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Volumetric evaluation of fluid responsiveness using a modified passive leg raise maneuver during experimental induction and correction of hypovolemia in anesthetized dogs
Correspondence: Vaidehi V Paranjape, Department of Small Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, 205 Duck Pond Dr, Blacksburg, VA 24061, USA.
To demonstrate if modified passive leg raise (PLRM) maneuver can be used for volumetric evaluation of fluid responsiveness (FR) by inducing cardiac output (CO) changes during experimental induction and correction of hypovolemia in healthy anesthetized dogs. The effects of PLRM on plethysmographic variability index (PVI) and pulse pressure variation (PPV) were also investigated.
Study design
Prospective, crossover study.
Animals
A total of six healthy anesthetized Beagle dogs.
Methods
Dogs were anesthetized with propofol and isoflurane. They were mechanically ventilated under neuromuscular blockade, and normothermia was maintained. After instrumentation, all dogs were subjected to four stages: 1, baseline; 2, removal of 27 mL kg–1 circulating blood volume; 3, after blood re-transfusion; and 4, after 20 mL kg–1 hetastarch infusion over 20 minutes. A 10 minute stabilization period was allowed after induction of each stage and before data collection. At each stage, CO via pulmonary artery thermodilution, PVI, PPV and cardiopulmonary variables were measured before, during and after the PLRM maneuver. Stages were sequential, not randomized. Statistical analysis included repeated measures anova and Tukey’s post hoc test, considering p < 0.05 as significant.
Results
During stage 2, PLRM at a 30° angle significantly increased CO (mean ± standard deviation, 1.0 ± 0.1 to 1.3 ± 0.1 L minute–1; p < 0.001), with a simultaneous significant reduction in PVI (38 ± 4% to 21 ± 4%; p < 0.001) and PPV (27 ± 2% to 18 ± 2%; p < 0.001). The PLRM did not affect CO, PPV and PVI during stages 1, 3 and 4.
Conclusions and clinical relevance
In anesthetized dogs, PLRM at a 30° angle successfully detected FR during hypovolemia, and identified fluid nonresponsiveness during normovolemia and hypervolemia. Also, in hypovolemic dogs, significant decreases in PVI and PPV occurred in response to PLRM maneuver.
Fluid responsiveness (FR) describes a 10–15% increase in cardiac output (CO) or stroke volume after a fluid challenge, implying that the heart is preload responsive (
Dynamic changes in arterial waveform derived variables and fluid responsiveness in mechanically ventilated patients: a systematic review of the literature.
Dynamic prediction of fluid responsiveness during positive pressure ventilation: a review of the physiology underlying heart-lung interactions and a critical interpretation.
). Conversely, fluid nonresponsiveness is indicated by minimal change in CO following a fluid challenge. In humans, fluid resuscitation guided by evaluation of FR reduces patient mortality, duration of stay in critical care units and duration of mechanical ventilation (
). Ventilator-induced dynamic variables such as plethysmographic variability index (PVI) and pulse pressure variation (PPV) accurately assess FR in dogs (
). The accuracy of PPV and PVI is decreased in the presence of tidal volumes < 8 mL kg–1, spontaneous ventilation, intra-abdominal hypertension, low respiratory system compliance, cor pulmonale, cardiac arrhythmias and altered vascular tone (
Dynamic changes in arterial waveform derived variables and fluid responsiveness in mechanically ventilated patients: a systematic review of the literature.
The passive leg raise test in humans involves transferring a patient from a semi-recumbent position to lying down with the trunk oriented horizontally and legs lifted at a 30–45° angle (
). Further lowering of the trunk in addition to the leg raising can cause a gravitational transfer of about 150–300 mL blood from the splanchnic region and lower limbs towards the central circulatory compartment (
), the reliability of passive leg raise for detecting FR is well established. Moreover, this technique has been recommended for guiding hemodynamic stabilization of septic patients in the Surviving Sepsis Campaign (
). Considering interspecies variability in pelvic limb conformation, size and regional blood volume, the passive leg raise test was modified for use in anesthetized pigs by elevating both the caudal abdomen and the pelvic limbs (
Use of a modified passive leg-raising maneuver to predict fluid responsiveness during experimental induction and correction of hypovolemia in healthy isoflurane-anesthetized pigs.
