Abstract
Objective
We hypothesized that dehydrated calves treated with IV fluids containing 14 g of sodium bicarbonate, combined with oral electrolytes, would reduce mortality and improve recovery of anion gap compared to calves treated with IV fluids containing 14 g of sodium bicarbonate only or IV fluids with 14 g of sodium bicarbonate combined with milk replacer feeding.
Methods
In a randomized control study, dairy and beef-on-dairy cross calves (n = 460) were enrolled into the following groups at diagnosis of dehydration: sick controls treated with IV fluids only (Con-IV), calves treated with IV fluids plus oral force-fed electrolytes (ELE), calves treated with IV fluids plus oral force-fed milk replacer (MILK), and healthy controls (Con-Health). Mortality and IV fluid treatment counts were analyzed. Blood metabolites and fecal dry matter were measured (n = 80).
Results
Mortality for each group was as follows: Con-Health, 5.31% (95% CI, 2.4% to 11.3%); Con-IV, 13.91% (95% CI, 8.6% to 21.5%); ELE, 10.43% (95% CI, 6.0% to 17.5%); and MILK, 11.3% (95% CI, 6.6% to 18.5%). Bicarbonate concentrations in the Con-IV group returned to normal levels 1 hour after treatment. Anion gap in MILK calves was the highest after treatment. The relative risk of additional IV treatments for dehydration was 1.5 (95% CI, 1.2 to 1.8), 1.3 (95% CI, 1.1 to 1.6), and 2.1 (95% CI, 1.8 to 2.4) for the Con-IV, ELE, and MILK groups, respectively.
Conclusions
IV fluid with 14 g of sodium bicarbonate alone or combined with oral electrolytes was the most effective treatment for changes in acid-base balance in dehydrated bovine neonates in this study.
Clinical Relevance
IV therapy with sodium bicarbonate may practically rehydrate diarrheic calves in the field and correct acid-base balance. The use of forced feeding of ororuminal milk may not be beneficial for dehydrated and diarrheic calves.
Introduction
Diarrhea is the most common cause of morbidity and mortality in calves that are ≤ 30 days old and raised in calf ranches,1–3 producing significant economic losses in cattle operations.4 In addition, diarrhea may predispose calves to pneumonia and otitis.1 The most common cause of diarrhea in calves is infectious in nature and includes Cryptosporidium spp, Escherichia coli, Salmonella spp, Rotavirus spp, and Coronavirus spp, but diarrhea can also be caused by nutritional inconsistencies.5 Common pathophysiology of diarrhea in calves includes increased intestinal secretion and decreased intestinal absorption of fluids and nutrients, causing severe dehydration.6 Moreover, metabolic acidosis (blood pH ≤ 7.36)7 develops quickly in diarrheic calves because of the loss of bicarbonate ions in the feces and the increased lactic acid production due to greater bacterial fermentation of undigested carbohydrates by lactobacilli in the gastrointestinal tract.8 There are 2 isomers of lactic acid that are produced as a sequela to calf diarrhea: D- and L-lactic acid. D-lactic acidosis can occur in calves because of improper bacterial fermentation of milk.9 Improper ruminal milk fermentation takes place when milk or milk replacer leaks into the rumen because of failure of the esophageal groove reflex or backflow from the abomasum and bacteria breaks down the milk, producing D-lactic acid. These calves are known as ruminal drinkers.10 As a result of low blood pH, calves quickly develop clinical signs associated with impaired CNS function, including decreased palpebral reflex, ataxia, and loss of the suckling reflex.11 In a healthy calf, the esophageal groove reflex allows milk to bypass the underdeveloped rumen. However, in cases of milk flowing into the rumen, it may be subject to bacterial breakdown and support the development of potentially fatal ruminal acidosis.12,13
Given these complications, testing effective treatments to use in the field after the onset of diarrhea and dehydration is crucial to avoid further economic losses and improve animal welfare. The main objectives of an appropriate fluid therapy treatment for neonatal diarrhea and subsequent dehydration are to (1) recover blood volume and electrolyte balance; (2) restore acid-base balance; and (3) provide nutritional support to the diarrheic calf.4 Intravenous fluid therapy is successful in correcting dehydration by restoring circulating blood volume.14 Similarly, oral electrolyte fluid therapy has proven effective in recovering dehydrated calves from electrolyte losses, particularly of sodium and potassium.15
