Mortality 7 years after prolonged treatment on a surgical intensive care unit

DOI: https://doi.org/10.4414/SMW.2022.w30144

Introduction

“An intensive care unit is an organized system for the provision of care to critically ill patients that provides intensive and specialized medical and nursing care, an enhanced capacity for monitoring, and multiple modalities of physiologic organ support to sustain life during a period of acute organ system insufficiency” is the definition of an intensive care unit (ICU) according to the Task Force of the World Federation of Societies of Intensive and Critical Care Medicine [1]. This definition clearly states the tasks of intensive care medicine and ICUs including the monitoring, maintenance and, if necessary, replacement of vital functions. Usually, patients are treated in an ICU for only a few days. However, a small proportion requires a longer treatment period, with 5–10% of all patients developing a persistent or chronic critical illness [2–5]. Reasons for prolonged intensive care treatment may include: (1) absence of efficacious therapy for an underlying long-term disease, which is not immediately lethal; (2) complications during the ICU stay (e.g., persistent single-organ failure, cascade of multiorgan failure, prolonged mechanical ventilation due to muscle weakness or persistent delirium); and (3) system factors (e.g., patients cannot be transferred to the ward, patients with unrealistic expectations, lack of palliative care facilities) [5].

Long-term treatment in an ICU confers a substantial physical, psychological and social burden on patients and their relatives [6]. The treatment team can also reach its limits, and the costs of long-term intensive care treatment are considerable [7–9]. Stricker et al. showed that 11% of patients (583 out of 4898) who were treated >7 days in a mixed ICU consumed over 50% of the available resources [10]. A study from the USA found that patients (142 out of 2618, 5.4%) who received intensive care after heart surgery for 10 or more days accounted for 50% of the treatment days and caused 48% of the direct ICU costs [11]. Given these high costs in addition to the considerable burden on the patients receiving long-term intensive treatment, their families and caregivers, it is essential to know the outcome and to establish factors that possibly can predict mortality.

This study examined the mortality of patients who were treated continuously for 7 or more consecutive days in the surgical ICU of the University Hospital Basel and how survivors differ from the deceased in terms of various parameters. Only a few Swiss studies address this issue previously [10, 12, 13].

Methods

Design, setting and objectives

This retrospective observational study was performed in the 22-bed ICU of the University Hospital of Basel, a Swiss tertiary academic medical care centre, which treated approximately 2500 mainly surgical and trauma patients per year at the time of study. As there is no generally accepted definition of prolonged ICU stay [8, 14] (supplementary table S1 in the appendix), all patients who were treated in the surgical ICU for at least 7 consecutive days between 1 January 2011 and 31 December 2012 were included. The Ethics Committee of Northwest and Central Switzerland (EKNZ) approved this study (2018-00184). The objectives of this study were to assess mortality in the ICU and the nursing department in the year following the beginning of ICU treatment, and until the cut-off-date (30 September 2018) (fig. 1). We sought to identify factors associated with 1-year mortality.

Figure 1 Flow chart of included patients. ICU: intensive care unit

Data collection

Patient data, including patient age and sex, main surgical and secondary diagnoses, admission status, severity of illness using the simplified acute physiology score (SAPS II) [15], measurement of the nursing workload according to the nine equivalents of nursing manpower use score (NEMS) [16], ICU complications, ICU treatments including the duration, and hospital outcome, were collected from the patients’ charts. Survival after discharge was determined by hospital records or by contact with registration office or the family doctor. Follow-up was closed on 30 September 2018.

ICU complications were defined as follows: delirium as a transient, usually reversible, global cognitive dysfunction (screening for delirium was made using the Intensive Care Delirium Screening Checklist (ICDSC) every 8 hours); stroke as new ischaemic or haemorrhagic cerebral event evidenced on computed tomography (CT); tracheobronchitis as an inflammation of the airways between the larynx and the bronchioles; pneumonia as an inflammation of the lung tissue accompanied by infiltration of alveoli; pleural empyema as a collection of pus in the pleural cavity; acute respiratory distress syndrome (ARDS) as acute onset of respiratory failure, bilateral infiltrates on chest radiograph, and hypoxaemia; septic shock as persisting hypotension requiring vasopressors, and a serum lactate level >2 mmol/l (18 mg/dl) despite adequate volume resuscitation; acute renal failure as an acute increase of creatinine of >26.4 μmol/l (0.3 mg/dl), a percentage increase creatinine >50%, or a reduction of urine output; acute on chronic renal insufficiency as increased serum creatinine by 50% or more from index serum creatinine prior to this acute illness, critical illness polyneuropathy as a peripheral neuropathy involving both motor and sensory fibres accompanied by limb and respiratory muscle weakness.

