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Keywords:
Abstract
discharge;
Objective: Early unplanned readmission to the intensive care unit (ICU) carries a poor prognosis, and
readmission;
post-ICU mortality may be related, in part, to premature ICU discharge. Our objectives were to identify
death;
independent risk factors for early post-ICU readmission or death and to construct a prediction model.
intensive care unit;
Design: Retrospective analysis of a prospective database was done.
score(or scoring system)
Setting: Four ICUs of the French Outcomerea network participated.
Patients: Patients were consecutive adults with ICU stay longer than 24 hours who were discharged
alive to same-hospital wards without treatment-limitation decisions.
Main results: Of 5014 admitted patients, 3462 met our inclusion criteria. Age was 60.6 ± 17.6 years,
and admission Simplified Acute Physiology Score II (SAPS II) was 35.1 ± 15.1. The rate of death or
☆
Conflicts of interest: The authors have no personal or financial conflicts of interest to declare.
☆☆
Financial support: Outcomerea is supported by nonexclusive educational grants from Pfizer, Aventis Pharma France, Wyeth France, and Ely Lilly and
by public grants from the Centre National de la Recherche Scientifique and Institut National de la Santé et la Recherche Medicale. The Outcomerea data
warehouse project was also supported by a grant from the Agence Nationale de Valorisation de la Recherche. These grants had no role in the design or conduct of
the study; the collection, management, analysis, or interpretation of the data; or the preparation, review, or approval of the manuscript.
★
The results reported in this manuscript were presented, in part, at the 2009 annual meetings of the French Society of Intensive Care Medicine, French
Society of Anesthesia and Intensive Care, and European Society of Intensive Care Medicine.
⁎ Corresponding author. Service de Réanimation, Fondation Hôpital Saint-Joseph, 185 rue Raymond Losserand, 75014 Paris, France. Tel.: +33 1 44 12 34
15; fax: +33 1 44 12 32 80.
E-mail address: bmisset@hpsj.fr (B. Misset).
1
The members of the Outcomerea Study Group are listed in the appendix.
0883-9441/$ – see front matter © 2012 Elsevier Inc. All rights reserved.
doi:10.1016/j.jcrc.2011.08.003
422.e2 I. Ouanes et al.
ICU readmission within 7 days after ICU discharge was 3.0%. Independent risk factors for this outcome
were age, SAPS II at ICU admission, use of a central venous catheter in the ICU, Sepsis-related Organ
Failure Assessment and Systemic Inflammatory Response Syndrome scores before ICU discharge, and
discharge at night. The predictive model based on these variables showed good calibration. Compared
with SAPS II at admission or Stability and Workload Index for Transfer at discharge, discrimination was
better with our model (area under receiver operating characteristics curve, 0.74; 95% confidence
interval, 0.68-0.79).
Conclusion: Among patients without treatment-limitation decisions and discharged alive from the ICU,
3.0% died or were readmitted within 7 days. Independent risk factors were indicators of patients'
severity and discharge at night. Our prediction model should be evaluated in other ICU populations.
© 2012 Elsevier Inc. All rights reserved.
2.2. Data collection and baseline data were linear in the logit was checked using cubic polynomials
and graphic methods. In the absence of log linearity,
In each participating ICU, a specifically trained physician continuous variables were transformed into qualitative
collected the data daily on a case report form using VIGIREA variables according to the slope of the cubic polynomial
and RHEA data capture software (OUTCOMEREA, Rosny- functions and to the distribution of the variables. A pooled
sous-Bois, France). All codes and definitions were established test of clinically relevant 2-way interactions was performed
before study initiation. The following information were on the final model, and correlations between selected
recorded for each patient: age and sex, admission category variables were verified. We checked for potential colinearity
(medical, scheduled, or unscheduled surgery), McCabe score of the variables included in the final model. R values of less
[17], and origin (home, ward, or emergency department). than 0.2 were considered acceptable.
