What is Sepsis?
Sepsis can be thought of as a series of physiological responses to the presence of an infection, culminating in organ system dysfunction or failure, with potential long-term consequences among its survivors. It is not a single disease process, but a complex syndrome involving as yet ill-defined interactions between host and pathogen.
Sepsis has been defined as the presence of the systemic inflammatory response or SIRS, in the presence of a known or suspected source of infection. Severe sepsis was defined as sepsis with organ system dysfunction and septic shock, a subset of severe sepsis, where hypotension and high lactate levels persist despite adequate fluid resuscitation.
SIRS Criteria and Severe Sepsis Criteria
|SIRS criteria (two or more of the following)||Severe sepsis criteria (sepsis plus any one of the following)|
|Temperature >38°C or <36°C||SBP <90 mmHg or MAP <65 mmHg or lactate >2.0 mmol/L (after initial fluid challenge)|
|Heart rate >90/min||INR >1.5 or a PTT >60 s|
|Respiratory rate >20/min or PaCO2 <32 mmHg||Bilirubin >34 μmoL/L|
|WCC >12 or >10% immature band forms||Urine output <0.5 mL/kg/hr for 2 h|
|Additional SIRS criteria were added in 2001 to include hyperglycaemia (glucose >7.7 mmol/L) in the absence of diabetes mellitus and the presence of an acutely altered mental state.||Creatinine >177 μmoL/L|
|Platelets <100 × 109/L|
|SpO2 <90% on room air|
It has long been recognised that SIRS is an imperfect qualifier of sepsis. In hospital populations, many exhibit SIRS but do not develop other clinical features of sepsis. In one study, one in eight patients with infection and new organ system dysfunction criteria did not meet current criteria for diagnosis of sepsis.
In 2016, sepsis was defined by the third consensus task force as a ‘life-threatening organ dysfunction due to a dysregulated host response to infection’. The ‘official definition of sepsis changed two points in the quick SOFA (Sequential Organ Failure Assessment) score in the context of infection and can be defined as;
- The presence of a known or suspected infection.
- Two or more of the following organ dysfunction criteria:
- Respiratory rate >22/min.
- Systolic BP <100 mmHg.
- Altered mental status (any GCS <15).
It should be noted that subsequent validation of this assessment framework suggest that existing ‘track and trigger systems may be as or more effective in detecting the deteriorating patient.
Septic shock represents a condition of cellular and metabolic stress associated with worse outcomes when compared with the rest of the sepsis population and can be defined as;
- Persistent hypotension, with vasopressors required to support a mean arterial pressure >65 mmHg A.
- Lactate >2 mmol/L, despite adequate fluid resuscitation.
HOW DO PATIENTS WITH SEPSIS PRESENT?
Patients are likely to present to the hospital with systemic manifestations of an infective process, such as pyrexia, rigours, tachycardia, tachypnoea and altered level of consciousness. They may also present with symptoms and signs relating to the site of the underlying infectious process, such as:
- Lung – Cough, dyspnoea, chest pain and sputum production.
- Genitourinary tract – Dysuria, discharge, abdominal/flank pain.
- Skin and soft tissue – Rashes, erythema, skin breakdown, joint pain.
- Central nervous system – Headaches, convulsions, photophobia, neckm pain.
- GI tract – Diarrhoea, vomiting, abdominal pain, jaundice.
HOW IS SEPSIS MANAGED?
Once recognised, sepsis should be considered a medical emergency. Clinical studies have shown that delays, particularly in initial resuscitation of the patient with sepsis, and in the administration of antimicrobial therapies, have been associated with dramatically worse outcomes.
Initial resuscitation in sepsis, as with most other critically ill patients, follows a classical ABCDE approach.
- Ensure airway compromise is neither present nor imminent.
- Assess the patient’s chest; signs may be present indicating a pulmonary focus of infection.
- Assess the amount of work the patient is doing in breathing (Respiratory rate, accessory muscle use, fatigue), and assess the efficacy of that breathing (check oxygen saturation and/or blood gases).
- Apply oxygen if appropriate (aim for saturations of at least 94% if there is no risk of chronic CO2 retention).
- Consider the use of non-invasive or invasive ventilation if there is severe compromise unresponsive to basic measures.
- Look for signs of vasodilation due to sepsis – a warm periphery, bounding pulses, tachycardia >90/min.
