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September 2, 2016

There is a significant burden of mortality in the modern ICU, typically attributed to a high severity of acute illness and a propensity to secondary complications in those who have a longer stay in critical care. Recent work has demonstrated a progressive reduction in ICU mortality in the resource-rich setting (1), which may be due to a combination of factors.

The aim of this study (2) by Martin-Loeches and colleagues was to investigate which factors influence time to death in hospital in critically ill patients worldwide, including the possible impact of gross national income (GNI). They hypothesised that non-survivors in high-income countries may have longer lengths of stay (LOS) because sophisticated life support is more readily available, and financial resources are sufficient to sustain prolonged organ support – allowing for delays in end-of-life decision-making.

Methods

A predefined post-hoc analysis was conducted of the Intensive Care Over Nations (ICON) database, encompassing adults (>16 years old) in 82 participating countries. These countries were classified into three income groups (low/low middle, upper middle, and high) using the World Bank Atlas classification. Data were collected prospectively between 8th May and 18th May 2012. Patients who stayed in the ICU for <24hours for routine post-operative monitoring were excluded. Non-survivors were categorised into three groups according to the time to death after ICU admission: early (≤5 days), intermediate (6–28 days), or late (≥28-60days).

Results

•    2062 60-day in-hospital non-survivors (22.3%) among the 9258 patients with available data included.
•    Time to death for in-hospital non-survivors was early in 52%, intermediate in 39%, and late in 9%.
•    Patients who died early had higher severity scores and were more likely to require mechanical ventilation on ICU admission.
•    Those who died late were more likely to be older, be surgical patients, or have had an infection on ICU admission or during their ICU stay.
•    Higher gross national income was associated with a stepwise increase in the risk of intermediate or late death on multivariate analysis.
•    Likelihood of late death in high income vs low/lower middle GNI: odds ratio 4.78 (1.94-11.76), p <0.001.
•    Likelihood of late death in upper middle vs low/lower middle GNI: odds ratio 1.64 (1.10-2.45), p =0.02.
•    Countries in the same GNI group had significant inter-hospital variation in risk of late death (p =0.03)

Discussion

This is the first study to investigate the effect of GNI on time to in-hospital death in the critically ill. The results demonstrate that the time to in-hospital death in critically ill patients varies according to GNI, with intermediate and late deaths more common as GNI increases. The authors suggest that these longer times to death may be due to the greater availability of sophisticated life-sustaining technology.

They identify several groups at higher risk of late death. Older patients are more likely to have diminished physiological reserve (3), which may hamper their recovery from critical illness and predispose them to later nosocomial infections. Given that 30 day mortality after surgery is a global quality indicator, this may influence the timing of end-of-life decision-making in these patients (4).

It is of interest that significant inter-hospital variations in late death were seen within the same income group. This suggests that local factors (including timing of end-of-life decisions, views on reversibility of pathology, concepts of an acceptable quality of life, and cultural/legal factors) may influence the timing of death in the critically ill.

This study has several limitations. It was a voluntary registry with an overrepresentation of academic centres. Secondly, data were from a single 10 day period, and so may not be representative of the variation in decision-making between physicians and between seasons. Thirdly, the pre-ICU hospital stay was not characterised, nor was the nature of complications post discharge to the ward. To elucidate the possible explanations for the results described, it would have been useful to have information on variations in end-of-life decision making, as well as the degree of income inequality within the countries studied.

Take home message

The length of hospital stay prior to death in critically ill patients is greater with increased gross national income. It is also greater in older patients, surgical patients, and patients with infection. These findings have important ethical and organisational implications.

Article review prepared by Ehsan Ahmadnia on behalf of the ESICM Journal Review Club.


References

1.    Kaukonen KM, Bailey M, Suzuki S, Pilcher D, Bellomo R. Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000-2012. JAMA. 2014;311(13):1308-1316.
2.    Martin-Loeches I, Wunderink RG, Nanchal R, Lefrant JY, Kapadia F, Sakr Y, Vincent JL, on behalf of the ICON investigators. Determinants of time to death in hospital in critically ill patients around the world. Intensive Care Med 2016; 42:1454–1460.
3.    Bagshaw SM, Stelfox HT, McDermid RC, Rolfson DB, Tsuyuki RT, Baig N, Artiuch B, Ibrahim Q, Stollery DE et al (2014) Association between frailty and short? and long?term outcomes among critically ill patients: a multi? centre prospective cohort study. CMAJ 186:E95–102.
4.    Watters DA, Hollands MJ, Gruen RL, Maoate K, Perndt H, McDougall RJ, Morriss WW, Tangi V, Casey KM, McQueen KA (2015) Perioperative mortality rate (POMR): a global indicator of access to safe surgery and anaesthesia. World J Surg 39:856–864.

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