Long-term survival after intensive care unit discharge in Thailand: a retrospective study

Hospital mortality amongst intensive care unit (ICU) patients is high throughout the world, typically ranging from 14 to 44% [1‐6]; in Thailand the reported range is between 24 and 40% [5‐7]. Interventions to improve the quality of ICU care have the potential to reduce this mortality. Examples of such interventions include development of clinical guidelines [8, 9], improvements to infection control practices [10], and appropriate use of medical devices [11].

There is growing interest not just in the effectiveness of such interventions at reducing mortality, but in their cost-effectiveness, and formal economic evaluation is increasingly used to aid decisions about allocation of scarce health care resources in these settings [12]. Such analyses consider both costs of the interventions and the associated health benefits. Outcomes such as the number of life years (LYs) or quality adjusted life years (QALYs) gained or disability adjusted life years (DALYs) averted are commonly used to represent the benefit of particular interventions. However, to estimate the change in LYs caused by preventing a single ICU death, estimates of post-ICU survival are needed. A number of studies have assessed long-term survival (defined as survival for at least one year post-ICU discharge) [2, 13‐29]. All but one of these studies were conducted in high-income countries and high quality data are lacking from lower and middle income countries [26]. The aim of this study was to quantify the long-term survival of post-ICU patients in Thailand and to estimate life expectancy (LE) in this population.

There were 11,985 adult patients admitted to an ICU in Sappasithiprasong Hospital between 2004 and 2005 and discharged before 1 January 2006. After verifying the hospital dataset, 1,664 patients (13.9%) were not eligible for this analysis due to missing data, incomplete or invalid ID numbers, or coming from other countries (and therefore not recorded in the regional mortality records). As a result, 10,321 patients were included in this analysis. There were 7,223 patients who were discharged alive from the ICU; 153 of these died within two days and were counted as ICU deaths. Of these 61 (39.9%) died at the hospital and 92 (60.1%) died at home. We studied five-year survival in the remaining 7,070 patients who were discharged from the ICU alive (31.5% ICU fatality rate). Patient-flow is shown in Figure 1. Demographics and ICD10 codes in the group of patients who were discharged alive differed slightly from those in patients who died within the ICU (Table 1). In contrast, the group of post-ICU patients who died within five years of discharge tended to be older and much less likely to have ICD10 codes relating to injury, poison and other external causes than those who were alive after five years (Table 2). Of the 7,070 patients who were discharged alive, 79.3% survived the first year, then 74.0%, 70.3%, 66.9% and 64.2% survived each subsequent year (Figure 2). Overall, within five years, 2,527 of the original 7,070 (35.7%) had died. The Kaplan-Meier survival curve indicated a greatly elevated risk of death in the first year post-ICU discharge, with 9.5% (241 of 2,527) of all deaths occurring within seven days. Of these, 67 (27.8%) died at the hospital and 174 (72.2%) died at home. Of the total 2,527 deaths over five years, 21.4% (540) occurred within the first month, 35.5% (896) within three months, 46.0% (1,162) within six months, and 57.9% (1,464) within the first year. Mortality rates became close to those in the general population between years two to five after ICU discharge. The annual risks of death for each year during these periods were 0.21, 0.07, 0.05, 0.05 and 0.04, respectively. In the general population, the annual risk of death (matched for age and sex with those discharged alive from the ICU) was 0.03. Overall, half of the post-ICU patients would have been expected to die within 12.1 years of ICU discharge under base case assumptions. In a sample of the general population matched for age and sex, half would be expected to die within 21.2 years (Figure 3). The LE under base case assumptions and the sensitivity analysis are presented in Table 3. The overall LE amongst post-ICU patients was estimated to be 18.3 years while the LE in the general population (matched for age and sex) was estimated to be 25.2 years. The sensitivity analysis yielded estimates of LE 1.6% higher than under the base case assumption.

Survival categorised by specific diagnostic categories is presented in Figure 4 and Table 4. The lowest survival within six months of discharge was seen in patients admitted with cerebrovascular disease, though at five years post-discharge the lowest survival (33.6%) was seen in patients with neoplasms. The highest survival rates were consistently seen in those admitted due to injury, poisoning or other external causes; 86.5% of patients in this group survived at least five years.

In the systematic search for studies of long-term survival amongst post-ICU patients in low and middle income countries, we found only one study evaluating post-ICU survival across all diagnostic categories [26]. This study followed up 187 post-ICU patients in Malaysia for two years. It was reported that 97 of 105 post-ICU patients (92.4%) who responded to a questionnaire survived for two years. However, the high loss to follow-up in this study (43.8%, 82 from 187) makes interpretation of these findings difficult.

