esophageal doppler ultrasound-based cardiac output ... · evidence on the clinical effectiveness...

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TITLE: Esophageal Doppler Ultrasound-Based Cardiac Output Monitoring for Adults undergoing Surgery: A Review of Clinical and Cost-Effectiveness

DATE: 18 March 2013 CONTEXT AND POLICY ISSUES Optimal management of cardiac output and fluid balance is considered one of the key elements in improving outcomes in high-risk surgical patients and in critically ill patients.1-3 Cardiac output refers to the amount of blood that is pumped by the heart in unit time and is calculated by multiplying the stroke volume by the heart rate.2 Stroke volume refers to the amount of blood pumped by the left ventricle in one contraction.2 Sufficient blood flow is required to provide adequate oxygen and nutrients to cells and tissues and to assist in the clearance of waste products.2,4 For patients undergoing surgery or in intensive care, optimization of intravenous fluid replacement is essential for maintaining adequate organ perfusion. If patients do not receive adequate additional fluids, there is possibility of hypovolemia (abnormally low levels of blood plasma) followed by hypotension and organ failure. On the other hand, excessive fluid addition may trigger heart failure.2 Several procedures for monitoring and optimizing intravenous fluid are available. These include thermodilution by pulmonary artery catheterization, the dye dilution method involving dye injection into the pulmonary artery and measurement of dye concentration at the femoral or radial artery, the lithium dilution method using an arterial catheter with an attached lithium sensor, pulse contour analysis involving measurement of arterial pulse pressure waveform using an arterial catheter, methods using the Fick principle, thoracic electrical bioimpedance, transesophageal echocardiography, ultrasonic cardiac output monitoring, central venous pressure monitoring (CVP), esophageal Doppler monitoring, and conventional clinical assessment (CAA) which generally refers to non-invasive measurement of clinical markers.2,4,5 Esophageal Doppler monitoring (EDM) is the focus of this report. It is a minimally invasive procedure used to measure cardiac output. A small probe, which emits an ultrasound beam, is placed via the oral or nasal route in the esophagus of a patient, usually under anesthesia. Blood flow velocity in the descending aorta is measured by the change in frequency (Doppler shift) of this beam as it reflects off a moving object. Blood flow velocity together with an estimate of cross-sectional area of the aorta is used to determine the cardiac output.2,5

Esophageal Doppler Ultrasound-based Cardiac Output Monitoring for Adults 2

The purpose of this report is to assist in the decision making with respect to EDM by providing evidence on the clinical effectiveness and cost-effectiveness of intraoperative fluid management guided by esophageal Doppler ultrasound-based cardiac output monitoring devices in adult patients undergoing surgery. RESEARCH QUESTIONS

1. What is the clinical-effectiveness of intraoperative use of esophageal Doppler ultrasound-based cardiac output monitoring devices in adult patients undergoing surgery?

2. What is the cost-effectiveness of intraoperative use of esophageal Doppler ultrasound-

based cardiac output monitoring devices in adult patients undergoing surgery? KEY FINDINGS No studies were identified which compared esophageal Doppler monitoring (EDM) with methods specifically using an arterial line or arterial catheter. In most instances, available evidence suggested a trend towards reduction in length of hospital stay, complication rates and mortality for intraoperative fluid management strategies using EDM compared to those using central venous pressure monitoring (CVP) or conventional clinical assessment (CAA), in adults undergoing surgery. However results need to be interpreted with caution as the differences were not statistically significant in several instances. Strategies with EDM combined with CVP or CAA appeared to be more cost-effective than strategies which involved CVP or CAA alone or in combination in the absence of EDM. METHODS Literature Search Strategy A limited literature search was conducted on key resources including PubMed, The Cochrane Library (2013, Issue 1), University of York Centre for Reviews and Dissemination (CRD) databases, Canadian and major international health technology agencies, as well as a focused Internet search. No filters were applied to limit the retrieval by study type. Where possible, retrieval was limited to the human population. The search was also limited to English language documents published between January 1, 2008 and February 14, 2013. Selection Criteria and Methods One reviewer screened the titles and abstracts of the retrieved publications and selected potentially relevant articles for retrieval of full-text publications for further investigation. A second reviewer evaluated the full-text publications for final selection, according to the criteria listed in Table 1.


Table 1: Selection Criteria

Population

Adults undergoing surgery

Intervention

Esophageal Doppler Ultrasound-based cardiac output monitoring during surgery (aka intra-operatively)

Comparator

Arterial line or arterial catheter

Outcomes

Question 1: length of stay, adverse events, resource utilization

Question 2: cost-effectiveness and resource utilization

Study Designs

Health technology assessment (HTA), systematic review (SR) and meta-analysis (MA), randomized controlled trial (RCT) and non-randomized studies Economic study (cost-effectiveness study)

Exclusion Criteria Studies were excluded if they did not satisfy the selection criteria in Table 1, if they were published prior to 2008, or duplicate publications of the same study and did not provide additional relevant information. Individual studies which were included in at least one of the included systematic reviews were excluded. Systematic reviews in which all included studies were included in more recent or comprehensive systematic reviews or health technology assessments were excluded. Non-comparative studies were excluded unless no comparative studies were available. Critical Appraisal of Individual Studies Critical appraisal of a study was conducted based on an assessment tool appropriate for the particular study design. The AMSTAR checklist6 was used for systematic reviews; the Downs and Black checklist7 for RCTs and non-randomized studies; the checklist of Drummond et al.8 for economic studies. For the critical appraisal, a numeric score was not calculated. Instead, the strength and limitations of the study were described. SUMMARY OF EVIDENCE Quantity of Research Available The literature search yielded 153 citations. Upon screening titles and abstracts, 135 articles were excluded and 18 potentially relevant articles were selected for full-text review. Five potentially relevant articles were identified from the grey literature. Of these 23 articles, 15 did not satisfy the inclusion criteria and were excluded. One health technology assessment, two systematic reviews, two RCTs, two non-randomized studies, and one cost-effectiveness study were relevant and selected for inclusion. The health technology assessment included a systematic review of RCTs and an economic evaluation. Details of the study selection process are outlined in Appendix 1.


Summary of Study Characteristics Characteristics of the included health technology assessment, systematic reviews, RCTs, non-randomized studies and economic studies are summarized below and details are provided in Appendix 2. Health technology assessment The included health technology assessment1 was published in 2009 from the United Kingdom (UK). It included a systematic review of 10 RCTs and an economic evaluation. This health technology assessment was based on a previously published AHRQ systematic review2 which included eight RCTs and was supplemented with two additional RCTs. The 10 RCTs included 959 patients undergoing surgery or in critical care. Strategies with Esophageal Doppler monitoring (EDM) for optimizing fluid management in these patients were compared with control strategies including procedures such as central venous pressure monitoring (CVP) and conventional clinical assessment (CCA). The EDM device used was CardioQ in eight RCTs, Hemosonic 100 in one RCT and TECO in one RCT. The age of patients in the EDM group ranged between 33 and 82 years and in the control group between 40 and 85 years. Outcomes reported were length of hospital stay, complications and mortality. The authors of this health technology assessment intended to include also a systematic review of economic evaluations but no relevant studies could be identified. They conducted an economic evaluation using partial economic modeling involving pairwise comparisons between strategies with and without EDM. The EDM devices considered were CardioQ and CardioQP. CardioQ supports adult probes and CardioQP supports both adult and pediatric probes. The EDM device was assumed to have a lifetime of five years. Results were expressed as additional cost (£) per additional QALY and average extra cost (£) per additional survivor that would need to be incurred before EDM would no longer be considered cost-effective. Cost data used were for the period 2006 to 2008. Systematic reviews Two relevant systematic reviews9,10 comparing strategies with and without EDM were identified. Both were from New Zealand with one9 published in 2008 and one10 in 2011. Both systematic reviews included five RCTs, of which four overlapped. In addition, these four RCTs were also included in the health technology assessment report1 mentioned above. Of the four overlapping RCTs, three were specific to colorectal surgery and one included patients undergoing urological, gynaecological and general surgical procedures. The unique RCT in one systematic review9 was specific to colorectal surgery and the unique RCT in the second systematic review10 was specific to upper gastro-intestinal surgery. The total number of patients was not specified in one systematic review9 and was 428 in the second systematic review.10 The age of patients, the proportion of females and males or the EDM devices used were not specified. Both systematic reviews reported on length of hospital stay, complications and some physiological parameters. One systematic review9 also reported on mortality.


