Received: 27 August 2019 Accepted: 13 March 2020 DOI: 10.1111/jvim.15770 STANDARD ARTICLE Plasma iron concentrations and systemic inflammatory response syndrome in neonatal foals Júlia Sanmartí 1,2 | Lara Armengou1,2 | Judit Viu1,3 | Eduardo Alguacil2,4 | 5 6 1,2 Sandra Civit | José Ríos | Eduard Jose-Cunilleras Printed by [Wiley Online Library - 083.042.103.159 - /doi/epdf/10.1111/jvim.15770] at [29/07/2020]. 1 Servei de Medicina Interna Equina, Departament de Medicina i Cirurgia Animals, Abstract Facultat de Veterinària, Universitat Autònoma Background: Sparse information regarding plasma iron concentration in neonatal de Barcelona, Barcelona, Spain 2 foals and its utility as an inflammatory marker in this population has been published. Unitat Equina, Fundació Hospital Clínic Veterinari, Universitat Autònoma de Objectives: To determine the physiologic plasma iron concentration in neonatal foals. Barcelona, Barcelona, Spain To assess its utility as an inflammatory marker to predict systemic inflammatory 3 Hospital Veterinario Sierra de Madrid, 28750-San Agustín de Guadalix, Madrid, Spain response syndrome (SIRS) and as a prognostic marker. 4 Uplands Way Vets Low Road, Bressingham, Animals: Forty-seven ill neonatal foals admitted to a referral equine hospital were IP22 2AA Diss, Norfolk, UK divided in 2 groups based on the SIRS criteria (24 SIRS and 23 non-SIRS). Two control 5 Ganaderia JM, Barcelona, Spain 6 groups of 43 hospital and 135 stud farm healthy neonatal foals were also included. Unitat de Bioestadística, Facultat de Medicina, Universitat Autònoma de Barcelona, Methods: Observational prospective study. Data were summarized by mean and its Barcelona, Spain 95% confidence interval and absolute frequency and percentage for quantitative Correspondence andqualitative variables. One-way ANOVA, ANCOVA (group and age effects) and Eduard Jose-Cunilleras, Servei de Medicina Dunnett as posthoc analysis were used to compare plasma iron concentration among Interna Equina, Departament de Medicina i Cirurgia Animals, Facultat de Veterinària, groups. Universitat Autònoma de Barcelona, Results: Neonatal foals with SIRS did not have had any statistically significant differ- 08193-Bellaterra, Barcelona, Spain. Email: eduard.jose.cunilleras@uab.cat ent plasma iron concentrations compared to non-SIRS (P = .56) and stud farm control group (P = .99), 172.8 g/dL (95% CI; 126.0-219.6), 193.1 g/dL (139.1-247.2), and 181.8 g/dL (171.3-192.4), respectively. Plasma iron concentration had a large vari- ability in healthy neonatal foals, and was negatively correlated with age in hospital controls (rho = −0.387) and sick neonatal foals (rho = −0.598) (P < .001). Conclusions and Clinical Importance: Plasma iron was not a useful marker of SIRS in neonatal foals and was not associated with outcome. KEYWORDS critical care, monitoring, neonatal foals, plasma iron, systemic inflammatory response syndrome 1 | INTRODUCTION Sepsis in neonatal foals is associated with higher death rate compared Abbreviations: RBC, red blood cell; SIRS, systemic inflammatory response syndrome. with other medical conditions affecting neonatal foals.1 Early detection This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine. J Vet Intern Med. 2020;34:1325–1331. wileyonlinelibrary.com/journal/jvim 1325 1326 SANMARTÍ ET AL. of systemic inflammation is essential in order to provide appropriate ill neonatal foals were divided in 2 groups: SIRS (n = 24) and non-SIRS treatment. 2 The original systemic inflammatory response syndrome (n = 23). The SIRS group was defined as meeting 2 or more of: (1) hyper- (SIRS) criteria in neonatal foals have a significant association with pre- or hypo-thermia (rectal temperature >39.2 C or <37.2 C), (2) leukocy- 3 diction of sepsis and nonsurvival. tosis or leukopenia (peripheral white blood cell count >12.5 × 103/L The SIRS term provides a reference for the complex findings that or <4 × 103 /L) or >10% immature (“band”) neutrophils, (3) tachycardia resulted from a systemic activation of the innate immune response, regard- (>120 beats/min), and (4) tachypnea (>30 breaths/min).3,5-8 4 less of the cause. Systemic inflammatory response syndrome describes Foals that did not meet the SIRS criteria were classified as non- the clinicopathologic effects of the inflammatory response to a variety SIRS. The hospital control group (n = 43) included