). A 15° inclination from horizontal plane was used to recruit blood from the caudal abdomen and the pelvic limbs during 20% and 40% blood loss to evaluate FR (
Use of a modified passive leg-raising maneuver to predict fluid responsiveness during experimental induction and correction of hypovolemia in healthy isoflurane-anesthetized pigs.
The present study was designed to: 1) describe a modified passive leg raise (PLRM) maneuver in anesthetized dogs; 2) assess FR during experimental induction and correction of hypovolemia and hypervolemia; and 3) evaluate the effect of PLRM on PPV and PVI values. We hypothesized that: 1) PLRM maneuver is feasible in dogs; 2) the maneuver would accurately identify FR during hypovolemia and nonresponsiveness during normovolemia and hypervolemia; and 3) PPV and PVI will change in response to the maneuver.
Materials and methods
Animals
All study procedures were approved by Virginia Tech University Institutional Animal Care and Use Committee (no. 20-235). A total of six healthy male, adult purpose-bred, university-owned Beagle dogs (aged 9–13 months; weighing 8.7 ± 0.1 kg) were included in this prospective, nonrandomized, crossover study. Dogs were housed in a controlled temperature environment, with free access to water, food and enrichment toys. All dogs were determined healthy through a physical examination, complete blood count and serum chemistry panel. Using a literature search of studies performed in humans identifying CO response to the passive leg raise test (
Use of a modified passive leg-raising maneuver to predict fluid responsiveness during experimental induction and correction of hypovolemia in healthy isoflurane-anesthetized pigs.
) and a pilot study in dogs, an a priori power analysis indicated that a sample size of six dogs was necessary to show a minimum 15% significant difference in CO assuming a statistical power of 0.8 and an alpha level of 0.05 (G∗Power 3.1; Heinrich-Heine-Universität Düsseldorf, Germany; http://estatistica.bauru.usp.br/calculoamostral/).
Induction of anesthesia and monitoring
After completing 2 weeks of acclimatization in the laboratory, food was withheld for 12 hours prior to the experiment, with water ad libitum. For each dog, a 20 gauge, 3 cm catheter (SurFlash; Terumo Medical Corp. NJ, USA) was aseptically placed in the right cephalic vein, and oxygen was supplemented (4 L minute–1) for 5 minutes using a loose-fitting facemask. Propofol (Propoflo; Zoetis Inc., MI, USA) was titrated intravenously (IV) to induce general anesthesia until the trachea could be intubated with a cuffed endotracheal tube (Sheridan; Jorgensen Laboratories Inc., CO, USA). The endotracheal tube was connected to an anesthesia machine with an integrated ventilator (Datex-Ohmeda Aestiva 5/7900; GE Healthcare, WI, USA) via a rebreathing system. Anesthesia was maintained with isoflurane (Fluriso; VetOne, ID, USA) in oxygen (1–2 L minute–1) at an end-tidal concentration of isoflurane (Fe′Iso) of 1.6–1.8%, which was continuously monitored by an infrared gas analyzer linked to a multiparameter monitor (Datex-Ohmeda S/5 Compact anesthesia monitor; GE Healthcare). The gas was sampled from the rostral end of the endotracheal tube at 120 mL minute–1. This gas analyzer was calibrated before each experiment with a standard calibration gas mixture (755581-HEL QUICK CAL Calibration Gas CO2/O2/N20; GE Healthcare). The same monitor also recorded standard lead II electrocardiogram, heart rate (HR), esophageal temperature and partial pressure of end-tidal carbon dioxide (Pe′CO2). The dogs were positioned in dorsal recumbency for the entire anesthetic event. Maintenance fluids were not administered to prevent skewing of hemodynamic data arising from any changes in blood volume.
Dynamic compliance (Cdyn) was calculated by Cdyn = VT/(PIP – PEEP) where tidal volume (VT) was in liters, peak inspiratory pressure (PIP) in cmH2O and positive end-expiratory pressure (PEEP) in cmH2O.
