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Sepsis at ICU admission does not decrease 30-day survival in very old patients: a post-hoc analysis of the VIP1 multinational cohort study

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Background: The number of intensive care patients aged ≥ 80 years (Very old Intensive Care Patients; VIPs) is growing. VIPs have high mortality and morbidity and the benefits of ICU admission are frequently questioned. Sepsis incidence has risen in recent years and identification of outcomes is of considerable public importance. We aimed to determine whether VIPs admitted for sepsis had different outcomes than those admitted for other acute reasons and identify potential prognostic factors for 30-day survival. Results: This prospective study included VIPs with Sequential Organ Failure Assessment (SOFA) scores ≥ 2 acutely admitted to 307 ICUs in 21 European countries. Of 3869 acutely admitted VIPs, 493 (12.7%) [53.8% male, median age 83 (81-86) years] were admitted for sepsis. Sepsis was defined according to clinical criteria; suspected or demonstrated focus of infection and SOFA score ≥ 2 points. Compared to VIPs admitted for other acute reasons, VIPs admitted for sepsis were younger, had a higher SOFA score (9 vs. 7, p < 0.0001), required more vasoactive drugs [82.2% vs. 55.1%, p < 0.0001] and renal replacement therapies [17.4% vs. 9.9%; p < 0.0001], and had more life-sustaining treatment limitations [37.3% vs. 32.1%; p = 0.02]. Frailty was similar in both groups. Unadjusted 30-day survival was not significantly different between the two groups. After adjustment for age, gender, frailty, and SOFA score, sepsis had no impact on 30-day survival [HR 0.99 (95% CI 0.86-1.15), p = 0.917]. Inverse-probability weight (IPW)-adjusted survival curves for the first 30 days after ICU admission were similar for acute septic and non-septic patients [HR: 1.00 (95% CI 0.87-1.17), p = 0.95]. A matched-pair analysis in which patients with sepsis were matched with two control patients of the same gender with the same age, SOFA score, and level of frailty was also performed. A Cox proportional hazard regression model stratified on the matched pairs showed that 30-day survival was similar in both groups [57.2% (95% CI 52.7-60.7) vs. 57.1% (95% CI 53.7-60.1), p = 0.85]. Conclusions: After adjusting for organ dysfunction, sepsis at admission was not independently associated with decreased 30-day survival in this multinational study of 3869 VIPs. Age, frailty, and SOFA score were independently associated with survival.
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Ibarzetal. Ann. Intensive Care (2020) 10:56
https://doi.org/10.1186/s13613-020-00672-w
RESEARCH
Sepsis atICU admission does notdecrease
30-day survival invery old patients: apost-hoc
analysis oftheVIP1 multinational cohort study
Mercedes Ibarz1* , Ariane Boumendil2, Lenneke E. M. Haas3, Marian Irazabal4, Hans Flaatten5,28,
Dylan W. de Lange6, Alessandro Morandi7,8, Finn H. Andersen9,10, Guido Bertolini11, Maurizio Cecconi12,13,
Steffen Christensen14, Loredana Faraldi15, Jesper Fjølner14, Christian Jung16, Brian Marsh17, Rui Moreno18,
Sandra Oeyen19, Christina Agwald Öhman20, Bernardo Bollen Pinto21, Ivo W. Soliman6, Wojciech Szczeklik22,
Andreas Valentin23, Ximena Watson24, Tilemachos Zaferidis25, Bertrand Guidet2,26, Antonio Artigas1,4,27 and the
VIP1 study
Abstract
Background: The number of intensive care patients aged 80 years (Very old Intensive Care Patients; VIPs) is grow-
ing. VIPs have high mortality and morbidity and the benefits of ICU admission are frequently questioned. Sepsis
incidence has risen in recent years and identification of outcomes is of considerable public importance. We aimed to
determine whether VIPs admitted for sepsis had different outcomes than those admitted for other acute reasons and
identify potential prognostic factors for 30-day survival.
Results: This prospective study included VIPs with Sequential Organ Failure Assessment (SOFA) scores 2 acutely
admitted to 307 ICUs in 21 European countries. Of 3869 acutely admitted VIPs, 493 (12.7%) [53.8% male, median age
83 (81–86) years] were admitted for sepsis. Sepsis was defined according to clinical criteria; suspected or demon-
strated focus of infection and SOFA score 2 points. Compared to VIPs admitted for other acute reasons, VIPs admit-
ted for sepsis were younger, had a higher SOFA score (9 vs. 7, p < 0.0001), required more vasoactive drugs [82.2% vs.
55.1%, p < 0.0001] and renal replacement therapies [17.4% vs. 9.9%; p < 0.0001], and had more life-sustaining treat-
ment limitations [37.3% vs. 32.1%; p = 0.02]. Frailty was similar in both groups. Unadjusted 30-day survival was not
significantly different between the two groups. After adjustment for age, gender, frailty, and SOFA score, sepsis had no
impact on 30-day survival [HR 0.99 (95% CI 0.86–1.15), p = 0.917]. Inverse-probability weight (IPW)-adjusted survival
curves for the first 30 days after ICU admission were similar for acute septic and non-septic patients [HR: 1.00 (95% CI
0.87–1.17), p = 0.95]. A matched-pair analysis in which patients with sepsis were matched with two control patients
of the same gender with the same age, SOFA score, and level of frailty was also performed. A Cox proportional hazard
regression model stratified on the matched pairs showed that 30-day survival was similar in both groups [57.2% (95%
CI 52.7–60.7) vs. 57.1% (95% CI 53.7–60.1), p = 0.85].
Conclusions: After adjusting for organ dysfunction, sepsis at admission was not independently associated with
decreased 30-day survival in this multinational study of 3869 VIPs. Age, frailty, and SOFA score were independently
associated with survival.
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Open Access
*Correspondence: mibarzvillamayor@gmail.com
1 Department of Intensive Care Medicine, Hospital Universitario Sagrat
Cor, Viladomat 288, 08029 Barcelona, Spain
Full list of author information is available at the end of the article
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Ibarzetal. Ann. Intensive Care (2020) 10:56
Introduction
e proportion of patients aged 80years admitted to
intensive care units (ICU), so-called Very Old Intensive
Care Patients (VIPs), is growing fast due to ageing of the
population [1]. Nowadays, VIPs represent 10% to 20% of
all ICU admissions [27].
Infection is one of the most frequent reasons for acute
ICU admission of older patients, with increasing inci-
dences over the last decades [813]. Sepsis develops
when the host’s response to infection becomes dysregu-
lated and leads to life-threatening organ dysfunction
[14]. Older patients account for a small proportion of the
overall population, but a large proportion of sepsis cases;
about 60% of septic patients are aged > 65years. e inci-
dence of sepsis increases with age and increases steeply
in persons aged 80 years [810]. Very old persons are
at particularly high risk due to pre-existing comorbidi-
ties, impaired immune function (immunosenescence),
sarcopenia, decrease in reserve capacities related to age-
ing, and many times malnutrition and polypharmacy
[810, 15]. Moreover, mortality rates in VIPs with sepsis
are high, with an estimated ICU mortality of 50% to 60%
[6], reaching 92% at 6months in those with circulatory
failure [16]. In addition, survivors are at increased risk of
developing cognitive impairment and functional disabili-
ties, estimated at 16% to 40% [1719].
e relatively high risk of mortality and shorter life
expectancy amongst VIPs with sepsis, combined with
increasing pressure on healthcare facilities including
ICUs, result in uncertainty about the appropriateness of
admitting VIPs with sepsis to ICUs, especially if they are
frail or have severe comorbidities. Given the goal of long-
term survival with a satisfactory quality of life (QoL)
according to patients’ expectations, it is often difficult to
predict the benefits of ICU treatment in VIPs, [19, 20].
To determine whether VIPs with sepsis should be admit-
ted to ICUs, healthcare providers need more information
about outcomes and risk factors [21].
We aimed to determine whether VIPs admitted with
sepsis had a different 30-day outcome than VIPs admit-
ted for other acute reasons and to identify potential prog-
nostic factors for 30-day survival.
Materials andmethods
Study design andsetting
e present study is a post-hoc analysis of the VIP1 mul-
tinational cohort study [1]. Patients with sepsis were
identified as a group of interest and before the end of
the VIP1 study, we decided to analyse the cohort of VIPs
admitted for sepsis versus VIPs admitted for another
acute reason.
In brief, the VIP1 study was a prospective observational
study to measure outcomes in patients aged 80 years
in 311 ICUs in 21 European countries. Each participat-
ing ICU included the first consecutive 20 VIPs admitted
within a 3-month inclusion period; data were collected
between October 2016 and May 2017. A website was
designed to provide information about the study and to
enable data entry using an electronic case record form;
the electronic case record form and database ran on a
secure server at Aarhus University, Denmark. e study
was registered at ClinicalTRials.gov (ID: NCTO3134807).
Participants
From the original VIP1 study, only acute admissions in
patients 80 years of age were eligible. We excluded
patients admitted for postoperative care after planned
surgery; all the other 11 reasons for acute ICU admis-
sions were accepted (Additional file1: TableS1).
Study variables anddata collection
Demographic and clinical characteristics were recorded
for all patients, including age, gender, hospital length of
stay (LOS) prior to ICU admission, LOS in ICU, SOFA
score at admission [22], and frailty measured with the
Clinical Frailty Scale (CFS) [23].
e main outcome variable was survival in the 30days
following ICU admission. We also recorded the use of the
following: invasive mechanical ventilation, non-invasive
ventilation, vasoactive drugs, renal replacement therapies
(RRT), and orders to withhold or withdraw life-sustain-
ing treatment (LST).
Denitions
Admission categories
e most appropriate clinical reason for ICU admission
was chosen by the site investigator from a predefined
list of 11 acute categories (respiratory failure, circulatory
failure, combined respiratory/circulatory failure, sepsis,
severe trauma without head injury, severe trauma with
head injury, isolated head injury, intoxication, non-trau-
matic brain injury, postoperative care after emergency
surgery, or other) (Additional file1: TableS1).
Severe sepsis admission category
Patients were included in sepsis category according to
clinical criteria.
Keywords: Sepsis, Very old, Intensive care, Severity of illness, Outcome, Survival, Mortality
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Ibarzetal. Ann. Intensive Care (2020) 10:56
Clinical criteria adopted since 2015 are ¨suspected or
documented infection and an acute increase of 2 SOFA
points (a proxy for organ dysfunction) ¨. It was updated
in 2016 in sepsis-3 criteria [14]: ¨Sepsis is a life-threat-
ening organ dysfunction caused by a dysregulated host
response to infection. For clinical operationalisation,
organ dysfunction can be represented by an increase in
the Sequential [Sepsis-related] Organ Failure Assessment
(SOFA) score of 2 points or more, which is associated
with a in-hospital mortality greater than 10%”.
Frailty
It was assessed according to the Clinical Frailty Scale
[23]. is scale is composed of nine classes from very fit
to terminally ill (Additional file2: Figure S1). We deter-
mined the frailty level present before hospital admission
and not affected by the acute illness. Patients were classi-
fied according to the CFS as “fit” (CFS 3), “vulnerable”
(CFS = 4), or “frail” (CFS 5).
Statistical analysis
No formal sample-size calculation was performed for
this observational study. Nevertheless, with the number
of subjects included in our sample, to test whether the
hazard ratio of septic vs non-septic patients is equal to
1.5, the power is 99. To test whether survival of septic is
equivalent to that of non-septic patients, the power is 99.