The importance of continued feeding of milk or milk replacers to diarrheic calves is well-known to prevent malnourishment and weight loss.5 To provide nutrients to diarrheic and dehydrated calves despite anorexia and loss of suckle reflex, cattle producers often use an ororuminal tube to feed milk when the calves refuse to or cannot drink.16 Feeding milk to calves via ororuminal tubes has been shown to be detrimental, as researchers have induced D-lactic metabolic acidosis and ruminal acidosis in calves by administering unpasteurized milk intraruminally using this method.17
Although oral rehydration solutions have been shown to be an effective treatment for dehydration and acidosis in calves,14 there are minimal data on the effects of combining oral rehydration solutions with IV therapy despite being standard practice among producers. This study aimed to measure the effects of different combinations of IV fluid therapy and force-fed ororuminal milk and electrolytes on mortality and anion gap to help determine an efficient treatment for dehydrated calves. We hypothesized that dehydrated calves treated with IV fluids containing 14 g of sodium bicarbonate combined with force-fed oral electrolytes would reduce mortality and improve recovery of anion gap rather than calves treated with IV fluids with 14 g of sodium bicarbonate only or IV fluids with 14 g of sodium bicarbonate combined with milk replacer.
Methods
Study population and treatments
All animal procedures for this study were approved by the Washington State University IACUC (protocol No. 6878). Animals were enrolled between May and July 2022. Farm records from until October 2022 for these animals were obtained. Calves were located at a 30,000-head calf ranch located in Central Washington. Calves were housed in single calf hutches that were 4 feet in width and 8 feet in length, with straw bedding. The calves were 1 to 3 days old at arrival to the facility. Calves were in these hutches from their arrival until 80 days of age, when they were moved to group pens. Calves were not weighed at arrival; therefore, average daily gain was not estimated during this study. While in the hutches and between 0 and 20 days of age, calves were fed twice daily at 07:00 and 15:00, starting with 1.9 L of milk replacer (Lawley’s Inc) in 2.8-L nursing bottles. Between 20 and 35 days of age, the calves received 2.8 L of milk replacer twice a day. Between 35 and 40 days of age, the calves went back to receiving 1.9 L of milk replacer twice a day. Finally, between 40 and 50 days of age, the calves’ feeding was reduced to only 0.9 L of milk replacer daily to encourage grain consumption. The milk replacer composition was crude protein 26%, crude fat 24%, crude fiber 0.15 %, vitamin A 6,818 IU/kg, vitamin D 3,863 IU/kg, vitamin E 68 IU/kg, and ash < 9%. From arrival at the calf ranch, calves were offered less than 0.4 kg of grain and water ad libitum. The calves’ grain ration went up to 3.6 kg per day between 40 and 80 days of age. Water buckets were refilled once daily unless outside temperatures were > 30 °C, in which case they were refilled 3 times a day. A total of 460 calves between 5 and 14 days of age were randomly enrolled in blocks of 4 animals into 1 of the 4 groups: sick controls treated with IV fluids only (Con-IV), calves treated with IV fluids plus oral force-fed electrolytes (ELE), calves treated with IV fluids plus oral force-fed milk replacer (MILK), and healthy controls (Con-Health). Randomization was generated with PROC PLAN (SAS, version 9.4; SAS Institute Inc). Our sample size calculation aimed to find a reduction in the mortality rate of 20% (eg, mortality reduction from 30% vs 24%) and an α of 0.05, power of 80%, and 5% loss in follow-up. The sample size was calculated with an online sample size calculator.18 The number of calves per group was 120, and there were 4 different groups in our study: (1) healthy group (Con-Health), (2) sick control (Con-IV), (3) electrolytes (ELE), and (4) milk (MILK). Dehydrated and diarrheic calves (n = 345) were enrolled when the farm personnel diagnosed severe dehydration in ambulatory calves. Dehydrated calves were those with more than one of the following clinical signs: hydration score ≥ 1, depression score ≥ 1, and fecal score ≥ 3, as depicted in Supplementary Table S1.19,20 Comatose and nonambulatory calves were excluded from this study. The Con-Health–group calves (n = 162) did not exhibit signs of dehydration, diarrhea, pyrexia, otitis, or respiratory disease. The Con-Health calves were subject to a similar health examination as the treatment groups to ensure they could be considered healthy animals. Con-Health calves were also intended to match the treatment groups’ calves by age and provided normal calves’ parameters under the current farm management conditions. The Con-Health calves were selected from a nearby hutch and enrolled on the same day as the treatment calves within each block.
