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Published by Elsevie

http://dx.doi.org/10

E-mail: legrandg

* Address correspo 75010 Paris, France.

journal homepage: www.elsevier .com/ locate / jva l

Goal-Directed Fluid Therapy Guided by Cardiac Monitoring During High-Risk Abdominal Surgery in Adult Patients: Cost- Effectiveness Analysis of Esophageal Doppler and Arterial Pulse Pressure Waveform Analysis Guillaume Legrand, MD, MSc1,2,*, Laura Ruscio, MD3, Dan Benhamou, MD, PhD3,4, Nathalie Pelletier-Fleury, MD, PhD5

1Department of Urology and Transplantation, Saint-Louis Hospital, Paris, France; 2Center of Research, Medicine, Sciences, Mental Health, Society (CERMES 3), Villejuif, France; 3Department of Anesthesia and Reanimation, Bicêtre Hospital, Le Kremlin Bicêtre, France; 4French Society of Anesthesia and Reanimation (SFAR), Paris, France; 5Team 1 “Health Economic – research on Health Service”. Center of Research in Epidemiology and Health of Populations (UMR 1018), Villejuif, France

A B S T R A C T

Background: Several minimally invasive techniques for cardiac out- put monitoring such as the esophageal Doppler (ED) and arterial pulse pressure waveform analysis (APPWA) have been shown to improve surgical outcomes compared with conventional clinical assessment (CCA). Objective: To evaluate the cost-effectiveness of these techni- ques in high-risk abdominal surgery from the perspective of the French public health insurance fund. Methods: An analytical decision model was constructed to compare the cost-effectiveness of ED, APPWA, and CCA. Effectiveness data were defined from meta- analyses of randomized clinical trials. The clinical end points were avoidance of hospital mortality and avoidance of major complica- tions. Hospital costs were estimated by the cost of corresponding diagnosis-related groups. Results: Both goal-directed therapy strat- egies evaluated were more effective and less costly than CCA. Perioperative mortality and the rate of major complications were reduced by the use of ED and APPWA. Cost reduction was mainly due to the decrease in the rate of major complications. APPWA was

ee front matter Copyright & 2015, International S

r Inc.

.1016/j.jval.2015.04.005

uillaum@gmail.com.

ndence to: Legrand Guillaume, Service d’Urologie et

dominant compared with ED in 71.6% and 27.6% and dominated in 23.8% and 20.8% of the cases when the end point considered was “major complications avoided” and “death avoided,” respectively. Regarding cost per death avoided, APPWA was more likely to be cost-effective than ED in a wide range of willingness to pay. Con- clusions: Cardiac output monitoring during high-risk abdominal sur- gery is cost-effective and is associated with a reduced rate of hospital mortality and major complications, whatever the device used. The two devices evaluated had negligible costs compared with the observed reduction in hospital costs. Our comparative studies suggest a larger effect with APPWA that needs to be confirmed by further studies. Keywords: abdominal surgery, arterial pulse pressure waveform analysis, cost-effectiveness, esophageal Doppler, goal-directed fluid therapy.

Copyright & 2015, International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc.

Introduction

Goal-directed fluid therapy based on cardiac output monitoring during high-risk surgery is associated with better tissue perfu- sion, decreased risk of perioperative complications, improved postoperative rehabilitation, and reduction in hospital length of stay compared with standard hemodynamic monitoring based on clinical parameters (blood pressure, heart rate, and urinary out- put) or use of a central venous catheter [1–3].

Initially, the criterion standard for cardiac output monitoring was the thermodilution method, which required the insertion of a pulmonary artery catheter, an invasive procedure with signifi- cant morbidity and whose clinical benefit has been questioned [4].

Over the last 15 years, several new minimally invasive devices have been developed and have become commercially available: esophageal Doppler (ED), the most widely used technique, meas- ures blood flow velocity in the descending thoracic aorta through a probe inserted in a patient’s esophagus during general anes- thesia. This technique allows for continuous estimation of the corrected flow time, stroke volume, and cardiac output. A predetermined decision algorithm is used to guide fluid therapy according to the cardiac output variation. Another minimally invasive technique, the arterial pulse pressure waveform analysis (APPWA), allows a similar way to measure continuous cardiac output thanks to an arterial catheter connected to a monitor analyzing pulse pressure waveform.

ociety for Pharmacoeconomics and Outcomes Research (ISPOR).

Transplantation, Hôpital Saint-Louis. 1 Avenue Claude Vellefaux.

 

 

APPWA + CCA

Fig. 1 – Economic decision model tree comparing three strategies of intraoperative hemodynamic monitoring.

