A Multicentre, Prospective Study to Evaluate Costs of Septic Patients in Brazilian Intensive Care Units

Pharmacoeconomics 2008; 26 (5): 425-434ORIGINAL RESEARCH ARTICLE 1170-7690/08/0005-0425/$48.00/0

© 2008 Adis Data Information BV. All rights reserved.

A Multicentre, Prospective Study toEvaluate Costs of Septic Patients inBrazilian Intensive Care UnitsAna M.C. Sogayar,1 Flavia R. Machado,2 Alvaro Rea-Neto,3 Amselmo Dornas,4Cintia M.C. Grion,5 Suzana M.A. Lobo,6 Bernardo R. Tura,7 Carla L.O. Silva,8Ruy G.R. Cal,1 Idal Beer,1 Vilto Michels Jr,8 Jorge Safi Jr,9 Marcia Kayath9 andEliezer Silva1,8 for the Costs Study Group – Latin American Sepsis Institute1 Hospital Israelita Albert Einstein, Sao Paulo, Brazil2 Hospital Sao Paulo (UNIFESP), Sao Paulo, Brazil3 Hospital das Clinicas da Universidade Federal do Parana (UFPR), Curitiba, Brazil4 Hospital Mater Dei, Belo Horizonte, Brazil5 Hospital Universitario da Universidade Estadual de Londrina, Londrina, Brazil6 Hospital de Base, Sao Jose do Rio Preto, Brazil7 Instituto Nacional de Cardiologia, Rio de Janeiro, Brazil8 Instituto Latino Americano para Estudos da Sepse, Sao Paulo, Brazil9 Eli Lilly do Brasil, Sao Paulo, Brazil

Background: Sepsis has a high prevalence within intensive care units, withAbstractelevated rates of morbidity and mortality, and high costs. Data on sepsis costs arescarce in the literature, and in developing countries such as Brazil these data arelargely unavailable.Objectives: To assess the standard direct costs of sepsis management in Brazilianintensive care units (ICUs) and to disclose factors that could affect those costs.Methods: This multicentre observational cohort study was conducted in adultseptic patients admitted to 21 mixed ICUs of private and public hospitals in Brazilfrom 1 October 2003 to 30 March 2004. Complete data for all patients admitted tothe ICUs were obtained until their discharge or death. We collected only directhealthcare-related costs, defined as all costs related to the ICU stay.

Enrolled patients were assessed daily in terms of cost-related expendituressuch as hospital fees, operating room fees, gas therapy, physiotherapy, bloodcomponents transfusion, medications, renal replacement therapy, laboratory ana-lysis and imaging. Standard unit costs (year 2006 values) were based on theBrazilian Medical Association (AMB) price index for medical procedures and theBRASINDICE price index for medications, solutions and hospital consumables.Medical resource utilization was also assessed daily using the Therapeutic Inter-vention Scoring System (TISS-28). Indirect costs were not included.Results: With a mean (standard deviation [SD]) age of 61.1 ± 19.2 years, 524septic patients from 21 centres were included in this study. The overall hospitalmortality rate was 43.8%, the mean Acute Physiology And Chronic HealthEvaluation II (APACHE II) score was 22.3 ± 5.4, and the mean Sequential OrganFailure Assessment (SOFA) score at ICU admission was 7.5 ± 3.9.

The median total cost of sepsis was $US9632 (interquartile range [IQR]4583–18 387; 95% CI 8657, 10 672) per patient, while the median daily ICU cost

426 Sogayar et al.

per patient was $US934 (IQR 735–1170; 95% CI 897, 963). The median dailyICU cost per patient was significantly higher in non-survivors than in survivors,i.e. $US1094 (IQR 888–1341; 95% CI 1058, 1157) and $US826 (IQR 668–982;95% CI 786, 854), respectively (p < 0.001). For patients admitted to public andprivate hospitals, we found a median SOFA score at ICU admission of 7.5 and 7.1,respectively (p = 0.02), and the mortality rate was 49.1% and 36.7%, respectively(p = 0.006). Patients admitted to public and private hospitals had a similar lengthof stay of 10 (IQR 5–19) days versus 9 (IQR 4–16) days (p = 0.091), and themedian total direct costs for public ($US9773; IQR 4643–19 221; 95% CI 8503,10 818) versus private ($US9490; IQR 4305–17 034; 95% CI 7610, 11 292)hospitals did not differ significantly (p = 0.37).Conclusions: The present study provides the first economic analysis of directcosts of sepsis in Brazilian ICUs and reveals that the cost of sepsis treatment ishigh. Despite similar ICU management, there was a significant difference regard-ing patient outcome between private and public hospitals. Finally, the mediandaily costs of non-survivor patients were higher than survivors during ICU stay.

