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Plethysmography variability index for prediction of fluid responsiveness during graded haemorrhage and transfusion in sevoflurane-anaesthetized mechanically ventilated dogs
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Veterinary Anaesthesia and Analgesia 2017, xxx, 1e10
http://dx.doi.org/10.1016/j.vaa.2017.07.007
RESEARCH PAPER
Plethysmography variability index for prediction of fluid responsiveness during graded haemorrhage and transfusion in sevoflurane-anaesthetized mechanically Q7
Q6
ventilated dogs Yusuke Endoa, Koudai Kawasea, Taku Miyashob, Tadashi Sanob, Kazuto Yamashitaa & William W Muirc a
Department of Small Animal Clinical Sciences, School of Veterinary Medicine, Rakuno Gakuen
University, Ebetsu, Hokkaido, Japan b
Department of Veterinary Nursing Science, School of Veterinary Medicine, Rakuno Gakuen
University, Ebetsu, Hokkaido, Japan c
College of Veterinary Medicine, Lincoln Memorial University, Harrogate, TN, USA
Correspondence: Kazuto Yamashita, Department of Small Animal Clinical Sciences, School of Veterinary Medicine, Rakuno Gakuen Q2
University, Ebetsu, Hokkaido 069-8591, Japan. E-mail: [email protected]
Q1
Abstract Objective To examine the accuracy of plethysmography variability index (PVI) as a noninvasive indicator of fluid responsiveness in hypovolaemic dogs. Study design Prospective experimental study. Animals Six adult healthy sevoflurane-anaesthetized Beagle dogs. Methods Dogs were anaesthetized with 1.3-fold their individual minimum alveolar concentration of sevoflurane. The lungs were ventilated using a ventilator after neuromuscular blockade with vecuronium bromide. Cardiopulmonary variables including mean arterial blood pressure (MAP), central venous pressure (CVP), transpulmonary thermodilution cardiac output (TPTDCO), stroke volume (SV), perfusion index (PI), pulse pressure variation (PPV), stroke volume variation (SVV) and PVI were determined before and after six stages of graded venous blood withdrawal (5 mL kg1 increments) followed by six stages of graded infusion (5 mL kg1 increments) of shed blood. The cardiopulmonary variables were analysed using paired t test or Wilcoxon signed rank test. Correlations between PPV and SVV or PVI were analysed by linear regression. The accuracy of
PPV, SVV and PVI for predicting fluid responsiveness was examined by using receiver operating characteristic curve analysis. A value of p < 0.05 was considered statistically significant. Results Blood withdrawal resulted in significant increases in PPV and PVI and decreases in MAP, CVP, TPTDCO, SV and PI. Blood infusion resulted in significant increases in PPV, PVI, MAP, CVP, TPTDCO, SV and PI. PPV and PVI showed a relevant correlation (p < 0.001, r2 ¼ 0.62) and threshold values of PPV 16% (sensitivity 71%, specificity 82%) and PVI 12% (sensitivity 78%, specificity 72%) for identifying fluid responsiveness. SVV did not change. Conclusions and clinical relevance Noninvasive measurement of PVI predicted fluid responsiveness with moderate accuracy equal to PPV in sevoflurane-anaesthetized mechanically ventilated dogs. Provisional threshold values for identification of fluid responsiveness were PPV 16% and PVI 12%. Clinical trials are needed to confirm these threshold values in dogs. Keywords dogs, fluid responsiveness, plethysmography variability index, pulse pressure variation, stroke volume variation.
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Please cite this article in press as: Endo Y, Kawase K, Miyasho T et al. Plethysmography variability index for prediction of fluid responsiveness during graded haemorrhage and transfusion in sevoflurane-anaesthetized mechanically ventilated dogs, Veterinary Anaesthesia and Analgesia (2017), http://dx.doi.org/10.1016/j.vaa.2017.07.007
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Plethysmography variability index in dogs Y Endo et al.
Introduction
Q3
Intravascular fluid resuscitation is an indispensable treatment for increasing cardiac preload and cardiac output (CO) in small animals (Muir et al. 2011; Davis et al. 2013). Intravenous (IV) fluids are routinely administered to treat hypotension during general anaesthesia and in critically ill animals. However, developing pulmonary congestion can be a consequence of excessive fluid administration (Aarnes et al. 2009; Muir et al. 2011). Therefore, it is important to assess the intravascular volume status and whether the administration of fluid will increase CO. It is well known that static measures of cardiac preload, such as ventricular end-diastolic pressure, central venous pressure (CVP) and pulmonary artery occlusion pressure are not reliable measures of fluid responsiveness in humans and dogs (Kumar et al. 2004; Muir et al. 2014). By contrast, dynamic measures of cardiac function will identify fluid responsiveness (Hofer et al. 2005; Cannesson et al. 2008a; Drvar et al. 2013). Pulse pressure variation (PPV) and stroke volume variation (SVV) are dynamic preload-dependent variables that can be obtained semi-invasively from the arterial pressure waveform and used to indicate fluid responsiveness in human patients (Hofer et al. 2005; Drvar et al. 2013). These dynamic preload variables are derived from fluctuations in the arterial pressure waveform caused by changes in intrathoracic pressure during mechanical ventilation. Changes in both PPV and SVV are indicative and predictive of preload status, and increase in hypovolaemic dogs after 24e35 mL kg1 of blood withdrawal (Fujita et al. 2004; Brekenstadt et al. 2005; Taguchi et al. 2011; Diniz et al. 2014). Determination of PPV and SVV requires a procedure for arterial access that is not currently a standard of care in small animal practice except in large multidiscipline practices. Plethysmography variability index (PVI) is a noninvasive preload-dependent variable that is derived from the pulse oximetry plethysmographic waveform (Cannesson et al. 2008b; Keller et al. 2008; Chandler et al. 2012). Perfusion index (PI) is the ratio of the pulsatile blood flow to the nonpulsatile static blood flow in a patient’s peripheral tissue. Mechanical ventilation causes changes in intrathoracic pressure that result in alterations in the pulse oximetry plethysmographic waveform and changes in the PI. The PVI is derived from fluctuations in this waveform and can be used to identify fluid responsiveness in human patients (Cannesson et al. 2
2008a,b; Zimmermann et al. 2010; Hood & Wilson 2011; Loupec et al. 2011). Reported threshold values for PVI that are indicative of fluid responsiveness are 9.5e17% in adult human patients (Cannesson et al. 2008a; Zimmermann et al. 2010; Hood & Wilson 2011; Loupec et al. 2011). The threshold values of PVI for detecting fluid responsiveness in dogs have not been determined, although a few reports are available on threshold values for SVV and PPV (Fantoni et al. 2017; Sasaki et al. 2017). We hypothesized that PVI could be used to predict fluid responsiveness and that a specific threshold value could be obtained in mechanically ventilated dogs under oxygen-sevoflurane anaesthesia. Materials and methods Experimental animals The study was approved by the Animal Care and Use Committee of Rakuno Gakuen University (no. VH15B23). Three male and three female Beagle dogs, 4 years old and weighing 10.6 ± 0.4 kg [mean ± standard deviation (SD)], were enrolled. All dogs were judged to be healthy and without cardiac disease based upon a physical examination, haemogram, serum biochemical profile, electrocardiogram (ECG) and echocardiographic examinations. Approximately 1 month before the experiment, the minimum alveolar concentration (MAC) of sevoflurane was determined in each dog using the tail clamp method (Yamashita et al. 2008, 2009). Food, but not water, was withheld from the dogs for 12 hours prior to the experiment. Anaesthesia Anaesthesia and instrumentation were performed according to a previous study of transpulmonary thermodilution CO (TPTDCO) measurement in dogs (Itami et al. 2016). The dog was anaesthetized with sevoflurane (Sevoflo; DS Pharma Animal Health Co. Ltd., Japan) using a facemask and orotracheally intubated with a cuffed endotracheal tube (internal diameter, 7.5 mm). Anaesthesia was maintained at an end-tidal sevoflurane concentration (FeSevo) of 1.3 individual MAC. Sevoflurane was delivered in oxygen (inspired oxygen fraction of 1.0, flow rate of 2 L minute1) using a circle rebreathing system and anaesthetic machine (Beaver 20; Kimura Medical Instrument Co., Japan) with an out-of-circuit vaporizer (Sevotech III; Datex-Ohmeda KK, Japan). To avoid artefacts produced by spontaneous respiratory
© 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved., ▪, 1e10
Please cite this article in press as: Endo Y, Kawase K, Miyasho T et al. Plethysmography variability index for prediction of fluid responsiveness during graded haemorrhage and transfusion in sevoflurane-anaesthetized mechanically ventilated dogs, Veterinary Anaesthesia and Analgesia (2017), http://dx.doi.org/10.1016/j.vaa.2017.07.007
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Plethysmography variability index in dogs Y Endo et al.