V A L U E I N H E A L T H 1 8 ( 2 0 1 5 ) 6 0 5 – 6 1 3606

Several randomized control trials (RCTs) and meta-analyses have shown clinical benefit with ED and APPWA compared with conventional clinical assessment (CCA) in high-risk surgery and high dependency units (HDUs) [1,2,5,6]. Two systematic reviews have recently studied the contribution of ED in terms of reduction in the rate of complications, hospital length of stay, and mortality compared with CCA [5,7]. In the United Kingdom, the National Institute of Health and Care Excellence published in 2011 good practice guidelines for ED and has argued that in an enhanced recovery program, the cost saving per patient when ED was used instead of a central venous catheter in the perioperative period was about £1100 based on a 7.5-day hospital stay [8]. These recommendations, however, have been discussed because they were based on a small number of RCTs with quite small and heterogeneous populations: Interventions studied were as diverse as cardiac, orthopedic, and abdominal surgery, in oper- ative rooms or in HDUs [9]. More recently, other RCTs have been published focusing on abdominal surgery [10–15], but their results remain to be synthetized.

Actually, cardiac output monitoring during high-risk surgery is not systematically implemented and costs could be a barrier to its adoption. This is especially disturbing because it can be suspected that, depending on the device used, morbidity, mortality, and length of stay could be different. Economic evaluation can help decision makers reach an optimal allocation of resources [16].

To date, only two economic studies have evaluated ED and have shown that it is an efficient strategy compared with CCA alone [5,17], but, to our knowledge, costs and consequences of using other techniques of minimally invasive cardiac output monitoring such as APPWA have never been investigated.

The aim of this study was to evaluate the cost-effectiveness ratio of ED and APPWA in comparison to that of CCA in intermediate- and high-risk abdominal surgery from the French public health insurance fund perspective.

APPWA, arterial pulse pressure waveform analysis; CCA, conventional clinical assessment; ED, esophageal Doppler.

Methods

Economic Model

A decision tree was constructed to compare the cost-effectiveness ratios of three hemodynamic monitoring and fluid therapy strat- egies in intermediate- and high-risk abdominal surgery (Fig. 1). Interventions compared were CCA, including measurements of heart rate, blood pressure, and urinary output with or without central venous catheter monitoring; measurement of cardiac out- put with ED (CardioQ-ODM, Deltex Medical) associated with stand- ard monitoring (ED þ CCA); and measurement of cardiac output with APPWA (Vigileo/FloTrac, Edwards Lifesciences) associated with standard monitoring (APPWA þ CCA).

Following each strategy, three individual outcomes were possi- ble: death of the patient, occurrence of major complications, and discharge without any major complication, occurring with a prob- ability P depending on the clinical effectiveness of each outcome.

The time horizon considered was the hospital period, extend- ing from entrance until hospital discharge. It was assumed that hemodynamic optimization and fluid administration during sur- gery would not influence outcomes after discharge. This assump- tion was also made in all the RCTs.

Clinical-Effectiveness Data

The two effectiveness criteria considered were avoidance of mortality and avoidance of major complications. A complication was considered as major when resulting in hospitalization in the intensive care unit or revision surgery, reported as grade 3 or 4 complications in Dindo et al.’s classification [18].

A comprehensive review of the literature was performed in January 2013 without any time or language restriction using PUBMED, EMBASE, and COCHRANE databases, and complementary research was performed on the basis of the bibliography section of articles, unpublished studies, and proceedings from scientific confer- ences. Key words used were “esophageal Doppler,” “goal directed therapy,” hemodynamic,” “arterial pulse pressure waveform analy- sis,” and “surgery.” All RCTs comparing CCA with a minimally invasive method of cardiac output monitoring during abdominal surgery and related mortality or major complications were included, whatever the number of patients. Studies conducted in pediatrics, in HDUs or in nonabdominal surgery, were excluded. A second author performed data extraction independently, and the methodological quality of the trials was assessed using the Jadad score [19].

Based on the selected articles, meta-analyses of effectiveness data were performed to estimate probabilities.

CCA For CCA, the probability of an event (death or major complication) corresponded to the overall proportion of the event, and the 95% confidence interval (CI) was calculated from a meta-analysis of single-proportion control groups that we performed, considering all RCTs and comparing the CCA strategy with another strategy (ED þ CCA and APPWA þ CCA). These values were used for the base-case analysis.

ED and APPWA For both alternatives to CCA (ED þ CCA and APPWA þ CCA), the probability for an event (death or major complication) was

 

 

V A L U E I N H E A L T H 1 8 ( 2 0 1 5 ) 6 0 5 – 6 1 3 607

estimated as the product of the probability for the CCA strategy and the relative risk (RR) associated with the corresponding alternative. RR was used instead of pooled proportion to estimate probabilities of event because no event was observed in the intervention groups of some trials.