Introduction is responsible for more than 53 685 hospital admis-sions per year, with a mean length of stay of 12.1

Sepsis is highly prevalent within intensive care days and a mortality rate of 40.9%. The mean aver-units (ICUs) and is associated with elevated rates of age cost related to sepsis, according to this database,morbidity and mortality,[1-3] and high costs.[4-7] For is approximately $US600. However, this value isthese reasons, healthcare providers, managers, gov- certainly underestimated, because it pertains only toernment authorities and insurance companies have the government reimbursement related to the initialfocussed their attention on strategies that could re- diagnosis. It does not take into account actual re-duce its economic and social burden. In the health- source use.care system, ICUs consume a significant amount of Hence, the objectives of this study are to assessresources and have been frequently considered the the direct costs of sepsis management in Braziliantarget for efforts to reduce escalating medical ex- ICUs and to disclose factors that could affect thosepenses. costs.

The direct cost of care for patients with sepsis hasbeen shown to be 6-fold higher than caring for ICU Methodspatients without sepsis.[8] According to US data,each septic patient consumes, during hospitaliza-

Study Design and Settingtion, about $US25 000, corresponding to approxi-mately $US17 billion annually.[9] These figures may A multicentre observational cohort study wasincrease when patients progress to septic shock and conducted from 1 October 2003 to 30 March 2004,multiple organ dysfunctions, requiring highly ex- involving adult septic patients admitted to 21 mixedpensive therapeutic and diagnostic interventions, ICUs of private and public hospitals in Brazil, locat-and a longer hospital stay.[10]

ed in three different regions (south, southeast andDespite this, more complete data on sepsis costs northeast), with the south and southeast regions

are scarce in the literature, and this problem is even being the most populated. Hospitals were selected inmore evident in developing countries such as Brazil. accordance with that demographic feature.Two major issues with cost analysis in sepsis are thelack of data on resource use in ICUs (clinical staff Subjectsrarely record everything that is done for a patient),[6]

and the lack of standardized templates. According to All adult patients who met the diagnostic criteriathe Brazilian Healthcare Database,[11] ‘septicaemia’ for sepsis, severe sepsis or septic shock were con-

© 2008 Adis Data Information BV. All rights reserved. Pharmacoeconomics 2008; 26 (5)

Costs of Septic Patients in Brazilian ICUs 427

secutively enrolled. The study protocol was ap- tory, coagulation, hepatic, renal or neurological)proved by the local Ethics Committee, and written or hypoperfusion (lactic acidosis, oliguria orinformed consent was obtained from patients or acute alteration of mental status) or sepsis-in-their legal representative. Patients who were aged duced hypotension (systolic arterial pressure<18 years or who could not provide informed con- <90 mmHg or a fall >40 mmHg from the base-sent were not included in this study. line);

• septic shock was defined as severe sepsis requir-Measurements and Outcome Evaluation ing vasopressor administration in spite of ade-

quate fluid resuscitation.Complete data for all septic patients admitted to The diagnosis of infection was based on clinical,

the ICUs were recorded until their discharge or image and microbiological parameters. Accordingdeath. Clinical and demographic data were recorded to attending physician’s discretion, blood, trachealat study entry, including age, sex, hospital and ICU secretion, urine, CSF and wound/skin secretionadmission diagnoses (according to the International samples could be obtained for culture. The infectionClassification of Diseases, 10th Revision [ICD-10]), source was classified by the attending physician asAcute Physiology and Chronic Health Evaluation II lung/respiratory tract, urine, primary bloodstream or(APACHE II) score,[12] and associated underlying wound/surgical site.diseases. Additionally, we computed the Sequential

In each participating centre, physicians and re-Organ Failure Assessment (SOFA) score[13] and re-search nurses were trained to collect data; a coordi-corded diagnostic criteria for systemic inflammatorynator research nurse validated those data. A coordi-response syndrome (SIRS), sepsis, severe sepsis andnating centre (The Latin American Sepsis Institute)septic shock. For calculation of the APACHE II andsupported data registration at each centre, and allSOFA scores, all laboratory and clinical data notdata were checked to be within acceptable rangesavailable were considered to be within normaland were collected through an electronic web-basedranges. Neurological status of patients receivingcase report form (CRF). An operational manualsedative drugs was assessed by the Glasgow Comaprecisely defined all collected variables.Scale, as measured or estimated before sedation.

