Acute Respiratory Failure in the US - Incidence and 31 Day Survival

8/7/2019 Acute Respiratory Failure in the US - Incidence and 31 Day Survival

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DOI 10.1378/chest.118.4.11002000;118;1100-1105Chest

Carolyn E. Behrendt

: Incidence and 31-Day Survival*StatesAcute Respiratory Failure in the United

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Acute Respiratory Failure in the UnitedStates*

Incidence and 31-Day Survival

Carolyn E. Behrendt, PhD

Study objectives: To estimate the incidence of acute respiratory failure (ARF) in the United Statesand to analyze 31-day hospital mortality among a cohort of patients with ARF.Design and setting: Retrospective cohort drawn from the Nationwide Inpatient Sample of 6.4million discharges from 904 representative nonfederal hospitals during 1994.Patients: All 61,223 patients in the sample whose discharge records indicated all of the following:acute respiratory distress or failure, mechanical ventilation, > 24 h of hospitalization, and age> 5 years.Results: An estimated 329,766 patients discharged from nonfederal hospitals nationwide in 1994met study criteria for ARF. The incidence of ARF was 137.1 hospitalizations per 100,000 USresidents age > 5 years. Incidence increased nearly exponentially each decade until age 85 years.Overall, 35.9% of patients with ARF did not survive to hospital discharge. At 31 days, hospital

mortality was 31.4%. According to the proportional hazards model, significant mortality hazardsincluded age (> 80 years and > 30 years), multiorgan system failure (MOSF), HIV, chronic liverdisease, and cancer. Hospital admission for coronary artery bypass, drug overdose, or trauma otherthan head injury or burns was associated with a reduced mortality hazard. Interaction was presentbetween age and MOSF, trauma, and cancer. A point system derived from the hazard model classifiedpatients into seven groups with distinct 31-day survival probabilities ranging from 24 to 99%.Conclusions: The incidence of ARF increases markedly with age and is especially high among persons> 65 years of age. Nonpulmonary hazards explain short-term (31-day) survival.

(CHEST 2000; 118:11001105)

Key words: acute disease; adult; aged; child; hospital mortality; incidence; respiratory insufficiency; survival analysis; UnitedStates

Abbreviations: APACHE

acute physiology and chronic health evaluation; ARF

acute respiratory failure; BMT

bonemarrow transplant; CABG coronary artery bypass graft; ICD-9-CM International Classification of Diseases, 9th Revision,Clinical Modification; MOSFmultiorgan system failure

Apicture of the epidemiology of acute respiratory

failure (ARF) is emerging, but significant gapsremain. Surveys of ICU patients have estimated theincidence of ARF to be 77.6 cases per 100,000population age 15 years in Sweden, Denmark, andIceland and 88.6 cases per 100,000 residents in

Berlin.1,2

The incidence of ARF in the United States,however, is unknown. Rates of hospital mortalityamong ICU patients with a diagnosis of ARF orrequiring mechanical ventilation range from 28 to58%.112 Higher mortality rates have been observed

among ARF patients with AIDS or hematologicmalignancy (65% and 83% mortality, respective-ly).13,14

Independent hazards for ARF mortality includeolder age,1,2,4 6,8,11,12,14 severe chronic comorbidities(HIV, active malignancy, cirrhosis),1,5,6,810,12 certain

precipitating events (trauma,3,6,8,11

drug overdose,8,9

bone marrow transplant [BMT]13), and multipleorgan system dysfunction or failure (MOSF).3,4,7,913

Mortality has also been associated with acute lunginjury9,12 or bilateral infiltrates on chest radiograph,1

and with an elevated acute physiology score1,6,7 orAPACHE (acute physiology and chronic health eval-uation) score.9,10

To my knowledge, no study to date has appliedsurvival analysis to a representative cohort of USARF patients, surgical as well as medical, children aswell as adults. Such a cohort can be extracted from

*From Childrens Hospital, San Diego, CA.Manuscript received November 16, 1999; revision acceptedMarch 28, 2000.Correspondence to: Carolyn E. Behrendt, PhD, 4065 3413Pase o de l Campo, Palos V erdes , CA 9 02 74 ; e -mail :[email protected]

1100 Clinical Investigations in Critical Care

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the Nationwide Inpatient Sample, a database of allpatients discharged from a representative sample of904 nonfederal hospitals throughout the UnitedStates during 1994.15 Using data on these ARFpatients, the current study estimates age-specificincidences of ARF and constructs a proportionalhazards model to explain the associated hospitalmortality. These findings will enhance the epidemi-

ologic picture of ARF, increasing the informationavailable to support clinical decision making, coun-seling of ARF patients and their families, and inves-tigation of new therapies.

