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From the University of Pittsburgh School of Medicine, Pittsburgh, PA.
A list of study investigators is given in the Appendix.
Correspondence to: Lakshmipathi Chelluri MD, MPH, FCCP, University of Pittsburgh School of Medicine, 200 Lothrop St, 608 Scaife Hall, Pittsburgh, PA 15213; e-mail: chelluril{at}anes.upmc.edu
| Abstract |
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Design: Prospective cohort study.
Setting: Four ICUs at a tertiary-care institution.
Patients: Eight hundred seventeen patients who received prolonged MV.
Interventions: None.
Measurements and results: Median age, sex distribution, and median Charlson comorbidity score of the 817 patients were 65 years, 45.8% women, and 1, respectively. The median scores on Katz Activities of Daily Living, Instrumental Activities of Daily Living Deficits, and Medical Outcomes Study Short-Form 36 surveys before hospitalization were 0, 1, and 50, respectively. Median APACHE (acute physiology and chronic health evaluation) III score and probability of hospital death for the cohort were 64 and 0.31, respectively. Median duration of MV was 9 days. Two-month mortality was 43%. Independent predictors of mortality at 2 months were age, comorbidities, and prehospital functional status. The adjusted odds of dying within 2 months increased 34% for each decade increase in age. Functional status deteriorated at 2 months compared to functional status prior to hospitalization, and 35% of the survivors were at risk for clinical depression. Among the 2-month survivors for whom the need for a caregiver was assessed, 78% had a caregiver.
Conclusions: Older age, in addition to functional status and comorbidities, was associated with increased mortality at 2 months. Functional status of survivors declined at 2 months.
Key Words: age functional status mechanical ventilation mortality
| Introduction |
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75 years and
patients < 75 years old. Other studies6
7
8
9
10
evaluating mortality after MV have shown a higher in-hospital mortality
rate in older, compared to younger, patients receiving MV.
However, the association of age with this in-hospital
mortality, independent of other risk factors such as comorbidities and
severity of illness, is not clear. In addition, sex may have an impact
on mortality. Kollef et al11
reported increased
in-hospital mortality in women requiring MV, although severity of
illness was a major independent predictor of mortality. Although many
investigators evaluated the in-hospital outcomes of patients receiving
MV, few report on post-hospital-discharge outcomes such as functional
status, quality of life, and mortality. We previously documented that
increased mortality from critical illness continues following hospital
discharge, and measures of functional status of survivors deteriorate
initially, but improve over a longer period.12
That study
was limited, however, by focusing only on elderly critically ill
patients and it did not include many patients receiving MV. As MV is
burdensome and expensive, it would be helpful to have a better
understanding of factors related to survival and quality of life after
discharge from the hospital in patients receiving MV. Such knowledge
could help physicians and patients in making decisions about
life-sustaining therapy. We therefore performed a prospective study of patients receiving MV for at least 48 h to study the association of age and sex on mortality and functional status at 2 months after the need for MV. We also describe the need for support after discharge from the hospital.
| Materials and Methods |
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During a recruitment period beginning in June 1997 and continuing through July 1999, trained interviewers screened consecutive patients admitted to the ICUs to determine if they were eligible for participation. Eligible patients, or their proxies (usually next of kin) in the event that the patient could not respond, were asked to provide informed consent.
All patients receiving MV were screened, and patients receiving MV for at least 48 h were included. For patients with multiple admissions to the ICU, the first ICU admission with MV for > 48 h was used as the index admission. Exclusion criteria were patients hospitalized following solid-organ transplantation, subjects < 18 years of age, non-English-speaking persons, prisoners, and persons who were chronically ventilator-dependent at home or at a long-term ventilator facility. Patients who were transferred from other hospitals after intubation for > 24 h prior to admission to the UPMC were also excluded. In addition, recruitment was greater than expected several months into the study, so 10% of eligible participants were randomly excluded by not recruiting persons whose Social Security numbers had a terminal digit of "9." There were no patients with burns in the group, as UPMC does not have a burn unit. The University of Pittsburgh Institutional Review Board approved the QOL-MV study protocol.
Data Collection
Trained research assistants screened the ICUs daily and
identified patients receiving MV. Patient medical records were reviewed
and eligibility status ascertained. Eligible subjects or family member
proxies participated in a baseline interview in the hospital (during or
after discharge from the ICU), and follow-up interviews occurred 2
months after the participants had been receiving MV for 48 h.