Randomized controlled trials (RCTs)

Two relevant RCTs11,12 were identified. Both RCTs were published in 2012, one11 from Denmark and one12 from UK. Both RCTs involved patients undergoing colorectal surgery, one11 included 150 patients and one12 included 179 patients. The mean age was between 66 and 68 years. Fluid management with the goal of achieving near-maximal stroke volume guided by EDM was compared with the goal of zero balance and normal body weight (zero balance approach, formerly known as “restricted approach”) in one RCT.11 In the second RCT12 goal directed fluid management with EDM was compared with standard care. The EDM device used was CardioQ in one RCT12 and CardioQ-ODM in the second RCT.11 Both RCTs reported on length of hospital stay, complications, mortality and physiological changes (such as bowel movement, gastro-intestinal function, and diet tolerance). Non-randomized studies Two relevant non-randomized studies13,14 were identified. Both were published from the UK, one13 published in 2013 and one14 in 2011. One study13 was a prospective study comparing EDM with CVP monitoring. It included 104 patients undergoing free perforated flap surgery. The mean age in the EDM and CVP groups were 39 and 44 years respectively and both groups contained a higher proportion of female patients than males. The study reported on length of hospital stay, complications, and physiological changes. The second study14 was a before and after EDM implementation study. It included 1,307 patients undergoing various types of surgery and of age ≥ 60 years. The study reported length of hospital stay, reoperation, readmission to hospital and mortality Economic evaluation Two economic evaluations1,15 were identified of which one1 was part of a health technology assessment report. Characteristics of this economic evaluation have been discussed with the characteristics of the health technology assessment. One economic study15was published in 2011 from a group in Spain. It examined the cost-effectiveness of cardiac output monitoring and hemodynamic function optimization using various strategies including one or more options such as conventional clinical assessment (CCA), central venous pressure monitoring (CVP), and esophageal Doppler monitoring (EDM). The authors constructed an analytical decision model to compare four strategies ([CCA+ CVP+ EDM] versus [CCA+ CVP] versus [CCA+ EDM] versus CCA) as these were some of the most commonly used in clinical settings and RCTs. The time horizon considered was until discharge from hospital, assuming that cardiac output control systems and fluid administration during surgery would not impact outcomes after discharge. The perspective was that of a hospital which is considered to be a good proxy for an overall health care system perspective. Estimates of effectiveness were obtained from meta-analyses or individual RCTs. For patients undergoing CCA+ CVP or CCA alone it was assumed that the length of hospital stay was the same. For the base case analysis, it was assumed that the equipment would last for 5 years and usage would be 125 times per year. Sensitivity analyses were conducted with other utilization rates. To adjust for consecutive years of usage an inflation rate of 3% was applied. Cost data were obtained from the Madrid Health System, the La Paz University Hospital finance department and from


device manufactures. The cost data was compared with published cost data and no significant differences were observed. Costs were presented in € for the year 2007. Quality adjusted life year (QALY) and incremental cost-effectiveness ratio (ICER) were calculated. Strategies with lower effectiveness and higher cost were considered as dominated and for these cases ICERs were not calculated. Summary of Critical Appraisal Critical appraisal of the included health technology assessment, systematic reviews, RCTs, non-randomized studies and economic studies are summarized below and details are provided in

Appendix 3.

Health technology assessment The authors of the health technology assessment report1 based their report on the AHRQ report2 which they considered to be good quality. They supplemented the information with two additional studies. Objectives, inclusion and exclusion criteria were stated and a comprehensive literature was undertaken. Lists of included and excluded studies were provided. Characteristics of the individual RCTs were available. Quality assessments of the included studies were conducted. Article selection and data extraction was conducted by one reviewer and a second reviewer was consulted in case of uncertainty. Conflict of interest was declared and there was none. Publication bias was not explored. For the economic section, clinical effectiveness data were taken from the systematic review. The form of economic evaluation, time horizon and perspective were stated. Sensitivity analyses were conducted. Cost data were provided. Systematic reviews For the two included systematic reviews9,10 the objectives, inclusion and exclusion criteria were stated, a comprehensive literature was undertaken, lists of included studies were provided and quality assessment was conducted. However, in these two systematic reviews the list of excluded studies, or description of the study selection process were not provided and it was unclear if article selection and data extraction were done in duplicate. In one systematic review9 publication bias was explored and there appeared to be none. Conflict of interest statements were provided and no conflicts were declared. In this systematic review characteristics of the individual studies were not provided and the results were presented qualitatively. In the second systematic review10 characteristics of the individual studies were provided but with few details, and pooled estimates were provided. However, publication bias was not explored and conflict of interest was not stated. Randomized controlled trials (RCTs)

In the two included RCTs,11,12 objectives were stated, patient characteristics, interventions, outcomes and sample size calculations were described. Intent-to treat analyses were conducted and P-values were provided. Both studies were double-blind. As with RCTs, generalizability was limited due to restrictive inclusion criteria. In one RCT11 there was some potential for selection bias as the presence of the investigating anesthetist and surgeon were mandatory for screening of patients.


Non-randomized studies Two relevant non-randomized studies13,14 were included. In one prospective non-randomized study13 objectives were stated and inclusion and exclusion criteria were provided. Patient characteristics, interventions and outcomes were described. There was no apparent significant difference between the two groups studied with respect to patient demographics and operative indications. All patients were included in the analyses and P-values were provided. Sample size calculation was not described and the authors mentioned the possibility of the study being underpowered. The second non-randomized study14 was a before and after EDM implementation study. In this study, objectives were stated and patient characteristics, interventions and outcomes were described but few details were provided. All patients were included in the analyses and P-values were provided. Prospective data from consecutive patients following implementation of EDM were compared with retrospective data from controls matched by specialty and severity of surgery. The control group had differences in age and physical status scores but perioperative risk indicator was similar. This study was generalizable to some extent as data was collected from three hospitals in England with different size, geographical location and case mix. Economic evaluation Two economic evaluations1,15 were identified, of which one1 was part of a health technology assessment report. Quality assessment of this economic evaluation has been discussed in the health technology assessment section above. In the second economic evaluation the objective, form of economic evaluation, time horizon and perspective were stated. Clinical effectiveness data were obtained from meta-analyses or individual RCTs. Sensitivity analyses were conducted. Sources of cost data were stated. Summary of Findings The overall findings are summarized below and details of the findings of the included health technology assessment, systematic reviews, RCTs, non-randomized studies and economic evaluations are provided in Appendix 4. What is the clinical-effectiveness of intraoperative use of esophageal Doppler ultrasound-based cardiac output monitoring devices in adult patients undergoing surgery? Length of hospital stay was reported in one HTA,1 two systematic reviews,9,10 two RCTs,11,12 and two non-randomized studies13,14 and is shown in Table 2. Hospital stay was less for strategies with EDM compared to those without EDM but the difference was not statistically significant in the majority of cases. One RCT included in a systematic review reported an increase in hospital stay with EDM compared with no EDM, however it was not mentioned if the difference was statistically significant.