movements during measurements of SVV, PPV and PVI, paralysis was achieved with vecuronium (Musculate; Fuji Pharma Co., Japan) using a loading dose of 0.2 mg kg1 IV followed by 0.1 mg kg1 hour1 (Nagahama et al. 2006). Mechanical ventilation was applied with peak inspiratory pressure (PIP) of 10 cmH2O, frequency of 12 breaths minute1 and inspiratory:expiratory time ratio of 1:2 using a timecycled ventilator (Nuffield Anaesthesia Ventilation Series 200; Penlon Ltd., UK). Then, tidal volume (VT) was adjusted to maintain a partial pressure of arterial carbon dioxide (PaCO2) of 35e45 mmHg (4.7e6.0 kPa) during the experiment. Lactated Ringer’s solution (LRS; Solulact; Terumo Co., Japan) was administered IV at 10 mL kg1 hour1 during instrumentation only. End-tidal gases were sampled from the circle Y-piece by a side-stream gas sampling system and FeSevo was measured using a physiological monitor (BP-608V; Omron Colin Co. Ltd., Japan) calibrated immediately prior to each experiment using a calibration gas composed of 2.0% desflurane, 5.0% CO2, 33.0% N2O, 55.0% O2 and 5.0% N2 (AG Calibration Gas and Adaptor Set; Omron Colin Co. Ltd.). Oesophageal temperature (T) was maintained throughout the experiment between 37.5 C and 38.5 C using a warm air blanket (FKCL3; Sanyo Electric Co. Ltd., Japan). Instrumentation A 22 gauge, 2.5 cm catheter (Supercath; Medikit Co. Ltd., Japan) was placed in each cephalic vein following the induction of anaesthesia for the administration of vecuronium and fluid. The hair was clipped from the skin over the left and right jugular veins and each site was aseptically prepared and desensitized by a subcutaneous (SC) injection of approximately 0.5 mL 2% lidocaine (Xylocaine; AstraZeneca KK, Japan). A 16 gauge, 30 cm central venous (CV) catheter (CV Catheter; Medikit Co. Ltd.) was inserted into the left jugular vein for measuring CVP and injecting ice-cold saline solution for determination of CO. Another 16 gauge CV catheter was inserted into the right jugular vein for blood withdrawal and transfusion of withdrawn blood. The tip of each CV catheter was located in the cranial vena cava (not in the right atrium) and its position was confirmed by echocardiography and pressure waveform. The medial surface area of the left thigh was clipped, aseptically prepared and desensitized, and a 4 Fr, 16 cm thermistor-tipped pulse contour CO (PiCCO) catheter (PV2014L16; PULSION Medical
Systems AG, Germany) inserted into the left femoral artery through a small skin incision for TPTDCO, mean arterial pressure (MAP) measurements and pulse contour analysis using a PiCCO system (PiCCO2; PULSION Medical Systems AG). Measurements of dynamic variables determining cardiac preload TPTDCO was determined by injecting ice-cold saline (0.2 mL kg1; Isotonic Sodium Chloride Solution; Terumo Co.) through the left CV catheter and was analysed and digitally displayed by the PiCCO system. TPTDCO was performed at end-expiration and repeated until three consecutive values with a difference of <10% were obtained (Itami et al. 2016). Stroke volume (SV), SVV and PPV were recorded by the PiCCO system. The PI and PVI were digitally displayed (Masimo Radical-7 Version V1.1.6.3i; Masimo Japan Co., Japan) using a clip-type pulse oximeter probe (LNOP TC-I, Tip Clip; Masimo Japan Co.), which was positioned on the mid-portion of the tongue near the median groove. The PVI was calculated as (PImaximum PIminimum)/PImaximum 100 (Cannesson et al. 2008a,b). To optimize the PI signal and obtain reliable PVI data, the tongue was gently massaged and the probe was repositioned approximately 3 minutes before data collection at each time point (Klein et al. 2016). Measurements of cardiopulmonary variables The left CV catheter and the PiCCO catheter were used for measurement of CVP and MAP, respectively, using a pressure transducer (PiCCO Monitoring Kit PV8215; PULSION Medical Systems AG) for each catheter. The zero reference point for the pressure transducers was level with the manubrium. These catheters were flushed periodically with saline containing 10 U mL1 sodium heparin (Novo-heparin for injection; Mochida Pharmaceutical Co., Japan). Arterial blood samples were obtained anaerobically from the PiCCO catheter into a plastic syringe heparinized with 1000 U mL1 sodium heparin after evacuation of all air. Blood samples were analysed immediately after collection (<5 minutes) for arterial pH (pHa), partial pressure of arterial oxygen (PaO2) and PaCO2 using a blood gas analyser and corrected for T (GEM Premier 3000; Instrumentation Laboratory Japan Co. Ltd., Japan). PIP was measured at the one-way valve of the inspiratory limb using a manometer that detected
© 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved., ▪, 1e10
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Please cite this article in press as: Endo Y, Kawase K, Miyasho T et al. Plethysmography variability index for prediction of fluid responsiveness during graded haemorrhage and transfusion in sevoflurane-anaesthetized mechanically ventilated dogs, Veterinary Anaesthesia and Analgesia (2017), http://dx.doi.org/10.1016/j.vaa.2017.07.007
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Plethysmography variability index in dogs Y Endo et al.
30 minutes
15 minutes Blood withdrawal
Blood transfusion
T1 T2 T3 T4 T5 T6 T7
T8 T9 T10 T11 T12 T13 T14
Instrumentation
Time point Volume of blood deficit (mL kg–1)
0
5
10 15 20 25 30
Volume of blood transfusion (mL kg–1)
0
5
10 15 20 25 30
Figure 1 Timeline of the study design. Baseline cardiopulmonary variables were recorded 30 minutes after instrumentation (T1). Blood (5 mL kg1) was withdrawn over 5 minutes and cardiopulmonary variables were measured 10 minutes later (T2). This procedure was repeated 6 times for a total of 30 mL kg1 blood loss. After a resting period of 15 minutes, cardiopulmonary variables were recorded (T8). The collected blood was infused in 5 mL kg1 increments, each over 5 minutes and cardiopulmonary variables were recorded 10 minutes later. The transfusions were repeated until the 30 mL kg1 of blood was administered.
pressure within the rebreathing system. VT was measured at the one-way valve of the expiratory limb of the rebreathing system using a ventilometer (Exhalometer; Kohken Medical Co. Ltd., Japan). T, heart rate (HR) and ECG (lead II) were recorded from the physiological monitor (BP-608V; Omron Colin Co. Ltd.). Experimental protocol Each experiment followed the same format (Fig. 1). LRS administration was discontinued and the dog was allowed to stabilize for 30 minutes in right lateral recumbency after completion of instrumentation. Baseline values of cardiopulmonary variables (HR, MAP, CVP, TPTDCO, SV, SVV, PPV, PI, PVI, pHa, PaO2, PaCO2, PIP and VT) were obtained (Fig. 1; T1). Venous blood was withdrawn from the right CV catheter at 1 mL kg1 minute1 into 50 mL syringes containing a volume of citrateephosphatee dextroseeadenine (CPDA-1) appropriate for the volume of blood (14 mL CPDA-1 per 100 mL blood) and then transferred from the syringes into sterile bags (Teruflex; Terumo Co.). After 5 mL kg1 of blood was withdrawn, 10 minutes elapsed before cardiopulmonary variables were measured and recorded (T2). This procedure was repeated six times, resulting in a total blood loss (T2eT7) of 30 mL kg1. No further intervention occurred for 15 minutes before cardiopulmonary variables were recorded (Fig. 1; T8). The reverse procedure was initiated by manually transfusing collected blood through the right CV catheter at 1 mL kg1 minute1 for 5 4
minutes. Ten minutes elapsed after each 5 mL kg1 of blood transfusion and before cardiopulmonary variables were recorded (Fig. 1). This procedure was repeated six times until 30 mL kg1 of shed blood was transfused (T9eT14). The vecuronium infusion was discontinued after T14 data collection and sugammadex (4 mg kg1; Bridion; MSD K.K., Japan) was administered IV to reverse muscle paralysis. The dogs were recovered from anaesthesia and monitored for general condition and food and water intake for 24 hours after the experiment. Buprenorphine (0.01 mg kg1; Otsuka Pharmaceutical Co. Ltd., Japan) was administered by intramuscular injection and meloxicam (0.2 mg kg1; Metacam; Boehringer Ingelheim Vetmedica Japan Co. Ltd., Japan) SC during recovery from anaesthesia and twice daily for 3 days after the experiment. Statistical analysis Statistical analysis was performed using JMP Version 11.0 for MAC (SAS Institute Inc., NC, USA). Data are expressed as the mean ± SD. The cardiopulmonary variables measured during blood withdrawal and transfusion were compared with each baseline value by using paired t test for normally distributed continuous variables or the Wilcoxon signed rank test for non-normally distributed variables. Linear regression analysis was performed in order to examine correlation between PPV and SVV or PVI. Receiver operating characteristic (ROC) curve analysis was performed to examine the performance of
© 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved., ▪, 1e10
Please cite this article in press as: Endo Y, Kawase K, Miyasho T et al. Plethysmography variability index for prediction of fluid responsiveness during graded haemorrhage and transfusion in sevoflurane-anaesthetized mechanically ventilated dogs, Veterinary Anaesthesia and Analgesia (2017), http://dx.doi.org/10.1016/j.vaa.2017.07.007
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a
b 30
30
20
20
PVI (%)
SVV (%)
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Plethysmography variability index in dogs Y Endo et al.
10
0
y = 0.32x + 11.14 r = 0.34 p = 0.002
0
10
20
30
y = 0.85x + 1.80 r = 0.79 p < 0.001
10
0
0
10
20
30
PPV (%)
PPV (%)
Figure 2 Correlations between (a) stroke volume variation (SVV) and pulse pressure variation (PPV), and (b) plethysmography variability index (PVI) and PPV in six anaesthetized dogs in response to blood withdrawal up to 30 mL kg1 and to reinfusion of the collected blood.
PPV and SVV or PVI as indicators of fluid responsiveness, and to determine threshold values during transfusion. Dogs that increased their SV by 15% in response to blood transfusion were considered to be responders and those that did not were defined as
nonresponders. This cut off value (SV increase 15%) was selected based upon previous reports investigating the ability of SVV, PPV and PVI to identify fluid responsiveness in human patients (Hofer et al. 2005; Renner et al. 2011). Responders and
Table 1 Cardiopulmonary variables measured during blood withdrawal in six dogs anaesthetized with sevoflurane and mechanically ventilated Variables
HR (beats minute1) MAP (mmHg) CVP (mmHg) TPTDCO (L minute1) SV (mL beat1) SVV (%) PPV (%) PI (%) PVI (%) pHa PaO2 (mmHg) PaO2 (kPa) PaCO2 (mmHg) PaCO2 (kPa) PIP (cmH2O) VT (mL kg1)
Volume of blood deficit T1 0 mL kg¡1
T2 5 mL kg¡1
T3 10 mL kg¡1
T4 15 mL kg¡1
T5 20 mL kg¡1
T6 25 mL kg¡1
T7 30 mL kg¡1
109 ± 4 78 ± 3 3.1 ± 1.4 1.9 ± 0.3
109 ± 4 76 ± 2 2.6 ± 1.0 1.8 ± 0.2
107 ± 5 72 ± 3 2.3 ± 0.8 1.7 ± 0.2
107 ± 4 67 ± 3 2.0 ± 1.2 1.6 ± 0.2*
105 ± 4 63 ± 3* 1.5 ± 1.2 1.4 ± 0.1*
105 ± 6 61 ± 3* 0.8 ± 0.9* 1.3 ± 0.1y
109 ± 5 57 ± 3y 0.5 ± 0.8* 1.3 ± 0.1y
17.5 ± 2.3 16 ± 3 13 ± 2 0.8 ± 0.4 9±3 7.363 ±0.028 552 ± 37 74 ± 5 39 ± 2 5.2 ± 0.2 10 ± 1 16 ± 2
16.1 ± 2.3 17 ± 4 14 ± 4 0.7 ± 0.5 11 ± 4 7.378 ± 0.022 549 ± 44 73 ± 6 37 ± 2 5.0 ± 0.2 10 ± 1 16 ± 2
15.8 ± 2.3 17 ± 4 17 ± 4* 0.7 ± 0.5 13 ± 5* 7.360 ± 0.037 566 ± 25 75 ± 3 38 ± 2 5.1 ± 0.3 10 ± 1 16 ± 2
14.6 ± 2.1y 18 ± 3 19 ± 2y 0.6 ± 0.4 15 ± 6y 7.358 ± 0.036 568 ± 31 76 ± 4 39 ± 3 5.2 ± 0.4 10 ± 1 16 ± 2
13.1 ± 2.0y 19 ± 2 20 ± 3y 0.5 ± 0.3 15 ± 3y 7.336 ± 0.045 566 ± 23 75 ± 3 39 ± 3 5.2 ± 0.4 10 ± 1 16 ± 2
12.6 ± 1.7y 20 ± 3 22 ± 2y 0.4 ± 0.2 17 ± 4y 7.325 ± 0.045 576 ± 21 77 ± 3 40 ± 3 5.3 ± 0.4 10 ± 1 15 ± 2
12.1 ± 1.7y 19 ± 4 23 ± 4y 0.4 ± 0.2 17 ± 4y 7.291 ± 0.043 572 ± 23 76 ± 3 42 ± 4 5.5 ± 0.5 10 ± 1 15 ± 2
HR, heart rate; MAP, mean arterial pressure; CVP, central venous pressure; TPTDCO, transpulmonary thermodilution cardiac output; SV, stroke volume; SVV, stroke volume variation; PPV, pulse pressure variation; PI, perfusion index; PVI, plethysmography variability index; pHa, arterial blood pH; PaO2, arterial partial pressure of oxygen; PaCO2, arterial partial pressure of carbon dioxide; PIP, peak inspiratory pressure; VT, tidal volume. The values are mean ± standard deviation. *p < 0.05, yp < 0.01 significant difference compared with the baseline value (T1).