We compared baseline characteristics, treatment,
and outcomes between septic and non-septic VIPs. We
expressed categorical variables as frequencies and per-
centages, and continuous variables as medians and inter-
quartile ranges. ere are no missing values amongst the
variables used in the analysis, except for 2 patients with
missing date of ICU discharge. To compare groups, we
used Chi square tests for categorical variables and the
Mann–Whitney U test for continuous variables.
To study 30-day survival, all patients were censored at
day 30. For patients discharged from the ICU and dead
at day 30, the precise date of death is unknown; for those,
we assumed that the survival time was the middle of the
interval between date of discharge and day 30. is mid-
point imputation is a simple method to deal with inter-
val-censored data and has been shown to give similar
estimates than more advanced methods [24].
Unadjusted survival curves were estimated using
the standard Kaplan–Meier estimator and compared
between groups by means of a log-rank test.
To estimate associations between variables and survival
30days after ICU admission, we used a Cox proportional
hazard regression model. To check the proportional-
ity assumption for each covariate, we plotted the scaled
Schoenfeld residuals against time along with smooth
curves and detected no violation of the assumption.
Inverse probability weights (IPW) were used to produce
survival curves adjusted for covariates [25]. e weights
were estimated using the same covariates included in the
Cox model, namely frailty, age, gender, type of admis-
sion (septic vs. non-septic), and SOFA score to estimate
the weights. Informally, each subject is weighted by the
inverse of the probability of having sepsis or not condi-
tionally on the covariates.
We also performed a matched-pair analysis. For each
septic patient, we identified a non-septic patient of the
same age, gender, level of frailty, and an SOFA score equal
to that of the septic patient plus or minus 0.1. To estimate
associations between sepsis and survival at 30days after
ICU admission in the matched sample, we used a Cox
proportional hazard regression model stratified on the
matched pairs. We plotted the Kaplan–Meier survival
curves of septic and non-septic patients in the matched
sample and used the usual log-rank test to compare the
curves [26].
P values less than 0.05 were considered statistically sig-
nificant. All analyses were performed with R software,
version 3.2.2 (R foundation for Statistical computing).
Results
Participants
e VIP1 study included 5132 VIPs; 5021 (98%) com-
pleted the 30-day follow-up. Amongst patients who com-
pleted the 30-day follow-up, we excluded the 906 (18%)
admitted primarily for postoperative care after elec-
tive surgery. Moreover, we excluded 246 (4.9%) patients
with Sequential (Sepsis-related) Organ Failure Assess-
ment (SOFA) score < 2; thus, we analysed data from 3869
patients (Fig.1). Regions and countries of the included
patients are listed (Additional file3: TableS2).
Patient characteristics
We included 3869 VIPs [median age 84 (82–86) years;
2013 (52%) male; median SOFA score 8 (5–11); 47%
frail; 32.8% with limitations on LST] admitted as acute
patients to 307 ICUs in 21 countries in the context of the
multicentre VIP-1 study. LOS before ICU was 1day (0–3)
(see Table1).
e median number of patients recruited per coun-
try was 143 (range 3–719), and the median number of
patients per ICU was 13 (range 1–67).
Comparison betweenVIPs admitted forsepsis andthose
admitted forother acute reasons
Patients admitted for sepsis accounted for 12.7%
(493/3869); there was no gender difference, but the sepsis
group were younger, had a higher SOFA score on admis-
sion, more often received vasoactive drugs and RRT, but
were less frequently given mechanical ventilation and
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Ibarzetal. Ann. Intensive Care (2020) 10:56
Fig. 1 Study flowchart. VIP1 study [1]. Septic patients: patients admitted to ICU for sepsis; non-septic patients: patients admitted to ICU for another
acute reason. SOFA Sequential Organ Failure Assessment
Table 1 Comparison ofacute patients admitted forsepsis versusacute patients admitted forother reason
LOS length of stay, SO FA S equential Organ Failure Assessment, CFS Clinical Frailty Scale, RRT renal replacement therapy, LST Life-sustaining treatment
a Expressed as median, IQR
No missing values except for length of ICU stay; 2 patients had a missing date of discharge
Admission category All acute patients Other categories Sepsis p value
N (%) 3869 (100%) 3376 (87.3%) 493 (12.7%)
Age (years)a84 (82–86) 84 (82–87) 83 (81–86) < 0.0001
Gender (male) 2013 (52%) 1748 (51.8%) 265 (53.8%) 0.4402
Hospital LOS before ICU (days)a1 (0–3) 1 (0–3) 1 (0–3) 0.4600
SOFA score at admissiona8 (5–11) 7 (5–11) 9 (6–12) < 0.0001
ICU LOS (days)a2.96 (1.17–6.81) 2.88 (1.12–6.67) 3.54 (1.5–8) 0.0036
Frailty (CFS)
Fit (CFS 1–3) 1331 (34.4%) 1166 (34.5%) 165 (33.5%) 0.0737
Vulnerable (CFS 4) 719 (18.6%) 643 (19%) 76 (15.4%)
Frail (CFS 5–9) 1819 (47%) 1567 (46.4%) 252 (51.1%)
Fit or vulnerable 2050 (53%) 1809 (53.6%) 241 (48.9%) 0.0568
Frail 1819 (47%) 1567 (46.4%) 252 (51.1%)
Interventions in ICU
At least 1 intervention 3196 (82.6%) 2760 (81.8%) 436 (88.4%) 0.0003
No interventions 673 (17.4%) 616 (18.2%) 57 (11.6%)
Mechanical ventilation 2087 (53.9%) 1853 (54.9%) 234 (47.5%) 0.0024
Non-invasive ventilation 1047 (27.1%) 939 (27.8%) 108 (21.9%) 0.0069
Vasoactive drugs 2265 (58.5%) 1860 (55.1%) 405 (82.2%) < 0.0001
RRT 421 (10.9%) 335 (9.9%) 86 (17.4%) < 0.0001
Life-sustaining treatment limitations
No LST limitations 2601 (67.2%) 2292 (67.9%) 309 (62.7%) 0.0243
LST limitations 1268 (32.8%) 1084 (32.1%) 184 (37.3%)
Withholding 679 (17.5%) 571 (16.9%) 108 (21.9%) 0.0196
Withdrawing ± withholding 589 (15.2%) 513 (15.2%) 76 (15.4%)
Outcome
ICU mortality 1072 (27.7%) 918 (27.2%) 154 (31.2%) 0.0686
30-day mortality 1577 (40.8%) 1357 (40.2%) 220 (44.6%) 0.0687
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Ibarzetal. Ann. Intensive Care (2020) 10:56
NIV. Limitations of life-sustaining treatment (LST) were
more frequently performed, and LOS was increased in
patients admitted with sepsis (Table1).
Unmatched analysis
No significant differences between groups were observed
in survival after ICU admission (p = 0.1); survival at day 4
was 78.2% (95% CI 74.6–82.0) in septic patients vs. 82.8%
(95% CI 81.5–84.1) in non-septic patients and survival at
day 30 was 54.8% (95% CI 50.5–59.5) in septic patients
vs. 57.8% (95% CI 56.1–59.5) in non-septic VIPs; HR for
septic vs. non-septic patients was 1.13 (95% CI 0.98–1.3),
p = 0.0986. After adjustment for age, frailty, gender, and
SOFA score, sepsis had no effect on survival after ICU
admission [HR: 0.99 (95% CI 0.86–1.15), p = 0.917]
(Table2A).
Inverse-probability weight (IPW)-adjusted survival
curves for the first 30days after ICU admission were sim-
ilar for septic and non-septic patients [HR: 1.00 (95% CI
0.87–1.17), p = 0.947] (Fig.2b).
Inverse-probability weight (IPW) survival curves for
quartiles of the SOFA score in septic and non-septic
patients showed no significant differences (Additional
file4: Figure S2).
Matched analysis
Likewise, 30-day survival in the matched sample (443
septic patients vs. 824 patients without sepsis, 62 patients
had only one match and 55 could not be matched—
Table3) was similar in septic and non-septic VIPs [57.2%
(95% CI 52.7–60.7) vs. 57.1% (95% CI 53.7–60.1); HR:
1.02 (95% CI 0.85–1.22), p = 0.854] (Fig.2c).
Prognostic factors ofsurvival inall acute admitted patients
In the multivariate analysis, age, frailty, and SOFA score
were independently associated with survival, but sepsis
was not (Table2A).
Separate analyses for septic and non-septic patients
yielded similar results (Table2B, C).
A possible centre effect was assessed comparing the
log partial likelihood of a model including only sepsis
and that of the same model integrating a random centre
effect. e p value for the random effect was < 0.001 sug-
gesting a significant random effect across centre. We thus
built a Cox model using the same variables and integrat-
ing a random centre effect. e coefficients and degree of
significance of the parameters are comparable to those
of the model without random effect (Additional file 5:
TableS3).
Discussion
We found that the 30-day survival rate in patients with
sepsis was similar to the survival of patients admitted for
another acute reason. Sepsis, after adjusting for organ
dysfunction, did not significantly influence. Age, frailty,
and SOFA score were the independent factors associated
Table 2 Factors aecting 30-day survival of ICU patients aged 80 years with SOFA 2 at admission, multivariate
analysis
HR (95% CI) p value
A. Results of the Cox analysis considering all acutely admitted patients (n = 3869)
Sepsis 0.99 (0.86–1.15) p = 0.9173
Age (per 5-year increase) 1.16 (1.09–1.25) p < 0.0001
Frailty: vulnerable vs. fit 1.16 (1–1.35) p = 0.0556
Frailty: frail vs. fit 1.47 (1.31–1.66) p < 0.0001
Male vs. female 1.16 (1.05–1.28) p = 0.0043
SOFA score (per one-point increase) 1.13 (1.12–1.14) p < 0.0001
B. Results of the Cox analysis considering only acute patients admitted for sepsis (n = 493)
Age (per 5-year increase) 1.33 (1.1–1.61) p = 0.0029
Frailty: vulnerable vs. fit 1.54 (1.02–2.34) p = 0.0416
Frailty: frail vs. fit 1.47 (1.07–2.02) p = 0.0182
Male vs. female 1.12 (0.85–1.47) p = 0.4202
SOFA score (per one-point increase) 1.13 (1.1–1.17) p < 0.0001
C. Results of the Cox analysis considering only acute patients admitted for other reason than sepsis (n = 3376)
Age (per 5-year increase) 1.14 (1.06–1.23) p = 0.0005
Frailty: vulnerable vs. fit 1.11 (0.95–1.31) p = 0.1939
Frailty: frail vs. fit 1.48 (1.31–1.68) p < 0.0001
Male vs. female 1.16 (1.04–1.3) p = 0.0064
SOFA score (per one-point increase) 1.13 (1.12–1.14) p < 0.0001
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Ibarzetal. Ann. Intensive Care (2020) 10:56
Fig. 2 Kaplan–Meyer survival curves in septic and acute non-septic patients. a Non-adjusted. b Inverse-probability weight (IPW)-adjusted overall
survival (the weights were estimated using frailty, age, gender, type of admission, and SOFA score). c Matched cohort survival analysis
Page 7 of 12
Ibarzetal. Ann. Intensive Care (2020) 10:56
with 30-day survival in patients admitted to ICU for sep-
sis, similar to all acute VIPs with SOFA 2. is prob-
ably indicates that severity of illness (as expressed by the
SOFA score) is the factor that predicts survival indepen-
dently of whether it is due to sepsis or to other reasons.
erefore, admission for sepsis should not be a factor to
limit an ICU admission in this old population.