Statistical analysis

Variables were summarised by comparing patients who survived less than one year with patients who survived longer than one year. We compared between these groups using the chi-square test for nominal variables. Continuous variables were compared using t-tests or, if strongly skewed, using the non-parametric Kruskal-Wallis test. No correction for multiple testing (i.e., alpha inflation) was performed. For normally distributed numerical variables, mean and standard deviation (SD) were calculated. For non-normal numerical data, median and interquartile range (IQR) were computed. Categorical data are summarised in percent. Kaplan-Meier curves including a table for number at risk were fit to compare survival of groups concerning age, with and without comorbidities, complications, and treatment. All statistical analyses were performed using R Statistical Language and Environment.

Results

In the years 2011 and 2012, a total of 4926 patients were treated in the examined ICU. Of the 4676 patients (94.9%) requiring short-term care, 147 (3.2%) died during their ICU stay. A total of 250 patients (5.1%) needed a treatment of ≥7 consecutive days, three of whom were lost to follow up. Therefore, further evaluation included 247 patients (fig. 1).

Fifty-two long-term patients (21.1%) died in the ICU, 25 (10.1%) after transfer to the normal ward (table 1). Thirty-one patients (12.5%) died within 1 year after the beginning of intensive care treatmen. Altogether, the 1-year mortality was 43.7% (108 patients) (table 2). At the end of follow-up after 6 to 7 years, 99 patients (40.1%) were still alive (table 1).

The median age of all long-term patients was 66 years (IQR 56–75) and two thirds were men. Almost 70% of them were admitted to the hospital as emergency patients. The median length of stay of was 12.7 days (IQR 9.0–18.6), the mean SAPS-II was 48.7 points (SD 17.3) and the mean NEMS 1467.4 points (SD 1092.1). Eighty-four patients (34%) were treated more than once in the ICU. Ninety-nine patients (40.1%) underwent heart surgery; 39 (15.8%) were post-abdominal surgery patients. A total of 42 patients suffered a polytrauma (31 patients, 12.6%) or isolated traumatic brain injury (11 patients, 4.5%). All other diagnosis groups included less than 10% of patients for each group. More than 90% of patients with polytrauma survived until the cut-off date. Among cardiac surgery patients, 37 of 99 patients (37.4%), and after abdominal surgery, 11 of 39 patients (28.2%) survived. All 15 patients who underwent lung surgery died.

Delirium occurred in more than half of the patients (140 patients, 56.7%). Eighty-four patients (34.0%) suffered from septic shock, 62 (25.1%) from tracheobronchitis, 96 (38.9%) from pneumonia, and 74 (30.0%) from acute renal failure. On average, 2.4 complications occurred per patient. Almost all patients (232 patients, 93.9%) were transferred intubated to the ICU or were intubated at least once during the course of treatment. Median ventilation time was 7 days (IQR 4–11). Seventy-three patients (29.2%) had to be tracheotomised. Renal replacement therapy (RRT) was necessary in 54 patients (21.9%), an intra-aortic balloon pump (IABP) in 25 (10.1%, corresponding to 25% of the cardiac surgery patients), an extracorporeal membrane oxygenation (ECMO) device in 9 (3.6%), and an intracranial pressure (ICP) measurement in 28 (11.3%) (table 1).

Patients who died within one year of beginning treatment in the ICU were significantly older (median 71 vs 63 years, p <0.001), had a higher Charlson comorbidity index (CCI) (mean 2.3 vs 1.2, p <0.001), a longer ICU stay (median 13.9 vs 10.6 days, p = 0.001), a higher SAPS-II (mean 52.7 vs 45.6, p = 0.001), a higher NEMS (mean 1772.4 vs 1230.4, p <0.001) and more complications (mean 2.9 vs 2.0, p <0.001) compared with those surviving at least one year. Moreover, the deceased more frequently developed pneumonia (50.9% vs 29.5%, p = 0.001), pleural empyema (13.0% vs 2.9%, p = 0.005), septic shock (51.9% vs 20.1%, p <0.001), or critical illness polyneuropathy (16.7% vs 2.9%, p <0.001). They also more frequently required RRT (30.6% vs 15.1%, p = 0.006) (table 2).

