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Information ⬇

Author(s): Guy Glover and Manu Shankar-Hari

  • Make a working diagnosis of sepsis (Box 35.1) if a patient has organ dysfunction in the context of suspected or proven infection. Because infection may be occult consider the diagnosis whenever organ dysfunction is unexplained.
  • Septic shock (Box 35.1) is a subset of sepsis in which underlying circulatory, cellular and metabolic abnormalities are associated with a greater risk of mortality than sepsis alone.
  • Escherichia coli, Staphylococcus aureus and Streptococcus pneumoniae (pneumococcus) are the commonest pathogens.

A good outcome depends on prompt diagnosis, adequate fluid resuscitation, timely administration of appropriate initial antibiotic therapy, and drainage of any infected collection. An overview of the principles of clinical management is shown in Box 35.2.

Priorities ⬆ ⬇

Manage patients with sepsis according to a sepsis bundle, for example Surviving Sepsis Campaign Bundle (Box 35.2) or the United Kingdom ‘Sepsis 6’.

  1. If systolic BP is <100 mmHg and/or the serum lactate is elevated, give crystalloid IV 500 mL over 15 min using one, if necessary two, large bore (16G or larger) cannulae. Give further IV fluid up to at least 30 mL/kg if hypotension or hyperlactataemia persists. Give high flow oxygen by mask initially, adjusted as needed to maintain arterial oxygen saturation >94% once adequate monitoring is in place.
  2. Examine for a focus of infection (Table 35.1).
    • The clinical setting may make it obvious, for example signs of pneumonia (Chapters 62, 63) or meningitis (Chapter 68) or recent instrumentation of the urinary or biliary tract.
    • Check for neck stiffness, focal lung crackles or bronchial breathing, heart murmur, abdominal tenderness or guarding, acute arthritis, cellulitis, soft tissue abscess and signs of infection at the site of IV lines.
    • Obtain a surgical opinion if you suspect an abdominal or pelvic source of sepsis.
    • Many patients with neutropenic sepsis (Chapter 101) have no detectable clinical focus.
  3. Investigations required urgently are given in Tables 35.2 and 35.3.
    • Early confirmation of infection is from microscopy or Gram staining or PCR panels or antigen detection tests. Take blood cultures and cultures from other relevant sites urgently in sepsis.
    • A raised lactate is an important marker of septic shock and is associated with increased mortality (other causes include liver dysfunction, seizures, metformin and salbutamol).
  4. Start antibiotic therapy as soon as blood has been taken for culture and well within one hour. Mortality rises with any delay.
    • Principles of good antibody practice are given in Table 35.4. The antibiotic used should be guided by a hospital protocol or an infection specialist based on the likely organism, taking account of the source of sepsis if known (Table 35.5), whether the infection is community or hospital-acquired, results of previous isolates from the patient and the local pattern of antibiotic resistance in patients.
    • Gentamicin levels need to be monitored and doses should be reduced in renal impairment (consult the British National Formulary).
    • Substitute amikacin for gentamicin if gentamicin resistance is prevalent.
    • Substitute vancomycin for flucloxacillin if methicillin-resistant Staphylococcus aureus (MRSA) infection is possible. Serum levels of vancomycin should be measured.

  5. ‘Red flag’ signs:

    • Systolic blood pressure<90 mmHg (or >40 mmHg fall from baseline)
    • Heart rate >130/min
    • Oxygen saturations <91%
    • Respiratory rate >25/min
    • Responds only to voice or pain/unresponsive
    • Lactate >2.0 mmol/L

    Presence of one or more of red flag signs is an emergency. Refer to the Critical Care Outreach Team for further management of these patients in an intensive care or high-dependency unit.

  6. Patients with sepsis are at risk of rapid deterioration and should be monitored closely every 30–60 min:
    • Heart rate
    • Blood pressure
    • Respiratory rate
    • Arterial oxygen saturation
    • Temperature
    • Conscious level
    • Fluid balance including hourly urine output

Further Management ⬆ ⬇

Outline

Hypotension and Organ Dysfunction!!navigator!!

Management requires invasive monitoring and critical care expertise.

Arterial and central venous monitoring will be required if the patient is in septic shock or once in the ICU but placement should not delay initial priorities.

The first priority is adequate fluid resuscitation, using a balanced crystalloid (e.g. Hartmann's solution). This should be guided by a clinical assessment of the circulation and tissue perfusion. A CVP of +8–12 (12–15 mmHg in mechanically ventilated patients) has been proposed as a target to guide fluid resuscitation, although more sophisticated measures may also be used which include response to passive leg raising, echocardiography or cardiac output monitoring.

If the patient remains hypotensive despite adequate fluid correction, start norepinephrine (dose range 0.05–1.0µgm/kg/min). This must be administered via a central line. Aim for mean arterial pressure >65 mmHg. The goal is to restore tissue perfusion. Monitor with:

  • Vital signs, capillary refill time, pulse and skin findings
  • Urine output (aim for >0.5 mL/kg/hr)
  • Arterial lactate (aim for normalization)
  • Central venous O2 saturation (ScvO2) (aim for ≥70%)

If evidence of end organ hypoperfusion persists, perform a bedside echocardiogram and / or measure the cardiac output. Consider measures to improve oxygen delivery, such as transfusion of packed red cells or adding inotropic therapy, for example dobutamine.