We collected data from a large cohort in 307 ICUs
from 21 European countries. Sepsis was the main rea-
son for admission in 12.7% of the VIPs, a rate similar to
those reported in previous studies (9–12%) [8, 15, 19,
20, 27]. Our sample was slightly different to the one ana-
lysed in the original VIP1 study, because we excluded
the subgroup of patients admitted after planned surgery
and compared all acute admissions with the sepsis sub-
group. is might explain changes in the results, and in
the significance of the lack of variable gender in the pre-
sent analysis. e original VIP1 paper was designed to
study the occurrence of frailty and to assess its impact
on 30-day mortality in patients 80years of age or older
admitted to European ICUs. e secondary objective was
to report the intensity of care and treatment restrictions
whilst in the ICU in this patient group. e original VIP-1
study demonstrated an inverse relation between frailty
and 30-day mortality and high mortality rates for VIPs
admitted to the ICU with sepsis. We studied and better
characterised the subgroup of very old septic patients,
identifying the variables associated with outcome, rein-
forcing that frailty and severity of illness (SOFA) as well
as age, and are the determinant factors affecting outcome
in VIPs admitted for sepsis. Moreover, we confirmed that
sepsis at admission was not a determinant factor on out-
come in this population with the analysis of a matched
sample with septic and non-septic patients.
Our results are important because relatively few well-
designed studies have addressed the impact of sepsis in
older patients. Reported ICU-survival rates amongst
octogenarians with sepsis vary widely [6, 16, 27, 28], and
the risk factors for mortality in these patients have not
been completely elucidated. A recent systematic review
including 4256 patients aged 80 years from 18 stud-
ies [29] reported mortality rates of 43% in the ICU, 47%
in the hospital, and 68% 1 year after ICU admission.
Reported rates for 30-day mortality range from 30 [27] to
50% [6, 29].
To our knowledge, this is the first study to compare
frequencies of therapeutic interventions, limitations on
life-supporting treatments, risk factors for mortality, and
outcomes between VIPs admitted with sepsis and those
admitted for other acute reasons. In the present study,
elective surgical patients were excluded because various
other publications [23, 2832] demonstrated that such
patients have a better outcome with much lower mortal-
ity rates.
Previous studies reported that limitations on life-
sustaining treatment were applied more frequently and
earlier in aged patients than in younger patients [27],
and moreover, limitations on LST often preceded VIPs’
death in the ICU [27, 33, 34]. However, the intensity
of treatment in VIPs has increased over time, and this
increase has been associated with a decrease in mor-
tality adjusted for severity [3]. e incidence of LST
limitations reported in recent studies ranges from 10 to
27%, being higher in aged patients and reaching 41.6%
in very old, frail patients [3336]. Guidet et al. [37]
studied decisions to limit LST in the VIP-1 cohort and
demonstrated that acute admission, frailty, age, SOFA
score at admission, and country were associated with
the application of limitations. We found that patients
admitted for sepsis received more therapeutic interven-
tions, mainly vasoactive drugs and RRT. Decisions to
Table 3 Description ofthematched sample
443 patients with sepsis were matched to 824 patients without sepsis
62 patients had only one match and 55 could not be matched
Survival was similar; sepsis HR 1.02 (95% CI 0.85–1.22), p = 0.854
LOS length of stay, SO FA S equential Organ Failure Assessment, CFS Clinical Frailty
Score, RRT renal replacement therapy, LST life-sustaining treatment
a Expressed in median, IQR
Admission category Other categories Sepsis p value
N824 443
Age (years)a82 (81–85) 83 (81–85) 0.5618
Gender (male) 435 (52.8%) 233 (52.6%) 0.9941
Hospital LOS before ICU
admission (days)a1 (0–3) 1 (0–3) 0.28
SOFA score at
admissiona8 (6–11) 8 (6–12) 0.5468
ICU LOS (days)a3.29 (1.33–7.85) 3.88 (1.67–8.53) 0.2454
Frailty (CFS) 0.6963
Fit (CFS 1–3) 273 (33.1%) 144 (32.5%)
Vulnerable (CFS 4) 105 (12.7%) 64 (14.4%)
Frail (CFS 5–9) 446 (54.1%) 235 (53%)
Therapeutic interventions in ICU
At least one 723 (87.7%) 389 (87.8%) 0.999
Mechanical ventilation 480 (58.3%) 202 (45.6%) < 0.0001
Non-invasive ventilation 239 (29%) 100 (22.6%) 0.0164
Vasoactive drugs 500 (60,7%) 361 (81.5%) < 0.0001
RRT 115 (14%) 77 (17.4%) 0.1238
Life-sustaining treatment limitations
No LST limitations 568 (68.9%) 286 (64.6%) 0.1284
LST limitations 256 (31.1%) 157 (35.4%)
Withholding 128 (15.5%) 98 (22.1%) 0.0124
Withdrawing ± with-
holding 128 (15.5%) 59 (13.3%)
ICU mortality 239 (29%) 126 (28.4%) 0.8841
30-day mortality 337 (40.9%) 187 (42.2%) 0.6942
Page 8 of 12
Ibarzetal. Ann. Intensive Care (2020) 10:56
limit LST (mainly as withholding therapy) were more
common in septic patients (22% vs 17%) and this could
be explained because they were frailer and had more
organ dysfunction.
Our study’s strengths include its large prospective
sample, multicentre design, international participa-
tion, and acutely admitted non-septic control group.
Furthermore, recruiting all patients prospectively in a
period of 8months reduced time bias.
Our study, however, has several limitations. First,
data in VIP1 study were prospectively collected [1] but
the data analysis on septic patients was retrospectively
done after closure of the database of the original study.
Second, admission categories were mutually exclusive
and the site investigator in every centre decided to
include the patient in one or another category accord-
ing to the main diagnosis. Severe sepsis was defined
according to clinical criteria [14] and we must assume
that the individual ICUs appropriately used this defi-
nition. However, we cannot fully exclude that some
patients may have been misclassified, for example as
acute circulatory or respiratory failure. In other words,
patients with acute or respiratory failure may also have
had a sepsis.
ird, we were not able to analyse the subgroup of
patients with septic shock since lactate levels were not
available in the registry. Anyhow, 82.2% of the septic
patients received vasopressors to maintain a mean arte-
rial pressure of 65mmHg and mean SOFA at admission
was 9. Fourth, the focus of infection was not registered
and occurrence of sepsis after ICU admission was nei-
ther reported. Fifth, we have no data about patients
who were not admitted to the ICU due to triage deci-
sions. Sixth, we did not analyse reasons for LST limi-
tations, because it was not the aim of the study, it is
fully analysed in another article [36]. Seventh, the only
datum about prior health status recorded was frailty, so
no information about comorbidities or previous cogni-
tive status was available. And last, no follow-up of the
patients was performed.
Nevertheless, our results provide insight into the out-
come and factors associated with 30-day survival in VIPs
admitted for sepsis in comparison to VIPs admitted for
other acute reasons. e fact that sepsis at admission,
after adjusting for organ dysfunction, was not indepen-
dently associated with survival suggests that the best
option today is assessing very old patients according to
their age, frailty, and severity of illness, independently of
their diagnostic category. Once admitted to ICU, we can
establish goals of care and reassess the intensity of thera-
peutic interventions after a reasonable period of time,
according to response to treatment, expected outcomes,
and patient/family wishes [38].
Conclusion
Mortality 30days after ICU admission is high in very old
patients admitted with sepsis. However, we did not find
admission for sepsis to be an independent risk factor for
decreased survival. Frailty, older age, and higher SOFA
score at admission were the significant factors associated
with decreased 30-day survival in this population. ere-
fore, sepsis at admission should not be the only determin-
ing factor either in the decision of admission to the ICU
or in the establishment of LST in very elderly patients.
Future research is required to optimise care for these
patients. We also need more information about long-
term survival and quality of life in VIPs admitted for sep-
sis and a reliable risk prediction model.
Supplementary information
Supplementary information accompanies this paper at https ://doi.
org/10.1186/s1361 3-020-00672 -w.
Additional le1: TableS1. Admission acute categories SOFA 2.
Additional le2: Figure S1. Clinical Frailty Scale (CFS).
Additional le3: TableS2. Information about region and country of the
included patients.
Additional le4: Figure S2. Inverse probability weighted survival curves
for quartiles of the SOFA SCORE.
Additional le5: TableS3. Results of the Cox analysis integrating a
random centre effect.
Abbreviations
ICU: Intensive care unit; VIPs: Very Old Intensive Care Patients; RRT : Renal
replacement therapy; SOFA: Sequential Organ Failure Assessment; CFS: Clinical
Frailty Scale; LOS: Length of stay; LST: Life-sustaining treatment; QoL: Quality
of life.
