Anesthetizing wildlife and zoo animals in field settings is associated with many inherent challenges. For example, preanesthetic health screening (eg, physical examination and routine hematologic analysis) is rarely practical,1 and hemodynamic and respiratory monitoring is typically limited.2 Nevertheless, anesthetic monitoring is desirable because administration of anesthetic drugs frequently results in cardiopulmonary instability.3 An ideal monitoring method for field settings would be noninvasive and cost-effective and involve equipment that is durable, portable, and easy to use.4 The lack of practical monitoring methods and limitations inherent in monitoring pose a substantial health threat to animals that must be anesthetized.
The MAP is related to cardiac output (ie, heart rate × stroke volume) and systemic vascular resistance. Ideally, MAP should be monitored in any anesthetized patient as an indicator of perfusion to tissues. However, because of the aforementioned limitations, monitoring of MAP is not always performed on wildlife and zoo animals in field settings. In contrast, pulse oximetry (determination of Spo2) is a simple, noninvasive method performed with portable monitoring equipment that can be used to measure hemoglobin oxygen saturation and has the ability to provide information pertaining to the cardiovascular status of an animal. For example, the photoplethysmogram is a waveform displayed on most pulse oximeters. It depicts the pulsatile component of an infrared signal that provides an indirect measure of blood volume or pulsatile strength at the target tissue.5 Two physiologic indices (ie, PI and PVI) can be derived from the photoplethysmographic waveform. The PI is an indicator of peripheral blood flow and derived from the relationship between pulsatile and nonpulsatile blood flow.6 The PI is related to the plethysmographic signal7 and is influenced by stroke volume and blood flow.8 Specifically, a constant amount of infrared light is absorbed by the skin, other tissues, and nonpulsatile arterial blood, whereas a variable amount of infrared light is absorbed by pulsating arterial blood. The PI is calculated by comparing the pulsatile infrared signal to the nonpulsatile infrared signal. It is expressed as a percentage, as determined by use of the following equation7: PI = (AC/DC) × 100, where AC is the pulsatile infrared signal, and DC in the nonpulsatile infrared signal.
The PVI is calculated on the basis of changes in PI induced by alterations in blood flow at the site of probe placement during the respiratory cycle, as determined by use of the following equation7: PVI = ([PImax – PImin]/PImax) × 100, where PImax is the maximum PI, and PImin is the minimum PI. During spontaneous inspiration, intrathoracic pressure decreases, which causes an increase in return of venous blood to the heart. This augmented blood flow to the right atrium increases stroke volume; thus, there is an increase in cardiac output and concomitant increases in PI and PVI. In contrast, during positive-pressure ventilation, the increase in intrathoracic pressure impedes return of venous blood to the heart, which causes a decrease in stroke volume. These respiratory-induced variations in return of venous blood to the heart and stroke volume also affect PI and PVI. In humans, PVI is useful for evaluating certain homeostatic conditions (eg, hypovolemia) and is considered a noninvasively measured variable that can be effectively used for monitoring goal-directed fluid administration.8,9
Clinical benefits of PVI monitoring have been reported in the veterinary literaturea,b; however, to the authors' knowledge, no study has been conducted to investigate the relationship between MAP and PI or PVI in dogs. Nonetheless, if there were a relationship between PI or PVI and MAP, then PI or PVI might be useful as surrogates for blood pressure measurement and could play an important role in anesthetic monitoring of zoo and wildlife animals. Therefore, the objective of the study reported here was to evaluate whether PI and PVI were correlated with MAP for 3 blood pressure conditions (hypotensive, normotensive, and hypertensive). It was hypothesized that PI and PVI values would be correlated with changes in MAP.
Materials and Methods
Animals
Eight (4 males and 4 females) healthy adult (4 to 17 years old) tigers (Panthera tigris) were enrolled in the study. The animals were part of a zoological sanctuary collection. The sanctuary's management provided consent for use of the tigers, and the study was approved by the Institutional Animal Care and Use Committee of the University of Tennessee (protocol No. 2415-0216).
