Sepsis
Background
The mortality from acute bacterial sepsis in the intensive care population remains high, at around 30%, with little change over the past decade, despite considerable advances in intensive care therapies. Currently, there is a global initiative to promote the early recognition of sepsis and rapid and aggressive delivery of sepsis care ‘bundles’.
Learning outcomes
1 Define the key recognition points of sepsis and septic shock
2 Understand the principles of the rapid delivery of the ‘Sepsis Six’ bundle
3 Outline the principles of the intensive care management of a patient with ALI secondary to pneumonia.
CPD matrix matches
2C01; 2C03
Case history
A 46-year-old man is brought into the ED by ambulance. He gives a history of gradually worsening shortness of breath and fever. His past medical history is unremarkable. He is on no medication and has no allergies. His initial observations are: HR 140 bpm, RR 35/min, BP 70/45 mmHg, and his temperature is 39.5°C. SpO2 on 15 L/min oxygen via a non-rebreathing face mask is 90%. He seems confused. He is using his accessory muscles of breathing and is cool and clammy peripherally, and, on auscultation, he has reduced breath sounds at the left lung base extending to the midzone. His CXR is as shown in Figure 2.6.
Fig. 2.6 CXR demonstrating left basal consolidation.
Blood gas analysis gives the following results: pH: 7.21, PaO2 9.2 kPa, PaCO2 3.2 kPa, HCO3– 16 mmol/L. The ED resident is concerned about his clinical state and calls you as the on-call ICU registrar to assist in the ongoing management of this patient.
What are your immediate treatment priorities?
Treatment priorities for this patient should follow an ABC approach. Full minimal monitoring (SpO2, NIBP, ECG) should be applied. He is already receiving high-flow oxygen via a non-rebreathing face mask. IV access should be obtained.
The presumptive diagnosis here is severe community-acquired pneumonia (CAP) which has rendered the patient, an otherwise fit and well man, very unwell with signs of severe sepsis.
Severe sepsis is part of a spectrum of physiological derangement, ranging from the systemic inflammatory response syndrome (SIRS) to septic shock, and is defined as*:
1 SIRS:
(a) Two or more of:
(i) Temperature >38°C or <36°C
(ii) HR >90 bpm
(iii) RR >20 breaths/min or PaCO2 4.3 kPa
(iv) WCC >12 000 cells/mm3 or >10% immature forms
2 Sepsis:
(a) SIRS with evidence or clinical suspicion of infection
3 Severe sepsis:
(a) Sepsis associated with organ dysfunction or hypoperfusion
4 Septic shock:
(a) Sepsis with the presence of end-organ hypoperfusion despite adequate fluid resuscitation.
In recent years, there has been increasing emphasis on early recognition and goal-directed treatment of sepsis. A UK initiative (available at: <http://survivesepsis.org>) defines the ‘Sepsis Six’ as six tasks to be completed within 1 hour following the recognition of sepsis:
◆ Give high-flow oxygen
◆ Take blood cultures
◆ Give IV antibiotics
◆ Start IV fluid resuscitation
◆ Check Hb and lactate
◆ Monitor accurately hourly urine output.
Implementation of these tasks has been shown to reduce mortality from sepsis.
Going through the ‘Sepsis Six’ bundle, what would be an appropriate choice of antibiotic for this patient?
This man has a CAP. The British Thoracic Society guidelines for the management of CAP recommends a broad-spectrum β-lactamase stable antibiotic, such as co-amoxiclav, together with a macrolide, such as clarithromycin, as initial IV antibiotic therapy.
How much fluid do you give him, and what fluid do you give?
Resuscitation should commence with a 20 mL/kg bolus of IV fluid. There is some evidence to suggest 4.5% human albumin solution may have a mortality benefit in patients with severe sepsis, but its availability and cost are such that other fluids are more likely to be used. Balanced electrolyte solutions, as they are physiologically balanced solution, is less likely to cause iatrogenic hyperchloraemic metabolic acidosis, compared to resuscitation with normal saline. The patient’s clinical response to the initial bolus (peripheral perfusion, HR, BP, mental state, urine output) should be used as a guide to ongoing fluid resuscitation therapy.