Meta-analyses of RCTs were conducted to assess the RR (with 95% CI) of mortality and major complications for ED and APPWA compared with CCA. The Mantel-Haenzel method with fixed- effect model was used. We drew funnel plots to check for the existence of publication bias.

Cost Data

Only direct medical costs were considered, i.e., hospital costs and costs of equipment. Hospital costs were valued as the cost of the corresponding diagnosis-related group (DRG). In France, each hospital stay is assigned to a DRG on the basis of principal diagnosis, procedures performed, length of stay, and level of severity (comorbidities and complications). These costs include expenses of clinical activity, costs of supporting activities, logistic costs, and management overheads and expenses. There is one national DRG system in France used as the basis of hospital payment since 2004–2005. As recommended by the Department of Economics and Public Health Assessment of the French National Authority for Health (Haute Autorité de Santé) in 2012, the preferred source of data to approximate the production cost of a hospital stay is the national cost study (Etudes Nationales de Coûts à méthodologie Commune [ENCC]), performed by the Technical Agency for Hospital Information (Agence Technique de l’Information sur l’Hospitalisation). The data from the ENCC are based on the hospital-cost accounting system by DRGs. The production costs from the ENCC represent average costs, with the limit of masking some variations between establishments [20]. We took this into account in the sensitivity analysis.

The costs used at baseline and for sensitivity analysis were the DRG costs for colic and rectal surgeries performed in a public hospital, ranging from levels 1 to 4 based on comorbidities and complications. Levels 1 or 2 corresponded to colic or rectal surgery with minor comorbidities (i.e., controlled hypertension or diabetes) or complication(s) (i.e., wall abscess or minor infec- tion). Levels 3 or 4 corresponded to colic or rectal surgery with major complication(s) (i.e., peritonitis, myocardial infarction, acute heart failure, stroke, sepsis). Because death occurs most generally after a major complication, level 3 valued death at baseline.

Equipment costs applied only to devices monitoring cardiac output. It was assumed that CCA costs were included into hospital costs. For ED and APPWA, equipment costs were provided by manufacturers and included costs of disposable probes and monitoring equipment. The prices provided by the manufacturers were list prices that could be negotiated by each hospital depend- ing primarily on the number of surgical procedures provided per year. This was taken into account in the sensitivity analysis. Equipment cost for each usage of the system was calculated. The calculation assumed that the equipment would last 5 years and would be used 300 times per year (other utilization rates were tested in sensitivity analyses). Capital costs of devices were converted to an equivalent annual cost by applying a 5% discount rate to adjust for consecutive years of usage.

The costs used in the present analysis are presented in 2011 euros.

Cost-Effectiveness Analysis

The cost-effectiveness ratio of each strategy was calculated and compared in pairs. Incremental cost-effectiveness ratios (ICERs) were calculated: cost per major complication avoided and cost

per death avoided. A more effective and less costly strategy was considered a dominant strategy. Conversely, a less effective and more expensive strategy was considered a dominated strategy. ICERs were not calculated in these cases.

Sensitivity Analysis

One-way deterministic sensitivity analyses were performed by individually varying each variable of cost and effectiveness to identify those with the greatest influence on the results. Upper and lower bounds of 95% CI were used to define minimal and maximal values of probabilities.

Probabilistic sensitivity analysis was performed using the Monte-Carlo method to consider the impact of the uncertainty associated with different values of the variables on the cost- effectiveness ratio. Several values were randomly assigned to different costs and effectiveness variables of the model on the basis of a probability distribution. We considered that the probabilities were distributed according to a beta distribution, and RRs were distributed according to a lognormal distribution. For costs, we chose a triangular distribution with lower and upper bounds used in the one-way sensitivity analysis. An overall estimate of the distribution of the cost-effectiveness ratio was obtained by performing 1000 iterations, illustrated by cost- effectiveness planes. The results of this analysis are also pre- sented as cost-effectiveness acceptability curves. Central to the assessment of cost-effectiveness is the value that society would place on gaining an additional unit of effectiveness. Therefore, by knowing a particular willingness-to-pay (WTP) value on the horizontal axis, the probability that an option will be cost- effective can be obtained from the vertical axis.

Results

Clinical Effectiveness

A comprehensive literature search identified a total of 13 RCTs: 10 RCTs comparing CCA with ED þ CCA [10–13,15,21–25], including three unpublished studies [13,15,22] and three RCTs comparing CCA with APPWA þ CCA in high-risk abdominal surgery [6,26,27]. None has been deemed to be of inadequate methodological quality (Table 1).