healthy neonatal of insults, including bacterial infection, endotoxemia, ischemia, hypoxia, foals admitted to the same referral equine hospital from 2005 to 2011 trauma, and burns.5 The original SIRS criteria used to describe this clinical that had a normal physical examination and were accompanying their syndrome in neonatal foals included presence of 2 or more of: (1) hyper- sick dams. Another control group was added, including 135 healthy or hypo-thermia (rectal temperature >39.2  C or <37.2 C); (2) leuko- neonatal foals from a nearby endurance stud farm over the 2017 cytosis or leukopenia (peripheral white blood cell count >12.5 × 103/L foaling season. These were 24-48 hour-old foals with history of normal Printed by [Wiley Online Library - 083.042.103.159 - /doi/epdf/10.1111/jvim.15770] at [29/07/2020]. or <4 × 10 3/L) or > 10% immature (“band”) neutrophils; (3) tachycardia foaling, normal physical exam at birth and serum immunoglobulin G 3,5-8 (>120 beats/min); and (4) tachypnoea (> 30 breaths/min). The SIRS (IgG) concentration above 800 mg/dL within 24-48 hours postpartum. criteria is much simpler and faster to use than sepsis scores and might serve Sick foals (ie, SIRS and no SIRS groups) were also classified as a more rapid screening tool for sepsis in neonatal foals. A positive result according to outcome into survivors (n = 29) and nonsurvivors to the original SIRS criteria has a sensitivity of 60% and specificity of 69% (n = 18). The nonsurvivor group included both cases of natural 3,9,10 to predict sepsis when compared to other proposed SIRS criteria and deaths (n = 4) and euthanized because of poor prognosis (n = 14). could be more useful for predicting nonsurvival associated with sepsis.3 None of the foals included in the nonsurvivor group was euthanized Based on the human pediatric literature, an updated SIRS score for foals because of financial restraints. was proposed but it does not provide an improved ability in predicting sepsis.3,11 SIRS criteria for foals of the aforementioned study required the presence of at least 3 of: (1) fever or hypothermia, (2) tachycar- 2.2 | Blood sampling and measured variables dia, (3) tachypnea, (4) leukocytosis, leukopenia, >5% band neutro- phils, (5) venous blood lactate concentration, or (6) venous blood Blood samples from ill neonatal foals were collected at admission in glucose concentration; at least one of which had to be abnormal ethylenediaminetetraacetic acid (EDTA) and lithium heparin tubes. temperature or leukocyte count. 9 Similarly, blood samples from healthy hospital neonatal foals (hospital In adult horses, plasma iron concentration acutely decreases in cases control group) were collected at different times during hospitalization, with systemic inflammation. 2 Low iron and high fibrinogen plasma concen- usually within the first 48 hours of admission. Finally, blood samples trations are both sensitive indicators of systemic inflammation in horses, from stud farm control group were collected from 24 to 48 hours with sensitivity of 90 and 82%, respectively.12 Rapid development of after birth. hypoferremia is particularly valuable during the earliest phases of infection, Blood collected in EDTA from sick foals was used to determine before other components of innate and adaptive immunity are mobilized.2 manual hematocrit, total protein by refractometry, manual fibrinogen Red blood cell (RBC) mass in human neonates is highly variable, by heat precipitation method,16 and also to perform Diff-Quick stained because of changes in both the mass and the composition of RBCs occur- blood smears and complete cell blood count using automated hematol- ring during the transition from the intra uterine to the extra uterine environ- ogy analyzers (Advia 120, Siemens Health Care Diagnostics SL, Barce- ment.13 Sparse information is published about iron in neonatal foals.14,15 lona, Spain; LaserCyte, Idexx laboratories, Inc, Netherlands). In the The objectives of this study were to determine the physiologic hospital control group, in addition to a normal physical examination, values of plasma iron concentrations in neonatal foals (<14 days old), hematocrit, total protein and fibrinogen concentrations were deter- and to assess its utility as both an early inflammatory marker to pre- mined to support that foals were healthy to be included in this group dict SIRS