Plasma aldosterone, vasopressin and atrial natriuretic peptide in hypovolaemia: a preliminary comparative study of neonatal and mature horses

REASON FOR PERFORMING STUDY: Neonatal foals succumb rapidly to hypovolaemic shock in comparison to mature horses; they do not consistently increase their heart rate in response to hypotension and respond differently to fluid administration. The hormonal responses to hypovolaemia in the horse and foal require investigation. HYPOTHESIS: The hormonal responses to hypovolaemia and fluid administration differ between mature and neonatal horses. METHODS: Five mature horses and 5 neonatal foals fulfilling predetermined criteria for hypovolaemia, were included in the study. A blood sample was taken at admission and after normalisation of fluid balance. These were analysed for plasma aldosterone, vasopressin (AVP) and atrial natriuretic peptide (ANP). Normally distributed variables were compared using the Student's t test and nonparametric data using the Mann-Whitney U test. RESULTS: ANP, AVP and aldosterone were higher before fluid resuscitation than after fluid resuscitation in mature horses. Aldosterone was higher before than after fluid resuscitation in foals, and was higher in foals both before and after fluid resuscitation than in mature horses. ANP was lower in mature horses after fluid resuscitation than in foals. No other comparisons were significantly different. CONCLUSIONS: The hormonal responses of the mature and neonatal horses are different during hypovolaemia and following fluid resuscitation. POTENTIAL RELEVANCE: The differences in the hormonal responses to hypovolaemia and fluid resuscitation may be important when considering fluid resuscitation of hypovolaemic horses and foals, and warrants further investigation.     

Post-Transfusion Survival of 50Cr-Labeled Erythrocytes in Neonatal Foals

Erythrocytes transfused allogeneically into mature horses have a short survival (less than 4 days) compared with an expected erythrocyte life span of 140-150 days. Yet, foals undergo transfusions for neonatal isoerythrolysis successfully. The authors have determined the survival of transfused erythrocytes in neonatal foals, using the stable isotope, 50Cr, to label the erythrocytes. Normal foals underwent transfusions with labeled erythrocytes from three sources: their own erythrocytes (autologous), the erythrocytes of their dam, and the erythrocytes of an unrelated castrated male. After transfusion, samples were taken at 15 minutes and then daily for a week and every 2 or 3 days for 20 days. A stable isotope of iron (57Fe) and 50Cr were determined on diluted-packed erythrocytes by inductively coupled argon-coupled mass spectrometry techniques. 57Fe was used as measure of the sample hemoglobin concentration. The ratio of 50Cr to 57Fe decreased exponentially in all foals. Half-time (T1/2) was 11.7 days (standard error = 2.2) for four foals that underwent autologous transfusions, 5.5 +/- 1.0 days for five foals that underwent transfusions with the erythrocytes of their dams, and 5.2 +/- 1.1 days for five foals that had transfusions with erythrocytes from an unrelated gelding. The authors conclude that erythrocytes that are transfused allogenically into neonatal foals will survive longer than those transfused into mature horses and that 50Cr labeling can be used to measure survival of transfused erythrocytes.     

Comparison of lithium dilution and thermodilution cardiac output measurements in anaesthetised neonatal foals

Knowledge of cardiac output is expected to help guide the treatment of hypotension associated with critical illness and/or anaesthesia in neonatal foals. However, a practical and safe method of measuring cardiac output has not been described for the foal. Lithum dilution, a new method of cardiac output determination not requiring cardiac catheterisation, has recently been reported in mature horses. We compared this method to thermodilution in isoflurane-anaesthetised foals age 30-42 h and found good agreement between the 2 methods in a range of cardiac outputs 5.4-20.4 l/min. The lithium dilution technique is a practical and reliable method of measuring cardiac output in anaesthetised neonatal foals, and warrants investigation in critically ill conscious foals.     