Following farm protocols, dehydration in ambulatory calves was treated with an IV fluid mix of 1 L of lactated Ringer solution and 5 mL of vitamin B12 (VETone; containing 100 µg/mL of B12). The research team added around 14 g of sodium bicarbonate (Great Value) to the IV mix intended for the enrolled calves to optimize alkalinization and correct severe acidosis.9 This process was done to add an alkalizing agent to the farm’s existing protocol of treating with lactated Ringer solution. The fluid mixture, consisting of 1 L of lactated Ringer solution and 14 g of sodium bicarbonate solution, had a calculated osmolarity of approximately 605 mOsmol/L, making it a slightly hypertonic solution. Trained farm personnel administered the IV solution as a single bolus to calves in the Con-IV, ELE, and MILK groups using a 14-gauge, 5-cm IV catheter and a Simplex IV set. The treatments were provided within 1 hour of diagnosis, immediately following the morning feedings. The research team force-fed the ELE group 2 L of water containing 80 g of Calf Gold Lyte electrolyte mix (Bio-Vet Inc) and the MILK group 2 L of calf milk replacer (Lawley’s Inc). The research group mixed 226 g of milk replacer with 2 L of water at 49 °C following the manufacturer instructions. The farm personnel were blinded to the treatment groups, as the research team administered the different oral electrolyte solutions and oral milk replacer.
Farm personnel monitored all the calves for common diseases (eg, diarrhea, pneumonia, and dehydration) twice a day, provided treatments following farm protocols, and kept electronic records of diseases, treatments, and mortality using the management platform BoviSync (BoviSync LLC). The treatments analyzed in this study consisted of additional IV fluid treatments administered from enrollment through weaning, which occurred at 50 days of age per farm standard operating procedures.
Sample and data collection
The timeline and criteria for calf enrollment are depicted in Figure 1. Blood sampling took place between 06:30 and 09:30. Blood sample collection was intended before morning feeding, which started at 07:00. The research team stayed ahead of the farm personnel so that no blood samples were taken after the calves had been fed. Blood was sampled from the jugular vein with 20-gauge, 2.54-cm needles and 10-mL blood collection tubes (Becton, Dickinson and Co) containing either 158 USP of sodium heparin or no anticoagulant for plasma or serum separation, respectively. All blood samples were immediately placed on ice after collection, then placed into a –20 °C freezer until further analysis upon return to the mobile lab.
Experimental design and timeline of sample collection during the study.
Citation: Journal of the American Veterinary Medical Association 2025; 10.2460/javma.24.11.0700
Fecal samples were collected at each time point except after the treatment, as represented in Figure 1. Fecal samples were obtained by digital stimulation of a calf’s rectum. At least 10 g of fecal material was collected aerobically and stored inside a plastic bag. Fecal samples were stored on ice and then at –80 °C until further analysis.
The physical examination was performed by first obtaining a rectal body temperature, then pre-established fecal scores ranging from 0 to 4.21 Other health scores, including nasal discharge, ocular discharge, dehydration, and depression, were assigned, as described in Supplementary Table S1, adapted from a previously published calf scoring system.4
Measurement of PCV and total protein
Whole blood from heparinized blood tubes was loaded into glass microhematocrit tubes (Thermo Fisher Scientific). The end of the hematocrit tube was sealed with sealing clay. The tubes were placed and balanced in a microhematocrit centrifuge, with the clay-filled ends against the gasket, and centrifuged at 6,000 X g for 5 minutes. Packed cell volume was then determined by reading the height of the column of RBCs along the microhematocrit tube by use of the scale on a microhematocrit card reader.22
Sodium heparin tubes and tubes with no anticoagulant were placed in the centrifuge at 2,050 X g for 20 minutes. Then, samples were carefully removed from the centrifuge without inversion or mixing the serum and plasma. Disposable transfer pipettes were used to draw up the serum and plasma to prevent cross-contamination between samples. A few drops of serum were placed and evenly distributed throughout the measuring surface of a Brix refractometer (MISCO) to determine the total protein. The glass reader surface was cleaned with deionized water and dried off with Kimwipes (Uline) between samples.