and a prognostic marker in sick neonatal foals. (data not shown). In the stud farm control group, serum IgG and plasma iron concentration were the only measured variables. Serum IgG was determined using a portable quantitative analyzer (DVM Rapid TestTM 2 | MATERIALS AND METHODS II - Multi-Test Analyzer Tests, Florida) for the stud farm control group and semiquantitative turbidimetric test (ZnSO4 test) for the hospital 2.1 | Animals control group and sick group. Plasma iron concentration was measured from lithium heparin plasma samples with an automated chemistry Neonatal foals (<14 days old) referred to the Equine Unit of the Fun- analyzer (Olympus AU400, Hamburg, Germany) using a conventional dació Hospital Clínic Veterinari of the Universitat Autònoma de Barce- enzymatic colorimetric assay (Olympus System Reagent, Beckman lona from January 2005 to December 2011 were included if a blood Coulter, Galway, Ireland) by the TPTZ [2,4,6-Tri-(2-piridil)-5-triacina] sample was taken before any treatment was administered. Forty-seven as chromogen. SANMARTÍ ET AL. 1327 2.3 | Data analysis The 95% CI limits of plasma iron concentration of the sick group were similar to the stud control group (P = .99) (Table 1; Figure 1). The The main objective of this study was to establish the usefulness of hospital control group had significantly lower 95% CI limits of plasma iron concentration for diagnosis and prognosis in neonatal foals and iron concentrations and lower mean plasma iron concentration than obtain an estimate of limits of abnormality (ie, reference range) in neo- sick group (P = .002) (Table 1; Figure 1). With ANCOVA analysis, there natal foals. These limits were estimated by calculation of individual was no significant difference between the hospital control and sick 95% confidence intervals (95% CI) (ie, from the SD as a measure of foals (P = .06) but age effect was present (P = .001; Figure 2). A nega- variability), and absolute range (minimum and maximum) for plasma tive moderate correlation with age was seen in the hospital control iron concentration for each group, defined as sick, hospital control group (rho = −0.387) and in the sick group (rho = −0.598), so the and stud farm control groups. One-way ANOVA and Dunnett as post- higher the age the lower the iron concentration. Greater variability hoc analysis of group comparisons detected differences between and higher iron plasma concentrations were specially seen in the first groups. To evaluate the effect of age on plasma iron concentration, 3 days of life (Figure 2). ANCOVA analysis of group as independent factor and age as covari- Both individual 95% CI and absolute range of plasma iron concen- Printed by [Wiley Online Library - 083.042.103.159 - /doi/epdf/10.1111/jvim.15770] at [29/07/2020]. ate was performed. Additionally, using t test for independent groups, tration of SIRS group overlapped with the non-SIRS group (Table 2; differences between SIRS, non-SIRS, and outcome were explored Figure 3). Plasma iron concentration of non-SIRS group (193.10 g/dL) from 95% CI of mean (ie, using SE as measure of variability). Cutoffs was not statistically significant different to SIRS group (172.77 g/dL) of less than 59, 79, and 105 g/dL were tested in order to evaluate (P = .56; Figure 3). the utility of external limits of plasma iron concentration and a Fisher's exact test was performed. Other variables were described by mean and their 95% CI and absolute frequency and percentage for quantita- tive and qualitative variables, respectively. All statistical analyses were performed using a statistical software package (SPSS version 25, SPSS Inc, Chicago, Illinois) and all analyses were performed with a 2-sided Type I error of 5%. 