The onset of sepsis, severe sepsis or septic shockCost Evaluationwas defined as the time at which screening and

confirmatory criteria were first documented. This study included only ICU care-related costs,which were allocated in blocks as follows (table I):

Definitions1. clinical support services (cost block 1)2. consumables (cost block 2)Sepsis and sepsis-related conditions were diag-3. staff (cost block 3) andnosed according to the criteria proposed by the4. hospital fee (cost block 4).American College of Chest Physicians/Society of

Critical Care Medicine (ACCP/SCCM),[14] as fol- Hospital fee is a daily and fixed charge indepen-lows: dent of the type of disease. This fee is used at the

discretion of the hospital. Hospital fees are incorpo-• SIRS was defined by two or more of the follow-rated in the general budget of the hospital and areing criteria: temperature >38°C or <36°C, tachy-then allocated to cover costs that may or may not becardia (heart rate >90 beats/min), tachypnoearelated to the ICU, making them impossible to track.(>20 breaths/min or PaCO2 <32 mmHg or

mechanical ventilation), altered white blood cell Costs related to equipment usage, estates (e.g.count (>12 000 cells/μL, <4000 cells/μL or costs related to infrastructure, electricity charges,>10% of band forms); security systems, etc.) and non-clinical support ser-

vices, as well as indirect costs (productivity losses),• sepsis was defined as a systemic inflammatorywere not included (see table I).response due to infection;

• severe sepsis was defined as sepsis plus at least Enrolled patients were assessed daily, onlyone organ dysfunction (cardiovascular, respira- during ICU stay. We analysed cost-related expendi-


428 Sogayar et al.

Table I. Resources attributed to cost blocks 1, 2, 3 and 4

Cost block 1: clinical support services Cost block 2: consumables Cost block 3: staff Cost block 4: ‘others’Pharmacy Drugs, fluids and nutrition Medical staff (consultants) Hospital fees

Physiotherapy Blood and blood products Medical staff (non-consultants)

Radiology Disposables Technicians

Dieticians Nursing staff

Othersa

Laboratory servicesa Includes cardiology, renal support from outside the ICU and clinical neuro-services.

tures such as hospital fees, operating room fees, gas Statistical Analysistherapy (e.g. oxygen support), physiotherapy, bloodcomponents transfusion, medications, renal replace- Results are expressed as mean ± SD for variablesment therapy, laboratory analysis and imaging. that putatively exhibit a Normal distribution. On

After completion of data collection, all interven- rejection of the normality hypothesis (by Ryan-Join-tions were priced. Standard values were based on the er test), or for ordinal variables, we used the medianBrazilian Medical Association (AMB) price index and interquartile range (IQR). All costs are reportedfor medical procedures[15] and on the Brasindice as median and 95% confidence interval (CI). Stu-price index[16] for medications, solutions and hospi- dent’s t-test for independent samples was appliedtal consumables. In both price indices, every re- to data with a Normal distribution.[18] When normal-source corresponds to a specific value (in Brazilian ity was rejected or for ordinal variables, the Mann-currency). In mixed healthcare systems, especially Whitney U-test for independent samples wasin Brazil, there are significant discrepancies in used.[19] For categorical variables, the Pearson’s testcharges between private and public health systems. or Fisher’s exact test were applied as appropriate.[20]

We therefore decided to use standard price lists, and Crude odds ratios, with 95% CI, were calculatednot prices adopted by every institution, so we could for each independent variable, by univariate logisticprovide useful comparisons. Furthermore, we as- regression modelling. A multivariate logistic regres-sessed a daily Therapeutic Intervention Scoring Sys- sion model was then computed by a stepwise ap-tem (TISS-28) score[17] for capturing some medical proach, and adjusted odds ratios with 95% CIs wereand nursing procedures. Those procedures were also calculated for all variables. Variables with a p-valuepriced according to the AMB index. ≤0.25 in the univariate analysis were considered for

entry into a stepwise multiple logistic regression,Cost comparisons between different subgroupsand a p-value ≤0.10 was required for a variable to(i.e. survivors vs non-survivors, patients from publicstay in the model.[21] All p-values were two-sidedvs from private hospitals) were also performed.and a p-value <0.05 was considered statisticallyCosts are presented in $US ($US1 = 2 Braziliansignificant. Marginal significance was defined as aReais [$Brz]), year 2004 values. As we collectedp-value between 0.05 and 0.10.data from 2004, we adjusted all values using a 10%

inflation rate to year 2006 values, according to Bra- Statistical analyses were conducted using Min-zilian indexes for that period. itab software package for Windows® (release 13.1;

Table II. Demographic and clinical data of the study population

Parameter All (n = 524) Survivors (n = 291) Non-survivors (n = 233) p-ValueAge [year (mean ± SD)] 61.1 ± 19.2 58.6 ± 19.9 64.2 ± 17.9 0.001

Male/female (%) 58.6/41.4 58.4/41.6 58.8/41.2 0.930

Median ICU stay [days (IQR)] 10 (5–18) 11 (5–19) 9 (4–18) 0.012

≥2 organ dysfunctions (%) 67.9 56.7 81.9 <0.0001

SOFA score (mean ± SD) 7.5 ± 3.9 6.3 ± 3.5 9.1 ± 3.7 <0.0001

APACHE II score (mean ± SD) 22.3 ± 8.5 19.6 ± 7.7 25.7 ± 8.3 <0.0001APACHE II = Acute Physiology And Chronic Health Evaluation II; IQR = interquartile range; SOFA = sequential organ failure assessment.



Minitab Inc., State College, PA, USA) and SAS 9.1(Statistical Analysis System, Cary, NC, USA).