The probability of mortality and major complications with CCA calculated from pooled data from 13 (N ¼ 653) [6,10–13,15,21– 27] and 7 (N ¼ 366) studies [6,10–12,21,22,24] was 0.04 (95% CI 0.02–0.07) and 0.16 (95% CI 0.10– 0.24), respectively.

ED was associated with a significant decrease in perioperative mortality when compared with CCA with a fixed-effect model based on data from 10 studies (N ¼ 1 078) [10–13,15,21–25] (RR ¼ 0.47; 95% CI 0.24–0.91). The RR of major complications, calculated from six studies (N ¼ 603) [10–12,21,22,24], showed a trend toward better results with ED (RR ¼ 0.69; 95% CI 0.44–1.09) (Fig. 2).

Mortality was two times lower with APPWA than with CCA based on the meta-analysis of three studies (N ¼ 213) [6,26,27] (RR ¼ 0.54; 95% CI 0.19–1.51) (Fig. 2). The RR of major complica- tions with APPWA was calculated from only one study (N ¼ 120) [6]; it was approximately three times lower than with CCA (RR ¼ 0.3; 95% CI 0.13–0.69).

Probability values and their distribution, which were used to implement the model, are summarized in Table 2. As shown by the funnel plots of study size against treatment effect, there was no evidence of publication bias (Fig. 3).

Cost Data

At baseline, a hospital stay without death or major complication was valued at €9465, corresponding to a DRG of level 2 colic

 

 

Table 1 – Characteristics of the selected studies.

Study Intervention N Type of surgery Mean age (y)

ASA 42 (%) Mean P- POSSUM

Mean BMI (kg/m2)

S C S C S C

Srinivasa et al. [10] ED 85 Colorectal 69 72 39 9 9 26.9 26.4 Challand et al. [11] ED 179 Colorectal 66 65.9 30 – – Brandstrup et al.

[12] ED 150 Colorectal 66.9 68.1 16 – 24.8 25.6

Karas et al. [13] ED 91 Colorectal 57 57 80 8 8 27.5 27.7 Szturz et al. [15] ED 230 Nephrectomy,

prostatectomy, cystectomy

61.5 62.8 – – –

Conway et al. [21] ED 57 Colorectal 66.5 67.5 – – – Dodd et al. [22] ED 40 Colorectal 76.3 76.3 – – 25.3 23.9 Wakeling et al. [23] ED 134 Colorectal 69.1 69.6 – 17 18 24.5 26 Noblett et al. [24] ED 108 Colorectal 62.3 67.6 – 16 16 25.9 26.4 Senagore et al. [25] ED 64 Colorectal – – – – Benes et al. [6] APPWA 120 Colorectal,

pancreatic, vascular

66.7 66.3 79 21 20 –

Lopes et al. [26] APPWA 33 Colorectal, gastric, liver, urologic

63 62 82 – 24 23

Mayer et al. [27] APPWA 60 Colorectal, gastric, esophagus, liver

73 72 – 22 21 26.4 25.8

APPWA, arterial pulse pressure wave analysis; ASA, American Society of Anesthesiology; BMI, body mass index; C, control group; ED, esophageal Doppler; P-POSSUM, physiologic component of Physiologic and Operative Severity Score for the enUmeration of Mortality and Morbidity; S, study group.

V A L U E I N H E A L T H 1 8 ( 2 0 1 5 ) 6 0 5 – 6 1 3608

surgery. Values used for sensitivity analyses ranged from €6452 (lower bound of level 1 colic surgery) to €12,118 (upper bound of level 2 rectal surgery). The cost of a hospital stay when at least one major complication occurred was valued at €13,900, corre- sponding to a DRG of level 3 colic surgery, with values used for sensitivity analyses ranging from €12,213 (lower bound of level 3 colic surgery) to €31,667 (upper bound of level 4 rectal surgery). Baseline value for a death was €13,900, corresponding to level 3 of colic surgery, and values used for sensitivity analyses ranged from €6,452 (lower bound of level 1 colic surgery) to €31,667 (upper bound of level 4 rectal surgery) [31].

Manufacturers provided the costs of devices. For ED, the cost of the monitor (CardioQ-ODM) was €13,300, the equivalent annual cost was €3,072, and the cost of one probe was €150. For APPWA, the cost of the monitor (Vigileo/FloTrac) was €10,166, the equiv- alent annual cost was €2,348, and the cost of one probe was €167. Based on a mean of 300 procedures per year with bounds used for sensitivity analyses from 100 to 500, the total cost per patient was €160 (€156–€180) and €174 (€171–€191), respectively, for ED and APPWA.