A 22 gauge, 2.5 cm catheter (SurFlo; Terumo Medical Corp.) was inserted aseptically in the dorsal pedal artery for collection of blood and measurement of systolic, diastolic and mean (MAP) arterial pressures. The catheter was connected to a transducer (Deltran II; Utah Medical Products Inc., UT, USA) via saline-filled noncompliant tubing and a three-way stopcock. Prior to anesthesia for each dog, the accuracy and linearity of the transducer was verified against a mercury manometer at pressures of 0, 50, 100 and 150 mm Hg. Another multi-parametric monitor (Carescape B850; GE Healthcare, IL, USA) calculated PPV and measured CO via pulmonary artery (PA) thermodilution. An advanced pulse oximetry (Rainbow SET Pulse CO-oximetry; Masimo Corporation, CA, USA) with a clip-on probe was positioned on the thinnest portion of the tongue and continuously displayed peripheral hemoglobin saturation of oxygen (SpO2), PVI and perfusion index (PI). To enhance the PI signal and increase the reliability of PVI values, the tongue was gently massaged and the probe was repositioned approximately 5 minutes before data collection at each stage.
To prevent ventilator–animal dyssynchrony, neuromuscular blockade was induced with IV rocuronium (Rocuronium Bromide Injection; Almaject Inc., NJ, USA) administered as a bolus 0.4 mg kg–1 followed by a constant rate infusion of 0.4 mg kg–1 hour–1. The efficacy of the blockade was monitored by a supramaximal train-of-four electrical stimulus (STIMPOD 450X, Xavant Technology Ltd; Bell Medical Inc., MO, USA) of the common peroneal nerve. Volume-controlled ventilation with 12 mL kg–1 VT and 8–18 breaths minute–1 respiratory frequency (fR) was initiated to maintain arterial partial pressure of carbon dioxide (PaCO2) at 35–45 mmHg (4.7–6.0 kPa).
Instrumentation for cardiac output
A 5 Fr, 13 cm double-lumen catheter (MILA International Inc., KY, USA) was aseptically inserted in the left jugular vein and secured with skin sutures. This catheter served the purpose of blood withdrawal, collection of blood for measurement of packed cell volume (PCV) and total protein (TP) and for infusion of blood and colloid solution. A 6 Fr, 8.5 cm hemostasis introducer (Fast-Cath; Abbott Cardiovascular, MN, USA) was aseptically placed and secured in the right jugular vein, for introduction of a 5 Fr, 75 cm thermistor-tipped PA thermodilution catheter (Swan-Ganz; Edwards Lifesciences Corp., CA, USA). The catheter was advanced until the tip was located in the PA based on observation of characteristic pressure waveforms and pressures on the monitor screen (Carescape B850; GE Healthcare). The proximal and distal ports of the catheter provided measurements of central venous pressure (CVP), and PA and pulmonary artery occlusion pressures (PAOP), respectively. The pressure transducers (Deltran II; Utah Medical Products Inc.) were filled with heparinized saline (2 IU mL–1), placed at a height that approximated the location of the right atrium (location determined by the midpoint of an imaginary vertical line connecting the sternum to the opposite spinous process at the level of the fourth intercostal space), and zeroed to atmospheric pressure. For each CO measurement, 3 mL of chilled (2–5 °C) 0.9% sodium chloride solution was injected manually over < 3 seconds at end-expiration into the central venous port of the catheter (
Comparison of transpulmonary thermodilution and calibrated pulse contour analysis with pulmonary artery thermodilution cardiac output measurements in anesthetized dogs.
). CO was recorded as the mean of three consecutive measurements within 10% variation. The catheter thermistor in the PA also measured core body temperature (Tcore). A forced-air warming device (Bair-Hugger; 3M United States, MN, USA) and circulating water blanket (Maxitherm; Jorgensen Laboratories Inc.) were used to maintain Tcore within 36.7–38.3 °C throughout the experiment.
