In this large nationwide registry study on adult patients admitted to Finnish ICUs, we evaluated the patients’ SOFA scores during the first 24 h in the ICU and assessed the prevalence of different organ failures, defined as the organ system-specific SOFA score of 3 or 4, and their associations with mortality. Cardiovascular failure, observed in 53% of patients, was the most common, followed by respiratory failure (23%), neurologic (18%), renal failure (8%), coagulation failure (3%) and hepatic failure (1%). Mortality increased with increasing SOFA scores. However, scores reflecting dysfunctions of different organ systems were not equivalent as metrics of risk. In particular, high cardiovascular SOFA scores did not imply as high a risk of death as high scores of other SOFA components. In addition, OF combinations including cardiovascular failure were associated with lower mortality than other OF combinations: hospital mortality was in the range 25-45% for patients with cardiovascular failure together with another organ failure, whereas mortality exceeded 50% for all other organ failure combinations except the combination of neurologic and respiratory failure (40%).
Our findings contradict those of the 1999 study by the Working Group on Sepsis Related Problems, where cardiovascular SOFA scores contributed more strongly than scores of other components to poor outcomes . However, our results are in accordance with the study by Gupta et al. on 2,796 septic patients with in-hospital mortality of 10%. Coagulation dysfunction or failure predicted a higher and cardiovascular dysfunction or failure a lower risk increase compared to dysfunctions of other organ systems .
Although high SOFA scores often indicate a poor prognosis, cardiovascular scores seem to be an exception. This may reflect a change in clinical practices in recent years. The SOFA score was introduced in an era of more restricted use of vasopressors. During the last two decades, the use of norepinephrine has become more common [23-25]. Vasopressor treatment is initiated earlier without preceding large doses of resuscitation fluids [26-29]. An infusion of norepinephrine lasting at least one hour, even at a small dose, assigns three points to the cardiovascular component of the SOFA score. Moreover, an infusion rate exceeding 0.1 µg/kg/min, which is not a particularly high dose in contemporary intensive care, gives four points. Because of this change in clinical practice, the cardiovascular SOFA score seems to have suffered from inflation. In addition, variations in blood pressure targets and concomitant treatments, particularly sedation, are likely to contribute to the amount of norepinephrine administered and thus to cardiovascular SOFA scores.
The distribution of the cardiovascular SOFA score had two peaks, made up of categories 0−1 and 3−4. A score of 2 was uncommon, present for roughly 1% of the patients. Two cardiovascular SOFA points are scored to patients who are administered dopamine at a dose less than 5 µg/kg/minute or dobutamine at any dose. A number of recent guidelines recommend against or advise specific caution for monotherapy use of these inotropes in circulatory shock [30, 31]. However, administering dopamine to brain-dead organ donors with the intention to support renal function was relatively common in Finland during the study period , which may partly explain the high mortality in this SOFA category.
The impact of the SOFA component scores on mortality seems to be somewhat dependent on the length of follow-up. Hepatic failure was associated with increased ICU mortality but even more remarkably with 12-month mortality. A plausible explanation for this finding is that severe hepatic failure is often an acute-on-chronic type of disease associated with poor long-term prognosis . In the 1999 study by Moreno et al., increased hepatic SOFA scores were the only ones without any association with outcome . However, the endpoint was vital status at ICU discharge. Hepatic failure seems to become more important when the follow-up is longer.
In our study, increased neurologic SOFA scores were associated with both short-term and long-term mortality with no marked change in odds ratios for death over time. In turn, failures of the respiratory, coagulation, cardiovascular and renal organ systems were more strongly associated with short-term mortality than 12-month mortality. This phenomenon was most prominent for cardiovascular OF, which only slightly increased the risk of death within 12 months. Previous studies observing the predictive value of SOFA score have mainly focused on short-term mortality. Pekkarinen et al. observed the association of the first 24 hours extracerebral SOFA scores in cardiac arrest patients with 12-month survival. In line with our findings, they found the cardiovascular SOFA scores as the only ones without association with unfavourable long-term outcome . To the best of our knowledge, however, our study is the first one assessing the predictive value of SOFA score components with a 12-month follow-up in unselected population.
Risk of death increases with an increasing amount of failing organ systems [35, 36]. Our findings imply that some OFs are more likely to occur concurrently than other failures. Moreover, mortality was dependent on which organ systems were failing. The Working group on sepsis-related problems demonstrated a pattern for concurrently occurring organ failures by means of principal components analysis . The group identified two common organ failure combinations. The first combination comprised respiratory, cardiovascular and neurologic OFs, whereas the second comprised coagulation, hepatic and renal OFs. In our study, this first combination of respiratory, cardiovascular and neurologic OFs was also the most common of the combinations with three OFs, affecting 37% of patients with at least three concurrently failing organ systems. However, these three organ systems were most commonly failing systems in general.
Remarkably, we found that the second combination, which comprised coagulation, hepatic and renal OFs, occurred 44 times more often than one would have expected by observing merely the frequency of these organ failures in the whole study population. It is also noteworthy that the most common OF combination with respiratory, cardiovascular and neurologic failures was associated with more favourable outcomes than other combinations of three concurrent OFs. The in-hospital and 12-month mortalities associated with this particular combination were 41% and 55%, respectively, whereas in-hospital and 12-month mortalities of patients with other triple OF combinations ranged between 56-82% and 63-88%, respectively.
Outcomes of ICU patients have improved over the years. In 1998, Vincent et al. reported an ICU mortality of 90% in patients with a SOFA score above 15 , whereas in-hospital mortality for patients with first-day SOFA score above 15 was 72% in our study (Fig. 2).
There is growing interest in employing the SOFA score as a surrogate endpoint for mortality in clinical trials . Our findings suggest that this may not be without problems. Regarding risk of death, weights of different SOFA component scores are different, and the prognosis of patients with multi-organ failure is dependent on which organ systems fail. In addition, different organ failures may have different impacts on long-term mortality despite comparable effects on short-term mortality.
Our study population consisted of a large unselected group of patients treated in Finnish ICUs in 2012-2015. All general ICUs in Finland were included. Therefore, our study population is well representative of Finnish adult ICU patients. We do not know whether the results are generalizable to health care systems in other countries. However, early use of norepinephrine has become more common in other countries as well , and it is likely that the relation between cardiovascular SOFA scores and mortality may have weakened also in other countries.
Strengths and limitations of the study
Our study has several strengths. We performed a nationwide multicentre study with a final cohort of 63,756 patients aged 18 years or older. The data were retrieved from a high-quality national database with all Finnish general ICUs participating.
A major limitation of our study is that the SOFA scores are based only on measurements during the first 24 hours after admission to the ICU, whereas previous studies have shown that a change in SOFA score over time is the most reliable predictor of mortality [37, 38].