Blood arginine vasopressin, adrenocorticotropin hormone, and cortisol concentrations at admission in septic and critically ill foals and their association with survival

BACKGROUND: Sepsis is an important cause for neonatal foal mortality. The hypothalamic-pituitary-adrenal axis (HPAA) responses to sepsis are well documented in critically ill humans, but limited data exist in foals. The purpose of this study was to evaluate the HPAA response to sepsis in foals, and to associate these endocrine changes with survival. HYPOTHESIS: Blood concentrations of arginine vasopressin (AVP), adrenocorticotropin hormone (ACTH), and cortisol will be higher in septic foals as compared with sick nonseptic and healthy foals. The magnitude of increase in hormone concentration will be negatively associated with survival. ANIMALS: Fifty-one septic, 29 sick nonseptic, and 31 healthy foals of < or =7 days of age were included. METHODS: Blood was collected at admission for analysis. Foals with positive blood culture or sepsis score > or =14 were considered septic. Foals admitted with disease other than sepsis and healthy foals were used as controls. AVP, ACTH, and cortisol concentrations were measured using validated immunoassays. RESULTS: AVP, ACTH, and cortisol concentrations were increased in septic foals. Septic nonsurvivor foals (n = 26/51) had higher plasma ACTH and AVP concentrations than did survivors (n = 25/51). Some septic foals had normal or low cortisol concentrations despite increased ACTH, suggesting relative adrenal insufficiency. AVP, ACTH, and cortisol concentrations were higher in sick nonseptic foals compared with healthy foals. CONCLUSIONS AND CLINICAL IMPORTANCE: Increased plasma AVP and ACTH concentrations in septic foals were associated with mortality. Several septic foals had increased AVP : ACTH and ACTH : cortisol ratios, which indicates relative adenohypophyseal and adrenal insufficiency.     

Efficacy and Safety of a Commercial Fresh-Frozen Hyperimmune Plasma in Foals With Failure of Passive Transfer of Immunity

In foals more than 12 hours old, the only effective therapy for the treatment of failure of passive transfer (FPT) of immunity is transfusion of equine plasma. Use and efficacy of equine plasma for prophylaxis and treatment of sepsis, a condition primarily associated with FPT, are widely reported. However, plasma- and recipient-related factors associated with extent of IgG transfer and catabolism are not completely defined. Efficacy and safety of transfusion of a commercial fresh-frozen hyperimmune plasma were evaluated in hospitalized foals younger than 7 days of age with total or partial FPT. Sixty-two foals, classified as affected by FPT only, septic (infection plus systemic inflammatory response syndrome [SIRS]), and nonseptic sick, were included, and serum IgG concentration was measured at admission and 24 hours after plasma transfusion. In 25/62 foals, IgG level after 72 hours was also determined. The impact of different classification criteria for septic foals on IgG transfer was evaluated. Serum IgG measured 24 hours and 72 hours after plasma transfusion was significantly greater than at admission, but no significant difference was found in transfer efficacy (TE) between FPT, FPT septic, and FPT nonseptic foals and no significant difference was found in IgG concentration comparing foals with total and partial FPT or survivors and nonsurvivors. No significant difference was found comparing IgG concentration between bacteremic and nonbacteremic foals and foals with or without SIRS. No foal experienced adverse reactions to plasma transfusion. IgG TE and catabolism did not result significantly affected by the presence of sepsis or illness or by the outcome.     

Uveal Inflammation in Septic Newborn Foals

Background: Septicemia in humans is described as a leading cause of uveitis, which eventually can induce blindness. Hypothesis/Objectives: Uveal inflammatory findings could be related to sepsis severity in newborn foals and might be used as an indirect indicator for survival. Animals: Seventy‐four septic foals, 54 nonseptic foals, and 42 healthy foals. Methods: Prospective observational clinical study. A detailed blinded, ophthalmic examination was performed by boarded ophthalmologists on all admitted newborn foals. Foals were grouped as septic (when blood culture resulted positive or the sepsis score was ≥14), nonseptic, and controls. Based on blood culture results, the septic group was subdivided into bacteremic and nonbacteremic foals. Results: Blood culture was performed in 62/74 septic foals, from which 35 (56%) were bacteremic and 27 (44%) were nonbacteremic. Anterior uveitis was diagnosed in a significantly (P < .005) higher number of septic/bacteremic foals (14/35, 40%) than in septic/nonbacteremic foals (5/27, 19%), nonseptic foals (4/54, 7%), and control foals (0%). Anterior chamber fibrin was only observed in 4/14 (29%) septic/bacteremic foals with anterior uveitis. Anterior uveitis was also associated with posterior uveitis in 6/35 (19%) septic/bacteremic foals. The diagnosis of uveitis was related to nonsurvival (P= .001, odds ratio = 6.2, 95% confidence interval = 2.1–18.2). Conclusions and Clinical Importance: Anterior uveitis is highly prevalent in septic newborn foals, especially in those with a positive blood culture, and it should be considered as a survival prognostic factor.     