© 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved., ▪, 1e10
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Please cite this article in press as: Endo Y, Kawase K, Miyasho T et al. Plethysmography variability index for prediction of fluid responsiveness during graded haemorrhage and transfusion in sevoflurane-anaesthetized mechanically ventilated dogs, Veterinary Anaesthesia and Analgesia (2017), http://dx.doi.org/10.1016/j.vaa.2017.07.007
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Plethysmography variability index in dogs Y Endo et al.
nonresponders were compared with those recorded at the prior stage of each transfusion using Student’s t test for normally distributed continuous variables or the ManneWhitney test for non-normally distributed variables. A ROC curve was generated to assess the ability of SVV, PPV and PVI to identify responders and nonresponders. The areas under the ROC curves (AUCs) were calculated and compared (Hanley & McNeil 1983; Akobeng 2007). Optimal threshold values (the value that maximizes the sum of both sensitivity and specificity) for SVV, PPV and PVI were determined from the ROC curves. A value of p < 0.05 was considered statistically significant. Results The mean ± SD for sevoflurane MAC values in all dogs was 2.1 ± 0.2%. The total anaesthesia time from mask induction to the cessation of anaesthesia was 685 ± 47 minutes. Instrumentation was completed at 70 ± 16 minutes after initiation of mask induction. The dogs recovered from anaesthesia without complications and were extubated at 9 ± 6 minutes after sevoflurane was discontinued. Blood withdrawal resulted in significant decreases in MAP, TPTDCO, SV, CVP and PI, and increases in
1
PPV and PVI. The total of 30 mL kg blood loss resulted in significant decreases in MAP (p ¼ 0.017), CVP (p ¼ 0.011), TPTDCO (p ¼ 0.008) and SV (p ¼ 0.002), and significant increases in PPV (p < 0.001) and PVI (p < 0.001), compared with each baseline value (Table 1). Transfusion of the previously withdrawn blood resulted in significant increases in MAP (p < 0.001), CVP (p ¼ 0.006), TPTDCO (p < 0.001) and SV (p ¼ 0.003), and significant decreases in PPV (p ¼ 0.002) and PVI (p ¼ 0.005), compared with pretransfusion hypovolaemic values at T8 (Table 2). SVV was not significantly changed during blood withdrawal or transfusion. PaCO2 and PIP were constant at all time points with a minimum adjustment of VT. A total of 72 data points (36 each from the stages of blood withdrawal and transfusion) were obtained for SVV, PPV and PVI from the six dogs. There were significant correlations between PPV and SVV (p ¼ 0.002, coefficient of determination r ¼ 0.34) and between PPV and PVI (p < 0.001, r ¼ 0.79; Fig. 2). Five dogs responded and one dog was a nonresponder to blood transfusion at T9 and T10, and at T11 and T13 two dogs were responders and four dogs were nonresponders. All six dogs were nonresponders at T12 and T14. The PPV and PVI were significantly
Table 2 Cardiopulmonary variables recorded during blood transfusion in six hypovolaemic dogs anaesthetized with sevoflurane and mechanically ventilated Variables
HR (beats minute1) MAP (mmHg) CVP (mmHg) TPTDCO (L minute1) SV (mL beat1) SVV (%) PPV (%) PI (%) PVI (%) pHa PaO2 (mmHg) PaO2 (kPa) PaCO2 (mmHg) PaCO2 (kPa) PIP (cmH2O) VT (mL kg1)
Volume of blood transfused T8 0 mL kg¡1
T9 5 mL kg¡1
T10 10 mL kg¡1
T11 15 mL kg¡1
T12 20 mL kg¡1
T13 25 mL kg¡1
T14 30 mL kg¡1
109 ± 11 56 ± 3 0.3 ± 0.8 1.2 ± 0.3
110 ± 10 61 ± 4y 0.5 ± 0.8 1.5 ± 0.3y
110 ± 8 65 ± 4y 1.5 ± 1.3 1.8 ± 0.3y
112 ± 8 69 ± 3y 2.0 ± 0.8* 2.1 ± 0.5y
113 ± 9 73 ± 3y 2.5 ± 1.3* 2.2 ± 0.5y
112 ± 10 76 ± 5y 3.5 ± 1.3y 2.4 ± 0.5y
117 ± 11 82 ± 5y 3.7 ± 1.6y 2.7 ± 0.7y
11.6 ± 3.8
14.1 ± 3.9y
16.6 ± 4.2y
18.8 ± 4.9y
19.6 ± 5.2y
21.6 ± 5.2y
23.5 ± 6.7y 16 ± 1 13 ± 2* 16 ± 3 16 ± 5 13 ± 4 15 ± 7 13 ± 5 20 ± 3 17 ± 2y 16 ± 2y 15 ± 2y 13 ± 1y 11 ± 1y 11 ± 1y 0.5 ± 0.3 0.6 ± 0.4 0.7 ± 0.4 0.8 ± 0.4* 0.8 ± 0.4 0.9 ± 0.5 1.0 ± 0.6 15 ± 3 14 ± 3 12 ± 3 10 ± 4 9±4 7 ± 2* 6 ± 2y 7.298 ± 0.025 7.284 ± 0.040 7.290 ± 0.049 7.290 ± 0.050 7.3 02 ± 0.038 7.316 ± 0.049 7.316 ± 0.045 571 ± 26 568 ± 18 522 ± 57 552 ± 39 556 ± 28 522 ± 67 545 ± 30 76 ± 3 75 ± 2 70 ± 7 73 ± 5 74 ± 3 70 ± 8 72 ± 4 43 ± 4 46 ± 4 45 ± 6 46 ± 6 46 ± 6 45 ± 6 46 ± 7 5.7 ± 0.5 6.1 ± 0.4 6.0 ± 0.8 6.1 ± 0.8 6.1 ± 0.8 6.0 ± 0.8 6.1 ± 0.9 10 ± 1 10 ± 1 10 ± 1 10 ± 1 10 ± 1 10 ± 1 10 ± 1 15 ± 3 15 ± 3 14 ± 3 15 ± 3 15 ± 3 15 ± 3 15 ± 3
HR, heart rate; MAP, mean arterial pressure; CVP, central venous pressure; TPTDCO, transpulmonary thermodilution cardiac output; SV, stroke volume; SVV, stroke volume variation; PPV, pulse pressure variation; PI, perfusion index; PVI, plethysmography variability index; pHa, arterial blood pH; PaO2, arterial partial pressure of oxygen; PaCO2, arterial partial pressure of carbon dioxide; PIP, peak inspiratory pressure; VT, tidal volume. The values are mean ± standard deviation. *p < 0.05, yp < 0.01 significant difference compared with the baseline value (T8).
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© 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved., ▪, 1e10
Please cite this article in press as: Endo Y, Kawase K, Miyasho T et al. Plethysmography variability index for prediction of fluid responsiveness during graded haemorrhage and transfusion in sevoflurane-anaesthetized mechanically ventilated dogs, Veterinary Anaesthesia and Analgesia (2017), http://dx.doi.org/10.1016/j.vaa.2017.07.007
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increased in responders (p ¼ 0.012 and p ¼ 0.005, respectively; Table 3). These data yielded optimal threshold values for fluid responsiveness of SVV 15% [sensitivity 64%; 95% confidence intervals (CI) 35e87%, specificity 50%; 95% CI 28e71%, AUC ¼ 0.52], PPV 16% (sensitivity 71%; 95% CI 42e92%, specificity 82%; 95% CI 60e95%, AUC ¼ 0.74) and PVI 12% (sensitivity 78%; 95% CI 50e95%, specificity 72%; 95% CI 50e90%, AUC ¼ 0.71; Fig. 3). Discussion This study describes and confirms the utility of PPV and PVI for predicting fluid responsiveness in mechanically ventilated, sevoflurane-anaesthetized hypovolaemic dogs. Both PVI and PPV were moderately accurate predictors of fluid responsiveness and generated provisional threshold values for identifying fluid responsiveness of 12% and 16%, respectively. Anaesthesia was maintained at FeSevo of 1.3 MAC for three reasons: 1) MAC is a useful concept for comparing the effects of inhaled anaesthetics within and among experiments; 2) MAC corresponds to the effective dose required to prevent movement in 50% of the participants (ED50) and 1.2e1.4 MAC is the dose corresponding to the ED95, which is more clinically relevant and closely aligned with a surgical plane of anaesthesia; and 3) higher FeSevo may produce significant cardiovascular depression in dogs (Mutoh et al. 1997). However, the MAC of isoflurane is reduced in dogs with hypovolaemia resulting from haemorrhage (Mattson et al. 2006). Thus controlled haemorrhage in the dogs in this study may have affected the depth of anaesthesia and the haemodynamic changes. Using individual MAC values at a
Figure 3 Receiver operating characteristic (ROC) curves comparing the ability of pulse pressure variation (PPV), stroke volume variation (SVV), and plethysmography variability index (PVI) to discriminate between responders and nonresponders during blood transfusion in six anaesthetized hypovolaemic dogs. AUC, area under the ROC curve.
fixed FeSevo of 1.3 MAC was an attempt to minimize individual animal variability as a source of error. TPTDCO measured by the PiCCO system has been evaluated in previous studies that assessed indicators of cardiac preload in halothaneefentanyl- or halothaneenitrous-oxide-anaesthetized, mechanically ventilated dogs (Fujita et al. 2004; Brekenstadt et al. 2005). TPTDCO has exhibited good agreement with CO measured by standard thermodilution technique (TDCO) during IV crystalloid or colloid administration in sevoflurane-anaesthetized dogs (Itami et al. 2016).