Results

With a mean age of 61.1 ± 19.2 years, 524 septicpatients from 21 centres were included in the study.The overall hospital mortality rate was 43.8%, themean APACHE II score was 22.3 ± 5.4 and themean SOFA score at ICU admission was 7.5 ± 3.9.The overall median ICU length of stay was 10 (IQR5–18) days. Table II shows the principal demo-graphic and clinical characteristics of the patients.

The primary site of infection was identified asfollows: respiratory tract infection in 53.5%; abdo-men/surgical wound in 19.5%; urinary tract in 8.9%;skin in 5%; and other/unknown sites in 13.1%. Themost frequent organ dysfunctions at ICU admissionwere respiratory and cardiovascular (74.6% and54%, respectively). Forty-four patients (8.4%) metthe sepsis criteria. Severe sepsis criteria were ful-filled in 85 (16.2%) and septic shock in 395 (75.4%)patients.

Regarding ICU costs of sepsis management, wefound that the median total cost per patient was$US9632 (IQR 4583–18 387; 95% CI 8657,10 672), while the median daily ICU cost was$US934 (IQR 735–1170; 95% CI 897, 963). Usingpredefined blocks to better understand the directcosts, we found that the median costs for blocks 1, 2and 3 were $US2607 (IQR 890–5482; 95% CI 2274,2982), $US3389 (IQR 1311–6794; 95% CI 2908,3773) and $US2138 (IQR 1131–3837; 95% CI1867, 2343), respectively (table III), which wereresponsible for 30.5%, 36.1% and 20.9% of totalcosts, respectively (table IV). All other costs (12.6%of total costs) were related to hospital fees (costblock 4), summing to $US1210 (IQR 605–2178;95% CI 1089, 1331).

Total and daily costs were dichotomized intoupper and lower 50th percentiles. Using multiplelogistic regression, two factors had a significantimpact on the upper 50th percentiles of total costs(ICU length of stay [odds ratio (OR) 1.02; 95% CI1.01, 1.04; p = 0.0041] and haematological dysfunc-tion [OR 0.59; 95% CI 0.38, 0.92; p = 0.020]). Ofnote, respiratory dysfunction (OR 1.44; 95% CI0.97, 2.17; p = 0.079) only had a marginal signif-


Tab

le I

II. O

vera

ll co

sts

($U

S,

year

200

6 va

lues

) in

sep

sis

man

agem

ent

acco

rdin

g to

dis

char

ge s

tatu

s an

d in

stitu

tion

mai

n ch

arac

teris

tics

Cat

egor

yA

llS

urvi

vors

Non

-sur

vivo

rsp-

Val

ueP

rivat

e ho

spita

lP

ublic

hos

pita

lp-

Val

ue(n

= 5

24)

(n =

291

)(n

= 2

33)

(n =

196

)(n

= 3

28)

Dai

ly I

CU

cos

t93

4 (7

35–1

170)

826

(668

–982

)10

94 (

888–

1342

)<

0.00

0197

7 (7

34–1

322)

914

(737

–113

4)0.

514

[med

ian

(IQ

R)]

Tot

al I

CU

cos

ta96

32 (

4583

–18

387)

1016

1 (3

806–

1819

9)94

25 (

5031

–19

585)

0.49

9994

90 (

4305

–17

034)

9773

(46

43–1

922

1)0.

3703

[med

ian

(IQ

R)]

Cos

t bl

ock

126

07 (

890–

5482

)2

676

(880

–536

5)24

79 (

907–

5732

)0.

8415

2324

(83

7–44

52)

2895

(92

7–59

67)

0.06

73[m

edia

n (I

QR

)]

Cos

t bl

ock

233

89 (

1310

–679

4)3

501

(112

3–65

57)

3315

(16

06–7

126)

0.13

0832

60 (

1207

–672

5)35

30 (

1519

–692

9)0.

3146

[med

ian

(IQ

R)]

Cos

t bl

ock

321

38 (

1130

–383

7)1

789

(912

–346

7)23

71 (

1313

–402

9)0.

0011

2294

(10

73–4

461)

1969

(11

50–3

485)

0.39

97[m

edia

n (I

QR

)]

Cos

t bl

ock

412

10 (

605–

2178

)1

331

(605

–229

9)10

89 (

484–

2178

)0.

0226

1089

(48

4–19

36)

1210

(60

5–22

99)

0.12

36[m

edia

n (I

QR

)]

aT

otal

s ca

lcul

ated

fro

m r

aw d

ata.

IQ

R =

inte

rqua

rtile

ran

ge.

430 Sogayar et al.

3806–18 199; 95% CI 8383, 11 246), respectively(p = 0.4999). However, the median daily ICU costwas significantly higher in non-survivors than insurvivors: $US1094 (IQR 888–1341; 95% CI 1058,1157) and $US826 (IQR 668–982; 95% CI 786,854), respectively (p < 0.001) [table III]. Plotting themedian daily ICU costs, we can observe differentpatterns of expenditure from day 1 to day 14 (figure1).

