Admission lactate concentration has predictive value for death or severe complications within 30 days after admission in cattle with long-bone fractures

Caroline Constant AO Research Institute Davos, Davos, Switzerland
Department of Clinical Sciences, Université de Montréal, St-Hyacinthe, QC, Canada

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Emma Marchionatti Department of Clinical Sciences, Université de Montréal, St-Hyacinthe, QC, Canada
Clinic for Ruminants, Vetsuisse Faculty, University of Bern, Bern, Switzerland

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André Desrochers Department of Clinical Sciences, Université de Montréal, St-Hyacinthe, QC, Canada

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Marie Babkine Department of Clinical Sciences, Université de Montréal, St-Hyacinthe, QC, Canada

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Sylvain Nichols Department of Clinical Sciences, Université de Montréal, St-Hyacinthe, QC, Canada

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Abstract

OBJECTIVE

To determine the prognostic value of lactate concentration measurements at admission in cattle with long-bone fractures.

ANIMALS

43 cattle with long-bone fractures between July 2016 and Dec 2018.

PROCEDURES

In this prospective cohort study, lactate concentration was measured in systemic venous blood and locally in capillary blood sampled from the fractured and contralateral limbs of cattle and assessed for outcome prediction. The cutoff value was determined by maximizing the Youden index from receiver-operating characteristic curves. Multivariable logistic regression was employed to verify whether higher lactate concentrations compared with the cutoff value were an independent risk factor for poor outcomes at 30 days or 3 years after admission.

RESULTS

Poor outcome was associated with higher capillary lactate concentration in the fractured limb (P < .001) and greater difference with systemic blood (P = .005). A cutoff value of lactate difference ≥ 2.4 mmol/L (sensitivity = 0.80; specificity = 0.965) between capillary lactate in the fractured limb and systemic blood was the best predictor of death ≤ 30 days after admission (P < .001). Multivariable analysis revealed that this cutoff value was an independent risk factor for 30-day and 3-year outcomes (P < .001).

CLINICAL RELEVANCE

Admission blood lactate concentration difference ≥ 2.4 mmol/L between the fractured limb and systemic blood was a robust and independent predictor of outcome for cattle of the present report. Lactate metabolism is locally impaired in fractured limbs of nonsurviving or at higher complication risk cattle, which may help identify patients at high risk for poor outcomes.

Abstract

OBJECTIVE

To determine the prognostic value of lactate concentration measurements at admission in cattle with long-bone fractures.

ANIMALS

43 cattle with long-bone fractures between July 2016 and Dec 2018.

PROCEDURES

In this prospective cohort study, lactate concentration was measured in systemic venous blood and locally in capillary blood sampled from the fractured and contralateral limbs of cattle and assessed for outcome prediction. The cutoff value was determined by maximizing the Youden index from receiver-operating characteristic curves. Multivariable logistic regression was employed to verify whether higher lactate concentrations compared with the cutoff value were an independent risk factor for poor outcomes at 30 days or 3 years after admission.

RESULTS

Poor outcome was associated with higher capillary lactate concentration in the fractured limb (P < .001) and greater difference with systemic blood (P = .005). A cutoff value of lactate difference ≥ 2.4 mmol/L (sensitivity = 0.80; specificity = 0.965) between capillary lactate in the fractured limb and systemic blood was the best predictor of death ≤ 30 days after admission (P < .001). Multivariable analysis revealed that this cutoff value was an independent risk factor for 30-day and 3-year outcomes (P < .001).

CLINICAL RELEVANCE

Admission blood lactate concentration difference ≥ 2.4 mmol/L between the fractured limb and systemic blood was a robust and independent predictor of outcome for cattle of the present report. Lactate metabolism is locally impaired in fractured limbs of nonsurviving or at higher complication risk cattle, which may help identify patients at high risk for poor outcomes.