Baseline data were collected by hospital chart review if neither the
patient nor a proxy could be interviewed. Follow-up interviews were
conducted in person whenever possible. Follow-up interviews were
conducted by telephone if the patient lived outside a 50-mile radius or
if the patient preferred a telephone interview. If neither the patient
nor the proxy could participate in a full follow-up interview, a
"mini follow-up" interview was conducted in which only the
patients vital status, current residence, and employment status were
collected. Interviewers were trained to administer the forms by study
investigators and were required to successfully administer practice
interviews before starting independent data collection.
The following data were collected during baseline interviews:
1. Demographic variables, including age, sex, race, education, income, employment, and occupation.
2. Medical data, including admitting diagnoses to the ICU and comorbidities. The Charlson comorbidity score was used to assess comorbidity.13 The Charlson comorbidity score is a weighted index that takes in to consideration specific diseases and their severity. A higher score is indicative of poor prognosis. Functional status was evaluated with Katz Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL), and the physical functioning part of the Medical Outcomes Study Short-Form 36 (SF-36).14 15 16 ADL assesses the need for help in performing basic activities of daily living, such as bathing, dressing, using the toilet, transfer in and out of bed or chair, continence, and feeding. IADL assesses a higher level function, such as ability to perform household chores and shopping. A higher score for ADL and IADL is indicative of more dependence. The physical function part of SF-36 evaluates ability to perform various physical activities, such as walking and climbing stairs. A higher score on SF-36 indicates better ability to perform these activities.
3. Length of stay in the ICU and hospital, duration of MV, need for tracheostomy, and resuscitation status. Length of stay of patients who needed MV within 24 h of extubation, or who were readmitted to an ICU within 24 h discharge from the ICU, was considered to be part of the same episode of MV and ICU admission. APACHE (acute physiology and chronic health evaluation) III score17 and mortality probability in the ICU and hospital were obtained from a hospital database.
4. Hospital charges obtained from the hospital financial database, and total hospital cost calculated by multiplying department charges by Medicare cost/charge ratio for individual departments. Cost per day was calculated by dividing the total hospital cost by hospital length of stay in days. Cost per hospital survivor and per 2-month survivor was calculated by dividing total hospital costs for the group by the number of patients discharged alive from the hospital, and the number of survivors at 2 months, respectively.10
The following data were collected during follow-up interviews: socioeconomic status (ie, income, education level attained), religiosity, social support, memory of the ICU experience, patient preference for undergoing MV, functional status data (ADL, IADL, and SF-36), and depressive symptoms using the Center for Epidemiologic Studies Depression Scale (CES-D).18 CES-D evaluates depressive symptomatology, and a score > 16 is used as a screen for presence of depression. The individual domains for SF-36 were combined into physical (physical functioning, role- physical, bodily pain, general health) and mental (vitality, social functioning, role-emotional, mental health) components. Caregivers, who were identified by the patients or the person identifying himself or herself as the caregiver, provided data on caregiver burden19 and involvement with patient care. The interviews with caregivers were done at the same time as the interviews with patients, and were performed in person or by phone based on subject preference or distance from UPMC. Vital status information was collected by prospectively following up the subjects. Dates of death were collected through interviews with family members of deceased subjects. Date of death information was verified, and cause of death was ascertained by reviewing death certificates. For any patient who was unavailable for follow-up, we performed a minimum of two searches of death certificates in his or her state of residence. The final death certificate search occurred at least 1 year following the last date of contact. If no death certificate was found after these searches, the patient was assumed to have survived. The analysis to identify factors related to 2-month mortality was performed both including and excluding those subjects who were unavailable for follow-up, in order to test the effect, if any, of classifying the unavailable subjects into the survival group.
Statistical Analysis
The QOL-MV sample is described using measures of central
tendency and variability for continuous variables and frequency
distributions for categorical variables. Statistics are presented
overall and for the 2-month nonsurvivor group.