Table 2: Length of hospital stay (days) Study Comparison Finding

Effect measure Effect

HTA1 (2 RCTs; N= 157

surgical patients) (EDM+ CVP+ CCA) vs (CVP+ CAA)

WMD (95% CI) -1.82 (-2.98, -0.65)

HTA1 (1 RCT; N= 61

surgical patients) (EDM+ CCA) vs (CVP+ CAA)

Mean 13.5 vs 13.3 (p= 0.96)


surgical patients) (EDM+ CCA) vs (CAA)

Mean difference Decrease: Significant (1 RCT), non-significant (1 RCT) and significance NR (1 RCT)


critically ill patients) (EDM+ CVP+ CCA) vs (CVP+ CAA)

Mean difference Decrease : Significant (1 RCT), and significance NR (1 RCT)

SR9 (4 RCTs, N= NR) EDM vs no EDM Mean difference Decrease: (2 RCT)

Increase: (1 RCT)

SR10

(4 RCTs; N= 368 surgical patients)

EDM vs conventional methods

WMD (95% CI) -1.60 (-2.58, -0.62)

RCT11

(N= 150 surgical patients)

EDM vs zero fluid balance approach (Z)

Mean ± SD 8.45 ± 7.5 vs 7.66 ± 8.2 (p= 0.54)

RCT12

(N= 179 surgical patients)*

EDM vs standard care

Median (interquartile range)*

8.8 (6.0- 11.9) vs 6.7 (4.8- 13.3); (p= 0.09)

Non randomized prospective study

13 (N= 104

surgical patients)

EDM vs CVP Mean ± SD 8.9 ± 3.6 vs 10.8 ± 6.2; (p= 0.147)

Non randomized implementation study

14 (N=

1,307 surgical patients)

Before and after implementation of EDM

Mean ± SD 15.1 ± 16.7 vs 18.7 ± 24.4 (p= 0.002)

CCA= conventional clinical assessment, CI= confidence interval, CVP= central venous pressure monitoring, EDM= esophageal Doppler monitoring, HTA= health technology assessment, N= number of patients, RCT= randomized controlled trial, SD= standard deviation, SR= systematic review, WMD= weighted mean difference *mentioned as post-operative days not specified as length of hospital stay

Complication rates were reported in one HTA,1 two systematic reviews,9,10 two RCTs,11,12 and two non-randomized studies13,14 and are shown in Table 3. Complications appeared to be fewer for strategies with EDM compared to those without EDM. However, in three instances the differences were statistically significant, in five instances the differences were not statistically significant and in two instances statistical significance was not mentioned.


Table 3: All complications Study Comparison Finding




OR (95% CI) 0.43 (0.26, 0.71)

HTA1 (1 RCT; N= 61


OR (95% CI) 0.61 (0.21, 1.72)

HTA1 (1 RCT; N= 59


OR (95% CI) 0.41 (0.14, 1.16)



OR (95% CI) 0.49 (0.30, 0.81)

SR9 (4 RCTs, N= NR) EDM vs no EDM Rate Decrease: (3 RCT)

Increase: (1 RCT)

SR10

(4 RCTs; N= 368 surgical patients)


OR (95% CI) 0.28 (0.17, 0.46)

RCT11



Rate 23 (32%) vs 24 (30%); (p= 0.791)


13 (N= 104

surgical patients)

EDM vs CVP Incidence EDM: None CVP: 1 episode of Horner syndrome and 5 incidences of symptomatic hematomas


14 (N=

1,307 surgical patients)*


Rate 5.9% vs 8.4%; (p=0.08)

CCA= conventional clinical assessment, CI= confidence interval, CVP= central venous pressure monitoring, EDM= esophageal Doppler monitoring, HTA= health technology assessment, N= number of patients, OR= odds ratio, RCT= randomized controlled trial, SR= systematic review * complications were not mentioned but reoperation was mentioned

Major or serious complications were reported in one HTA,1 and two RCTs11,12 and are shown in Table 4. Major or serious complications appeared to be fewer for strategies with EDM compared to those without EDM. However, in one instance the difference was statistically significant, and in two instances the differences were not statistically significant. Table 4: Major or serious complications Study Comparison Finding




Peto OR (95% CI)

0.12 (0.04, 0.31)

RCT11



Rate 14% vs 10% (p= 0.616)

RCT12



Rate 10/89 vs 13/90 (p= 0.47)

CCA= conventional clinical assessment, CI= confidence interval, CVP= central venous pressure monitoring, EDM= esophageal Doppler monitoring, HTA= health technology assessment, N= number of patients, OR= odds ratio, RCT= randomized controlled trial,


Mortality was reported in one HTA,1 one systematic review,10 two RCTs,11,12 and one non-randomized study14 and is shown in Table 5. Mortality appeared to be less for strategies with EDM compared to those without EDM. However, the difference was not statistically significant in seven instances and statistically significant in only one instance. Table 5: Mortality Study Comparison Finding




OR (95% CI) 0.13 (0.02, 0.96)

HTA1 (1 RCT; N= 61


Rate 3/30 versus 6/31; (p= 0.3)



OR (95% CI) 0.81 (0.23, 2.77)



OR (95% CI) 0.84 (0.41, 1.70)

SR9 (5 RCTs, N= NR) EDM vs no EDM - NR

SR10

(4RCTs; N= 300 surgical patients)


OR (95% CI) 0.62 (0.16, 2.45)

RCT11



Rate 1% vs 1%; (p= 1.0)

RCT12



Rate 2/89 vs 2/90; (p= 1.0)


13 (N= 104

surgical patients)

EDM vs CVP - NR


14 (N=

1,307 surgical patients


Rate 2.8% vs 3.5%; (p=0.37)

CCA= conventional clinical assessment, CI= confidence interval, CVP= central venous pressure monitoring, EDM= esophageal Doppler monitoring, HTA= health technology assessment, N= number of patients, OR= odds

ratio, RCT= randomized controlled trial, SR= systematic review.

