LITHUANIAN UNIVERSITY OF HEALTH SCIENCES FACULTY OF MEDICINE, DEPARTMENT OF ANESTHESIOLOGY

(1)

LITHUANIAN UNIVERSITY OF HEALTH SCIENCES

FACULTY OF MEDICINE,

DEPARTMENT OF ANESTHESIOLOGY

Comparison of Different Methods for Hemodynamic

Monitoring: Thermodilution vs. Fick Method

Final Master Thesis

Author: Aiswarya Mohan

Supervisor: Dr. Tadas Lenkutis

Kaunas

2020/2021

(2)

2

1. SUMMARY

Author: Aiswarya Mohan

Title: Comparison of different methods for hemodynamic monitoring: Thermodilution Vs Fick method. Aim: The aim of this literature review is to compare the Thermodilution hemodynamic monitoring with Fick method.

Objectives:

The objectives or goals of this literature review are:

1. To review on cardiac output monitoring by Thermodilution method and Fick method and their significance.

2. To assure between Thermodilution and Fick method for cardiac patients with low left ventricle ejection fraction and pulmonary hypertension, which access is better.

3. To report on the advantages and disadvantages of both methods and which one is more accurate in hemodynamic monitoring.

Methodology:

Literature was identified by searching PubMed, science direct, Google scholar with combination of the following terms: “hemodynamic monitoring” OR “cardiac output monitoring” OR “continuous cardiac output monitoring in heart diseases” and “Fick method” OR “Thermodilution method” OR comparison of Thermodilution and Fick method”. Initial search resulted in 4657 articles. Further application of filters (human studies, English language) provided 134 articles. The articles selected for this review were comparative studies and research articles in English, and this was manually sorted according to inclusion and exclusion criteria.

Results:

The total of 34 articles were considered eligible for this literature review. 11 articles were clinical trials, that was conducted between 2010 and 2020 were eligible for the scope of this review. 4 of them indicate the mean ±CO assessed by different hemodynamic measurement methods, especially Thermodilution and Fick method and the rest addressed the important hemodynamic parameters determined by Thermodilution and Fick method in various study population, mainly focusing on patients with PAH and cardiac insufficiency. Also the efficacy and drawbacks of both methods faced during clinical trials.

(4)

4 Conclusion:

In terms of reviewing main clinical studies and articles of hemodynamic monitoring based on both Thermodilution and Fick method, it seems that different conditions need different approaches, each patient has various requirements and hemodynamic monitoring should be in terms of clinical condition, invasiveness and cost effectiveness. In that case Thermodilution and Fick method are gold standard methods in hemodynamic monitoring and very useful in tracking a patient status efficiently. The most frequent used technique in ICU is Thermodilution even though it is invasive, clinicians consider it to be the better option in continuous cardiac output monitoring. In patients with expected good prognosis in heart failure or pulmonary artery hypertension, Fick is the Gold standard. Nevertheless, further research is needed to investigate monitoring efficacy and more clinical studies are needed regarding the outcomes of both methods.

Practical Recommendations

One way could be to combine the methods and compare them, with a large number of clinical trials and comparative analysis with other pre-existing methods. This could give way to higher specificity in results. In this review Thermodilution and Fick method shows the most promise, however the question remains about how available it can be in clinical practice, because the cost effectiveness and accessibility should be taken into consideration and researched further.

(5)

2. ACKNOWLEDGEMENTS

I would like to extend my sincere gratitude to my supervisor, Dr. Tadas Lenkutis for his guidance and immense support throughout this literature review.

I would also like to thank my beloved family, friends and teachers for their support and help during this entire journey.

3. CONFLICT OF INTEREST

Author reports no conflicts of interest for this review.

4. ETHICS COMMITTEE APPROVAL

(6)

6

5. ABBREVIATIONS LIST

AUC: Area under the curve BMI: Body mass index BSA: Basal Surface area

CCO: Continuous cardiac output CI: Cardiac index

CO: Cardiac output

CVP: Central venous pressure DFCO: Direct Fick cardiac output EDV: End diastolic volume ESV: End systolic volume HR: Heart rate

ICU: Intensive care unit

IFCO: Indirect Fick cardiac output IFM: Indirect Fick method

LVEF: Left ventricular ejection fraction PAC: Pulmonary artery catheter

RA: Right atrium RR: Respiratory rate RV: Right ventricle

(7)

RVEDV: Right Ventricular End diastolic volume RVEF: Right ventricular ejection fraction

SOFA: sequential organ failure assessment SV: Stroke Volume

SVR: Stroke volume rate TD: Thermodilution

TDCO: Thermodilution cardiac output TPTD: Trans pulmonary thermos dilution

(8)

6. INTRODUCTION

The Hemodynamic monitoring term is used to designate “measuring an organism’s ability to deliver oxygen to its tissues”. However, this single hemodynamic parameter is not sufficient in determining a patient’s perfusion status because tissue perfusion depends on oxygenation and cardiac output (CO), which is further dependent on preload, afterload, cardiac contractility, and heart rate [3]. Hemodynamic monitoring can be suggestive of types of shocks and cardiac insufficiency, so it is considered as the main component in an intensive care unit (ICU) and operating rooms [4].

Analysing different methods like for hemodynamic monitoring during the past several decades, two important methods for measuring Cardiac output (CO) have been developed are Thermodilution and Fick principle. The invention of a pulmonary artery catheter (PAC), which Swan, Ganz and, Forrester launched in the 1970s is still the gold standard. When comparing these two hemodynamic monitoring techniques, these procedures can be categorized as calibrated or non-calibrated or based on their invasiveness level (invasive, less invasive, and otherwise non-invasive). The more encouraged methods are less invasive and non-invasive technologies to reduce accompanying threats of invasiveness [29]. It is necessary to monitor all participants treated in the Intensive care unit, but the monitoring standard will vary. Perhaps hemodynamically healthy patients only need continuous ECG monitoring such as regular measurements of blood pressure, and peripheral pulse oximetry (peripheral oxygen saturation or SpO2). On the other hand, those who are at risk of instability or unstable like sepsis should receive invasive continuous blood pressure monitoring through the arterial line and regular blood gasses analysis.