Table 3 Dynamic variables of fluid responsiveness before (previous time point) and after each 5 mL kg1 blood volume transfusion (a total of 36 transfusions in six dogs) At each time point, dogs were designated responders or nonresponders to volume expansion based on changes in stroke volume: an increase of 15% defined a responder (n ¼ 14) and <15% defined a nonresponder (n ¼ 22). Within these categories, the corresponding values (mean ± standard deviation) for stroke volume variation (SVV), pulse pressure variation (PPV) and plethysmography variability index (PVI) are listed. n ¼ number of time points Variable
SVV (%) PPV (%) PVI (%)
Responders
Nonresponders
Before
After transfusion
Before
After transfusion
15 ± 3 18 ± 3 13 ± 3
15 ± 4 16 ± 3* 11 ± 4y
15 ± 5 14 ± 3 10 ± 4
14 ± 5 13 ± 2 9±3
*p < 0.05, yp < 0.01 significant difference from the value recorded at the previous time point.
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The TPTDCO baseline value determined before blood withdrawal was equal to previously reported TDCO and TPTDCO values in anaesthetized, mechanically ventilated dogs with stable haemodynamics (Fujita et al. 2004; Brekenstadt et al. 2005; Yamashita et al. 2007; Itami et al. 2016; Klein et al. 2016). Furthermore, changes in TPTDCO produced by blood withdrawal were similar to those in TDCO and TPTDCO in previous reports (Fujita et al. 2004; Brekenstadt et al. 2005; Klein et al. 2016). Changes in other haemodynamic variables, including HR, MAP, CVP and SV, produced by blood withdrawal were also similar to those observed in hypovolaemic mechanically ventilated dogs under isoflurane anaesthesia (Klein et al. 2016). Increases in PPV > 12e13% are associated with decreases in CO during hypotension or graded haemorrhage and are used to predict fluid responsiveness in human medicine and dogs (Brekenstadt et al. 2005; Michard 2005; Wyffels et al. 2007; Marik et al. 2009; Desgranges et al. 2011). In the present study, a similar response in PPV values was recorded during haemorrhage with a threshold value for predicting fluid responsiveness of 16%. Cannesson et al. (2008a) were the first to report that PVI could identify fluid responsiveness noninvasively in anaesthetized, mechanically ventilated human patients when the threshold value for PVI was >14%. Additional studies comparing PPV and PVI in humans produced correlation coefficients (r) of 0.50e0.72 (Cannesson et al. 2008b; Loupec et al. 2011; Chandler et al. 2012). Since then, other studies have confirmed that PVI will identify fluid responsiveness with moderate to high accuracy and report threshold PVI values for identification of fluid responsiveness from >9.5% to 12% in adult human patients (Zimmermann et al. 2010; Desgranges et al. 2011; Hood & Wilson 2011). The authors of one recent study in isoflurane-anaesthetized dogs subjected to haemorrhage (25 ± 5 mL kg1) concluded that PPV and PVI may be useful indicators for identifying fluid responsiveness but threshold values were not provided (Klein et al. 2016). The results of the present study support their conclusion and propose provisional threshold values of 16% and 12% to identify fluid responsiveness for PPV and PVI, respectively. Fluid responsiveness was not identified by SVV in the present study, whereas an increase in SVV has been documented as a valid indicator of fluid responsiveness in mechanically ventilated adult 8
human patients (Hofer et al. 2005; Zimmermann 2010; Drvar et al. 2013). Several studies have reported that SVV can reflect preload status but it is not a sensitive indicator of dynamic preload changes in dogs after either severe hypovolaemia (haemorrhage 50% of blood volume) or the fluid-overload period in dogs (Fujita et al. 2004; Brekenstadt et al. 2005; Taguchi et al. 2011). Indeed Taguchi et al. (2011) demonstrated that SVV decreased significantly following blood withdrawal in dogs. Similarly, decrease in SVV was observed during the stable period between T7 (SVV 19 ± 4%) and T8 (SVV 16 ± 1%) in the present study. It has been suggested that the decreased sensitivity of SVV for predicting fluid responsiveness in dogs subjected to haemorrhage may result from a change in the relation of the SV to the aortic pulse pressure when aortic filling is decreased (Brekenstadt et al. 2005). The present study had several limitations. First, the derived threshold values for fluid responsiveness were determined from a small number of dogs under strictly controlled conditions. These provisional threshold values need to be confirmed by larger clinical trials evaluating fluid responsiveness in this species. Second, SVV was measured by the algorithm of the PiCCO system and could not be directly compared with SVV measured by other systems. Third, a clip-type of pulse oximeter probe was used on the tongue and this type of probe may have decreased PI by local tissue compression. Furthermore, it has been reported that the threshold values of PVI for predicting fluid responsiveness differ with the site of measurement (Desgranges et al. 2011). In addition, PPV and PVI values are influenced by VT and/or PIP setting for mechanical ventilation, intra-abdominal pressure, arrhythmias, HR:respiratory rate ratio, vascular tone, lung compliance, right ventricular function, anaesthesia and fluid challenge (Monnet et al. 2016). Further studies are required to determine the effects of various sensor types and locations and the effects of these various factors on SVV, PPV and PVI in dogs. In conclusion, PPV and noninvasive measurement of PVI predicted fluid responsiveness with moderate accuracy in haemorrhaged and transfused sevoflurane-anaesthetized, mechanically ventilated dogs. Threshold values for identification of fluid responsiveness were PPV 16% and PVI 12%. The results are based on a small number of dogs, therefore, further studies are needed to confirm the threshold values for these variables in dogs.
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Please cite this article in press as: Endo Y, Kawase K, Miyasho T et al. Plethysmography variability index for prediction of fluid responsiveness during graded haemorrhage and transfusion in sevoflurane-anaesthetized mechanically ventilated dogs, Veterinary Anaesthesia and Analgesia (2017), http://dx.doi.org/10.1016/j.vaa.2017.07.007
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Acknowledgements We thank Taku Hirokawa, Department of Small Animal Clinical Sciences, School of Veterinary Medicine, Rakuno Gakuen University, for assistance with measurements. Authors' contributions YE: study design, performed the experiments, statistical analysis, preparation of manuscript. KK: performed the experiments, data management. TM, TS: performed the experiments. KY, WWM: study design, preparation of manuscript. All authors contributed to drafting of the manuscript and read and approved the final manuscript. Conflict of interest The authors declare no conflict of interest. References Aarnes TK, Bednarski RM, Lerche P et al. (2009) Effect of intravenous administration of lactated Ringer's solution or hetastarch for the treatment of isofluraneinduced hypotension in dogs. Am J Vet Res 70, 1345e1353. Akobeng AK (2007) Understanding diagnostic tests 3: receiver operating characteristic curves. Acta Paediatr 96, 644e647. Brekenstadt H, Friedman Z, Preisman S et al. (2005) Pulse pressure and stroke volume variation during severe haemorrhage in ventilated dogs. Br J Anaesth 94, 721e726. Cannesson M, Desebbe O, Rosamel P et al. (2008a) Pleth variability index to monitor the respiratory variations in the pulse oximeter plethysmographic waveform amplitude and predict fluid responsiveness in the operating theatre. Br J Anaesth 101, 200e206. Cannesson M, Delannoy B, Morand A et al. (2008b) Does the Pleth variability index indicate the respiratoryinduced variation in the plethysmogram and arterial pressure waveforms? Anesth Analg 106, 1189e1194. Chandler JR, Cooke E, Petersen C et al. (2012) Pulse oximeter plethysmograph variation and its relationship to the arterial waveform in mechanically ventilated children. J Clin Monit Comput 26, 145e151. Davis H, Jensen T, Johnson A et al. (2013) AAHA/AAFP fluid therapy guidelines for dogs and cats. J Am Anim Hosp Assoc 49, 149e159. Desgranges FP, Desebbe O, Ghazouani A et al. (2011) Influence of the site of measurement on the ability of plethysmographic variability index to predict fluid responsiveness. Br J Anaesth 107, 329e335. Diniz MS, Teixeira-Neto FJ, C^ andido TD et al. (2014) Effects of dexmedetomidine on pulse pressure variation
changes induced by hemorrhage followed by volume replacement in isoflurane anesthetized dogs. J Vet Emerg Crit Care (San Antonio) 24, 681e692. Drvar Z, Pavlek M, Drvar V et al. (2013) Stroke volume and pulse pressure variation are good predictors of fluid responsiveness in sepsis patients. Acta Med Croatica 67, 407e414 [in Croatian]. Fantoni DT, Ida KK, Gimenes AM et al. (2017) Pulse pressure variation as a guide for volume expansion in dogs undergoing orthopedic surgery. Vet Anaesth Analg 44, 709e717. Fujita Y, Yamamoto T, Sano I et al. (2004) A comparison of changes in cardiac variables during graded hypovolemia and hypervolemia in mechanically ventilated dogs. Anesth Analg 99, 1780e1786. Keller G, Cassar E, Desebbe O et al. (2008) Ability of pleth variability index to detect hemodynamic changes induced by passive leg raising in spontaneously breathing volunteers. Crit Care 12. http://dx.doi.org/ 10.1186/cc6822 [Epub ahead of print]. Q5 Hanley JA, McNeil BJ (1983) A method of comparing the areas under receiver operating characteristic curves derived from the same cases. Radiology 148, 839e843. Hofer CK, Müller SM, Furrer L et al. (2005) Stroke volume and pulse pressure variation for prediction of fluid responsiveness in patients undergoing off-pump coronary artery bypass grafting. Chest 128, 848e854. Hood JA, Wilson RJ (2011) Pleth variability index to predict fluid responsiveness in colorectal surgery. Anesth Analg 113, 1058e1063. Itami T, Endo Y, Hanazono K et al. (2016) Comparison of cardiac output measurements using transpulmonary thermodilution and conventional thermodilution techniques in anaesthetized dogs with fluid overload. Vet Anaesth Analg 43, 388e396. Klein AV, Teixeira-Neto FJ, Garofalo NA et al. (2016) Changes in pulse pressure variation and plethysmographic variability index caused by hypotensioninducing hemorrhage followed by volume replacement in isoflurane-anesthetized dogs. Am J Vet Res 77, 280e287. Kumar A, Anel R, Bunnell E et al. (2004) Pulmonary artery occlusion pressure and central venous pressure fail to predict ventricular filling volume, cardiac performance, or the response to volume infusion in normal subjects. Crit Care Med 32, 691e699. Loupec T, Nanadoumgar H, Frasca D et al. (2011) Pleth variability index predicts fluid responsiveness in critically ill patients. Crit Care Med 39, 294e299. Marik PE, Cavallazi R, Vasu T, Hirani A (2009) Dynamic changes in arterial waveform derived variables and fluid responsiveness in mechanically ventilated patients: s systematic review of the literature. Crit Care Med 37, 2642e2647. Mattson SF, Kerr CL, Dyson DH, Mirakhur KK (2006) The effect of hypovolemia due to hemorrhage on the