Stages of the study
Upon completing instrumentation, each dog was subjected to four sequential nonrandomized stages (Fig. 1). Stage 1: collection of baseline data. Stage 2: blood (27 mL kg–1) was collected over 20 minutes from the jugular vein catheter by gravity flow into collection bags containing an anticoagulant (CPDA-1 Blood Collection System; Animal Blood Resources International, MI, USA). Stage 3: the collected blood was reinfused over 20 minutes through a filter (Hemo-Nate; Animal Blood Resources International) using an infusion pump (BD Alaris Carefusion; Becton Dickinson and Company, NJ, USA). Stage 4: 6% hydroxyethyl starch (HES) 130/0.4 in 9% sodium chloride (20 mL kg–1, VetStarch; Zoetis Inc.) was administered over 20 minutes using the same infusion pump. After each procedure in each stage, 10 minutes elapsed until data collection before the PLRM maneuver, after 5 minutes of PLRM and after 5 minutes of being returned to the horizontal position.
Figure 1Timeline of the experimental design and data collection for evaluating modified passive leg raise (PLRM) maneuver in six healthy, anesthetized Beagle dogs in dorsal recumbency. After anesthetic induction and instrumentation, each dog underwent four stages in a sequential order: stage 1: baseline; stage 2: 27 mL kg–1 withdrawal of circulating blood volume; stage 3: autologous blood transfusion; stage 4: infusion of 6% hydroxyethyl starch 130/0.4 in 9% sodium chloride (20 mL kg–1). Data were collected immediately before application of PLRM (Pre-PLRM), after 5 minutes of PLRM (PLRM) and 5 minutes after abdomen and limbs were returned to horizontal position (Post-PLRM). A 10 minute stabilization period was provided after induction of each stage and before data collection.
Two wooden planks of equal sizes connected by hinges were placed between the dog and the table surface with the hinge level with the xiphoid process (Fig. 2a). The cranial plank remained horizontal supporting the dog from head to the xiphoid process, with the remainder of the dog supported by the caudal plank. During PLRM, with the cranial plank horizontal, the caudal plank was elevated to create a 30° angle (measured by a protractor) between the table surface and the plank that was supporting the caudal abdomen and pelvic limbs (Fig. 2b). This elevated position was maintained for 5 minutes before data were collected, followed by returning the entire dog to the horizontal position. After 5 minutes in this position, another set of data was collected.
Figure 2Graphical illustration depicting a modified passive leg raise (PLRM) maneuver performed in six healthy, anesthetized Beagle dogs in dorsal recumbency. (a) Before application of PLRM maneuver, two wooden planks of equal sizes connected by hinges were placed between the dog and the table surface with the hinge (black arrow) level with the xiphoid process. The cranial plank remained horizontal supporting the dog from head to the xiphoid process and the dog caudal to the hinge supported by the caudal plank. (b) PLRM maneuver: keeping the cranial plank horizontal, the caudal plank was elevated to a 30 ° angle between the table surface and the plank that was supporting the caudal abdomen and pelvic limbs. Illustration by V. Paranjape and J. Mauragis.
At every time point, HR, Pe′CO2, SpO2, Tcore, Cdyn, MAP, CVP, PA, PAOP, PPV, PVI and PI were recorded followed by CO. All hemodynamic data were collected at end-expiration. One researcher was assigned to perform the PLRM, while the others recorded data from specific monitors and were blinded to the measurements performed by others. During all stages, FR was defined as > 15% increase in CO and nonresponsiveness was ≤ 15% change in CO (
Dynamic changes in arterial waveform derived variables and fluid responsiveness in mechanically ventilated patients: a systematic review of the literature.
Rocuronium infusion was discontinued after the final data were obtained, the jugular and arterial catheters were removed and recovery was initiated. Upon extubation, the dogs were transferred to individual cages and their cardiopulmonary variables and catheter sites were monitored every 30 minutes for the first 3 hours, after that hourly monitoring for the next 8 hours, followed by every 4 hours for a total of 72 hours. Post-procedure analgesia was administered as needed based on pain assessment using the Glasgow Composite Pain Scale short form (
) and evaluation of HR, fR and noninvasive blood pressure measurements periodically. Methadone (0.3 mg kg–1, Methadone Hydrochloride Injection; Akorn, IL, USA) was administered IV as a rescue analgesic. All dogs were adopted into private homes 3 weeks after the study ended.