There are various techniques of hemodynamic monitoring available in the present days but this review mainly focuses on only two main methods that are considered equally important; Thermodilution and Fick method. Both methods have their indications and are truly dependent on the anaesthesiologists’ preference of these methods. Additionally, a more precise detailed discussion is needed to identify the advantages and disadvantages of both methods before considering its application in clinical settings, thus it can affect the outcome of treatment. Many invasive methods can be more accurate in diagnosis however it has shown to increase the rate of mortality later. Subsequently, one of the main particularities of minimally and non-invasive techniques is their ability to provide the measurement of continuous cardiac output (CO) and fluid responsiveness variables in real-time [24,30].

Comparing these two methods has given a brief idea in determining the efficiency of these methods in hemodynamic monitoring. This review aims to provide an overview of these comparative studies and explore their usefulness in early diagnosing and to increasing therapeutic outcomes.

(9)

7. AIM AND OBJECTIVES

Aim:

The aim of this literature review is to compare the Thermodilution hemodynamic monitoring with Fick method.

Objectives:

1. To review cardiac output monitoring by the Thermodilution method and the Fick method their significance.

2. To assure between Thermodilution and Fick method for cardiac patients with low left ventricle ejection fraction and pulmonary hypertension.

3. To report on the advantages and disadvantages of both methods and which one is more accurate in hemodynamic monitoring.

(10)

8. LITERATURE REVIEW

8.1. Hemodynamic Monitoring.

In the management of the cardiovascular patients, it is imperative that the haemostatic monitoring system must be used. There should be continuous monitoring of the blood flow and the pressures being exerted in the veins, arteries, and chambers of the heart. It helps to detect hemodynamic changes, diagnose the causes behind them, and improve the delivery of oxygen to tissues. Recent advances include the shift from static to dynamic variables to less-invasive or non-invasive techniques to assess cardiac preload and fluid responsiveness conditions [2].

Mainly hemodynamic monitoring is indicated when there is a potential or actual fluctuation in CO and a possible chance of alteration in fluid volume. To improve patient outcomes, hemodynamic status should be understood early [3]. Following Table.1 shows some important hemodynamic parameter measurements [1].

Hemodynamic Variables Abbreviations Normal values

Heart rate HR 60-100 beats/

min

Cardiac Output CO 4-6 L/min

Cardiac Index CI 2.5-4 L/min/m2

Stroke Volume SV 40-80 ml

Stroke Volume Index SVI 33-47 ml/m2

Global end diastolic volume index GEDVI 680-800 ml/m2

Systolic Blood Pressure Diastolic Blood Pressure

SBP DBP

90 - 140 mmHg 60 - 90 mmHg

Mean arterial pressure MAP 70-105 mmHg

Central venous pressure CVP 0-8 mmHg

Right atrial pressure RAP 0-8 mmHg

Mean pulmonary artery pressure MPAP 10-20 mmHg

(11)

When there is an alteration in normal measurements (Table.1) it is considered pathology as according to author’s Pinsky MR et al. [4]. Therefore, it is crucial to monitor if there are any changes in the functional hemodynamic variables as it may indicate a pathology as listed in Fig.1[4].

Fig.1 Clinical representation for change in hemodynamic variables obtained from Pinsky MR et al. [4]

In operation room and critical care environments, measuring cardiac output has important consequences. A persistently low cardiac output has been linked to a longer stay in intensive care along with higher morbidity and mortality rates. Monitoring is therefore important to ensure accuracy [18].

8.2. Cardiac Output (CO).

The total oxygen supply to each organ is determined by cardiac output (CO). We can use it as a parameter to assess critically ill patients who require hemodynamic management and appropriate cardiovascular treatment. [21]

Specifically, CO measures the left ventricular output and act as a clinical indicator of left ventricular function. Therefore, factors that affect HR or SV then directly affect CO [19].

According to Thiele RH et al. [18] “CO is the total volume of blood pumped by the heart per unit time”. It is the product of HR (heart rate) and SV (stroke volume). SV is ascertained by preload, contractility, and afterload [18].

(12)

CO= SV × HR [19]

CO = Cardiac Output SV= Stroke Volume HR= Heart rate

(normal CO range =4-6 litres)

Several factors influence the CO measurement but among them, the stroke volume is affected by mainly these variables: preload, afterload, contractility, and venous return [19].

8.3. Cardiac Index (CI).

CI = CO/ BSA or (HR *SV) / BSA

(CO = Cardiac Output, SV= Stroke Volume, HR= Heart rate, BSA= Body Surface Area)

A drop in the cardiac index (CI) is a direct warning indication that something has to be done to change the condition. Awareness of the cardiac index alone does not offer sufficient clinical decision-making guidance as the CI is affected by many factors such as HR, stroke volume, preload, afterload and contractility [24].

8.4. CO influencing factors.

Two main factors directly affect the CO are HR and SV. [19]

HR (Heart rate) can be affected by various factors like hormones, age and autonomic innervations. when there is an increase in HR, CO gradually increases.

Stroke Volume: SV = EDV – ESV

(EDV - volume of blood remaining in ventricle after diastole)

(ESV-volume of blood in the ventricle after contraction).

The amount of blood pumped by each ventricle within one beat. Normal is 80ml [32] main factors that affect SV are preload, afterload, and contractility.

Preload: The degree to which cardiomyocytes are stretched before contraction. It is mainly influenced by venous return.

(13)

Venous Return: the volume of blood returning to the right atrium and stretched ventricles through the vein in each minute. If the venous return is increased, EDV tends to increase, therefore SV increases, left and right ventricles have an equal amount of venous return; therefore, blood does not backflow in the heart.

Contractility: contractile strength of heart (due to increased Ca 2+_{) causes increased release of blood}

therefore it results in lower ESV.

Afterload: the force at which the heart is required to contract to overcome the higher pressure in the aorta. The force at which blood is ejected from ventricles is constant in healthy individuals. However, in people with hypertension, there is increased arterial blood pressure and vascular tone which leads to increases ESV and decreases SV.

CO monitoring can be done using numerous methods, two types of Hemodynamic monitoring that has been done are invasive and non-invasive monitoring. The main principle used for monitoring CO is the Fick principle.

8.5. Fick Method

Presently Fick principle is used in hemodynamic cardiovascular studies all over the world to determine cardiac output and quantify intracardiac shunts. The concept was first presented in 1870 by Adolf Fick [19]. Blood flow through a single organ could be calculated by measuring the arteriovenous concentration gradient of an indicator [21,22].