Introduction

Long-bone fracture is a common orthopedic condition encountered in ruminants of all ages and accounts for up to 10% of the caseload at referral centers.17 While the clinical presentation and significance can vary according to the fracture location, most long-bone fractures in cattle are a dramatic cause of non–weight-bearing lameness. To avoid animal suffering and surrender a successful outcome from inadequate initial care, a prompt decision must be made to treat or euthanize the animal. Radiography can be used to evaluate fracture configuration and aid in the prognosis establishment according to specific criteria such as fracture location and degree of comminution. However, practitioners do not always have an x-ray machine in their vehicle and must rely on clinical examination to give a reliable prognosis and a good treatment choice. The latest includes the recommendation to send the animal to a referral clinic for further evaluation and fracture fixation if considered necessary. In commercial operation, good prognostication, including the risk of complications, need for hospitalization, and expected number of cast changes is required since the cost of treatment of long-bone fracture at a referral center can be considerable and easily exceed the value of the animal.8

Based on the patient presentation, long-bone fractures can be addressed by conservative management involving stall confinement, external coaptation such as fiberglass cast and splint-cast combination, or by surgical treatment including internal fixation.17 Cattle usually have a good predisposition for bone callus formation and thus secondary (indirect) bone healing, making them good fracture repair candidates.8 The bone-healing process is a well-choreographed series of cellular signals driving complex biological events in a defined temporal sequence and relies on the mechanic and tissues’ biology at the fracture site.9 Successful fracture healing requires sufficient mechanical stability and efficient restoration of vascularity.10 When a bone is fractured, the direction of blood flow to the bone is changed from centrifugal (inside to outside because of the high-pressure nutrient artery system and low-pressure periosteal system) to centripetal (outside to inside), and the resulting blood flow from the periosteum and muscular tissues plays a substantial role in the commencement of the bone-healing process.11,12 Additionally, the soft tissues supply the fracture site with cells possessing high osteogenic potential and undifferentiated mesenchymal cells, which serve as crucial promoters for tissue repair following fracture trauma.13 Severe soft tissue injury or traumatic interruption of vascular supply can result in inadequate vascularization and hypoperfusion of the fractured limb and compromise bone healing.14

L-lactate is the end product of the anaerobic metabolism of glucose to meet energy demands in the absence of adequate oxygen supply. Consequently, inadequate oxygen delivery to the tissue increases blood lactate concentrations (type A hyperlactatemia). Lactate is a valuable marker for determining perfusion deficits since its concentration generally correlates with oxygen delivery and uptake by the tissues.15 Lactate concentration is an established diagnostic, therapeutic, and prognostic marker in critically ill human and veterinary patients.1518 In cattle, a positive correlation between high lactate concentration and poorer prognosis has been established in abomasal and respiratory disorders.1922 Similarly, an increase in lactate concentration has been correlated with deterioration in body condition in young calves, increased stress in Holstein steers, and after strenuous exercise in bulls.2325 Lactate concentration can be used as a prognostic indicator and predict death in human patients diagnosed with hip or pertrochanteric fractures.2630 Additionally, long-bone and pelvic fracture repair in human patients with increased lactate concentration has been associated with greater postoperative morbidity.31,32

The determination of whether lactate concentrations are of prognostic value in cattle diagnosed with a long-bone fracture has not been studied previously. If of predictive value, the possibility to perform lactate concentration measurements at the farm using a portable analyzer at a low cost (US $3.00 per measurement, and US $300 for the portable analyzer) and with results available within 60 seconds would make this test attractive for evaluating cattle with fractures. Thus, the objective of the study reported here was to determine the prognostic value of lactate concentration measurements at admission in cattle with long-bone fracture, using a prospective single-center approach. We hypothesized that local hyperlactatemia from capillary blood samples taken at the fractured limb without systemic hyperlactatemia would be associated with an increased risk of complications or death.

Materials and Methods

Case selection

Cattle admitted for fracture treatment to the veterinary teaching hospital of the Université de Montréal between July 2016 and December 2018 were prospectively enrolled in the study. The study protocol was reviewed and approved by the institutional research ethics committee and was performed in compliance with institutional guidelines for the care and use of animals (CEUA-15A). Prior to inclusion in the study, informed owner consent was obtained. Cattle were excluded if no radiographic examination was performed or if no long-bone fracture was diagnosed. Patients were included if all lactate concentration measurements were obtained for analysis immediately after hospital admission and if the owners signed written informed consent. Collection of demographic data and patient’s history related to the events preceding hospital admittance was performed at admission.