Statistical analysis
The normality of each physiological variable at each major time point for all stages was assessed using Shapiro–Wilk and Anderson–Darling tests. Data was represented as mean ± standard deviation (SD) for all normally distributed physiological variables. A one-way analysis of variance for repeated measures was used for comparing differences across variables among the three data acquisition times within each stage and between the four experimental stages. A post hoc Tukey adjustment was used when multiple pairwise comparisons were performed. The Greenhouse and Geisser corrections were applied to the analyses for cases where lack of sphericity was observed. This was followed by a Student t test and Wilcoxon signed-rank test for paired sample analysis. For all analyses, values of p < 0.05 were considered significant. All analyses were conducted using SAS Version 9.4 (SAS Institute Inc., NC, USA).
Results
All dogs successfully completed the experiment and recovered without complications. There were no missing data reported. All dogs were administered one dose of methadone immediately after the study and two dogs were administered another dose approximately 10 hours after extubation. The mean ± SD time from anesthetic induction to extubation was 367 ± 13 minutes, with no significant differences in this duration among the six dogs (p = 0.34). Looking at cumulative assessment of readings noted every 5 minutes during anesthesia, Fe′Iso was 1.68 ± 0.06% and Tcore was 37.2 ± 0.3 °C. Blood volume withdrawn during stage 2 was 233.5 ± 3.1 mL. SpO2 values were not different among stages (p = 0.23) or among the PLRM time points (p = 0.49; Table 1). The PI was significantly lower in stages 2–4 than in stage 1 (p < 0.001), but it was higher in stages 3 and 4 than in stage 2 (p = 0.014). The Pe′CO2 decreased in stage 2 from stage 1 (p = 0.027), but was not different in stages 3 and 4 (p = 0.003). There was no change in Cdyn throughout the experiment and Cdyn was unaffected by PLRM (p = 0.66).
Table 1Cardiopulmonary variables recorded in six healthy, mechanically ventilated, isoflurane-anesthetized dogs undergoing four stages in a sequential order: stage 1: baseline; stage 2: 27 mL kg–1 withdrawal of circulating blood volume; stage 3: autologous blood transfusion; stage 4: infusion of 6% hydroxyethyl starch 130/0.4 in 9% sodium chloride (20 mL kg–1). Data were collected immediately before application of modified passive leg raise (PLRM) maneuver (Pre-PLRM), after 5 minutes of PLRM (PLRM) and 5 minutes after the abdomen and limbs were returned to horizontal position (Post-PLRM). Data are presented as mean ± standard deviation.
∗Significant difference from stage 1 at the same time point (p < 0.05). †Significant difference from stage 2 at the same time point (p < 0.05). ‡Significant difference from stage 3 at the same time point (p < 0.05). §Significant difference from Pre-PLRM within the same stage (p < 0.05). ¶Significant difference from PLRM within the same stage (p < 0.05).
A sinus, regular cardiac rhythm was noted in all dogs during the data collection. In stage 2, before PLRM, MAP was significantly decreased by 39% of stage 1 but was increased during PLRM (Table 1). In stages 3 and 4, MAP was not different from stage 1 at all time points of PLRM. In stages 2–4, HR was increased above stage 1 at all time points but in stages 3 and 4, HR was lower than stage 2 before application of PLRM (p < 0.001; Table 1). In stage 2, HR was lowered by 12% by PLRM (p = 0.006). CVP and PAOP were significantly higher in stages 1, 3 and 4 than in stage 2 before application of PLRM (Table 1). During stage 2, PLRM resulted in increases in CVP (p = 0.028) and PAOP (p = 0.043) to values similar to stage 1. After removal of PLRM, CVP and PAOP in stage 2 decreased to values similar to before PLRM, but were significantly different from stage 1 at the same time point. In stage 2, blood loss resulted in increased PPV and PVI, with decreased CO (p < 0.001; Table 1). During stage 2 in all dogs, performing PLRM significantly increased CO by about 28% (p < 0.001). Hence, by the definition of FR and nonresponsiveness, dogs were considered as fluid responders in stage 2 but were fluid nonresponders in stages 1, 3 and 4. In response to PLRM maneuver, significant decrease (p < 0.001) in PPV (approximately 32%) and PVI (approximately 44%) was observed in stage 2. However, these values were not affected when PLRM was performed during stages 1, 3 and 4. Effects of PLRM on CO, PPV, PVI, CVP and PAOP were short-lived and were reversed when PLRM was removed.