Serum bile acids concentrations in healthy and clinically ill neonatal foals

BACKGROUND: Reference ranges for serum bile acids (SBA) concentration are well established in healthy adult horses. Increased values are indicative of hepatic disease. HYPOTHESES: SBA concentrations are significantly greater in the neonatal period compared with mature horses, and illness in the neonatal period will further increase SBA. ANIMALS: Ten healthy mature horses, 12 healthy foals, and 31 clinically ill foals. METHODS: Prospective cross-sectional study. Blood samples were obtained once from the mature horses, from healthy foals immediately after birth, at 2 days, and at 1, 2, 3, 4, and 6 weeks of age; and from ill foals less than 1 month of age at the time of admission to the Veterinary Teaching Hospital. SBA concentrations were determined enzymatically and by radioimmunoassay. Total and direct bilirubin and triglyceride concentrations were measured, as well as sorbitol dehydrogenase (SDH) and gamma-glutamyltransferase (GGT) activities. RESULTS: There was a significant negative correlation between age and SBA concentration. Compared with mature horses, SBA concentrations were significantly greater in healthy foals at each collection time over the first 6 weeks of life. Radioimmunoassay values were lower than enzymatic SBA values, with increasing bias as the mean difference between values increased. When comparing age-matched values between healthy and ill foals, there were no significant differences in SBA. None of the ill foals had a primary diagnosis of hepatic disease. There was no significant correlation between the SBA concentration and the bilirubin or triglyceride concentrations or the GGT activity. There was a significant direct correlation between increased SBA and serum SDH activity in healthy foals only. CONCLUSION AND CLINICAL IMPORTANCE: SBA concentrations in foals are significantly higher in the early neonatal period, underscoring the importance of using age-matched references when evaluating clinical pathology values during the neonatal period.     

A review of equine sepsis

Sepsis is defined as an exaggerated, systemic inflammatory response to infection and is a common condition in horses. Systemic inflammatory response syndrome (SIRS) associated with bacterial infection is a hallmark of sepsis. Sepsis in neonatal foals is a common sequela of failure of passive transfer and, in addition to development of SIRS, may be characterised by bacteraemia, pneumonia, enterocolitis, omphalophlebitis, meningoencephalitis or arthritis. Sepsis in mature horses is most commonly observed secondary to gastrointestinal lesions that result in disrupted mucosa and bacterial translocation into circulation (endotoxaemia). Pleuropneumonia and metritis may also cause sepsis in mature horses. Diagnosis of sepsis is based on SIRS criteria as well as suspected or confirmed infection. Due to the relatively low sensitivity of microbial culture and the subjectivity of sepsis scoring, many sepsis biomarkers are being studied for their usefulness in diagnosis and prognostication of sepsis in horses. Treatment of sepsis requires an intensive care approach that includes antimicrobial drug administration, fluid resuscitation and pressure support, and treatment for inflammation, endotoxaemia and coagulopathy. Early recognition of sepsis and prompt antimicrobial drug treatment are critical for a successful outcome. Multiple organ dysfunction syndrome may occur in severe cases of sepsis, with common manifestations including laminitis and coagulopathies. Although prognosis for septic mature horses depends highly on the primary disease process, the overall survival rate in septic neonatal foals ranges from 26 to 86%, with most studies indicating a survival rate of 45–60%.     

Clostridium difficile diarrhea: infection control in horses.

C difficile has emerged as an important cause of diarrheic disease in horses. C difficile diarrhea is usually diagnosed in mature horses, mostly when they are treated with antimicrobials and hospitalized. It is important for clinicians at veterinary hospitals to have knowledge about the organism and the infection. To prevent C difficile diarrhea, judicious use of antimicrobials is important, as is minimizing different stress factors at the animal hospital or clinic. Infected horses must be isolated. Routine examination for C difficile and toxin A or B is recommended in horses with antibiotic-associated diarrhea. When treating foals for R equi pneumonia, it is important to avoid accidental ingestion of erythromycin by the dams. To reduce the number of environmental spores, thorough cleaning and surface disinfection of the animal hospital and clinic are important. Routine handwashing should be performed by all staff.     