The Fick principle states that “at a steady state the uptake or elimination of substance by an organ is the product of the blood flow through that organ and the arteriovenous concentration difference of the substance” [19].

Direct Fick method: an invasive method which measures VO2, determined by spirometry, PVO2 –

obtained from any peripheral artery, PAO2 – from the pulmonary artery and is determined from

pulmonary blood flow through pulmonary artery catheter (PAC) commonly. The Fick Technique derives cardiac output CO from oxygen uptake (VO2):

𝐶𝑂 = 𝑉𝑂2

𝐶𝑎𝑂_{2−𝐶𝑣𝑂}₂

(VO2 = oxygen uptake (i.e. oxygen content difference between inspired and exhaled gas), CaO2 =

(14)

The important benefit of this method is that it is highly accurate and the main drawbacks are this method is both invasive and time-consuming and there is an increased chance of arrhythmias and infections.

Indirect Fick method: uses Fick principle and records changes in CO2 elimination and estimate VO2 (3.5

mL/Kg), same as that of direct method but CO2 excretion by lungs is measured by spirometry. PACO2

from alveolar air. PVCO2 – from rebreathing into a closed bag. It is a Non-invasive method and has

comparable accuracy of values to the invasive method but the main drawback is that gives estimated value so it can get easily affected by external factors and also applicable only to mechanically ventilated patients.

8.6. Thermodilution Method.

This method is the dilution of two types of fluids with different temperatures: blood and water. At the end of the 19th century, George Neil Stewart identified the procedure of Thermodilution as he inserted a sodium solution bolus in a central vein detected in a contralateral femoral artery [15]. The change in blood saturation was proportional to cardiac activity [24]. The main principle used in this technology is the indicator dilution principle but uses heat instead of colour as an indicator. The injection of saline and determination of temperature is done by a specialized catheter which is inserted into the heart. CO is calculated using the modified Stewart-Hamilton indicator dilution equation. After injection, the temperature is plotted as a function of time to produce a Thermodilution curve. The shape of the Thermodilution curve is used to calculate CO.

Thermodilution method has been recently modified to calculate the CCO as well as monitoring the function of the right ventricle. It also has several advantages; i.e., the indicator has no toxicity, so measurements can be performed repeatedly. [26]

Modified Stewart-Hamilton equation for Thermodilution. (Obtained from Hoeper MM et.al [30])

[24]

(Tb = Blood temperature, Ti = Injectate temperature, Vi = Injectate volume, AUC = Area under the Thermodilution curve

(15)

There are two main techniques used in Thermodilution, PATD (Pulmonary Artery Thermo Dilution) and TPTD (Trans pulmonary Thermo Dilution). Fig.2 represents a graph that shows the comparison of Thermodilution curve by PATD and TPTD. The CO is inversely proportional to the mean blood temperature depression and the duration of transit of cooled blood i.e.; AUC (area under the curve) [27].

Fig.2 Graph representing AUC. Reuter DA et al. [29]

Chamos et al. [31] suggest that there is a characteristic delay in peak temperature change in the TPTD curve as compared to PATD suggest the importance of the existence of the principle of PAC [30].

8.6.1. Thermodilution using PAC (invasive method)

The Thermodilution method used by a PAC remains as the gold standard for cardiac output assessment in most cardiothoracic surgical units.

A specially designed flow-directed catheter, so-called Swan–Ganz Thermodilution catheter, is widely used for cardiac output measurements [1]. Ganz et al.1971, and Swan et al. 1970 say that the catheter in Fig.3shows the configuration of “2.3–2.5 mm in the outer diameter and a thermistor consist of time

constant between 0.2–0.4 is attached near the tip then an injection port located 25–30 cm from the tip”. Additional lumens are available for pressure measurement or medication in commercial catheter” [27].

(16)

The catheter shown in Fig.3 is placed through RA, RV then into PA. An amount of 5-10ml of cold saline (normally 00_{c) is injected to the port of the catheter placed in the RA and saline gets mixed with the}

blood in RA and RV. The change represented in temperature is then evaluated by the thermistor located downstream in the PA. This procedure can be repeated many times (3-5 times) to get an accurate result and the calculations are computerised

.

Fig.4 depicts how the catheter is placed through the heart

chambers.

The CO measurement by PAC is not true continuous monitoring as there will be changes in CO when there is a fluid change i.e.; after preload and afterload. PAC is widely recommended to be used in patients with right heart failure or patients with pulmonary hypertension as it is capable of direct measurements from the right heart and pulmonary circulation compared with other techniques (RVEF, RVEDV, right and left SV measurements, systemic and pulmonary vascular resistance) [31]. Although PAC is widely accepted the survival benefits if the technique is not yet clearly studied

.

Fig.4 Represents catheter placement through heart chambers obtained from Monnet X et al. [27]

8.6.2. Transpulmonary Thermodilution TPTD (Less invasive method)

TPTD measures cardiac output using the modified Stewart–Hamilton principle. For the measurement, only a fraction of the total injected indicator is needed to pass the detection site, as it is only the change in temperature over time that is relevant. It also allows calculation of various hemodynamic parameters i.e. cardiac preload which can be calculated by advanced analysis of the curve. TPTD technology is a less invasive method for monitoring the volume status and cardiovascular function, so presently it is widely accepted [16].

Compared to PAC, the difference with TPTD is that an amount of cold saline is injected not in the right atrium but in a central vein and the blood temperature is measured in the systemic artery, not in the

(17)

pulmonary artery. According to numerous studies, the TPTD way of measuring cardiac activity is more precise than the pulmonary artery catheter and the Fick method. In addition to its performance, the TPTD technique often has a valuable capacity to accurately monitor cardio performance changes [18].

TPTD is also considered the gold standard as it gives both intermittent and continuous CO and SV measurements despite fluid changes especially in conditions where preload changes. Chamos et al. [31] state that it also measures various parameters as Global End Diastolic Volume (GEDV), Global Ejection Fraction(GEF), Intrathoracic Blood Volume(ITBV), and Extravascular Lung Water (EVLW), contractility, and Systemic Vascular Resistance (SVR), Pulmonary Vascular Permeability Index(PVPI). Although it is less invasive there are certain limits for the technique as it is not applicable in conditions with low HR or low RR ratio, arrhythmias, open thorax, mechanical ventilation with low tidal volume (TV) [31].