Plasma C‐Reactive Protein and Haptoglobin Concentrations in Critically Ill Neonatal Foals

Background

Accurate diagnostic markers for sepsis in neonatal foals are needed. Plasma C‐reactive protein concentration (p[CRP]) and haptoglobin concentration (p[Hp]) are well‐established biomarkers of infection in humans, but studies are lacking in foals.

Hypotheses

p[CRP]) and p[Hp] are increased in septic foals compared to sick nonseptic and healthy control foals, and are predictive of survival.

Animals

Eighty critically ill foals (40 septic, 40 sick nonseptic) and 39 healthy control foals <1 week of age.

Methods

Multicenter, prospective observational clinical study. Venous blood was collected at admission from septic and sick nonseptic foals and from clinically healthy foals at 24 h of age. A diagnosis of sepsis was made based on positive blood culture or a sepsis score >11, and p[CRP] and p[Hp] were measured by using ELISA tests. Data were analyzed by using the Mann‐Whitney U‐test and forward stepwise multivariable linear regression. P < .05 was considered significant.

Results

Plasma [CRP] was positively associated with age, serum globulin, adrenomedullin, and bilirubin concentrations, aspartate aminotransferase activity, glutamyl‐transferase activity, band neutrophil count, and rectal temperature, and was increased in foals with toxic neutrophils, enterocolitis, colic, rib fractures and septic arthritis. Surprisingly, p[Hp] was lower in septic foals than in sick nonseptic foals. Neither p[CRP] or p[Hp] was predictive of survival in critically ill foals.

Conclusions and Clinical Importance

Plasma [CRP] increases with inflammation in neonatal foals but is not indicative of sepsis. Single time point, admission sampling of p[CRP] and p[Hp] do not appear to be useful biomarkers for sepsis in foals.     

Insulin, glucagon, and leptin in critically ill foals

Background: Endocrine dysregulation of hormones of energy metabolism is well documented in critically ill humans, but limited information exists in septic foals. The purpose of this study was to provide information on the hormonal response to energy metabolism in critically ill foals, focusing on insulin, glucagon, and leptin. Hypothesis: Concentrations of insulin, glucagon, leptin, and triglycerides will be higher, whereas glucose concentration will be lower in septic foals than in healthy and sick nonseptic foals. The magnitude of these differences will be associated with severity of disease and nonsurvival. Animals: Forty‐four septic, 62 sick nonseptic, and 19 healthy foals <7 days of age. Methods: In this prospective multicenter cross‐sectional study, blood samples were collected at admission. Foals with positive blood culture or sepsis score ≥12 were considered septic. Results: Septic foals had lower glucose and insulin and higher triglyceride and glucagon concentrations than did healthy foals. Glucagon concentrations were not different between septic foals that died (n = 14) or survived (n = 30). Higher insulin and lower leptin concentrations were associated with mortality. Quantitative insulin‐sensitivity check index was higher in septic foals. Conclusions and Clinical Importance: Energy metabolism and the endocrine response of related hormones in septic foals are characterized by hypoglycemia, hypertriglyceridemia, low insulin concentration, and high glucagon concentration. Leptin and insulin may have prognostic value for nonsurvival in septic foals. The hormonal response related to energy metabolism in critical illness differs between foals and humans.     