3 | RESULTS A total of 225 neonatal foals (<14 days old) were included in the study. Forty-seven out of 225 were sick neonatal foals with mean age of 3.0 days (95% CI; 2.2-3.9 days). Sick neonatal foals were divided into SIRS group (n = 24), mean age 3.5 days (95% CI; 2.2-4.8 days), and non-SIRS group (n = 23), mean age 2.6 days (95% CI; 1.5-3.7 days). F I G U R E 1 Scatterplot of plasma iron concentrations (g/dL) in Forty-three were healthy foals admitted to the hospital, with mean age stud farm controls (open circles), hospital controls (solid circles), and 4.5 days (95% CI; 3.4-5.6 days) and the 135 healthy neonatal foals left sick neonatal foals (solid triangles). Horizontal line indicates mean were from a stud farm with mean age 1.5 days (95% CI; 1.5-1.5 days). plasma iron concentration for each group TABLE 1 Individual 95% confidence intervals Stud farm controls Hospital controls Sick foals Iron (g/dL) Ind (95% CI) (58.8; 305) (0.0; 303) (0.0; 420) Range 35.0-339.1 13.9-394.8 20.7-474.9 Mean (95% CI) 181.8a (171.3; 192.4) 126.1b (99.2; 153.1) 183.2a (148.5; 217.8) N 135 43 47 c c c Age (days) Mean (95% CI) 1.5 (1.5; 1.5) 4.5 (3.4; 5.6) 3.0 (2.2; 3.9) Range 1.5-1.5 1-13 1-11 N 135 43 47 Note: Data presented as individual 95% confidence interval (Ind (95% CI)); range, (minimum and maximum); mean (95% CI), 95% confidence intervals of the mean; N, number of foals. a Indicates no significant difference between groups (P > .5). b Indicates significant difference between groups (P < .05). c Indicates significant difference between groups with the ANCOVA model (P < .001). 1328 SANMARTÍ ET AL. Printed by [Wiley Online Library - 083.042.103.159 - /doi/epdf/10.1111/jvim.15770] at [29/07/2020]. F I G U R E 2 Scatterplot of the relationship of plasma iron concentrations (g/dL) and age (days) in healthy [stud farm controls (open circles) and hospital controls (solid circles)] and sick neonatal foals (solid triangles) TABLE 2 Plasma iron concentration Non-SIRS SIRS P-value N 24 23 in sick neonatal foals with SIRS versus non-SIRS Iron (g/dL) Ind (95% CI) 193 (0.0; 458) 173 (0.0; 397) Range 20.7–474.9 37.5-369.6 Mean (95% CI) 193.1 (139.1; 247.2) 172.8 (126.0; 219.6) .56 Iron < 59 g/dL No 20 (83.3%) 20 (87.0%) 1.0 Yes 4 (16.7%) 3 (13.0%) Iron < 79 g/dL No 19 (79.2%) 19 (82.6%) 1.0 Yes 5 (20.8%) 4 (17.4%) Iron < 105 g/dL No 18 (75.0%) 16 (69.6%) .75 Yes 6 (25.0%) 7 (30.4%) Note: Data presented as individual 95% confidence interval (Ind 95% CI); range, (minimum and maximum); Mean (95% CI), 95% confidence intervals of the mean; N, number of foals. Sick neonatal foals were divided according to outcome into survival group (n = 29) and nonsurvival group (n = 18) (Figure 3). Survival group showed mean plasma iron concentration of 184.58 g/dL with 95% CI limits of concentration (136.71-232.46 g/dL) and nonsurvival group 180.84 g/dL with 95% CI limits of concentration (127.48-234.20). Plasma iron concentration was not statistically associated with outcome (P = .92). External cutoff values (less than 59, 79, and 105 g/dL) were applied for plasma iron concentration with no statistically significant differences between those (Table 2). 4 | DISCUSSION F I G U R E 3 Scatterplot of plasma iron concentrations (g/dL) in sick neonatal foals: SIRS survivors (upright solid triangles), SIRS The main findings of this study were: (1) the large variability of plasma nonsurvivors (upside down solid triangles), non-SIRS survivors (upright open triangles) and non-SIRS nonsurvivors (upside down iron concentration in healthy neonatal foals, (2) the lack of statistically open triangles). Horizontal line indicates mean plasma iron significant differences in plasma iron concentration in sick and SIRS concentration for each group affected foals relative to those in healthy foals, and (3) a negative SANMARTÍ ET AL. 1329 correlation between plasma iron concentration and age for the first Studies of plasma iron concentrations in neonatal foals with SIRS 2 weeks of life. are sparse or nonexistent. The SIRS criteria have been defined in veter- Neonatal foals in the stud control group (n = 135), only had a inary medicine by different authors.3,7,24,25 The standard variables 24 hours range of age dispersion between all individuals, and their mean reported to define SIRS have been: (1) temperature, (2) heart rate plasma iron concentration was 181.84 g/dL, which is similar to the (HR), (3) respiratory rate (RR), and (4) white blood cell counts (WBC) estimated average concentrations in neonatal foals of 1 day of age 14; or presence of immature neutrophils. Comparison between various but presented a wider distribution (58.8-305 g/dL) compared to previ- studies of SIRS in neonatal foals could be hampered given the differ- ously published plasma iron concentration in adults (105-277 g/dL).2,12 ences in criteria and cutoff values relative to the definition of criteria In healthy foals at birth, plasma iron and ferritin concentrations are of SIRS in neonatal foals. Some authors suggest different cutoff values