(18)

9. RESEARCH METHODOLOGY

Search strategy:

Literature was identified by searching PubMed, Google Scholar and Science Direct with a combination of the following terms: “Hemodynamic monitoring” OR “Cardiac output monitoring”, “Thermodilution method” “Fick method” and “Comparison of different methods in cardiac output monitoring” OR “Invasive and Non-invasive technique in Cardiac output monitoring” Also “pulmonary hypertension”, “Left ventricular ejection fraction”. These terms were used in the initial search (Table 2) and resulted in 4657 articles in total.

After this further, filters were applied (using the advanced filter section on these data basis): Date range: mostly within ten years (2010 -2020), Species: Human, Language: English, Population type: >18 years old (Table 2).

Table 2: List of terms used in Data extraction:

Main terms

- Hemodynamic monitoring - Cardiac output monitoring - Thermodilution method - Fick method

Additional terms

- Invasive hemodynamic methods - Non-invasive hemodynamic methods - Pulmonary hypertension

(19)

Table 3: criteria for Inclusion and exclusion.

INCLUSION CRITERIA EXCLUSION CRITERIA

Full free text articles in English Abstracts, summaries ,paid full text articles and non-English articles are excluded

Clinical trials published after 2010 included in results

Clinical trials published before 2010 are excluded from results

Patients with suspected sepsis ,PAH are included

Patients with oncologic diseases are excluded

Studies related to humans Studies performed in animals

Population range >18yrs. included Neonates and population <18 yrs. are excluded

Articles in English Articles in any other languages

PAH: Pulmonary arterial hypertension.

Search strategy results:

Then, the resulting 134articles were manually arranged according to the inclusion/exclusion criteria as shown in Table.2 by reading the title and abstract. The total number of articles included in this comparative study is 34, out of that 11 publications which were either comparative studies, cohort studies, observational studies, clinical trials, or single center studies are included in the results. Rest of the articles are referred in to literature review part. The articles included were free texts, with a specific study population that excluded patients with the oncological background but added population with cardiac insufficiencies or pulmonary hypertension. Also, patients treated in the ICU and perioperative care were included as part of this literature review. Additionally, any articles that studied the population<18 years old, Articles that did not offer free text, meta-analysis, and those that were abstracts only with no external links were excluded from this literature review.

(20)

10. RESULTS

In the results section of this review, a total of 11 studies have been analysed. Table.4 contains the summary of the 4 studies reviewed regarding the objective of comparing 4 different CO monitoring methods in patients having PAH under different circumstances and discussing the efficacy of each method. And Table .5 discusses the most suitable methods among Thermodilution and Fick method for the patients in ICU with shock and decreased cardiac function.

Also Tables 4 and 5gives a brief idea about the conclusion of the research that each study has finalised, which makes it easier to go through the relevant data in the study that this literature review mainly discuss about.

Table. 4: Summary of the studies reviewed in the comparison of CO measurement by different methods in PAH patients [5-8]

NO. Author, Year and Reference Type of Study Design Aim or Objective of the Study Sample Size and Age Range

Methods Conclusions Remarks

1 Rich JD et al.(2013) [5]

Cohort study To compare the precision and

accuracy of three CO measuring methods in patients with PAH.

Sample size: 50 Age range:54±13 Thermodilution ,Indirect Fick method and NICOM This study recommends Fick or NICOM over Thermodilution in measuring CO in patients with PAH.

Thermodilution when comparing with Fick and NICOM showed very high CO measurements before and after fluid infusion.

(21)

2 Fares WH et al. (2012) [6] Retrospective Cross sectional study To describe the relationship

between two methods to determine CO monitoring in

population with PAH and without PAH.

Sample size: 198

Age range: 54 ±13

Thermodilution and Indirect Fick method

Indirect Fick is the preferred method here because

Thermodilution did not show much difference in values between sample with PAH and without PAH. Thermodilution showed >10% difference in hemodynamic values measured by Indirect Fick method 3 Alkhodair A et al.(2018) [7] Retrospective cohort study Comparison of TDCO and IFCO to identify accurate CO measurement in patients with PAH.

Sample size:168 Age

range:63±13

This study give predominance to Thermodilution because Fick method showed inaccurate values in patients with PAH.

Indirect Fick method showed error values while recording female patients with PAH and patients with High BMI 4 Hsu S et al. (2017)

[8]

Retrospective Single center study

To compare between TDCO and DFCO in patients with exertional dyspnoea to determine EIPH. Sample size: 20 Age range:56±13 Thermodilution and Direct Fick method

Direct Fick method is more accurate,

Thermodilution diagnosed excess EIPH patients while monitoring.

Thermodilution recorded very low CO values

compared to Fick method that led to misdiagnosis of EIPH in many patients.

CO: Cardiac Output, BMI: Body mass index, NICOM: non-invasive cardiac output monitor, EIPH: exercise-induced pulmonary hypertension, TDCO: Thermodilution cardiac output, DFCO: Direct Fick cardiac output, IFCO: Indirect Fick cardiac output, PAH: Pulmonary artery Hypertension.

(22)

Table 5: Summary of the studies reviewed in the comparison of hemodynamic variables by different methods in critical care setting. [10-16]

NO. Author, Year and Reference Type of Study Design Aim or Objective of the Study Sample Size and Age Range

Methods Conclusions Remarks

1 Kresoja et al.(2019) [10]

Retrospective single- center study

Aim of the study is to research the

correlation between Thermodilution and estimated Fick

method in low LVEF.

Sample size: 155

Age

range:75.1±6.8

Both methods had very less difference in determining hemodynamic values. But Thermodilution is considered as gold standard. Thermodilution when comparing with Fick and NICOM showed very high CO measurements before and after fluid infusion. 2 Optowsky AR et al. (2017) [11] Retrospective Cohort study To determine the agreement between Thermodilution and estimated Fick method and also to compare how good these methods can assess mortality in congestive heart failure patients. Sample size: 12,232 Age range: 20.0 Thermodilution and Indirect Fick method

There was no significant difference between both methods in determining CO and CI. But Thermodilution values predicted more precise mortality rate. Thermodilution showed >10% difference in hemodynamic values measured by Indirect Fick method 3 Grensemann J et al.(2016) [12] Single center study To compare uncalibrated pulse contour method and Fick method with Trans pulmonary

Sample size: 21 Age range:20-86

Uncalibrated pulse contour method, Fick method and Trans pulmonary

Thermodilution.