Cost-Effectiveness Analysis

Avoided Major Complications At baseline, the two goal-directed fluid therapy strategies were more effective and less costly compared with CCA. Moreover, APPWA was dominant compared with ED, as shown in Table 3.

In one-way sensibility analysis, APPWA was always dominant compared with CCA, and ED was dominant most of the time compared with CCA. ED was dominant over APPWA in three situations, but was dominated in all others. The results were sensitive to variation in probabilities of death and major compli- cations but not to variation in cost data (Table 3).

In probabilistic sensitivity analysis, APPWA and ED were dominant compared with CCA in 97.3% and 76.1% of cases,

respectively, and were dominated in 0% and 13.3% of cases, respectively. ED compared with APPWA was dominant in only 23.8% of cases and was dominated in 71.6% of cases (Fig. 4). In the remaining 4.6% of cases, the probability of being cost-effective depended on the WTP for a major complication avoided.

Avoided Death At baseline, the two goal-directed fluid therapy strategies were more effective and less costly compared with CCA. ED was more effective but more costly than APPWA, with an ICER equal to €79,600 per avoided death (Table 3).

In one-way sensitivity analysis, ED and APPWA were largely dominant compared with CCA. When the minimum value was applied to the probability of death in the CCA strategy, the latter became more effective and more costly compared with the two goal-directed strategies. ED was dominant over APPWA in three situations and was dominated in two situations. In other cases, the ICER between the two strategies ranged from €11,177 to €457,140 per avoided death (Table 3).

In probabilistic sensitivity analysis, APPWA and ED were dominant compared with CCA in 92.9% and 69.5% of cases, respectively, and were dominated in 0.2% and 4.1%, respectively. ED compared with APPWA was dominant in 20.8% and was dominated in 27.6% of cases (Fig. 4). Figure 5 shows that APPWA is more likely than ED to be cost-effective over a wide range of WTP. The difference in probabilities is larger (0.4) when the WTP is close to zero than when the WTP is at €100,000 (0.2).

Discussion

This economic study is the first to compare several methods of intraoperative minimally invasive cardiac output monitoring with standard monitoring based on the measurement of clinical parameters.

 

 

Study

Fixed effect model Heterogeneity: I-squared=0%, tau-squared=0, p=0.7652

SRINIVASA CONWAY WAKELING BRANDSTRUP NOBLETT CHALLAND SENAGORE DODD BERGAMASCHI SZTURZ

Events

0 0 0 1 0 5 0 1 0 3

Total

529

37 29 64 71 51 89 21 20 32 115

Experimental Events

2 1 1 1 1 4 0 2 0

12

Total

549

37 28 64 79 52 90 22 20 42

115

Control

0.01 0.1 1 10 100

Risk Ratio RR

0.47

0.20 0.32 0.33 1.11 0.34 1.26

0.50

0.25

95%-CI

[0.24; 0.91]

[0.01; 4.03] [0.01; 7.58] [0.01; 8.03] [0.07; 17.46] [0.01; 8.15] [0.35; 4.55]

[0.05; 5.08]

[0.07; 0.86]

W(fixed)

100%

9.6% 5.9% 5.8% 3.7% 5.7%

15.3% 0.0% 7.7% 0.0%

46.3%

Study

Fixed effect model Heterogeneity: I-squared=27.9%, tau-squared=0.1512, p=0.2255

SRINIVASA CONWAY BRANDSTRUP NOBLETT CHALLAND DODD

Events

7 0 9 1 5 4

Total

297

37 29 71 51 89 20

Experimental Events

7 4 7 7 9 5

Total

306

37 28 79 52 90 20

Control

0.01 0.1 1 10 100

Risk Ratio RR

0.69

1.00 0.11 1.43 0.15 0.56 0.80

95%-CI

[0.44; 1.09]

[0.39; 2.57] [0.01; 1.90] [0.56; 3.64] [0.02; 1.14] [0.20; 1.61] [0.25; 2.55]

W(fixed)

100%

17.9% 11.7% 17.0% 17.7% 22.9% 12.8%

Study

Fixed effect model Heterogeneity: I-squared=0%, tau-squared=0, p=0.7277

BENES MAYER LOPES

Events

1 2 2

Total

107

60 30 17

Experimental Events

2 2 5

Total

106

60 30 16

Control

0.1 0.5 1 2 10

Risk Ratio RR

0.54

0.50 1.00 0.38

95%-CI

[0.19; 1.51]

[0.05; 5.37] [0.15; 6.64] [0.08; 1.67]

W(fixed)

100%

21.9% 21.9% 56.3%

Fig. 2 – Meta-analysis of perioperative mortality and major complication risk with ED and APPWA compared with conventional clinical assessment. APPWA, arterial pulse pressure waveform analysis; CI, confidence interval; ED, esophageal Doppler; RR, relative risk.