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undergoing cardiovascular surgery. Vet Anaesth Analg 44, 7e16. Taguchi H, Ichinose K, Tanimoto H et al. (2011) Stroke volume variation obtained with Vigileo/FloTra™ system during bleeding and fluid overload in dogs. J Anesth 25, 563e568. Wyffels PAH, Durnez PJ, Helderweirt J et al. (2007) Ventilation-induced plethysmographic variations predict fluid responsiveness in ventilated postoperative cardiac surgery patients. Anesth Analg 105, 448e452. Yamashita K, Ueyama Y, Miyoshi K et al. (2007) Minimally invasive determination of cardiac output by transthoracic bioimpedance, partial carbon dioxide rebreathing, and transesophageal Doppler echocardiography in beagle dogs. J Vet Med Sci 69, 43e47. Yamashita K, Okano Y, Yamashita M et al. (2008) Effects of carprofen and meloxicam with or without butorphanol on the minimum alveolar concentration of sevoflurane in dogs. J Vet Med Sci 70, 29e35. Yamashita K, Iwasaki Y, Umar MA, Itami T (2009) Effect of age on minimum alveolar concentration (MAC) of sevoflurane in dogs. J Vet Med Sci 71, 1509e1512. Zimmermann M, Feibicke T, Keyl C et al. (2010) Accuracy of stroke volume variation compared with pleth variability index to predict fluid responsiveness in mechanically ventilated patients undergoing major surgery. Eur J Anaesthesiol 27, 555e561. Received 18 January 2017; accepted 29 July 2017. Available online xxx
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http://dx.doi.org/10.1016/j.vaa.2017.07.007
RESEARCH PAPER
Plethysmography variability index for prediction of fluid responsiveness during graded haemorrhage and transfusion in sevoflurane-anaesthetized mechanically Q7
Q6
ventilated dogs Yusuke Endoa, Koudai Kawasea, Taku Miyashob, Tadashi Sanob, Kazuto Yamashitaa & William W Muirc a
Department of Small Animal Clinical Sciences, School of Veterinary Medicine, Rakuno Gakuen
University, Ebetsu, Hokkaido, Japan b
Department of Veterinary Nursing Science, School of Veterinary Medicine, Rakuno Gakuen
University, Ebetsu, Hokkaido, Japan c
College of Veterinary Medicine, Lincoln Memorial University, Harrogate, TN, USA
Correspondence: Kazuto Yamashita, Department of Small Animal Clinical Sciences, School of Veterinary Medicine, Rakuno Gakuen Q2
University, Ebetsu, Hokkaido 069-8591, Japan. E-mail: [email protected]
Q1
Abstract Objective To examine the accuracy of plethysmography variability index (PVI) as a noninvasive indicator of fluid responsiveness in hypovolaemic dogs. Study design Prospective experimental study. Animals Six adult healthy sevoflurane-anaesthetized Beagle dogs. Methods Dogs were anaesthetized with 1.3-fold their individual minimum alveolar concentration of sevoflurane. The lungs were ventilated using a ventilator after neuromuscular blockade with vecuronium bromide. Cardiopulmonary variables including mean arterial blood pressure (MAP), central venous pressure (CVP), transpulmonary thermodilution cardiac output (TPTDCO), stroke volume (SV), perfusion index (PI), pulse pressure variation (PPV), stroke volume variation (SVV) and PVI were determined before and after six stages of graded venous blood withdrawal (5 mL kg1 increments) followed by six stages of graded infusion (5 mL kg1 increments) of shed blood. The cardiopulmonary variables were analysed using paired t test or Wilcoxon signed rank test. Correlations between PPV and SVV or PVI were analysed by linear regression. The accuracy of
PPV, SVV and PVI for predicting fluid responsiveness was examined by using receiver operating characteristic curve analysis. A value of p < 0.05 was considered statistically significant. Results Blood withdrawal resulted in significant increases in PPV and PVI and decreases in MAP, CVP, TPTDCO, SV and PI. Blood infusion resulted in significant increases in PPV, PVI, MAP, CVP, TPTDCO, SV and PI. PPV and PVI showed a relevant correlation (p < 0.001, r2 ¼ 0.62) and threshold values of PPV 16% (sensitivity 71%, specificity 82%) and PVI 12% (sensitivity 78%, specificity 72%) for identifying fluid responsiveness. SVV did not change. Conclusions and clinical relevance Noninvasive measurement of PVI predicted fluid responsiveness with moderate accuracy equal to PPV in sevoflurane-anaesthetized mechanically ventilated dogs. Provisional threshold values for identification of fluid responsiveness were PPV 16% and PVI 12%. Clinical trials are needed to confirm these threshold values in dogs. Keywords dogs, fluid responsiveness, plethysmography variability index, pulse pressure variation, stroke volume variation.
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Please cite this article in press as: Endo Y, Kawase K, Miyasho T et al. Plethysmography variability index for prediction of fluid responsiveness during graded haemorrhage and transfusion in sevoflurane-anaesthetized mechanically ventilated dogs, Veterinary Anaesthesia and Analgesia (2017), http://dx.doi.org/10.1016/j.vaa.2017.07.007
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Introduction
Q3
Intravascular fluid resuscitation is an indispensable treatment for increasing cardiac preload and cardiac output (CO) in small animals (Muir et al. 2011; Davis et al. 2013). Intravenous (IV) fluids are routinely administered to treat hypotension during general anaesthesia and in critically ill animals. However, developing pulmonary congestion can be a consequence of excessive fluid administration (Aarnes et al. 2009; Muir et al. 2011). Therefore, it is important to assess the intravascular volume status and whether the administration of fluid will increase CO. It is well known that static measures of cardiac preload, such as ventricular end-diastolic pressure, central venous pressure (CVP) and pulmonary artery occlusion pressure are not reliable measures of fluid responsiveness in humans and dogs (Kumar et al. 2004; Muir et al. 2014). By contrast, dynamic measures of cardiac function will identify fluid responsiveness (Hofer et al. 2005; Cannesson et al. 2008a; Drvar et al. 2013). Pulse pressure variation (PPV) and stroke volume variation (SVV) are dynamic preload-dependent variables that can be obtained semi-invasively from the arterial pressure waveform and used to indicate fluid responsiveness in human patients (Hofer et al. 2005; Drvar et al. 2013). These dynamic preload variables are derived from fluctuations in the arterial pressure waveform caused by changes in intrathoracic pressure during mechanical ventilation. Changes in both PPV and SVV are indicative and predictive of preload status, and increase in hypovolaemic dogs after 24e35 mL kg1 of blood withdrawal (Fujita et al. 2004; Brekenstadt et al. 2005; Taguchi et al. 2011; Diniz et al. 2014). Determination of PPV and SVV requires a procedure for arterial access that is not currently a standard of care in small animal practice except in large multidiscipline practices. Plethysmography variability index (PVI) is a noninvasive preload-dependent variable that is derived from the pulse oximetry plethysmographic waveform (Cannesson et al. 2008b; Keller et al. 2008; Chandler et al. 2012). Perfusion index (PI) is the ratio of the pulsatile blood flow to the nonpulsatile static blood flow in a patient’s peripheral tissue. Mechanical ventilation causes changes in intrathoracic pressure that result in alterations in the pulse oximetry plethysmographic waveform and changes in the PI. The PVI is derived from fluctuations in this waveform and can be used to identify fluid responsiveness in human patients (Cannesson et al. 2
2008a,b; Zimmermann et al. 2010; Hood & Wilson 2011; Loupec et al. 2011). Reported threshold values for PVI that are indicative of fluid responsiveness are 9.5e17% in adult human patients (Cannesson et al. 2008a; Zimmermann et al. 2010; Hood & Wilson 2011; Loupec et al. 2011). The threshold values of PVI for detecting fluid responsiveness in dogs have not been determined, although a few reports are available on threshold values for SVV and PPV (Fantoni et al. 2017; Sasaki et al. 2017). We hypothesized that PVI could be used to predict fluid responsiveness and that a specific threshold value could be obtained in mechanically ventilated dogs under oxygen-sevoflurane anaesthesia. Materials and methods Experimental animals The study was approved by the Animal Care and Use Committee of Rakuno Gakuen University (no. VH15B23). Three male and three female Beagle dogs, 4 years old and weighing 10.6 ± 0.4 kg [mean ± standard deviation (SD)], were enrolled. All dogs were judged to be healthy and without cardiac disease based upon a physical examination, haemogram, serum biochemical profile, electrocardiogram (ECG) and echocardiographic examinations. Approximately 1 month before the experiment, the minimum alveolar concentration (MAC) of sevoflurane was determined in each dog using the tail clamp method (Yamashita et al. 2008, 2009). Food, but not water, was withheld from the dogs for 12 hours prior to the experiment. Anaesthesia Anaesthesia and instrumentation were performed according to a previous study of transpulmonary thermodilution CO (TPTDCO) measurement in dogs (Itami et al. 2016). The dog was anaesthetized with sevoflurane (Sevoflo; DS Pharma Animal Health Co. Ltd., Japan) using a facemask and orotracheally intubated with a cuffed endotracheal tube (internal diameter, 7.5 mm). Anaesthesia was maintained at an end-tidal sevoflurane concentration (FeSevo) of 1.3 individual MAC. Sevoflurane was delivered in oxygen (inspired oxygen fraction of 1.0, flow rate of 2 L minute1) using a circle rebreathing system and anaesthetic machine (Beaver 20; Kimura Medical Instrument Co., Japan) with an out-of-circuit vaporizer (Sevotech III; Datex-Ohmeda KK, Japan). To avoid artefacts produced by spontaneous respiratory