Measurement of fecal dry matter
To thaw the samples, they were taken out of the freezer and placed at room temperature for 8 to 12 hours. Approximately 10 g of feces was weighed out with a digital Scout Pro scale (OHAUS) that had been previously calibrated and balanced. The fecal sample was thoroughly mixed before the subsample of 10 g was obtained. The feces were placed on an aluminum weighing dish (Eagle Thermoplastics Inc). After the weights of the empty weighing dish and the wet sample on the weighing dish were recorded, the fecal samples were placed in a forced-air drying oven (Avantor; VWR International LLC) at 44 °C for 7 days. The dry matter percentage of the fecal samples was obtained by dividing the dry samples’ weight by the wet samples’ weight.
Blood sample analysis
Blood serum samples were sent to the Cornell University Animal Health Diagnostics Center to be quantitatively analyzed for the following blood analytes: sodium, potassium, chloride, bicarbonate, anion gap, urea nitrogen, creatinine, calcium, magnesium, phosphate, total protein, albumin, globulin, and glucose. All analytic tests were run with a Cobas 6000 c501 analyzer (Roche Diagnostics). The anion gap was calculated by subtracting the sum of the chloride and bicarbonate concentration from the sum of the sodium and potassium concentration. The globulin concentration was calculated by subtracting the albumin concentration from the total protein concentration.
Statistical analysis
The primary outcomes of the study were mortality and the recovery of the anion gap over time, aimed at identifying effective treatment for dehydrated calves. The secondary outcomes included relevant blood metabolites associated with dehydration, changes in fecal dry matter (FDM) over time, and the need for additional IV fluid treatments after enrollment.
The χ2 tests were performed in PROC FREQ in SAS (version 9.4; SAS Institute Inc) for differences in categorical variables such as age, sex, and breed. Treatments and mortality were analyzed between enrollment and weaning for all calves. Mixed linear models (PROC Mixed in SAS, version 9.4; SAS Institute Inc) were used to analyze differences in the continuous outcomes (eg, blood metabolite concentrations, FDM) between the control and treatment groups. Five covariance structures were tested for the differences in continuous outcomes (simple, compound symmetry, autoregressive order 1, Toeplitz, and unstructured), and the covariance structure with the lowest Akaike information criterion was selected. Treatment was included as a fixed effect, and the REPEATED statement was used for the time variable. Other plausible fixed-effects terms (eg, sex, breed) were tested and not included in the final model if the P value was ≥ .05. The treatment X time interaction was forced in the model. Other plausible interaction terms were tested and not included in the final model if the P value was ≥ .05. The Tukey post hoc test was used for multiple comparison correction of P values for all pairwise comparisons of least square means (LSMs) among the different treatment groups. The Tukey post hoc test is conservative because it uses a more strict criterion for significance than other tests, reducing the risk of type I error. Normality and homoscedasticity of residuals were visually evaluated for the model fit. When normality was not observed in continuous outcomes, they were log-transformed and back-transformed.
A univariate ANOVA was used to establish the difference in the mortality rates between the control and treatment groups. Results from all variables are presented as geometric means and 95% CIs unless stated otherwise. For the counts of additional IV fluid treatments required for each calf to be rehydrated after enrollment, Poisson regression was fitted with the PROC GENMOD procedure with a log link and Poisson distribution. Deviance-scaled Pearson χ2 statistics for the Poisson models were evaluated.