For patients admitted to public and private hospi-tals, we found a median SOFA score at ICU ad-mission of 7.5 and 7.1, respectively (p = 0.02), and amortality rate of 49.1% and 36.7%, respectively (p =0.006). Patients admitted to public and private hos-pitals had similar lengths of stay of 10 (IQR 5–19)days versus 9 (IQR 4–16) days (p = 0.091), while themedian total direct costs did not differ significantlyfor public ($US9773; IQR 4643–19 221; 95% CI8503, 10 818) versus private ($US9490; IQR4305–17 034; 95% CI 7610, 11 292) hospitals (p =0.37).

Discussion

This study presents the first economic analysis ofthe costs of sepsis in Brazilian ICUs, and revealsthat the cost of sepsis treatment is high and is notevenly distributed among patients. Importantly,there was a significant difference in mortality rates

Table IV. Breakdown (%) of total direct costs of sepsis manage-ment according to resource consumed

Block 1Electrophysiology (0.1)Lab tests (1.0)Cultures (0.3)Parenteral and enteral nutrition (18.1)Dialysis methods (3.4)Respiratory physiotherapy (0.7)Invasive and noninvasive ventilation (6.1)x-Ray (0.8)Total: 30.5

Block 2Intravenous or oral medications (including antibiotics) [32.8]Colloids (0.3)Albumin (2.6)Frozen fresh plasma (0.1)Packed red blood cells (0.3)Total: 36.1

Block 3Standard monitoring (6.0)Sample blood or other fluids collection (0.5)Central venous catheter (5.3)Pulmonary artery catheter (1.7)Dialysis catheter (intravenous or peritoneal) (2.8)Intracranial pressure monitoring (0.01)Arterial catheter (0.8)Clothes changes (1.7)Caring for drainages (0.1)Cardiopulmonary resuscitation (0.1)Tracheotomy (0.6)Laparotomy (0.3)Neurosurgery (0.4)Thoracotomy (0.2)Other surgeries (0.1)Total: 20.9

Block 4Hospital fees (12.6)Total: 12.6

icant effect. For daily costs, statistical significancewas found with age (OR 0.98; 95% CI 0.97, 0.99;p = 0.0045), cardiac dysfunction (OR 2.39; 95% CI1.58, 3.61; p < 0.0001), SOFA >7 (OR 1.84; 95% CI1.22, 2.79; p = 0.0039), death (OR 5.80; 95% CI3.77, 8.93; p < 0.0001) and private institution (OR2.06; 95% CI 1.34, 3.16; p < 0.001).

We analysed the costs of sepsis managementaccording to discharge status (survivors or non-survivors) and institution main characteristics (pri-vate or public). Although the median ICU length ofstay was higher in survivors than in non-survivors,total costs associated with ICU management of sep-sis were not significantly higher in non-survivorsthan in survivors: $US9425 (IQR 5031–19 584;95% CI 7776, 10 398) versus $US10 161 (IQR

1413121110987654321Days

1400

1300

1200

1100

1000

900

800

Cos

ts (

$US

)

Non-survivorsSurvivors

Fig. 1. Median daily intensive care unit costs (year 2006 values) perpatient, including error bars (95% CI), for survivor and non-survivorseptic patients.



between private and public hospitals. Finally, the and pricing factors prevent an easy comparison. Inmedian daily costs of non-survivor patients were addition, the case mix for sepsis should be taken intohigher than survivors during the ICU stay. account. Therefore, in contrast to the findings of

clinical studies, results of economic evaluations canThe information on the costs of sepsis is scarce,not be readily transferred from one country to an-mainly due to lack of data on resource use andother.standardized methods for determining the direct cost

of ICU care,[6] combined with inadequate data on Data from the Brazilian Healthcare DatabaseICU unit costs. Our study adopted a ‘bottom-up’ (DATASUS) show that hospital costs related toapproach in which the major components are de- sepsis are about $US600 per patient, while in thescribed by ‘cost blocks’.[6] Furthermore, we includ- present study we found a median total ICU cost ofed only ICU direct costs related to clinical support $US9 632 per patient. However, the cost in the(i.e. pharmacy, physiotherapy, radiology), consum- DATASUS relates only to the government reim-ables (i.e. drugs, fluid, nutrition, blood products) bursement for the initial diagnosis, according to theand personnel (medical and nursing staff). Costs ICD-10 code. In our study, we valued every re-related to equipment depreciation, estate and man- source consumed in the management of sepsis. Inagement activities were not included. This approach addition, the prevalence and mortality rates of sepsismakes different institutions comparable, not in in DATASUS were likely underestimated. Twoterms of values but in terms of resource utilization. large epidemiological sepsis studies, BASES[2] andWe believe that this simplified economic analysis Sepse Brasil,[26] have disclosed mortality rates muchcan provide reliable and interchangeable data. How- higher than those reported in DATASUS – and theever, it is important to emphasise that ICU costs same is true for prevalence. Both studies have re-accounted for only 38% of the total hospital costs in ported that about 15% of ICU beds are occupied byQuebec[22] and direct costs represented only 20–30% patients with severe sepsis, hence one could expectof the true cost of illness in septic patients in Ger- about 400 000 patients with severe sepsis annuallymany.[23] in Brazil. Such differences could be explained by