Acknowledgements
VIP1 study contributors: René Schmutz, B5, Hospital of St. John of God Vienna,
Austria; Franz Wimmer, Interne Intensiv, Kardinal Schwarzenberg´sches
Krankenhaus, Austria; Philipp Eller, Intensivstation der Univ.-Klinik für Innere
Medizin, Medical University Graz, Austria; Michael Joannidis, MICU, University
Hospital Innsbruck, Austria; Pieter De Buysscher, Department of Intensive Care,
AZ Sint-Lucas Ghent, Belgium; Nikolaas De Neve, Department of Intensive
Care, O.L.Vrouwhospital Aalst, Belgium; Sandra Oeyen, Department of
Intensive Care, Ghent University Hospital, Belgium; Walter Swinnen,
Department of Intensive Care Medicine, AZ Sint-Blasius Dendermonde,
Belgium; Bernardo Bollen Pinto, Peri-Interventional Intermediate Care (SINPI),
Geneva University Hospitals, Switzerland; Paul Abraham, Adult Intensive Care
(SIA), Geneva University Hospitals, Switzerland; Leila Hergafi, Service des Soins
intensifs, Hôpital Fribourgeois, Fribourg, Switzerland; Joerg C. Schefold,
Universitätsklinik für Intensivmedizin, Inselspital, Bern University Hospital,
University of Bern, Switzerland; Ewelina Biskup, Medical ICU, University
Hospital Basel, Switzerland; Petr Piza, KARIP, IKEM, Czech Republic.; Ioannis
Taliadoros, CY001, Nicosia General Hospital, Cyprus; Jesper Fjølner, ITA, Randers
Regional Hospital, Denmark; Nilanjan Dey, Intensiv Herning, Regions Hospital
Herning, Denmark; Christoffer Sølling, I-25, Regionshospital Viborg, Denmark;
Bodil Steen Rasmussen, ICU, Aalborg University Hospital, Denmark; Steffen
Christensen, OPI Ost, Aarhus University Hospital Skejby, Denmark; Xavier
Forceville, Réanimation médico chirurgical, Centre Hospitalier de Meaux,
France; Guillaume Besch, Département d´Anesthésie Réanimation Chirurgi-
cale, Centre Hospitalier Régional Universtaire de Besançon, France; Herve
Mentec, Service de Réanimation Polyvalente, Centre Hospitalier Victor Dupouy
Argenteuil, France; Philippe Michel, Réanimation médico-chirurgicale, CH
Carnelle - Portes de l’Oise, France; Philippe Mateu, Réanimation Polyvalente,
Page 9 of 12
Ibarzetal. Ann. Intensive Care (2020) 10:56
CH de Charleville-Mézières, France; Philippe Michel, Réanimation médico-
chirurgicale, CH René Dubos, France; Lucie Vettoretti, Réanimation Médicale,
CHRU de Besançon, France; Jeremy Bourenne, Reanimation des Urgences et
Médicale, CHU Marseille - Timone, France; Nathalie MARIN, reanimation
médicale, hopital cochin, France; Max Guillot, Réanimation médicale, Hôpital
de Hautepierre, France; Nadia Aissaoui, Réanimation médicale, hopital
européen georges pompidou, France; Cyril Goulenok, Réanimation Médicale,
Hopital Privé Jacques CARTIER, France; Nathalie Thieulot-Rolin, Intensive care
medicine department, Hospital Marc Jacquet 77,000 Melun, France; Jonathan
Messika, Réanimation Médico-Chirurgicale, Louis Mourier, France; Lionel
Lamhaut, Polyvalente adult ICU, Necker (APHP), France; Bertrand Guidet,
Réanimation médicale, Saint Antoine, France; Cyril Charron, Medical-surgical
ICU, University Hospital Ambroise Paré, de Paris Boulogne-Billancourt, France,
France; Alexander Lauten, 1) Department of Cardiology, 2) DZHK Berlin partner
side, Charité Universitaetsmedizin Berlin, Germany; Anna Lena Sacher,
Department of Anesthesiology, Charité Universitaetsmedizin Berlin, Germany;
Thorsten Brenner, Department of Anesthesiology, Heidelberg University
Hospital, Germany; Marcus Franz, Department of Internal Medicine, Jena
University Hospital, Friedrich-Schiller University, Germany; Frank Bloos,
Department of Anesthesiology, Jena University Hospital, Friedrich-Schiller
University, Germany; Henning Ebelt, Department for Medicine II, Catholic
Hospital “St. Johann Nepomuk”, Germany; Stefan J Schaller, Department of
Anesthesiology, Klinikum rechts der Isar, Technical University of Munich,
Munich, Germany; Kristina Fuest, Department of Anesthesiology, Klinikum
rechts der Isar, Technical University of Munich, Munich, Germany, Germany;
Christian Rabe, Department Of Clinical Toxicology, Klinikum rechts der Isar,
Technical University of Munich, Munich, Germany, Germany; Thorben Dieck,
Department of Anaesthesiology and Intensive Care, Medical School Hospital
Hannover, Germany; Stephan Steiner, Department of Cardiology, Pneumology
and Intensive Care, St. Vincenz Krankenhaus Limburg, Germany; Tobias Graf,
Department of Cardiology, University Heart Center Luebeck, Germany; Amir M
Nia, Division of Cardiology and Intensive Care, University Hospital Düsseldorf,
Heinrich-Heine University, Germany; Christian Jung, Division of Cardiology and
Intensive Care, University Hospital Düsseldorf, Heinrich-Heine University,
Germany; Rolf Alexander Janosi, Department of Cardiology and Vascular
Diseases, University Hospital Essen, Germany; Patrick Meybohm of the
Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy,
Frankfurt University Hospital, Frankfurt, Germany; Philipp Simon, Department
of Anaesthesiology and ICM, University Hospital of Leipzig, Germany; Stefan
Utzolino, Department of General and Visceral Surgery, Universitätsklinikum
Freiburg, Germany; Tim Rahmel, Department of Anaesthesiology, Intensive
Care Medicine, University Hospital Knappschaftskrankenhaus Bochum,
Germany; Eberhard Barth, Department of Anaesthesiology, University of Ulm,
Germany; Christian Jung, University Hospital Düsseldorf, Heinrich-Heine-
University Düsseldorf, Medical Faculty, Division of Cardiology, Pulmonology
and Vascular Medicine, Düsseldorf, Germany, Germany; Michael Schuster,
Department of Anaesthesiology, University Hospital Mainz, Germany; Zoi
Aidoni, ICU, UGHT AHEPA, Greece; Stavros Aloizos, ICU, Army Share Fund
Hospital, Athens, Greece; Polychronis Tasioudis, ICU, G. Gennimatas hospital of
Thessaloniki, Greece; Kleri Lampiri, ICU, General Hospital Of Kavala, Greece;
Vasiliki Zisopoulou, ICU1, General Hospital Of Larissa, Greece; Ifigenia Ravani,
ICU, General hospital of Patras, Greece; Evmorfia Pagaki, ICU, General hospital
of Trikala, Greece; Angela Antoniou, ICU, Volos General Hospital, Greece;
Theodoros A. Katsoulas, ICU, “Ag Anargyroi” General Hospital, Greece; Aikaterini
Kounougeri, ICU, Konstantopouleion General Hospital, Athens, Greece; George
Marinakis, ICU, “Korgialenio-Benakio” G. Hospital of Athens, Greece; Fotios
Tsimpoukas, ICU, Lamia General Hospital, Greece; Anastasia Spyropoulou, ICU,
Panarkadian General Hospital of Tripolis, Greece; Paris Zygoulis, General ICU,
University hospital of Larisa, Greece; Aikaterini Kyparissi, ICU, “HIPPOCRATEIO”
General Hospital of Athens, Greece; Manish Gupta, MICU, MAX SUPER
SPECIALTY HOSPITAL, Vaishali, India; Mohan Gurjar, Department of Critical Care
Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences, India;
Ismail M Maji, MICU, St Johns Medical Colleg Hospital, Bangaluri, India; Ivan
Hayes, CUH GICU, Cork University Hospital, Ireland; Brian Marsh, Department of
Critical Care Medicine, Mater Misericordiae University Hospital, Ireland;
Yvelynne Kelly, General ICU, St. Jamess Hospital, Ireland; Andrew Westbrook,
ICU, St. Vincents University Hospital, Ireland; Gerry Fitzpatrick, Tallaght intensive
Care, Tallaght Hospital, Ireland; Darshana Maheshwari, UHG ICU, University
hospital galway, Ireland; Catherine Motherway, ICU, University Hospital
limerick, Ireland; Giovanni Negri, Rianimazione, A.S.S.T. Covets Milanese
- Presidio Di Magenta - Rosedale G. Forwardly (Magenta), Italy; Savino Spadaro,
Unit di Terapia Intensiva del Serio di Anestesia, Asiana Ospedaliera Universi-
taria Sant Anna (Ferrara), Italy; Guisepepe Nattino, Rianimazione generale,
ASST Lecco - Ospedale A.Manzoni (Lecco), Italy; Matteo Pedeferri, Rianimazi-
one, AO della Provincia di Lecco - Presidio Ospedaliero S.Leopoldo Mandic,
Merate, Italy; Annalisa Boscolo, Giustiniani I e II (Istar), Azienda Ospedaliera di
Padova (Padova), Italy; Simona Rossi, Servizio Anestesia Rianimazione, Azienda
Ospedaliera G.Salvini - Presidio Ospedaliero di Rho, Italy; Giuseppe Calicchio,
Centro di Rianimazione, Azienda Ospedaliera Universitaria San Giovanni di Dio
e Ruggi d’Aragona, Italy; Lucia Cubattoli, Rianimazione Generale, Azienda
Ospedaliera Universitaria Senese (Siena), Italy; Gabriella Di Lascio, Terapia
Intensiva di Emergenza, Azienda Ospedaliero Universitaria Careggi (Firenze),
Italy; Maria Barbagallo, UO 2 Anestesia Rianimazione Terapia Intensiva, Azienda
Ospedaliero-Universitaria di Parma (Parma), Italy; Francesco Berruto,
rianimazione, Ospedale E. Agnelli (Pinerolo), Italy; Daniela Codazzi, Unità
Terapia Intensiva, Fondazione IRCCS Istituto Nazionale dei Tumori (Milano),
Italy; Andrea Bottazzi, Rianimazione 2, Fondazione IRCCS Policlinico S.Matteo
(Pavia), Italy; Paolo Fumagalli, Rianimazione 1, Fondazione Policlinico San
Matteo (Pavia), Italy; Giancarlo Negro, Anestesia e Rianimazione 1, Ospedale
Francesco Ferrari (Casarano), Italy; Giuseppe Lupi, Servizio Anestesia e
Rianimazione, Ospedale Maggiore (Cremona), Italy; Flavia Savelli, Anestesia e
Rianimazione - TI 2, Ospedale Maurizio Bufalini (Cesena), Italy; Giuseppe A.
Vulcano, Terapia Intensiva, Ospedale Civile Nicola Giannettasio (Rossano), Italy;
Roberto Fumagalli, Anestesia e Rianimazione 1, Ospedale Niguarda Ca’ Granda
(Milano), Italy; Andrea Marudi, Rianimazione Neurorianimazione, Nuovo
Ospedale Civile Sant Agostino Estense (Modena), Italy; Ugo Lefons, Terapia
intensiva, Ospedale Alta Val d’Elsa (Poggibonsi), Italy; Rita Lembo, Rianimazi-
one generale, Ospedale Castelli di Verbania (Verbania), Italy; Maria Babini,
Servizio Anestesia e Rianimazione, Ospedale Civile Lugo (Lugo), Italy;
Alessandra Paggioro, Struttura Semplice di Rianimazione e Terapia Intensiva,
Ospedale degli Infermi di Biella - ASL BI (Biella), Italy; Vieri Parrini, Anestesia e
Rianimazione, Ospedale del Mugello (Borgo San Lorenzo), Italy; Maria Zaccaria,
Rianimazione e Terapia Intensiva, Ospedale di Ciriè (Torino), Italy; Stefano
Clementi, terapia intensiva polivalente, Ospedale di Sesto San Giovanni (Sesto
San Giovanni), Italy; Carmelo Gigliuto, Rianimazione, Ospedale di Vigevano
- AziendaOspedaliera della Provincia di Pavia (Vigevano), Italy; Francesca
Facondini, Reparto di Rianimazione e Terapia Intensiva, Ospedale Infermi
(Rimini), Italy; Simonetta Pastorini, Servizio Anestesia-Rianimazione, Ospedale
P. Cosma-AUSL 15 Alta padovana (Camposampiero), Italy; Susanna Munaron,
Unità di Terapia Intensiva, Ospedale San Giacomo (Castelfranco Veneto), Italy;
Italo Calamai, Rianimazione, Ospedale San Giuseppe (Empoli), Italy; Anna
Bocchi, Terapia Intensiva, Ospedale San Luca (Trecenta), Italy; Adele Adorni,
Unità di Terapia Intensiva Rianimatoria, Ospedale Valduce (Como), Italy; Maria
Grazia Bocci, Centro di Rianimazione, Policlinico Agostino Gemelli (Roma),
Italy; Andrea Cortegiani, Unità di Terapia Intensiva Polivalente, Policlinico P.
Giaccone. University of Palermo, Italy; Tariana Casalicchio, Terapia Intensiva,
Hopedale San Giovanni Bosco (Torino), Italy; Serena Melia, Unità di Terapia
Intensiva, Ospedale Santa Maria della Misericordia (Perugia), Italy; Elia Graziani,
Unità Operativa Anestesia e Rianimazione, Santa Maria delle Croci (Ravenna),
Italy; Massimo Barattini, Rianimazione, Ospedale Santa Maria Nuova (Firenze),
Italy; Elisabetta Brizio, Servizio di Rianimazione, Ospedale SS Annunziata, Italy;
Maurizio Rossi, UO Anestesia e Rianimazione, Zenda Ospedaliera Sant’Anna
Como – Presidio di Manage, Italy; Michael Hahn, ICU, Augend hospital,
Norway; Hans Flattens, General ICU, Haukeland University Hospital, Norway;
Nicolai Kemmerer, ICU, Kongsberg hospital, Norway; Hans Frank Streiter, ICU,
Kristiansund Hospital, Norway; Knut Dybwik, ICU, Nordlandssykehuset Bodo,
Norway; Terje Legernaes, ICU, Hamar hospital, Norway; Pål Klepstad, Dept
Intensive Care Medicine, St Olavs University Hospital, Norway; Even Braut
Olaussen, ICU, Stavanger University Hospital, Norway; Knut Inge Olsen, ICU,
Namsos Hospital, Norway; Ole Marius Brresen, ICU, Telemark Hospital, Skien,
Norway; Geir Bjorsvik, ICU, University Hospital Tromso, Norway; Finn H.