Thermodilution is the preferred method compared to Fick and pulse contour in ICU

Indirect Fick method showed error values while recording female patients

(23)

Thermodilution in critically ill patients in ICU.

for continuous monitoring.

with PAH and patients with High BMI 4 Palmers PJ et al. (2012) [13] Observational study To compare accuracy of three CCO monitoring methods with TPTD, in ICU patients. Sample size: 23 Age range:63±14 Uncalibrated peripheral pulse contour measurement (FCCO), calibrated central pulse contour measurement (PCCO), and CCO obtained by indirect Fick principle (NCCO) and

TPTDCO.

Thermodilution has turned out to be gold standard in

monitoring critically ill patients in ICU. But pulse contour showed good agreement with Thermodilution being independent of SVRI change. Thermodilution recorded very low CO values compared to Fick method that led to misdiagnosis of EIPH in many patients. 5 Tehrani DM et al. (2017) [14] Retrospective observational study To compare CO assessment between both Indirect Fick method and Thermodilution in CF-LVAD patients. Sample size: 111 Age range: 56±11 Thermodilution and Indirect Fick method.

This study recommends Fick method over Thermodilution in CF-LVAD patients. Thermodilution showed inaccuracy in measuring hemodynamic variables at low flow rate and it was considered unnecessary to implement such an invasive method in heart failure patients.

(24)

6 Perny JJ et al. (2014) [15] Prospective observational study To evaluate CFI measured by Thermodilution as an indicator for LVEF in cardiogenic shock.

Sample size: 35 Age range: 66 ±16

Thermodilution This study proposes Thermodilution in evaluating CFI in patients with cardiogenic shock as the measurements were unaffected by fluid change. As LVEF is an important parameter in ICU, Thermodilution showed high sensitivity and specificity indicating low LVEF in ICU patients in this study. 7 Hilty MP et al. (2017) [16] Single center study To determine TPTD validity in critically ill patients in ICU and hemodynamically stable patient. Sample size: 29 Age range: 62 ±7 Trans pulmonary Thermodilution(TPTD) CO measurement by Thermodilution was unaffected by fluid change and cardiomyopathy but were not sensitive in predicting low LVEF. Thermodilution gives accurate measurements critically ill patients but can give error values in patients with valve defects and dilated

cardiomyopathy.

ICU: Intensive care unit HF: Heart failure, CI: Cardiac Index, CO: Cardiac output, CFI: Cardiac function index, FM: Fick method, LVEF: Left ventricular ejection fraction, TD: Thermodilution, IFM: Indirect Fick method TDCO (Thermodilution cardiac output), IFCO: Direct Fick cardiac output, FCCO: uncalibrated peripheral pulse contour measurement PCCO: calibrated central pulse contour measurement.

(25)

Table 6: Results of 4 studies reviewed in the comparison of CO measurement by different methods in PAH patients [5-8].

No . Author, Year and Reference

Findings Throughout the Study TDCO (L/Min) IFCO (L/Min) DFCO (L/Min) NICOM (L/Min) 1 Rich JD et al. (2013) [5]

Mean ±CO in patients with PAH

After vasodilator challenge mean ±CO in patients with PAH

4.84±1.39 7.02±1.84 5.69±1.74 5.83±1.75 N/A N/A 4.73±1.15 5.53±1.46 2 Fares WH et al. (2012) [6]

Mean ±CO in PAH patients

Mean ±CO in Non PAH patients

5.40±1.99 5.57±1.99 5.67±2.05 6.05±2.48 N/A N/A N/A N/A 3 Alkhodair A et al. (2018) [7]

Mean ±CO in patients with PAH 4.8 ± 1.6 4.2 ± 1.5 N/A N/A

4 Hsu S

et al. (2017) [8]

(26)

Table 7: Results of 5 studies reviewed in comparison of hemodynamic variables by different methods in critical care setting [10-14].

No Author

Year and Reference

Methods CO (L/Min) CI (L/Min) SV (L/Min) GEF% mPAP 1 Kresoja KP et al. (2019) [10] -TDCO -IFCO(Lf) -IFCO(De) -IFCO(Be) 4.49 ±1.33 4.08 ±1.27 4.76 ±1.32 5.30 ± 1.54 2.36 ±0.56 2.14 ± 0.56 2.51 ± 0.63 2.78 ± 0.70 N/A 32.8 ±11.8 2 Opotowsky AR et al. (2017) [11] -TD -IFM 5.3 (1.7) 5.3 (1.6) 2.5 (0.7) 2.5 (0.7) N/A N/A N/A N/A N/A N/A 3 Grensemann J et al. (2016) [12] -TDCO Baseline T4 -IFCO Baseline T4 -FCCO 3.7 ± 0.7 3.5 ± 0.6 5.2 ± 1.8 4.8 ± 1.7 N/A 14 ± 9 14 ± 9 N/A Baseline- 87 ± 13 T4- 88 ± 14

(27)

Baseline T4 3.8 ± 0.7 3.8 ± 1.2 13 ± 8 15 ± 9 4 Palmers PJ et al. (2012) [13] -TPTD-CO -PCCO -FCCO -NCCO 6.9 ± 1.8 6.9 ± 2.1 5.9 ± 1.5 6 ± 2 N/A N/A 26.9 ± 6.7 83.8 ± 17.9 5 Tehrani DM et al. (2017)[14] -TD -IFM 4.65 ± 1.33 5.37 ±1.51

(28)

Table 8: Results of 2 studies showing Thermodilution measurements in low LVEF [15],[16] . No Author Year and Reference Methods CIF (L/Min) CI (L/Min) GEDV (L/Min) GEF(%) LVEF(%) 1 Perny J el at. (2014) [15] -TD before inotrope infusion -TD after inotrope infusion 2.75±0.87 3.28±1.26 2.21 ±0.55 2.95 ±0.92 788 ±185 879 ±255 11.4 ±3.9 13.6 ±4.5 27 ±9 30.2 ±9.4 2 Hilty MP et al. (2017)[16] -TD with normal LVEF -TD with low LVEF 3.7 ± 0.7 3.5 ± 0.9 N/A N/A 22 ± 4 21 ± 6 67 ± 7 33 ± 13

(29)

The following tables below represents the additional relevant findings extracted from the studies demonstrated in Tables 4 and 5.