This study found that post-ICU patients had a substantially higher mortality rate (and substantially reduced LE) compared to the general population, with most of the difference seen in the first year post-discharge. Overall, the LE among the post-ICU patients was estimated to be seven years lower than in the general population and the number of life years gained from preventing one ICU death was found to be about two-thirds that from preventing one death in the general population (matched for age and sex).

Results from this study are broadly consistent with those from previous studies conducted elsewhere in high-income countries [2, 13, 14, 16‐18, 36‐38]. Our estimate that cumulative mortality over the five years was 35.7% (or 2.5 times higher than in an age- and sex-matched general population) is slightly higher but comparable with estimates from previous studies which found that the five years cumulative mortality rate ranged from 17.9 to 33.5% [2, 13, 14, 16‐18, 36‐38]. Our estimate of the risk of death in year five, 0.04, is at the upper end of the range estimated in studies conducted in high-income countries (0.01 to 0.04) [14, 36, 37]. The mortality rates among post-ICU patients in our study were high in the first 12 months, then decreased rapidly, and were projected to closely approximate those of the general population by year eight post-ICU discharge. Studies conducted in Finland, Norway and Scotland [13, 36, 37] also demonstrated substantially greater risk of death during the first year, but these became similar to the general population within one to four years. On the other hand, studies conducted in the United Kingdom [16] and Australia [38] found that the mortality rate amongst former ICU patients was higher than the general population over a 5-year and 15-year follow-up period, respectively.

There are several possible reasons for differences in the time for post-ICU mortality rates to approach those in the general population. Firstly, there was considerable variation between the studies in the frequency of different diagnostic categories. Our study had a relatively high proportion of patients with ICD10 codes relating to injury, poisoning and other external causes (23% compared to a range of 7 to 15% in other studies) [18, 36‐38]. Conversely, there was a low proportion of patients with ICD10 codes relating to the respiratory system (5% compared with a range of 8 to 36%) [13, 36, 37]. Figure 4 suggests that these differences are likely to be associated with both a shorter period for post-ICU mortality to approach that in the general population and a relatively high five-year post-ICU survival rate.

Quality of care in different settings [39, 40] is another possible factor that could impact on long-term survival rates. Higher quality of care should reduce ICU mortality, but could potentially either increase or decrease the long-term survival in patients discharged alive from ICU. The latter could occur if higher quality of care prevents ICU deaths in patients with poor long-term prognosis (where some of these patients would have died in the ICU if in lower quality of care settings). Quantifying such competing effects is challenging, but important for evaluating the cost-effectiveness of interventions to improve quality of ICU care in low and middle income countries.

Currently, however, there are few studies of long-term survival following ICU stays in lower and middle income countries. While the systematic search identified a small number of studies evaluating long-term survival following ICU discharge in specific diagnostic categories (liver transplants, myocardial infarction, metastatic solid cancer, chronic obstructive pulmonary disease) [41‐45], long-term follow-up of representative ICU cohorts was lacking.

Our analysis accounted for the common practice in Southeast Asia of discharging moribund patients to die at home by classifying deaths occurring within two days of discharge as ICU deaths. The two-day cut-off was chosen because post-ICU mortality showed a clear spike on day two post-discharge (with 116 deaths, or 1.12% of total ICU patients) but showed a gradual decline from day three (48 (0.47%), 46 (0.45%), 36 (0.35%), 28 (0.27%) and 29 (0.28%) for days three to seven, respectively). This resulted in only slightly higher ICU mortality than would have been obtained had we only considered deaths occurring during the admission (31.5% versus 30.0% mortality, or 153 more deaths), and consequently, slightly lower cumulative five-year mortality amongst the non-ICU deaths (37.1% versus 35.7%).

The mortality rates during years six and seven post-ICU discharge are likely to be somewhat lower than assumed in the base case (which assumed the same relative risk for death as in year five), but somewhat higher than assumed in the sensitivity analysis (which assumed a relative risk of one). However, these two assumptions yielded estimates of LE that differed by less than 2% (Table 3) indicating that improved estimates of mortality in years six and seven would have negligible impact on the results.

Interestingly, among individuals over 75 years of age, the mortality rate was higher in the post-ICU group than in the general population in the first two years, but lower in the following years, resulting in a slightly longer LE than the general population. This might be explained by the possibility that these patients are on average healthier than the general population, having survived their ICU admission.

This study represents one of the first attempts to estimate long-term post-ICU survival in a developing country context. Post-ICU patients had higher mortality than members of the general population (matched for age and sex) over the five-year follow-up period. The estimated LE is useful for economic evaluations and should support decision-makers considering potential investments in interventions that could prevent unnecessary deaths during ICU or hospital admissions.