Study design
Each tiger was anesthetized once. Food and water were withheld from tigers for 12 hours prior to anesthesia. The morning of anesthesia, tigers were transported unsedated to our veterinary teaching hospital. At the time of arrival, tigers were injected IM with medetomidinec (target dose, 0.025 mg/kg) and midazolamd (target dose, 0.1 mg/kg) on the basis of estimated body weight. After the tigers were sedated, ketamine hydrochloridee (target dose, 2.5 mg/kg) was administered IM. Once each tiger was completely immobilized, it was removed from the transport unit, positioned in lateral recumbency on a padded gurney, and weighed. Isofluranef in oxygen was then administered via face mask until endotracheal intubation was possible. After an endotracheal tube was inserted, anesthesia was maintained with isoflurane (Petiso, 1.2% to 2.5%) in oxygen (2 L/min) by use of a rebreathing anesthesia circuit.g
Physical examination was performed, and a 16-gauge, 4.5-cm catheterh was inserted in a medial saphenous vein. A venous blood sample was collected from the catheter and submitted for a CBC and biochemical analysis, and the catheter subsequently was used for fluid and drug administration. Simultaneously, tigers were instrumented for anesthetic monitoring,i which included assessment of end-tidal partial pressure of carbon dioxide, Petiso, esophageal temperature, and results of ECG. A pulse oximeterj probe was placed on the tongue for evaluation of Spo2, PI, and PVI. A 20-gauge, 2.5-cm catheterh was inserted in a dorsal pedal artery and used for collection of arterial blood samples and direct measurement of blood pressure with a blood pressure transducer.k Tigers were mechanically ventilatedg (tidal volume, 10 to 20 mL/kg; peak inspiratory pressure, < 20 cm H2O) to maintain the end-tidal partial pressure of carbon dioxide between 35 and 45 mm Hg. Vital parameters were continuously monitored and recorded every 5 minutes throughout the anesthetic period. An arterial blood sample (1 mL) was collected at the time of catheter placement into the dorsal pedal artery (baseline sample) and immediately analyzedl to determine Pao2, Paco2, pH, and base excess and HCO3−−, BUN, and electrolyte concentrations. In addition, samples were analyzed by use of a cageside analyzerm to determine blood lactate concentration.
Approximately 20 minutes after anesthesia was induced and after each tiger was fully instrumented and at a surgical plane of anesthesia, blood pressure was maintained constant for a minimum of 20 minutes at each of 3 target MAP conditions, which were defined as hypotensive (MAP = 50 ± 5 mm Hg), normotensive (MAP = 70 ± 5 mm Hg), and hypertensive (MAP = 90 ± 5 mm Hg). Order of the targeted blood pressures was based on the starting blood pressure after achieving a surgical plane of anesthesia. Subsequent target blood pressure conditions were achieved and maintained via adjustment of Petiso, administration of dobutamined (1 to 10 μg/kg/min, IV) by use of a fluid pump,n or both. Monitoring of vital parameters continued throughout each target blood pressure condition. An arterial blood sample (1 mL) was collected 15 minutes after the start of each blood pressure condition, and it was analyzed as described for the baseline sample. An isotonic electrolyte solutiono was administered throughout the anesthetic episode at a rate of 3 mL/kg/h.
After data collection was completed, anesthesia was terminated by discontinuation of isoflurane. All catheters were removed, tigers were returned to the transport enclosure, and atipamezolep (0.25 mg/kg, IM) was administered. Extubation was performed when the tigers were able to swallow and had resumed spontaneous respiration. Tigers were closely observed until they were capable of maintaining sternal recumbency and were responsive to external stimuli, at which time they were transported back to their housing facility at the sanctuary.