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The results show that a fluid therapy strategy guided by optimizing cardiac output (regardless of the device used) provides better results. In most cases, this strategy was more effective in terms of both reduction in perioperative mortality and major complications and was less costly. Better results were achieved with APPWA compared with ED, but varied with the end point consid- ered. The interpretation of these results must take into account the uncertainty associated with the values assigned to the various parameters of cost and effectiveness in the model. According to one-way sensitivity analysis, the most critical parameter was the transition probabilities in different health states (i.e., the probability of death and the probability of having major complication).

Effectiveness data were calculated from meta-analyses of several rigorously selected RCTs according to the Mantel- Haenszel method with a fixed-effect model, which provides robustness to this study. These meta-analyses took into consid- eration recent studies [10–13,15] that were not evaluated in

previous meta-analyses [1,2,5,7,28]. Some unpublished studies have also been collected to obtain comprehensive data [13,15,22]. Regarding ED, several meta-analyses have demonstrated a clin- ical benefit in abdominal surgery [2,17,28]. A recent one con- ducted by Srinivasa et al. [29] showed that ED did not influence length of hospital stay or complications after colorectal surgery. The authors note that, unlike earlier studies, newer trials did not show any benefit from cardiac monitoring and suggest a possible publication bias [29]. All the studies selected by Srinivasa et al. in their meta-analysis have been included in ours. These studies concerned only colorectal surgery. In our study, four additional RCTs, including digestive and urologic surgery, were used. This could explain why our results are different. To our knowledge, our study is the first to demonstrate a statistically significant reduction in mortality compared with CCA.

Concerning APPWA, the literature was poor, few RCTs have been published, and neither meta-analysis nor economic studies

 

 

Table 2 – Clinical-effectiveness data used in base-case and sensitivity analysis.

Intervention Outcome Studies Value SD 95% CI Distribution

RR ED þ CCA vs. CCA Mortality (I) [10–13,15,21–25] 0.47 0.34 0.24 0.91 Lognormal Major complication

(II) [10–12,21,22,24] 0.69 0.23 0.44 1.09

APPWA þ CCA vs. CCA

Mortality (III) [6,26,27] 0.54 0.52 0.19 1.51 Major complication

(IV) [6] 0.32 0.13 0.69

Probability CCA Mortality (V) [6,10–13,15,21–27] 0.039 0.061 0.016 0.068 Beta Major complication

(VI) [6,10–12,21,22,24] 0.163 0.093 0.099 0.239

ED þ CCA Mortality (I) � (V) 0.018 0.004 0.062 Major complication (II) � (VI) 0.112 0.044 0.261

APPWA þ CCA Mortality (III) � (V) 0.021 0.003 0.103 Major complication (IV) � (VI) 0.052 0.013 0.165

Note. Probability to have an event in the control intervention group (ED þ CCA or APPWA þ CCA) is estimated as the product of the probability for the control group (CCA) and the RR associated with the corresponding alternative. APPWA, arterial pulse pressure waveform analysis; CCA, conventional clinical assessment; CI, confidence interval; ED, esophageal Doppler; RR, relative risk. Values in bold were used as probability p in the model.

V A L U E I N H E A L T H 1 8 ( 2 0 1 5 ) 6 0 5 – 6 1 3610

were available. We were the first to conduct a meta-analysis of three studies on mortality risk [6,26,27]. Only one study was available for the risk of major complications, and this could be a limitation [6]. Results of such a meta-analysis must be inter- preted with caution, as suggested by Morris [30] in a recent editorial. According to Morris, some data have emerged from evidence-based medicine raising concerns about the safety of intravascular volume expanders that are being used with goal- directed fluid therapy.

To date, only one economic study has evaluated ED during abdominal surgery. In this cost-effectiveness study, conducted by Maeso et al. [17], strategies were evaluated comparing ED and CCA with CCA alone. The authors showed that the use of ED was associated with a statistically significant lower rate of total and major complications, but not of mortality. Cost savings were mainly due to fewer complications, shorter hospital stays, and shorter intervention times. Our study used the same design, but also evaluated another strategy of cardiac output monitoring, namely, APPWA. The costs related to devices were negligible compared with hospital costs, whatever the number of annual procedures. Investment costs should not be an obstacle to device

0.02 0.05 0.10 0.20 0.50 1.00 2.00 5.00

1. 5

1. 0

0. 5

0. 0

St an

da rd

e rr

or

0.05 0.10 0.20 0.5

1. 5

1. 0

0. 5

0. 0

St an

da rd

e rr

or

Rela�ve Risk Rela�

Fig. 3 – Funnel plot of study size against treatment effect. (A) Stu (B) Studies comparing ED þ CCA vs. CCA for reduction in major for reduction in mortality. APPWA, arterial pulse pressure wave esophageal Doppler.

