MOF is a high mortality rare syndrome by any definition. The annual incidence of MOF was 0.8/100,000 people in NSW, Australia’s most densely populated state, 2% among all major trauma patients, or 23% among the most severely injured at-risk polytrauma patients. Compared to previous cohorts that used the same MOF definition (Denver > 3 after 48 h) and study inclusion criteria, the contemporary incidence of MOF has increased, and in a now a decade older patient population alongside the documented shift from crystalloid to haemostatic resuscitation [6, 12, 13]. This is an extremely high-acuity syndrome. MOF patients stayed a median of 13 days in ICU, 27 days in hospital, with a mortality rate of 25%.

The definition of a rare disease varies between regions and organisations. Among heterogenous prevalence thresholds, it was found that the average definition threshold for a rare disease is 40–50/100,000 people [14]. This qualifies postinjury MOF as a truly rare syndrome among the general population. In contrast, a quarter of the most severely injured patients are expected to develop MOF during their ICU admission. Therefore, MOF demands specific focus for research and advocacy for funding as a sequela to the disease of polytrauma [15, 29].

This study demonstrated that as our population evolves, so too does the epidemiology of MOF. In this severely injured cohort (median ISS = 26), the incidence of MOF was 23%, and the overall mortality rate was 11%. In comparison to previous investigations that used the same MOF definition (Denver > 3) and study inclusion criteria, the incidence of MOF in this cohort was higher than the 13% and 14% incidences of MOF reported by the Denver group between 1990 and 1993 and 2003–2010 respectively [4, 16], and the 15% reported by the Newcastle group between 2007 and 2012 [3]. Expectedly, the overall incidence of MOF in our study was lower than the 33% reported by Frohlich in their analysis of 31,154 patients from the German trauma registry (TR-DGU) between 2002 and 2011 [17]. This may have been due to their use of the more sensitive SOFA to define MOF, and unlike the present study, they also included MOF that was diagnosed within the first 48 h [10]. Interestingly, a recent study by Cole et al. [18]. found that the incidence of MOF was 56% in a point-prevalence study conducted across 29 UK major trauma centers, although they used the same MOF definition of SOFA > 6 (including organ dysfunctions before 48 h, unlike most American and Australian studies) as Frohlich et al. [17].

The 11% overall mortality rate in this study was lower than in the cohort of 31,154 TR-DGU patients by Frohlich et al. [17]. (mortality = 16%, mean ISS = 28), similar to the rate reported by the Denver group (mortality = 8-11%, mean ISS = 24–33), and higher than the rate reported by the Newcastle group earlier (mortality = 6%, mean ISS = 30) [3, 4, 16, 19].

Males comprised 76% of our study population, and continue to predominate the polytrauma cohort. In keeping with temporal trends, the age of patients at-risk continues to rise, with our results suggesting that these polytrauma patients are a decade older than they would have been 20 years ago [17, 19, 20]. Indirectly, a similar mortality rate despite increasing age and its associated comorbidities suggests that our management of MOF is improving.

This study did not identify the apparent historically reported second peak in MOF onset beyond the first few days in hospital. Kaplan-Meier modelling of time-to-MOF demonstrated that with contemporary trauma care, at-risk polytrauma patients would be unlikely to develop postinjury MOF outside of the first fortnight. Seminal reports had initially described postinjury MOF as a bimodal phenomenon, where late MOF, which occurred after the patient was physiologically stabilized following the initial insult, then proceeded to develop MOF after day 3, was postulated to be triggered by ‘second hits’ [11, 21]. The historic second peak in MOF tended to be due to sepsis, primarily abdominal sepsis, and we did not see that in our population. Other potential contributors may include general improvements in critical care, less catheter, maxillofacial sinus, and acalculous cholecystitis related sepsis, and advances in wound management techniques such as freely draining open wounds under vacuum sealed dressings instead of soaked gauze dressings changed in the ICU. Ultimately, we do not know the exact reason why MOF has evolved a unimodal phenomenon, and we may not be able to answer this unless a center sees bimodal distribution.

Our findings corroborate more recent studies showing that the onset of MOF for the most part is early, with 59% of patients in this study developing MOF day 3 [3, 20, 22]. This suggests that our efforts should be focussed on preventing MOF early. Although MOF has evolved into a uniformly early phenomenon, we found that it also represents a continuous burden of low-grade organ dysfunction. The daily proportion of patients from this study who remained in the ICU with organ dysfunction (Denver > 0) was 57%. This residual sub-MOF organ dysfunction is common, and is a potential major contributor to resource consumption in these patients.

We found that the heart was the first and most common organ to fail, in contrast to historical precedents, where the lungs had been reported to be the first and most common organ to fail. Regel et al. [23]. found that the lungs were the first to fail in 20/39 (64%) MOF patients (74% MOF patients had lung failures overall), whereas the heart was the first organ to fail in just 5/39 (13%) of MOF patients (21% of MOF patients had cardiac failures overall). Faist et al. [24]. postulated that MOF was not possible without the catalyst of respiratory failure. In their study of 433 polytrauma patients, 8% developed MOF, all of whom developed respiratory failure, among whom the mortality was 55%. In contrast, cardiac failures occurred in only 12% of MOF patients, although mortality in this subgroup was 75%. Two recent short inclusion term prospective cohort studies conducted in the United Kingdom reported that respiratory and cardiac failures were the first and second most common organ failures in 245 MOF patients (97% respiratory and 91% cardiac) [25] and 860 MOF patients (92% respiratory and 77% cardiac) respectively per the SOFA definition [18]. By comparison, only 39/136 (29%) of our MOF patients acquired respiratory failure. However, patients with respiratory failure had the longest hospital stays. Patients with renal and hepatic failures had the highest mortality. This may be because cardiac and respiratory failures were earlier phenomena, meaning that by the time the kidneys and liver failed, that the odds of death were higher. Furthermore, the threshold to define kidneys and liver failure may be disproportionately higher relative to the cardiac and respiratory failure on the spectrum of dysfunction compatible with life [26,27,28]. While these possible explanations are speculative at this stage, this study has identified the epidemiology of each individual organ failure, which can serve to improve definitions and investigate specific causes of organ failures in isolation and in combinations.

This study had several limitations. Although differences in patient management can occur between centers, one aim of this observational study was to describe the contemporary population-based epidemiology of MOF to provide a benchmark our progress in the management of MOF, provide a baseline for future power analyses. Whilst the Denver > 3 is a sensitive, validated and frequently utilized MOF definition in trauma cohorts, it has lower sensitivity than the SOFA, which is another common definition more frequently used for mixed ICU cohorts. While all participating centres were oriented to record inotrope medication only when used for supporting cardiac contractility instead of systemic vascular resistance or cerebral perfusion pressure, there is a chance of slight over-reporting of cardiac failure. Statistical modelling of time-to-MOF as binary phenomenon are blunt measures of continuous biological processes that fluctuate around a threshold on any scoring system.