Statistical analysis
A 1-way repeated-measures ANOVAq was used to evaluate effects of the 3 blood pressure conditions (normotensive, hypotensive, and hypertensive) on PI, PVI, Spo2, Pao2, Paco2, pH, base excess, heart rate, and concentrations of K+, lactate, HCO3−−, and BUN. The same statistical method was used to compare values for the variables during the 3 blood pressure conditions with their respective baseline value. Tiger and blood pressure condition were included as class variables in the model; tiger was treated as a random factor, and blood pressure condition was considered as a within-subject factor. The assumption that the residuals from the model would have a normal distribution was tested by use of the Shapiro-Wilk test, and the homogeneity of variance assumption was tested by use of the Levene test. Values for the dependent variable PI were transformed (natural logarithm) to normalize the residuals from the model. In addition, dependent variables Paco2, BUN concentration, and K+ concentration were rank transformed because the residuals were not consistent with normality. The Fisher least significant difference mean separation test was used as a post hoc analysis to detect differences between baseline values and blood pressure conditions. The Pearson correlation coefficient was used to assess the correlation of PI and PVI with MAP. An individual growth model was used to predict MAP by use of PI or PVI as an independent variable, with tiger as a random factor. The MAP values were divided into 2 categories: hypotensive and nonhypotensive, with 60 mm Hg as the cutoff point. An ROC curve was generated to illustrate the ability to diagnose hypotension by use of PVI as the predictor, and the area under the curve was calculated. Finally, PVI values were divided into 2 categories: PVI < 18% and PVI > 18%. A 2 × 2 contingency table was generated by use of the categories defined for MAP and PVI, and the OR (with 95% confidence interval) for the occurrence of hypotension between the 2 PVI categories was calculated. Data were reported as mean ± SD. For all tests, significance was set at P < 0.05.
Results
Animals were considered healthy on the basis of results of a physical examination and laboratory analyses. Actual body weight ranged from 113 to 159 kg; therefore, administered drug doses were 0.023 to 0.026 mg/kg for medetomidine, 0.11 to 0.13 mg/kg for midazolam, and 2.2 to 2.6 mg/kg for ketamine. Anesthetic induction, tracheal intubation, and placement of venous and arterial catheters were performed without clinical problems. None of the tigers had abnormalities on the ECG throughout the anesthetic episode. Dobutamine infusion (rate, 1 to 5 μg/kg/min for 5 to 35 minutes) was required for 5 tigers to achieve normotensive or hypertensive conditions. All tigers were anesthetized for approximately 80 minutes, and all tigers recovered without complications.
Mean ± SD values of PI were 1.82 ± 2.38%, 1.17 ± 0.77%, and 1.71 ± 1.51% for hypotensive, normotensive, and hypertensive conditions, respectively; these values did not differ significantly. Mean PVI values were 16.00 ± 5.07%, 10.44 ± 3.55%, and 8.17 ± 3.49% for hypotensive normotensive, and hypertensive conditions, respectively (Table 1). The PVI for the hypotensive condition was significantly greater than the PVI for the normotensive (P = 0.005) and hypertensive (P < 0.001) conditions; however, the PVI values did not differ significantly between the normotensive and hypertensive conditions. There was a significant negative correlation (r = −0.657; P < 0.001) between PVI and MAP (Figure 1). However, no correlation was detected between PI and MAP or between PI and PVI.
Mean ± SD values for MAP, PI, and PVI for 3 blood pressure conditions in 8 anesthetized tigers (Panthera tigris).
Variable | Hypotensive | Normotensive | Hypertensive |
---|---|---|---|
MAP (mm Hg) | 51 ± 3.14 | 70 ± 4.26 | 90 ± 3.62 |
PI (%) | 1.82 ± 2.38 | 1.17 ± 0.77 | 1.71 ± 1.51 |
PVI (%) | 16.00 ± 5.07a | 10.44 ± 3.55b | 8.17 ± 3.49b |
The 3 blood pressure conditions were hypotensive (mean ± SD; MAP = 50 ± 5 mm Hg), normotensive (MAP = 70 ± 5 mm Hg), and hypertensive (MAP = 90 ± 5 mm Hg).
Values with different superscript letters differ significantly (P < 0.05).
When MAP (n = 98 observations) was categorized on the basis of an MAP of 60 mm Hg as the cutoff point for hypotension, 62 (63.3%) and 36 (36.7%) observations were included in the nonhypotensive and hypotensive categories, respectively. Area under the ROC curve was 0.85. Analysis of the 2 × 2 contingency table created with categorized MAP and PVI values revealed that for PVI ≥ 18%, 15 of 16 (93.8%) observations were hypotensive and 1 (6.2%) was nonhypotensive. For PVI < 18%, 21 of 82 (25.6%) observations were hypotensive and 61 (74.4%) were nonhypotensive. The OR for the occurrence of hypotension for PVI ≥ 18% (compared with occurrence of hypotension for PVI < 18%) was 43.6 (95% confidence interval, 5.4 to 350.2).