Fibrin deposits and organ failure in newborn foals with severe septicemia

Background: Septicemia in human neonates frequently is complicated by activation of the coagulation system, disseminated intravascular coagulation (DIC) and multiple organ failure syndrome, which may contribute to high mortality. In adult horses with DIC, the lung has been the organ most frequently affected by fibrin deposits. In addition, in vivo studies suggest that hemostatic mechanisms may be immature in foals <1‐day old. Hypothesis: Newborn foals with severe septicemia have fibrin deposits in their tissues independently of their age, and these fibrin deposits are associated with organ failure. Animals: Thirty‐two septic and 4 nonseptic newborn foals euthanized for poor prognosis. Methods: Tissue samples (kidney, lung, and liver) collected on postmortem examination were stained with phosphotungstic acid hematoxylin (PTAH) and immunohistochemistry (IHC) for blind histologic examination. A fibrin score (grades 0–4) was established for each tissue sample and for each foal. Medical records were reviewed for assessing clinical evidence of organ failure during hospitalization. Results: Fibrin deposits were found in most septic foals (28/32 when using IHC and 21/32 when using PTAH), independently of the age of the foal. The lung was the most affected tissue (97% of the septic foals). Additionally, organ failure was diagnosed in 18/32 septic foals (8 with respiratory failure, 14 with renal failure), although a statistical association with severe fibrin deposition was not identified. Conclusions and Clinical Importance: Nonsurviving septic foals have fibrin deposits in their tissues, a finding consistent with capillary microthrombosis and DIC.     

Plasma Adrenomedullin Concentrations in Critically Ill Neonatal Foals

Background

Bacterial sepsis remains a leading cause of morbidity and mortality in neonatal foals, but accurate diagnostic and prognostic markers are lacking. Adrenomedullin (AM) is a polypeptide with diverse biologic effects on the cardiovascular system that increases in septic humans and laboratory animals.

Hypotheses

Plasma AM concentration (p[AM]) is increased in septic neonatal foals compared to sick nonseptic and healthy control foals, and p[AM] is predictive of survival in septic neonatal foals.

Animals

Ninety critically ill (42 septic, 48 sick nonseptic) and 61 healthy foals <1 week of age.

Methods

A prospective observational clinical study was performed. Venous blood was collected from critically ill foals at admission and from healthy foals at 24 hours of age. Critically ill foals were categorized as septic or sick nonseptic based on blood culture results and sepsis score. Plasma [AM] was measured by using a commercially available ELISA for horses. Data were analyzed by using the Mann‐Whitney U‐test and P < .05 was considered significant.

Results

Plasma [AM] was not significantly different between septic and sick nonseptic foals (P = .71), but critically ill foals had significantly increased p[AM] compared to healthy controls (P < .0001). In critically ill foals, p[AM] was not predictive of survival (P = .051). A p[AM] cutoff concentration of 0.041 ng/mL provided a test sensitivity of 91% and specificity of 54% to predict illness.

Conclusions and Clinical Relevance

Plasma [AM] shows promise as a marker of health in neonatal foals, but p[AM] increases nonspecifically during perinatal illnesses and is not necessarily associated with sepsis.     

Serum lactoferrin and immunoglobulin G concentrations in healthy or ill neonatal foals and healthy adult horses

BACKGROUND: Lactoferrin is a colostral glycoprotein with antimicrobial properties. HYPOTHESES: (1) Serum lactoferrin and immunoglobulin G (IgG) concentrations are correlated and increase in healthy foals after ingestion of colostrum; (2) compared to healthy foals, ill foals will have lower lactoferrin concentrations that correlate with their IgG concentration, neutrophil count, the diagnosis of sepsis, and survival; and (3) plasma concentrations of lactoferrin will be less than serum concentrations. ANIMALS: Healthy foals (n = 16), mature horses (n = 10), and ill foals 1-4 days old (n = 111) that were examined for suspected sepsis were used for blood collection. Colostrum was obtained from 10 healthy mares unrelated to the foals. METHODS: Blood was obtained from the healthy foals at birth and 1-3 days of age and from the ill foals at admission. Serum IgG was quantified by single radial immunodiffusion (SRID). Lactoferrin concentrations in colostrum and blood were determined by an enzyme-linked immunosorbant assay. The sepsis score, blood culture results, neutrophil counts, and survival were obtained on ill foals. RESULTS: The mean colostral lactoferrin concentration was 21.7 microg/mL. Compared to values at birth, serum IgG (18+/-2 versus 2,921+/-245 mg/dL, SEM) and lactoferrin (249+/-39 versus 445+/-63 ng/mL, SEM) concentrations were significantly greater in healthy foals 1-3 days old. Serum lactoferrin concentration in 1-3-day-old healthy foals was not different from mature horses or ill foals. IgG and lactoferrin concentrations were significantly correlated only in healthy foals. Serum lactoferrin concentrations were significantly lower in ill neutropenic foals. The serum IgG concentration was significantly lower in ill foals as compared to healthy foals. Only serum IgG was significantly less in ill foals with a positive sepsis score and in nonsurvivors, Plasma lactoferrin concentrations were lower than serum concentrations, although values were significantly correlated. CLINICAL IMPORTANCE: Although both serum IgG and lactoferrin concentrations increase in healthy foals after ingestion of colostrum, only serum IgG is significantly correlated with the sepsis score and outcome.     

