Association of aldosterone and arginine vasopressin concentrations and clinical markers of hypoperfusion in neonatal foals K. A. DEMBEK, S. D. HURCOMBE, A. J. STEWART † , B. S. BARR ‡ , K. C. MACGILLIVRAY § , M. KINEE ‡ , J. ELAM § and R. E. TORIBIO* College of Veterinary Medicine, The Ohio State University, Columbus, USA † College of Veterinary Medicine, Auburn University, Alabama, USA ‡ Rood and Riddle Equine Hospital, Lexington, Kentucky, USA § Hagyard Equine Medical Institute, Lexington, Kentucky, USA. *Correspondence email: toribio.1@osu.edu; Received: 29.05.14; Accepted: 19.11.14 Summary 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. Keywords: horse; equine neonates; sepsis; hypotension Introduction Hypoperfusion and hypotension are common pathophysiological findings in premature, septic, traumatic and post surgical human and equine patients [1–4]. The most frequent factors associated with hypoperfusion in critically ill human and equine neonates include hypovolaemia from systemic inflammation, impaired peripheral vasoregulation and myocardial dysfunction [1,5]. The diagnosis and management of hypotension remain controversial issues in paediatric medicine. The physiological response to low blood pressure and hypoperfusion is different between neonates and adults with neonates maintaining lower baroreflex sensitivity and higher vascular resistance; therefore, different clinical and laboratory factors should be taken into consideration [2,6]. Blood pressure is a function of blood flow and systemic vascular resistance; however, several studies have shown that in critically ill children blood pressure does not always reflect organ perfusion [1,6,7]. In fact, there is some evidence that in sick infants clinical and laboratory markers of hypoperfusion give a better assessment of organ function than blood pressure [1,2]. It is likely that similar age-related differences exist between sick equine neonates and horses. Recent studies in newborn foals with experimental hypotension found that in the equine neonate there is a delay in the maturation in the baroreflex and endocrine response necessary to maintain adequate blood pressure [8,9]. While direct and indirect blood pressure measurements provide an estimation of tissue perfusion in critically ill foals, often markers of hypoperfusion such as hyperlactataemia, azotaemia and haemoconcentration are used in the clinical setting to monitor and treat volume and haemodynamic disturbances [5,10,11]. Endocrine factors such as aldosterone and arginine vasopressin (AVP) are released in response to volume depletion, hypotension and hyperosmolality to restore blood pressure and organ perfusion [10,12–14]. Thus, it is expected that foals with clinical evidence of hypoperfusion will have increased concentrations of aldosterone and AVP which will be associated with markers of volume depletion and impaired tissue perfusion such as L-lactate. A number of studies in critically ill human patients, adult horses and foals have shown that blood L-lactate concentrations reflect tissue hypoperfusion and can be used as a prognostic indicator of morbidity and mortality [5,10,11,15–17]; however, a direct association among aldosterone, AVP, hyperlactataemia and clinical, and laboratory signs of hypoperfusion in equine neonates remains to be made. The purpose of this study was to: 1) define clinical hypoperfusion in neonatal foals based on clinical and laboratory findings (tachycardia, hyperlactataemia, haemoconcentration and azotaemia), 2) measure aldosterone and AVP concentrations in clinically hypoperfused and normoperfused foals and 3) determine the association between hormone concentrations with clinical and laboratory indicators of hypoperfusion, severity of disease and likelihood of survival in newborn foals. We hypothesised that hospitalised foals with clinical hypoperfusion will have higher concentrations of aldosterone, AVP and L-lactate than normoperfused foals and that hormone and L-lactate concentrations will be associated with clinical and laboratory markers of hypoperfusion and nonsurvival. 176 Equine Veterinary Journal 48 (2016) 176–181 © 2015 EVJ Ltd Equine Veterinary Journal ISSN 0425-1644 DOI: 10.1111/evj.12393