Mean ± SD heart rate was 75 ± 27 beats/min, 72 ± 20 beats/min, and 67 ± 14 beats/min for hypotensive, normotensive, and hypertensive conditions, respectively; there was no significant difference in heart rate among blood pressure conditions. No significant difference was detected in blood pH, Paco2, or base excess or K+, lactate, HCO3−−, or BUN concentrations among blood pressure conditions or when values for blood pressure conditions were compared with baseline values (Table 2). Mean baseline Pao2 (291 ± 160 mm Hg) was significantly (P < 0.001) lower than Pao2 for the hypotensive (496 ± 67 mm Hg), normotensive (525 ± 48 mm Hg), and hypertensive (536 ± 36 mm Hg) conditions. However, there was no significant difference in Pao2 among the blood pressure conditions.
Mean ± SD values of blood gas and biochemical variables for measurements obtained immediately after anesthetic induction and insertion of a catheter in a dorsal pedal artery (baseline) and at each of 3 blood pressure conditions in 8 anesthetized tigers.
Variable | Baseline | Hypotensive | Normotensive | Hypertensive |
---|---|---|---|---|
pH | 7.27 ± 0.07 | 7.28 ± 0.05 | 7.26 ± 0.06 | 7.28 ± 0.07 |
K+ (mmol/L) | 3.83 ± 0.41 | 3.34 ± 0.87 | 3.66 ± 0.35 | 3.79 ± 0.28 |
Lactate (mmol/L) | 0.76 ± 0.39 | 0.73 ± 0.16 | 0.70 ± 0.13 | 0.77 ± 0.10 |
Pao2 (mm Hg) | 290.56 ± 160.43a | 495.73 ± 66.97b | 524.84 ± 47.96b | 535.85 ± 36.14b |
Paco2 (mm Hg) | 38.96 ± 13.17 | 40.78 ± 5.20 | 44.14 ± 5.77 | 40.90 ± 6.59 |
HCO3−− (mmol/L) | 19.50 ± 2.39 | 19.30 ± 2.26 | 20.09 ± 2.08 | 19.08 ± 2.28 |
Base excess (mEq/L) | −6.56 ± 2.27 | −6.51 ± 2.63 | −6.23 ± 2.52 | −6.75 ± 2.52 |
BUN (mg/dL) | 32.57 ± 14.25 | 33.40 ± 11.15 | 37.00 ± 16.09 | 35.20 ± 19.18 |
See Table 1 for key.
Discussion
Results of the study reported here indicated that PVI and MAP were significantly correlated, and PVI values for the hypotensive condition were significantly higher, compared with PVI values for the normotensive and hypertensive conditions. Furthermore, for PVI ≥ 18%, the odds for hypotension were much greater than the odds for normotension or hypertension.
Traditional methods used to monitor the cardiovascular status of patients undergoing general anesthesia include assessment of results of ECG and blood pressure measurements. Monitoring of respiratory-induced changes of some hemodynamic variables has been investigated, and they are collectively known as dynamic indices.10 These methods primarily include assessment of variations in pulse pressure, systolic pressure, or stroke volume in association with changes in intrathoracic pressure during respiration, and they are used to evaluate a patient's circulating volume (eg, hypovolemia) and to guide therapeutic interventions (eg, administration of fluids).5,10,11 Despite high efficacy of such advanced monitoring methods, clinical application, particularly in field settings, has been limited. For example, many dynamic indices are derived from analysis of the arterial waveform, which therefore requires placement of an arterial catheter as well as access to a monitoring unit with appropriate software. On the other hand, PVI is a noninvasively measured variable obtained from variations in the photoplethysmograph waveform, and its efficacy for use in the management of some clinical conditions has been confirmed. For example, when PVI was used in goal-directed fluid management, the volume of fluid administered intraoperatively was less than for the control group (2,394 vs 2,918 mL, respectively), and the number of patients with postoperative lactate concentrations > 1.7 mmol/L was less than for the control group (2 vs 28, respectively).12 In another study13 of humans, preanesthetic PVI values were strongly correlated with the incidence of hypotension after induction of anesthesia.