Materials and Methods

Data Source

The 1994 Nationwide Inpatient Sample was designed toinclude acute care discharges from representative hospitals acrossthe United States during a 1-year period.15 A systematic random

sample of 904 hospitals was drawn from 2,135 nonfederal generaland specialty hospitals stratified by geographic region, urban orrural location, control (government nonfederal, private not-for-profit, and private investor-owned), teaching status, and bed size.All discharges from the selected hospitals were included, for atotal of 6,385,011 inpatients. Available data included patientdemographics, sampling weights, International Classification ofDiseases, 9th Revision, Clinical Modification (ICD-9-CM) dis-charge codes for diagnoses and procedures, duration of hospital-ization, discharge disposition, and hospital characteristics.

Definitions

Patients in the Nationwide Inpatient Sample were consideredto have ARF if they had a diagnostic code for acute respiratory

distress or failure (ICD-9-CM 518.5, 518.81, or 518.82) together with a procedure code for continuous mechanical ventilation(ICD-9-CM 96.7). Such ventilation included positive end-expi-ratory pressure but excluded continuous positive airway pressure,intermittent positive-pressure breathing, and oxygen by facemask or nasal cannula. Total hours of ventilation were notrecorded in the database, so no minimum period of mechanical

ventilation was specified. Instead, ARF patients were limited tothose who remained in the hospital at least 24 h. Infants andchildren 5 years were excluded.

Additional clinical conditions were ascertained using ICD-9-CM codes. MOSF was defined as one or more of the followingin addition to respiratory failure: acute renal failure, cardiacarrest, shock, acute cerebrovascular event, disseminated intravas-

cular coagulation, acute intestinal vascular insufficiency, acutehepatic failure, head injury with loss of consciousness for 24 hor until death, and burns involving 20% of body surface.Trauma refers to a primary diagnosis of crushing or internalinjury, open wounds, superficial injury or contusion, sprains orstrains, fractures other than isolated hip fracture, spinal cordinjury, other injuries, or ARF with lung contusion. Head injury

with loss of consciousness for 24 h or until death and burnsinvolving 20% of body surface were categorized as MOSFrather than trauma.

Statistical Analysis

National sampling weights were used in all analyses (SUDAAN7.5.3 software; Research Triangle Institute; Research Triangle

Park, NC) except the generation of survival plots (SAS 6.12software; SAS Institute; Cary, NC). For the national estimates ofARF incidence, US Census Bureau estimates of the residentpopulation as of July 1, 1994, served as the population denomi-nators.16

The SEs of proportions and 95% confidence intervals aroundproportional hazard estimates were calculated using Taylor serieslinearization.17,18 This method takes into account the intraclustercorrelation that may result from the survey design, which in-

cluded all patients at selected hospitals rather than selectedpatients from all hospitals.The follow-up period began at 24 h after hospital admission

and continued through 31 days. After this time, the acceleratednature of several hazards (age 80 years, MOSF, coronary arterybypass graft [CABG], and drug overdose) undermined the req-uisite assumption of proportional hazards.19 Survivors includedpatients who were discharged alive at any time and also those

who died in the hospital after the follow-up period; survival timeswere censored at 31 days. Terms were retained in the multivar-iate model if they were significant at p 0.0001 and improvedthe 2 log-likelihood ratio.

Results

Patients

Among the Nationwide Inpatient Sample, 62,642patients with acute respiratory distress or failurereceived mechanical ventilation and were hospital-ized 24 h. After excluding the 2.3% of thesepatients who were 5 years of age, a total of 61,223ARF patients remained. Their median age was 69years (5th to 95th percentile range, 30 to 87 years).Children aged 5 to 17 years comprised 1.4% ofpatients. Half (51.1%) of all patients were male.

The highest frequency of head injury, burns, andother trauma combined (20.8%) was among patientsaged 30 years, whereas the greatest prevalence ofcongestive heart failure (47.2%) and COPD (39.0%)was among patients aged 50 years. The frequencyof asthma decreased steadily with age, from 16.6%among children aged 5 to 17 years to 2.9% amongadults aged 80 years.

Incidence

The ARF patients in the sample corresponded to329,766 discharges nationwide or 137.1 hospitaliza-

tions per 100,000 US residents aged 5 years. ARFincidence increased markedly with age, resulting inan 88-fold difference in risk between the youngestand oldest age groups (Fig 1).

