Severe sepsis is very common, accounting for 27% of admissions to intensive care units in England, Wales and Northern Ireland1 This group of patients uses up 46% of all intensive care unit bed days and the median total hospital length of stay is 4 weeks1 Mortality remains unacceptably high at 44% and the annual cost of treating severe sepsis has been estimated in the USA as exceeding US$16 billion.1 2 The Surviving Sepsis Campaign (SSC) was launched in 2002 with a primary focus of achieving a 25% relative reduction in the mortality of severe sepsis.3 The SSC produced evidence-based guidelines for the management of severe sepsis that were initially published in 2004 and updated in 2008.4 5 The SSC worked alongside the Institute for Healthcare Improvement to distil the guidelines into two care bundles; the resuscitation bundle (care in the first 6 h from diagnosis) and the management bundle (care on the intensive care unit in the first 24 h).

The resuscitation bundle comprises a number of simple therapeutic interventions (taking blood cultures, giving antibiotics and fluids), together with the application of a more advanced form of resuscitation known as early goal-directed therapy (EGDT) in those patients who have shock unresponsive to fluid challenges. EGDT involves measuring the central venous oxygen saturations via a central venous catheter. The therapeutic interventions described in the resuscitation bundle should be completed within 6 h following the recognition of severe sepsis.

In a study carried out at two acute hospitals in England, non-compliance with the 6-h resuscitation care bundle was shown to be associated with more than a twofold increase in mortality.6

When carried out within the first 6 h after diagnosis, EGDT can dramatically improve survival from severe sepsis.7 EGDT outperforms (in terms of numbers needed to treat) thrombolysis and balloon angioplasty for acute coronary syndrome (ACS). Despite this, sepsis receives far less attention or funding than ACS, and standards in its recognition and treatment are not set nationally. Recent surveys show that currently only 18% of emergency departments (ED) in England have implemented EGDT,8 and only 12% of acute medicine units in the UK have the minimum facilities to comply with the 6-h resuscitation bundle,9 despite evidence that significant numbers of patients presenting to the ED have severe sepsis.10 An earlier survey in the USA contacted 30 academic ED and reported similar findings, with only 7% carrying out EGDT.11 Targeted educational programmes do appear to improve bundle compliance. In Spain a national sepsis educational programme led to improved resuscitation and management bundle compliance and lower hospital mortality; however, the improvements in the resuscitation bundle had lapsed after one year.12 There is undoubtedly an opportunity for ED staff, and indeed prehospital staff, to improve care for the patient with sepsis.

The efforts of the SSC and the critical care community have concentrated on educating staff from the ED and critical care to promote collaboration for the introduction of EGDT.13^–16 Poor implementation of EGDT and the resuscitation bundle has led to a move to target the education of staff working in areas outside of critical care, including the implementation of an operationalised resuscitation bundle known as the “sepsis six”:17 18 (1) high-flow oxygen (15 l/minute via non-rebreathe mask); (2) blood cultures; (3) intravenous antibiotics; (4) fluid resuscitate; (5) measure serum lactate and haemoglobin; (6) urinary catheter and measure urine output (spontaneous voiding with accurate hourly monitoring is acceptable if the patient is fully cooperative).

The “sepsis six” can be carried out by hospital staff with limited specialist skills in the first hour following the diagnosis of severe sepsis and can make a significant contribution to decreasing mortality (unplanned interim analysis of author’s research currently in progress).

What to our knowledge has not been considered in the UK is the role and contribution that prehospital care staff could make to improving sepsis care. Significant numbers of patients with severe sepsis are admitted to hospital via the ED—many of these will have been treated and transported to hospital by prehospital staff. This represents an opportunity for prehospital staff to improve mortality in sepsis, analogous to their time-critical role with patients with acute myocardial infarction (AMI) or stroke. As a direct analogy to AMI care, in septic shock the administration of antibiotics within 1 h has been shown to be associated with significantly reduced mortality compared with administration in the second or later hours.19 Although prehospital sepsis care is unusual, prehospital cardiac care is the norm.20 In order to improve prehospital sepsis care the first step must be to adopt a similar approach to that taken with ACS—accepting that care is time limited and that delays are unacceptable. Screening patients for severe sepsis and the initiation of some elements of the “sepsis six” could be carried out en route to hospital. The need for some elements of the six such as urinary catheterisation in the prehospital environment is questionable. In situations in which there is a long delay in transporting a patient to hospital catheterisation en route may be beneficial.