No. Author, Year and Reference

Additional data in the study

1 Rich JD et al.(2013) [5]  Out of 50 patients 56% were female.

 Before and after vasodilator challenge NICOM measurements were s more precise compared to TD. So Other than Thermodilution and Fick method NICOM were the most accurate method in this study. 2 Alkhodair A et

al.(2018) [7]

 Out of 168 patients in the study 64% were females

 The disagreement between Fick method and Thermodilution was more visible in females and with higher BMI

3 Kresoja et al.(2019) [10]

 Out of 155 consecutive patients 57.7% were male and 20% of the population had heart failure with reduced ejection fraction.

 Rest of the population 14 % had mild range of reduced ejection fraction and 65% had preserved ejection fraction

4 Optowsky AR et al. (2017) [11]

 A total of 12,232 patients assessed predominantly male population and there was a high prevalence of systemic hypertension and congestive heart failure.

5 Perny J et al. (2014) [15]

 In this study 35 patients with cardiogenic shock having 19 men (54.3%) and 16 women (45. 7%) also 60% having pre-existing cardiomyopathy.

 Patients are assessed before and after inotrope infusion for determining any changes in CFI and GEF as an indicator for LVEF.

(30)

11. DISCUSSION

Overall, analysing the results of this literature review shows that the comparison between Thermodilution and Fick principle in hemodynamic or CO monitoring is relevant. The main factors analysed were its efficacy, advantages, or disadvantages in various clinical settings.

In addition, this review tried to establish the correlation between two methods in precise hemodynamic estimation and determine the central and most efficient methods in CO monitoring in patients with PAH; according to the study conducted by Rich JD et al. 2018 [5], Transpulmonary Thermodilution was compared with indirect Fick method and another alternative Pulse contour analysis method, where pulse contour analysis and indirect Fick method was more accurate, feasible and showed superior precision as Thermodilution showed large variation after fluid challenge. This claim was also supported by Fares WH et al.’s 2012 [6] study showed that there was >20% of difference between both Indirect Fick method(IFM) and Thermodilution in patients having PAH and also tricuspid regurgitation affects the accuracy of Thermodilution. Therefore, it is crucial for the health professionals or anaesthesiologists must pay attention to the changes that occur after fluid administration and any existing systemic diseases. Alkhodair A et al. 2018 [7] conducted a retrospective cohort study which showed larger limits of agreement between the Fick method and Thermodilution in patients with increased BMI, and as indirect Fick method is more recommended to use over Thermodilution method in patients with PAH. In support of this study Hsu S et al. 2017 [8] demonstrates that Thermodilution showed excess of exercise induced pulmonary hypertension (EIPH) patients compared with DFCO and Tricuspid regurgitation also affects the values of TDCO so the study proposes DFCO over TDCO that direct Fick method gives more precise values of cardiac output measurements.so according to the recent studies evaluated indirect or direct Fick method is more appreciated in monitoring population with PAH. But there was only one study that reviewed the difference between direct Fick method and Thermodilution there can be an emergence of some risk factors such as pulmonary artery disruption or arrhythmias that can be visible with further additional researches [8].

According to Kresoja KP et al. (2019) [10], a retrospective study was using 155 consecutive patients where 20% of the population had heart failure with reduced ejection fraction and 14% with mildly reduced ejection fraction and in another cohort study by Opotowsky AR et al. (2017) [11], which had a high prevalence of systemic hypertension and congestive heart failure. While in both study compares Thermodilution and Fick method accuracy in determining a correlation between cardiac output and cardiac index measurements. As a result, they suggest that Thermodilution shows more accuracy compared to the indirect Fick method in a population with low ejection fraction and heart failure.

(31)

In critically ill patients admitted in ICU, it is recommended to use Thermodilution according to Grensemann J et al. (2016) [12] due to non-negligible variation showed by the Fick method and alternative pulse contour analysis. But Palmers PJ et al. (2012) [13] states that in an ICU setting in measuring continuous CO proposes pulse contour will be better established as it is non-invasive and is not affected by a change in SVRI but further studies regarding this non-invasive technique should be conducted to conclude this result.

According to Tehrani DM et al. (2017) [14] TD measurement accuracy is diminished in cases of a low flow rate and it also states that the indirect Fick method should be considered over Thermodilution in patients having heart failure or CF-LVADs. This is further demonstrated, in studies by Perny J et al. (2014) [15] and a recent study conducted by Hilty MP et al. (2017) [16], where they evaluated the sensitivity and specificity of these two methods in recording cardiac functional index (CFI)and Fick principle was statistically significant in predicting LVEF. However, on the other hand, both studies contradict as Perny J et al. (2014) [15] says that CFI determined by Thermodilution can be reliable in patients with cardiogenic shock, but recently conducted studies pinpoint the accuracy of Thermodilution in recording accurate CFI as an indicator of LVEF in patients having dilated cardiomyopathy and therefore it is not recommended [16]. Different studies analysed in this review showed that there are several factors like BMI, age, and other comorbidities that affect the hemodynamic parameters.

As a summary of this review, Thermodilution reported a variety of values regarding CO measurements, considering it as a gold standard in ICU units for patients in shock. This method is less invasive meaning that it is gaining more popularity because it may decrease further invasive complications and shows a good prognosis. The Fick method has comparable values to Thermodilution as it is more suggestive in patients with cardiac insufficiency, valve defects because it will be more supportive to the further maintenance and treatment outcome of the patient. Kresoja KP et al. (2019) [10] presents a table considering the advantages and disadvantages of Thermodilution, indirect and direct Fick method it can be guidance for the future and further studies should be investigated to conclude these result. Revising on other studies conducted recently shows that assessment of parameters in fluid responsiveness and preload value makes non-invasive techniques more attractive and it is considered to be safer in surgical patients [3].

The studies that have been conducted over last the 10 years concluded that because of the complexity of the response for intermittent or continuous cardiac output (CCO) monitoring, currently there are no standardised guidelines developed to determine a single effective method that can be used in clinical practice. Both Thermodilution and Fick method has a different outcome with specificity, due to varying fluid changes, age, BMI the type of maintenance, and associated health conditions. From the results, we

(32)

can propose that clinicians should always be aware of the patient’s hemodynamic status and hence choose the best available procedure accordingly.