Biochemical markers of cardiac injury in normal, surviving septic, or nonsurviving septic neonatal foals

The cardiac biomarkers cardiac troponin T (cTnT) and I (cTnI) and the cardiac isoenzyme of creatine kinase (CKMB) are used extensively in human medicine to diagnose and provide valuable prognostic information in patients with ischemic, traumatic, and septic myocardial injury. We designed a study to establish normal values for these markers in healthy, neonatal foals and to compare them with values obtained from septic neonates in a referral hospital population. The 25th, 50th, 75th, and 95th percentiles for cTnI and CKMB in the healthy-foal population were 0.08, 0.14, 0.25, 0.49 ng/mL and 1.4, 2.3, 4.0, 7.4 ng/mL, respectively. The values obtained for cTnT were frequently (43/52 foals; 83%) below the lower limit of detection of the assay (0.009 ng/mL), but the median and range were 0.009 and 0.009-0.041 ng/mL, respectively. In the septic foal population, the 25th, 50th, 75th, and 95th percentile values for cTnI and CKMB were 0.05, 0.12, 0.22, and 1.10 ng/mL and 2.0, 4.4, 7.8, and 24 ng/mL, respectively. The values obtained for cTnT were less frequently below the lower limit of detection (23/38 foals; 60%) compared with the healthy foal population, and the median and range were 0.009 and 0.009-0.20 ng/mL, respectively. Significantly higher values were observed for cTnT and CKMB in septic foals compared with the healthy neonatal foal population, but there were no differences among septic foals in survivors compared with nonsurvivors. These findings suggest that myocardial injury occurs during septicemia in neonatal foals but that the injury is not associated with survival among septic foals.     

Prognostic value of clinicopathologic variables obtained at admission and effect of antiendotoxin plasma on survival in septic and critically ill foals

This prospective study compared survival rates of critically ill and septic foals receiving 1 of 2 different types of commercial equine plasma and analyzed admission variables as possible predictors of survival. Standardized clinical, hematologic, biochemical, and hemostatic admission data were collected and foals received either conventional commercially available hyperimmune equine plasma or equine plasma specifically rich in antiendotoxin antibodies in a double-blinded, coded fashion. Sepsis was defined as true bacteremia or sepsis score >11. Overall survival rate to discharge was 72% (49/68). Foals that were nonbacteremic and demonstrated a sepsis score of < or = 11 at admission had a 95% (18/19) survival rate. The survival rate to discharge for septic foals was 28/49 (57%), with truly bacteremic foals having a survival rate of 58% (14/24), whereas that for nonbacteremic, septic foals was 56% (14/25). Sensitivity and specificity for sepsis score >11 as a predictor of bacteremia were 74 and 52%, respectively. For the entire study population, a higher survival rate to discharge was documented for those foals receiving hyperimmune plasma rich in antiendotoxin antibodies (P = .012, odds ratio [OR] 6.763, 95% confidence interval [CI]: 1.311, 34.903). Administration of plasma rich in antiendotoxin antibodies also was associated with greater survival in septic foals (P = .019, OR 6.267, 95% CI: 1.186, 33.109). Statistical analyses demonstrated that, among 53 clinical and clinicopathologic admission variables, high sepsis score (P < .001), low measured IgG concentration (P = .01), high fibrinogen concentration (P = .018), low segmented neutrophil count (P = .028), and low total red blood cell numbers (P = .048) were the most significant predictors of overall mortality.     