Andersen, ICU, Ålesund hospital, Norway; Sameer Maini, Medical ICU,
Aalesund Hospital, Norway; Lutz Fehrle, ICU, Molde hospital, Norway; Mirosław
Czuczwar, 2nd Department of Anesthesiology and Intensive Care Medical
University of Lublin, Poland; Paweł Krawczyk, Department of Anaesthesiology
and Intensive Care Medicine, Jagiellonian University Medical College, Poland;
Mirosław Ziętkiewicz, Department of Anaesthesiology and Intensive Care
Medicine, Jagiellonian University Medical College & Thoracic Anaesthesia and
Respiratory ICU, John Paul II Hospital, Poland; Łukasz R. Nowak, Maria
Skłodowska-Curie Memorial Institute of Oncology, Cancer Centre, Poland;
Katarzyna Kotfis,Department of Anesthesiology, Intensive Therapy and Acute
Intoxications, University Hospital No. 2, Pomeranian Medical University in
Page 10 of 12
Ibarzetal. Ann. Intensive Care (2020) 10:56
Szczecin, Poland; Katarzyna Cwyl, Anesthesia and Intensive Care Unit, Regional
Health Center in Lubin, Poland; Ryszard Gajdosz, Faculty of medicine and
Health Sciences Krakow University A.F. Modrzewski &St.Raphael Hospital,
Department of Anaesthesiology and Intensive Care, Poland; Jowita
Biernawska, Pomeranian Medical University SPSK 1, Clinical Anesthesiology
and Intensive Therapy PUM, Poland; Romuald Bohatyrewicz, Pomeranian
Medical University SPSK 1, Clinical Anesthesiology and Intensive Therapy PUM,
Poland; Ryszard Gawda, Department of Anesthesiology and Intensive Care,
Opole University Hospital, Poland; Paweł Grudzień, Department of Anaesthesi-
ology and Intensive Therapy, Edward Szczeklik Specialist Hospital in Tarnów,
Poland; Paweł Nasiłowski, Department of Anaesthesiology and Intensive
Therapy, Department of Anaesthesiology and Intensive Care, Gabriel
Narutowicz Specialist Hospital in Kraków, Poland; Natalia Popek, Department
of Anaesthesiology and Intensive Therapy, Stefan Żeromski Specialist Hospital
in Kraków, Poland; Waldemar Cyrankiewicz, Department of Anaesthesiology
and Intensive Therapy, Antoni Jurasz University Hospital No. 1 in Bydgoszcz,
Poland; Katarzyna Wawrzyniak, Department of Anaesthesiology and Intensive
Therapy, Antoni Jurasz University Hospital No. 1 in Bydgoszcz, Poland; Marek
Wnuk, Department of Aanesthesiology and Intensive Therapy, John Paul II
Memorial Hospital in Bełchatów, Poland; Dariusz Maciejewski, Faculty of Health
Science, ATH Bielsko-Biała & Department of Anaesthesiology and Intensive
Therapy, Regional Hospital in Bielsko-Biała, Poland; Dorota Studzińska,
Department of Anaesthesiology and Intensive Care, St. John Grande Hospital,
Poland; Maciej Żukowski, Department of Anesthesiology, Intensive Therapy
and Acute Intoxications, University Hospital No. 2, Pomeranian Medical
University in Szczecin, Poland; Szymon Bernas, Department of Anaesthesiol-
ogy and Intensive Therapy Centre for Artificial Extracorporeal Kidney and Liver
Support, Dr Władysław Biegański Regional Specialist Hospital in Łódź, Poland;
Mariusz Piechota, Department of Anaesthesiology and Intensive Therapy
Centre for Artificial Extracorporeal Kidney and Liver Support, Dr Władysław
Biegański Regional Specialist Hospital in Łódź, Poland; Centre for Artificial
Extracorporeal Kidney and Liver Support, Poland; Wojciech Szczeklik,
Department of Intensive Care and Perioperative Medicine, Jagiellonian
University Medical College, Poland; Ilona Nowak-Kózka, Department of
Intensive Care and Perioperative Medicine, Jagiellonian University Medical
College, Poland; Jakub Fronczek, Department of Intensive Care and
Perioperative Medicine, Jagiellonian University Medical College, Poland; Marta
Serwa, Anaesthesia and Intensive Care Clinic, Central Clinical Hospital CKD,
University Medical College in Łódź, Poland; Waldemar Machała, Anaesthesia
and Intensive Care Clinic, Central Clinical Hospital CKD, University Medical
College in Łódź, Poland; Jan Stefaniak, Department of Anaesthesiology and
Intensive Therapy, Medical University of Gdańsk, Faculty of Medicine, Poland;
Maria Wujtewicz, Department of Anaesthesiology and Intensive Therapy,
Medical University of Gdańsk, Faculty of Medicine, Poland; Małgorzata
Szymkowiak, Department of Anaesthesiology and Intensive Therapy, Józef
Struś Specialist Hospital in Poznań, Poland; Barbara Adamik, Department of
Anesthesiology and Intensive Therapy, Wrocław Medical University, Poland;
Kamil Polok, Department of Intensive Care and Perioperative Medicine,
Jagiellonian University Medical College, Poland; Anna Włudarczyk, Depart-
ment of Intensive Care and Perioperative Medicine, Jagiellonian University
Medical College, Poland; Jacek Górka, Department of Intensive Care and
Perioperative Medicine, Jagiellonian University Medical College, Poland;
Natalia Kozera, Department of Anesthesiology and Intensive Therapy, Wroclaw
Medical University, Poland; Waldemar Goździk, Department of Anesthesiology
and Intensive Therapy, Wroclaw Medical University, Poland; Nuno Catorze,
UCIP, C. H. Médio TEJO, Portugal; Miguel Castelo Branco, Unidade de Cuidados
Intensivos, Centro Hospitalar Cova da Beira, EPE, Portugal; Inês Barros, Unidade
de Cuidados Intensivos Polivalente, Centro Hospitalar Tondela-Viseu, Portugal;
Nelson Barros, Serviço Medicina Intensiva, Centro Hospitalar Trás-os-Montes e
Alto Douro, Portugal; Andriy Krystopchuk, Intensive Care and Emergency
Department, Centro Hospitalar do Algarve-Hospital de Faro, Portugal; Teresa
Honrado, Unidade Cuidados INtensivos Polivalente, Hospital de São João,
Portugal; Cristina Sousa, UCI, Hospital da Luz, Portugal; Francisco Munoz, UMI,
Hospital do SAMS, Portugal; Marta Rebelo, UCIP, Hospital de Egas Moniz,
Portugal; Rui Gomes, UCI, Hospital Garcia de Orta, Portugal; Jorge Nunes,
Unidade de Cuidados Intensivos, Hospital Lusiadas Lisboa, Portugal; celeste
dias, Neurocritical ICU, Hospital de São João, Portugal; Ana Margarida
Fernandes, UCI Neurocríticos, Hospital S. José - CHLC EPE, Portugal; Cristina
Petrisor, Anaesthesia and Intensive Care 1, Clinical Emergency County Hospital
Cluj, Portugal; Bodolea Constantin, ATI, Municipal Hospital, Portugal; Vladislav
Belskiy, Department of Anesthesiology and Intensive Care, Privolzhskiy District
Medical Center, Russia; Boris Boskholov, Dept of intensive care, Zhadkevich
Clinical Hospital, Russia; Enver Rodriguez, UCI, General Universitario de
Castellón, Spain; Sergio Rebollo, ICU, HGU Santa Lucia,Cartagena, Murcia,
Spain; Gerardo Aguilar, Unidad de Reanimación - Surgical ICU, Hospital Clínico
Universitario de Valencia, Spain; Gaspar Masdeu, Servei Medicina Intensiva,
Hospital de Tortosa Verge de la Cinta, Spain; Marián Irazábal Jaimes, Critical
Care Unit, Hospital General de Catalunya, Spain; Ángela Prado Mira, Medicina
Intensiva, Hospital General Universitario de Albacete, Spain; Maria A. Bodi,
General ICU, Hospital Universitari de Tarragona Joan XXIII, Spain; Jesus A. Barea
Mendoza, Servicio de Medicina Intensiva, Hospital Universitario 12 de Octubre,
Spain; Sonia López-Cuenca, Servicio de Medicina Intensiva y Grandes
Quemados, Hospital Universitario de Getafe, Spain; Marcela Homez Guzman,
ICU, Hospital Universitario del Henares, Spain; Jesús Rico-Feijoo, Postoperative
Critical Care Unit and Reanimation, Hospital Universitario Río Hortega de
Valladolid, Spain; Mercedes Ibarz, ICU Hospital Universitario Sagrado Corazon,
Barcelona, Spain; Josep Trenado Alvarez, Intensive Care Department.