Hypotension is a common condition in animals undergoing general anesthesia because most anesthetic drugs can induce hypotension, particularly when administered to dehydrated, sick, or debilitated animals. Anesthetic-related complications that may result in hypotension include decreases in return of venous blood to the heart, cardiac filling pressures, and cardiac output.14 Anesthetic-induced hypotension is commonly associated with relative hypovolemia (vasodilatation) attributable to the vasodilatative effects of anesthetic drugs (particularly inhalation anesthetics) and suppression of compensatory homeostatic mechanisms. Hypotension during anesthesia has been associated with a higher mortality rate in dogs and cats,15–17 which further indicates the importance of monitoring and prompt treatment of this condition. In the present study, hypotension was induced by increasing the concentration of isoflurane, and blood pressure was increased by administration of dobutamine. Isoflurane reduces systemic vascular resistance and results in relative hypovolemia, which in turn decreases the return of venous blood to the heart as well as stroke volume and, therefore, MAP18 and, in theory, PI and PVI. In contrast, the use of dobutamine enhances cardiac contractility (positive inotropy) and leads to an increase in stroke volume19 with subsequent alterations in MAP, PI, and PVI.
Results of the present study indicated a significant correlation between PVI and MAP in anesthetized tigers, but they also indicated a significant increase in PVI values during hypotension (defined as an MAP of 50 ± 5 mm Hg). Furthermore, PVI was useful for discriminating hypotensive from nonhypotensive blood pressure conditions, as indicated by the ROC curve. In a study20 of dogs with induced hemorrhage, the mean ± SD PVI at an MAP of 45 mm Hg was 18 ± 4%, which approximates the results reported for the present study (PVI of 16 ± 5% at an MAP of 50 ± 5 mm Hg). The findings of the present study are also consistent with results of other studies20–22,r that indicated an increase in other dynamic indices in dogs with induced hypotension.
For the present study, a PVI of 18% was used as the cutoff point to evaluate the ability of PVI to predict hypotension. For humans, PVI values > 10% to 14% (adults) and > 13% to 18% (pediatric patients) have been used as thresholds for discriminating between patients who will respond to fluid administration and patients who are nonresponders.23 Unfortunately, such thresholds for PVI have not been established for veterinary species, and extrapolation from human data may be misleading, primarily because of presumed differences in the compliance of the chest wall and lungs, as has been documented in dogs.11,24,25 Greater compliance of the chest wall would presumably lead to a decrease in intrathoracic pressure and smaller increases in pleural pressure during mechanical ventilation and, therefore, would have a smaller effect on PVI, compared with effects in humans.25 Thus, establishing unique threshold values for each species would appear to be necessary. Nevertheless, PVI values of the present study that were correlated with hypotension were similar to those that have anecdotally been used to determine the likelihood of responsiveness to fluid administration in dogs. By use of a PVI value of 18% as the cutoff point, results of the present study indicated that for PVI ≥ 18%, hypotension (MAP < 60 mm Hg) can be presumed and thus various treatment interventions, which are based on the probable cause of the hypotension, can be instituted.
The PI values for the study reported here did not differ significantly among the 3 blood pressure conditions and were not correlated with PVI or MAP. The PI is a numeric representation of peripheral blood flow at the site of probe placement and may substantially change over the course of a respiratory cycle. In the present study, PI values were recorded every 5 minutes and during different parts of the respiratory cycle, and this method of data collection limits the value of PI for representing overall status of blood flow. Remarkably, the lack of a correlation between PI and PVI for the tigers of the present study is similar to results of a report7 for human patients in which there was a lack of correlation between PI and PVI.
In the present study, Pao2 values during anesthesia were greater than baseline values regardless of blood pressure condition, which was an expected finding because of the administration of high concentrations of inspired oxygen (> 90%) after endotracheal intubation. However, electrolyte concentrations and the measured indicators of metabolic status (pH, base excess, and lactate concentration) did not change over the course of the anesthetic episode when compared with the baseline values. During hypotension, an increase in blood lactate concentration and a decrease in base excess and pH can be expected as a result of anaerobic cellular metabolism consequent to impaired tissue perfusion. However, the lack of changes in these variables in the study reported here may have been attributable to the fact the hypotension was mild (MAP, approx 50 mm Hg) and of relatively short duration (approx 20 minutes).