lower than in adult horses, followed by a rapid increase in the first for HR, RR, WBC in neonatal foals as well as including blood glucose 14 24 hours as a result of absorption of colostrum iron. Colostrum and and lactate concentrations3,9,10,26 and others, include a fifth criteria; milk are the major source of iron for neonatal foals with an average iron evidence of sepsis, cerebral hypoxia, ischemia, or trauma.8 The true 17 concentration of 0.79 mg/L in colostrum and 0.34 mg/L in milk. Dur- clinical utility of the SIRS criteria in neonatal foals remains to be deter- Printed by [Wiley Online Library - 083.042.103.159 - /doi/epdf/10.1111/jvim.15770] at [29/07/2020]. ing the first 3 weeks of life, concentrations fall below concentrations of mined.3 In the present study a decision was made to use the original 18 adults, reaching a nadir at 3 weeks of age. The same rapid changes SIRS criteria rather than the neonatal SIRS criteria including glucose occur after delivery in human newborns, when hemoglobin breakdown and lactate concentrations, because a higher sensitivity (60% versus leads to storage of the iron by-products for future erythrocyte produc- 42%) to predict sepsis has been demonstrated.3 Although one of the tion. Within the first week after delivery, hemoglobin and hematocrit weak points of the original SIRS criteria is that foals presenting only values are higher and begin to drop in response to the higher ambient tachycardia and tachypnea could be misclassified in the SIRS group, in oxygen concentration ex utero.13 Based on previous studies of iron our population considering the updated neonatal SIRS criteria afore- metabolism in foals16 where plasma iron concentration and several mentioned, only 3 of 24 SIRS foals would be in this situation. Plasma hematologic values changed rapidly during the first days of life in iron concentrations for these neonatal foals were 345, 369.6, and healthy foals we expected fluctuations depending on foals’ age; how- 359.9 g/dL, respectively. Using both SIRS criteria (original and updated) ever, it was unexpected to observe a large variability of plasma iron con- 14 of 47 sick neonatal foals would be classified in the SIRS group. centrations in neonatal foals of a given age (ie, 24-48 h). In addition, Although SIRS criteria are much simpler and faster screening tool significant differences between healthy and SIRS foals were expected in for sepsis detection than sepsis scores, the clinician must be cognizant this study but were not observed. Perhaps, grouping foals according to of the fact that SIRS can be caused by a number of causes other than age (ie, 1-3 days, 3-7 days, and <14 days) would have helped us to bet- infection such as trauma, burns, pancreatitis, ischemia, hemorrhage, ter assess plasma iron dynamics. and anaphylaxis.5,7 In the present population of foals classified with In the studied population of neonatal foals, there was no significant the original SIRS criteria, no differences were seen in plasma iron con- difference in mean plasma iron concentrations between healthy foals centration between SIRS and non-SIRS sick foals. The expected find- and sick foals (P = .99). In equine medicine, previous reports suggest ing would have been higher plasma iron concentrations in hospital that plasma iron concentrations in adult horses are an acute and sensi- controls and significantly lower plasma iron concentrations in neonatal tive indicator of systemic inflammation. 2,12 In adult horses plasma iron foals with SIRS. Data on the incidence of SIRS and the usefulness of concentration is considered decreased when values fall below the ref- biomarkers of SIRS in veterinary medicine are scarce. 27 Other markers 2 erence interval (105-277 g/dL). We expected to find lower iron of systemic inflammation currently validated in equine neonatology plasma concentrations in sick foals compared to healthy foals, as occurs are plasma fibrinogen, serum amyloid A28,29 and C-reactive protein in the equine adult population because of the iron withholding mecha- concentrations.30 nism. In the setting of infectious, inflammatory, and neoplastic diseases, In the study herein reported, surprisingly, different plasma iron a primitive defense mechanism of the organism is to withhold iron from concentrations resulted from each healthy control groups (hospital- microorganisms.20 The iron