11.1. Study limitations

First, since only one person collected data for this thesis, the type and number of articles chosen may have been affected. Second, the data and papers were searched for in three databases (Google Scholar, PubMed and science direct) from 2010 to 2020 in order to form an overview; however, this only revealed a small number of articles related to the subject and goals that may have affected the time range evaluation of this review, implying that other important articles on other valued databases could have been missed. Finally, the use of an English language filter could have restricted the number of papers that may have been acceptable.

(33)

12. CONCLUSIONS

1) In terms of reviewing main clinical studies and articles of hemodynamic monitoring based on both Thermodilution and Fick method, it seems that different conditions need different approaches, each patient has various requirements and hemodynamic monitoring should be in terms of clinical condition, invasiveness and cost effectiveness. Also, the place where the patient is further evaluated like in a normal ward or in intensive care units, and his or her responsiveness to fluid replacement and other cardiac conditions should be taken into consideration. Because notifying very slight changes in the parameters can be very important in disease diagnostics and patient maintenance so cardiac output monitoring is very significant. The measurements can vary depending on the methods used, the severity of diseases and the age of patients.

2) The gold standard method used in ICU and critical care settings is Thermodilution. All patients in ICU have SOFA assessment done, so continuous cardiac output (CCO) monitoring is significant. So when there is a patient in ICU with suspected sepsis or with any kind of shock it is recommended to use Thermodilution for better treatment outcomes. While for a patient having diminished cardiac activity due to several conditions such as valve defects, cardiomyopathy, and heart failure it is better to be monitored using Fick method as it will be the better choice for the prognosis of the patient.

3) To report on the advantages and disadvantages of both methods; Thermodilution and Fick, which doesn’t meet the consistency, accuracy, operator flexibility, rapid response, non-invasive and continuous measurement requirements, simplicity, low cost, and lack of complications. The direct Fick for O2, for

example, is time consuming and invasive, but it is very reliable and precise. Indirect Fick method although it is non-invasive gives an estimated value that cannot be fully depended on in many cases because the patients should be on mechanical ventilation but provides comparable values to the direct Fick method. Continuous Thermodilution procedure does not have a quick response but highly applicable in patients that need continuous cardiac output monitoring (CCO). Pulmonary artery catheter (PAC) and Trans pulmonary Thermodilution (TPTD) need multiple measurements, qualified personnel to introduce the PAC and is invasive. So the selection of methods depends on the anaesthesiologists, the hospital infrastructure, and the availability of methods.

(34)

13. PRACTICAL RECOMMENDATION

One way could be to combine the methods and compare them, with a large number of clinical trials and comparative analysis with other pre-existing methods. This could give way to higher specificity in results. In this review, Thermodilution and Fick methods are shown to be the most promising. However, the question remains how available it can be in clinical practice, as cost effectiveness and accessibility has to be taken into consideration and researched further.

With regards to the results conducted from studies over the last decade, more studies are needed to be undertaken to provide more accurate results. It would be ideal to associate it with patients or within the context of the clinical situation and aim for better cardiac output monitoring techniques.

(35)

14. REFERENCES

1. Nair A. Chapter 12 - Swan-Ganz Catheters and Cardiac Hemodynamics, Editor(s): Glenn N. Levine, Cardiology Secrets (Fifth Edition), Elsevier, 2018, Pages 103110.https://doi.org/10.1016/B978-0-323-47870-0.00012-X.

2. Scheeren TW, Ramsay MA. New developments in hemodynamic monitoring. Journal of cardiothoracic and vascular anaesthesia. 2019 Aug 1;33: S67-https://doi.org/10.1053/j.jvca.2019.03.043.

3. Orsenigo S, Pulici M. Invasive and Non-invasive Hemodynamic Monitoring. In: Aseni P, De Carlis L, Mazzola A, Grande AM, editors. Operative Techniques and Recent Advances in Acute Care and Emergency Surgery. Cham: Springer; 2019.https://doi.org/10.1007/978-3-319-951140_5.

4. Pinsky MR, Payen D. Functional hemodynamic monitoring. Crit Care. 2005;9(6):566–

https://doi.org/10.1186/cc3927PMID:16356240

5. Rich JD, Archer SL, Rich S. Non-invasive cardiac output measurements in patients with pulmonary

hypertension. Eur Respir J. 2013

Jul;42(1):12533.https://doi.org/10.1183/09031936.00102212PMID:23100501 6. Fares WH, Blanchard SK, Stouffer GA, Chang PP, Rosamond WD, Ford HJ, et al.

Thermodilution and Fick cardiac outputs differ: impact on pulmonary hypertension evaluation. Can Respir J. 2012 Jul-Aug;19(4):261–6.https://doi.org/10.1155/2012/261793PMID:22891186 7. Alkhodair A, Tsang MY, Cairns JA, Swiston JR, Levy RD, Lee L, et al. Comparison of thermodilution

and indirect Fick cardiac outputs in pulmonary hypertension. Int J Cardiol. 2018 May;258:228– 31.https://doi.org/10.1016/j.ijcard.2018.01.076PMID:29426632

8. Hsu S, Brusca SB, Rhodes PS, Kolb TM, Mathai SC, Tedford RJ. Use of thermodilution cardiac output overestimates diagnoses of exercise-induced pulmonary hypertension. Pulm Circ. 2017 Jan;7(1):253– 5.https://doi.org/10.1086/690629PMID:28680584

9. Liu YH, Dhakal BP, Keesakul C, Kacmarek RM, Lewis GD, Jiang Y. Continuous non-invasive cardiac output monitoring during exercise: validation of electrical cardiometry with Fick and thermodilution methods. Br J Anaesth. 2016 Jul;117(1):129–

31.https://doi.org/10.1093/bja/aew156PMID:27317712

10. Kresoja KP, Faragli A, Abawi D, Paul O, Pieske B, Post H, et al. Thermodilution vs estimated Fick cardiac output measurement in an elderly cohort of patients: A single-centre experience. PLoS One. 2019 Dec;14(12):e0226561.https://doi.org/10.1371/journal.pone.0226561PMID:31860679

11. Opotowsky AR, Hess E, Maron BA, Brittain EL, Barón AE, Maddox TM, et al. Thermodilution vs estimated Fick cardiac output measurement in clinical practice: an analysis of mortality from the Veterans Affairs Clinical Assessment, Reporting, and Tracking (VA CART) Program and

(36)

Vanderbilt University. JAMA Cardiol. 2017 Oct;2(10):1090–9.

https://doi.org/10.1001/jamacardio.2017.2945PMID:28877293

12. Grensemann J, Defosse JM, Wieland C, Wild UW, Wappler F, Sakka SG. Comparison of PulsioFlex® uncalibrated pulse contour method and a modified Fick principle with transpulmonary thermodilution measurements in critically ill patients. Anaesth Intensive Care.