The relations between patient factors and 2-month mortality were
examined through logistic regression analyses. The outcome (dependent)
variable in the logistic regression analysis was whether or not the
patient survived for 2 months following MV. A multiple logistic
regression model was fit to identify independent predictors of 2-month
mortality. The following covariates were included in the model: age
(measured on a continuous scale with the unit of measurement equal to 1
decade), sex (female subjectsreference group), race (white
subjectsreference group, nonwhites), Acute Physiology Score (APS) on
the enrollment day (continuous, unit of measurement was a 10-point
score change), Charlson comorbidity scores (continuous), type of
patient (medicalreference group, surgical, or trauma patient), and
IADL scores (score = 0reference group, score
1, missing score).
A missing score on the IADL scale typically indicated that the patient
was unable to participate in the baseline interview due to severe
physical or mental impairment, or that the patient died prior to
contact with the family. In addition to the main effects model, all
pairwise interactions were examined in a stepwise model-building
fashion. Entry and exit criterion for the pairwise interactions was
statistical significance of 0.05. The Hosmer-Lemeshow goodness-of-fit
statistic was calculated.20
Also, the area under the
receiver operating characteristic (ROC) curve was computed to determine
the predictive properties of the final model.21
Two-month functional status measures are reported for those that survived to the 2-month follow-up interview. Data are presented separately by respondent (patient or proxy) because many of the 2-month follow-up interviews were conducted with a family-member surrogate due to the patients inability to complete the interview.
| Results |
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48
h. Two hundred twenty-nine patients were excluded because they had
pretransplantation or posttransplantation status, were chronically
ventilator dependent, were intubated for 24 h prior to ICU
admission, or did not speak English. Of the remaining 894 patients, 77
patients or their families refused to participate in the study. Thus,
the final sample is based on 817 subjects. The 2-month mortality rate
was 43%. Among the 466 survivors, we were unable to interview 98
survivors (21%) at 2 months. Eighty-three of these 98 subjects were
known to be alive at 2 months since we were able to interview them at
later follow-up interviews (ie, 6 months or 12 months),
while 15 patients were unavailable for follow-up at 2 months. As we
were unable to find any evidence of these 15 subjects being deceased
through two death certificate searches, we assumed that they were alive
at 2 months. There were no statistically significant differences
between these 15 subjects and the 802 patients we were able to
successfully follow up in terms of age, sex, race, education, APACHE
III scores on the first ICU day, IADL, and SF-36 physical functioning.
Patient recruitment is described in Figure 1
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Median total hospital cost and daily cost were $56,100 (25th to 75th percentile, $31,900 to $83,400), and $2,700 (25th to 75th percentile, $2,200 to $3,400, respectively). Costs per hospital survivor and 2-month survivor were $96,223 and $116,872, respectively. One hundred ten hospital survivors (21%) were discharged to home, 190 survivors (36.1%) were discharged to rehabilitation facilities, 144 survivors (27.4%) went to nursing homes, 48 survivors (5.9%) went to chronic ventilator facilities, and the remaining 34 survivors (6.5%) were discharged to other hospitals.
2-Month Mortality: Univariate Analysis
The 2-month mortality rate was 43.0% (351 of 817 patients) when
counting the 98 patients unavailable for follow-up at 2 months (for
whom two searches yielded no death certificates) as survivors.
Nonsurvivors tended to be older than survivors (odds of dying within 2
months were 31% higher for every decade increase in age). There was
not a significant difference in 2-month survival rates by sex. Though
2-month mortality was slightly higher among nonwhites compared to
whites, the difference was not statistically significant (p = 0.10).
Mortality at 2 months did not differ significantly by education,
income, or marital status. Two-month mortality was higher in patients
admitted from a nursing home, rehabilitation, or other facility
compared to patients admitted from home (55.7% vs 41.4%, p = 0.01).