Significant decreases in PCV, TP, arterial pH and PaCO2 occurred in stage 2 after hemorrhage (p < 0.001; Table 2). These measurements subsequently improved in stages 3 and 4. Conversely, lactate concentrations significantly increased in stage 2 but decreased with autologous blood transfusion and HES (p < 0.001).
Table 2Hematologic variables in six healthy, mechanically ventilated, isoflurane-anesthetized dogs, recorded once during each of four stages. Stage 1: baseline; stage 2: 27 mL kg–1 withdrawal of circulating blood volume; stage 3; autologous blood transfusion; stage 4: infusion of 6% hydroxyethyl starch 130/0.4 in 9% sodium chloride (20 mL kg–1). Data are presented as mean ± standard deviation.
Significant difference from stage 1 for the same variable (p < 0.05). †Significant difference from stage 2 for the same variable (p < 0.05). ‡Significant difference from stage 3 for the same variable (p < 0.05).
Significant difference from stage 1 for the same variable (p < 0.05). †Significant difference from stage 2 for the same variable (p < 0.05). ‡Significant difference from stage 3 for the same variable (p < 0.05).
Significant difference from stage 1 for the same variable (p < 0.05). †Significant difference from stage 2 for the same variable (p < 0.05). ‡Significant difference from stage 3 for the same variable (p < 0.05).
Significant difference from stage 1 for the same variable (p < 0.05). †Significant difference from stage 2 for the same variable (p < 0.05). ‡Significant difference from stage 3 for the same variable (p < 0.05).
Significant difference from stage 1 for the same variable (p < 0.05). †Significant difference from stage 2 for the same variable (p < 0.05). ‡Significant difference from stage 3 for the same variable (p < 0.05).
Significant difference from stage 1 for the same variable (p < 0.05). †Significant difference from stage 2 for the same variable (p < 0.05). ‡Significant difference from stage 3 for the same variable (p < 0.05).
41 ± 3† (5.4 ± 0.4)†
44 ± 2† (5.8 ± 0.3)†
PaO2 (mmHg) (kPa)
413 ± 36 (55.0 ± 4.8)
400 ± 22 (53.3 ± 2.9)
384 ± 34 (51.2 ± 4.5)
387 ± 39 (51.6 ± 5.2)
PaCO2, arterial partial pressure of carbon dioxide; PaO2, arterial partial pressure of oxygen; PCV, packed cell volume; TP, total protein.
∗ Significant difference from stage 1 for the same variable (p < 0.05). †Significant difference from stage 2 for the same variable (p < 0.05). ‡Significant difference from stage 3 for the same variable (p < 0.05).
In healthy, mechanically ventilated, isoflurane-anesthetized Beagle dogs, PLRM accurately evaluated FR after loss of 27 mL kg–1 circulating blood volume by increasing CO by 28%. During normovolemia and hypervolemia, there was minimal difference in CO during PLRM suggesting nonresponsiveness. The potential reasons for an animal to be a ‘fluid nonresponder’ include vasodilation where volume fails to increase venous pressure, or collateral increase in CVP or mean systemic filling pressure, or positioning on the plateau portion of Frank–Starling cardiac curve causing preload unresponsiveness. The latter was the most probable reason during stages 1, 3 and 4. However, not all euvolemic animals are fluid nonresponders. When a crystalloid or colloid bolus was administered to euvolemic dogs in a state of relative hypovolemia caused by vasodilatory effects and reduced cardiac function of anesthetics, CO significantly increased (
Arterial blood pressure as a predictor of the response to fluid administration in euvolemic nonhypotensive or hypotensive isoflurane-anesthetized dogs.