2016 Jul;44(4):484–90.https://doi.org/10.1177/0310057X1604400407PMID:27456179

13. Palmers PJ, Vidts W, Ameloot K, Cordemans C, Van Regenmortel N, De Laet I, et al. Assessment of three minimally invasive continuous cardiac output measurement methods in critically ill patients and a review of the literature. Anaesthesiol Intensive Ther. 2012 OctDec;44(4):188–99.PMID:23348485 14. Tehrani DM, Grinstein J, Kalantari S, Kim G, Sarswat N, Adatya S, Sayer G, Uriel N. Cardiac output

assessment in patients supported with left ventricular assist device: discordance between thermodilution and indirect Fick cardiac output measurements. ASAIO journal (American

Society for Artificial Internal Organs: 1992). 2017

Jul;63(4):433.https://doi.org/10.1097/MAT.0000000000000528.

15. Perny J, Kimmoun A, Perez P, Levy B. Evaluation of cardiac function index as measured by transpulmonary thermodilution as an indicator of left ventricular ejection fraction in cardiogenic shock. BioMed Res Int. 2014;

2014:598029.https://doi.org/10.1155/2014/598029PMID:25013790

16. Hilty MP, Franzen DP, Wyss C, Biaggi P, Maggiorini M. Validation of transpulmonary thermodilution variables in hemodynamically stable patients with heart diseases. Ann Intensive

Care. 2017 Aug;7(1):86.https://doi.org/10.1186/s13613-017-0307-0PMID:28831765

17. Trepte CJ, Eichhorn V, Haas SA, Richter HP, Goepfert MS, Kubitz JC, et al. Thermodilutionderived indices for assessment of left and right ventricular cardiac function in normal and impaired cardiac function. Crit Care Med. 2011 Sep;39(9):2106–12.

https://doi.org/10.1097/CCM.0b013e31821cb9baPMID:21572331

18. Boehne M, Baustert M, Paetzel V, Köditz H, Schoof S, Happel CM, et al. Determination of cardiac output by ultrasound dilution technique in infants and children: a validation study against direct Fick principle. Br J Anaesth. 2014 Mar;112(3):469–76.https://doi.org/10.1093/bja/aet382PMID:24335550. 19. Geerts BF, Aarts LP, Jansen JR. Methods in pharmacology: measurement of cardiac output. Br J

Clin Pharmacol. 2011 Mar;71(3):316–30.https://doi.org/10.1111/j.1365- 2125.2010.03798.xPMID:21284692

20. Thiele RH, Bartels K, Gan TJ. Cardiac output monitoring: a contemporary assessment and review. Crit Care Med. 2015 Jan;43(1):177–

(37)

21. Holmes TW, Williams DJ. Cardiac output measurement. Anaesth Intensive Care Med. 2010 Feb;11(2):58–61.https://doi.org/10.1016/j.mpaic.2009.10.011.

22. Roguin A. Adolf Eugen Fick (1829-1901) - The Man Behind the Cardiac Output Equation. Am J Cardiol. 2020 Oct; 133:162–5.https://doi.org/10.1016/j.amjcard.2020.07.042PMID:33172590

23. Xu WD, Fang JC. Back to the Future: Circulation Time Revisited. J Card Fail. 2016 Nov;22(11):928–9.https://doi.org/10.1016/j.cardfail.2016.09.001PMID:27615065

24. Jhanji S, Dawson J, Pearse RM. Cardiac output monitoring: basic science and clinical application. Anaesthesia. 2008 Feb;63(2):172–81.https://doi.org/10.1111/j.1365-

2044.2007.05318.xPMID:18211449

25. Fick A. Uber die Messung des Blutquantums in den Hertzventrikeln. In: Wurzburg Physikalische Medizinische Gesellschaft. Wurzburg, 1870

26. Vincent JL. Understanding cardiac output. Crit Care.

2008;12(4):174.https://doi.org/10.1186/cc6975PMID:18771592

27. Monnet X, Persichini R, Ktari M, Jozwiak M, Richard C, Teboul JL. Precision of the transpulmonary

thermodilution measurements. Crit Care. 2011

Aug;15(4):R204.https://doi.org/10.1186/cc10421PMID:21871112 28. Brahme A. Comprehensive biomedical physics. Newnes; 2014 Jul 25.

29. Reuter DA, Huang C, Edrich T, Shernan SK, Eltzschig HK. Cardiac output monitoring using indicator-dilution techniques: basics, limits, and perspectives. Anesth Analg. 2010

Mar;110(3):799–811.https://doi.org/10.1213/ANE.0b013e3181cc885aPMID:20185659

30. Hoeper MM, Maier R, Tongers J, Niedermeyer J, Hohlfeld JM, Hamm M, et al. Determination of cardiac output by the Fick method, thermodilution, and acetylene rebreathing in pulmonary hypertension. Am J Respir Crit Care Med. 1999 Aug;160(2):535–41.

https://doi.org/10.1164/ajrccm.160.2.9811062PMID:10430725

31. Chamos C, Vele L, Hamilton M, Cecconi M. Less invasive methods of advanced hemodynamic monitoring: principles, devices, and their role in the perioperative hemodynamic optimization. Perioper Med (Lond). 2013 Sep;2(1):19.https://doi.org/10.1186/2047-0525-219PMID:24472443 32. Huygh J, Peeters Y, Bernards J, Malbrain ML. Hemodynamic monitoring in the critically ill: an

overview of current cardiac output monitoring methods. F1000 Res. 2016 Dec;5:5.https://doi.org/10.12688/f1000research.8991.1PMID:28003877

33. Teboul JL, Saugel B, Cecconi M, De Backer D, Hofer CK, Monnet X, et al. Less invasive hemodynamic monitoring in critically ill patients. Intensive Care Med. 2016 Sep;42(9):1350–9.

https://doi.org/10.1007/s00134-016-4375-7PMID:27155605 34. Vincent JL. Understanding cardiac output. Crit Care.

LITHUANIAN UNIVERSITY OF HEALTH SCIENCES FACULTY OF MEDICINE, DEPARTMENT OF ANESTHESIOLOGY