What is the cost-effectiveness of intraoperative use of esophageal Doppler ultrasound-based cardiac output monitoring devices in adult patients undergoing surgery? Two relevant economic studies1,15 were identified. One economic study15 evaluated four strategies and conducted a cost-effectiveness analysis. These strategies were (EDM+ CVP+ CCA), (CVP+ CCA), (EDM+ CCA) and CCA alone. Considering that there were 1.1 fewer days of hospital stay for patients managed with (EDM+ CVP+ CCA) compared with those managed with (CVP+ CCA), the cost savings per patient was €911. As length of hospital stay is the main driver of cost, if there was no difference in length of hospital stay for these strategies, the cost savings per patient with (EDM+ CVP+ CCA) would be reduced to €369. Cost values were those for year 2007. As the difference in mortality rates of (EDM+ CVP+ CCA) compared with (CVP+ CCA) was not statistically significant, (EDM+ CVP+ CCA) did not always appear to be the best option. The ICER for (EDM+ CVP+ CCA) compared with (EDM+ CCA) was €118.65 per QALY. Strategies such as that did not include esophageal


Doppler ultrasound appeared to have lower effectiveness and higher cost and were considered as dominated. For these cases ICERs were not calculated. The economic study included in the health technology assessment report1 was an economic evaluation using partial economic modeling involving pairwise comparisons. The strategies investigated were (EDM+ CVP+ CCA), (CVP+ CCA), (EDM+ CCA) and CCA alone. From a Monte Carlo analysis with 1000 iterations and considering a threshold of £30,000/QALY it appeared that compared with (CVP+ CCA), (EDM+ CVP+ CCA) was more effective and less costly for both best case and worst case scenarios. Best and worst case scenarios differed in terms of the costs associated with EDM, length of hospital stay, facility used (general ward or intensive care unit [ICU]) and length of survival per additional survivor. Similar analyses suggested that (EDM+ CCA) was more effective and less costly than CCA. The additional cost per additional survivor that would need to be incurred before EDM would no longer be considered cost-effective is shown in Table 6. The results were statistically significant for (EDM+ CVP+ CCA) compared with (CVP+ CAA) but not statistically significant for (EDM+ CCA) compared with CCA. Table 6: Average additional cost per additional survivor

Comparison Patient type

Scenario Average extra cost per additional survivor that would need to be incurred before EDM would no longer be considered cost-effective (95% CI)

[EDM+ CVP+ CCA] versus [CVP+ CCA]

High risk surgical patients

Best case £4,441 (£2,151 to £6,732)

Worst case £642 (£225 to £1060)

[EDM+ CCA] versus [CCA]


Best case £11,588 (-£2,529 to £25,705)

Worst case £1,879 (-£920 to £4678)

CCA= conventional clinical assessment, CI= confidence interval, CVP= central venous pressure monitoring, EDM= esophageal Doppler monitoring Limitations Though evidence on EDM was available, none of the studies compared EDM with methods specifically using an arterial line or arterial catheter. There was overlap of RCTs included in the health technology assessment report and the two systematic reviews; four RCTs were included in all three reports. Hence, it should be noted that the results of the three reports are not completely exclusive and effects may be over-emphasized. Not all outcomes were reported in all studies. Complication rates were reported in most studies but data on major or serious complications were sparse. It was not always clear what constituted major or severe complications. Though in most of the studies, colorectal surgery was mainly considered there was some heterogeneity in the surgical procedures considered. Laparoscopic and open surgeries, and colon and rectal surgeries were considered together. While this could increase generalizability, it is difficult to know specifically which types of surgeries would benefit most from using EDM.


Standard of care could be different in different institutions and this could affect the outcomes achieved and confound the comparison of outcomes achieved by different methods. Length of the surgical procedure could have an impact on the outcome investigated. There is potential for subjectivity in the determination of length of hospital stay as the surgeon’s perception of readiness of a patient to be discharged could vary. Comparisons of EDM strategies with all available strategies for intraoperative fluid management in adults undergoing surgery were not available. The results presented here pertain to some specific strategies. None of the included studies were conducted in Canada hence results may not be generalizable to the Canadian setting. CONCLUSIONS AND IMPLICATIONS FOR DECISION OR POLICY MAKING Evidence for EDM was available from one health technology assessment report comprising of a systematic review and economic evaluation, two systematic reviews, four clinical studies comprising of two RCTs and two non-randomized studies, and one economic study. No studies comparing EDM with methods specifically using an arterial line or arterial catheter were identified. In most instances, available evidence suggests a trend towards reduction in length of hospital stay, complication rates and mortality for intraoperative fluid management strategies using EDM compared to those using CVP or CAA in adults undergoing surgery. However, results need to be interpreted with caution as the differences were not statistically significant in several instances. Strategies with EDM appeared to be more cost-effective than CVP or CAA strategies without EDM. It should be noted that recent advances in peri-operative care could offset some of the clinical benefits observed in previously published studies. Standard of care could vary at different institutions and this could impact the outcomes achieved. Such implications could impact the decision making. PREPARED BY: Canadian Agency for Drugs and Technologies in Health Tel: 1-866-898-8439 www.cadth.ca

http://www.cadth.ca/


REFERENCES

1. Mowatt G, Houston G, Hernandez R, de VR, Fraser C, Cuthbertson B, et al. Systematic

review of the clinical effectiveness and cost-effectiveness of oesophageal Doppler monitoring in critically ill and high-risk surgical patients. Health Technol Assess [Internet]. 2009 Jan [cited 2013 Feb 20];13(7):iii-xii, 1. Available from: http://www.hta.ac.uk/project/1633.asp

2. Agency for Healthcare Research and Quality. Esophageal Doppler ultrasound-based cardiac output monitoring for real-time therapeutic management of hospitalized patients: a review [Internet]. Rockville (MD): AHRQ; 2007. 131 p. [cited 2013 Mar 1]. (Technology Assessment Program). Available from: https://www.ecri.org/Documents/EPC/Esophageal_Doppler_Ultrasound-Based_Cardiac_Output_Monitoring.pdf

3. Walsh SR, Tang T, Bass S, Gaunt ME. Doppler-guided intra-operative fluid management during major abdominal surgery: systematic review and meta-analysis. Int J Clin Pract. 2008 Mar;62(3):466-70.

4. Straight from the heart [Internet]. Plymouth Meeting (PA): ECRI; 2009 Dec. (Health Devices). [cited 2013 Mar 7]. Available from: http://www.ecri.org

5. Alhashemi JA, Cecconi M, Hofer CK. Cardiac output monitoring: an integrative perspective. Crit Care [Internet]. 2011 [cited 2013 Jul 3];15(2):214. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3219410/pdf/cc9996.pdf

6. Shea BJ, Grimshaw JM, Wells GA, Boers M, Andersson N, Hamel C, et al. Development of AMSTAR: a measurement tool to assess the methodological quality of systematic reviews. BMC Med Res Methodol [Internet]. 2007 Feb 15 [cited 2013 Feb 25];7:10. Available from: http://www.biomedcentral.com/1471-2288/7/10

7. Downs SH, Black N. The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions. J Epidemiol Community Health [Internet]. 1998 Jun [cited 2013 Jan 10];52(6):377-84. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1756728/pdf/v052p00377.pdf

8. Drummond MF, Jefferson TO. Guidelines for authors and peer reviewers of economic submissions to the BMJ. BMJ [Internet]. 1996 Aug 3 [cited 2013 Mar 4];313(7052):275-83. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2351717/pdf/bmj00553-0039.pdf

9. Srinivasa S, Taylor MH, Sammour T, Kahokehr AA, Hill AG. Oesophageal Doppler-guided fluid administration in colorectal surgery: critical appraisal of published clinical trials. Acta Anaesthesiol Scand. 2011 Jan;55(1):4-13.