Results
The population demographics are presented in Table 1. There were no differences in the sex and breed of the calves enrolled in our study among the different groups. Calves in the Con-IV, ELE, and MILK groups had more scores ≥ 2 for depression and dehydration than the Con-Health group (P < .001). There was no difference in the LSM (95% CI) age in days at enrollment among the Con-Health, Con-IV, ELE, and MILK groups, with ages of 8.2 days (7.9 to 8.5 days), 7.9 days (7.6 to 8.2 days), 8.3 days (7.9 to 8.6 days), and 8.1 days (7.8 to 8.4 days), respectively (P = .39).
Description of the study population, including sex and breed.
| Characteristic | Treatment group | P value | |||
|---|---|---|---|---|---|
| Con-Health | Con-IV | MILK | ELE | ||
| Sex | 0.45 | ||||
| Female | 65 | 79 | 74 | 75 | |
| Male | 97 | 83 | 88 | 87 | |
| Breed | 0.15 | ||||
| Angus | 43 | 39 | 30 | 35 | |
| Charolais | 43 | 66 | 66 | 65 | |
| Holstein | 24 | 17 | 20 | 14 | |
| Jersey | 0 | 0 | 0 | 1 | |
| Limousin | 52 | 40 | 41 | 52 | |
Con-Health = Healthy calves that were not treated at enrollment. Con-IV = Dehydrated calves treated only with an IV fluid mix of 1 L of lactated Ringer solution, 5 mL of vitamin B12, and 14 g of sodium bicarbonate. ELE = Dehydrated calves treated with an IV fluid mix of 1 L of lactated Ringer solution, 5 mL of vitamin B12, and 14 g of sodium bicarbonate combined with 2 L of oral electrolytes force-fed through an ororuminal tube. MILK = Dehydrated calves treated with an IV fluid mix of 1 L of lactated Ringer solution, 5 mL of vitamin B12, and 14 g of sodium bicarbonate combined with 2 L of milk force-fed through an ororuminal tube.
Fecal dry matter distribution over time
At enrollment, 20.7 %, 83.4%, 85.6%, and 77.2% of the 5- to 14-day-old calves had a fecal score ≥ 3 for the Con-Health, Con-IV, ELE, and MILK groups, respectively (P < .001). The LSM (95% CI) of FDM percentage (FDM%) for the control and treatment groups from time of enrollment until 168 hours after treatment is shown in Figure 2. These results confirmed that the Con-Health group did not experience severe diarrhea, while most calves in the treatment groups were affected by severe diarrhea at enrollment. The FDM% was different at enrollment between the Con-Health and Con-IV, ELE, and MILK groups, with values of 23.8% (19.1% to 29.6%), 13.0% (10.4% to 16.3%), 9.0% (7.2% to 11.2%), and 9.9% (7.9% to 12.5%), respectively (P < .001). The difference in FDM% among the Con-Health, Con-IV, ELE, and MILK groups was also noted 24 hours after treatment, with values of 23.9% (19.2% to 29.8%), 10.3% (10.4% to 16.3%), 6.6% (5.3% to 8.3%), and 7.3% (5.9% to 9.1%), respectively (P < .001). The MILK group was the only treatment group with an FDM% below 20% at 120, 144, and 168 hours, with values of 18.2% (14.4% to 22.9%), 18.6% (14.7% to 23.4%), and 18.4% (14.6% to 23.2%), respectively.
The fecal dry matter (DM) changes over time in least square mean (LSM) and 95% CI. Treatment group differences (P < .05) after controlling for pairwise LSM comparisons with the Tukey post hoc procedure are indicated with an asterisk. Con-Health = Healthy calves that did not receive treatment at enrollment. Con-IV = Dehydrated calves treated only with an IV fluid mix of 1 L of lactated Ringer solution, 5 mL of vitamin B12, and 14 g of sodium bicarbonate. ELE = Dehydrated calves treated with an IV fluid mix of 1 L of lactated Ringer solution, 5 mL of vitamin B12, and 14 g of sodium bicarbonate combined with 2 L of oral electrolytes force-fed through an ororuminal tube. MILK = Dehydrated calves treated with an IV fluid mix of 1 L of lactated Ringer solution, 5 mL of vitamin B12, and 14 g of sodium bicarbonate combined with 2 L of milk force-fed through an ororuminal tube.