Plasma Endotoxin Concentrations in Clinically Normal and Potentially Septic Equine Neonates

Plasma endotoxin concentrations were measured at 1 to 2 and 5 to 6 days of age in clinically normal foals and in potentially septic neonatal foals admitted to North Carolina State University's Veterinary Teaching Hospital for a variety of conditions. In 1 to 2 and 5 to 6 day old normal foals, median plasma endotoxin concentrations were 2.17 (range, 1.61–2.54; n = 6) and 2.89 (range, 2.61–3.50; n = 7) endotoxin units/mL (EU/mL), respectively. Median plasma endotoxin concentration in potentially septic foals with negative blood cultures or gram positive isolates (n = 8) was 2.73 (range, 0.59–4.04) EU/mL. In hospitalized foals with gram negative isolates (n = 6), median plasma endotoxin concentration was 78.06 (range, 0.76–2,696.41) EU/mL, but individual endotoxin values were only increased in foals that were extremely sick and died within hours of sampling. Plasma endotoxin concentrations were significantly greater in foals with sepsis scores ≥ 11 compared with foals with sepsis scores ≤ 10. Increased plasma endotoxin concentrations appear to predict an unfavorable outcome in septic foals, but normal endotoxin concentrations do not appear to have any predictive value. (Journal of Veterinary Internal Medicine 1993; 7:296–302. Copyright © 1993 by the American College of Veterinary Internal Medicine.)     

Antithrombin: Could It be a Diagnostic and Prognostic Marker in Septic Neonatal Foals?

Antithrombin (AT) levels are lower in human neonates affected by sepsis and in nonsurvivors compared with survivors. The aims of this study were to evaluate AT profile in healthy newborn foals and its diagnostic and prognostic role in septic foals during the first week of life. Fifteen healthy foals and 35 septic foals were enrolled. Blood samples were collected from each healthy foal at 30 minutes, 3 and 12 hours from birth, daily from days 1–7, and at days 10 and 14. Blood was collected from each septic foal twice a day from admission to discharge or death. The AT analysis was performed by chromogenic method. Healthy foals showed decreasing levels of AT between 3 hours and 2 days, followed by an increasing trend. Septic foals did not show any difference during the period of observation, and no differences were found between healthy and septic age-matched foals. The analysis of AT activity on the day of admission in septic foals showed higher levels compared with healthy foals, in animals hospitalized at 12 and 24 hours of age (P < .01). No differences were found at admission between foals affected by sepsis and that with septic shock. Nonsurviving foals showed significantly lower levels at 3 and 4 days of age compared with surviving foals; when surviving and nonsurviving foals were compared independently by the age, nonsurviving foals showed significant (P < .05) lower levels 12 hours after admission. In conclusion, AT seems to show neither a diagnostic nor a prognostic role in septic neonatal foals.     

Synovial fluid D-dimer concentration in foals with septic joint disease

Background: Increased synovial fibrinolytic activity (detected by increases in synovial D‐Dimer concentrations) has been observed in different joint diseases in humans and adult horses, presumably in order to minimize fibrin deposition within the joint and thus avoid its detrimental effects. Objective: To investigate fibrinolytic pathway activation in joint sepsis in foals by measuring synovial D‐Dimer concentrations. Animals: Eighteen septic foals with septic joints, 9 septic foals without septic joints, 9 systemically healthy foals with septic joint, and 3 controls are included. Methods: Prospective observational clinical study of foals admitted for septic arthritis. Synovial D‐Dimer concentration and routine synovial fluid analysis were performed. Diagnosis of joint sepsis was made whenever synovial total nucleated cell count was >30,000 cells/μL, synovial total protein >4 g/dL, and neutrophil percentage of >80%, or synovial fluid culture resulted positive. Results were compared among groups by general lineal models. Results: Synovial D‐Dimer concentration was significantly (P < .001) higher in the foals with septic joints compared with foals without joint disease (P < .001). Conclusions and Clinical Importance: Septic joint disease is associated with a marked increase of synovial D‐Dimer concentration (marked activation of the fibrinolytic activity) within the affected joint. Although further studies are needed, the measurement of synovial D‐Dimer concentration may be considered a complementary diagnostic marker of septic joint disease.     