10. Abbas SM, Hill AG. Systematic review of the literature for the use of oesophageal Doppler monitor for fluid replacement in major abdominal surgery. Anaesthesia. 2008 Jan;63(1):44-51.

http://www.hta.ac.uk/project/1633.asp

https://www.ecri.org/Documents/EPC/Esophageal_Doppler_Ultrasound-Based_Cardiac_Output_Monitoring.pdf

https://www.ecri.org/Documents/EPC/Esophageal_Doppler_Ultrasound-Based_Cardiac_Output_Monitoring.pdf

http://www.ecri.org/

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3219410/pdf/cc9996.pdf

http://www.biomedcentral.com/1471-2288/7/10

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1756728/pdf/v052p00377.pdf

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2351717/pdf/bmj00553-0039.pdf


11. Brandstrup B, Svendsen PE, Rasmussen M, Belhage B, Rodt SA, Hansen B, et al. Which goal for fluid therapy during colorectal surgery is followed by the best outcome: near-maximal stroke volume or zero fluid balance? Br J Anaesth. 2012 Aug;109(2):191-9.

12. Challand C, Struthers R, Sneyd JR, Erasmus PD, Mellor N, Hosie KB, et al. Randomized controlled trial of intraoperative goal-directed fluid therapy in aerobically fit and unfit patients having major colorectal surgery. Br J Anaesth. 2012 Jan;108(1):53-62.

13. Figus A, Wade RG, Oakey S, Ramakrishnan VV. Intraoperative esophageal Doppler hemodynamic monitoring in free perforator flap surgery. Ann Plast Surg. 2011 Dec 9.

14. Kuper M, Gold SJ, Callow C, Quraishi T, King S, Mulreany A, et al. Intraoperative fluid management guided by oesophageal Doppler monitoring. BMJ. 2011;342:d3016.

15. Maeso S, Callejo D, Hernandez R, Blasco JA, Andradas E. Esophageal Doppler monitoring during colorectal resection offers cost-effective improvement of hemodynamic control. Value Health. 2011 Sep;14(6):818-26.


ABBREVIATIONS ASA American Society of Anesthesiologists Score

CCA conventional clinical assessment

CI confidence interval

CVP central venous pressure

DB double blind

EDM esophageal Doppler monitoring

GDT goal-directed therapy

HTA health technology assessment

ICER incremental cost effectiveness ratio

ICU intensive care unit

N number of patients

NR not reported

OR odd’s ratio

QALY quality adjusted life year

RCT randomized controlled trial

SD standard deviation

SR systematic review

TECO transesophageal cardiac output

UK United Kingdom

WMD weighted mean difference

Z zero fluid balance approach


APPENDIX 1: Selection of Included Studies

135 citations excluded

18 potentially relevant articles retrieved for scrutiny (full text, if

available)

5 potentially relevant reports retrieved from other sources (grey

literature, hand search)

23 potentially relevant reports

15 reports excluded: - intervention or comparison not of interest (2) - outcomes not of interest (2) -study design not of interest (2) -studies in systematic review already included in a more recent or comprehensive HTA or systematic review (3) - duplicate (1) -article unavailable (1) -other (review articles, editorials, guidance document)(4)

8 reports included in review

153 citations identified from electronic literature search and

screened


APPENDIX 2: Characteristics of Included Studies

First Author, Publication Year, Country

Study Design, Duration

Patient Characteristics, Sample Size (n)

Intervention Comparators/ comparisons

Outcomes Measured

Health Technology Assessment (HTA) Mowatt,

1 2009,

UK HTA (SR included10 RCTs, 1 economic modeling); The SR was based on the AHRQ report

2 plus 2

additional RCTs) During surgery or hospitalization for critical care

SR Adults undergoing surgery (hip fracture repair, cardiac, bowel, colorectal, general, urological or gynaecological) or adults managed in critical care facility who require cardiac output monitoring. Age (years): EDM: 33- 82, Control: 40- 85 Female: 273 (39%) Male: 421 (61%), NR: 265 N= 959

SR EDM (CardioQ [8 RCTs], HemoSonic 100 [1 RCT], TECO [1 RCT])

SR During surgery: (EDM+ CVP+ CCA) vs (CVP+ CCA), 5 RCT, 453 patients. (EDM+ CCA) vs (CVP+ CCA), 1 RCT, 61 patients. (EDM+ CCA) vs CCA, 3 RCTs, 139 patients. In critically ill patients: (EDM+ CVP+ CCA) vs (CVP+ CCA), 2 RCT, 336 patients.

SR Mortality, length of hospital stay, complications

HTA (economic modeling and SR); Cost- effectiveness analysis (partial economic modeling using pairwise comparisons)

Economic evaluation High risk surgical patients. Critically ill hospitalized patients.

Economic evaluation EDM+ CVP+ CCA] versus [CVP+ CCA] and [EDM+ CCA] versus [CCA] for high risk surgical patients EDM+ CVP+ CCA] versus [CVP+ CCA] for critically ill patients. (EDM device: CardioQ and CardioQP. CardioQ supports only adult probes and CardioQP supports both adult and pediatric probes)

Economic evaluation Additional cost per additional QALY (presented as Incremental cost effectiveness plane) and average extra cost per additional survivor (presented as histograms)

Systematic review and meta-analysis

Srinivasa,9 2011,

New Zealand SR (included 5 RCTs)

Adults undergoing

EDM (Device

Control (details not

Length of hospital stay,






Outcomes Measured

Duration not specified

surgery (4 RCTs specifically on colorectal surgery and 1 RCT included patients undergoing urological, gynecological and general surgical procedures) Age (years): NR Female/Male: NR N= NR

names not reported)

provided) complications, and physiological parameters

Abbas,10

2008, New Zealand

SR (included 5 RCTs)

Adults undergoing surgery (colorectal, upper GI, major abdominal) Age (years): NR Female/Male: NR N= 428

EDM (Device names not reported)

Intravenous fluid therapy according to conventional measures of CVP, heart rate and arterial blood pressure.

Mortality, hospital stay, admission to ICU, return of gut function, use of inotropes, complications, and other outcomes (such as colloid/crystalloid use, urine output, oxygen delivery)

Randomized controlled trial (RCT)

Brandstrup,11

2012, Denmark

Multicenter, DB RCT FU= 30 days

Adults undergoing elective colorectal surgery Age (years) (mean± SD)- EDM: 66.9±14.9, Z group: 68.1± 14.9 Male (number [%]): EDM: 39 (55%) Z group: 47 (59%) N= 150

EDM (CardioQ-ODM)

Zero fluid balance approach (formerly known as “restricted approach”). In this approach, all measured fluid losses are replaced with a goal of zero fluid balance without the replacement of the loss-to-

Mortality, complications, length of hospital stay, readiness for discharge, need for antiemetic or diuretic treatment and physiological changes






Outcomes Measured

(EDM=71, Z group= 79)

third space.