Severity of illness was evaluated on the first ICU day using the Our assessment of model performance was goodness of fit
Simplified Acute Physiology Score (SAPS II) [18] and as evaluated by the Hosmer-Lemeshow statistic and
Logistic Organ Dysfunction (LOD) score [19]. Knaus scale calibration curves. Lower Hosmer-Lemeshow values and
definitions were used to record preexisting chronic organ higher P values (N.05) indicate better fit. We assessed
failures [20]. Organ dysfunctions were quantified daily using discrimination using the area under the curve (AUC) of the
the Sepsis-related Organ Failure Assessment (SOFA) [21] and receiver operating characteristics (ROC) curve.
LOD scores. Nursing workload was assessed with the Nine The model was validated using bootstrap resampling with
Equivalents of nursing Manpower Score (NEMS) [22]. 500 replicates from the development cohort of 3462 patients.
Discharge at night was considered between 9 PM and 7 AM The quartiles of the 500 ROC-AUC values provided the
[23]. According to French law, this database study did not confidence interval for model discrimination. The final
require informed consent. The study was approved by the model was evaluated comparatively with other existing
institutional review board of the Clermont-Ferrand University models using the method of McNeil and Hanley [24] to
Hospital, Clermont-Ferrand, France (CECIC [Comité d’Ethi- compare ROC-AUC values. Analyses were computed using
que des Centres d’Investigation Clinique] institutional review the SAS 9.1.3 package (SAS Institute, Cary, NC), R, and
board number 5891; approval number : 2007-16). Medcalc 5.00 (Medcalc, Ghent, Belgium).
had more severe organ dysfunction at ICU discharge, and these patients had lower systolic arterial pressure, higher
had been more often discharged at night. Among the blood urea nitrogen, more hypo- or hyperleucocytosis, hypo-
subclasses of the SAPS II score at admission (e-Table 1), or hyperkalemia, and lower serum bicarbonates. They had a
50
45
40
35
Number of patients
Death Readmission
30
25
20
15
10
0
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 > 31
Fig. 2 Distribution of the daily death and ICU readmission after ICU discharge.
Short-term death or readmission after ICU discharge 422.e5
Table 1 Characteristics at first and second admission of the 74 patients who were readmitted to the ICU within 7 days of ICU discharge
during the same hospital stay
First admission Second admission
SAPS II score at admission, median (IQ) 40 (19) 36 (19)
Main symptom at admission, n (%)
Acute respiratory failure 20 (27.0) 31 (40.5)
Cardiogenic shock 3 (4.1) 11 (14.9)
Coma 11 (14.9) 11 (14.9)
Acute renal failure 7 (9.5) 7 (12.2)
Septic shock 16 (21.6) 12 (8.1)
Hemorrhagic shock 3 (4.1) 2 (2.7)
Scheduled surgery 14 (18.9) 0 (0)
Type of ICU stay, n (%)
Medical 49 (66.2) 54 (73)
Emergent surgery 8 (10.8) 20 (27)
Scheduled surgery 17 (23) 0 (0)
The main symptom responsible for both the first and the second admissions was the same in 25 (34%) of 74 patients.
higher maximum value of Systemic Inflammatory Response ICU discharge was 6.6%. The incidence was 3.0% within 7
Syndrome (SIRS) score in the last 2 days of ICU stay and a days of ICU discharge, and independent risk factors for this
higher score for all the subclasses of SOFA on the day of outcome were the patients' age, indicators of severity during
ICU discharge. The patients who died had more comorbid- the ICU stay, sepsis, organ dysfunction at ICU discharge,
ities and severity scores at admission than those who were and discharge at night. We developed a probability model
readmitted (e-Table 2). that predicted death or ICU readmission within 7 days after
Through multivariate analysis, 6 variables independently ICU discharge with good calibration and fair discrimination.