data collection differences: DATASUS considersIn the present study, the median total ICU costonly the diagnosis at hospital admission. For in-per patient was $US9632 (IQR 4583–18 387), whilestance, if a patient is admitted with severe com-the median daily ICU cost per patient was $US934munity-acquired pneumonia and then develops sep-(IQR 735–1170). These values are lower than thosesis, this patient will not be included in the number ofreported in other studies.[4,9,24] However, other stud-patients with septicaemia (sepsis).ies have reported mainly hospital costs rather than

ICU costs. For instance, Angus et al.[9] found a total We also addressed the impact of different clinicalhospital cost of $US22 100 per patient in a retro- features on total and daily ICU costs through aspective study in ICU and non-ICU septic patients in multiple logistic regression. ICU length of stay andthe US. In similar populations, Braun et al.[24] and haematological dysfunction were independentlyMoerer and Schmid[4] reported even higher costs, associated with higher or lower costs. Length of stayranging from $US26 820 to €23 296 per patient. is one of the most important isolated factors in cost

escalation.[5] Also, respiratory dysfunction was mar-Costs can vary according to severity of the dis-ginally associated with higher costs, probably due toease and to outcome. Chalfin and Burchardi[25]

oxygen and mechanical ventilation utilization, needanalysed 1405 patients and estimated mean totalfor a respiratory therapist, and nurse workload.charges per patient of $US38 304 in survivors andHowever, we were not able to adequately explain$US49 182 in non-survivors. Similarly, Brun-Buis-how haematological dysfunction could affect ICUson et al.[10] reported costs from €26 256 tocosts negatively. Such occurrence will drive us to€35 185 per patient, depending on the severity offurther explore in future studies questions regardingillness. However, simple, direct comparison amongthe impact of specific interventions on ICU costs.all those studies and the present study is not feasible.

Country-specific healthcare systems, reimburse- Interestingly, in our study, the costs of non-survi-ment rates and regulations as well as different cost vors increased day by day, while the costs of survi-


432 Sogayar et al.

vors decreased after the first few days. To our know- cribe these costs on a daily basis. Perhaps the relia-ledge, this pattern has not been previously demon- bility of the data, taken in a prospective daily basis,strated. This finding suggests that those patients allowed this finding.who receive proper treatment and respond will de-

Study Limitationsvelop less organ dysfunction, with consequent re-duced costs. Specifically for severe sepsis, the Sur-

Our study also has some limitations. First, indi-viving Sepsis Campaign[27] provides recommenda-rect costs (e.g. productivity losses), costs related totions for early treatment, which can likely reduceequipment usage, estates and non-clinical supportmortality and, consequently, costs. Our study rein-services were not included in this economic ana-forces the need for urgent implementation of evi-lysis. Second, we did not capture any cost generateddence-based protocols, as survivors consume, on abefore ICU admission or after ICU discharge. Wedaily basis, fewer resources than non-survivors.believe that this approach makes our data more

Although resource constraints are more pro-useful for Brazilian institutions, allowing them to

nounced in Brazilian public than in private hospi-plan for strategies to reduce ICU costs, which really

tals, the cost of sepsis management was similar. Thisimpact on the total hospital cost. However, there is

is true even when the separated blocks are consid-strong evidence that hospital survivors of severe

ered, meaning that the resource utilization such assepsis remain at considerably increased risk for

clinical support services, consumables and staff arerehospitalization[7] and continue to consume health-

likely to be the same. However, there was a signifi-care resources. Third, we did not classify our hospi-

cantly higher mortality rate in public hospitals. Thistals according to teaching status. As already shown

finding has already been reported in a previousby Angus et al.,[9] teaching hospitals tend to expend

epidemiological study.[2] At that time, we hypothe-more money in treating their patients. The cost of

sized that this higher mortality could be the conse-care appears lower at non-teaching hospitals, pre-

quence of a shortage of resources, but this was notsumably attributable to differences in case mix or in

confirmed. However, the difference might be asso-caring (such as the costs of teaching), or both. This

ciated with other factors, such as a delay in receivingmight have contributed to the absence of difference

proper treatment caused, for example, by ICU bedbetween public and private hospitals, as university

shortages, or even subtle differences related to thehospitals are generally public. However, many of

case mix of patients arriving in public ICUs.the private hospitals, although not linked to any