UCI-Semicritics, Hospital Universitario Mutua Terassa, Spain; Rafael Kawati,
central ICU, Akademiska sjukhuset, Sweden; Joakim Sivik, IVA Alingsås Lasarett,
Alingsås Lasarett, Sweden; den; Joakim Sivik, IVA Alingsås Lasarett, Sweden;
Jessica Nauska, Intensivvårdsavdelning 31, Blekingesjukhuset Karlsk rona,
Sweeden; Daniel Smole, IVA, Centralsjukhuset i Karlstad, Sweden; Fredric
Parenmark, IVA, Gävle sjukhus, Sweden; Johanna Lyrén, Intensivvårdsavdeln-
ing, Hudiksvalls sjukhus, Gävleborg,, Sweden; Katalin Rockstrohm, IVA, Kalmar
Länssjukhus, Sweden; Sara Rydén, Karolinska ICU Huddinge, Karolinska
University Hospital, Sweden; Martin Spångfors, Intensiven, Kristianstad,
Sweden; Morten Strinnholm, ICU KungälvsHospital, Sweden; Sten Walther,
Cardiothoracic ICU, Linköping University Hospital, Sweden; Lina De Geer, ICU,
Linköping University Hospital, Sweden; Peter Nordlund, OP/IVA Kliniken,
Länssjukhuset Ryhov, Sweden; Staffan Pålsson, Intensivvårdsavdelningen,
Norrtälje, Sweden; Harald Zetterquist, IVA, Nyköpings lasarett, Sweden; Annika
Nilsson, IVA, Örnsköldsviks hospital, Sweden; Karin Thiringer, ICU, Sahlgrenska
University Hospital Mölndal, Sweden; Mårten Jungner, ICU SUS Malmö, Skane
University Hospital, Sweden; Björn Bark, IVA Lund, Skåne University Hospital,
Sweden; Berit Nordling, IVA Sundsvall, Sweden; Hans Sköld, ICU, Torsby
Sjukhus, Sweden; Camilla Brorsson, ICU University Hospital Northern Sweden,
Sweden; Stefan Persson, Intensivvårsdavdelningen USÖ, University hospital
Örebro, Sweden; Anna Bergström, ICU Vrinnevi hospital, Sweden; Johan
Berkius, ICU Västerviks hospital, Sweden; Johanna Holmström, ICU Västerås,
Västmanlands hospital, Sweden; I. van Dijk, Intensive Care, Alrijne Ziekenhuis,
The Netherlands; Lenneke E.M. Haas, Intensive Care, Diakonessenhuis Utrecht,
The Netherlands; D.Ramnarain, Intensive Care, Elisabeth Tweesteden Hospital
Tilburg, The Netherlands; Tim Jansen, Intensive Care, HagaZiekenhuis, The
Netherlands; Fleur Nooteboom, IC LZR, Laurentius Ziekenhuis, The Nether-
lands; Peter HJ van der Voort, ICU OLVG, OLVG, The Netherlands; Dylan de
Lange, Department of Intensive Care Medicine, UMC Utrecht, The Netherlands;
Willem Dieperink, Department of Critical Care, University Medical Center
Groningen, The Netherlands; Monique C. de Waard, Intensive Care Adults, VU
University Medical Center Amsterdam, The Netherlands; Annemarie GE de
Smet, Intensive Care Unit, University Medical Centre, University of Groningen,
The Netherlands; Laura Bormans, Intensive Care, Zuyderland Medical Centrer,
Heerlen, The Netherlands; Tom Dormans, Intensive Care, Zuyderland Medical
Center, Heerlen, The Netherlands; Ged Dempsey, Critical Care Unit, Aintree
University Hospital NHS Foundation Trust, UK; Shiju J Mathew, ICU, Alexandra
Hospital, UK; Ashok S Raj, ICU, Barts Health NHS Trust, Whipps Cross Hospital,
UK; Irina Grecu, ITU/HDU, Basingstoke and North Hampshire Hospital, UK;
Jason Cupitt, Critical Care Unit, Blackpool Teaching Hospitals NHS Foundation
Trust, UK; Tom Lawton, Critical Care Unit, Bradford Royal Infirmary, UK; Richard
Clark, ICU, Central Manchester Foundation Trust, UK; Monica Popescu, ICU,
Chelsea and Westminster Foundation Trust, West Middlesex University
Hospital, UK; Nick Spittle, ICU, Chesterfield Royal Hospital, UK; Maria Faulkner,
ICU, Countess of Chester Hospital NHS Foundation Trust, UK; Amanda Cowton,
ICU, Darlington memorial Hospital (CDDFT), UK; Esme Elloway, ICU, Derriford
Hospital, UK; Patricia Williams, Critical Care Unit, Dorset County Hospital, UK;
Michael Reay, Critical Care Unit, Dudley Group of Hospitals NHSFT, Russells Hall
Hospital, UK; Srikanth Chukkambotla, Critical Care Unit, East Lancashire
Hospitals NHS Trust, UK; Ravi Kumar, CCU, East Surrey Hospital, UK; Nawaf
Al-Subaie, ICU, Espsom and St Helier University Hospitals, UK; Linda Kent,
Critical Care Unit, Fairfield General Hospital, UK; Tiina Tamm, ICU, Frimley
Health, Wexham Park Hospital, UK; Istvan Kajtor, ICU, Frimley Park Hospital, UK;
Karen Burns, ICU, Furness General, UK; Richard Pugh, Critical Care Unit, Glan
Clwyd Hospital, UK; Marlies Ostermann, ICU, Guys and St Thomas Hospital, UK;
Page 11 of 12
Ibarzetal. Ann. Intensive Care (2020) 10:56
Elisa Kam, ICU, Hillingdon Hospital, UK; Helen Bowyer, Critical Care Centre,
Hinchingbrooke Healthcare NHS Trust, UK; Neil Smith, HICU 1&2, Hull Royal
Infirmary, UK; Maie Templeton, Critical Care UNIT, Imperial College Healthcare
NHS Trust, UK; Jeremy Henning, ICU2&3, James Cook Univeristy Hospital, UK;
Kelly Goffin, ICU, James Paget University Hospital, UK; Ritoo Kapoor, K&C ITU,
Kent and Canterbury Hospital, UK; Shondipon Laha, CrCU, Lancashire Teaching
Hospitals NHS Foundation Trust, UK; Phil Chilton, Critical Care Unit, Leighton
Hospital, UK; Waqas Khaliq, ITU/HDU, Lewisham and Greenwich NHS Trust, UK;
Alison Crayford, ITU/HDU, Maidstone, UK; Samantha Coetzee, ICU, Medway
NHS Foundation Trust, UK; Moira Tait, Adult ICU, Musgrove Park, UK; Wendy
Stoker, ICU, Northumbria Specialist Emergency Care Hospital, UK; Marc
Gimenez, ICU, Papworth Hospital NHS Foundation Trust, UK; Alan Pope, Critical
Care Unit, Peterborough City Hospital, UK; Julie Camsooksai, Critical Care Unit,
Poole Hospital NHS Trust, UK; David Pogson, Department of Critical Care,
Queen Alexandra Hospital Portsmouth, UK; Kate Quigley, ICU, Queen Elizabeth
Hospital, UK; Jenny Ritzema, Critical Care Department, Queen Elizabeth
Hospital, Gateshead, UK; Anil Hormis, Critical Care Unit, Rotherham NHS
Foundation Trust, UK; Carole Boulanger, ICU, Royal Devon and Exeter NHS
Foundation Trust, UK; M. Balasubramaniam, ICU and HCU, Royal Bolton NHS
hospital trust, UK; Luke Vamplew, Critical Care Unit, Royal Bournemouth
Hospital, UK; Karen Burt, Critical Care Unit, Royal Cornwall Hospital NHS Trust,
UK; Daniel Martin, ICU, Royal Free London NHS Foundation Trust, UK; Irina
Grecu, ICU, Royal Hampshire County Hospital, UK; Jayne Craig, ICU, Royal
Lancaster Infirmary, UK; John Prowle, Adult Critical Care Unit, Royal London
Hospital, UK; Nanci Doyle, ICU, Royal Surrey County Hospital, UK; Jonathon
Shelton, Ward 38 ICU, Royal Victoria Infirmary, UK; Carmen Scott, Ward 18 ICU,
Royal Victoria Infirmary, UK; Phil Donnison, ICU, Salisbury District Hospital, UK;
Sarah Shelton, ICU, Sherwood Forest Hospitals NHS Foundation Trust, UK;
Christian Frey, ITU/HDU, South Tyneside District Hospital, UK; Christine Ryan,
GICU, St Georges Hospital, UK; Dominic Spray, Cardiothoracic ICU, St Georges
Hospital, UK; Christine Ryan, Acute Dependency Unit, St Georges Hospital NHS
Trust London, UK; Veronica Barnes, Neuro ICU, St Georges University Hospital
NHS Foundation Trust, UK; Kerry Barnes, ITU, st helier hospital, UK; Stephanie
Ridgway, Critical Care Unit, NHS Foundation Trust, Tameside General Hospital,
UK; Rajnish Saha, Critical Care Unit, The Princess Alexandra NHS Hospital, UK;
Linda Kent, ICU, The Royal Oldham Hospital, UK; Thomas Clark, ICU, Torbay
Hospital, UK; James Wood, ICU, Tunbridge Wells Hospital, UK; Clare Bolger,
General Intensive Care, Univeristy Hospital Southampton NHS Foundation
Trust, UK; Christopher Bassford, General Critical Care, University Hospital
Coventry, UK; Amanda Cowton, ICU, University hospital of North Durham, UK;
john lewandowski, Critical Care Unit, University Hospital of North Tees, UK;
Xiaobei Zhao, ICU (Level 6), Watford General Hospital/West Hertfortshire NHS
trust, UK; Sally Humphreys, Critical Care, West Suffolk NHS Foundation Trust,
UK; Susan Dowling, Ward 4E Critical Care unit, Whiston, UK; Neil Richardson,
ICU, William Harvey Hospital, Ashford, UK; Andrew Burtenshaw, Critical Care
Unit, Worcestershire Royal Hospital, UK; Carl Stevenson, ICU, Wye Valley NHS
Trust, UK; Danielle Wilcock, Critical Care Unit, York Teaching Hospital NHS
Foundation Trust, UK; Yuiry Nalapko, Anaesthesia and Intensive Care, Lugansk
State Medical University, Ukraine.
Authors’ contributions
MI and AA designed the study. MI, AB, LH, BG, and AA performed the analyses
and drafted and coordinated the manuscript. AB performed the statistical
analyses and helped with interpreting the results and writing the manuscript.
HF was principal investigator of the VIP-1 study, provided his expertise, and
made substantial contributions to the interpretation of the results and to
drafting and revising the manuscript for important intellectual content. JF run
the database and the eCRF. All other authors were country coordinators and
validated the manuscript. All authors read and approved the final manuscript.
Funding
No specific funding was received, but the study was endorsed by the Euro-
pean Society of Intensive Care Medicine.
Availability of data and materials
The datasets generated and/or analysed during the current study are not
publicly available due privacy issues of the study populations.
Ethics approval and consent to participate
An institutional research ethics board at each study site approved the study.
Most patients provided written informed consent before inclusion in the
study but in some countries given its non-interventional nature, informed
consent was waived.
Consent for publication
Not applicable.
Competing interests
None of the authors have competing interests; all authors have read the
current “Instructions to authors” and accept the conditions posed therein.
This manuscript is original and has not been and will not be simultaneously
submitted elsewhere for publication. None of the material from this study is
included in another manuscript, has been published previously, or has been
posted on the internet.
Author details
1 Department of Intensive Care Medicine, Hospital Universitario Sagrat Cor,
Viladomat 288, 08029 Barcelona, Spain. 2 Assistance Publique-Hôpital de Paris,
Hôpital Saint-Antoine, Service de Réanimation Médicale, 75012 Paris, France.
3 Department of Intensive Care Medicine, Diakonessenhuis Utrecht, Utrecht,
The Netherlands. 4 Department of Intensive Care Medicine, Hospital Universi-
tario General de Cataluña, Sant Cugat del Valles, Spain. 5 Department of Anaes-
thesia and Intensive Care, Haukeland University Hospital, Bergen, Norway.
6 Department of Intensive Care Medicine, University Medical Center, University
of Utrecht, Utrecht, The Netherlands. 7 Department of Rehabilitation Hospital
Ancelle di Cremona, Cremona, Italy. 8 Geriatric Research Group, Brescia, Italy.
9 Department of Anaesthesia and Intensive Care, Ålesund Hospital, Ålesund,
Norway. 10 NTNU, Department of Circulation and Medical Imaging, Trondheim,
Norway. 11 Laboratorio di Epidemiologia Clinica, Centro di Coordinamento
GiViTI Dipartimento di Salute Pubblica, IRCCS - Instituto di Ricerche Farma-
cologiche “Mario Negri” Ranica, Bergamo, Italy. 12 Department of Anesthesia
and Intensive Care Medicine, Humanitas Clinical and Research Center - IRCCS,
Via Alessandro 13 Manzoni, 56, 20089 Rozzano, MI, Italy. 13 Department of Bio-
medical Sciences, Humanitas University, Pieve Emanuele, MI, Italy. 14 Depart-
ment of Anaesthesia and Intensive Care Medicine, Aarhus University Hospital,
Aarhus, Denmark. 15 ASST Grande Ospedale Metropolitano Niguarda, Milan,
Italy. 16 Department of Cardiology, Pulmonology and Angiology, University
Hospital, Düsseldorf, Germany. 17 Mater Misericordiae University Hospital,
Dublin, Ireland. 18 Unidade de Cuidados Intensivos Neurocríticos e Trauma,
Hospital de São José, Centro Hospitalar de Lisboa Central, Faculdade de Ciên-
cia Médicas de Lisboa, Nova Médical School, Lisbon, Portugal. 19 Department
of Intensive Care 1K12IC, Ghent University Hospital, Ghent, Belgium. 20 Karo-
linska University Hospital, Stockholm, Sweden. 21 Department of Anaesthesiol-
ogy, Pharmacology and Intensive Care, Geneva University Hospitals, Geneva,
Switzerland. 22 Intensive Care and Perioperative Medicine Division, Jagiellon-
ian University Medical College, Kraków, Poland. 23 Kardinal Schwarzenberg
Hospital, Schwarzach, Austria. 24 St George’s University Hospital, London, UK.