predicted death or ICU readmission within 7 days after ICU A systematic review [25] showed that early ICU
discharge (Table 3): age, SAPS II at ICU admission, use of a readmission occurred in 5% to 10% of patients [1-5]. Our
central venous catheter during the ICU stay, maximum value relatively low rate may be because of exclusion of those
of the SIRS score during ICU stay, SOFA score at ICU patients who had treatment-limitation decisions, a population
discharge, and discharge at night. at high risk for rapid death [15,16]. We had decided not to
The model exhibited good calibration (Hosmer-Lemeshow include patients with treatment-limitation decisions to
χ 2, P = .93) and fair discrimination (ROC-AUC, 0.74; 95% construct a score that helps to identify patients with a
confidence interval, 0.68-0.79). Based on this predictive preventable risk of life-threatening post-ICU ward events. In
model, we constructed the Minimizing ICU Readmission other studies, premature ICU discharge was associated with
(MIR) score, for minimized ICU readmission, calculated in increased hospital mortality [26].
points. The scoring table is displayed in e-Table 3. A score Among the independent risk factors for death or ICU
more than 150 points is associated with a positive predictive readmission within 7 days after ICU discharge in our study,
value (risk of death or readmission within 7 days) of 8% and having a higher severity at ICU admission and at ICU
negative predictive value of 98% (e-Table 4). discharge is consistent with those factors identified in other
studies [15,16]. These authors found that these 3 factors
3.3. Comparison with previous models together with do-not-resuscitate orders were the main risk
factors for post-ICU inhospital mortality. When assessing
We compared the performance MIR score to SAPS II at severity of illness measured with the APACHE or SAPS
admission and Stability and Workload Index for Transfer systems at ICU admission or discharge, the risk of ICU
(SWIFT) on the day of ICU discharge. Goodness of fit was readmission may increase by 43% with each severity score
satisfactory for all models. Our MIR model showed better increase of 1 SD [27]. The use of a central venous catheter
discrimination than the other 2 models. The ROC-AUCs (95% is an indicator of therapeutic intensity and may represent
IQ range) were 0.74 (0.68-0.79), 0.64 (0.59-0.70), and 0.61 the persistence of severity during the ICU stay. A high
(0.55-0.67) for MIR, SAPS II, and SWIFT, respectively (Fig. 3). SIRS score during the last 2 days, because of either
community- or ICU-acquired infection demonstrates that all
the acute diseases of the patient may not have been solved
4. Discussion before discharge.
The decision to discharge the patient from the ICU is
In our cohort of patients without treatment-limitation usually based on the personal conviction of the physician at a
decisions, the incidence of death or ICU readmission after given time. A patient can be discharged before he/she has
422.e6 I. Ouanes et al.
Table 2 Characteristics of the patients during their first ICU stay according to their status on day 7 after ICU discharge
Alive and not readmitted to the ICU Dead or readmitted to the ICU P
Patients, n 3360 102
Age, mean (SD) 60.4 (17.6) 65.9 (14.2) .002
Female sex, n (%) 1295 (38.5) 30 (29.4) .06
Transfer from ward, n (%) 1677 (49.9) 57 (55.9) .23
Days from hospital to ICU admission, median (IQ) 0 (3) 1 (2) .70
Location before first ICU admission, n (%) .35
Ward 1723 (51.2) 59 (57.9)
Home 22 (0.7) 0 (0.0)