Mean platelet component as an indicator of platelet activation in foals and adult horses

BACKGROUND: Mean platelet component (MPC) is a new platelet variable, measured by modern commercial complete blood count analyzers, that is reduced during platelet activation in humans and small animals. HYPOTHESIS: MPC decreases in horses with clinical conditions that cause platelet activation and disseminated intravascular coagulation (DIC). ANIMALS: We obtained 418 CBCs from 100 sick and 20 healthy neonates and 178 sick and 45 sound adult horses. Sick neonates were classified into septic and nonseptic, and DIC and non-DIC groups. Adults were grouped by diagnoses (systemic inflammatory disorders, gastrointestinal problems, and thrombocytopenia). METHODS: MPC together with platelet count, mean platelet volume, platelet distribution width, and platelet component distribution width were measured with a commercial analyzer and compared between the different disease and control groups in neonates and in adults. RESULTS: MPC values were significantly lower in the septic and nonseptic neonates (24.0 +/- 3.5 g/dL and 26.6 +/- 2.6 g/dL, respectively) than in the control group (28.1 +/- 1.7 g/dL). Neonates with DIC had the lowest MPC values (23.8 +/- 6.3 g/dL). MPC values in adult horses were significantly lower in the inflammatory (23.5 +/- 4.7 g/dL), gastrointestinal obstruction (23.0 +/- 5.0 g/dL), enteritis (23.6 +/- 4.6 g/dL), ischemic (23.9 +/- 5.1 g/dL), and thrombocytopenia (20.2 +/- 5.7 g/dL) groups when compared with control horses (26.2 +/- 3.5 g/dL). Other platelet variables were not different between the control and the disease groups. CONCLUSION AND CLINICAL IMPORTANCE: MPC might be a useful variable for quickly and easily detecting platelet activation in sick neonates and adult horses.     

Neutrophilic myeloperoxidase index and mean light absorbance in neonatal septic and nonseptic foals

Background: Two neutrophilic indices reported by the ADVIA 120 Hematology Analyzer, neutrophilic myeloperoxidase index (MPXI), and mean light absorbance (neutrophil X mean [NXM]) have been proposed as indicators of systemic inflammatory disease in horses and of neutrophil activation in coronary ischemic syndromes in people. Objective: The aim of this study was to evaluate NXM and MPXI in healthy, sick nonseptic, and sick septic foals to determine whether conditions likely associated with neutrophil activation result in decreases in these variables. Methods: In this retrospective study, CBC data from 61 neonatal foals presented to the Equine Teaching Hospital of Barcelona were evaluated for correlations between MPXI, NXM, percentage of large unstained cells, neutrophil count, and percentage of band neutrophils. Results obtained in septic (n=32), sick nonseptic (n=22), and healthy foals (n=7) were compared. In addition, results recorded in septic/neutropenic (n=12), septic/non‐neutropenic (n=20), nonseptic/neutropenic (n=8), nonseptic/non‐neutropenic (n=14), and healthy foals (n=7) were also compared. Results: A weak negative correlation was found between MPXI and neutrophil count and between NXM and percentage of band neutrophils. Septic/neutropenic foals had significantly higher MPXI values (median 17.9, minimum–maximum 4.7–42.5) than did septic/non‐neutropenic (1.5, ?24.4 to 22.3), nonseptic/neutropenic (6.6, 0.6–17.9), and nonseptic/non‐neutropenic foals (8.8, ?10.1 to 16.8) but did not differ significantly from controls (12.8, ?8.5 to 20.4). Conclusions: Significant differences in NXM or MPXI were not found when disease groups were compared with controls; however, septic/neutropenic foals had significantly higher median MPXI than other groups of sick foals. Further prospective studies are needed to clarify if this finding is related to decreased neutrophil function or activation in septic/neutropenic foals.     