). Dynamic variables such as noninvasive PVI and minimally invasive PPV responded to the hemodynamic variations during PLRM in stage 2, but not during stages 1, 3 and 4. Performing the PLRM maneuver decreased PVI and PPV by 44% and 32%, respectively. A significant decrease in Pe′CO2 and PaCO2 during stage 2 was also recorded that probably resulted from decreased CO and reduced perfusion. However, these values did not improve with PLRM, contradicting results from human studies that reported Pe′CO2 variation ≥ 2 mmHg (
) during passive leg raise was associated with FR.
The crucial role of sympathetic autonomic nervous system during hemorrhagic shock is well recognized, where the baroreceptor activity decreases when blood pressure falls, producing a reflex-mediated increase in HR and peripheral resistance to compensate for hypotension and hypoxia (
). This physiological phenomenon occurred in the present study, where MAP decreased during hemorrhage, thus triggering a compensatory rise in HR. The PLRM-induced ‘self-transfusion’ mimicked a fluid challenge, and elevated MAP and simultaneously lowered HR. The PLRM effects on CO, PVI, PPV, HR and MAP were transient and only lasted during the maneuver, which were then reversed during horizontal recumbency. Among hematological variables, although reduction in PCV and TP was noted after blood loss, differences in PCV were not significant as the dogs transitioned through different volume stages. In dogs, this could be attributed to splenic contraction induced by the physiologic stress from acute hemorrhage that prompted mobilization of abdominal organ blood reserves into splanchnic circulation (
). Also, since blood withdrawal and reinfusion occurred over a short duration, changes in PCV were not truly reflected. Conversely, peripheral lactate concentration appeared to be a sensitive indicator of hypoperfusion in these dogs.
In humans, the passive leg raise test is standardized and if precise steps are not followed, accuracy of estimating FR can be impacted (
). Initially, the patient is placed in the 45° angled semi-recumbent position and is then transitioned into a leg raise position by moving the bed only, and not the patient. This prevents pain-induced sympathetic stimulation arising from manipulating the hip joint which may affect validity of this test (
). In animals, raising only the pelvic limbs may not be as effective in recruiting significant blood volume to mimic the effect of a fluid challenge based on the assumption that the blood volume in human limbs and pelvic limbs of quadrupeds is different. For the present study, the modified approach to passive leg raise was used as previously described in pigs where the pelvic limbs and caudal abdomen were elevated relative to the horizontal plane of the table (
Use of a modified passive leg-raising maneuver to predict fluid responsiveness during experimental induction and correction of hypovolemia in healthy isoflurane-anesthetized pigs.
). Selection of a 30 ° inclination in the present study provided a 28% increase in CO during blood loss. Considering the circulatory effects of passive leg raise are transient in humans (
), data were obtained 5 minutes after initiating PLRM and 5 minutes after horizontal recumbency in order to capture a complete hemodynamic response of PLRM. The inclination angle and PLRM time points were chosen based on unpublished preliminary data in dogs and the duration of maneuver response acquired from previous pig study (
Use of a modified passive leg-raising maneuver to predict fluid responsiveness during experimental induction and correction of hypovolemia in healthy isoflurane-anesthetized pigs.
The blood pressure may not be a true reflection of CO in animals with low vascular tone or systemic vascular resistance, even in presence of FR. It has been determined that the accuracy of the passive leg raise test is poor in humans when the relevance is assessed by changes in blood pressure alone (
). Given the transient effects of this test, direct evaluation of CO is recommended to detect rapid variations in hemodynamics. Measuring CO is not practical in clinical patients owing to the risks associated with invasiveness, required expertise, equipment and cost of instrumentation. Hence, minimally or noninvasive techniques, such as pulse contour analysis, esophageal doppler, bioreactance and echocardiography, have been investigated for measuring CO with passive leg raise (
). The dogs in the present study were research dogs and PA thermodilution measurement of CO could be used as a reference method. No published study was found that describes use of the PLRM maneuver in dogs. However, future research in dogs using feasible, reliable and user-friendly CO methods to study the PLRM is imperative.
