Recipient Organization
NORTH CAROLINA STATE UNIV
(N/A)
RALEIGH,NC 27695
Performing Department
Population Health and Pathobiology
Non Technical Summary
Neonatal diarrhea is a major source of economic loss to the cattle industry and the leading cause of calf mortality in most countries. The major goals of treatment are to correction dehydration, increase blood pH (correct acidemia), restore electrolyte concentrations and provide nutritional support. Accomplishing these goals frequently involves the administration of oral electrolyte solutions which can often accomplish all of the major treatment goals to some degree. However in some calves intravenous fluids are utilized and the use of subcutaneous fluid therapy seems to be growing in popularity despite virtually no data on the efficacy of this route of fluid administration in calves. We also learned that the use of rapidly delivery of hypertonic saline combined with oral electrolyte fluid administration provide superior resuscitation when compared to only oral fluid therapy.1,3,6 It is quite possible that the use of oral electrolytes (with and/or without IV hypertonic saline) in calves with moderate dehydration and acidosis is of equal or perhaps even greater benefit than giving large volumes of fluids either intravenously or subcutaneously. Therefore the primary purpose of this study is to compare different treatment methods on the ability to resuscitate calves using a reliable and consistent model for inducing calf diarrhea.
Animal Health Component
(N/A)
Research Effort Categories
Basic
100%
Applied
(N/A)
Developmental
(N/A)
Goals / Objectives
To compare the ability of oral electrolytes (Diaque®) with both intravenous and subcutaneous fluid therapy to resuscitate calves with diarrhea. Specifically this will include they ability to rehydrate calves (increase plasma volume), increase blood pH, and restore electrolyte concentrations.
Project Methods
Forty Holstein bull calves will be identified and purchased for use in this study. All calves will be housed at Piedmont Research Station in Salisbury, NC Calves will be acclimated to their housing and normal diet until they are between 5 and 14 days of age. They will be fed milk replacer twice a day throughout the study period and will have free-choice access to water. Osmotic/maldigestive diarrhea and dehydration will be induced by adding sucrose solution (2 grams sucrose per kg) to the milk replacer at each feeding. In addition, calves with be given a combination of diuretic drugs to promote dehydration including spironolactone (1 mg/kg, PO q 8h), hydrochlorothiazide (1 mg/kg, PO, q 8h) and furosemide (2 mg/kg, IM, q 6h). This model has been well described as practical and reliable for inducing diarrhea and moderate to severe dehydration in calves within 48-72 hours5 and has been frequently used in previous studies evaluating the efficacy of different fluid therapy protocols to resuscitate calves with diarrhea.1,2,4,6After calves have sucrose added to their milk replacer, physical exams will be done every 8 hours to include heart rate, rectal temperature, clinical hydration score, depression status, fecal consistency score and body weight. Hydration, depression and fecal scoring are defined below:Hydration scoring: 0 = normal (eyes are bright and not recessed into orbit, skin feels pliable), 1 = mild dehydration (slight loss of skin elasticity, skin tent duration 2-3 seconds, eyes normal to mildly recessed into orbit), 2 = moderate dehydration (skin tent > 3 seconds but less than 10 seconds, eyes moderately recessed into orbit); 3 = severe dehydration (skin tent > 10 seconds, eyes markedly recessed into orbit)Depression scoring: 0 = normal, 1 = mild depression (calf suckles but not vigorously), 2 = moderate depression (calf able to stand, suckle is weak or disorganized), 3 = severe depression (calf unable to stand or suckle).Fecal consistency: 0 = normal (manure is normal and well formed), 1 = abnormal feces but not diarrhea (pasty manure, softer than normal), 2 = mild diarrhea (semi-liquid but still has a solid component), 3 = severe diarrhea (pure liquid - splashes when it hits the ground and does not form any solid structure).This model reliably induces diarrhea and moderate dehydration within 48 hours. Therefore physical examinations will be done every 6-8 hours until calves have achieved moderate dehydration (score of 2), a depression score of at least 1 and a fecal consistency score of 2-3. Jugular catheters will be placed in each calf following a sterile preparation of the vein. When the calves qualify to enter the treatment phase of the study - they will be divided into one of the following 4 groups:Group 1 (n = 10 calves) - oral electrolytes - calves will receive a packet of Diaque® mixed with water according to label directions (2 quarts or 1,891 ml of water). Calves will be allowed to suckle the oral electrolyte solution but will be fed using an esophageal feeder if necessary.Group 2 (n = 10 calves) - IV fluids - calves will received 1,891 ml of Lactated Ringers through a jugular catheter over a 30 minute period. This group will NOT receive any oral electrolytes during the trial.Group 3 (n = 10 calves) - SC fluids - calves will received 1,891 ml of Lactated Ringers given subcutaneously. The fluids will be administered over 10-15 minutes at 250 ml per site over the thorax. This group will NOT receive any oral electrolytes during the trial.Group 4 (n = 10 calves) - hypertonic saline + oral electrolytes - calves will receive an infusion of 7.2% hypertonic saline through a jugular catheter at a dose of 4 ml per kg of body weight over 5 minutes. This will immediately be followed by a feeding of Diaque® mixed in water according to label directions.Blood will be collected at baseline (prior to treatment) and then at 1 hour, 2 hours, 4 hours and 8 hours after fluid administration is completed to determine plasma volume, electrolyte concentrations and blood gas analysis. Using a portable blood chemistry analyzer (VetScan i-Stat, Abaxis Veterinary Reference Laboratory), the following will be measured at each time point - blood pH, pCO2, bicarbonate, base excess, hematocrit, hemoglobin, glucose, sodium, potassium, and anion gap concentrations. In addition, plasma protein and albumin concentrations will be determined by the North Carolina State University clinical pathology laboratory. The change in plasma volume will be determined by the following formulas:(Pt=0 - Pt=x) x 100/Pt=x - where Pt=0 is the plasma protein concentration before and Pt=x `is the plasma protein concentration at each measured time point after treatment.100 X (PCVinitial - PCVfinal)/(PCVfinal)Both of these formulas are widely used for calculating changes in plasma volume and should give roughly equivalent answers. We will calculate plasma volume changes using both formulas to see which one appears to be the most consistent.Approximately 12 to 18 hours after initial therapy, calves will receive a 2nd fluid administration staying in their assigned groups (ie. Group 1 will again receive oral electrolytes, Group 2 will again receive 1,891 ml of LRS IV, etc). Blood will again be collected at baseline (immediately prior to the administration of the second fluid treatment) as well as 1, 2, 4, 8 and 24 hours after treatment to assess further changes of fluid therapy on plasma volume, acid-base status and electrolyte concentrations. After this data has been collected, calves will be humanely euthanized with an overdose of pentobarbital. The key parameters that will be compared statistically between the 4 groups are:Changes in Plasma Volume - calves are expected to be moderately dehydrated - plasma volume should improve in each of the four groups - but the magnitude of plasma volume increase will be compared across each route of fluid therapy.Acid-base status - We will follow change in blood pH over time (over several hours) after calves have received each of the groups.Electrolyte concentrations - We will also determine the change in electrolyte concentrations (including glucose) associated with fluid resuscitation in each of the 4 groupsPhysical examination - During each period of blood collection we will do a complete physical exam as described above noting clinical hydration score, depression score, etc.