acquisition for institutions, given the clinical and economic benefits of cardiac output monitoring. Choosing between ED and APPWA, however, remains an issue: One may be tempted to prefer APPWA, but one should remain cautious because results are based on the few available studies and depend on the cost-effectiveness ratios thresholds considered acceptable, especially when the measure of effectiveness is avoided death. The choice of a threshold is questionable, and it may be advisable to refer to the acceptability curve to determine the probability for one strategy to be more efficient than another, depending of the decision maker’s WTP [16]. The time horizon chosen in our study can be discussed. It was assumed that cardiac output control systems and fluid administration during surgery would not influence outcomes after discharge. This assumption was also made in all the RCTs. If, however, we think about stroke or myocardial infarction, these major complications probably have an impact on patient’s morbidity, survival, and/or quality of life, and also on costs after discharge, and this could be examined using modeling. The main reason why we chose this time horizon was for the purpose of local decision making.

0 1.00 2.00 5.00 10.00 0.05 0.10 0.20 0.50 1.00 2.00 5.00

1. 2

1. 0

0. 8

0. 6

0. 4

0. 2

0. 0

St an

da rd

e rr

or

ve Risk Rela�ve Risk

dies comparing ED þ CCA vs. CCA for reduction in mortality. complications. (C) Studies comparing APPWA þ CCA vs. CCA form analysis; CCA, conventional clinical assessment; ED,

 

 

Table 3 – Results of cost-effectiveness analysis in base-case scenario and in one-way sensitive analysis.

Variable Major complication avoided Death avoided

ED þ CCA vs. CCA

APPWA þ CCA vs. CCA

ED þ CCA vs. APPWA þ CCA

ED þ CCA vs. CCA

APPWA þ CCA vs. CCA

ED þ CCA vs. APPWA þ CCA

Incremental cost (€) �159.3 �398.1 238.8 �159.3 �398.1 238.8 Incremental effectiveness 0.072 0.129 �0.057 0.021 0.018 0.003 ICER Dominant Dominant Dominated Dominant Dominant 79,600

Variable Value ICER

Cost per major complication avoided Cost per mortality avoided

ED þ CCA vs. CCA

APPWA þCCA vs. CCA

ED þ CCA vs. APPWA þ CCA

ED þ CCA vs. CCA

APPWA þ CCA vs. CCA

ED þ CCA vs. APPWA þ CCA

pD (ED þ CCA) Min 0.004 Dominant Dominant Dominated Dominant Dominant 11,177.1 Max 0.062 1279.3 Dominant Dominated Dominant Dominant Dominated

pC (ED þ CCA) Min 0.044 Dominant Dominant Dominant Dominant Dominant Dominant Max 0.261 Dominated Dominant Dominated 167,165 Dominant 304,305.0

pD (APPWA þ CCA)

Min 0.003 Dominant Dominant Dominated Dominant Dominant Dominated Max 0.103 Dominant Dominant Dominant Dominant 746.1 Dominant

pC (APPWA þ CCA)

Min 0.013 Dominant Dominant Dominated Dominant Dominant 137,253.3 Max 0.165 Dominant Dominant Dominant Dominant 5,724.4 Dominant

pD (CCA) Min 0.016 Dominant Dominant Dominated 28,657.5 61,883.0 84,033.3 Max 0.068 Dominant Dominant Dominated Dominant Dominant 84,033.3

pC (CCA) Min 0.099 15,565 Dominant Dominated 5,929.5 Dominant 84,033.3 Max 0.239 Dominant Dominant Dominated Dominant Dominant 84,033.3

cC Min 12,213 Dominant Dominant Dominated Dominant Dominant 48,606.3 Max 31,667 Dominant Dominant Dominated Dominant Dominant 457,140.3

cD Min 6,452 Dominant Dominant Dominated Dominant Dominant 91,481.3 Max 31,667 Dominant Dominant Dominated Dominant Dominant 66,266.3

cW Min 6,452 Dominant Dominant Dominated Dominant Dominant 144,293.3 Max 12,118 443.9 Dominant Dominated 1,509.3 Dominant 30,973.3

cED Min 156 Dominant Dominant Dominated Dominant Dominant 82,700.0 Max 180 Dominant Dominant Dominated Dominant Dominant 90,700.0

cAPPWA Min 171 Dominant Dominant Dominated Dominant Dominant 85,033.3 Max 190 Dominant Dominant Dominated Dominant Dominant 78,700.0

APPWA, arterial pulse pressure waveform analysis; cAPPWA, cost of arterial pulse pressure waveform analysis; CCA, conventional clinical assessment; ICER, incremental cost-effectiveness ratio; pC, probability to have major complication; pD, probability of death; cC, hospital cost when a major complication occurs (in euros); cD, hospital cost when death occurs (in euros); cED, cost of cardioQ-ODM device (in euros); cAPPWA, cost of Vigiléo/FloTrac device (in euros); cW, hospital cost when no death or complication occurs (in euros); ED, esophageal Doppler.