Respiratory support

Mechanical ventilation in sepsis is indicated for:

  • Severe acidosis
  • Multi-organ failure
  • Reduced consciousness
  • Respiratory failure, for example due to pneumonia or the acute respiratory distress syndrome (ARDS). ARDS is characterized by acute-onset hypoxia and bilateral pulmonary infiltrates in the absence of a cardiac cause (excluded by pulmonary artery occlusion pressure measurement or echocardiography).

The principles of ARDS management include:

  • Mechanical ventilation with positive end expiratory pressure (PEEP) and low tidal volumes (6 mL/kg predicted body weight)
  • A conservative fluid regimen
  • Ventilation in the prone position for moderate or severe ARDS
  • Neuromuscular blocking drugs for severe ARDS
Acute kidney injury (see Chapter 25)Acute kidney injury (see Chapter 25)

Acute kidney injury (AKI) is common in sepsis and is associated with a worse outcome. The principles of treatment of AKI in sepsis are:

  • Rule out additional obstruction
  • Optimize fluid replacement and correction of tissue perfusion
  • Consider renal replacement (usually with continuous veno-venous haemofiltration or haemodialysis) for refractory oliguria, fluid overload, acidosis, hyperkalaemia or azotaemia

Source control

When a persisting source of sepsis exists it is unlikely that antibiotics alone will be effective. Consider empyema, appendicitis, pyelonephrosis, necrotizing fasciitis. Indwelling cannulae, especially central venous lines, should be removed (and the tip sent for culture)

Antibiotic de-escalation and stewardship

Once the pathogenic organism is known the spectrum should be narrowed. Change to oral therapy once the patient is improved and apyrexial for >24 h. Most guidelines recommend a 7–10 day course but a shorter course (e.g. 5 days) may be safe if clinical resolution has occurred. In some situations, prolonged courses are necessary, for example infective endocarditis, lung abscess or bone infection: seek advice from a microbiologist. To avoid the development of resistance and the development of health-care associated infection (e.g. Clostridium difficile diarrhoea) antibiotics should not be overused:

  • Document the indication for the drug
  • Review the need for continuing antibiotics early and repeatedly
  • If the diagnosis of sepsis is refuted the antibiotic should be stopped

Problems!!navigator!!

Sepsis in the neutropenic patient (see Chapter 101)Sepsis in the neutropenic patient (see Chapter 101)

Patients with neutrophil counts <0.5×109/L are at high risk of bacterial infection, particularly from Gram-negative rods and Staphylococcus aureus and epidermidis. If the neutropenic patient has a single temperature >38°C, or two spikes of fever of >37.5°C during a 24-h period, the likely cause is bacterial infection and empiric broad spectrum antibiotic therapy should be started. Search for a focus of infection. Examination should include the entire skin including the perineum and perianal region, indwelling IV line and other IV sites, and the mouth, teeth and sinuses. Investigations required urgently are given in Tables 35.2 and 35.3. Several antibiotic regimens have been shown to be effective in neutropenic patients without localizing signs:

Ask for advice from a haematologist.

Sepsis associated with IV drug use

Several causes of fever must be considered (Table 35.7). Right-sided endocarditis may not give rise to abnormal cardiac signs. Antibiotic therapy must cover staphylococci.

Disseminated intravascular coagulation

Disseminated intravascular coagulation (DIC) is a complication of sepsis (as well as a number of non-infective disorders). This should be suspected in patients with sepsis and also in patients with septic shock who develop purpura, prolonged oozing from puncture sites, bleeding from surgical wounds or bleeding from the gastrointestinal and respiratory tracts. Confirm by a low platelet count (<100×1012/L), prolonged prothrombin and activated partial thromboplastin times, and a high plasma concentration of fibrin degradation products. Ask advice on management from a haematologist.

If there is active bleeding or a significant invasive procedure (i.e. surgery or radiological drainage) is needed, give fresh frozen plasma and platelet concentrates, although this is not usually necessary for invasive lines in the ICU (seek senior advice). There is no conclusive evidence for the use of heparin in the treatment of DIC, but this should be considered if there is thromboembolism. Give vitamin K 10 mg IV to reverse possible vitamin K deficiency which may contribute to the coagulopathy, although there is no evidence base addressing this specific question in sepsis.

Further Reading ⬆

Long B, Koyfman A (2016) Clinical mimics: An Emergency Medicine–focused review of sepsis mimics. Journal of Emergency Medicine . 52, 34–42.

Seymour CW, Liu VX, Iwashyna TJ, et al. (2016) Assessment of clinical criteria for sepsis: For the Third International Consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 315, 762–774.

Shankar-Hari M, Phillips GS, Levy ML, et al. (2016) Developing a new definition and assessing new clinical criteria for septic shock: For the Third International Consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 315, 775–787.

Singer M, Deutschman CS, Seymour CW, et al. (2016) The Third International Consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 315, 801–810.

Surviving Sepsis Campaign Guidelines. http://www.survivingsepsis.org/Guidelines/Pages/default.aspx.

Vincent J-L, Mira J-P, Antonelli M. (2016) Sepsis: older and newer concepts. Lancet Respir Med 4, 237–240.