An evidence-based “sepsis six” for prehospital care practitioners may include:

It has been argued that an out-of-hospital sepsis score should be developed.21 A screening tool for the identification of severe sepsis has been developed based on consensus definitions,22 and prehospital practitioners could use an adapted form of this tool such as that shown in fig 1 to help identify patients with severe sepsis.

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Figure 1

Prehospital severe sepsis screening tool. lpm, litres per minute; NRB, non-rebreathe (facemask); PGD, patient group direction; UTI, urinary tract infection.

In 1991, a consensus definitions conference headed by the American College of Chest Physicians and Society of Critical Care Medicine was convened to provide guidance on nomenclature and diagnosis. For the first time, healthcare practitioners had a precise set of diagnostic criteria with which to identify the presence of sepsis, and an agreement on the terms to be used to describe the process. This, and subsequent revisions, have facilitated not only the recognition and care of these patients, but also epidemiological work, observational studies and research into their care. The systemic inflammatory response syndrome criteria originating from the 1991 conference have since been revised. In 2001, a second consensus conference bringing together the Society of Critical Care Medicine, European Society of Intensive Care Medicine, American College of Chest Physicians, American Thoracic Society and Surgical Infection Society expanded the list of diagnostic criteria for sepsis.22

The temperature range in the prehospital screening tool is 38.3°C and not 38°C. Although the 2001 conference adopted a temperature of greater than 38°C, the SSC has since revised this in light of current consensus to greater than 38.3°C. This is adapted from the 2001 paper with permission of Professor M Levy, the lead author.22 A lactate of greater than 2 mmol/l denotes one of the diagnostic criteria for organ dysfunction to qualify as severe sepsis. A lactate of greater than 4 mmol/l persisting after fluid resuscitation defines shock.22

Similar screening tools appear to be effective in the prehospital setting for identifying patients with conditions such as stroke,23 and many patients are screened for AMI and then receive out-of-hospital thrombolysis.24

In the USA and Canada the role of prehospital staff in sepsis care has already been considered.25 26 In the USA a prehospital sepsis project has also recently been established. This includes a website and a web-based educational training package, which is currently under development.27 The prehospital sepsis project carried out a study to assess the knowledge and attitudes of prehospital care providers about the diagnosis and management of sepsis.28 The study involved 226 advanced emergency medical services providers (82% paramedics, 17.8% nurses and physicians assistants). Four clinical scenarios were used to assess the knowledge of sepsis diagnosis and management. Only 9.8% answered all four scenarios correctly. When asked if they would find a web-based educational package useful, the vast majority of respondents answered “yes” (>180). Respondents were also asked if they would find a portable lactate monitor a useful tool. Over 50% of respondents said that they would find it useful.

The Joint Royal Colleges Ambulance Liaison Committee29 clinical practice guidelines currently do not have a specific guideline for the care of patients with severe sepsis.

High-flow oxygen

Currently recommended by Joint Royal Colleges Ambulance Liaison Committee guidelines for almost all unstable patients.29 Sepsis dramatically increases the body’s metabolic rate and therefore its oxygen requirements—there is little argument against this recommendation. In order to maximise the oxygen available for respiration septic patients should be placed on high-flow oxygen via a non-rebreathe facemask with a reservoir bag. The patient should have their haemoglobin oxygen saturation measured by a pulse oximeter—saturation should be maintained at 94% or greater.17

Measure lactate

Lactate accumulates as a result of anaerobic respiration, due to the physiological demand of the septic state. Lactate has been shown to be a reliable and independent indicator of mortality in sepsis and of admission to the intensive care unit.30 It can be particularly useful as a means of identifying patients with cryptic shock. This occurs when the patient has a raised lactate (>4 mmol/l) indicating tissue hypoxia, but has a normal blood pressure. A recent study in the USA,31 assessed the prevalence of cryptic shock in a cohort of patients transported by emergency medical services with sepsis. The study demonstrated a high prevalence of cryptic shock and recommended that the utility of prehospital point-of-care lactate monitors should be evaluated in an effort to promote the early diagnosis and management of sepsis. The National Academy of Clinical Biochemistry draft guidelines on point-of-care testing conclude that more rapid turnaround times of lactate results in critically ill patients can lead to improved outcomes.32 There are a number of point-of-care lactate measurement devices on the market (Lactate Scout, etc), which are popular with athletes and their coaches. Prehospital lactate measurement could potentially change treatment in a patient with no signs of organ dysfunction other than a raised lactate. The diagnostic benefit of these devices within the prehospital environment has not yet been fully evaluated and this would be a fundamental prerequisite before their adoption into practice.