There are some strengths to our study. First, this university, could also be considered teaching institu-is a prospective study, with daily data collection, tions, if they run fellowship or residency program-predefined inclusion criteria and a homogeneous mes. Fourth, there were significant discrepancies inand reliable population sample. To our knowledge, costs between private and public health systems. Weonly one study has adopted our approach, but it decided to use standard price lists, and not pricescollected data from a single centre.[10] Second, it was adopted by every institution, in order to providea nationwide study, with 21 centres in three different useful comparisons. Hence, our cost estimation inBrazilian regions. Different types of hospital were public hospitals could be inflated. Finally, both,included, both private and public, many of them hospital costs and mortality rates are all-cause esti-being teaching hospitals. This heterogeneity of hos- mates and not the actual costs or mortality ratespitals and regions makes our study a relevant source exclusively related to sepsis. Thus, preventing sep-of information regarding costs of sepsis in Brazil. In sis altogether would only diminish these costs.this context, it is also important to emphasise thatthis is the first Brazilian study of the costs of sepsis. ConclusionsFinally, this is the first study to clearly demonstratea difference in the pattern of costs between survivors This prospective, multicentre, Brazilian study,(decremental) and non-survivors (incremental). Our shows that sepsis treatment is expensive and thatfindings are in accordance with previous reports of costs are not evenly distributed among patients.higher costs in non-survivors and, in addition, des- More money and resources appear to be expended



3. Martin GS, Mannino DM, Eaton S, et al. The epidemiology ofon non-survivors than survivors, and the costs ofsepsis in the United States from 1979 through 2000. N Engl J

non-survivors increase on a daily basis. Additional- Med 2003; 348: 1546-544. Moerer O, Schmid A, Hofmann M, et al. Direct costs of severely, there was a significant difference regarding pa-

sepsis in three German intensive care units based on retrospec-tient outcome between public and private institu- tive electronic patient record analysis of resource use. Inten-sive Care Med 2002 Oct; 28 (10): 1440-6tions, which might be explained, among other rea-

5. Burchardi H, Schneider H. Economic aspects of severe sepsis: asons, by early access to qualified healthcare and ICUreview of intensive care unit costs, cost of illness and cost

admission in private institutions. effectiveness of therapy. Pharmacoeconomics 2004; 22 (12):793-813

6. Edbrooke D, Hibbert C, Ridley S, et al., and The Intensive CareAcknowledgementsWorking Group on Costing. The development of a method forcomparative costing of individual intensive care units. Anaes-In addition to the authors, the following institutions andthesia 1999; 54: 110-20investigators participated in the study as clinical sites. 7. Lee H, Doig CJ, Ghali WA, et al. Detailed cost analysis of care

Hospital Sao Paulo (UNIFESP): Gutemberg de Souza for survivors of severe sepsis. Crit Care Med 2004; 32 (4):Cardoso, Ley Bueno; Hospital das Clinicas (UFPR): Nazah 981-5

8. Edbrooke DL, Hibbert CL, Kingsley JM, et al. The patient-Cherif Youssef; Hospital Mater Dei: Adriano Dantas; Hos-related cost of care for sepsis patients in a United Kingdompital de Base: Adriana Carta, Marco Aurelio Spegioriu;adult general intensive care unit. Crit Care Med 1999; 27:Hospital Universitario Regional Norte do Parana (UEL):1760-7

Cintia M.C. Grion; Hospital Laranjeiras (Instituto Nacion- 9. Angus DC, Linde-Zwirble WT, Lidicker J, et al. Epidemiologyal de Cardiologia): Bernardo R. Tura; Hospital Geral do of severe sepsis in the United States: analysis of incidence,Grajau: Tatiana Mohovic, Regina Helena Lima Caltabiano; outcome, and associated costs of care. Crit Care Med 2001; 29:

1303-10Hospital Israelita Albert Einstein: Elias Knobel, Evandro10. Brun-Buisson C, Roudot-Thoraval F, Girou E, et al. The costs ofJose de Araujo Figueiredo, Thereza Phitoe Abe Ferreira;

septic syndromes in the intensive care unit and influence ofHospital Pro-Cardiaco: Rubens Costa Filho, Andre Assis dehospital-acquired sepsis. Intensive Care Med 2003; 29:

Albuquerque, Mauricio Vaisman; Hospital Sao Lucas 1464-71(PUC): Iuri C. Wawrzeniak, Fernando S. Dias; Hospital 11. Ministerio da Saude. Brazilian healthcare database: DATASUSMunicipal Professor Alipio Correa Neto: Fatima Barbosa [online]. Available from URL: http://tabnet.datasus.gov.br