Medical patients had significantly higher mortality than those admitted
for surgery or trauma. All measures of functional status and patient
acuity we examined were related to 2-month mortality. For every
additional comorbidity, as assessed by the Charlson comorbidity score,
the odds of dying by 2 months increased by 24% (95% confidence
interval [CI] for odds ratio [OR], 1.17 to 1.32). The ORs for
mortality for each additional ADL and IADL requiring assistance were
1.24 (95% CI, 1.15 to 1.34) and 1.23 (95% CI, 1.16 to 1.31),
respectively. Higher SF-36 physical functioning scores, implying better
physical well-being, were related to a decreased odds of 2-month
mortality (OR, 0.85; 95% CI, 0.81 to 0.89). Measures from the APACHE
III system were significantly associated with 2-month mortality. For
example, the odds of dying by 2 months increased by 34% for each 10-U
increase in the ICU day 1 APACHE score. Those with longer lengths of
stay in the hospital and ICU and longer time receiving MV had
significantly reduced odds of 2-month mortality (Table 3
) because those who died within 2 months were likely to die soon after
they received MV for 48 h. Increased total hospital costs were
inversely associated with odds of 2-month mortality, as 2-month
mortality decreased by 9% for every $10,000 increase in total hospital
costs, likely due to the strong relationship between hospital length of
stay and total costs. However, average daily hospital costs were
positively associated with odds of 2-month mortality (OR for each
$1,000 increase, 1.52; 95% CI, 1.32 to 1.76), implying greater
intensity of resource utilization for those who ultimately died.
|
1 were 63% higher than that for subjects with IADL scores
of zero. Patients with missing IADL scores (primarily patients with
physical or mental conditions that prevented their participation in the
baseline interview or who had died prior to contact with the family)
were at nearly five times the risk of dying by the 2-month follow-up
than those with an IADL score of zero. Age and Charlson comorbidity
score was the only interaction that entered (and remained) in the
regression model. The interaction was such that mortality among older
subjects with greater comorbidity was less than multiplicative. Sex,
race, and diagnostic group (medical, surgical, or trauma) were not
significantly related to dying by 2 months (p > 0.05). The
Hosmer-Lemeshow statistic had a p value of 0.10, implying that there
was no evidence of lack of model fit. The model had good predictive
properties, as the area under the ROC curve was 0.82. Detailed results
of the regression analysis are presented in Table 4
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16, indicating that many patients are at risk for clinical
depression. Fifty percent of the patients described their general
health at the 2-month interview as good, very good, or excellent, and
16% stated that their current health status was better compared
to a year before. Seventy-eight percent of the patients for whom
caregiver data were available had a caregiver, and 17% were living
alone without a caregiver. | Discussion |
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Hospital outcomes are one measure of the effectiveness of therapeutic interventions. However, hospital outcomes are inadequate as the sole measures of therapeutic effectiveness. Evaluation of patient outcomes after hospital discharge, including functional status, morbidity, quality of life, return to work and usual activities, and mortality, are important as well. A vital issue for evaluating hospital services is how long after discharge patient outcomes should be assessed. Furthermore, hospital outcomes are influenced by discharge strategies. For example, hospitals that are able to discharge patients to other facilities (eg, rehabilitation, nursing homes) sooner than other hospitals will have shorter length of stay and lower in-hospital mortality. Hence, hospital mortality rates are not comparable across studies.
We report a 2-month mortality of 43%. We found that patients with medical diagnoses had a higher mortality rate than those with trauma or a surgical diagnosis. Kollef et al11 reported similar findings for hospital mortality. Our data show that those who did not survive at 2 months were on average more severely ill on entry into the ICU and into the QOL-MV study than those who did survive, as indicated by severity-of-illness and functional-status measures, and were on average older and more likely to have been admitted from a nursing home or rehabilitation facility than survivors. Nonsurvivors had lower average total hospital cost and shorter length of stay, indicating that nonsurvivors died earlier during hospitalization. Also, in this sample, every decade of increase in age increased the risk of death at 2 months by 34%. This association between age and outcome following prolonged MV was constant across the entire age range. This result is different from that reported by Ely et al,5 who found no difference in hospital mortality in older and younger patients, but they did not report post-hospital discharge mortality. Similar to other studies, we report that comorbidity and functional status prior to hospitalization were also risk factors for increased 2-month mortality.24 25
2-Month Functional Status
These data show that functional status, as measured by ADL, IADL,
or SF-36, was worse at 2 months compared to patients prehospital
levels. Additionally, SF-36 scores were lower than those reported for
the general population.16
Similar decline in function was
reported after critical illness in elderly patients, patients requiring
intensive care for a prolonged period, and patients with ARDS and lung
injury.26
27
28
29
30
Engoren et al31
studied
survival and functional status of patients receiving MV support
7
days after cardiac surgery. The follow-up interval was variable. They