Survival

Overall, 35.9 0.3% of ARF patients did notsurvive to hospital discharge. Most (87.5%) deathsoccurred within the 31-day follow-up period. Me-dian length of stay (5th to 95th percentile range) was13 days (3 to 55 days) among survivors and 10 days (1to 50 days) among nonsurvivors.

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A cohort of 61,113 ARF patients was appropriatefor survival analysis. Patients admitted to the hospitalfor BMT (n 86 or 0.14%) were excluded. Becauseof the variable lag time between admission for BMTand onset of ARF, their survival curve could not bealigned with that of the rest of the cohort. Another24 patients (0.04%) who lacked data on survivalstatus at follow-up were also excluded.

At the end of 31 days, hospital mortality among thecohort was 31.4 0.2%. As shown in Table 1,hazards for 31-day mortality included age, MOSF,

HIV, chronic liver disease, and cancer. Mortalityhazard was significantly reduced among patientsadmitted for CABG, drug overdose, or trauma otherthan head injury or burns (hereafter referred tosimply as trauma).

Significant interaction was present between ageand MOSF, trauma, and cancer. Mortality hazardincreased at age 30 years (but only among patientswithout MOSF or trauma) and again at age 80 years.MOSF was a significant hazard among all age groupsbut had proportionally greater impact among pa-tients aged 80 years, especially those 30 years

and those admitted to the hospital for trauma.Cancer was a significant hazard until age 80 years;thereafter, mortality among patients with and with-out cancer did not differ.

Trauma patients aged 30 to 79 years who did notdevelop MOSF had a mortality rate as low as thatamong uncomplicated patients aged 30 years; thesegroups were combined to serve as the models referentcategory. The fit of the model was further improved bycombining cancer and chronic liver disease into a singleterm (severe chronic comorbidity) and by combining

drug overdose and CABG into another term (low-riskprecipitating event). The model was not improved byincluding a term for sepsis.

A point system, shown in the far right column ofTable 1, converted the hazard profiles of individualpatients into scores from 1 to 5 (Table 2). Theobserved survival curves associated with these scores(Fig 2) were each significantly different from thenext (log-rank test, p 0.001 for all pairs). Thesteepest curve was the least smooth, owing to thesmall number of patients (n 101) with the maxi-mum score.

Figure 1. Cases and incidence of ARF in the United States, 1994, by age. Bars denote the numbersof ARF cases; diamonds indicate incidence per 100,000 US residents. Age-specific incidence estimatesare, from left to right, 9.7, 21.6, 32.3, 52.3, 99.9, 231.3, 493.5, 765.5, and 852.9 cases per 100,000.




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Discussion

As in previous studies of ARF incidence, thecurrent case definition excluded persons who werenot admitted to a hospital as well as inpatients who

did not receive mechanical ventilation or who weredischarged within 24 h.1,2 Unlike earlier studies, thecurrent study did not restrict ARF cases to ICUpatients and did not specify a minimum period ofmechanical ventilation. These broader inclusion cri-teria help to explain why the current study yielded ahigher incidence estimate than previous studies. Thetrue incidence of ARF may have been underesti-

mated, however, because the Nationwide InpatientSample did not include patients admitted to federalhospitals and because some ARF patients may nothave been coded as such at discharge.

The gap between the current estimate (137.1/100,000 residents aged 5 years) and that previ-ously published from Berlin (88.6/100,000 residents)narrows once the Berlin estimate has been adjustedfor age.2 Adjustment is necessary because, whereasthe entire population of Berlin served as the esti-mates denominator, its numerator was restricted toARF cases 14 years. Assuming that children 14

Table 2Survival Among ARF Patients (n 61,113)

by Hazard Score

Score nDeaths Through

31 Days, No.31-d Survival*

(SEM), %

1 267 2 99.3 (0.4)0 4,231 320 92.6 (0.3)1 25,344 4,794 81.2 (0.3)2 13,435 4,668 65.3 (0.4)3 11,274 5,389 52.4 (0.4)4 6,461 4,010 38.0 (0.5)5 101 78 24.0 (3.1)

Total 61,113 19,261 68.6 (0.2)

*Percent cumulative survival at 31 days, calculated using nationalsampling weights.