withholding defense system includes con- ized controls: 126.1 [99.2-153.1]  g/dL and stud controls: 181.8 stitutive iron-binding components such as transferrin, lactoferrin, and [171.3-192.4] g/dL, mean and [95% CI of the mean], respectively). It ovotransferrin, as well as the suppression of iron efflux from macro- could be reasonable to think that sick dams can be hypogalactic,17 phages, reduction in plasmatic iron, and increased synthesis of ferritin and as explained before, colostrum and milk are the major source of by macrophages to accommodate iron from phagocytised lactoferrin iron for newborns. Perhaps measuring plasma and colostrum/milk iron iron.21 At baseline and in response to nutritional iron deficiency, infec- concentration of the mares and the amount of colostrum ingested 22 tion, bleeding and pregnancy, hepcidin regulates iron metabolism. would have been useful in explaining the differences between the Hepcidin is potently induced by inflammation, predominantly by the control populations. On the other hand, these results could also be cytokine IL-6, and has shown to be essential for innate immunity explained by the effect of the age (P < .001). Age differences between to gram-negative bacteria.22 This hormone controls iron flows into the stud control and healthy hospitalized foals (1.5 versus 4.5 days, plasma through inhibition of the only known mammalian cellular iron respectively) could at least partly explain the differences observed in exporter ferroportin.23 Hepcidin is feedback-regulated by iron status plasma iron concentrations (Figure 2). To rule out the age effect and strongly modulated by inflammation and erythropoietic demand.23 in future studies, we suggest classifying foals according to age 1330 SANMARTÍ ET AL. (ie, 1-3 days, 3-7 days, and <14 days), in order to differentiate plasma 2. Borges AS, Divers TJ, Stokol T, Mohammed OH. Serum iron and iron concentrations in SIRS and non-SIRS neonates as some other plasma fibrinogen concentrations as indicators of systemic inflamma- tory diseases in horses. J Vet Intern Med. 2007;21:489-494. authors have done measuring age-dependent plasma biochemical vari- 3. Wong DM, Ruby RE, Dembek KA, et al. Evaluation of updated sepsis ables in neonatal foals. 31 scoring systems and systemic inflammatory response syndrome Another of the limitations of this study could be the absence criteria and their association with sepsis in equine neonates. J Vet of information regarding iron metabolism in the animals included, Intern Med. 2018;32:1185-1193. because, except for plasma iron concentration, no other variables 4. Levy MM, Fink MP, Marshall JC, et al. 2001 SCCM/ESICM/ACCP/ ATS/SIS International Sepsis Definitions Conference. Intensive Care related to iron metabolism were analyzed. Iron metabolism in equine Med. 2003;29:530-538. medicine can be directly evaluated by measuring the amount of iron 5. Bone R, Balk R, Cerra F, et al. ACCPL/SCCM consensus conference: in the blood, including: plasma iron concentration, the capacity of the definitions for sepsis and organ failure and guidelines for the use of blood to transport iron by measuring transferrin or total iron binding innovative therapies in sepsis. Chest. 1992;101:1644-1655. capacity (TIBC) and the amount of iron storage measuring ferritin. 18 6. Corley KT, McKenzie HC, Amoroso LM, Furr MO. Initial experience with norepinephrine infusion in hypotensive critically III foals. J Vet Another limitation of this study could be the lack of a full hematology Emerg Crit Care. 2000;10:267-276. Printed by [Wiley Online Library - 083.042.103.159 - /doi/epdf/10.1111/jvim.15770] at [29/07/2020]. data from the stud control group. All samples were taken from 7. McKenzie HC, Furr MO. Equine neonatal sepsis: the pathophysiology healthy foals based on: normal foaling, normal physical exam, and of severe inflammation and infection. Compend Equine Ed. 2001;23: serum immunoglobulin G concentration above 800 mg/dL within 3-8. 24-48 hours postpartum. Despite this limitation, we considered that 8. Corley KTT, Donaldson LL, Furr MO. Arterial lactate concentration, hospital survival, sepsis and SIRS in critically ill neonatal foals. Equine a large homogeneous healthy group, with a daily close veterinary Vet J. 2005;37:53-59. follow-up was still of a great value for the study. 9. 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