Sepsis Pathophysiological & Organisational Timing

Overview

This project proposes to measure delay to admission to Intensive Care (ICU). Delays in the United Kingdom NHS are widely reported possibly because there are fewer ICU beds than in many other developed health care systems. Patients are inevitably admitted with more severe illness. Scores measuring this severity are used for research and benchmarking. However, although patients deteriorate over time, severity is probably neither directly nor linearly related to the duration of illness. Instead it is likely that the characteristics of severity change with time. In sepsis there is good biological evidence of this so that there is an early pro-inflammatory stage followed by later changes in metabolic, neuroendocrine, and immune systems. In addition to examining the effect of duration of illness prior to ICU admission, the investigators will also therefore investigate how severity changes over time. SPOT(Light) is a prospective observational study. Treatment is not modified in anyway. Patients evaluated on the ward by critical care outreach teams, and subsequently admitted to critical care will be eligible. Severity of illness at the time of initial evaluation and eventual admission will be compared, and the effect of the duration of illness on 90 day survival investigated.

It is useful to consider time in critical illness from two perspectives. The first of these begins logically with onset of the pathology. With the exception of conditions such as myocardial infarction or trauma where this moment is marked by a classic symptom or an external event, then defining time zero is difficult. For this reason, an organisational frame of reference, such as hospital admission or time of referral to specialist team, is more commonly used. Delay following this organisational time is important because it is often a modifiable factor with regard to the delivery of health care. However, pathophysiological timing remains relevant because if the disease process is dynamic (and this is part of the hypothesis of this study) then it determines the phenotype of disease at any particular moment. This project proposes to measure delay to admission to Intensive Care (ICU) using both organisational and pathophysiological timing. Delays in the United Kingdom NHS are widely reported {McQuillan:1998p127, Hillman:2001p90} possibly because there are fewer ICU beds than in many other developed health care systems.{Wunsch:2008p121} We intend to measure the chronological time between the moment when a patient is 'referred and assessed as requiring Critical Care', and their actual time of admission. We will determine how often delays occur, and whether they affect outcome. Requirements for critical care are not, however, absolute. Importantly, the assessment of a prospective patient is not made in isolation. If ICU beds are already fully occupied, then decision makers must organise a transfer to another unit (with risks to the patient), organise a premature discharge of another patient, or defer admission. We will also therefore consider such deferments alongside delays, and their impact on survival. In addition, the project will consider pathophysiological timing. This is of particular importance in sepsis where current biological models suggest that there is a phased response to infection.{Riedemann:2003p82} In this case, it is possible that patients are admitted to critical care at different phases of disease; moreover, these phases may be clinically relevant and affect response to treatment. pathophysiological delay will be estimated using the concept of illness trajectories (which also may have a biological correlate){Osuchowski:2006p2107}. This means that a patient who is slowly deteriorating is likely to have been ill for longer. In other words, their pathophysiological time zero will be earlier than another patient who is is rapidly deteriorating. This illness trajectory will be estimated by measuring the change in severity of illness between ward assessment and ICU admission. The effect of these illness trajectories, and therefore of the pathophysiological timing of ICU admission, will be evaluated with particular attention to severe sepsis.