V A L U E

IN H

E A L T H

1 8

(2 0 1 5 ) 6 0 5 – 6 1 3

611

 

 

Incremental cost-effectiveness, ED + CCA vs. CCA

Incremental cost-effectiveness, APPWA + CCA vs. CCA

Incremental cost-effectiveness, ED + CCA vs. APPWA + CCA

Incremental effectiveness (avoided mortality)

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Incremental effectiveness (avoided major complication including mortality)

Incremental effectiveness (avoided mortality)

Incremental effectiveness (avoided mortality)

Incremental cost-effectiveness, ED + CCA vs. APPWA + CCA

Incremental effectiveness (avoided major complication including mortality)

Incremental effectiveness (avoided major complication including mortality)

Incremental cost-effectiveness, ED + CCA vs. CCA

Incremental cost-effectiveness, APPWA + CCA vs. CCA

In cr

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Fig. 4 – Incremental cost-effectiveness ratio comparing ED þ CCA vs. CCA, APPWA þ CCA vs. CCA, and ED þ CCA vs. APPWA þ CCA in probabilistic sensitivity analysis. APPWA, arterial pulse pressure waveform analysis; CCA, conventional clinical assessment; ED, esophageal Doppler.

V A L U E I N H E A L T H 1 8 ( 2 0 1 5 ) 6 0 5 – 6 1 3612

A number of potential biases need to be recognized to relativize the superiority of cardiac output monitoring compared with clinical assessment in this study. First, RCTs on cardiac monitoring are unlikely to be blinded and clinicians might be more aware of the information provided by these new devices, which may overestimate their effect. Second, among the various studies, three were not published and the data were collected

after contacting the authors. Concerning heterogeneity between studies, the study by Szturz et al. [15] accounted for 46.3% of the RR of mortality with ED versus CCA and this possibly influences the results, especially because this study also included oncological urologic surgery (prostatectomy, cystectomy, nephrectomy), for which outcomes may differ from colorectal surgery [15]. There was also some heterogeneity between studies

 

 

Willingness to pay for an extra death avoided (€)

Pr ob

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Fig. 5 – Acceptability curves showing the likelihood of ED to be cost-effective compared with APPWA at different levels of willingness to pay for a death avoided (in euros). APPWA, arterial pulse pressure waveform analysis; ED, esophageal Doppler.

V A L U E I N H E A L T H 1 8 ( 2 0 1 5 ) 6 0 5 – 6 1 3 613

evaluating ED and those evaluating APPWA when the type of surgery was analyzed: Studies evaluating APPWA included not only colorectal surgery but also urologic, vascular, and upper abdominal (liver and pancreatic resection) surgery, whereas ED studies included only colorectal and urologic surgery. The former, however, are known to cause more complications, and cardiac output monitoring would be more beneficial in these situations because of longer time of surgery, more fragile vascular patients, and frequent hemodynamic changes related to arterial clamping, strengthening the argument in favor of APPWA.

Conclusions

Cardiac output monitoring during high-risk abdominal surgery is cost-effective and is associated with a reduced rate of hospital mortality and major complications, whatever the device used. The two devices evaluated had negligible costs compared with the reduction in-hospital costs. Our comparative studies suggest a larger effect with APPWA that needs to be confirmed by further studies.

R E F E R E N C E S

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[15] Szturz PS, Maca JM, Tichy JT, et al. Maintenance of cardiac index within normal range is associated with mortality reduction in patients undergoing major urological surgery. Crit Care 2010;14(Suppl.):S43. (Oral presentation).

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  • Goal-Directed Fluid Therapy Guided by Cardiac Monitoring During High-Risk Abdominal Surgery in Adult Patients:…
    • Introduction
    • Methods
      • Economic Model
      • Clinical-Effectiveness Data
        • CCA
        • ED and APPWA
      • Cost Data
      • Cost-Effectiveness Analysis
      • Sensitivity Analysis
    • Results
      • Clinical Effectiveness
      • Cost Data
      • Cost-Effectiveness Analysis
        • Avoided Major Complications
        • Avoided Death
    • Discussion
    • Conclusions
    • References

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