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Please cite this article in press as: Endo Y, Kawase K, Miyasho T et al. Plethysmography variability index for prediction of fluid responsiveness during graded haemorrhage and transfusion in sevoflurane-anaesthetized mechanically ventilated dogs, Veterinary Anaesthesia and Analgesia (2017), http://dx.doi.org/10.1016/j.vaa.2017.07.007
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movements during measurements of SVV, PPV and PVI, paralysis was achieved with vecuronium (Musculate; Fuji Pharma Co., Japan) using a loading dose of 0.2 mg kg1 IV followed by 0.1 mg kg1 hour1 (Nagahama et al. 2006). Mechanical ventilation was applied with peak inspiratory pressure (PIP) of 10 cmH2O, frequency of 12 breaths minute1 and inspiratory:expiratory time ratio of 1:2 using a timecycled ventilator (Nuffield Anaesthesia Ventilation Series 200; Penlon Ltd., UK). Then, tidal volume (VT) was adjusted to maintain a partial pressure of arterial carbon dioxide (PaCO2) of 35e45 mmHg (4.7e6.0 kPa) during the experiment. Lactated Ringer’s solution (LRS; Solulact; Terumo Co., Japan) was administered IV at 10 mL kg1 hour1 during instrumentation only. End-tidal gases were sampled from the circle Y-piece by a side-stream gas sampling system and FeSevo was measured using a physiological monitor (BP-608V; Omron Colin Co. Ltd., Japan) calibrated immediately prior to each experiment using a calibration gas composed of 2.0% desflurane, 5.0% CO2, 33.0% N2O, 55.0% O2 and 5.0% N2 (AG Calibration Gas and Adaptor Set; Omron Colin Co. Ltd.). Oesophageal temperature (T) was maintained throughout the experiment between 37.5 C and 38.5 C using a warm air blanket (FKCL3; Sanyo Electric Co. Ltd., Japan). Instrumentation A 22 gauge, 2.5 cm catheter (Supercath; Medikit Co. Ltd., Japan) was placed in each cephalic vein following the induction of anaesthesia for the administration of vecuronium and fluid. The hair was clipped from the skin over the left and right jugular veins and each site was aseptically prepared and desensitized by a subcutaneous (SC) injection of approximately 0.5 mL 2% lidocaine (Xylocaine; AstraZeneca KK, Japan). A 16 gauge, 30 cm central venous (CV) catheter (CV Catheter; Medikit Co. Ltd.) was inserted into the left jugular vein for measuring CVP and injecting ice-cold saline solution for determination of CO. Another 16 gauge CV catheter was inserted into the right jugular vein for blood withdrawal and transfusion of withdrawn blood. The tip of each CV catheter was located in the cranial vena cava (not in the right atrium) and its position was confirmed by echocardiography and pressure waveform. The medial surface area of the left thigh was clipped, aseptically prepared and desensitized, and a 4 Fr, 16 cm thermistor-tipped pulse contour CO (PiCCO) catheter (PV2014L16; PULSION Medical
Systems AG, Germany) inserted into the left femoral artery through a small skin incision for TPTDCO, mean arterial pressure (MAP) measurements and pulse contour analysis using a PiCCO system (PiCCO2; PULSION Medical Systems AG). Measurements of dynamic variables determining cardiac preload TPTDCO was determined by injecting ice-cold saline (0.2 mL kg1; Isotonic Sodium Chloride Solution; Terumo Co.) through the left CV catheter and was analysed and digitally displayed by the PiCCO system. TPTDCO was performed at end-expiration and repeated until three consecutive values with a difference of <10% were obtained (Itami et al. 2016). Stroke volume (SV), SVV and PPV were recorded by the PiCCO system. The PI and PVI were digitally displayed (Masimo Radical-7 Version V1.1.6.3i; Masimo Japan Co., Japan) using a clip-type pulse oximeter probe (LNOP TC-I, Tip Clip; Masimo Japan Co.), which was positioned on the mid-portion of the tongue near the median groove. The PVI was calculated as (PImaximum PIminimum)/PImaximum 100 (Cannesson et al. 2008a,b). To optimize the PI signal and obtain reliable PVI data, the tongue was gently massaged and the probe was repositioned approximately 3 minutes before data collection at each time point (Klein et al. 2016). Measurements of cardiopulmonary variables The left CV catheter and the PiCCO catheter were used for measurement of CVP and MAP, respectively, using a pressure transducer (PiCCO Monitoring Kit PV8215; PULSION Medical Systems AG) for each catheter. The zero reference point for the pressure transducers was level with the manubrium. These catheters were flushed periodically with saline containing 10 U mL1 sodium heparin (Novo-heparin for injection; Mochida Pharmaceutical Co., Japan). Arterial blood samples were obtained anaerobically from the PiCCO catheter into a plastic syringe heparinized with 1000 U mL1 sodium heparin after evacuation of all air. Blood samples were analysed immediately after collection (<5 minutes) for arterial pH (pHa), partial pressure of arterial oxygen (PaO2) and PaCO2 using a blood gas analyser and corrected for T (GEM Premier 3000; Instrumentation Laboratory Japan Co. Ltd., Japan). PIP was measured at the one-way valve of the inspiratory limb using a manometer that detected
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Please cite this article in press as: Endo Y, Kawase K, Miyasho T et al. Plethysmography variability index for prediction of fluid responsiveness during graded haemorrhage and transfusion in sevoflurane-anaesthetized mechanically ventilated dogs, Veterinary Anaesthesia and Analgesia (2017), http://dx.doi.org/10.1016/j.vaa.2017.07.007
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Plethysmography variability index in dogs Y Endo et al.
30 minutes
15 minutes Blood withdrawal
Blood transfusion
T1 T2 T3 T4 T5 T6 T7
T8 T9 T10 T11 T12 T13 T14
Instrumentation
Time point Volume of blood deficit (mL kg–1)
0
5
10 15 20 25 30
Volume of blood transfusion (mL kg–1)
0
5
10 15 20 25 30
Figure 1 Timeline of the study design. Baseline cardiopulmonary variables were recorded 30 minutes after instrumentation (T1). Blood (5 mL kg1) was withdrawn over 5 minutes and cardiopulmonary variables were measured 10 minutes later (T2). This procedure was repeated 6 times for a total of 30 mL kg1 blood loss. After a resting period of 15 minutes, cardiopulmonary variables were recorded (T8). The collected blood was infused in 5 mL kg1 increments, each over 5 minutes and cardiopulmonary variables were recorded 10 minutes later. The transfusions were repeated until the 30 mL kg1 of blood was administered.
pressure within the rebreathing system. VT was measured at the one-way valve of the expiratory limb of the rebreathing system using a ventilometer (Exhalometer; Kohken Medical Co. Ltd., Japan). T, heart rate (HR) and ECG (lead II) were recorded from the physiological monitor (BP-608V; Omron Colin Co. Ltd.). Experimental protocol Each experiment followed the same format (Fig. 1). LRS administration was discontinued and the dog was allowed to stabilize for 30 minutes in right lateral recumbency after completion of instrumentation. Baseline values of cardiopulmonary variables (HR, MAP, CVP, TPTDCO, SV, SVV, PPV, PI, PVI, pHa, PaO2, PaCO2, PIP and VT) were obtained (Fig. 1; T1). Venous blood was withdrawn from the right CV catheter at 1 mL kg1 minute1 into 50 mL syringes containing a volume of citrateephosphatee dextroseeadenine (CPDA-1) appropriate for the volume of blood (14 mL CPDA-1 per 100 mL blood) and then transferred from the syringes into sterile bags (Teruflex; Terumo Co.). After 5 mL kg1 of blood was withdrawn, 10 minutes elapsed before cardiopulmonary variables were measured and recorded (T2). This procedure was repeated six times, resulting in a total blood loss (T2eT7) of 30 mL kg1. No further intervention occurred for 15 minutes before cardiopulmonary variables were recorded (Fig. 1; T8). The reverse procedure was initiated by manually transfusing collected blood through the right CV catheter at 1 mL kg1 minute1 for 5 4
minutes. Ten minutes elapsed after each 5 mL kg1 of blood transfusion and before cardiopulmonary variables were recorded (Fig. 1). This procedure was repeated six times until 30 mL kg1 of shed blood was transfused (T9eT14). The vecuronium infusion was discontinued after T14 data collection and sugammadex (4 mg kg1; Bridion; MSD K.K., Japan) was administered IV to reverse muscle paralysis. The dogs were recovered from anaesthesia and monitored for general condition and food and water intake for 24 hours after the experiment. Buprenorphine (0.01 mg kg1; Otsuka Pharmaceutical Co. Ltd., Japan) was administered by intramuscular injection and meloxicam (0.2 mg kg1; Metacam; Boehringer Ingelheim Vetmedica Japan Co. Ltd., Japan) SC during recovery from anaesthesia and twice daily for 3 days after the experiment. Statistical analysis Statistical analysis was performed using JMP Version 11.0 for MAC (SAS Institute Inc., NC, USA). Data are expressed as the mean ± SD. The cardiopulmonary variables measured during blood withdrawal and transfusion were compared with each baseline value by using paired t test for normally distributed continuous variables or the Wilcoxon signed rank test for non-normally distributed variables. Linear regression analysis was performed in order to examine correlation between PPV and SVV or PVI. Receiver operating characteristic (ROC) curve analysis was performed to examine the performance of
© 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved., ▪, 1e10
Please cite this article in press as: Endo Y, Kawase K, Miyasho T et al. Plethysmography variability index for prediction of fluid responsiveness during graded haemorrhage and transfusion in sevoflurane-anaesthetized mechanically ventilated dogs, Veterinary Anaesthesia and Analgesia (2017), http://dx.doi.org/10.1016/j.vaa.2017.07.007
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a
b 30
30
20
20
PVI (%)
SVV (%)
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Plethysmography variability index in dogs Y Endo et al.
10
0
y = 0.32x + 11.14 r = 0.34 p = 0.002
0
10
20
30
y = 0.85x + 1.80 r = 0.79 p < 0.001
10
0
0
10
20
30
PPV (%)
PPV (%)
Figure 2 Correlations between (a) stroke volume variation (SVV) and pulse pressure variation (PPV), and (b) plethysmography variability index (PVI) and PPV in six anaesthetized dogs in response to blood withdrawal up to 30 mL kg1 and to reinfusion of the collected blood.
