Sepsis: a hidden healthcare problem

Sepsis is a syndrome which most health workers have heard of, but which few can describe accurately. It is characterised by an overwhelming inflammatory response secondary to an infection, most commonly arising in the lungs, abdomen or soft tissues, which unchecked will lead to organ dysfunction and death. The term represents a spectrum of disease, from ‘uncomplicated’ sepsis wherein a systemic inflammatory response is triggered by a new infection, through the development of one or more organ dysfunctions as a result of the inflammatory response (termed severe sepsis) through to the greatest severity disease present when multi-organ failure, and/or the subset of severe sepsis characterised by septic shock, ensue. It has only been 21 years since consensus was reached as to what defines sepsis.1,2 Thus, as a disease entity amenable to clinical research and improvement, it is relatively new, and the lack of awareness is understandable. It is not yet clearly understood whether all cases of sepsis will proceed to severe sepsis if unchecked, and there is some evidence that septic shock is triggered by differing pathways. But it is logical (and based on significant evidence) that early recognition and intervention will improve outcomes. Addressing this is of vital importance – patients with severe sepsis have an associated mortality of between 20% and 30% and represent the population at greatest risk of unchecked deterioration in our hospitals. Sepsis is a major killer in the UK. The incidence of severe sepsis (sepsis-induced organ dysfunction) in the EU has been estimated at 90.4 cases per 100,000 population, as opposed to 58 per 100,000 for breast cancer,3 and some estimates are far higher.4,5 Data from the Intensive Care National Audit and Research Centre (ICNARC) in 20056 demonstrated that over 8,300 intensive care patients died from severe sepsis in a six month period, though not all ICUs contributed data and only Level 3 patients were included (many patients are not treated in Level 3 facilities.)7 The 37,000 annual deaths we estimate to occur means that sepsis is likely to claim more lives than lung cancer, and more lives than breast, bowel and prostate cancers combined. The mean current risk of death for patients admitted to ITU with severe sepsis, according to ICNARC data, is around 32%. Shockingly, we appear to accept chaotic performance in delivery of care to these patients who are among our most seriously ill. The NHS is failing patients with sepsis, a situation it shares with the majority of developed health systems. International standards published in 2004 (revised in 2008, and about to undergo a further revision) by the Surviving Sepsis Campaign8,9 were distilled into two care bundles in collaboration with the Institute for Healthcare Improvement. These bundles, and the guidelines they represent, were adopted by over 20 professional bodies around the world, including the European Society of Intensive Care Medicine as the care standard. Yet, after a dedicated and funded international improvement programme over two years, and the voluntary submission of data sets from over 15,000 care episodes, compliance with the most widely-known of these bundles increased from 10.9% to just 21.5%.10 Data submitted by the remaining UK centres to the Surviving Sepsis Campaign after the study period ceased showed that compliance had fallen to just 14%. Fewer than one in seven patients currently receive care according to international standards. Critical Care Units (incorporating Intensive Care and High Dependency Care in most UK hospitals) comprise one of the most expensive areas to care for a patient. A large part of this expense – over 50% – arises from the high nurse-topatient ratio needed to provide the required level of care. Most units in the UK estimate that a typical bed day costs around £1,500. The cost for patients with severe sepsis is likely to be higher due to their greater dependency. It has been estimated in European studies that a typical episode of severe sepsis costs a healthcare organisation approximately Z25,000.11 Assuming that we see 100,000 cases of severe sepsis per annum, this equates to a direct cost to the NHS of over £2.3 bn.

Standards of care

The Resuscitation Bundle (Fig. 1) focuses on the first six hours following presentation of a patient with sepsis and encompasses basic aspects of care (including the sampling of blood cultures and administration of broad spectrum antibiotics within one hour) and a more aggressive targeted resuscitation bundle termed ‘Early Goal-Directed Therapy’ (EGDT) for those patients with septic shock. EGDT demands the insertion of a central venous catheter, and for many patients requires the administration of vasoactive infusions. The inclusion of EGDT, according to a protocol devised by Emanuel Rivers in 2001, was based upon the marked outcome benefits seen in his well conducted but single-centre randomised controlled trial.12 Unsurprisingly, EGDT as the ‘sexier’ end of the Resuscitation Bundle has generated far more discussion than the importance of reliable delivery of rapid, basic aspects of care, particularly in the emergency and acute medicine communities. Three major multi-centre studies are currently evaluating the external validity of Rivers’ protocol, with one of these also exploring an alternative strategy for early targeted therapy.13-15 It is unlikely that any of these will confirm that Rivers’ protocol is the ultimate answer, but it is likely that EGDT is here to stay. Despite Rivers demonstrating a 16% absolute risk reduction for mortality, the use of EGDT to restore the circulation in septic shock will achieve little without adequate pathogen recognition investigations, antimicrobial administration and source control strategies. These basic aspects of care are often neglected. In a landmark paper, Kumar showed that each hour’s delay in antibiotic administration in septic shock was associated with a 7.6% increased risk of death.16 Median time to delivery in this retrospective study, however, was six hours, and only 12% of patients received their antibiotics within the recommended one hour. More recently, it has been shown that patients receiving appropriate antibiotics within the first hour had an odds ratio for death of 0.3 compared with those receiving antibiotics later, but again only 15.7% of patients received their antibiotics according to international recommendations.17 Intravenous fluid resuscitation is a central tenet of sepsis management, aiming to restore the circulation through replacing relative (through vasodilatation) and absolute (through capillary leakage) reductions in circulating volume. EGDT mandates the delivery of fluid challenges of significant volume – 20-60 mL per kg body weight – in septic shock, but even in patients with septic shock this is unreliably achieved. In patients without shock, and particularly in those yet to develop shock, the delivery of intravenous fluids is less directed, meaning that patients may have to wait until their physiology deteriorates to the prescribed level before receiving optimal care.