Research Paper
Evaluation of the ability of haemodynamic variables obtained with minimally invasive techniques to assess fluid responsiveness in endotoxaemic Beagles

https://doi.org/10.1016/j.vaa.2021.02.008Get rights and content

Abstract

Objective

To examine the ability of different haemodynamic variables recorded by minimally invasive monitoring techniques to assess fluid responsiveness (FR) in endotoxaemic Beagles.

Study design

Prospective terminal experimental study.

Animals

A group of six healthy, purpose-bred Beagle dogs (three intact females and males), age 5–9.8 years (range) and weighing 11.4–17.9 kg.

Methods

Endotoxaemic shock was induced by injecting 1 mg kg–1 Escherichia coli lipopolysaccharide (LPS) intravenously in six sevoflurane-anaesthetized mechanically ventilated Beagles for another project. After 10 minutes, three Ringer’s acetate boluses (10 mL kg–1) were administered each over 10 minutes with collection of haemodynamic data immediately before and after each bolus. Thereafter, arterial hypotension was treated with noradrenaline ± dexmedetomidine until arterial pressures increased to a target value. After a wash-out period of 20 minutes another three boluses of fluid were administered and measurements were repeated equally. For each fluid bolus, FR was considered positive when change (Δ) in stroke volume measured by pulmonary artery thermodilution was ≥15%. To test predictive accuracy for FR, we recorded heart rate, invasive arterial, right atrial and pulmonary capillary wedge pressures, pulse wave transit time with haemodynamic monitors, calculated pulse pressure, shock index and rate over pressure evaluation (ROPE) and measured stroke distance and corrected flow time (FTc) with oesophageal Doppler monitoring.

Results

A total of 35 measurements (19 positive and 16 negative responses) were evaluated. A FTc < 330 ms, Δ pulse pressure ≥20%, Δ shock index ≤–14% and ΔROPE ≤–17% were the most significant indicators of positive FR with an area under the receiver operating characteristics curve between 0.72 and 0.74.

Conclusions and clinical relevance

In endotoxaemic Beagles, none of the assessed haemodynamic variables could predict FR with high sensitivity and specificity.

Introduction

Sepsis is a systemic, maladaptive and harmful immune response to infection linked to high mortality. Septic shock is associated with profound hypotension caused by vasoplegia (Rhodes et al. 2017). The recommended first-line therapy of septic shock consists of a rapid goal-directed fluid resuscitation (Kelm et al. 2015), although septic shock does not represent a typical volume-depleted state with fluids often being redistributed only and not lost. Approximately 50% of all septic human patients respond positively to fluid expansion (Marik & Weinmann 2019) and septic patients are therefore at a high risk of developing fluid overload. A deranged cardiac function and increased vascular permeability complicates the assessment of a patient’s need for fluid resuscitation. A prospective observational study involving 173 human patients with sepsis showed that a positive fluid balance was independently associated with an increased risk of death (Acheampong & Vincent 2015). Administration of fluids will improve the cardiovascular state when the cardiac output (CO) is preload-dependent. To avoid unnecessary fluid administration, the concept of fluid responsiveness (FR) has been introduced. To assess if a patient reacts positively to a fluid bolus, the stroke volume (SV) is measured before and after fluid administration. Currently, an increase in SV of 10–15% after a so-called fluid challenge is defined as a positive FR (Marik & Bellomo 2016; Bednarczyk et al. 2017). However, invasive, time-consuming and expensive measurements of SV are necessary to assess FR accurately. Because SV measurement is often not feasible under clinical conditions, especially in veterinary medicine, less invasive tools and techniques to assess FR have been introduced.

Conventional cardiovascular variables like changes (Δ) in heart rate (HR) and systemic arterial blood pressure are clinically still used to assess FR, although several authors discourage their use in humans (Marik 2009) and in dogs (Muir et al. 2014). The static preload variables right atrial pressure and pulmonary capillary wedge pressure are no longer recommended for the assessment of FR in humans (Marik & Cavallazzi 2013) or in dogs (Fantoni et al. 2017).

More recently, Δ pulse wave transit time detected ΔSV and reliably assessed FR in healthy anaesthetized Beagles (Sano & Chambers 2017; Sano et al. 2019). The pulse wave transit time is defined as the time between the rise point of the SpO2 plethysmogram and the peak of the R-wave in the ECG and can be measured with a multiparameter monitor. This time interval is inversely proportional to SV (Sugo et al. 2010).