Supplementary table S1 (appendix) lists patients with different treatment times. Ninety-two patients (37.2%) received intensive care for 7–9 days, 60 patients (24.3%) for 10–14 days, 49 patients (19.8%) for 15–20 days, and 46 patients (18.6%) for ≥21 days. The mortality among the four groups in the ICU or after transfer to the normal ward was 18.5%, 32.7%, 40.8% and 43.4% and increased until follow-up to 53.3%, 60%, 59.2% and 73.9%, respectively.

The four Kaplan-Meier curves comparing patient mortality in age groups >65 years and <66 years, patients with a CCI ≤3 or >4, patients with or without septic shock, and patients who received ≥2 treatments compared with just one are shown in figure 2. Short vertical lines crossing the curves indicate censoring (i.e., right censoring indicates end of follow-up). Tables below each Kaplan-Meier curve indicate the number of patients “at risk”, which corresponds to the number of patients still alive at this time point. The numbers at the 7-year time point are fragmentary, as not all patients were observed for 7 years in total.

Figure 2 Kaplan-Meier curves for age, Charlson comorbidity index, septic shock, and number of treatments.

Discussion

This study examines mortality after an ICU treatment of 7 or more consecutive days. Seventy-six of the 247 (30.8%) patients died in hospital, and another 32 (12.9%) within one year. At the end of follow-up, at least 6.6 years after the beginning of intensive care treatment, 99 patients (40.1%) were still alive. One-year mortality was significantly higher with increased age, higher CCI, longer length of ICU treatment, higher SAPS-II and NEMS score, the occurrence of pneumonia, sepsis or critical illness polyneuropathy, the need for RRT, and a higher number of complications.

As there is no generally accepted definition of prolonged ICU stay (PrLOS) [8, 14], we selected 7 days as the cut-off for long-term ICU treatment in this study. If the disease is more severe or if complications occur, ICU treatment can be prolonged, sometimes massively. The acute critical illness then turns into a persistent or chronic critical illness. Iwashyna et al. [17] defined a persistent critical illness as “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.” In a single-centre cohort study in Australia, Williams et al. found the long-term mortality to reach a plateau after 10 days of ICU treatment [18]. Baghsaw et al. determined this transition point to be approximately 9 days after ICU admission in a cohort of about 18,000 patients in 12 Canadian ICUs [19]. This point can show a wide range. Iwashyna and colleagues found it between day 7 and day 22 across diagnosis-based subgroups and between day 6 and day 15 across risk-of-death-based subgroups [8]. A retrospective observational cohort study of three large Anglo-American intensive care databases showed that the probability of future survival does not decrease further after 5 to 10 days, except for patients older than 75 years [14]. A cut-off of 7 days, therefore, seems to be an adequate threshold for PrLOS.

Obviously, this is not the first study examining the outcome of patients with a PrLOS. Supplementary table S2 summarises 32 of these studies. Only studies that also investigated factors associated with short- or long-term mortality were included. This includes 11 studies from the USA [9, 11, 20–28], six from Germany [29–34], three from Canada [35–37], two from Sweden [38, 39], and one each from Scotland [40], Switzerland [12], Italy [41], Israel [42], France [43], Austria [44], Belgium [45], New Zealand [46] and Taiwan [47]. Nine studies examined a mixed ICU [20, 34, 36, 40, 43–46, 48], three a surgical ICU [30, 32, 47] and five studies examined the outcome after trauma [9, 23, 24, 26, 28]. Most studies investigated patients after heart surgery [11, 12, 21, 22, 25, 27, 29, 33, 35, 37–39, 41, 42]. The definition of a PrLOS shows a wide variation. The number of days defined as cut-off varies from 3 to 90 days. A stay of at least 7 days [22, 29, 33, 41, 46] and more than 30 days were chosen most often [9, 26, 36, 40, 44]. Eight studies compared different groups of days [21, 23, 25, 27, 28, 31, 34, 45]. Despite a rather wide variation in hospital mortality, there is a trend towards increasing mortality with longer treatment time. If the length of stay is <10 days, hospital mortality is most often less than 18%. Exceptions include very old patients (hospital mortality 23.8%) [35] and patients on mechanical ventilation for longer than 7 days (hospital mortality) [41]. All but seven studies had a follow-up after 6 months to 5 years. Except for a few studies, total mortality at follow-up exceeded 50%, sometimes considerably. Trauma patients represent an exception, having a good short- and long-term prognosis, with a survival rate of usually over 90% [23, 28].