Measurement of lactate concentrations

At admission, the patient was restrained on a hydraulic tilt table or a gurney, and systemic venous lactate concentration ([SysLac]) was measured after 3 mL of whole venous blood was drawn by jugular vein puncture with an 18-gauge (adults) or 20-gauge (calves) needle and placed into a glass tube containing EDTA. Local capillary lactate concentration was measured before complete restraint of the limbs required for fracture treatment in the fractured ([FxLac]) and contralateral ([ConLac]) limbs on a drop of blood (0.05 mL) obtained from a single 22-gauge needle skin puncture located 1 cm proximal to the dorsal coronary band. All lactate concentration measurements were performed immediately after collection with a portable handheld lactate meter based on an amperometric method using an enzymatic reaction (Lactate Pro meter; Arkray Inc) previously validated for lactate concentration measurement in cattle.33 The fractured capillary-to-systemic venous ([Fx-Sys]) and fractured capillary-to-contralateral capillary ([Fx-Con]) lactate concentration differences were calculated by subtracting the concentration in systemic venous blood and local capillary in the contralateral limb from the local capillary concentration in the fractured limb, respectively.

Fracture evaluation and treatment

After hospital admission, the patients underwent complete examination as soon as possible, including standard physical examination and radiography of the fractured limb. Additional diagnostic tests, such as routine blood work, were performed when judged necessary by the attending veterinarian according to the patients’ comorbidities. The fracture was described according to its location, degree (complete or incomplete), articular involvement, degree of comminution and type, bone quality, displacement, angulation, rotation, and soft tissue injury. On the basis of the modified Gustilo-Anderson open fracture classification scheme,34 open fractures were categorized by type, as follows: type 1 (skin wound < 1 cm, clean, simple fracture pattern), type 2 (skin wound > 1 cm, simple fracture pattern, no extensive soft tissue damage, no tissue flaps or avulsions), type 3a (extensive soft tissue damage with adequate bone coverage), or type 3b (extensive soft tissue damage with bone exposure, periosteal stripping, and major wound contamination, alone or in combination).

The attending veterinarian selected fracture treatment on the basis of the clinical presentation, fracture configuration, patient’s comorbidities, and financial cost of treatment options after consulting with the patient’s owner. When external coaptation was chosen, it was carried out with minimal delay. If internal fixation was deemed necessary, a large-animal surgeon assisted in treatment selection, and the surgical correction was performed after the patient’s condition was stabilized. Systemic antimicrobial treatment was administered for open fracture according to the treating veterinarian and when surgical treatment was performed. Patients were kept in small box stalls to engage in early functional exercises and weight-bearing while limiting their activity level. If fracture treatment was not elected or discontinued, euthanasia by barbiturate overdose was performed by a veterinarian following AVMA guidelines.35

Follow-up and outcome

Fracture healing was monitored by radiographic examination at 2 to 3 weeks (patients less than 6 months old) or 3 to 4 weeks (patients more than 6 months old) after initial fracture treatment. Admission and follow-up radiographic images were independently reviewed by 1 author (CC) and fracture healing qualitatively assessed as expected, evidence versus no evidence of healing based on bone callus formation. Additionally, radiography reports were reviewed, including the written assessment from the treating veterinarian based on the expected healing and the radiology report from board-certified radiologists when available. Follow-up with the patients’ owners was obtained at 6 and 12 months after hospital discharge using a standardized questionnaire through a telephone interview with the owner. The follow-up inquired postoperative survival status; patient health, growth, and lameness; physical appearance of fractured limb; and use or productivity of the animal, if applicable.