What is the rationale behind measuring Hb and lactate in patients with severe sepsis?
Sepsis and severe sepsis are defined by the presence of end-organ hypoperfusion. Lactate is a by-product of anaerobic respiration, and, in the context of sepsis, lactic acidosis can be a measure of tissue hypoxia due to inadequate oxygen delivery. This is known as a type A lactic acidosis. Measurement of lactate gives an indication of tissue hypoxia and can be used as a guide to effectiveness of resuscitation efforts. There is evidence that failure to clear lactate in the first 6 hours of resuscitation is associated with increased mortality.
Oxygen delivery (DO2, in mL/min) is estimated by:
The oxygen content (CaO2) of arterial blood is described by the equation:
Thus, an anaemic patient will have reduced oxygen delivery, even in the face of an adequate cardiac output and adequate oxygenation. The Surviving Sepsis campaign, a set of evidence-based guidelines on early goal-directed sepsis therapy, recommends transfusing patients with a haematocrit of <0.3.
Case update
The patient’s HR and BP improve with fluid resuscitation and are now 120 bpm and 90/45 mmHg, respectively. He becomes increasingly drowsy and more tachypnoeic with a RR of 40 breaths/min. His SpO2 on 15 L/min oxygen deteriorates to 85%. You decide to anaesthetize and intubate this man before transferring him to the ICU.
Three days later, his CXR demonstrates changes, as shown in Figure 2.7.
Fig. 2.7 Bilateral interstitial infiltrates.
His ABG shows a PaO2 of 8.3 kPa. He is receiving an inspired fraction of inspired oxygen concentration (FiO2) of 0.9.
Comment on his chest X-ray and arterial blood gases
This patient has developed ARDS.
The American-European Consensus Conference (AECC) definition of ALI and its most severe subset ARDS is*:
1 ALI:
(a) Acute onset
(b) Bilateral infiltrates on frontal CXR
(c) PaO2/FiO2 ratio <300 mmHg (40 kPa)
(d) Pulmonary artery occlusion pressure (PAOP) ≤18 mmHg (or no clinical evidence of left atrial hypertension if PAOP not measured)
2 ARDS:
(a) As for ALI, except: PaO2/FiO2 ratio <200 mmHg (27 kPa).
These definitions of ALI/ARDS were updated in 2011. The ‘Berlin definition’ of ARDS was designed to address a number of issues with the AECC definition, including a lack of clear definition of acute onset, the influence of ventilator settings on PaO2/FiO2 ratio, the clinical difficulty of distinguishing hydrostatic pulmonary oedema from other causes of pulmonary oedema, and variability on CXR definition of infiltrates. The Berlin definition removes the term ALI altogether and instead defines ARDS as mild, moderate, or severe by the degree of oxygenation defect.
The Berlin definition of ARDS is:
◆ Onset within 1 week of a known clinical insult, or new or worsening respiratory symptoms
◆ Bilateral opacities on chest imaging: not fully explained by effusions, lobar or lingular collapse, or nodules
◆ Respiratory failure not fully explained by cardiac failure or fluid overload. Need objective assessment (e.g. echocardiography) to exclude hydrostatic oedema if no risk factors present
◆ Oxygenation defect:
• Mild: 200 mmHg < PaO2/FiO2 ratio ≤300 mmHg, with positive end-expiratory pressure (PEEP) or continuous positive airway pressure (CPAP) ≥5 cmH2O
• Moderate: 100 mmHg < PaO2/FiO2 ratio ≤200 mmHg, with PEEP ≥5 cmH2O
• Severe: PaO2/FiO2 ratio ≤100 mmHg, with PEEP ≥5 cmH2O.
What ventilator settings would you use in this man?
