Sepsis

Original Editors - Leana Louw

Top Contributors - Lucinda hampton, Leana Louw, Rachael Lowe, Kim Jackson, Aminat Abolade, Admin, Carina Therese Magtibay and Uchechukwu Chukwuemeka

Description

Systemic inflammatory response syndrome (SIRS) is an exaggerated defense response of the body to a noxious stressor ( eg.infection, trauma, surgery, acute inflammation, ischemia or reperfusion, malignancy) to localize and then eliminate the endogenous or exogenous source of the insult.

• It involves the release of acute-phase reactants which are direct mediators of widespread autonomic, endocrine, hematological and immunological alteration in the subject.
• Even though the purpose is defensive, the dysregulated cytokine storm has the potential to cause massive inflammatory cascade leading to reversible or irreversible end-organ dysfunction and even death.

The graph R shows the mortality assosiacted with sepsis

1. SIRS with a suspected source of infection is termed sepsis.
2. Sepsis with one or more end-organ failure is called severe sepsis
3. Sepsis with hemodynamic instability in spite of intravascular volume repletion is called septic shock. This can potentially lead to multiorgan failure where the body is unable to maintain haemostasis without medical intervention, a common cause of death in the ICU setting.

Together they represent a physiologic continuum with progressively worsening balance between pro and anti-inflammatory responses of the body.

Epidemiology

The incidence of sepsis is set at 50-95 per 100 000 with an suspected increase of 9% per year. This is further made up by:

• 2% of hospital admissions
• 9% of sepsis results in severe sepsis
• 3% septic shock
• 10% of ICU admissions per year
• Peak age around 60's

Etiology

The 2009 European Prevalence of Infection in Intensive Care (EPIC II study) determined that gram-negative bacterial infections far exceed other etiologies as the most common cause of sepsis syndromes with a frequency of 62%, followed by gram-positive infections at 47%.

• An increase in the prevalence of the latter may be attributable to the performance of more invasive procedures and increased incidence of nosocomial infections.
• Predominant micro-organisms isolated in patients include Staphylococcus aureus (20%), Pseudomonas (20%), and Escherichia coli (16%). Predominant sites of infection include respiratory (42%), bloodstream (21%), and genitourinary (10%).
• The influence of bacterial strain and site of infection on mortality was illustrated in a large meta-analysis. In this study, gram-negative infections were overall associated with higher mortality.

Sepsis syndromes caused by multidrug-resistant bacterial strains (methicillin-resistant Staphylococcus (MRSA), vancomycin-resistant enterococci (VRE)) are on the rise with a current incidence of up to 25%; viruses and parasites cause far fewer cases and are identified in 2% to 4% of cases

Risk factors:

• Diabetes
• Malignancy
• Chronic kidney and liver disease
• Use of corticosteroids
• Immunosuppressed state
• Burns
• Major surgery
• Trauma
• Presence of indwelling catheters
• Prolonged hospitalization
• Hemodialysis
• Extremes of age

80% of sepsis cases is the result of the following infections:

• Chest (e.g. pneumonia)
• Abdomen
• Genitourinary system
• Primary bloodstream

Mechanism of Injury / Pathological Process

Pathogens have the ability to trigger intercellular events in a variety of cells, including the neuroendocrine system, immune cells, epithelium and endothelium. Proinflammatory mediators attempt to eradicate the pathogens, a process that is controlled by anti-inflammatory mediators. This inflammatory process leads to tissue damage, changes in the leukocytes resulting in immune changes. When this natural control process fails, it leads to systemic inflammation and the infection is converted to sepsis or septic shock.

The hypothalamic thermostat is reset by the fever caused by sepsis. In an attempt to cool down, it results in peripheral vasodilatoation and subsequent depletion of the visceral perfusion. Excess nitric oxide production is stimulated by endotoxins and this leads to uncontrolled vasodilatation and a “functional haemorrhage”. Increased cardiac output is thus unsuccessful at maintaining an adequate blood pressure. This can lead to hypoxic tissue damage.

Shock in general normally runs the following course:

Insufficient tissue perfusion → anaerobic metabolism → lactic acidosis → metabolic acidosis → cellular damage → organ failure.

Clinical Presentation

Criteria

Two or more of the following:

• High grade (> 38˚C) or low grade (< 36˚C ) fevers
• Heart rate > 90/minute
• RR > 20/minute OR PaCO2 < 4.3kPa
• WCC > 12

Signs and symptoms

• Pyrexia
• Flushed presentation
• Tachypnea
• Hypotension
• Bounding pulse
• Restricted regional blood flow as the result of vasopressors
• Signs of tissue hypoperfusion:
  • Areas of mottled skin
  • Oliguria
  • Mental confusion
  • Delayed capillary refill
  • Hyperlactacidaemia

Diagnostic Procedures

Septic shock can only be diagnosed when it fits to the clinical criteria and a infection (and the pathogen if possible) is verified.