Short-term outcome assessment was based on death or development of severe complications in the first 30 days after hospital admission and was defined as unfavorable if the patient died or was euthanized or presented severe complications related to fracture healing (eg, osteomyelitis, no evidence of healing, or implants migration). Long-term outcome was based on the animal’s performance after hospital discharge using animal records obtained from the Canadian Dairy Network (https://www.cdn.ca/) and in accordance with the owner’s expectations obtained twice, as follows: 12 months after admission and at least 2 years later (3 years after admission). The expectations were based on milk or meat production, breeding and pregnancy, animal’s conformation, and complications. The retrieved data from the Canadian Dairy Network included information on survival, first calving age (for animals treated before the first lactation), independently scored conformation traits including limbs score, and milking records (305-day milk yield), when available. Long-term outcome was defined as favorable if the patient was productive or performed according to the owner’s expectations.

Statistical analysis

All statistical analyses were carried out using Prism software (version 8; GraphPad Software). Categorical (enumeration) data are provided as numbers (percentages) and measurements as mean ± SD. Enumeration data were analyzed by a χ2 test. Quantitative data sets were tested for normal distribution and homogeneity of variance using Shapiro-Wilk and Levene tests, respectively.

First, a 2-factor repeated-measures ANOVA was used to assess the effect of the different lactate measurements ([SysLac], [FxLac], [ConLac], [Fx-Sys], and [Fx-Con]) on death or development of severe complications ≤ 30 days after admission. The analysis was done with all patients included in the study and repeated without the patients that were euthanized immediately after admission for reasons not directly related to fracture severity, fracture configuration, or both (eg, diagnosis of nonpregnancy or cost of repair from lack of external fixation options in simple femoral or humeral fractures). The Sidak correction for multiple comparison post hoc tests was used.

Second, statistically significant ANOVA results were further investigated by constructing receiver-operating characteristic (ROC) curves to determine the lactate measurement with the best ability to predict death or development of severe complications ≤ 30 days after admission. The Youden index for each ROC analysis was used to determine the cutoff lactate measurement for which sensitivity and specificity to predict an unfavorable outcome were maximal. The area under the ROC curve (AUC) for sensitivity and specificity of this cutoff value was evaluated. The data used for the ROC curves analysis excluded the patients that were euthanized immediately after admission for reasons not directly related to fracture severity, fracture configuration, or both. Afterward, multivariable and univariable logistic regression models were used to verify whether a lactate measurement concentration greater than the cutoff value was an independent risk factor for death or development of severe complications ≤ 30 days after admission. The ORs and 95% CIs were reported. For all analyses, 2-tailed P values < .05 were considered statistically significant.

Results

Patients

Forty-three cattle, including 42 females and 1 male, were enrolled. Breeds represented included Holstein (n = 39), Jersey (2), Brown Swiss (1), and Angus (1). Mean age at admission was 6.4 ± 9.0 months (192 ± 269 days; median, 3 months; range, < 1 to 1,080 days) and comprised 17 calves ≤ 3 days old, including 11 that were < 24 hours old. The female productivity status had cows in lactation (3), pregnant heifers (4), heifers ready to be bred (2), and cattle that were too young to be bred (33). Among the 17 calves presented at ≤ 3 days old, 10 (59%) suffered a fracture during obstetrical manipulations from assisted delivery, with 6 of them being secondary to the use of obstetrical chains, and 4 (24%) were stepped on by the mom in the calving pen. The mean ± SD interval between onset of clinical signs of lameness and hospital admission was 30 ± 35 hours (range, 0 to 192 hours) for all patients.

Lactate concentrations measured

The mean [SysLac] of all patients was 2.14 ± 2.23 mmol/L. There were 15 of 43 (35%) patients diagnosed with hyperlactatemia (≥ 2.0 mmol/L), with most of them (10/15 [67%]) aged ≤ 3 days old. The [FxLac] was higher compared to the [SysLac] in 28 of 43 (65%) patients and to the [ConLac] in 29 (67%) patients.