This patient is at risk of ventilator-associated lung injury (VALI). This may manifest as:
◆ Barotrauma: the use of large tidal volumes results in the generation of high transpulmonary pressures, especially in the presence of pulmonary pathology, causing reduced pulmonary compliance such as ARDS. This may result in the rupture of alveoli, with gas tracking along the perivascular sheaths and breaching the mediastinal pleura, leading to the development of pneumothoraces, pneumomediastinum, and surgical emphysema
◆ Volutrauma: overdistension of alveoli by excessively high tidal volumes leads to damage of the alveolar–capillary barrier. Increased pulmonary vascular permeability leads to the alveolus becoming flooded with proteinaceous material, and the reduction in surfactant production by the damaged type 2 pneumocytes results in reduced pulmonary compliance, alveolar collapse, and impaired gas exchange due to increased venous admixture and physiological dead space
◆ Atelectrauma: repetitive recruitment and derecruitment of alveoli during the respiratory cycle can lead to diffuse alveolar damage. Loss of physiological PEEP due to endotracheal intubation, reduction in surfactant production by damaged type 2 pneumocytes, and the lung pathology itself (e.g. pneumonia) all contribute to alveolar derecruitment and thus predispose the lung to atelectrauma
◆ Biotrauma: damage to the alveolar–capillary interface by injurious mechanical ventilation leads to an influx of cytokines and other inflammatory mediators into the alveolar space. This leads to an intense inflammatory reaction within the lung parenchyma itself, and spillover of inflammatory mediators into the systemic circulation may result in a SIRS-type response.
The ARDSNet group published a trial in 2000 comparing low (6 mL/kg, end-inspiratory plateau pressure <30 cmH2O) and high (12 mL/kg, end-inspiratory plateau pressure <50 cmH2O) tidal volume strategies. To date, lung-protective ventilation using low tidal volumes is the only intervention shown to improve survival in ARDS, and it has become standard practice in ICU for patients with, or at risk of developing, ARDS.
Other strategies used in dealing with ALI/ARDS include:
◆ Permissive hypercapnia
◆ PEEP
◆ Restrictive fluid strategies
◆ Prone ventilation
◆ High-frequency oscillatory ventilation
◆ Extracorporeal membrane oxygenation (ECMO).
What strategies are used in your intensive care unit to reduce the incidence of ventilator-associated pneumonia?
VAP is associated with increased duration of mechanical ventilation, ICU length of stay, and mortality. Most ICUs in the UK have implemented care bundles to reduce the incidence of VAP.
A care bundle may be defined as a group of evidence-based interventions relating to a particular condition or event. When used together, the elements of the bundle will lead to better outcomes, compared to when the elements are used separately. The ‘Sepsis Six’ care bundle has already been described.
Components of a VAP prevention bundle typically include:
◆ Daily sedation holds, if appropriate
◆ Nursing patient in semi-recumbent (30–45° head-up) position: this reduces the passive regurgitation of gastric contents into the oropharynx
◆ Selective decontamination of the digestive tract (SDD) and selective oral decontamination (SOD): the rationale behind these interventions is to reduce the pathogenic colonization of the oral cavity and digestive tract without disrupting the normal gut flora. SOD involves the application of topical pastes to the mouth, containing a mixture of antibacterial and antifungal agents (e.g. tobramycin, amphotericin B, and colistin). SDD includes 4 days of IV broad-spectrum antibiotic administration (e.g. cefotaxime), in addition to the oral SDD regimen
◆ Oral decontamination with topical antiseptics such as chlorhexidine paste 1–2% (if SDD or SOD not used).
Summary
Sepsis, regardless of the aetiology, carries a high mortality. This can be ameliorated by early recognition, appropriate investigations, and treatment, including source control, if possible. Goal-directed therapy in sepsis involves attempting to maximize tissue oxygen delivery by manipulating cardiac output and arterial oxygen content. The definition of ALI has recently been modified to better reflect current imaging practice and ventilation strategies. It is important to remember that mechanical ventilation can be lifesaving, but injudicious ventilation can result in worsening lung injury. Lung-protective ventilation strategies are mandatory in a patient with ALI.
British Thoracic Society. Available at: <https://www.brit-thoracic.org.uk/guidelines-and-quality-standards/community-acquired-pneumonia-in-adults-guideline/>.
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No authors listed (2000). Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. New England Journal of Medicine, 342, 1301–8.
Rubenfeld GD, for the ARDS Definition Task Force (2012). Acute respiratory distress syndrome—the Berlin definition. Journal of the American Medical Association, 307, 2526–33.
Society of Critical Care Medicine. Surviving sepsis campaign. Available at: <http://www.survivingsepsis.org>.