Challand,11

2012, UK

Single center, DB RCT

Adults undergoing major colorectal surgery (open or laparoscopic) Age (years) (mean± SD)- EDM/GDT: 66± 15.36, Control: 65.9± 14.1 Male/Female- EDM/GDT: 54/35, Control: 48/42 N= 179 (EDM/GDT: 89, control: 90)

EDM guided intraoperative goal-directed fluid therapy (GDT) (CardioQ)

Control (Standard care)

Mortality, complications, length of hospital stay, readiness for discharge, physiological changes

Non-randomized study (NRS)

Figus,13

2013, UK

Single center, non-randomized study, prospective

Adults undergoing free perforated flap surgery Age (years) (mean± SD)- EDM: 38.9± 18.0 CVP: 44.4± 17.1 Male/Female- EDM:11/39=21.6%/88.4% CVP:16/36= 30.2%/69.8% N= 104 (EDM: 51, CVP: 53)

EDM (DP12 CardioQ)

CVP monitoring (CVP and/or arterial monitoring considered in this group)

Length of hospital stay, complications, return to theater, flap survival, fluid input, output and balance

Kuper,14

2011, UK

Multi-center non-randomized implementation study, (before and after

Patients undergoing surgery (colorectal surgery [1 center], major

After EDM implementation

Before EDM implementation (Control)

Length of hospital stay, in-hospital mortality, readmission to hospital, readmission to






Outcomes Measured

implementation of EDM)

elective and emergency surgery [1 center], colorectal and orthopaedic surgery [1 center]) Number (%) of patients in various age ranges

≤ 60 years EDM: 237 (36.5%) Control: 196 (29.8%)

61- 70 years EDM: 167 (25.7%) Control: 175 (26.6%)

≥ 71 years EDM: 245 (37.8%) Control: 287 (43.6%)

N= 1307 (After EDM: 649, Control: 658)

critical care, re-operation,

Economic evaluation

Maeso,15

2011, Spain

Cost-effectiveness analysis. Time horizon: until discharge Hospital perspective (a good proxy for overall health care system perspective)

Patients undergoing colorectal surgery

Four strategies compared: [CCA+ CVP+ EDM] versus [CCA+ CVP] versus [CCA+ EDM] versus CCA (EDM device used not specified)

ICER

CCA= conventional clinical assessment, CVP= central venous pressure, DB= double blind, EDM= esophageal Doppler monitoring, GDT= goal directed fluid therapy, ICER= incremental cost-effectiveness ratio, ICU= intensive care unit, N= number of patients, NR= not reported, SD= standard deviation, Z= zero fluid balance approach


APPENDIX 3: Summary of Study Strengths and Limitations


Strengths Limitations

Health Technology Assessment (HTA) Mowatt,

1 2009,

UK SR

The objective was stated.

The inclusion and exclusion criteria were stated.

Comprehensive literature search (multiple databases)

Study selection described and flow chart presented

List of included and excluded studies provided

Characteristics of individual studies were provided or were available in the AHRQ report on which this HTA was based

Methods used to combine the findings of studies were appropriate

Quality assessment was conducted of the AHRQ report and the additional individual studies.

Conflict of interest was stated and there was none

SR

Article selection and data extraction were done by one reviewer and a second reviewer was consulted in case uncertainty

Publication bias was not explored.

Economic

Objectives were stated.

The strategies compared were stated

The form of economic evaluation, the rationale for the choice of alternative strategies were stated

Clinical effectiveness data were obtained from meta-analyses or individual RCTs.

Time horizon and perspective were stated

Cost data were provided

Sensitivity analyses were conducted

Economic

Several assumptions were made which may not be applicable in all cases

Systematic review and meta-analysis (SR/MA)

Srinivasa,9

2011, New Zealand



Comprehensive literature search (two databases: Medline and

Study selection process was not described

List of excluded studies was not provided

Characteristics of the individual studies




EMBASE and reference lists of relevant articles) was conducted

List of included studies was provided

Quality assessment of studies was conducted

Publication bias (constructing Funnel plot) was explored and the authors mentioned there was no evidence of publication bias

Conflict of interest was stated and there was none

were not described in detail

Unclear if article selection or data extraction were done in duplicate

Results were presented qualitatively

Abbas,10

2008, New Zealand



Comprehensive literature search (two databases: Medline and EMBASE) was conducted

List of included studies was provided

Methods used to combine the findings of studies were appropriate

Quality assessment of studies was conducted

Study selection was not described

List of excluded studies was not provided

Characteristics of the individual studies were not described in detail. (However, it was mentioned that the patients in the included studies were comparable with respect to age, type of surgery, pre-operative hemoglobin levels and physiological scores and that there were no difference between theses parameters between the experimental and control groups.)

Unclear if article selection or data extraction were done in duplicate

Publication bias was not explored

No mention of conflict of interest


Brandstrup,11

2012, Denmark


Inclusion/ exclusion criteria were stated but few details.

Patient characteristics, interventions, and outcomes were described.

Randomized; double blind - patients and surgeons were blinded.

Sample size calculation was described

Intent-to-treat analysis

P-values provided

Potential for selection bias as the presence of both the investigating anaesthetist and surgeon was mandatory for screening patients for inclusion

Generalizability limited; uncertain as to whether study patients were representative of all patients.

Challand,12

2012, UK


Inclusion/ exclusion criteria were stated but few details.

Patient characteristics, interventions, and outcomes were





described.

Randomized; double blind – The EDM screen was concealed from everybody except the investigator. The attending anaesthetist was informed that the investigator would appear to give colloid boluses to all, but these would be sham activity in the control group.

Sample size calculation was described

Intent-to-treat analysis

P-values provided

Non randomized study (NRS)

Figus,13

2013, UK


Inclusion/ exclusion criteria were stated Patient characteristics, interventions, and outcomes were described

No apparent significant difference between the two groups with respect to patient demographics or operative indications

Prospective study

All patients were included in the analysis

P-values provided

Non-randomized study hence potential for selection bias

Sample size calculation was not described and the authors mentioned the possibility of underpowered sample size


Kuper,14

2011, UK


Patient characteristics, interventions, and outcomes were described but few details were provided

All patients were included in the analysis

P-values provided

Generalizable to some extent as data was collected from three hospitals in England with different size, geographical location and case mix

Non-randomized implementation study.

Prospective data from consecutive patients in the year following implementation of EDM were compared with retrospective data from controls matched by specialty and severity of operations

The control and EDM groups had differences in age and physical status scores, however the perioperative risk indicator (POSSUM, which includes age) was similar in the two groups, so similar outcomes would be expected.

There is a possibility that results could be confounded by other changes occurring during the study period.

Any implementation study of this type is subject to a Hawthorne effect, whereby close observation could result in improved performance




Economic evaluation

Maeso,15

2011, Spain


The strategies compared were stated

The form of economic evaluation, the rationale for the choice of alternative strategies were stated

Clinical effectiveness data were obtained from meta-analyses or individual RCTs.

Time horizon and perspective were stated

Sources of cost data were stated

Sensitivity analyses were conducted

Several assumptions were made which may not be applicable in all cases

Cost of patients who died were assumed to be same as those for patients with complications and this could result in over-estimation of cost

Additional long term results were presented but length of long term was not specified


APPENDIX 4: Main Study Findings and Authors’ Conclusions


Main Findings and Authors’ Conclusion

Health Technology Assessment (HTA)

Mowatt,

1 2009, UK

Main Findings: Clinical Outcomes obtained with [EDM+ CVP+ CCA] as compared to [CVP+ CCA] in surgical patients

Outcome No. of RCTs

No. of patients

OR (95% CI) or WMD (95% CI)*

Heterogeneity (I

2)

Length of hospital stay (days)

2 157 -1.82 (-2.98, -0.65)* 75.4%

Total complications (number of patients with complications)

3 288 0.43 (0.26, 071) 0%

Major complications† (number of patients with complications)

3 220 0.12 (0.04, 0.31) 0%

Mortality† 4 338 0.13 (0.02, 0.96) 0% *Indicates WMD (95% CI)

†Peto OR was presented

Note: 5 RCTs reported on length of hospital stay but only 2 were included as the data reported (median, range) for the other 3 did not allow precise effect size to be calculated. Major complications were generally defined as life-threatening or requiring intensive or high-dependency care and included severe tachyarrhythmias and chest infection, multiple organ failure, respiratory failure, cerebrovascular accident and paralytic ileus.