Calcium Regulating Hormones and Serum Calcium and Magnesium Concentrations in Septic and Critically Ill Foals and their Association with Survival

Background: Disorders of calcium regulation are frequently found in humans with critical illness, yet limited information exists in foals with similar conditions including septicemia. The purpose of this study was to determine whether disorders of calcium exist in septic foals, and to determine any association with survival.
Hypothesis: Blood concentrations of ionized calcium (Ca²⁺) and magnesium (Mg²⁺) will be lower in septic foals with concomitant increases in parathyroid hormone (PTH), calcitonin (CT), and parathyroid-related peptide (PTHrP) compared with healthy foals. The magnitude of these differences will be negatively associated with survival.
Animals: Eighty-two septic, 40 sick nonseptic, and 24 healthy foals of ≤7 days were included.
Methods: Prospective, observational study. Blood was collected at initial examination for analysis. Foals with positive blood culture or sepsis score ≥14 were considered septic. Foals with disease other than sepsis and healthy foals were used as controls. Hormone concentrations were measured with validated immunoassays.
Results: Septic foals had decreased Ca²⁺ (5.6 versus 6.1 mg/dL, P < .01) and increased serum PTH (16.2 versus 3.2 pmol/L, P < .05), and phosphorus concentrations (7.1 versus 6.3 mg/dL, P < .01). No differences in serum Mg²⁺, PTHrP, and CT concentrations were found. Nonsurviving septic foals (n = 42/82) had higher PTH concentrations (41.1 versus 10.7 pmol/L, P < .01) than survivors (n = 40/82).
Conclusions and Clinical Importance: Septic foals were more likely to have disorders of calcium regulation compared with healthy foals, where hyperparathyroidemia was associated with nonsurvival.     

Association of adrenocorticotrophin and cortisol concentrations with peripheral blood leukocyte cytokine gene expression in septic and nonseptic neonatal foals

Background

The hypothalamic‐pituitary‐adrenal (HPA) is influenced by the proinflammatory cytokines IL‐6, IL‐1β, and TNF‐α in critically ill humans. Information about the association of cytokines with the HPA axis in neonatal foals is lacking.

Hypothesis/Objectives

The objectives were to describe for hospitalized septic and nonseptic foals (1) temporal changes in blood concentrations of ACTH, and cortisol, and leukocyte cytokine gene expression, and (2) coassociation of these HPA axis hormones with blood leukocyte cytokine gene expression.

Animals

Hospitalized septic foals (N = 15) and hospitalized nonseptic foals (N = 11).

Methods

Blood samples, obtained from study foals at admission (T = 0), and 24 (T = 1), 48 (T = 2), 72 (T = 3), and 96 (T = 4) hours after admission, were processed to isolate RNA from leukocytes and to harvest plasma and serum for hormone assays. Plasma ACTH and serum cortisol concentrations were determined by radioimmunoassay. Leukocyte mRNA expression of IL‐1β IL‐6, IL‐8, IL‐10, and TNF‐α was determined using RT‐PCR.

Results

Cortisol concentrations were greater (P < .05) in foals at admission than at other time points. The expressions of IL‐8 and IL‐10 mRNA were lower (P < .05) at each time point in septic than in nonseptic foals. Among septic foals, ACTH was positively associated (P = .0026) with IL‐6 mRNA expression.

Conclusions

Sepsis influences secretion of the HPA axis hormones and expression of cytokines in foals. A positive association with the HPA axis and IL‐6 expression was detected. The clinical importance of these findings requires additional study.     

Pharmacokinetics of once-daily amikacin in healthy foals and therapeutic drug monitoring in hospitalized equine neonates

The objectives of this study were to investigate the pharmacokinetics of once-daily amikacin in healthy neonates, to determine amikacin concentrations in hospitalized foals, and to determine the minimum inhibitory concentrations (MICs) of amikacin against gram-negative isolates from blood cultures in septic foals. Median half-life, clearance, and volume of distribution of amikacin in healthy 2- to 3-day-old foals after administration of an intravenous bolus of amikacin (25 mg/kg) were 5.07 hours (4.86-5.45 hours), 1.82 mL/min/kg (1.35-1.97 mL/min/kg), and 0.785 L/kg (0.638-0.862 L/kg), respectively. Statistically significant (P <.05) decreases in area under the curve (14% decrease), mean residence time (19% decrease), and C24h plasma amikacin concentrations (29% decrease) occurred between days 2-3 and 10-11. Plasma amikacin concentrations in healthy foals at 0.5 hours (C0.5h) were significantly higher (P = .02) than those of hospitalized foals. Sepsis, prematurity, and hypoxemia did not alter amikacin concentrations. The MIC at which 90% of all gram-negative isolates from equine neonatal blood cultures were inhibited by amikacin was 4 microg/mL, suggesting that amikacin C0.5h of 40 microg/mL should be targeted to achieve a maximum serum concentration to MIC ratio of 10:1. The proportion of foals with C0.5h 40 microg/mL was significantly higher (P < .0001) in hospitalized foals receiving a dose of amikacin at 25 mg/kg (22/24 or 92%) than in foals receiving a dose at 21 mg/kg (9/25 or 36%), whereas no difference was found in the proportion of foals with C24h concentrations > or = 3 microg/mL between the 2 groups. An initial dose at 25 mg/kg is recommended for once-daily amikacin in equine neonates.     

