Study subjects
The very old intensive care patients (VIP) studies, VIP1 and VIP2, were prospective, multi-centre studies, registered on ClinicalTrials.gov (ID: NTC03134807, NCT03370692). Both studies included very old intensive care patients (VIPs), defined as patients admitted to an ICU and aged 80 years or older. The main results from these studies have been published previously [13, 14, 16, 17]. In summary, for both studies, each participating ICU could include either consecutive patients admitted over a six-month period or the first 20 consecutive patients fulfilling the inclusion criteria (all patients aged 80 years or older). The data collection for VIP1 took place between October 2016 and February 2017 and between May 2018 to May 2019 for VIP2. Both studies used similar inclusion criteria as described elsewhere [13]. Informed consent was obtained from study participants. Local ethical committees might have waived the need of informed consent.
In this post-hoc analysis of these two studies, all patients admitted acutely (non-electively) with complete data on age, gender, clinical frailty score (CFS), sequential organ failure assessment (SOFA) score, and ICU mortality were included. For this study, the elective patients included in VIP1 were excluded as their outcomes differ significantly compared with those admitted acutely, as previously shown [18]. The primary endpoint of this study was ICU-mortality, and the secondary endpoint was 30-day-mortality.
Scales, scores, and limitations in life-sustaining therapy
The SOFA score was recorded on admission; it could be calculated manually or using an online calculator. Frailty was assessed by the clinical frailty scale (CFS). The CSF distinguishes nine classes of frailty from very fit (CFS 1) to terminally ill (CFS 9). The respective visual and simple description for this assessment tool was used with permission [19,20,21].
The Katz Activities of Daily Living (Katz ADL) scale is a widely used graded instrument to assess disability in chronically ill or older patients. It evaluates six primary and psychosocial functions: bathing, dressing, going to the toilet, transferring, feeding, and continence. The patient receives 1 point for every independent and 0 for every dependent activity (6 = independent patient, 0 = very dependent patient). For the patients in the VIP2 trial, disability was defined by Katz ADL score ≤ 4.
For cognitive decline, VIP2 utilised the Short form of Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). IQCODE is a questionnaire, completed by carers, with 16 questions about cognitive decline over the past 10 years. For each question, 1 to 5 points can be assigned. An average of 3 points per question is considered “normal”. A cumulative IQCODE of ≥3.5 is regarded as “cognitive decline” [19,20,21].
The burden of co-morbidity was assessed using the co-morbidity and polypharmacy score (CPS) [22]. The CPS calculates the total number of chronic diagnoses and drugs taken. Standard ICU procedures were also documented.
In addition, limitations of therapy, such as withholding or withdrawing treatment, were recorded. Withholding life-sustaining therapy (e.g. mechanical ventilation, renal replacement therapy, cardiopulmonary resuscitation) was defined as not performing a measure that was indicated; withdrawing was defined as stopping any kind of life-sustaining therapy. All these decisions were at the discretion of the treating physicians and documented according to international recommendations. VIP2 recorded the exact date of treatment limitation, but VIP1 did not give specific details. Thus, the present analysis used withholding or withdrawing treatment as binary information at any time during the ICU-stay.
Statistical analysis
Post-hoc power calculations using the 7110 octogenarians and 790 nonagenarians, primary outcome event rates of 40% versus 45%, and an alpha of 0.05, the power of the study to detect differences in 30-day mortality is 77%. Continuous data points are expressed as median ± interquartile range. Differences between independent groups were calculated using the Mann Whitney U-test. Categorical data are expressed as numbers (percentage). The chi-square test was applied to calculate differences between groups. Sensitivity analysis, analysing only patients with SOFA scores below the 75th percentile SOFA score of 10 (i.e. all patients with SOFA < 10) was performed. Univariable and multivariable logistic regression analysis was performed to assess associations with treatment limitations and mortality. Odds ratios (OR) and adjusted odds ratios (aOR) with respective 95% confidence intervals (CI) were calculated. Two sequential random effects, multilevel logistic regression models were used to evaluate the impact of being a nonagenarian on ICU- and 30-days- mortality. All patients with valid data on ICU-mortality were included. First, a baseline model with being nonagenarian as a fixed effect and ICU as random effect (model-1) was fitted. Second, to model-1, patient characteristics (SOFA, CFS, sex) (model-2) were added to the model. Adjusted odds ratios (aOR) with respective 95% confidence intervals (CI) were calculated. Sensitivity analysis, analysing only patients with and without any treatment limitation was performed. All tests were two-sided, and a p-value of < 0.05 was considered statistically significant. SPSS version 23.0 (IBM, USA) and MedCalc Statistical Software version 19.1.3 (MedCalc Software bv, Ostend, Belgium; https://www.medcalc.org; 2019) were used for all statistical analyses.