Blood cultures

Ideally, blood cultures should be taken before the administration of antibiotics as long as this will not cause a significant delay in their administration.5 Obtaining blood cultures before giving antibiotics helps in the identification of the causative organism, as rapid sterilisation of blood cultures occurs within hours of having the first antibiotic dose. Identifying the causative organism facilitates the selection of appropriate antibiotics—significantly reducing the mortality from sepsis.33 Blood cultures could be drawn in the prehospital setting if antibiotics were going to be administered en route to hospital. This may be beneficial in situations such as a rural area, where journey times to the receiving hospital are longer.

Antibiotics

Evidence-based guidelines on the management of severe sepsis recommend that antibiotics should be given within 1 h of diagnosis.5 For the patient with hypotension secondary to sepsis, delays in giving antibiotics can increase mortality by up to 7.6% for each hour’s delay.19 Logic follows that the administration of prehospital antibiotics to this patient group (as long as they are administered in a safe and controlled manner) would improve outcome, particularly when journey times to hospital are longer such as in rural settings. It is worth noting that ambulance staff already give antibiotics via patient group direction for meningococcal septicaemia.29

An excellent starting point could be the prehospital treatment of pneumonia, the most common cause of severe sepsis,34 with more than 50% of hospitalised community-acquired pneumonia patients developing severe sepsis during the course of their disease.35 Furthermore, in patients with community-acquired pneumococcal pneumonia, giving prehospital antibiotic treatment is associated with less severe disease.36

The choice of antibiotics to be administered via patient group direction could be decided locally according to patterns of disease.

Intravenous fluids

Judicious early fluid challenges are key to the management of sepsis.5 Much controversy exists over whether a colloid (eg, Voluven) or a crystalloid (eg, Hartmann’s solution, 0.9% saline) is more appropriate in the acute resuscitative phase. A large meta-analysis of the various clinical trials has yet supplied no conclusive answer to this quandary. In the UK colloid preparations are not available to the majority of prehospital staff, crystalloid is the resuscitative fluid of choice.

If the septic patient is hypotensive, fluid challenges of 10 ml/kg colloid or 20 ml/kg crystalloid are recommended in repeated boluses of 500–1000 ml crystalloid or 300–500 ml colloid with re-assesment of physiological parameters between each bolus.5 7 14 This fluid challenge can be repeated twice, up to a total of three boluses (equivalent to 60 ml/kg crystalloid). Following these boluses, invasive monitoring techniques are recommended—the insertion of central lines in the prehospital setting is not recommended!

Alerting the receiving hospital

Ambulance crews may not always alert hospitals to critically ill patients—up to 56% of critically ill patients arrive at hospital unannounced.37 Tools exist to help ambulance crews identify which trauma patients they should alert hospitals about,29 such guidance does not extend to critically ill medical patients. The use of a prehospital severe sepsis screening tool (fig 1) may help prehospital practitioners identify patients for whom a hospital alert will be beneficial.

Prehospital screening and the initiation of early interventions such as the “sepsis six” may help to alert ED staff to triage these patients appropriately and start time-critical therapy in a timely manner.

CONCLUSION

In the past 2 years there has been a growing call for the emergency care community to support the SSC and in particular the implementation of EGDT into ED.

The care of the critically ill or injured patient often begins in the prehospital setting, and in time-critical conditions such as AMI or stroke, specific interventions by prehospital practitioners make a significant difference to mortality. Severe sepsis is no different—the use of a prehospital severe sepsis screening tool and the implementation of a modified “sepsis six” may significantly improve patient outcomes. The use of portable lactate monitors could aid in the diagnosis of severe sepsis (especially those patients with cryptic shock). The screening tool and interventions have the greatest utility in situations in which rescue times are prolonged, otherwise valuable time may be lost at the scene.

There is a need for further research to explore this field. The initiation of a prehospital sepsis screening tool and modified “sepsis six”, although intuitively improving patient outcomes, needs to be proved in practice in a prospective randomised manner. In addition, the current knowledge of severe sepsis among prehospital staff needs to be assessed—following this the design and implementation of targeted educational packages may be appropriate (this may be effectively delivered on-line). There is a need to look at current clinical guidelines for prehospital practitioners to ensure that the management of severe sepsis is included. Higher education institutions that train prehospital practitioners need to consider the inclusion of severe sepsis in their curriculum.