Emergency 1615 (48.1) 43 (42.2)
Type of patients, n (%) .70
Medical 2291 (68.2) 69 (67.6)
Emergent surgery 434 (12.9) 11 (10.8)
Scheduled surgery 634 (18.9) 22 (21.6)
Comorbidities, n (%)
Metastatic cancer 113 (3.4) 8 (7.8) .02
Immune deficiency 307 (9.1) 14 (13.7) .12
Diabetes 489 (14.6) 19 (18.6) .26
McCabe score, n (%) .48
No fatal disease 2297 (68.4) 64 (62.7)
Ultimately fatal disease 949 (28.3) 34 (33.3)
Rapidly fatal disease 112 (3.3) 4 (3.9)
Infection at admission, n (%) 525 (15.6) 21 (20.6) .17
Infection acquired in the ICU, n (%) 481 (14.3) 22 (21.6) .046
Days from last infection to ICU discharge, median (IQ) 5 (8) 6 (9) .70
Severity at first ICU admission, median (IQ)
LOD 3 (4) 5 (3) b.0001
SOFA 5 (5) 6 (4) b.0001
SAPS II 33 (20) 41 (21) b.0001
Procedures used during the ICU stay
Arterial catheter, n (%) 1051 (31.3) 50 (49.0) .0004
CVC, n (%) 1728 (51.4) 78 (76.5) b.0001
MV, n (%) 1780 (50.0) 60 (58.8) .09
MV duration, median (IQ) 4 (8) 5 (10) .17
NIV, n (%) 573 (17.1) 19 (18.6) .69
Days from MV weaning to ICU discharge, median (IQ) 2 (3) 3 (3) .36
Days from VA drug weaning to ICU discharge, median (IQ) 5 (8) 5 (8) .88
Severity on the day before discharge, median (IQ)
Pao2/FiO2 360 (200) 302 (168) b.0001
GCS 15 (0) 15 (1) .001
SOFA 2 (3) 3 (3) b.0001
LOD 1 (3) 3 (4) b.0001
NEMS 17 (7) 15 (7) .48
Maximal SIRS score in last 2 days before ICU discharge 2 (2-3) 3(2-3) .0001
ICU LOS, med (IQ) 4 (5) 5 (8) .45
Discharge at night, n (%) 143 (4.3) 12 (12) .002
Discharge during weekend, n (%) 514 (15.3) 17 (16.7) .67
Discharge when the ICU is full, n (%) 1627 (48.4) 46 (45.1) .55
Discharge to step down unit, n (%) 480 (21.6) 21 (26.3) .33
Discharge to a long-term facility 26 (1.2) 0 (0) 1
CVC indicates central venous catheter; MV, mechanical ventilation; NIV, noninvasive ventilation; PaO2/FiO2, ratio of partial pressure of arterial oxygen over
fraction of inspired oxygen; GCS, Glasgow Coma Scale score; LOS, length of stay; VA, vasoactive.
recovered enough autonomy to be admitted to a conventional Intensive care unit discharge is also influenced by the
ward because a patient in a more serious condition has to take necessity of high nurse staffing because patients may
his/her place in the ICU. Discharge at night is usually experience persistent high dependency after vital functions
considered as a marker of bed shortage [23]. have recovered. This may be taken on in down-step units that
Short-term death or readmission after ICU discharge 422.e7
Table 3 Independent predictors of death or ICU readmission within 7 days after ICU discharge as identified by multivariate logistic regression
Parameter Estimate SE Odds ratios 95% CI P
Intercept −5.59 0.32 – – – b.0001
Parameter related to the severity of the patient
SAPS II at admission 0.017 0.006 1.02 1.005 1.03 .007
Central venous catheter during stay 0.74 0.24 2.1 1.3 3.4 .003
SOFA at ICU discharge 0.19 0.03 1.2 1.1 1.3 b.0001
SIRS score N2 in last 2 days before ICU discharge 0.61 0.20 1.8 1.2 2.8 .003
Parameter related to admission and/or discharge policy
Discharged during night time 0.92 0.33 2.5 1.3 4.9 .006
CI indicates confidence interval.
are currently developing across the world [28,29]. In our ICU. Therefore, its calculation should be automatically
cohort, a high nursing workload at discharge, measured by computed by the software of the ICU database. The absence
the NEMS score, was not a risk factor for death or of digital medical record in several ICUs may be a limit to its
readmission. This may be because of the existence of routine use.