Influence of age and breed of equid on plasma copper and zinc concentrations

Plasma ceruloplasmin activities and plasma Cu and Zn concentrations were determined in 215 clinically normal equids of various ages and breeds. Newborn foals, regardless of breed, were hypocupremic, compared with adolescent and mature horses. The mean plasma Cu concentration of newborn Standardbred-Thoroughbred (STD-TB) foals was 2.9 mumol/L, which was about one-sixth of plasma Cu concentrations of mature horses. Newborn draft-cross foals had higher (4.6 mumol/L) plasma Cu concentrations than did newborn STD-TB foals, but plasma Cu content was only one-fifth of the dams' concentrations. Draft-cross horses, regardless of age, had plasma Cu concentrations 15% to 40% higher than did STD-TB horses. Plasma Cu concentrations of Quarter Horse yearlings were similar to those in draft-cross yearlings. Plasma ceruloplasmin activities revealed a curvilinear relationship to plasma Cu concentrations. Plasma Zn concentrations of newborn and 1-week-old STD-TB foals were 30% to 80% higher than those for yearling and mature STD-TB horses. There were no differences between draft-cross neonates and their dams in plasma Zn concentration. Plasma Zn concentrations of neonatal and mature draft-cross horses were 22% higher than those obtained for all other equids. Age and breed of equid should be a consideration in interpretations of plasma Cu and Zn concentrations in equids.     

Surgical management of complete diaphyseal third metacarpal and metatarsal bone fractures: Clinical outcome in 10 mature horses and 11 foals

Reasons for performing study: Osteosynthesis of third metacarpal (McIII) and third metatarsal (MtIII) bone fractures in horses is a surgical challenge and complications surrounding the repair are common. Retrospective studies evaluating surgical repair, complications and outcome are necessary to increase knowledge and improve success of long bone fracture repair in the horse. Objectives: To evaluate clinical findings, surgical repair, post operative complications and outcome of 10 mature horses and 11 foals with McIII or MtIII fractures that were treated with open reduction and internal fixation (ORIF). Methods: Medical records were reviewed and follow‐up information obtained by means of radiographs and/or telephone questionnaire. Results: Survival was achieved in 62% of the horses (3 mature/10 foals). On long‐term evaluation (>6 months) 11 horses (2 mature/9 foals) were fit for their intended activity, one mature horse had a chronic low grade lameness, and one foal was lost to follow‐up because it was sold. The main fracture types were simple transverse (33.3%) or simple oblique (28.6%) and 71.4% of the fractures were open, 3 Type I (one mature/2 foals) and 12 type II (7 mature/5 foals). The preoperative assessment revealed inadequate emergency treatment in 10 horses (5 mature/5 foals; 47.6%). Survival rate of horses with open fractures was 12.5% (1/8) in mature and 85.7% (6/7) in foals. Post operative incisional infection (4 mature, 3 foals) was only managed successfully in 2 foals. Fracture instability related to inadequate fracture fixation technique occurred in 4 horses (all mature) and was always associated with unsuccessful outcome. Conclusions: Age, bodyweight and infection are strongly associated with outcome in treatment of complete McIII/MtIII fractures. Clinical relevance: Rigid fixation using plates and screws can be successful in treatment of closed or open, complete diaphyseal McIII/MtIII fractures in mature horses and foals. Instable fixation, infection and a bodyweight >320 kg are major risk factors for unsuccessful outcome.     