Another minimally invasive monitoring technique, oesophageal Doppler monitoring (ODM) measures the velocity of blood flow in the descending aorta using a Doppler probe placed in the patient’s oesophagus. The velocity time integral equals the stroke distance and is a measure of the distance that blood travels within the aorta in one heartbeat. The stroke distance is a surrogate for SV and it was able to trend ΔSV in adult humans (Dépret et al. 2019) and paediatric human patients (Tibby et al. 2001). Flow time corrected (FTc), another variable measured with ODM, is defined as the duration of blood flow in the aorta during systole, normalized to a HR of 60 beats minute–1. This time is positively correlated to SV and negatively to vascular resistance.

The objective of this study was to evaluate the ability of different haemodynamic variables recorded by minimally invasive monitoring techniques to assess FR in endotoxaemic Beagles. The hypothesis was that minimally invasively measured haemodynamic variables can be used to predict FR during experimentally induced endotoxaemia in dogs.

Section snippets

Animals

Ethical approval (ZH057/17) was obtained from the Cantonal Veterinary Office of Zurich, Switzerland. A total of six purpose-bred Beagle dogs (three intact females and three males) with an age of 7.4 (5–9.8) years [median (range)] and a body weight of 13.7 (11.4–17.9) kg were included in this study. On the study days the dogs were transported to the study site in a travel cage. They were fasted for 12 hours but water was available ad libitum.

The dogs had been scheduled for euthanasia owing to

Results

A total of 35 measurements were obtained. During measurements, the blood temperature of the dogs was maintained between 37.2 °C and 38.9 °C. Of the 33 measurements obtained with the ODM, five were excluded from analysis because of incorrect HR, waveforms or marker placement. The recorded cardiovascular variables before and after 35 boluses are shown for positive and negative FR in Table 1. A total of 19 fluid boluses (54%) resulted in a ΔSV ≥15% and were considered positive FR. The remaining 16

Discussion

This study examined the ability of different minimally invasive cardiovascular monitoring techniques to predict FR in mechanically ventilated anaesthetized endotoxaemic dogs. The results of this study demonstrate that the haemodynamic variables we assessed did not provide good predictive values of FR. However, assessing FTc, Δ pulse pressure, Δ shock index or ΔROPE may offer fair FR predictive abilities. To our knowledge, this is the first study to assess the ability of a range of minimally

Conclusion

In anaesthetized Beagles during endotoxaemic shock after IV LPS, none of the minimally invasively measured haemodynamic variables could predict FR with high sensitivity and specificity.

Acknowledgements

We would like to thank Professor Dr. Zeki Yilmaz and PD Dr. Martin Schläpfer and his team for their professional advice.

References (38)

  • T. Berger et al.

    Shock index and early recognition of sepsis in the emergency department: pilot study

    West J Emerg Med

    (2013)
  • L. Byrne et al.

    Unintended consequences: fluid resuscitation worsens shock in an ovine model of endotoxemia

    Am J Respir Crit Care Med

    (2018)
  • R. Campbell et al.

    Validation of the pulse rate over pressure evaluation index as a detector of early occult hemorrhage: a prospective observational study

    J Trauma Acute Care Surg

    (2012)
  • S. Canfrán et al.

    Evaluation of an oesophageal Doppler device for monitoring cardiac output in anaesthetised healthy normotensive dogs

    J Small Anim Pract

    (2015)
  • D. Chemla et al.

    Total arterial compliance estimated by stroke volume-to-aortic pulse pressure ratio in humans

    Am J Physiol Heart Circ Physiol

    (1998)
  • A. Chohan et al.

    Evaluation of transesophageal Doppler in Beagle dogs as an aid to provide goal directed fluid therapy

    Vet Anaesth Analg

    (2019)
  • M.A. Christen et al.

    Quantification of cerebrospinal fluid flow in dogs by cardiac-gated phase-contrast magnetic resonance imaging

    J Vet Intern Med

    (2021)
  • F. Dépret et al.

    Esophageal Doppler can predict fluid responsiveness through end-expiratory and end-inspiratory occlusion tests

    Crit Care Med

    (2019)
  • W.F. Hamilton et al.

    Studies on the circulation

    Am J Physiol

    (1932)
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