Timing of onset and burden of persistent critical illness in Australia and New Zealand: a retrospective, population-based, observational study

Summary

Background

Critical care physicians recognise persistent critical illness as a specific syndrome, yet few data exist for the timing of the transition from acute to persistent critical illness. Defining the onset of persistent critical illness as the time at which diagnosis and illness severity at intensive care unit (ICU) arrival no longer predict outcome better than do simple pre-ICU patient characteristics, we measured the timing of this onset at a population level in Australia and New Zealand, and the variation therein, and assessed the characteristics, burden of care, and hospital outcomes of patients with persistent critical illness.

Methods

In this retrospective, population-based, observational study, we used data for ICU admission in Australia and New Zealand from the Australian and New Zealand Intensive Care Society Adult Patient Database. We included all patients older than 16 years of age admitted to a participating ICU. We excluded patients transferred from another hospital and those admitted to an ICU for palliative care or awaiting organ donation. The primary outcome was in-hospital mortality. Using statistical methods in evenly split development and validation samples for risk score development, we examined the ability of characteristics to predict in-hospital mortality.

Findings

Between Jan, 2000, and Dec, 2014, we studied 1 028 235 critically ill patients from 182 ICUs across Australia and New Zealand. Among patients still in an ICU, admission diagnosis and physiological derangements, which accurately predicted outcome on admission (area under the receiver operating characteristics curve 0·898 [95% CI 0·897–0·899] in the validation cohort), progressively lost their predictive ability and no longer predicted outcome more accurately than did simple antecedent patient characteristics (eg, age, sex, or chronic health status) after 10 days in the ICU, thus empirically defining the onset of persistent critical illness. This transition occurred between day 7 and day 22 across diagnosis-based subgroups and between day 6 and day 15 across risk-of-death-based subgroups. Cases of persistent critical illness accounted for only 51 509 (5·0%) of the 1 028 235 patients admitted to an ICU, but for 1 029 345 (32·8%) of 3 138 432 ICU bed-days and 2 197 108 (14·7%) of 14 961 693 hospital bed-days. Overall, 12 625 (24·5%) of 51 509 patients with persistent critical illness died and only 23 968 (46·5%) of 51 509 were discharged home.

Interpretation

Onset of persistent critical illness can be empirically measured at a population level. Patients with this condition consume vast resources, have high mortality, have much less chance of returning home than do typical ICU patients, and require dedicated future research. ICU clinicians should be aware that the risk of in-hospital mortality can change quickly over the first 2 weeks of an ICU course and be sure to incorporate such changes in their decision making and prognostication.

Funding

None.

Introduction

Patients can be intensive care unit (ICU) dependent in the sense that they are unable to survive for more than a few days without receipt of critical care. Such patients (or subsets of them) have been variously labelled as persistently critically ill,1, 2 chronically critically ill,3, 4, 5, 6, 7, 8 chronically medically complex,⁹ requiring prolonged mechanical ventilation,10, 11, 12, 13, 14 or long-stay patients.15, 16, 17 ICU clinicians find that care of such patients is stressful, expect outcomes to be poor, and suspect that care is not cost-effective.² Clinical trials, alternative models of care (eg, long-term acute care hospitals), and payment reform have been considered to improve the care of these patients.¹⁴ These efforts are a response to a new and increasing problem, which is a direct consequence of the advancement of medical science's ability to preserve life without restoring full function.

However, little evidence exists for how patients transition from acute critical illness to this new state. The timing and characteristics of this transition are not known at either the individual or population level. Such ignorance hampers mechanistic investigations, evidence-based clinical trial enrolment criteria, and accurate prognostic communication. Most existing labels of these patients have simply stipulated ad-hoc choices of timing based on expert opinion.¹⁴

We worked with the definition of persistent critical illness as occurring when a patient's “reason for being in ICU is now more related to their ongoing critical illness than their original reason for admission to the ICU”.² This definition had face and content validity in a survey of more than 100 ICU clinicians² and is amenable to population-level epidemiological measurement and cross-system comparison. We hypothesised that, among patients still alive and in an ICU, onset of persistent critical illness can be empirically identified as the day during critical illness beyond which admission diagnosis and physiological illness severity cease to predict outcome more accurately than do simple antecedent patient characteristics. We tested if such a transition exists for in-hospital mortality, measured its timing and the variation therein, and assessed the characteristics, burden of care, and hospital outcomes of patients with persistent critical illness.

Research in context

Evidence before this study

Damuth and colleagues published a systematic review on patients with prolonged mechanical ventilation, results of which showed wide variability in the length of time used to define “prolonged”. Before this study, we published a narrative review of different concepts of critical illness. We also did a survey of Australian and New Zealand intensive care unit (ICU) clinicians that revealed that persistent critical illness was believed to develop after a median of 10 days (IQR 7–14) and to be somewhat uncommon (occurring in 10% of all ICU patients [5–15]). From our engagement with relevant literature in the previous decade, we knew that few data existed providing an empirical test of the persistent critical illness hypothesis: that a day exists during critical illness beyond which admission diagnosis and physiological illness severity cease to predict outcome more accurately than do simple antecedent patient characteristics. Likewise, no data existed measuring the date of such transition if it occurred.

Added value of this study

This study uses binational data from many ICUs and patients and separate derivation and validation samples to minimise the potential for overfitting during risk score development. These data show that the transition point hypothesised to define persistent critical illness does in fact exist and occurred in this population as a whole after 10 days in the ICU. This study showed that patients staying in the ICU for 10 days or more, while accounting for only 5% of all ICU patients, use a very disproportionate amount of ICU resources and have outcomes that are markedly worse than are those for patients staying in the ICU for less than 10 days.

Implications of all the available evidence

Persistent critical illness can be empirically defined at a population level with a clinically relevant definition. In patients with persistent critical illness, the prognostic significance of admission diagnosis and severity of illness is markedly attenuated; by contrast, pre-ICU factors are more associated with their likelihood of in-hospital risk of death than are admission diagnosis and severity of illness. Clinicians should be aware of the risk of anchoring bias in their decision making and prognostication in the face of such rapidly changing prognostic factors. Future research should examine the mechanisms of persistent critical illness, develop and validate patient-level case definitions, and test strategies for prevention and salvage of persistent critical illness.