Fracture evaluation and treatment performed

The right limb was overrepresented in fracture laterality, with 58% (25/43) of the fractured bones being right-sided. The most frequently affected bones were the fused third and fourth metacarpal bones (63% [27/43]), followed by the radius, ulna, or both (12% [5/43]); fused third and fourth metatarsal bones (9% [4/43]); femur (7% [3/43]); tibia (5% [2/43]); and humerus (5% [2/43]). The most frequently fractured bone location was the diaphysis alone (44% [19/43]), followed by the physis with or without epiphysis involvement (35% [15/43]), a combination of the diaphysis and metaphysis (16% [7/43]), and the metaphysis alone (5% [2/43]). The fractures involving the physis were diagnosed as Salter-Harris type I (n = 10) or type II (5). An open fracture was diagnosed in 16 patients (37% [16/43]), with most open fractures being type I (n = 6), followed by type II (4), type IIIa (3), and IIIb (3).

Of the 43 patients, 6 (14%) were euthanized without treatment because of the expected high cost of repair from lack of external fixation options in simple femoral or humeral fractures (n = 3), the guarded prognosis based on fracture’s severity (2), or after a diagnosis of nonpregnancy (1). Of the 37 patients that underwent fracture treatment, the fracture was stabilized by immobilization with a fiberglass cast (51% [19/37]), with a pin-cast fixation (22% [8/37]), by open reduction and internal fixation (19% [7/37]), or with Thomas splint and cast combinations (8% [3/37]).

Follow-up and outcome

Overall, the 30-day postadmission outcome was unfavorable in 14 of 43 (32%) patients and resulted in early death in 10 (23%) patients. Of the 43 patients included in the study, 6 (14%) were euthanized without treatment as previously described, 4 (9%) were euthanized following fracture treatment because of severe complications development, and 4 (9%) presented severe complications related to fracture healing that were successfully managed and did not result in euthanasia. Of the 37 patients who underwent fracture treatment, 35 (95%) were discharged. Two animals were euthanized before hospital discharge because of the development of severe osteomyelitis (n = 1) and extensive necrosis of the fractured limb diagnosed at the first cast change (1). Two of the 35 patients discharged from the hospital were euthanized within the first 30 days because of delayed fracture healing with contralateral dropped fetlock (n = 1) or fracture nonunion (1).

Long-term follow-up was obtained for all cases. The long-term outcome was favorable for all patients that survived for ≥ 30 days after admission; therefore, no further analysis was conducted to assess the effect of the different lactate measurements on death > 30 days after admission. The 4 pregnant and 2 heifers ready to be bred calved at 2 years of age and reached their expected level of milk production. Three of the patients too young to be bred never calved and were culled for reasons unrelated to their fracture. While healed fracture did not seem to impact the conformation traits scoring, owners seldom reported mild to moderate angular limb deformity (n = 4) or straighter limb (2) without substantial lameness.

Impact of admission lactate concentrations on outcomes ≤ 30 days after admission

The lactate concentrations were higher for patients with unfavorable outcomes of death or severe complication development ≤ 30 days after admission (Figure 1; Supplementary Figure 1 [results according to the patients’ age at presentation: ≤ 3 days old and at > 3 days old]). Death or development of severe complications ≤ 30 days after admission was associated with higher [FxLac] (P < .001 for all patients and P < .001 excluding patients euthanized for other reasons) and with greater [Fx-Sys] and [Fx-Con] measurement differences (P = .005 and P = .018 for all patients, and P < .001 and P = .001 excluding patients euthanized for other reasons, respectively).

Figure 1
Figure 1

Lactate concentrations in whole blood samples obtained from jugular vein systemic circulation ([SysLac]) and capillary blood 1 cm proximal to the dorsal coronary band of the fractured limbs ([FxLac]) and contralateral limbs ([ConLac]) of 43 cattle with long-bone fractures between July 2016 and December 2018, grouped by outcome: favorable (n = 29; black), negative with all patients that died or were euthanized or presented severe complications related to fracture healing (14; red), or negative with only patients that underwent fracture repair treatment but did not survive to 30 days after admission or presented severe complications related to fracture healing (8; green). A—Bar graphs comparing the mean lactate concentration from systemic venous lactate [SysLac], local capillary lactate concentration in the fractured limb [FxLac], and local capillary lactate concentration in the contralateral limb [ConLac] across patient groups. For each bar, the top of the bar represents the mean and the error bar represents the SD. Asterisk bars indicate results that differed significantly (P < .05). B—Box-and-whisker plots of the mean difference in lactate concentrations between the capillary lactate concentration obtained at the fractured limb and the concentration obtained at the systemic venous concentration ([Fx-Sys]) and capillary concentration from the contralateral limb ([Fx-Con]) across patient groups. For each plot, the box represents the first and third interquartile (25th to 75th percentile) range, the line in the box represents the mean, and the whiskers represent the range (minimum and maximum values). Asterisk bars indicate results that differed significantly (P < .05). The gray horizontal line represents no difference in lactate concentration based on the location.