Many factors were shown to be associated with short or long-term mortality. Age [9, 20, 23, 24, 26, 28–30, 32, 34, 36, 39–42, 46, 48] and acute renal failure with or without renal replacement therapy [12, 20–23, 26, 27, 30, 31, 33, 36, 37, 39, 42–47] were found most frequently. Length of mechanical ventilation was associated with mortality in 10 studies [12, 22, 29, 32, 33, 36, 37, 41, 43, 45]. Length of the ICU or hospital stay was shown to be associated with short- or long-term mortality five times [33–35, 37, 42], and APACHE-II score [32, 35, 46, 48] and perioperative stroke four times [22, 23, 25, 42]. Other associated factors such as perioperative infarction [23, 29, 42], or the CCI [31] were reported less often.

These findings correlate well with the present study. Age, acute renal failure and the length of ICU stay were dominant in our data as well as in other studies, and the mortality of our patients – short- and long-term – was comparable. It is not surprising that age is associated with 1-year mortality. Some studies focussed particularly on outcome of older patients. Octogenarians after cardiac surgery and an ICU stay of at least 5 days have higher hospital mortality than those with a shorter stay (23.8% vs 5.5%) and a significantly lower 1- and 5-year functional survival [35]. In a review article, Conti et al. examined the outcome of elderly patients after intensive care treatment [49]. The 22 included studies had very different definitions to describe “elderly”, ranging from 65 to 90 years. Long-term mortality increased with older age. If mortality is adjusted according to disease severity and comorbidities, the difference diminishes. In recent years, the concept of frailty (i.e., the combination of decreased mobility, weakness, reduced muscle mass, poor nutritional status and diminished cognitive function) has received increasing attention and has been shown to have a prognostic value [50]. In a 2017 systematic review by Muscedere et al., both hospital and long-term mortality of frail patients was higher and discharge home less likely in 10 observational studies examining the outcome of frail patients after intensive care treatment [51]. Acute renal failure – particularly if RRT is needed – is the second important factor that can indicate a bad outcome after PrLOS [52]. It is often the result of septic shock and triggers a cascade of systemic effects by release of cytokines and inflammatory mediators [53]. In recent years several strategies to prevent acute renal failure have been proposed that have the potential to improve outcome [54, 55]. Surprisingly, delirium was more often observed in the group of 1-year survivors. In a systematic review of 42 studies, Salluh et al. found increased hospital mortality in ICU patients with delirium [56]. One possible explanation for our contradictory results is the longer period of mechanical ventilation in those patients who died in the ICU compared with those who survived at least one year (median 10 vs 7 days). A delirium could have been masked by intubation and sedation. 

Efforts were made to identify patients at risk for PrLOS or increased mortality. Wesch et al. presented a risk score assessed at day 7 for predicting a PrLOS for more than 20 days. This score includes the factors mechanical ventilation for >14 hours (98 points), need for parenteral nutrition on day 7 (36 points), lowest albumin <20 g/l (28 points), and a CCI >2 (23 points) with a cut-off at 100 points (sensitivity 88%, specificity 75%) [57]. The ProVent risk model uses the variables age >65 years (2 points), age 50–64 years (1 point), platelet count <150,000 /ml (1 point), vasopressors (1 point), haemodialysis (1 point) for patients requiring at least 21 days of mechanical ventilation [20]. A score >2 identifies patients who are at high risk of death within one year. For patients at risk for PrLOS, multimodal care management can optimise care and treatment [3, 57]. An evidence-based assessment and treatment plan includes early mobilisation, adapted nutrition, neurorehabilitation, scheduling daily activities and maintaining a diary. Ethical case discussions support the critical care team in end-of-life decision making for patients at high risk of death in hospital or soon after discharge [58, 59].

This study has some limitations. As a retrospective observational study involving one institution, the results cannot be generalised. It is possible that factors specific to this ICU will not be found in other ICUs. Our study focused on mortality, but this is only one important outcome. In recent years, quality of life after prolonged treatment in ICU has gained increasing attention.

Conclusion

Sixty percent of the patients who are treated for 7 or more consecutive days on a surgical ICU die within 7 years. One-year mortality (43.7%) is associated with age, CCI, length of ICU treatment, SAPS-II and NEMS scores, the occurrence of pneumonia, sepsis, critical illness polyneuropathy, the need for RRT and the number of complications. Scores combined with factors shown to be associated with increased short- and long-term mortality can help to identify patients at risk to die within one year after ICU treatment.

Acknowledgements

The authors thank Allison Dwileski, BS (Scientific Secretary, Department for Anesthesia, Intermediate Care, Prehospital Emergency Medicine and Pain Therapy, University Hospital Basel, Basel, Switzerland) for providing editorial assistance.

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Appendix: Supplementary tables