reported 59% survival at 5 years, and 59% of the survivors described
their health status as good. We reported more severe limitations in
physical function compared to mental function in our cohort. This
finding is similar to those reported by others27
28
29
after
acute lung injury or critical illness requiring intensive care. As
functional status was worse at 2 months, longer-term follow-up is
needed because recovery of functional abilities may take > 2 months
after a critical illness. The functional status of patients where a
proxy was the respondent was worse compared to the functional status of
those patients who participated in the interview. As there is a
significant difference in functional status based on whether the
respondent was patient or proxy, one should be cautious in combing
functional status data obtained from patient and proxy interviews. The
mean CES-D score for those who were able to complete the 2-month
interview was higher than that reported for general population and the
CES-D score at 1 month after discharge from the hospital found in a
group of elderly survivors of critical illness.12
18
The
prevalence of significant depressive symptomatology (
16 on CES-D)
was also higher than the 15 to 16% reported for older adults in the
general population, and indicates the need for assessment for
depression and treatment.32
33
Although the objective
measures of functional status were worse, 50% of the patients in this
study described their quality of life as good or better, and similar
results were reported by others.34
35
Patients scores on
the quality-of-life assessments differ from their scores on objective
scales because quality of life is not "a description of patients
health status" but rather "the way that patients perceive and react
to their health status."35
Not surprisingly, a large percentage (78%) of these patients had an informal caregiver providing support 2 months after entry into the study. The decline in functional status, increased prevalence of depressive symptoms, and involvement of a caregiver indicate that patient as well as caregiver evaluations are warranted after hospital discharge. These evaluations should be made to determine the health needs of the survivors of prolonged MV, and the impact on their caregivers, so that appropriate health and supportive services can be provided to both. It is very likely that the patients receive at least some follow-up services, but studies have shown that it is much less likely that their caregivers receive adequate assessments or services.36
Hospital Costs
Hospital costs for the patients were relatively high and costs for
nonsurvivors were slightly lower compared to survivors (median cost,
$47,100 vs $60,800 in nonsurvivors and survivors, respectively.) Median
cost per day was slightly higher for nonsurvivors compared to survivors
($2,900/d and $2,600/d, respectively), but the differences in total
hospital cost between nonsurvivors and survivors were mostly related to
the increased hospital length of stay for survivors (16 days for
nonsurvivors vs 23 days for survivors). Gracey et
al37
reported hospital costs for elderly patients
aged
65 years and receiving MV for
48 h as $31,896 in 1985,
which is comparable to that reported by us after adjusting for
health-care inflation between 1985 and 1997.38
Ely and
coworkers5
reported hospital costs of patients receiving
MV in different age groups (< 75 years of age and
75 years of
age) as $29,049 and $21,292 in the younger group and older group,
respectively. The lower costs in the study by Ely and
colleagues5
are probably related to the patient
population, which included only medical and coronary ICUs patients.
Costs per hospital and 2-month survivor in the current study were
$96,223 and $116,872, respectively. The cost per survivor that we
report is higher than that reported by Kurek et al10
for
patients receiving MV under diagnosis-related group 475 in New York
State in 1993. The difference is probably related to the entry
criterion, which was all patients receiving MV under diagnosis-related
group 475 in the study by Kurek et al,10
whereas the
current study included only patients receiving MV for
48 h. In
addition, we calculated costs from the hospital charges, whereas Kurek
et al10
used the hospital reimbursement, which may be
lower than the actual costs.
Limitations of this study include missing data on functional status, lack of physiologic data specific to the acute illness, and incomplete cost data. We obtained information on functional status at base line for 75 to 85% of the patients. It was difficult to obtain IADL and SF-36 data by chart review, and the missing data were mostly from patients who died before we could interview the patient/family. As our primary focus was long-term mortality and functional status and we had limited resources, we focused our data collection toward long-term follow-up and did not collect detailed physiologic information, except for APACHE III score, while the patients were in the ICU. We obtained follow-up functional status information on 79% of the survivors, and similar follow-up rates were reported by others.26 29 The functional status was based on data obtained by proxy interview, as many of the patients were not able to participate in the interview at 2 months. We did not obtain physician costs and costs after discharge from the hospital. So, our cost data underestimate total costs and cost per 2-month survivor.
| Conclusion |
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| Appendix 1 |
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| Footnotes |
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Supported by National Institute On Aging grant No. RO1AG11979.
Received for publication January 31, 2001. Accepted for publication August 15, 2001.
| References |
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