Citation: Journal of the American Veterinary Medical Association 261, 2; 10.2460/javma.22.04.0181

Predictive usefulness of lactate concentration on 30-day postadmission outcome

On the basis of ROC curves of the predictive models for [FxLac], [Fx-Sys], and [Fx-Con] to predict death or development of severe complications ≤ 30 days after admission, the predictor value of measurement of [Fx-Sys] was superior (AUC, 0.9527; P < .001) to that of [Fx-Con] (AUC, 0.8930; P = .005) and [FxLac] (AUC, 0.8897; P = .003; Figure 2). The ROC curve and sensitivity and specificity analyses revealed that a cutoff point of measurement difference [Fx-Sys] of 2.4 mmol/L yields a sensitivity of 80% and a specificity of 96.55% for predicting 30-day postadmission outcome. Death or severe complication development for patients with a measurement difference of [Fx-Sys] ≥ 2.4 mmol/L was 89% and 0.07% for patients with < 2.4 mmol/L. The positive and negative predictive values of [Fx-Sys] ≥ 2.4 mmol/L as a clinical test to predict adverse outcomes were 89% and 93%, respectively. The predictor value of [Fx-Sys] could also predict the long-term outcome after long-bone fracture with the same predictive ability (AUC, 0.9517; P < .001).

Figure 2
Figure 2

Receiver-operating characteristic curves of the 3 predictive lactate models of [FxLac] (gray solid line), [Fx-Sys] (blue solid line), and [Fx-Con] (purple dotted line) developed for prediction of outcomes within 30 days after admission for long-bone fracture in the cattle described in Figure 1. The 45° dotted line represents the line of no discrimination.

Citation: Journal of the American Veterinary Medical Association 261, 2; 10.2460/javma.22.04.0181

Multivariable analysis of a lactate concentration difference cutoff of 2.4 mmol/L on the 30-day postadmission outcome

Patients with an [Fx-Sys] ≥ 2.4 mmol/L at admission had greater odds (OR, 112.0; 95% CI, 8.473 to 1,250; P < .001) of death or severe complication development within 30 days after admission than did cattle with results below this cutoff concentration. After adjusting the patient’s age at admission, time from fracture to admission, fractured bone, fracture description, and status of the soft tissue wounding, patients with measurement difference [Fx-Sys] of ≥ 2.4 mmol/L (vs < 2.4 mmol/L) at admission had greater odds (OR, 7.35; 95% CI, 8.473 to 1,250; P < .001) of death or severe complication within 30 days after admission.

Discussion

Analysis of biomarkers using handheld analyzers can be very valuable in farm animal medicine and surgery to help guide case management (eg, monitoring treatment and prognostication) as they are associated with limited cost and may be used cow-side. In the present study, 35% (15/43) of cattle patients with long-bone fracture had systemic venous lactate concentrations ≥ 2 mmol/L at the time of hospital admission, and 65% of patients had an increased local lactate concentration in the fractured limb compared to systemic concentration. Results of the present study demonstrated that an increase in [FxLac] is expected in long-bone fractures in cattle, and [Fx-Sys] measurement difference is associated with unfavorable outcomes independent of the clinical presentation, fracture diagnosis, and status of the soft tissue wounding. We propose that an [Fx-Sys] lactate concentration measurement difference ≥ 2.4 mmol/L can be used as an indicator to estimate risk of death or severe complication development within 30 days of admission for cattle with a long-bone fracture and might assist veterinarians in the early detection of fractures associated with more severe tissue injury, prediction of outcomes, and guidelines for referral and treatment. The strong association of blood lactate concentration and outcome has been reliably confirmed in human medicine and veterinary medicine,1525 and this single-center prospective study provides further evidence.