PPV and SVV or PVI as indicators of fluid responsiveness, and to determine threshold values during transfusion. Dogs that increased their SV by 15% in response to blood transfusion were considered to be responders and those that did not were defined as
nonresponders. This cut off value (SV increase 15%) was selected based upon previous reports investigating the ability of SVV, PPV and PVI to identify fluid responsiveness in human patients (Hofer et al. 2005; Renner et al. 2011). Responders and
Table 1 Cardiopulmonary variables measured during blood withdrawal in six dogs anaesthetized with sevoflurane and mechanically ventilated Variables
HR (beats minute1) MAP (mmHg) CVP (mmHg) TPTDCO (L minute1) SV (mL beat1) SVV (%) PPV (%) PI (%) PVI (%) pHa PaO2 (mmHg) PaO2 (kPa) PaCO2 (mmHg) PaCO2 (kPa) PIP (cmH2O) VT (mL kg1)
Volume of blood deficit T1 0 mL kg¡1
T2 5 mL kg¡1
T3 10 mL kg¡1
T4 15 mL kg¡1
T5 20 mL kg¡1
T6 25 mL kg¡1
T7 30 mL kg¡1
109 ± 4 78 ± 3 3.1 ± 1.4 1.9 ± 0.3
109 ± 4 76 ± 2 2.6 ± 1.0 1.8 ± 0.2
107 ± 5 72 ± 3 2.3 ± 0.8 1.7 ± 0.2
107 ± 4 67 ± 3 2.0 ± 1.2 1.6 ± 0.2*
105 ± 4 63 ± 3* 1.5 ± 1.2 1.4 ± 0.1*
105 ± 6 61 ± 3* 0.8 ± 0.9* 1.3 ± 0.1y
109 ± 5 57 ± 3y 0.5 ± 0.8* 1.3 ± 0.1y
17.5 ± 2.3 16 ± 3 13 ± 2 0.8 ± 0.4 9±3 7.363 ±0.028 552 ± 37 74 ± 5 39 ± 2 5.2 ± 0.2 10 ± 1 16 ± 2
16.1 ± 2.3 17 ± 4 14 ± 4 0.7 ± 0.5 11 ± 4 7.378 ± 0.022 549 ± 44 73 ± 6 37 ± 2 5.0 ± 0.2 10 ± 1 16 ± 2
15.8 ± 2.3 17 ± 4 17 ± 4* 0.7 ± 0.5 13 ± 5* 7.360 ± 0.037 566 ± 25 75 ± 3 38 ± 2 5.1 ± 0.3 10 ± 1 16 ± 2
14.6 ± 2.1y 18 ± 3 19 ± 2y 0.6 ± 0.4 15 ± 6y 7.358 ± 0.036 568 ± 31 76 ± 4 39 ± 3 5.2 ± 0.4 10 ± 1 16 ± 2
13.1 ± 2.0y 19 ± 2 20 ± 3y 0.5 ± 0.3 15 ± 3y 7.336 ± 0.045 566 ± 23 75 ± 3 39 ± 3 5.2 ± 0.4 10 ± 1 16 ± 2
12.6 ± 1.7y 20 ± 3 22 ± 2y 0.4 ± 0.2 17 ± 4y 7.325 ± 0.045 576 ± 21 77 ± 3 40 ± 3 5.3 ± 0.4 10 ± 1 15 ± 2
12.1 ± 1.7y 19 ± 4 23 ± 4y 0.4 ± 0.2 17 ± 4y 7.291 ± 0.043 572 ± 23 76 ± 3 42 ± 4 5.5 ± 0.5 10 ± 1 15 ± 2
HR, heart rate; MAP, mean arterial pressure; CVP, central venous pressure; TPTDCO, transpulmonary thermodilution cardiac output; SV, stroke volume; SVV, stroke volume variation; PPV, pulse pressure variation; PI, perfusion index; PVI, plethysmography variability index; pHa, arterial blood pH; PaO2, arterial partial pressure of oxygen; PaCO2, arterial partial pressure of carbon dioxide; PIP, peak inspiratory pressure; VT, tidal volume. The values are mean ± standard deviation. *p < 0.05, yp < 0.01 significant difference compared with the baseline value (T1).
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Please cite this article in press as: Endo Y, Kawase K, Miyasho T et al. Plethysmography variability index for prediction of fluid responsiveness during graded haemorrhage and transfusion in sevoflurane-anaesthetized mechanically ventilated dogs, Veterinary Anaesthesia and Analgesia (2017), http://dx.doi.org/10.1016/j.vaa.2017.07.007
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1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65
Plethysmography variability index in dogs Y Endo et al.
nonresponders were compared with those recorded at the prior stage of each transfusion using Student’s t test for normally distributed continuous variables or the ManneWhitney test for non-normally distributed variables. A ROC curve was generated to assess the ability of SVV, PPV and PVI to identify responders and nonresponders. The areas under the ROC curves (AUCs) were calculated and compared (Hanley & McNeil 1983; Akobeng 2007). Optimal threshold values (the value that maximizes the sum of both sensitivity and specificity) for SVV, PPV and PVI were determined from the ROC curves. A value of p < 0.05 was considered statistically significant. Results The mean ± SD for sevoflurane MAC values in all dogs was 2.1 ± 0.2%. The total anaesthesia time from mask induction to the cessation of anaesthesia was 685 ± 47 minutes. Instrumentation was completed at 70 ± 16 minutes after initiation of mask induction. The dogs recovered from anaesthesia without complications and were extubated at 9 ± 6 minutes after sevoflurane was discontinued. Blood withdrawal resulted in significant decreases in MAP, TPTDCO, SV, CVP and PI, and increases in
1
PPV and PVI. The total of 30 mL kg blood loss resulted in significant decreases in MAP (p ¼ 0.017), CVP (p ¼ 0.011), TPTDCO (p ¼ 0.008) and SV (p ¼ 0.002), and significant increases in PPV (p < 0.001) and PVI (p < 0.001), compared with each baseline value (Table 1). Transfusion of the previously withdrawn blood resulted in significant increases in MAP (p < 0.001), CVP (p ¼ 0.006), TPTDCO (p < 0.001) and SV (p ¼ 0.003), and significant decreases in PPV (p ¼ 0.002) and PVI (p ¼ 0.005), compared with pretransfusion hypovolaemic values at T8 (Table 2). SVV was not significantly changed during blood withdrawal or transfusion. PaCO2 and PIP were constant at all time points with a minimum adjustment of VT. A total of 72 data points (36 each from the stages of blood withdrawal and transfusion) were obtained for SVV, PPV and PVI from the six dogs. There were significant correlations between PPV and SVV (p ¼ 0.002, coefficient of determination r ¼ 0.34) and between PPV and PVI (p < 0.001, r ¼ 0.79; Fig. 2). Five dogs responded and one dog was a nonresponder to blood transfusion at T9 and T10, and at T11 and T13 two dogs were responders and four dogs were nonresponders. All six dogs were nonresponders at T12 and T14. The PPV and PVI were significantly
Table 2 Cardiopulmonary variables recorded during blood transfusion in six hypovolaemic dogs anaesthetized with sevoflurane and mechanically ventilated Variables
HR (beats minute1) MAP (mmHg) CVP (mmHg) TPTDCO (L minute1) SV (mL beat1) SVV (%) PPV (%) PI (%) PVI (%) pHa PaO2 (mmHg) PaO2 (kPa) PaCO2 (mmHg) PaCO2 (kPa) PIP (cmH2O) VT (mL kg1)
Volume of blood transfused T8 0 mL kg¡1
T9 5 mL kg¡1
T10 10 mL kg¡1
T11 15 mL kg¡1
T12 20 mL kg¡1
T13 25 mL kg¡1
T14 30 mL kg¡1
109 ± 11 56 ± 3 0.3 ± 0.8 1.2 ± 0.3
110 ± 10 61 ± 4y 0.5 ± 0.8 1.5 ± 0.3y
110 ± 8 65 ± 4y 1.5 ± 1.3 1.8 ± 0.3y
112 ± 8 69 ± 3y 2.0 ± 0.8* 2.1 ± 0.5y
113 ± 9 73 ± 3y 2.5 ± 1.3* 2.2 ± 0.5y
112 ± 10 76 ± 5y 3.5 ± 1.3y 2.4 ± 0.5y
117 ± 11 82 ± 5y 3.7 ± 1.6y 2.7 ± 0.7y
11.6 ± 3.8
14.1 ± 3.9y
16.6 ± 4.2y
18.8 ± 4.9y
19.6 ± 5.2y
21.6 ± 5.2y
23.5 ± 6.7y 16 ± 1 13 ± 2* 16 ± 3 16 ± 5 13 ± 4 15 ± 7 13 ± 5 20 ± 3 17 ± 2y 16 ± 2y 15 ± 2y 13 ± 1y 11 ± 1y 11 ± 1y 0.5 ± 0.3 0.6 ± 0.4 0.7 ± 0.4 0.8 ± 0.4* 0.8 ± 0.4 0.9 ± 0.5 1.0 ± 0.6 15 ± 3 14 ± 3 12 ± 3 10 ± 4 9±4 7 ± 2* 6 ± 2y 7.298 ± 0.025 7.284 ± 0.040 7.290 ± 0.049 7.290 ± 0.050 7.3 02 ± 0.038 7.316 ± 0.049 7.316 ± 0.045 571 ± 26 568 ± 18 522 ± 57 552 ± 39 556 ± 28 522 ± 67 545 ± 30 76 ± 3 75 ± 2 70 ± 7 73 ± 5 74 ± 3 70 ± 8 72 ± 4 43 ± 4 46 ± 4 45 ± 6 46 ± 6 46 ± 6 45 ± 6 46 ± 7 5.7 ± 0.5 6.1 ± 0.4 6.0 ± 0.8 6.1 ± 0.8 6.1 ± 0.8 6.0 ± 0.8 6.1 ± 0.9 10 ± 1 10 ± 1 10 ± 1 10 ± 1 10 ± 1 10 ± 1 10 ± 1 15 ± 3 15 ± 3 14 ± 3 15 ± 3 15 ± 3 15 ± 3 15 ± 3
HR, heart rate; MAP, mean arterial pressure; CVP, central venous pressure; TPTDCO, transpulmonary thermodilution cardiac output; SV, stroke volume; SVV, stroke volume variation; PPV, pulse pressure variation; PI, perfusion index; PVI, plethysmography variability index; pHa, arterial blood pH; PaO2, arterial partial pressure of oxygen; PaCO2, arterial partial pressure of carbon dioxide; PIP, peak inspiratory pressure; VT, tidal volume. The values are mean ± standard deviation. *p < 0.05, yp < 0.01 significant difference compared with the baseline value (T8).