• Identification of infection:
  • Look for obvious signs - e.g. community-aquired pneumonia, prupura fulminans, cellulitis, wound discharge.
  • Blood tests / tissue biopsy or sample to determine pathogen
• Bloods:
  • PCR
  • Microarray based rapid
• Assess for issue hypoperfusion
  • Glasgow coma scale to determine mental confusion (unable to do in sedated patients)
  • Input and output measures to determine oliguria
• Multi-organ failure

Outcome Measures

• SOFA (sepsis-related organ failure assessment) score
• qSOFA (quick sepsis-related organ failure assessment)

Medical Management

Medical management is vital to prevent further inflammatory response. This is normally done by means of ventilatory and haemodynamic support. Treatment is aimed at controlling the cause of infection and restoring haemodynamic homeostasis. The key to improved outcomes is in early identification and appropriate management thereof in the initial hours after onset.

Aims

• Restoration of normal haemostasis
• Sustain tissue perfusion
• Avoid focusing on a single system
• Maintain oxygen delivery
  • Respiratory support
  • Inotropic support
  • Vasodilators
• Keeping pH > 7.35

Control infection source

• Antibiotics
• Removal of infected/necrotic tissue (where applicable)

Shock management

• Aim for restoration to the following values (if possible within 6 hours):
  • CVP: 8-12mmHg
  • MAP: 65-90
  • Sats > 70%
• Management strategies:
  • Fluids
    • Needs to be carefully administrated to avoid complications such as pulmonary oedema as a result of overload, as this will negatively affect oxygen delivery due to circulating volume problems.
    • For optimal cardiac output:  PAWP = 18cmH2O and CVP = 10-12cmHO
    • Repeat until cardiac output increase with > 10% with central venous pressure increase of < 3 mmHg
  • Vasopressors (if hypotension still present after management with fluids)
    • Dopamine or norepinephrine
    • Aim to restore MAP to 60-90
  • Inotropes
  • Blood transfusions
  • Mechanical ventilation

Organ dysfunction management

• In cases of renal failure: Renal replacement treatment
• In ARDS/acute lung injury: Mechanical ventilation with tidal volumes of 6-7ml/kg ideal body weight

Enhancing or replacing host responses

• Endocrine response:
  • Low-dose corticosteroids
  • Low-dose vasopresssin (if corticosteroids are not able to be administrated or not working)
• Haemostasis response: Drotrecogin alfa

Control of oxygen consumption

• Respiratory support:
  • Oxygen in cases of ARDS or acute lung injury
  • Mechanical ventilation with tidal volume aims of 6-7ml/kg ideal body weight
• Sedation
• Paralysis
• Avoidance of pyrexia and stressors
• Supportive:
  • Blood transfusion (packed red blood cells) - also aids in optimisation of haemodynamic status
  • Haemofiltration

Correction of metabolic acidosis (lactate-induced)

• Haemofiltration if pH < 7.2
• Changes to IPPV to improve PaCO2

Other

• Nutritional support is an important factor in the management of septic shock, as it can increase energy consumption up to 50%. It however negatively affects the utilization of nutrition, resulting in catabolism and subsequent muscle wasting.
  • Consider enteral supplementation
• Steroids (gram-negative septicaemia)
• Activated protein C
• Maintain HGT: 4-6 mmol/L
• Prevent hospital-acquired infections
• Administration of vaccines (where applicable)
• IVIG's

Physiotherapy management

See the page for the role of physiotherapy in the ICU.

Physiotherapy interventions in the ICU setting normally consists of respiratory physiotherapy focusing on airway clearance techniques and early mobilization. During acute sepsis or septic shock, patients are often too unstable for physiotherapy intervention, which only starts when the patient is haemodynamically stable.

Positioning plays a big role in the management of patients with sepsis. A heads-up position of 30-45 degrees is recommended to decrease the risk of aspiration pneumonia and ventilator-associated pneumonia, where prone positioning is recommended in sepsis induced ARDS with a PF ratio of less than 150.

A common result of these are critical illness neuropathy, and extensive rehabilitation should then be incorporated in the ICU, after discharge to the ward, as well as in the out-patient setting with the aim of getting the patient back to his baseline level of function and participation as per the ICF model.

Resources

• Surviving Sepsis Guidelines and Bundles
• Hospital Toolkit for Adult Sepsis Surveillance