Hyperlactatemia is typically a result of increased lactate production, decreased clearance, or a combination of both. Clinically, the most common cause of hyperlactatemia is tissue hypoxia that occurs with hypoperfusion or poor oxygen delivery.36 Interestingly, a poorer outcome or increased mortality with high lactate has been established in cattle with and without a specific diagnosis.1925 Different clinical cutoffs have been described for nonsurvivable prediction, among which 6 mmol/L and 4 mmol/L are frequently used because of their clinical relevance in 2 major syndromes in bovine medicine being right abomasal disorders in cows and bronchopneumonia in calves, respectively.19,21 These studies obtained systemic lactate concentration from venous samples. On the contrary to these previous reports, the results of the present study did not suggest an association between a rise in [SysLac] and unfavorable outcomes. We can hypothesize that tissue hypoperfusion in long-bone fractures may lead to minor systemic lactate concentration increase or may be less severe than in other disorders in cattle such as abomasal ischemia. In human patients, systemic lactate concentration is a prognostic indicator and can be used to predict death after a hip or pertrochanteric fracture.2630 The present study had not found a similar association between hyperlactatemia and death after a long-bone fracture in cattle. This difference is probably because the lactate concentration was mainly used to assess ischemia and hypoxia at the whole-body level of human patients more severely compromised than the cattle patients included in our study.28 In fact, patients with hip fractures are generally characterized by older age and multiple comorbidities and presented in a debilitating state, with severe ischemia and hypoxia in the tissues and organs.28,37 In our study population, the patients were young with an average age at presentation of only 6.4 months (median, 3 months). They were usually reported to be in good general health before the fracture occurred. Nevertheless, when used in comparison with the local lactate concentration in the fractured limb, [SysLac] became interesting in terms of outcome prediction, with [Fx-Sys] measurement differences being highly predictive of unfavorable outcomes. The amount of lactate released from the fractured limb into the venous blood may have been too small to cause an increase in [SysLac] because the distribution volume may be too large to register a systemic increase. A similar finding was previously reported in a study during which isolated exercise of a small muscle group led to a sharp rise in the local lactate concentration from lactate efflux from the muscle. In contrast, the systemic lactate concentration remained unchanged.38

Compared to patients with favorable outcomes, patients that presented an increased risk of death or severe complication development within 30 days after hospital admission had a higher [FxLac]. This measurement obtained from capillary blood was taken 1 cm above the coronary band of the fractured limb. Arterial blood is the preferred sample for lactate measurement because it is derived from mixed venous blood and thus provides a representative sum of all sources of tissue lactate production.39 Capillary blood, which is more easily obtained, is an alternative sample employed for lactate determination. In healthy volunteers or intensive care human patients, capillary lactate measurements were 47% higher than arterial blood lactate when sampled at the fingertip.40 While the present study did not evaluate arterial blood lactate, our results agree with increased capillary lactate concentration with a 63% and 23% higher concentration in the capillary blood from the fractured and contralateral limbs, respectively, than in systemic venous blood. The investigation of capillary blood lactate concentration in our study was based on the hypothesis that local lactate concentration may be increased while the systemic lactate concentration may remain unchanged38 and therefore may better reflect a local hypoxemic fracture environment or more severe interruption of vascular supply in the injured limb. Based on our results, [FxLac] seems to better represent an inadequate vascularization and hypoperfusion of the fractured limb than [SysLac]. However, [FxLac] probably does not reflect or correlate with the systemic hemodynamic status of the animal, and care should be used when interpreting the results of this measurement.

