Association of aldosterone and arginine vasopressin concentrations and clinical markers of hypoperfusion in neonatal foals.

REASONS FOR PERFORMING STUDY: Critically ill foals often present to veterinary hospitals with impaired organ perfusion which can be demonstrated by increased blood L-lactate concentrations. As a compensatory mechanism to low blood pressure and electrolyte abnormalities, aldosterone and arginine vasopressin (AVP) are released to restore organ perfusion and function. Several studies have investigated the ability of blood L-lactate concentrations to predict severity of disease and outcome in critically ill human patients, adult horses and foals. However, information on the aldosterone and AVP response to hypoperfusion and its association with L-lactate concentrations in neonatal foals is limited. OBJECTIVES: To determine the association between clinical hypoperfusion and endocrine markers of reduced tissue perfusion in normo- and hypoperfused foals. STUDY DESIGN: Prospective, multicentre, cross-sectional observational study. METHODS: Blood samples were collected on admission from 72 clinically hypoperfused, 110 normoperfused (73 hospitalised and 37 healthy) foals of ≤4 days of age. Foals were considered clinically hypoperfused if they had L-lactate concentrations ≥2.5 mmol/l and one of the 3 following findings: heart rate >120 beats/min, packed cell volume (PCV) >0.44 l/l or azotaemia (increased creatinine and blood urea nitrogen [BUN]). Blood concentrations of aldosterone and AVP were determined by radioimmunoassays. RESULTS: Aldosterone, AVP, creatinine and BUN concentrations and heart rate, PCV and blood osmolality were higher in clinically hypoperfused compared with normoperfused foals (P<0.05). Risk of hypoperfusion increased with the presence of hypothermic extremities (OR = 5.26) and with each one unit increase in albumin concentrations (OR = 3.5) (P<0.05). The proposed admission L-lactate cut-off value above which nonsurvival could be reliably predicted in hospitalised foals was 10.6 mmol/l with 82% of sensitivity and 74% of specificity. CONCLUSIONS: Hyperaldosteronaemia and hypervasopressinaemia as well as hypothermic extremities and increased albumin concentrations are potent predictors of hypoperfusion in hospitalised foals.

Renin-Angiotensin-aldosterone system and hypothalamic-pituitary-adrenal axis in hospitalized newborn foals.

BACKGROUND: The renin-angiotensin-aldosterone system (RAAS) and hypothalamic-pituitary-adrenal axis (HPAA) and their interactions during illness and hypoperfusion are important to maintain organ function. HPAA dysfunction and relative adrenal insufficiency (RAI) are common in septic foals. Information is lacking on the RAAS and mineralocorticoid response in the context of RAI in newborn sick foals. OBJECTIVES/HYPOTHESIS: To investigate the RAAS, as well as HPAA factors that interact with the RAAS, in hospitalized foals, and to determine their association with clinical findings. We hypothesized that critical illness in newborn foals results in RAAS activation, and that inappropriately low aldosterone concentrations are part of the RAI syndrome of critically ill foals. ANIMALS: A total of 167 foals ≤3 days of age: 133 hospitalized (74 septic, 59 sick nonseptic) and 34 healthy foals. METHODS: Prospective, multicenter, cross-sectional study. Blood samples were collected on admission. Plasma renin activity (PRA) and angiotensin-II (ANG-II), aldosterone, ACTH, and cortisol concentrations were measured in all foals. RESULTS: ANG-II, aldosterone, ACTH, and cortisol concentrations as well as ACTH/aldosterone and ACTH/cortisol ratios were higher in septic foals compared with healthy foals (P < .05). No difference in PRA between groups was found. High serum potassium and low serum chloride concentrations were associated with hyperaldosteronemia in septic foals. CONCLUSIONS AND CLINICAL IMPORTANCE: RAAS activation in critically ill foals is characterized by increased ANG-II and aldosterone concentrations. Inappropriately low cortisol and aldosterone concentrations defined as high ACTH/cortisol and ACTH/aldosterone ratios in septic foals suggest that RAI is not restricted to the zona fasciculata in critically ill newborn foals.

Presumptive nonthyroidal illness syndrome in critically ill foals.

REASONS FOR PERFORMING THE STUDY: Hypothalamic-pituitary-thyroid (HPT) axis dysfunction is associated with morbidity and mortality in critically ill people. To date, investigations of HPT axis in critically ill foals are limited. OBJECTIVES: To document the occurrence of low thyroid hormone concentrations (presumptive nonthyroidal illness syndrome; NTIS) in critically ill newborn foals and investigate whether NTIS is associated with severity of disease and outcome. HYPOTHESIS: NTIS occurs frequently in foals with sepsis and is associated with sepsis score and outcome. Reverse T3 (rT3) concentrations will be increased in septic foals and highest in nonsurvivors. METHODS: Thyroid hormones (total and free thyroxine [TT4 and fT4], total and free tri-iodothyronine [TT3 and fT3], reverse T3 [rT3]) were prospectively measured in healthy, sick nonseptic and septic foals. Clinical and laboratory information was retrieved from the medical records. Hormones were measured by validated radioimmunoassays. RESULTS: Concentrations of all thyroid hormones except rT3 (P = 0.69) were decreased in septic and sick nonseptic foals (P < 0.01). Reductions in hormone concentrations were associated with an increased sepsis score (P < 0.01). Nonsurviving septic foals had lower TT4, fT4, TT3 and fT3 concentrations than surviving septic foals (P < 0.01). rT3 concentrations were higher in nonsurviving septic prematurefoals than surviving septic premature foals (P < 0.05). CONCLUSIONS: NTIS (euthyroid sick syndrome) is frequently observed in critically ill and premature foals, and associated with severity of disease and mortality. POTENTIAL RELEVANCE: More research is needed to better understand the mechanism of this finding and determine whether manipulation of the HPT axis or thyroid replacement therapy could be beneficial.