Bacterial isolates from blood and their susceptibility patterns in critically ill foals: 543 cases (1991-1998)

OBJECTIVE: To assess microorganisms isolated from blood specimens obtained from critically ill neonatal foals and to evaluate their antimicrobial susceptibility patterns. DESIGN: Retrospective study. ANIMALS: 543 neonatal foals. PROCEDURE: Medical records of foals that were < 1 month old and were admitted to a referral neonatal intensive care unit were reviewed for results of bacteriologic culture of blood and antimicrobial susceptibility patterns. RESULTS: At least 1 microorganism was isolated from 155 of 543 (28.5%) foals. Escherichia coli was the most commonly isolated bacterium. A single gram-positive organism was detected in 49 foals. Although 90% of the E coli isolates were susceptible to amikacin, some gram-negative and gram-positive organisms had resistance against multiple antimicrobials. CONCLUSIONS AND CLINICAL RELEVANCE: Gram-negative bacteria remain the most common isolates from blood of neonatal foals; however, gram-positive organisms were also found, and with greater prevalence than reported elsewhere. Susceptibility patterns may vary, and resistance to multiple antimicrobials may develop. This is especially true for organisms such as Enterobacter spp and Enterococcus spp. Prudent empirical treatment for neonatal sepsis should include broad-spectrum antimicrobials.     

Therapy of Suspected Septicemia in Neonatal Foals Using Plasma-containing Antibodies to Core Lipopolysaccharide (LPS)

Equine antiserum to core lipopolysaccharide (LPS) was evaluated in a double-blind prospective study for therapeutic benefit in suspected septicemia in neonatal foals. Forty foals younger than 7 days of age were included in the study by satisfaction of clinical and laboratory criteria, suggestive of gram-negative septicemia. Twenty-two foals were treated with core LPS antiserum (plasma produced from horses which were hyperimmunized with rough gram-negative mutant bacterin) and 18 foals received "nonimmune" plasma (from horses prior to immunization against core LPS). All foals received antimicrobials, fluids, and other supportive care measures, depending on clinical signs and according to accepted current practice. The clinical and laboratory data of each foal were monitored and recorded daily for 14 days after plasma treatment or until death.
The overall survival rate of these 40 foals with septicemia was 52.5%. The most prevalent diagnoses in addition to septicemia were enteritis and pneumonia. Of 30 positive bacterial cultures, 93% were due to gram-negative organisms. There was no statistically significant increase in survival rate in the 22 foals given core LPS antiserum ( P ± 0.05).     

Systemic antimicrobial therapy in foals

Antimicrobial agents are commonly used in neonatal foals for the treatment or prevention of sepsis. However, due to concerns about the development of antimicrobial resistance and increasing pressure on veterinarians to rationalise antimicrobial use, we should be trying to reduce the unnecessary use of antimicrobials. This article reviews many of the important considerations when selecting an antimicrobial for use in neonatal foals. Firstly, we consider general differences in neonatal pharmacology and physiology. Secondly, we review common antimicrobial drugs and their indications. Finally, we review antimicrobial stewardship.     

Lung surfactant function and composition in neonatal foals and adult horses

BACKGROUND: Lung surfactant function and composition are varied and adapted to the specific respiratory physiology of all mammalian species. HYPOTHESIS: Lung surfactant function and composition are different in neonatal foals as compared to adult horses. ANIMALS: Six adult horses, 7 term foals (<24 hours old), and 4 premature foals were used. Animals were part of the Auburn University teaching herd except for 3 client-owned premature foals. METHODS: Bronchoalveolar lavage fluid (BALF) was obtained from all animals. Ultracentrifugation of cell-free BALF separated surfactant into crude surfactant pellets (CSP) and supernatant. Both fractions were analyzed for phospholipid and protein content with the Bartlett and bicinchoninic acid method, respectively. Phospholipid composition of the CSP was determined by using high-performance liquid chromatography with an evaporative light scatter detector. Surface tension of the CSP was measured with a pulsating bubble surfactometer. Results from term foals (<24 hours old) were compared statistically to those from adult horses. Values of P < .05 were considered significant. RESULTS: BALF phospholipid content was similar between adult horses and term foals, but BALF protein content was significantly decreased in term foals. Phosphatidylglycerol was significantly decreased, phosphatidylinositol was significantly increased, and the minimum surface tension was significantly increased in the CSP from term foals compared to adult horses. CONCLUSIONS AND CLINICAL IMPORTANCE: Surface tension and phospholipid composition of surfactant in neonatal foals are significantly different compared to adult horses. These changes may influence biophysical and immunologic functions of surfactant.     