This study showed that the [Fx-Sys] is closely related to the prognosis of cattle patients with a long-bone fracture and can be used as an indicator for death or severe complication development. Most frequently, long-bone fractures in cattle are secondary to external trauma. The energy required to break the bones can be extremely high, resulting in fractures with variable degrees of comminution. Delayed union is a common complication of comminuted fractures and causes prolonged healing, necessitating an extended immobilization period.41 For these reasons, patients presenting with such configuration were most likely to be euthanized without any treatment and were therefore at higher risk of early death. Since hyperlactatemia is associated with tissue hypoxia,36 an increased [Fx-Sys] may identify patients with more compromising fractures as they are usually caused by severe trauma, in which worse soft tissue injury and traumatic interruption of vascular supply can occur. In other words, [Fx-Sys] may have been higher in these patients, reflecting more compromised vascularization locally in the fractured limb leading to an increased risk of early euthanasia. Similarly, the raised risk of severe complication development with patients presenting an increased [Fx-Sys] can be linked to severe soft tissue injury or traumatic interruption of vascular supply resulting in hypoperfusion of the fractured limb, which can compromise bone healing.14 As a matter of fact, an inadequate blood supply is known to be a significant contributing factor for delayed fracture healing or nonunion.42,43 When ischemia is present in a fractured limb, a hypoxic environment is created around the fracture site.44 Low oxygen levels lead to cellular death, delayed chondrocyte and osteoblast differentiation, and impaired fracture healing.45 In addition, it should be noted that 23% of the studied population involved calves that suffered a fracture during obstetrical manipulations from forced extraction. The lack of soft tissue protection covering the fused third and fourth metacarpal and metatarsal bones makes them more prone to crushing damage inflicted by calving chains or ropes on the underlying soft tissue, possibly resulting in a disruption of the blood vessels. In this population, [Fx-Sys] could reflect the integrity of the blood supply to the distal part of the limb and be linked to unfavorable outcomes following the development of soft tissue or bone necrosis.

The main limitation of the present study was the lack of lactate concentration measurement at the farm before transport to the hospital, which could have influenced the measurements and limited the ability of our result to be extrapolated to a farm setting. The study was conducted in a single hospital. Not all consecutive fractured patients were enrolled in the study either because of owners’ refusal of consent or seldom absence of the principal investigator, which could inevitably lead to selection bias. The resulting small number of patients included may have limited the statistical power of the multivariable logistic regression in verifying lactate concentration as an independent risk factor and may have underestimated other associations that might have been identified if a larger population had been evaluated. Unmeasured potential confounding factors affecting lactate concentrations or the risk of death or severe complication development cannot be ruled out. Similarly, the normal capillary lactate concentrations may be different in newborn calves than in adults, and the impact of age on [FxLac] concentration remains unknown and should be taken into consideration when measuring [Fx-Sys] following a long-bone fracture. Therefore, the results of this study should be further verified by a larger cohort, in a multicenter prospective study including on-farm lactate concentration measurements before referral.

In conclusion, the fractured capillary-to-systemic venous lactate concentration ([Fx-Sys]) was found to be a good prognostic indicator of death or severe complication development risk at 30 days after hospital admission of cattle patients diagnosed with a long-bone fracture. Patients with an [Fx-Sys] cutoff concentration difference of 2.4 mmol/L were identified as a high-risk population. The [Fx-Sys] at admission revealed good short- and long-term prediction ability, which can help veterinary clinicians and surgeons to identify cattle with fracture configurations that warrant a poor prognosis and that would benefit from prompt euthanasia to avoid animal suffering and to construct individualized treatment plans for patients at higher risk of severe complications that may be life-threatening or will require additional treatment cost.

Supplementary Materials

Supplementary materials are posted online at the journal website: avmajournals.avma.org

Acknowledgments

The costs of this study were covered by internal research funding (Fonds Zoetis) from the Université de Montréal. No third-party funding or support was received in connection with this study or the writing or publication of the manuscript. Funding sources did not have any involvement in the study design, data analysis and interpretation, or writing and publication of the manuscript.

The authors declare no conflict of interest related to this report.

The authors thank Marco Bosa, Carl Bernard, Julie Choquette, and Virginie Roger for providing insight and technical assistance that greatly assisted the research.

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