Outcomes obtained with [EDM + CCA] as compared to [CVP+ CCA] in surgical patients

Outcome* Effect (EDM + CCA] vs [CVP+ CCA]) p-value


13.5 versus 13.3 0.96

Mortality 3/30 versus 6/31 0.30


10/30 versus 14/31 OR (95% CI)= 0.61 (0.21, 1.72)

NR

* Data from one RCT with 61 patients




Outcomes obtained with [EDM + CCA] as compared to [CCA] in surgical patients

Outcome Result


Length of stay was numerically less in the EDM group (from 3 RCTs with 170 patients), the difference being statistically non-significant (1 RCT), statistically significant (1 RCT), and statistical significance not reported (1RCT)

Mortality OR (95% CI)= 0.81 (0.23, 2.77), from 3 RCTs with 139 patients


OR (95% CI)= 0.41 (0.14, 1.16), from I RCT with 59 patients

Outcomes obtained with [EDM+ CVP+ CCA] as compared to [CVP+ CCA] in critically ill patients

Outcome Result


Length of stay was numerically less in the EDM group (from 2 RCTs with 236 patients), the difference being statistically significant (1 RCT), and statistical significance not reported (1 RCT)

Mortality OR (95% CI)= 0.84 (0.41, 1.70), from 2 RCTs with 236 patients


OR (95% CI)= 0.49 (0.30, 0.81), from 2 RCTs with 236 patients

Economic Results derived from incremental cost-effectiveness plane

Comparison Patient type Scenario Results as indicated by the incremental cost-effectiveness plane



Best case Majority of points lie within the second quadrant indicating that [EDM+ CVP+ CCA] is more effective and less costly than [CVP+ CCA]

Worst case



Best case Well over 50% of the points lie within the second quadrant indicating that [EDM+ CCA] is more effective and less costly than [CCA]

Worst case

EDM+ CVP+ CCA] versus [CVP+ CCA]

Critically ill hospitalized patients

Best case Almost 70% of points lie within the second quadrant indicating that [EDM+ CVP+ CCA] is more effective and less costly than [CVP+ CCA]

Worst case




Average extra cost per additional survivor

Comparison Patient type Scenario Average extra cost per additional survivor that would need to be incurred before EDM would no longer be considered cost-effective (95% CI)



Best case £4,441 (£2,151 to £6,732)

Worst case £642 (£225 to £1060)



Best case £11,588 (-£2,529 to £25,705)

Worst case £1,879 (-£920 to £4678)

EDM+ CVP+ CCA] versus [CVP+ CCA]

Critically ill hospitalized patients

Best case £4,978 (-£2,655 to £12,611)

Worst case £364 (-£1,271 to £1,998)

Authors’ Conclusion:

“The addition of ODM-guided fluid administration combined with CVP monitoring plus conventional assessment during major surgery results in fewer complications, a shorter length of hospital stay and possibly fewer deaths, and may be a cost-effective use of resources in the NHS.” p.47 “Although there is some evidence for reduced complication rates and hospital lengths of stay in subgroups of critically ill patients, there is insufficient evidence to recommend the widespread use of ODM in critically ill patients in the NHS.” p. 48 (CVP= central venous pressure, NHS= National Health Service, ODM= esophageal Doppler monitoring)

Systematic review and meta-analysis (SR/MA)

Srinivasa,

9 2011,

New Zealand

Main Findings: 5 RCTs comparing EDM with control (no EDM) were included in this systematic review. Compared to the control group, the EDM group had decreased length of hospital stay and complications in 2 RCTs, decreased length of hospital stay, nausea/vomiting and blood transfusion in 1 RCT, decreased length of critical care stay in 1 RCT and increased length of hospital stay and complications in 1 RCT

Authors’ Conclusion: “In conclusion, the published literature has demonstrated that ODM-guided fluid administration in colorectal surgery improves cardiac indices and tissue perfusion. However, procedure-specific evidence of clinical benefits is scarce and widespread use of ODM is based on small, single-centre trials. Moreover, the clinical benefits observed in published trials may be largely offset by the recent advances in perioperative care. Whether ODM-guided intraoperative fluid administration is superior to intraoperative fluid restriction and leads to clinically significant improvements in an otherwise optimized environment with patients who are largely either ASA 2 or 3 remains to be seen and should be




explored with a well-designed RCT.” p. 11 (ASA= American Society of Anesthesiologists Score, ODM= esophageal Doppler monitoring)

Abbas,

10 2008, New

Zealand

Main Findings: Outcomes with EDM compared to conventional methods in adults undergoing surgery

Outcome No. of RCTs

No. of patients

OR (95% CI) or WMD (95% CI)*

Heterogeneity (I

2)


4 368 -1.60 (-2.58, -0.62)* 10.4%

ICU admission 3 260 0.2 (0.07, 0.57) 4.0%

Complications† (number of patients with complications)

4 368 0.28 (0.17, 0.46) 9.0%

Mortality 4 300 0.62 (0.16, 2.45) 0%

*Indicates WMD (95% CI) †Complications included cardiovascular, renal, respiratory and gastro-intestinal complications

Authors’ Conclusion: “Overall, there were fewer complications and ICU admissions, and less requirement for inotropes in the intervention group. Return of normal gastro-intestinal function was also significantly faster in the intervention group. Oesophageal Doppler use for monitoring and optimisation of flow-related haemodynamic variables improves short-term outcome in patients undergoing major abdominal surgery.” p. 44


Brandstrup,

11 2012,

Denmark

Main Findings: Outcomes with EDM compared to zero fluid balance approach (Z) in adults undergoing colorectal surgery

Outcome EDM (N=71) Z group (N= 79) p-value

Mortality (N [%]) 1 (1%) 1 (1%) 1.000

All complications (N [%])

23 (32%) 24 (30%) 0.791

Major complications (N [%])

10 (14%) 8 (10%) 0.616

Minor complications (N [%])

20 (28%) 22 (28%) 0.965

Cardiopulmonary complications (N

5 (7%) 3 (4%) 0.477




[%])

Tissue-healing complications (N [%])

8 (11%) 13 (16%) 0.481

Length of hospital stay (days) (mean± SD)

8.45± 7.5 7.66± 8.2 0.539

Length of hospital stay (days) (median [range])

5.0 (2- 42) 6.0 (2- 61) 0.620

Readiness for discharge (days) (mean± SD)

8.04± 7.3 6.72± 8.0 0.293

Readiness for discharge (days) (median [range])

5.00 (2- 41) 5.00 (1- 61) 0.206

Authors’ Conclusion: “Goal-directed fluid therapy to near-maximal SV guided by ED adds no extra value to the fluid therapy using zero balance and normal BW in patients undergoing elective colorectal surgery.” p.191 (BW= body weight, ED= esophageal Doppler, SV= stroke volume)