[Accessed 2007 Aug 1]Cordeiro, Wilson Roberto Oliver, Elcio Tarkieutab; Hospital12. Knaus WA, Draper EA, Wagner DP, et al. APACHE II: aPortugues: Jose Mario Meira Teles; Hospital Santa Luzia:

severity of disease classification system. Crit Care Med 1985Marcelo de O. Maia, Henrique Marconi Sampaio Pinhati; Oct; 13 (10): 818-29Hospital Bandeirantes: Mario Lucio Alves Baptista Filho, 13. Vincent JL, Moreno R, Takala J, et al. The SOFA (Sepsis-Claudio Nazareno do Prazer Conceicao, Luiz Antonio related Organ Failure Assessment) score to describe organ

dysfunction/failure. Working Group on Sepsis-Related Prob-Carvalho Ribeiro; Hospital das Clinicas (UNESP): Analems of the European Society of Intensive Care Medicine.Lucia Gut, Mirna Matsui, Ana Lucia dos A. Ferreira; Casa deIntensive Care Med 1996 Jul; 22 (7): 707-10Saude Sao Jose: Fabio G. de Miranda; Hospital Municipal

14. Bone RC, Balk RA, Cerra FB, et al. Definitions for sepsis andSao Jose: Milton Caldeira Filho, Glauco Adrieno Westphal, organ failure and guidelines for the use of innovative therapiesFrancine Bagnati, Mariane De Cas De Aquim; Hospital in sepsis: the ACCP/SCCM Consensus Conference Commit-Beneficencia Portuguesa: Daniela Ortega, Renata Alberini, tee. American College of Chest Physicians/Society of Critical

Care Medicine. Chest 1992 Jun; 101 (6): 1644-55Haggeas da Silveira Fernandes; Hospital Vera Cruz:15. Brazilian Medical Association. Price index for medical proce-Dinalva Aparecida Mendes, Fernando Carvalho Neuen-

dures [online]. Available from URL: http://www.amb.org.brschwander, Eliane Maria Ferreira de Moura; Hospital Sirio[Accessed 2007 Aug 1]Libanes: Guilherme Schettino, Elton Scaramal; Hospital 16. Brasindice price index [online]. Available from URL: http://

Nossa Senhora das Gracas: Cassiana Pulgatti, Heitor Joao www.brasindice.com.br [Accessed 2007 Aug 1]Lagos. 17. Miranda DR, de Rijk A, Schaufeli W. Simplified therapeutic

intervention scoring system: the TISS-28 items. Results from aWe are also indebted to Frederico Rafael Moreira, whomulticenter study. Crit Care Med 1996 Jan; 24 (1): 64-73served as the statistics consultant.

18. Spiegel MR. Theory and problems of probability and statistics.This study was sponsored by an educational grant from New York: McGraw-Hill, 1992: 116-7Eli Lilly Brazil. Jorge Safi and Marcia Kayath were employ- 19. Lehmann EL. Nonparametric statistical methods based onees of Eli Lilly at the time the study was conducted. The ranks. New York: McGraw-Hill, 1975authors have no other conflicts of interest that are directly 20. Fisher LD, van Belle G. Biostatistics: a methodology for health

sciences. New York: John Wiley and Sons, 1993relevant to the content of this study.21. Hosmer DW, Lemeshow S. Applied logistic regression. 2nd ed.

New York: John Wiley and Sons, 2000References 22. Letarte J, Longo CJ, Pelletier J, et al. Patient characteristics and

1. Angus DC, Pereira CA, Silva E. Epidemiology of severe sepsis costs of severe sepsis and septic shock in Quebec. J Crit Carearound the world. Endocr Metab Immune Disord Drug Targets 2002; 17 (1): 39-492006 Jun; 6 (2): 207-12 23. Schmid A, Burchardi H, Clouth J, et al. Burden of illness

2. Silva E, Pedro MA. Brazilian Sepsis Epidemiological Study imposed by severe sepsis in Germany. Eur J Health Econ 2002;(BASES study). Crit Care 2004 Aug; 8 (4): R251-60 3 (2): 77-82


434 Sogayar et al.

24. Braun L, Riedel AA, Cooper LM. Severe sepsis in managed 27. Dellinger RP, Carlet JM, Masur H, et al. Surviving Sepsiscare: analysis of incidence, one-year mortality, and associated Campaign guidelines for management of severe sepsis andcosts of care. J Manag Care Pharm 2004 Nov-Dec; 10 (6): septic shock. Intensive Care Med 2004 Apr; 30 (4): 536-55521-30

25. Chalfin DB, Burchardi H. Definitions and methods of costassessment: an intensivist’s guide. ESICM section on health

Correspondence: Eliezer Silva, Latin American Sepsis Insti-research and outcome working group on cost effectiveness.Intensive Care Med 2002 Jun; 28 (6): 680-5 tute, Rua Jose Jannarelli, 199, conjunto 153, Morumbi, Sao

26. Sales Jr JA, David CM, Hatum R, et al. Sepse Brasil: estudo Paulo, CEP 05615-000, Brazil.epidemiologico da sepse em unidades de terapia intensivabrasileiras. RBTI 2006, 17 E-mail: [email protected]


Documents

A Multicentre, Prospective Study to Evaluate Costs of Septic Patients in Brazilian Intensive Care Units