Antimicrobial-induced endotoxin and cytokine activity in an in vitro model of septicemia in foals

OBJECTIVE: To determine which antimicrobials that are used to treat neonatal foals with septicemia attributable to Escherichia coli will minimize endotoxin release from bacteria and subsequent activity of inflammatory mediators while maintaining bactericidal efficacy. SAMPLE POPULATION: Blood samples from 10 healthy foals. PROCEDURE: Escherichia coli isolates A and B were isolated from 2 septicemic foals, and minimal inhibitory concentrations (MIC) were determined for 9 antimicrobials. Five of these antimicrobials were tested in vitro at 2 and 20 times their respective MIC. Whole blood or mononuclear cells grown in tissue-culture media were incubated with 105 colony-forming units of E. coli and each antimicrobial or saline (0.9% NaCl) solution. After 6 hours, number of viable bacteria remaining was determined, and supernatant was tested for endotoxin and tumor necrosis activity. RESULTS: Testing in whole blood was compromised by bactericidal effects of the blood itself. In mononuclear cell suspensions, each antimicrobial significantly reduced the number of viable bacteria to low or undetectable amounts. Antimicrobials did not differ significantly in efficacy of bacterial killing. Amikacin used alone or in combination with ampicillin resulted in significantly less endotoxin activity than did ampicillin, imipenem, or ceftiofur alone. There was a correlation between TNF-alpha and endotoxin activity. CONCLUSIONS AND CLINICAL RELEVANCE: Aminoglycosides appear less likely to induce endotoxemia and TNF-alpha synthesis during bactericidal treatment of E. coli septicemia, compared with beta-lactam antimicrobials. Use of ampicillin, imipenem, or ceftiofur in the treatment of septicemic neonatal foals should be accompanied by appropriate treatment for endotoxemia.     

Pathological changes in horses dying with equine influenza in Australia, 2007

Analysis of pathology results from the 2007 equine influenza (EI) outbreak in Australia indicate that young foals in na?ve horse populations are prone to developing broncho-interstitial pneumonia, and that this can be a rare manifestation of EI virus infection in mature horses. All horses may develop secondary bacterial bronchopneumonia, with mature horses more likely to die. EI outbreaks among heavily pregnant mares can result in increased neonatal losses because of premature placental separation and dystocia causing fetal hypoxia.     

Treatment and prevention of equine gastric ulcer syndrome.

EGUS is a common problem in horses and foals. Acids are the important causative factors and current therapy targets the suppression of gastric HCl and creation of a permissive environment for ulcer healing. Diagnosis is based on history, clinical signs, gastroscopy, and response to treatment. Of the products available, only GastroGard (FDA approved) and ranitidine have been shown to be efficacious in the treatment of EGUS. Ranitidine is often associated with treatment failure as a result of incorrect dosing and lack of owner compliance, because of the three times daily dosing required. Also, EGUS occurs in critically ill neonatal foals, but the pathogenesis may be different than in adult horses and acid-suppressive therapy may not be as effective.     

Clostridium difficile: prevalence in horses and environment,and antimicrobial susceptibility