Challand,

12 2012, UK

Main Findings: Outcomes with EDM guided goal directed therapy compared to control (standard care) in adults undergoing major colorectal surgery

Outcome EDM/GDT (N=89)

Control (N= 90) p-value

Mortality* (< 30 days)

2 2 1.0


5 4 0.72

Serious postoperative complications*

10 13 0.47

Renal complications*

20 13 0.17

Critical care admission*

24 17 0.26

Readmission* (<30 days)

18 13 0.35

Readiness for discharge† (days)

6.8 (4.0- 9.8) 4.9 (3.7- 8.8) 0.09

Postoperative stay† (days)

8.8 (6.0- 11.9) 6.7 (4.8- 13.3) 0.09

*Outcome data as number of patients, † Outcome data as median (interquartile range)




Outcomes with EDM guided goal directed therapy compared to control (standard care) in a subgroup of adults (classed as aerobically fit) undergoing major colorectal surgery

Outcome EDM/GDT (N=62)

Control (N= 61) p-value


1 2 0.46


2 3 0.43

Serious postoperative complications*

6 6 0.32

Critical care admission*

14 5 0.03

Readmission* (<30 days)

11 10 0.36

Readiness for discharge† (days)

7.0 (4.7- 9.6) 4.7 (3.0- 7.8) 0.01

Postoperative stay† (days)

8.8 (6.8- 11.0) 6.0 (4.1- 9.8) 0.01

*Outcome data as number of patients, † Outcome data as median (interquartile range)

Authors’ Conclusion: “Intraoperative SV optimization conferred no additional benefits over standard therapy. In an aerobically fit subgroup of patients, GDT was associated with detrimental effects on the primary outcome” p.53 (GDT= goal-directed therapy, SV= stroke volume)

Non randomized study (NRS)

Figus,

13 2013, UK

Main Findings: Outcomes with EDM compared to CVP in adults undergoing free perforator flap surgery

Outcome EDM (N= 51) CVP(N= 53) p-value

Hospital stay (days) (mean± SD)

8.9± 3.6 10.8± 6.2 0.147

Returned to theater (number [%])

7 (13.7%) 13 (24.5%) 0.215

Flap survival- total (number [%])

50 (98.0%) 50 (94.3%) 0.632

Flap survival- partial (number [%])

1 (2.0%) 3 (5.7%)

Flap survival- 0 (0%) 0 (0%)




failure (number [%])

Complications No esophageal Doppler probe-related complications

1 episode of iatrogenic Horner syndrome, which did not resolve in 6 months postoperatively. In patients with arterial cannulae, there were 5 incidences of symptomatic hematomas which resolved within 3 weeks

Authors’ Conclusion: “……Our results suggest that patients undergoing free perforator flap reconstruction may be managed equally well, if not better, with the use of ED probes. The obvious advantage of ED probes is the zero risk for complications, compared with invasive lines, and this seems argument enough to discontinue the use of invasive intraoperative monitoring. Further, intraoperative ED monitoring seems to encourage a favorable postoperative fluid balance with reductions in the risk of flap-related complications and a positive trend toward shorter hospital stays, for patients undergoing reconstructive free perforator flap surgery.” p. 306 (ED= esophageal Doppler)

Kuper,

14 2011, UK

Main Findings: Comparison of outcomes obtained in patients undergoing surgery, before and after implementation of EDM

Outcome After implementation of EDM (N=649)

Control (before implementation of EDM (N= 658)

p-value

Length of hospital stay (mean± SD)

15.1± 16.7 18.7± 24.4 0.002

In-hospital mortality (N [%])

18 (2.8) 23 (3.5) 0.37

Readmission to hospital (N [%])

25 (3.9) 36 (5.5) 0.20

Readmission to critical care (N [%])

14 (2.2) 22 (3.3) 0.20

Reoperation (N [%])

38 (5.9) 55 (8.4) 0.08




Length of hospital stay before and after implementation of EDM for each of the three hospital

Hospital Length of hospital stay (mean± SD) p-value

After implementation of EDM

Control (before implementation of EDM

Derby 8.4± 7.3 (N= 201)

10.9± 10.7 (N= 201)

0.007

Manchester 19.8± 23.2 (N= 224)

25.5± 34.8 (N= 232)

0.043

Whittington 13.4± 12.7 (N= 224)

15.7± 13.4 (N= 225)

0.108

Harm: The authors mentioned that there were no signs of harm from the implementation EDM, except one episode of pulmonary edema in a patient with sepsis and chronic renal failure

Authors’ Conclusion: “Even though patient groups differed at the three sites in type of urgency of surgery, a consistent benefit was seen. This indicates that implementing oesophageal Doppler monitoring may produce benefits in diverse healthcare settings.” p. 3 of 10

Economic

Maeso,15

2011, Spain

Main Findings: (CCA+ CVP+ EDM) dominated over the other alternatives ([CCA+ CVP], [CCA+ EDM], and CCA) as it was associated with lower mortality, fewer complications and lower costs. For patients who underwent EDM the total hospital stay was 1.1 days fewer.

Strategy Rate of survival

Rate of no major complication

Cost (€) per patient

Savings (€) per patient

CCA+ CVP+ EDM

99% 98% 8579 911

CCA+ CVP 98% 87% 9490

As length of hospital stay was the main driver of cost, if there was no difference in hospital stay for (CCA+ CVP+ EDM) compared to (CCA+ CVP), the cost of (CCA+ CVP+ EDM) would increase from €9490 to €9121, resulting in a lesser cost saving of €369. As the difference in mortality rates of (CCA+ CVP+ EDM) compared to (CCA+ CVP) was not statistically significant, (CCA+ CVP+ EDM) did not always appear to be the best option.




Results on utilities of the economic decision model analysis

Strategy Cost (€) QALY ICER (€/QALY)

CCA 14,830 13.21 Dominated

CCA+ CVP 15,244 14.37 Dominated

CCA+ EDM 14,256 13.24 (159/1.34) =118.65 for (CCA+ CVP+ EDM) over (CCA+ EDM)

CCA+ CVP+ EDM

14,415 14.58

Authors’ Conclusion: “In conclusion, if the results of the small size RCTs examined in the present study are confirmed in daily practice, the present assessment indicates that a strategy of hemodynamic monitoring that includes CCA+ CVP+ EDM during elective colorectal surgery would be cost-effective, improving health outcomes and saving health care resources. Further primary studies comparing other forms of monitoring, such as pulse wave analysis monitoring, are required. These studies should include economic assessments so that different strategies can be compared. Well designed studies are needed to confirm whether the estimated savings and improved outcomes obtained with EDM hold true in practice. Similar studies should also be performed in patients undergoing other types of surgery.” p. 825 (CCA= conventional clinical assessment, CVP= central venous pressure, EDM= esophageal Doppler monitoring, RCTs= randomized controlled trials)

BD= body weight, CCA= conventional clinical assessment, CVP= central venous pressure, CI= confidence interval, DB= double blind, EDM= esophageal Doppler monitoring, GDT= goal directed fluid therapy, ICER= incremental cost-effectiveness ratio, ICU= intensive care unit, N= number of patients, NR= not reported, OR= odd’s ratio, QALY= quality adjusted life year, SD= standard deviation, SV= stroke volume, WMD= weighted mean difference, Z= zero fluid balance approach