Use of mechanical ventilation is recommended for control of respiratory-induced variables when monitoring dynamic indices. This would appear to limit the applicability of the results of the present study because mechanical ventilation is rarely used in field settings. Nevertheless, studies26,27 of humans have indicated that PVI may also serve as a predictor of responsiveness to fluid administration in spontaneously breathing patients. In addition, the clinical efficacy of PVI for use in evaluating responsiveness to fluid administration in spontaneously breathing dogs has been reported,b and investigators of that study found a significant correlation between PVI and MAP. Nevertheless, until more studies are conducted to evaluate the efficacy of PVI in spontaneously breathing animals, controlling respiratory efforts via mechanical (or assisted manual) ventilation appears to be a more reliable approach for the use of PVI.
A limitation of the present study was the relatively narrow range of blood pressure conditions, particularly for the targeted hypertensive condition. Although MAP values > 90 ± 5 mm Hg are uncommon during balanced anesthesia, evaluating the efficacy of PVI at higher MAP values may reveal different results and is warranted. The use of dobutamine may also be considered a potential limitation because it may have altered results owing to its effect on cardiac output and, thus, PVI and PI. However, dobutamine was used only to achieve the normotensive or hypertensive conditions, and dobutamine was not administered during data collection for the hypotensive condition. Thus, results relevant to the hypotensive condition were not affected by dobutamine. The use of α2-adrenoceptor agonists may also be considered a limitation of the study because these drugs can alter blood flow distribution and thereby may have affected results for PI and PVI. The α2-adrenoceptor agonists induce changes in vascular resistance and cardiac output.28 Dexmedetomidine inhibits the expected changes in pulse pressure variation in response to controlled hemorrhage in dogs.21 Nevertheless, these agents are one of the essential components of anesthetic protocols in large felids. Finally, the tigers used in the study were healthy; therefore, these results may be applicable only to healthy animals undergoing general anesthesia for a moderate duration (approx 80 minutes).
In the present study, healthy tigers were anesthetized and mechanically ventilated. The PVI values were significantly correlated with the range of MAP values evaluated. A PVI ≥ 18% was significantly associated with odds of hypotension. Use of PVI can be considered an applicable adjunct monitoring method to provide an overall assessment of the homeostatic condition of an animal.
Acknowledgments
Supported by the Masimo Corp.
The authors declare that there were no conflicts of interest.
The authors thank Jessica Birdwell for technical assistance.
ABREVIATIONS
HCO3−− | Bicarbonate ion |
MAP | Mean arterial blood pressure |
Petiso | End-tidal partial pressure of isoflurane |
PI | Perfusion index |
PVI | Plethysmographic variability index |
ROC | Receiver operating characteristic |
Spo2 | Oxygen saturation measured by pulse oximetry |
Footnotes
Ricco C, Henao-Guerrero N, Shih A, et al. Pleth variability index derived from the radical-7 Masimo pulse oximeter as a non-invasive indicator of circulating volume changes in dogs (abstr). Vet Anaesth Analg 2013;40:8.
Paranjape V, Ko J, Weil A, et al. Relationship of perfusion index and plethysmographic variability index with various clinical factors in spontaneously breathing anesthetized dogs—a preliminary study (abstr). Vet Anaesth Analg 2014;41:A70.
Wildlife Pharmaceuticals, Fort Collins, Colo.
Hospira Inc, Lake Forest, Ill.
MWI Animal Health, Boise, Idaho.
Isoflo, Abbott Laboratories, North Chicago, Ill.
Narkomed 2B, North American Drager, Telford, Pa.
Surflo catheter, Terumo Medical Corp, Somerset, NJ.
Datex-Ohmeda modulus SE, Planar Systems Inc, Hillsboro, Ore.
Masimo Radical 7 pulse oximeter, provided by the Masimo Corp, Irvine, Calif.
Disposable pressure transducer system, Utah Medical Products Inc, Midvale, Utah.
pHOx Ultra, Nova Biomedical, Waltham, Mass.
Accutrend lactate analyzer, Roche, Manheim, Germany.
Heska Vet/IV infusion pump, Cuattro Veterinary USA, Loveland, Colo.
Plasmalyte-A, Abbott Laboratories, Abbott Park, Ill.
Pfizer Animal Health, Orion Corp, Espoo, Finland.
SAS, version 9.4, SAS Institute Inc, Cary, NC.
Ricco C, Henao-Guerrero N, Shih A, et al. Pulse pressure variation in a model of hemorrhagic shock in mechanically ventilated dogs (abstr). Vet Anaesth Analg 2013;40:9.
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