6
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Please cite this article in press as: Endo Y, Kawase K, Miyasho T et al. Plethysmography variability index for prediction of fluid responsiveness during graded haemorrhage and transfusion in sevoflurane-anaesthetized mechanically ventilated dogs, Veterinary Anaesthesia and Analgesia (2017), http://dx.doi.org/10.1016/j.vaa.2017.07.007
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Plethysmography variability index in dogs Y Endo et al.
increased in responders (p ¼ 0.012 and p ¼ 0.005, respectively; Table 3). These data yielded optimal threshold values for fluid responsiveness of SVV 15% [sensitivity 64%; 95% confidence intervals (CI) 35e87%, specificity 50%; 95% CI 28e71%, AUC ¼ 0.52], PPV 16% (sensitivity 71%; 95% CI 42e92%, specificity 82%; 95% CI 60e95%, AUC ¼ 0.74) and PVI 12% (sensitivity 78%; 95% CI 50e95%, specificity 72%; 95% CI 50e90%, AUC ¼ 0.71; Fig. 3). Discussion This study describes and confirms the utility of PPV and PVI for predicting fluid responsiveness in mechanically ventilated, sevoflurane-anaesthetized hypovolaemic dogs. Both PVI and PPV were moderately accurate predictors of fluid responsiveness and generated provisional threshold values for identifying fluid responsiveness of 12% and 16%, respectively. Anaesthesia was maintained at FeSevo of 1.3 MAC for three reasons: 1) MAC is a useful concept for comparing the effects of inhaled anaesthetics within and among experiments; 2) MAC corresponds to the effective dose required to prevent movement in 50% of the participants (ED50) and 1.2e1.4 MAC is the dose corresponding to the ED95, which is more clinically relevant and closely aligned with a surgical plane of anaesthesia; and 3) higher FeSevo may produce significant cardiovascular depression in dogs (Mutoh et al. 1997). However, the MAC of isoflurane is reduced in dogs with hypovolaemia resulting from haemorrhage (Mattson et al. 2006). Thus controlled haemorrhage in the dogs in this study may have affected the depth of anaesthesia and the haemodynamic changes. Using individual MAC values at a
Figure 3 Receiver operating characteristic (ROC) curves comparing the ability of pulse pressure variation (PPV), stroke volume variation (SVV), and plethysmography variability index (PVI) to discriminate between responders and nonresponders during blood transfusion in six anaesthetized hypovolaemic dogs. AUC, area under the ROC curve.
fixed FeSevo of 1.3 MAC was an attempt to minimize individual animal variability as a source of error. TPTDCO measured by the PiCCO system has been evaluated in previous studies that assessed indicators of cardiac preload in halothaneefentanyl- or halothaneenitrous-oxide-anaesthetized, mechanically ventilated dogs (Fujita et al. 2004; Brekenstadt et al. 2005). TPTDCO has exhibited good agreement with CO measured by standard thermodilution technique (TDCO) during IV crystalloid or colloid administration in sevoflurane-anaesthetized dogs (Itami et al. 2016).
Table 3 Dynamic variables of fluid responsiveness before (previous time point) and after each 5 mL kg1 blood volume transfusion (a total of 36 transfusions in six dogs) At each time point, dogs were designated responders or nonresponders to volume expansion based on changes in stroke volume: an increase of 15% defined a responder (n ¼ 14) and <15% defined a nonresponder (n ¼ 22). Within these categories, the corresponding values (mean ± standard deviation) for stroke volume variation (SVV), pulse pressure variation (PPV) and plethysmography variability index (PVI) are listed. n ¼ number of time points Variable
SVV (%) PPV (%) PVI (%)
Responders
Nonresponders
Before
After transfusion
Before
After transfusion
15 ± 3 18 ± 3 13 ± 3
15 ± 4 16 ± 3* 11 ± 4y
15 ± 5 14 ± 3 10 ± 4
14 ± 5 13 ± 2 9±3
*p < 0.05, yp < 0.01 significant difference from the value recorded at the previous time point.
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Please cite this article in press as: Endo Y, Kawase K, Miyasho T et al. Plethysmography variability index for prediction of fluid responsiveness during graded haemorrhage and transfusion in sevoflurane-anaesthetized mechanically ventilated dogs, Veterinary Anaesthesia and Analgesia (2017), http://dx.doi.org/10.1016/j.vaa.2017.07.007
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Plethysmography variability index in dogs Y Endo et al.
The TPTDCO baseline value determined before blood withdrawal was equal to previously reported TDCO and TPTDCO values in anaesthetized, mechanically ventilated dogs with stable haemodynamics (Fujita et al. 2004; Brekenstadt et al. 2005; Yamashita et al. 2007; Itami et al. 2016; Klein et al. 2016). Furthermore, changes in TPTDCO produced by blood withdrawal were similar to those in TDCO and TPTDCO in previous reports (Fujita et al. 2004; Brekenstadt et al. 2005; Klein et al. 2016). Changes in other haemodynamic variables, including HR, MAP, CVP and SV, produced by blood withdrawal were also similar to those observed in hypovolaemic mechanically ventilated dogs under isoflurane anaesthesia (Klein et al. 2016). Increases in PPV > 12e13% are associated with decreases in CO during hypotension or graded haemorrhage and are used to predict fluid responsiveness in human medicine and dogs (Brekenstadt et al. 2005; Michard 2005; Wyffels et al. 2007; Marik et al. 2009; Desgranges et al. 2011). In the present study, a similar response in PPV values was recorded during haemorrhage with a threshold value for predicting fluid responsiveness of 16%. Cannesson et al. (2008a) were the first to report that PVI could identify fluid responsiveness noninvasively in anaesthetized, mechanically ventilated human patients when the threshold value for PVI was >14%. Additional studies comparing PPV and PVI in humans produced correlation coefficients (r) of 0.50e0.72 (Cannesson et al. 2008b; Loupec et al. 2011; Chandler et al. 2012). Since then, other studies have confirmed that PVI will identify fluid responsiveness with moderate to high accuracy and report threshold PVI values for identification of fluid responsiveness from >9.5% to 12% in adult human patients (Zimmermann et al. 2010; Desgranges et al. 2011; Hood & Wilson 2011). The authors of one recent study in isoflurane-anaesthetized dogs subjected to haemorrhage (25 ± 5 mL kg1) concluded that PPV and PVI may be useful indicators for identifying fluid responsiveness but threshold values were not provided (Klein et al. 2016). The results of the present study support their conclusion and propose provisional threshold values of 16% and 12% to identify fluid responsiveness for PPV and PVI, respectively. Fluid responsiveness was not identified by SVV in the present study, whereas an increase in SVV has been documented as a valid indicator of fluid responsiveness in mechanically ventilated adult 8
human patients (Hofer et al. 2005; Zimmermann 2010; Drvar et al. 2013). Several studies have reported that SVV can reflect preload status but it is not a sensitive indicator of dynamic preload changes in dogs after either severe hypovolaemia (haemorrhage 50% of blood volume) or the fluid-overload period in dogs (Fujita et al. 2004; Brekenstadt et al. 2005; Taguchi et al. 2011). Indeed Taguchi et al. (2011) demonstrated that SVV decreased significantly following blood withdrawal in dogs. Similarly, decrease in SVV was observed during the stable period between T7 (SVV 19 ± 4%) and T8 (SVV 16 ± 1%) in the present study. It has been suggested that the decreased sensitivity of SVV for predicting fluid responsiveness in dogs subjected to haemorrhage may result from a change in the relation of the SV to the aortic pulse pressure when aortic filling is decreased (Brekenstadt et al. 2005). The present study had several limitations. First, the derived threshold values for fluid responsiveness were determined from a small number of dogs under strictly controlled conditions. These provisional threshold values need to be confirmed by larger clinical trials evaluating fluid responsiveness in this species. Second, SVV was measured by the algorithm of the PiCCO system and could not be directly compared with SVV measured by other systems. Third, a clip-type of pulse oximeter probe was used on the tongue and this type of probe may have decreased PI by local tissue compression. Furthermore, it has been reported that the threshold values of PVI for predicting fluid responsiveness differ with the site of measurement (Desgranges et al. 2011). In addition, PPV and PVI values are influenced by VT and/or PIP setting for mechanical ventilation, intra-abdominal pressure, arrhythmias, HR:respiratory rate ratio, vascular tone, lung compliance, right ventricular function, anaesthesia and fluid challenge (Monnet et al. 2016). Further studies are required to determine the effects of various sensor types and locations and the effects of these various factors on SVV, PPV and PVI in dogs. In conclusion, PPV and noninvasive measurement of PVI predicted fluid responsiveness with moderate accuracy in haemorrhaged and transfused sevoflurane-anaesthetized, mechanically ventilated dogs. Threshold values for identification of fluid responsiveness were PPV 16% and PVI 12%. The results are based on a small number of dogs, therefore, further studies are needed to confirm the threshold values for these variables in dogs.
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Please cite this article in press as: Endo Y, Kawase K, Miyasho T et al. Plethysmography variability index for prediction of fluid responsiveness during graded haemorrhage and transfusion in sevoflurane-anaesthetized mechanically ventilated dogs, Veterinary Anaesthesia and Analgesia (2017), http://dx.doi.org/10.1016/j.vaa.2017.07.007
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Acknowledgements We thank Taku Hirokawa, Department of Small Animal Clinical Sciences, School of Veterinary Medicine, Rakuno Gakuen University, for assistance with measurements. Authors' contributions YE: study design, performed the experiments, statistical analysis, preparation of manuscript. KK: performed the experiments, data management. TM, TS: performed the experiments. KY, WWM: study design, preparation of manuscript. All authors contributed to drafting of the manuscript and read and approved the final manuscript. Conflict of interest The authors declare no conflict of interest. References Aarnes TK, Bednarski RM, Lerche P et al. (2009) Effect of intravenous administration of lactated Ringer's solution or hetastarch for the treatment of isofluraneinduced hypotension in dogs. Am J Vet Res 70, 1345e1353. Akobeng AK (2007) Understanding diagnostic tests 3: receiver operating characteristic curves. Acta Paediatr 96, 644e647. Brekenstadt H, Friedman Z, Preisman S et al. (2005) Pulse pressure and stroke volume variation during severe haemorrhage in ventilated dogs. Br J Anaesth 94, 721e726. Cannesson M, Desebbe O, Rosamel P et al. (2008a) Pleth variability index to monitor the respiratory variations in the pulse oximeter plethysmographic waveform amplitude and predict fluid responsiveness in the operating theatre. Br J Anaesth 101, 200e206. Cannesson M, Delannoy B, Morand A et al. (2008b) Does the Pleth variability index indicate the respiratoryinduced variation in the plethysmogram and arterial pressure waveforms? Anesth Analg 106, 1189e1194. Chandler JR, Cooke E, Petersen C et al. (2012) Pulse oximeter plethysmograph variation and its relationship to the arterial waveform in mechanically ventilated children. J Clin Monit Comput 26, 145e151. Davis H, Jensen T, Johnson A et al. (2013) AAHA/AAFP fluid therapy guidelines for dogs and cats. J Am Anim Hosp Assoc 49, 149e159. Desgranges FP, Desebbe O, Ghazouani A et al. (2011) Influence of the site of measurement on the ability of plethysmographic variability index to predict fluid responsiveness. Br J Anaesth 107, 329e335. Diniz MS, Teixeira-Neto FJ, C^ andido TD et al. (2014) Effects of dexmedetomidine on pulse pressure variation
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Please cite this article in press as: Endo Y, Kawase K, Miyasho T et al. Plethysmography variability index for prediction of fluid responsiveness during graded haemorrhage and transfusion in sevoflurane-anaesthetized mechanically ventilated dogs, Veterinary Anaesthesia and Analgesia (2017), http://dx.doi.org/10.1016/j.vaa.2017.07.007
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© 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved., ▪, 1e10
Please cite this article in press as: Endo Y, Kawase K, Miyasho T et al. Plethysmography variability index for prediction of fluid responsiveness during graded haemorrhage and transfusion in sevoflurane-anaesthetized mechanically ventilated dogs, Veterinary Anaesthesia and Analgesia (2017), http://dx.doi.org/10.1016/j.vaa.2017.07.007
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