScvO2 can be considered a marker of the balance between oxygen supply and demand; if low (<70%), there is a relative deficiency ie inadequate supply and/or excessive demand
If ScvO2 is low, it may be improved by increasing oxygen content and myocardial contractility
Oxygen content can be improved with high-flow oxygen and transfusion to a target Hb of 70-90 g/L
Myocardial contractility can be improved by commencing an inotrope such as dobutamine
1: Central venous pressure (CVP) >8 mmHg
2: Mean arterial pressure (MAP) >65 mmHg or SBP >90 mmHg
3: Central venous oxygen saturations (ScvO2) >70%
Further management of sepsis
Ensure tight glycaemic control with a sliding scale if necessary to maintain glucose <8.3 mM
If mechanically ventilated, avoid excessive inspiratory pressures and aim for tidal volume 5-7 ml/kg
Treat any complications
Consider low dose steroids for septic shock refractory to fluid resuscitation and vasopressor therapy
Consider activated protein C for severe sepsis and high risk of death
Once a specific culprit organism has been identified from culture growth, switch to narrower-spectrum antibiotic(s) to which the organism is sensitive
As sepsis resolves and patient improves, consider switching antibiotics from IV to oral