Association of admission plasma D-dimer concentration with diagnosis and outcome in horses with colic

Background: Coagulopathies detected in horses with gastrointestinal problems seem to be associated with poor outcome. Plasma D‐Dimer concentration is a sensitive test for assessing coagulopathies. Hypothesis: Plasma D‐Dimer concentration tested on admission is related to diagnosis and outcome in horses with colic. Animals: Four hundred and ninety three horses referred for evaluation of abdominal pain. Methods: Prospective observational clinical study. Horses were grouped according to diagnosis (medical and surgical intestinal obstructions, ischemic disorders with and without intestinal resection, enteritis, peritonitis), outcome (survivors, nonsurvivors), and number of coagulopathies (normal profile, 1 or 2 coagulopathies, subclinical disseminated intravascular coagulation [DIC]). Blood samples were collected on admission and plasma D‐Dimer concentration, clotting times (PT and aPTT), and antithrombin activity were determined. Positive likelihood ratios (LR+) were calculated for evaluation of D‐Dimer cut‐off values, which were later tested in a logistic regression model. Results: Horses with enteritis or peritonitis had significantly (P < .001) higher plasma D‐Dimer concentrations and more severe coagulopathies on admission than horses with other diagnoses. Nonsurvivors also had significantly (P < .001) higher plasma D‐Dimer concentrations at presentation than did survivors, and those horses with subclinical DIC on presentation had an odds ratio (OR) 8.6 (95% confidence interval [CI], 3.3–22.5, P < .001) for nonsurvival. Finally, D‐Dimer concentrations >4,000 ng/mL had a LR+ of 5.9 and an OR 8.8 (95% CI, 4.5–17.1, P < .001) for nonsurvival. Conclusion and Clinical Importance: Plasma D‐Dimer concentration measured on admission can be used to facilitate diagnosis and outcome prediction in horses with colic. A potential cut‐off value for nonsurvival was found at approximately 4,000 ng/mL.     

Blood glucose concentrations in critically ill neonatal foals

Reasons for Performing Study: Critical illness is associated with hyperglycemia in humans, and a greater degree and duration of hyperglycemia is associated with nonsurvival. Hypoglycemia is also seen in critically ill humans, and is associated with nonsurvival. This might also be true in the critically ill foal.
Objectives: To investigate the association of blood glucose concentrations with survival, sepsis, and the systemic inflammatory response syndrome (SIRS).
Methods: Blood glucose concentrations at admission (515 foals) and 24 hours (159 foals), 36 hours (95), 48 hours (82), and 60 hours (45) after admission were analyzed. Logistic regression analyses were performed to investigate the association of glucose concentrations with survival, sepsis, a positive blood culture, or SIRS.
Results: 29.1% of foals had blood glucose concentrations within the reference range (76–131 mg/dL) at admission, 36.5% were hyperglycemic, and 34.4% were hypoglycaemic. Foals that did not survive to hospital discharge had lower mean blood glucose concentrations at admission, as well as higher maximum and lower minimum blood glucose concentrations in the 1st 24 hours of hospitalization, and higher blood glucose at 24 and 36 hours. Foals with blood glucose concentrations <2.8 mmol/L (50 mg/dL) or >10 mmol/L (180 mg/dL) at admission were less likely to survive. Hypoglycemia at admission was associated with sepsis, a positive blood culture, and SIRS.
Conclusions and Potential Relevance: Derangements of blood glucose concentration are common in critically ill foals. Controlling blood glucose concentrations may therefore be beneficial in the critically ill neonatal foal, and this warrants further investigation.