- Look for signs of a collapsed or collapsing circulation – a cold, clammy periphery, hypotension (systolic BP <100 mmHg), weak or thready pulse, poor urine output (<0.5 mL/kg/hr) and rising serum lactate.
- If circulatory compromise is identified, commence intravenous fluids in the form of a 250- to 500-mL bolus and assess the response. This can be repeated as necessary with suitable monitoring in place to a maximum of 30 mL/kg. Serial lactates should be measured.
- Look for the presence of depressed consciousness.
- Also look for the presence of altered mental status. This may be less easy to spot, and clues from family, carers and nursing staff may be useful; this is often an early sign in evolving sepsis.
- Check the patient’s capillary glucose level.
- Look for any potential clues to the source of sepsis; this might include open wounds, evidence of cellulitis, recent surgery, invasive procedures or trauma or presence of pain in the abdomen. Also look for indwelling catheters, cannulas and drains; all of these are potential routes for pathogens to enter.
- Obtain cultures of blood, and where indicated urine, sputum, CSF and wound exudate.
The previous teaching suggested a rigorous early goal-directed therapy (EGDT) approach to the management of septic shock, directed at rapid ‘normalisation’ of physiology. This approach aimed to achieve specific targets:
- Central venous pressure 8–12 mmHg (A measure of the patient’s overall intravascular filling state).
- Mean arterial pressure >65 mmHg (Normalisation of vascular relaxation present in sepsis).
- Urine output of at least 0.5 mL/kg/hr.
- Administration of blood products and/or inotropic therapy to achieve central venous oxygen saturations greater than 70%.
Subsequent clinical studies have suggested, however, that such a rigorous goal-directed approach offers little advantage over standard resuscitation. The central principles remain the correction of hypovolaemia, administration of vasopressors to correct hypotension and assessing for and correcting low cardiac output states.
Once in the ICU, patients may receive further intravenous fluids to optimise filling. This is usually continued in rapid boluses of 250–500 mL, and the effects on parameters such as CVP, mental state, urine output, lactate and peripheral temperatures observed. This process may be repeated, usually to a maximum of 30 mL/kg of fluid administered. Beyond this point, further IV fluid may become detrimental and invasive monitoring should be instituted.
A mean arterial blood pressure of 65 mmHg is sought as this represents a midpoint in the autoregulatory range of most organ system vascular beds; a higher target may be sought in hypertensive patients. The objective here is to ensure the organ systems receive an adequate supply of oxygenated blood.
Catecholamine based vasopressor drugs such as metaraminol (usually in the short term) or noradrenaline are normally used to accomplish this, with the latter requiring a central venous catheter for administration. In refractory cases, where high doses of noradrenaline fail to achieve this despite adequate filling, other drugs such as vasopressin and hydrocortisone may be added. In some cases, where cardiac function is felt to be depressed, either by sepsis directly, or by exacerbation of pre-existing cardiac disease, inotropic agents such as adrenaline or dobutamine may also be added.
Early administration of antimicrobials is crucial in managing sepsis. Although it is desirable to obtain microbiological specimens prior to antibiotic administration, this may not always be possible and administration of antibiotics within the first hour should be the goal.
In most cases, the initial antibiotic therapy will be empirical, designed to cover most potential causative organisms and may include a beta-lactam or extended-spectrum beta-lactam, in combination with an aminoglycoside and/or nitroimidazole. Such regimens cover most Gram-negatives and positives including anaerobes.
It is important to remember that antibiotics should be reviewed daily and the aim should be to rationalise agents to cover the causative organism as soon as possible, and then to discontinue treatment as soon as clinically appropriate. Excessive use of broad-spectrum antimicrobials may be harmful to the patient, by disrupting their normal microbiome and increasing the patients’ vulnerability to secondary infections such as Clostridium difficile. Excessive broad-spectrum antibiotics also increase the selection of resistant organisms and hence pose a wider risk to society. The control of any source of infection, such as an abscess or infected indwelling catheter, is crucial in preventing unnecessary antibiotic usage.
It is extremely useful to review the patient’s previous microbiological records to ascertain which antibiotics they may have been exposed to recently and whether they are known to be colonised with resistant organisms, such as MRSA. It is also important to elicit any history of allergy or intolerance.