REASONS FOR PERFORMING STUDY: Clostridium difficile has been associated with acute colitis in mature horses. OBJECTIVES: To survey C. difficile colonisation of the alimentary tract with age, occurrence of diarrhoea and history of antibiotic therapy; and to study the occurrence and survival of C. difficile in the environment and antimicrobial susceptibility of isolated strains. METHODS: A total of 777 horses of different breeds, age and sex were studied. Further, 598 soil samples and 434 indoor surface samples were examined. Antimicrobial susceptibility of 52 strains was investigated by Etest for 10 antibiotics. RESULTS: In horses that developed acute colitis during antibiotic treatment, 18 of 43 (42%) were positive to C. difficile culture and 12 of these (28%) were positive in the cytotoxin B test. Furthermore, C. difficile was isolated from a small number of diarrhoeic mature horses (4 of 72 [6%]) with no history of antibiotic treatment, but not from 273 healthy mature horses examined or 65 horses with colic. An interesting new finding was that, in normal healthy foals age < 14 days, C. difficile was isolated from 1/3 of foals (16 of 56 [29%]). All older foals (170) except one were negative. Seven of 16 (44%) nondiarrhoeic foals treated with erythromycin or gentamicin in combination with rifampicin were also excretors of C. difficile. On studfarms, 14 of 132 (11%) outdoor soil samples were positive for C. difficile in culture, whereas only 2 of 220 (1%) soil samples from farms with mature horses were positive for C. difficile (P = < 0.001). By PCR, it was demonstrated that strains from the environment and healthy foals can serve as a potential reservoir of toxigenic C. difficile. The experimental study conducted here found that C. difficile survived in nature and indoors for at least 4 years in inoculated equine faeces. The susceptibility of 52 strains was investigated for 10 antibiotics and all were susceptible to metronidazole (MIC < or = 4 mg/l) and vancomycin (MIC < or = 2 mg/l). CONCLUSIONS: C. difficile is associated with acute colitis in mature horses, following antibiotic treatment. Furthermore, C. difficile was isolated from 1 in 3 normal healthy foals age < 14 days. POTENTIAL RELEVANCE: Strains from healthy foals and the environment can serve as a potential reservoir of toxigenic C. difficile.     

Cochet-Bonnet aesthesiometer-determined corneal sensitivity in neonatal foals and adult horses

Corneal touch threshold (CTT) was measured in sick neonatal foals, healthy foals, and healthy adult horses with a Cochet-Bonnet aesthesiometer. The mean overall CTT for the adult horses, sick foals, and healthy foals was 4.82 +/- 0.87 cm, 3.21 +/- 0.24 cm, and 5.01 +/- 0.61 cm, respectively. The central cornea of adult horses was more sensitive than the limbal cornea. Corneal sensitivity was significantly reduced in sick neonatal foals compared to adults. The mean Schirmer I tear test values were significantly lower in foals than adults, and were 14.2 +/- 1.0 mm, 12.8 +/- 2.4 mm, and 18.3 +/- 2.1 mm wetting in sick neonatal foals, normal neonatal foals, and adult horses, respectively. Reduced corneal sensation and lower tear production may be associated with ulcerative keratitis and slow corneal healing in some foals.     

The effect of the sedative and analgesic detomidine for laryngoscopy of adult horses and foals]

Detomidine was used in this field trial effectively as a sedative and analgesic for laryngoscopic examinations in a total of 193 foals and 806 mature horses (Hanoverians). Detomidine was given either i.v. in foals 3 to 11 months old (20 micrograms/kg) and in mature horses (15 micrograms/kg), or i.m. in foals below 6 months of age (35 micrograms/kg). After i.v. administration, laryngoscopy was tolerated in more than 90% of all animals without additional use of a twitch, while in foals treated i.m. more than 70% required a twitch in order to enable this procedure. The effectiveness of detomidine was influenced by dose, route of administration, the time interval between treatment and examination and the degree of excitement before treatment, but not by sex. Profound bradycardia was evident in all treated animals, but arrhythmias were seen only in animals older than 4 months and were more pronounced in horses with a lower resting heart rate. These cardiovascular responses never endangered any of the treated animals. A transient dyspnea was seen in 13 foals (6.7%) and 10 horses (1.2%). Other side effects were rare. The foaling rate of 297 mares treated at any time during the first 8 months of pregnancy was 66.7%. A comparison with 5499 untreated, contemporary controls revealed a foaling rate of 61.0%. Hence treatments had no adverse effects on pregnancies.