25 Intensive Care Unit General Hospital of Larissa, Larissa, Greece. 26 Sor-
bonne Université, INSERM, Institut Pierre Louis d’Epidémiologie et de Santé
Publique, AP-HP, Paris, France. 27 Department of Intensive Care Medicine, CIBER
Enfermedades Respiratorias, Corporacion Sanitaria Universitaria Parc Tauli,
Autonomous University of Barcelona, Sabadell, Spain. 28 Department of Clini-
cal Medicine, University of Bergen, Bergen, Norway.
Received: 9 October 2019 Accepted: 4 May 2020
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... We found that the SOFA score, and CRP serum levels were the best predictors of in-hospital mortality in our population. This is not surprising given that previous studies have repeatedly demonstrated their association with short-term mortality, both in medical wards and ICU [19,[42][43][44][45][46]. Lactate serum levels also showed good ability to predict in-hospital mortality in the AUROC analyses, but this finding was not confirmed by the multivariate logistic regression. ...
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Background A prognostic stratification of mortality risk in older patients with sepsis admitted to medical wards is often challenging. Aims To evaluate the ability of the Sequential Organ Failure Assessment (SOFA) score, serum biomarkers (lactate and C-Reactive Protein, CRP), and measures of comorbidity and frailty in predicting in-hospital and 6-month mortality in a cohort of older patients admitted to an Acute Geriatric Unit (AGU) with a diagnosis of sepsis. Methods All patients aged 70 years and over consecutively admitted to our AGU with sepsis in the study period were included. At admission, a Comprehensive Geriatric Assessment including two measures of frailty (Clinical Frailty Scale [CFS], Frailty Index [FI]) was obtained. To assess the predictivity of candidate prognostic markers, the Area Under the Receiver-Operating Characteristic (AUROC) curves were analyzed. A multivariate logistic regression analysis was also performed. Results We included 240 patients (median age = 85, IQR = 80–89, 40.8% women), of whom 33.8% died before discharge, and 60.4% at 6 months. The SOFA score (AUROC = 0.678, 95% CI 0.610–0.747) and CRP serum levels (AUROC = 0.606, 95% CI 0.532–0.680) were good predictors of in-hospital mortality. The CFS (AUROC = 0.703, 95% CI 0.637–0.768) and the FI (AUROC = 0.677, 95% CI 0.607–0.746) better predicted 6-month mortality. Results of the regression analysis confirmed the findings of the AUROC study. The combined assessment of SOFA and measures of frailty improved the performance of the model both in the short and the long term. Conclusions Both the severity of organ dysfunction and frailty scores should be addressed on AGU admission to establish the short- and long-term outcomes of older patients with sepsis.
... This increase in mortality in the older population was also independent of comorbidities and the severity of illness at admission, as there was no significant difference in the modified Charlson Comorbidity Index and modified SAPS II between the old and young groups. In contrast, other studies have found no association between age and death (8-9), including a recent post-hoc analysis of the VIP1 multinational cohort in Europe whereby sepsis at admission was not independently associated with 30-day mortality in their very elderly ICU cohort (10). Various factors could have led to a different result being obtained in our local setting, such as variations in patient characteristics, implicated pathogens and their resistance pattern as well as differences in diagnostic and treatment modalities being practised in different settings. ...
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Sepsis is an important cause of morbidity and mortality in elderly patients, but there is a scarcity of data on sepsis in this specific cohort. We performed this study to review the impact of sepsis on outcomes in elderly patients admitted to our local intensive care unit (ICU). This was a secondary analysis of prospectively collected data of 159 consecutive adult patients with sepsis admitted to an ICU of a tertiary hospital in Malaysia over a three-year period. Of the 159 patients analysed, elderly patients constituted 18.9% of the cohort. Fifty percent of the older patients died within 30 days, compared to 24% of younger patients (P = 0.005). On multivariate analysis, old age was found to be independently predictive of 30-day mortality with an adjusted odds ratio (OR) of 2.5 (95% confidence interval [CI]: 1.05, 6.01) compared to younger patients (P = 0.021). In a Kaplan-Meier analysis, survival probability was significantly lower in patients of an older age compared to younger patients (P = 0.015). In conclusion, mortality from sepsis is considerably higher in elderly patients, with age as an independent risk factor for mortality.
... For our analysis, we used the Angus criteria to detect septic patients from a large electronic database of critically ill patients (18). This yielded a large cohort of patients with a relatively low absolute mortality compared to other cohorts evaluating old septic patients-for example, Ibarz et al. (21) recently reported a 43% 30 day-mortality in very old septic patients. The use of the Angus criteria might therefore constitute a limitation to our analysis. ...
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Purpose: Old (>64 years) and very old (>79 years) intensive care patients with sepsis have a high mortality. In the very old, the value of critical care has been questioned. We aimed to compare the mortality, rates of organ support, and the length of stay in old vs. very old patients with sepsis and septic shock in intensive care. Methods: This analysis included 9,385 patients, from the multi-center eICU Collaborative Research Database, with sepsis; 6184 were old (aged 65–79 years), and 3,201 were very old patients (aged 80 years and older). A multi-level logistic regression analysis was used to fit three sequential regression models for the binary primary outcome of ICU mortality. A sensitivity analysis in septic shock patients ( n = 1054) was also conducted. Results: In the very old patients, the median length of stay was shorter (50 ± 67 vs. 56 ± 72 h; p < 0.001), and the rate of a prolonged ICU stay was lower (>168 h; 9 vs. 12%; p < 0.001) than the old patients. The mortality from sepsis was higher in very old patients (13 vs. 11%; p = 0.005), and after multi-variable adjustment being very old was associated with higher odds for ICU mortality (aOR 1.32, 95% CI 1.09–1.59; p = 0.004). In patients with septic shock, mortality was also higher in the very old patients (38 vs. 36%; aOR 1.50, 95% CI 1.10–2.06; p = 0.01). Conclusion: Very old ICU-patients suffer from a slightly higher ICU mortality compared with old ICU-patients. However, despite the statistically significant differences in mortality, the clinical relevance of such minor differences seems to be negligible.
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Probably the most frequently reported outcome in healthcare in general, and in intensive care in particular, is survival or its counterpart mortality. Obviously, other patient-centered outcomes are very often connected and even dependent on a patient that survives. It makes no meaning to talk about quality of life in patients not surviving the ICU stay, but for survivors post-hospital discharge, other issues than merely survival become more and more important.
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Background In older adult patients, bloodstream infections cause significant mortality. However, data on long-term prognosis in very elderly patients are scarce. This study aims to assess 1-year mortality from bacteraemia in very elderly patients. Methods Retrospective cohort study in inpatients aged 80 years or older and suspected of having sepsis. Patients with (n = 336) and without (n = 336) confirmed bacteraemia were matched for age, sex, and date of culture, and their characteristics were compared. All-cause mortality and risk of death were assessed using the adjusted hazard ratio (aHR). Results Compared to controls, cases showed a higher 1-year mortality (34.8% vs. 45.2%) and mortality rate (0.46 vs. 0.69 deaths per person-year). Multivariable analysis showed significant risk of 1-year mortality in patients with bacteraemia (aHR: 1.31, 95% confidence interval [CI] 1.03–1.67), quick Sepsis Related Organ Failure Assessment (qSOFA) score of 2 or more (aHR: 2.71, 95% CI 2.05–3.57), and age of 90 years or older (aHR 1.53, 95% CI 1.17–1.99). Conclusions In elderly patients suspected of sepsis, bacteraemia is associated with a poor prognosis and higher long-term mortality. Other factors related to excess mortality were age over 90 years and a qSOFA score of 2 or more.
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Purpose To explore the clinical value of serum calcium (Ca) in elderly patients with sepsis. Materials and methods The clinical data and laboratory data of elderly patients with sepsis (n = 165) and elderly population for physical examination (n = 67) in a tertiary hospital from January 2020 to November 2020 were collected. We analyzed serum Ca levels in sepsis and septic shock firstly, and then continued to investigate them in the survival group and the death group. Meanwhile, we also assessed the correlation between serum Ca and PCT. Results The serum Ca levels of the elderly patients with sepsis were lower than that of the control group (median 1.98 vs 2.31 mmol/L, P < 0.001), and the more severe the sepsis, the lower the serum Ca levels. Sepsis patients with decreased serum Ca had higher shock rate and mortality. There was a negative correlation between serum Ca and PCT (r = −0.2957, P < 0.001). Conclusion Serum Ca has a certain value for the early recognition of elderly patients with sepsis and the judgment of the severity of the disease.
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Relevance . Sepsis is a life-threatening organ dysfunction caused by dysregulation of the body's response to infection. It is estimated that the annual number of sepsis cases worldwide could be 48 million. An increase in the role of nosocomial infections, an increase in concomitant pathology, and the rapid development of complications lead to negative dynamics in the sepsis incidence and mortality. Aims . Review of the epidemiological characteristics of sepsis in the world and the Russian Federation, study of the etiology, risk factors, complications and prevention of sepsis. Conclusions . The data obtained indicate that sepsis remains an unsolved public health problem in many countries of the world. According to modern data, the annual sepsis (ICD-10: A00-B99, A30-A49, A41) incidence among the adult population in accordance with «Sepsis-3» is 838 per 100 ths. So, assessing the incidence of sepsis and mortality from it, we can identify the negative dynamics of recent years, which is typical for the United States of America, Europe and Asia. For example, the incidence of all forms of sepsis ranges from 25 per 100 ths in Italy (2006) to 883 per 100 ths in Sweden (2019). Moreover, every fourth case of sepsis (24.4%) in the world was acquired during a stay in an ICU. Hospital mortality from all forms of sepsis in various countries ranged from 17.5% in Spain (2013) to 46.3% as a whole and 64.5% with admission to ICU in Brazil (2006–2015). Unfortunately, in the Russian Federation, there are no large studies aimed at assessing sepsis incidence and mortality. According to the results of studies conducted on the basis of ICU in hospitals of St. Petersburg, sepsis incidence was 35 per 100 ICU patients (2006–2007) and 15 per 100 ICU patients (2015). When studying the epidemiological features of sepsis, the following difficulties can be identified: changing the criteria for diagnosing sepsis, comparing data on sepsis, severe sepsis and septic shock, evaluating data on community-acquired and in-hospital sepsis. So, sepsis prevention plays an important role in the public health of many countries. Major preventive strategies to reduce sepsis incidence include raising awareness of sepsis; identification of persons at risk; early diagnosis of sepsis; treatment of comorbid pathology leading to the potential development of sepsis and progression of its complications. The epidemiological status continues to deteriorate due to the growth of antibioticresistant strains, an increase in the proportion of fungal agents, late antibiotic therapy, an unfavorable comorbid status and other factors. Early diagnosis and timely clinical management of sepsis play the main role in the improvement in the quality of life. For example, treatment of chronic infectious diseases, minimization of manageable risk factors, and development of population screening programs will further reduce sepsis incidence and mortality.