Table 1Thirty-one-Day Hospital Mortality Among a Nationally Representative Sample (n 61,113) of PatientsWith ARF*

Variables n

Observed31-d

Mortality, %

ProportionalHazard

(95% CI)HazardPoints

MOSFYes

Age 80 yr 3,879 59.9 8.55 (7.77, 9.41) 4

Age 3079 yr 13,773 50.5Age 1829 yr 503 44.3 5.86 (5.34, 6.43) 3Age 517 yr 179 32.4

NoAge 80 yr 8,228 32.3 3.69 (3.36, 4.05) 2Age 3079 yr without trauma 31,024 21.3 2.07 (1.90, 2.27) 1Age 3079 yr with trauma 1,267 11.0Age 1829 yr 1,570 10.9 1.00 0Age 517 yr 690 6.5

HIV infectionYes 1,163 52.0 2.00 (1.86, 2.15) 1No 59,884 31.0 1.00

Severe chronic comorbidityCancer age 80 yr, no liver disease 4,990 45.2

Liver disease, no cancer age

80 yr 1,872 54.2 1.83 (1.77, 1.89)

1Both comorbidities 152 63.6Neither comorbidity 54,099 29.3 1.00

Low-risk precipitating eventDrug overdose or poisoning 1,280 17.9 0.39 (0.35, 0.43) 1CABG 1,140 7.8Neither event 58,693 32.2 1.00

*CI confidence interval.When these points are totaled according to an individual patients characteristics, the resulting score corresponds to one of seven 31-day survival

curves observed among ARF patients with the same score (see Fig 2).The frequency of MOSF (29.9% overall) was significantly higher among those ARF patients who underwent CABG (51.9%) or who had chronic

liver disease (48.2%) and significantly lower among trauma patients (22.5%), children ages 5 to 17 years (20.7%), and patients admitted for drugoverdose or poisoning (12.1%).

Trauma does not include head injury or burns; these conditions are categorized instead as MOSF.

Mortality was not associated with sex, pneumonia, aspiration pneumonitis, CHF, COPD, hypertension, diabetes mellitus, interstitial lung disease,neuromuscular disease, GI hemorrhage, pancreatitis, embolism, aneurysm, ketoacidosis, inhalational injury, or near-drowning.

CHEST / 118 / 4 / OCTOBER, 2000 1103



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years comprised 20% of the Berlin population (as was the case in the US population16), the age-

adjusted incidence of ARF in Berlin would beapproximately 110.8/100,000 residents aged 14years. It is unclear why another European survey ofARF yielded a much lower estimate of 77.6 per100,000 population aged 15 years.1

The incidence of ARF was found to increasenearly exponentially with each decade until age 85years. Comparable incidence estimates by age havenot been published.

The current 36% rate of mortality before dis-charge was similar to the 37% rate previouslyreported among ARF patients admitted to 40 US

hospitals6 and approached the 41% and 43% ratesreported among ARF patients in two Europeansurveys.1,2 Whether ARF incidence or mortalitydiffers significantly between the United States andEurope cannot be determined at this time, be-cause of varying case definitions among studies todate.

Because discharge data reflect the entire courseof hospitalization rather than the initial day offollow-up, the current survival analysis and thepoint system derived from it are explanatory ratherthan prognostic. The current survival analysis con-

firmed reports of associations between ARF mor-tality and older age, MOSF, HIV, cancer, chronicliver disease, trauma, and drug overdose.113 Theincrease in mortality at age 30 years and again atage 80 years observed in the current study hasbeen noted in previous studies of patients receiv-ing mechanical ventilation and ARF patients.5,8,12

Also consistent with earlier studies was the currentlack of association between ARF mortality and sex,pneumonia, COPD, congestive heart failure, anddiabetes.15,9,10,14 The current data did not confirman independent association between ARF mortal-ity and sepsis.3,9

The current survival analysis reflects the limita-tions as well as the strengths inherent in theNationwide Inpatient Sample database. The lackof data on acute lung injury and acute physiologicor APACHE score and the necessity of excludingBMT patients precluded testing of these potentialhazards in the multivariate model. However, thepresence of large numbers of children, youngadults, and the elderly within the sample permit-ted the significant interaction between age andother hazards for ARF mortality to be detected forthe first time.

Figure 2. Plot of survival among ARF patients (n 61,113) by hazard score.




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Conclusion

The incidence of ARF increases markedly with ageand is especially high among persons 65 years ofage. Nonpulmonary hazards explain short-term (31-day) survival.

ACKNOWLEDGMENT: The author thanks Alvaro Munoz,PhD, for valuable advice on the survival analysis.

References

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DOI 10.1378/chest.118.4.11002000;118; 1100-1105Chest

Carolyn E. BehrendtSurvival

: Incidence and 31-Day*Acute Respiratory Failure in the United States

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