The relationship between cardiac filling variables CVP and PAOP and FR is considered poor in clinical settings, probably because cardiac end-diastolic volume is affected by not just cardiac filling pressure but also by cardiac chamber compliance, venous tone and intrathoracic pressures (
). In stage 2 of the present study, CVP and PAOP showed reliable trends, that is lowering with hemorrhage, increasing with PLRM, and returning to before PLRM values during horizontal recumbency. These trends were similar during PLRM maneuver in hypovolemic pigs (
Use of a modified passive leg-raising maneuver to predict fluid responsiveness during experimental induction and correction of hypovolemia in healthy isoflurane-anesthetized pigs.
Passive leg raising-induced changes in pulse pressure variation to assess fluid responsiveness in mechanically ventilated patients: a multicentre prospective observational study.
). Following the modified maneuver in pigs and Beagle dogs, PVI and PPV closely tracked trends in CO. Moreover, the sensitivity of PPV and PVI was possibly increased in the present study because: 1) there was no change in the dynamic compliance of the respiratory system with PLRM; 2) PI was > 1% throughout the experiment yielding reliable PVI readings; and 3) there was no spontaneous breathing effort.
The present study presented several limitations. The sample size was small. The sequence of the experimental stages was not randomized because the fixed order of transition from normovolemia to hypovolemia back to normovolemia and eventually to hypervolemia was critical to evaluate whether the PLRM could evaluate FR. It was necessary to avoid the crossover effect of hypervolemia if induced prior to hypovolemia. The data were not collected beyond 5 minutes during PLRM or after limbs were returned to horizontal position; consequently, the total duration of circulatory response for PLRM and time required to normalize the hemodynamics after the limbs were lowered cannot be predicted. The study population consisted of healthy dogs placed in dorsal recumbency. This restricts the findings of this study from being extrapolated to clinical scenarios, for example, breeds with other limb conformations, ongoing surgical procedures, critically ill animals, relative hypovolemia, vasodilatory shock, abdominal hypertension, brain injury and peripheral vascular disease. CO is influenced by adrenergic stimulation associated with pain, discomfort, anxiety and awareness, confounding assessment of the PLRM maneuver. Therefore, cautious interpretation is recommended when PLRM is performed in canine patients administered vasopressors, sedatives or analgesics, as they may interfere with hemodynamics and alter effectiveness of this maneuver. In addition, testing PLRM during a surgical or diagnostic procedure may not be a practical approach for diagnosing FR.
Conclusions
During hypovolemia, the PLRM maneuver with a 30° angle in healthy, anesthetized dogs identified FR by increasing CO by 28%. A simultaneous decrease in PPV and PVI and increase in CVP and PAOP indicated a possible future role of these variables in monitoring a PLRM response. During normovolemia and hypervolemia, PLRM correctly detected nonresponsiveness confirmed by insignificant changes in CO, PPV, PVI, CVP and PAOP. These findings suggest that the PLRM can be useful for evaluating FR in healthy dogs with absolute hypovolemia. Future studies validating the predicting potential for FR using PLRM in clinically ill canine patients is required.
Authors’ contributions
VVP: study design and execution of the study, animal care and management, data collection, statistical analysis, data interpretation, preparation of manuscript, artwork. NHG and GM: data collection, data interpretation, preparation of manuscript. SS: statistical analysis, data interpretation, preparation of manuscript. All authors approved the final version of the manuscript.
Conflict of interest statement
Authors declare no conflict of interest.
Acknowledgements
The authors thank Dr. Andre C Shih and Dr. Fernando Garcia-Pereira for contributing to early study planning, Dr. Hyeon Jeong for helping with data collection and Jordi Mauragis for assistance with creating graphical artwork. This study was funded by Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University (no. 178592).
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Passive leg raising-induced changes in pulse pressure variation to assess fluid responsiveness in mechanically ventilated patients: a multicentre prospective observational study.
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Arterial blood pressure as a predictor of the response to fluid administration in euvolemic nonhypotensive or hypotensive isoflurane-anesthetized dogs.
Use of a modified passive leg-raising maneuver to predict fluid responsiveness during experimental induction and correction of hypovolemia in healthy isoflurane-anesthetized pigs.
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