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Background Although acute respiratory distress syndrome (ARDS) is associated with high mortality, its direct causal link with death is unclear. Clarifying this link is important to justify costly research on prevention of ARDS. Objective To estimate the attributable mortality, if any, of ARDS. Design First, we performed a systematic review and meta-analysis of observational studies reporting mortality of critically ill patients with and without ARDS matched for underlying risk factor. Next, we conducted a survival analysis of prospectively collected patient-level data from subjects enrolled in three intensive care unit (ICU) cohorts to estimate the attributable mortality of critically ill septic patients with and without ARDS using a novel causal inference method. Results In the meta-analysis, 44 studies (47 cohorts) involving 56 081 critically ill patients were included. Mortality was higher in patients with versus without ARDS (risk ratio 2.48, 95% CI 1.86 to 3.30; p<0.001) with a numerically stronger association between ARDS and mortality in trauma than sepsis. In the survival analysis of three ICU cohorts enrolling 1203 critically ill patients, 658 septic patients were included. After controlling for confounders, ARDS was found to increase the mortality rate by 15% (95% CI 3% to 26%; p=0.015). Significant increases in mortality were seen for severe (23%, 95% CI 3% to 44%; p=0.028) and moderate (16%, 95% CI 2% to 31%; p=0.031), but not for mild ARDS. Conclusions ARDS has a direct causal link with mortality. Our findings provide information about the extent to which continued funding of ARDS prevention trials has potential to impart survival benefit. PROSPERO Registration Number CRD42017078313
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Background There is currently no international recommendation for the admission or treatment of the critically ill older patients over 80 years of age in the intensive care unit (ICU), and there is no valid prognostic severity score that includes specific geriatric assessments. Main body In this review, we report recent literature focusing on older critically ill patients in order to help physicians in the multiple-step decision-making process. It is unclear under what conditions older patients may benefit from ICU admission. Consequently, there is a wide variation in triage practices, treatment intensity levels, end-of-life practices, discharge practices and frequency of geriatrician’s involvement among institutions and clinicians. In this review, we discuss important steps in caring for critically ill older patients, from the triage to long-term outcome, with a focus on specific conditions in the very old patients. Conclusion According to previous considerations, we provide an algorithm presented as a guide to aid in the decision-making process for the caring of the critically ill older patients. Electronic supplementary material The online version of this article (10.1186/s13613-018-0458-7) contains supplementary material, which is available to authorized users.
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Purpose: To document and analyse the decision to withhold or withdraw life-sustaining treatment (LST) in a population of very old patients admitted to the ICU. Methods: This prospective study included intensive care patients aged ≥ 80 years in 309 ICUs from 21 European countries with 30-day mortality follow-up. Results: LST limitation was identified in 1356/5021 (27.2%) of patients: 15% had a withholding decision and 12.2% a withdrawal decision (including those with a previous withholding decision). Patients with LST limitation were older, more frail, more severely ill and less frequently electively admitted. Patients with withdrawal of LST were more frequently male and had a longer ICU length of stay. The ICU and 30-day mortality were, respectively, 29.1 and 53.1% in the withholding group and 82.2% and 93.1% in the withdrawal group. LST was less frequently limited in eastern and southern European countries than in northern Europe. The patient-independent factors associated with LST limitation were: acute ICU admission (OR 5.77, 95% CI 4.32-7.7), Clinical Frailty Scale (CFS) score (OR 2.08, 95% CI 1.78-2.42), increased age (each 5 years of increase in age had a OR of 1.22 (95% CI 1.12-1.34) and SOFA score [OR of 1.07 (95% CI 1.05-1.09 per point)]. The frequency of LST limitation was higher in countries with high GDP and was lower in religious countries. Conclusions: The most important patient variables associated with the instigation of LST limitation were acute admission, frailty, age, admission SOFA score and country. Trial registration: ClinicalTrials.gov (ID: NTC03134807).
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Purpose: Very old critical ill patients are a rapid expanding group in the ICU. Indications for admission, triage criteria and level of care are frequently discussed for such patients. However, most relevant outcome studies in this group frequently find an increased mortality and a reduced quality of life in survivors. The main objective was to study the impact of frailty compared with other variables with regards to short-term outcome in the very old ICU population. Methods: A transnational prospective cohort study from October 2016 to May 2017 with 30 days follow-up was set up by the European Society of Intensive Care Medicine. In total 311 ICUs from 21 European countries participated. The ICUs included the first consecutive 20 very old (≥ 80 years) patients admitted to the ICU within a 3-month inclusion period. Frailty, SOFA score and therapeutic procedures were registered, in addition to limitations of care. For measurement of frailty the Clinical Frailty Scale was used at ICU admission. The main outcomes were ICU and 30-day mortality and survival at 30 days. Results: A total of 5021 patients with a median age of 84 years (IQR 81-86 years) were included in the final analysis, 2404 (47.9%) were women. Admission was classified as acute in 4215 (83.9%) of the patients. Overall ICU and 30-day mortality rates were 22.1% and 32.6%. During ICU stay 23.8% of the patients did not receive specific ICU procedures: ventilation, vasoactive drugs or renal replacement therapy. Frailty (values ≥ 5) was found in 43.1% and was independently related to 30-day survival (HR 1.54; 95% CI 1.38-1.73) for frail versus non-frail. Conclusions: Among very old patients (≥ 80 years) admitted to the ICU, the consecutive classes in Clinical Frailty Scale were inversely associated with short-term survival. The scale had a very low number of missing data. These findings provide support to add frailty to the clinical assessment in this patient group. Trial registration: ClinicalTrials.gov (ID: NCT03134807).
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Background Due to ageing of the general population, an increasing number of very old patients (> 80 years old) is admitted to the hospital and to the intensive care unit (ICU). Sepsis is one of the most frequent reasons for admission. However, it is questioned whether admission of these very old intensive care patients (VOPs) is always indicated, as survival is generally poor. To enhance decision making, more information about chances of VOPs is of the utmost importance for the physicians, the patients and relatives and policymakers. Methods A systematic search was performed in Medline and Embase up to 2017 to identify studies that described the outcome (either ICU-, hospital-mortality and/or any other short- or long-term outcome measure; e.g. 30-day mortality or one year mortality and also functional outcome and quality of life) of VOPs admitted for sepsis. Results We identified 4562 potentially relevant publications, 18 studies could be included. In total, 4256 patients aged 80 years and older were incorporated in this systematic review. The median ICU-mortality was 43% [range 30–79%], the median hospital-mortality 47% [31–84%] and the median 1-year mortality 68% [53–83%]. Conclusions Although relatively few studies are performed in VOPs admitted with sepsis, mortality rates seem to be high. Future studies are needed to identify factors that can predict survival and quality of life after discharge of VOPs in order to identify subgroups that benefit most from ICU treatment.
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Background As the population ages and cancer therapies improve, there is an increased call for elderly cancer patients to be admitted to the intensive care unit (ICU). This study aimed to assess short-term survival and prognostic factors in critically ill patients with solid tumors aged ≥65 years. Methods We conducted a retrospective study. The primary endpoint was ICU mortality. Resumption of anticancer therapy in patients who survived the ICU stay and 90-day mortality were secondary endpoints. All patients aged ≥65 years admitted to the ICU of Georges Pompidou Hospital (Paris, France) between 2009 and 2014 were eligible. ResultsOf 2327 eligible elderly patients (EP), 262 (75.0 ± 6.7 years) with solid tumors were analyzed. These patients were extremely critically ill (SAPS 2 61.9 ± 22.5), and 60.3% had metastatic disease. Gastrointestinal, lung and genitourinary cancers were the most common types of tumors. Mechanical ventilation was required in 51.5% of patients, inotropes in 48.1% and dialysis in 12.6%. Most patients (66.7%) were admitted for reasons unrelated to cancer, including sepsis (30.5%), acute respiratory failure (28.2%) and neurological problems (8.0%). ICU mortality in patients with cancer was 33.6 versus 32.6% among patients without cancer (p = 0.75). Among the cancer EP, the 90-day mortality was 51.9% (n = 136). In multivariate analysis, increased SAPS 2 score and primary tumor site were associated with 90-day death, whereas previous anticancer therapies and poor performance status were not. Among survivor patients from ICU with anti-tumoral treatment indication, 77 (52.7%) had resumption of anticancer treatment. Conclusions Elderly solid tumor patients admitted to the ICU had a mortality rate similar to EP without cancer. Prognostic factors for 90-day mortality were more related to severity of clinical status at admission than the presence or stage of cancer, suggesting that early admission of EP with cancer to the ICU is appropriate.
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We describe how to estimate progression-free survival while dealing with interval-censored data in the setting of clinical trials in oncology. Three procedures with SAS and R statistical software are described: one allowing for a nonparametric maximum likelihood estimation of the survival curve using the EM-ICM (Expectation and Maximization-Iterative Convex Minorant) algorithm as described by Wellner and Zhan in 1997; a sensitivity analysis procedure in which the progression time is assigned (i) at the midpoint, (ii) at the upper limit (reflecting the standard analysis when the progression time is assigned at the first radiologic exam showing progressive disease), or (iii) at the lower limit of the censoring interval; and finally, two multiple imputations are described considering a uniform or the nonparametric maximum likelihood estimation (NPMLE) distribution.
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Background: We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (≥80 years; VIP). Predictors of mortality, with special emphasis on frailty, were assessed. Methods: In total, 5063 VIPs were included in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality. Results: Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 ± 5 vs 7 ± 7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02). Conclusions: VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery. Trial registration: NCT03134807. Registered 1st May 2017.
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Aim: Admitting very elderly, critically ill patients to ICU is controversial. We compared our mortality data in a subgroup of elderly patients to internationally published outcomes. Methods: Tauranga Hospital ICU retrospectively investigated their mortality outcomes for patients with septic shock. The ANZICS adult database (AORTIC), Tauranga Hospital computer records and medical records were used to identify the study cohort and provide information on demographics, admission times and shock types between January 2009 and December 2014. Patients were divided into groups; not old (<74 years), old (75-84 years) and very old (>85 years) to compare survival statistics at ICU discharge, hospital discharge, 28 days, six months and 12 months. Results: Patients in the >85 year group at Tauranga ICU had a 38.5% survival. Conclusion: With careful selection, elderly patients with septic shock may have an acceptable outcome.
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The “very old intensive care patients” (abbreviated to VOPs; greater than 80 years old) are probably the fastest expanding subgroup of all intensive care unit (ICU) patients. Up until recently most ICU physicians have been reluctant to admit these VOPs. The general consensus was that there was little survival to gain and the incremental life expectancy of ICU admission was considered too small. Several publications have questioned this belief, but others have confirmed the poor long-term mortality rates in VOPs. More appropriate triage (resource limitation enforced decisions), admission decisions based on shared decision-making and improved prediction models are also needed for this particular patient group. Here, an expert panel proposes a research agenda for VOPs for the coming years.
Article
Background: To investigate long-term outcomes, post-hospital trajectories, and quality of life (QOL) in patients ≥ 80 years admitted to the intensive care unit (ICU) of a tertiary care hospital. Methods: A 1-year prospective observational cohort analysis was performed. All consecutive patients ≥ 80 years admitted to the ICU were screened for inclusion. Demographics, comorbidity, organ failures, and outcomes were analyzed. QOL before admission, 3 months, 1 year, and 7 years after ICU discharge was assessed using EuroQoL-5D (EQ-5D) and Medical Outcomes Study 36-item Short Form Health Survey (SF-36) questionnaires. Statistical significance was attained at P<0.05. Results: 131 patients with a median age of 83 years (IQR 81-85), a Charlson comorbidity index of 2 (IQR 0-4), a SOFA score of 4 (3-8) upon ICU admission and an APACHE II score of 20 (IQR 15-24) were included. ICU, hospital, 3 months, 1-year, and 7-years mortality rates were 17%, 29%, 39%, 50%, and 84% respectively. QOL decreased significantly over time. Most elderly considered QOL as acceptable and perceived only a worsening in physical functioning and self-care at long-term. Of the 1- year and 7-years survivors, 21% and 39% (P=0.122) lived in nursing homes, and 81% and 72% (P=0.423) preferred to be readmitted to an ICU department if necessarily. Conclusions: Most critically ill long-term elderly survivors lived at home, perceived their QOL as acceptable, and wanted to be readmitted to the ICU if necessarily. In older patients, age alone is a poor indicator of the possible value to be gained from an ICU admission.