download units in the participating hospitals. In the absence of a treatment-limitation decision, to
Other scores were constructed to predict ICU read- discharge a patient before his/her physical autonomy allows
mission. The Sabadell score, based on the physician's adequate care in a ward may be considered as premature. Our
subjective impression at ICU discharge, was found to predict score could alert the physician once he/she has decided to
post-ICU ward mortality [13]. The SWIFT score study [15] discharge a patient to check if the patient has a high
supports the usefulness of assessing disease severity at ICU probability to be shortly readmitted and then to reevaluate the
discharge, as respiratory and neurologic dysfunctions at necessity to keep him/her under intensive surveillance and/or
discharge were significant risk factors for ICU readmission. supportive care. This should be addressed through interven-
Our MIR model has a better discrimination than the main tional trials in other ICU populations. A high rate of
preexisting predictive models. For the SAPS II score, this is discharged patients with a high MIR score could be
because it was designed to predict hospital mortality and not indicative of inadequate observance of discharge procedures
ICU readmission. For the SWIFT score, it may be because or of shortage of beds and help to adjust local policies.
the score was tested in an external cohort, whereas MIR was
tested in the cohort used for construction. The validity of the
MIR score needs to be assessed in external cohorts. 5. Conclusion
Eventually, as the ROC-AUC value is not close to 1, the
possibility of unknown confounders remains high and should
In a cohort of ICU patients without treatment-limitation
be searched in further cohorts. Finally, the MIR score is more decisions, the rate of death or ICU readmission within 7 days
complex to calculate than the Sabadell and the SWIFT scores
after ICU discharge was 3.0%. The independent risk factors
because it includes a series of data from the entire stay in the
for this outcome reflect disease severity during the ICU stay
and discharge at night. They are easy to identify in current
100 databases. Our MIR probability model is well calibrated and
better in terms of discrimination than prior published models.
80 Its validity should be evaluated in other ICU populations.
Supplementary materials related to this article can be
found online at doi:10.1016/j.jcrc.2011.08.003.
Sensitivity
60 MIR
SAPS II
SWIFT
40
Appendix A. Members of the Outcomerea (ICU, Hôpital Louis Mourier, Colombes, France), Etienne
Study Group Pigné (ICU, Hôpital Louis Mourier, Colombes, France),
Carole Schwebel (University hospital A Michallon, Grenoble,
France), Jean-Francois Timsit (University hospital A Michal-
Scientific committee
lon, Grenoble, France ), Gilles Troché (Hôpital Antoine
Jean-François Timsit (Hôpital Albert Michallon and
Béclère, Clamart France), Marie Thuong (Agence de
Institut National de la Santé et la Recherche Medicale
Biomédicine, Saint Denis, France), Dany Golgran-Toledano
[INSERM] U823, Grenoble, France), Pierre Moine (Surgical
(CH Gonesse, France), and François Vincent (ICU, Hôpital
ICU, Denver, Colo), Elie Azoulay (Medical ICU, Hôpital
Avicenne, Bobigny, France).
Saint Louis, Paris, France), Yves Cohen (ICU, Hôpital
Clinical research assistants
Avicenne, Bobigny, France), Maïté Garrouste-Orgeas (ICU
Caroline Tournegros (Hôpital Albert Michallon), Silvia
Hôpital Saint- Joseph, Paris, France), Lilia Soufir (ICU,
Calvino (Hôpital Albert Michallon), Loic Ferrand (Hôpital
Hôpital Saint-Joseph, Paris, France), Jean-Ralph Zahar
Albert Michallon), Samir Bekhouche (Hôpital Saint Louis),
(Department of Microbiology, Hôpital Necker, Paris, France),
and Kaoutar Mellouk (Hôpital Saint-Joseph, Paris, France).
Christophe Adrie (Department of Physiology, Hôpital Cochin,
France), Adel Benali (Microbiology and Infectious Diseases,
Hôpital Saint-Joseph, Paris, France), Christophe Clec'h (ICU,
Hôpital Avicenne, Bobigny, France), and Jean Carlet (ICU,
Hôpital Saint-Joseph, Paris, France).
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