Citation: Journal of the American Veterinary Medical Association 2025; 10.2460/javma.24.11.0700
Calves in the treatment groups returned to a normal FDM around 96 hours after treatment, with values of 18.2% (14.5% to 22.6%), 20.2% (16.2% to 25.2%), 17.1% (13.7% to 21.4%), and 20.2% (16.1% to 25.3%) for the Con-Health, Con-IV, ELE, and MILK groups, respectively. The Con-Health calves had the lowest FDM% at 72 and 96 hours, with values of 19.2% (15.4% to 23.9%) and 18.16% (14.5% to 22.6%), respectively.
Blood metabolites
The LSM (95% CI) of all blood metabolite concentrations is depicted in Table 2. The changes over time in blood concentrations of sodium, chloride, potassium, magnesium, calcium, phosphate, and glucose are shown in Figure 3. There were no differences among the groups in sodium (P = .30) and chloride (P = .90) blood concentrations. The sodium levels were always within normal ranges (134 to 144 mM) for the treatment groups and were similar for the Con-Health group. However, we observed a difference in potassium blood concentrations at 1 hour after treatment between the Con-Health and ELE groups, with values of 5.2 mM (5.0 to 5.5 mM) and 4.5 mM (4.3 to 4.6 mM), respectively (P = .001). Nevertheless, the potassium blood concentration remained within normal ranges from enrollment through 168 hours for the 3 treatment groups and the Con-Health group. The MILK group had a lower calcium blood concentration than the Con-Health group from enrollment until 48 hours after treatment. The Con-IV and ELE groups had a lower calcium blood concentration than the Con-Health group during the first hour after treatment only. Blood glucose concentrations were lower in the Con-IV, ELE, and MILK groups compared with the Con-Health group at enrollment only.
Repeated-measures ANOVA least square mean (95% CI) concentrations of blood metabolites during the first 7 days after enrollment.
| Metabolite (mM) | Treatment groups | P value | |||||
|---|---|---|---|---|---|---|---|
| Con-Health | Con-IV | ELE | MILK | Tx | Time | Tx X time | |
| Sodium | 137.8 | 138.1 | 137.6 | 136.6 | .32 | < .001 | < .001 |
| (136.6–93.1) | (136.8–139.3) | (136.4–138.8) | (135.3–137.8) | ||||
| Potassium | 5.1a | 4.9ab | 4.9b | 5.0b | .02 | < .001 | .006 |
| (5.0–5.2) | (4.8–5.1) | (4.7–5.0) | (4.9–5.1) | ||||
| Chloride | 100.6 | 101.0 | 101.3 | 100.7 | .90 | < .001 | .001 |
| (99.1–102.2) | (99.4–102.6) | (99.8–102.9) | (99.1–102.3) | ||||
| Bicarbonate | 23.2a | 21.1ab | 19.6ab | 18.1b | .01 | < .001 | < .001 |
| (20.8–25.9) | (18.9–23.6) | (17.5–21.9) | (16.2–20.2) | ||||
| Anion gap | 19.07a | 20.86ab | 21.55ab | 22.77b | .01 | < .001 | .19 |
| (16.14–21.71) | (18.19–23.27) | (19.05–23.8) | (20.4–24.86) | ||||
| Glucose | 4.98ac | 4.50bc | 4.38b | 4.73c | < .001 | < .001 | .002 |
| (4.77–5.17) | (4.30–4.70) | (4.17–4.58) | (4.53–4.94) | ||||
| BUN | 3.10a | 4.27b | 4.6b | 4.33b | < .001 | < .001 | < .001 |
| (1.1–3.49) | (1.52–4.81) | (1.64–5.19) | (1.54–4.88) | ||||
| Creatinine | 0.092 | 0.088 | 0.084 | 0.087 | .50 | < .001 | .001 |
| (0.084–0.102) | (0.08–0.09) | (0.076–0.09) | (0.078–0.095) | ||||
| Phosphate | 2.63a | 2.36b | 2.41ab | 2.47ab | .03 | < .001 | .03 |
| (2.50–2.77) | (2.23–2.50) | (2.28–2.54) | (2.34–2.61) | ||||
| Calcium | 2.62a | 2.51b | 2.48b | 2.47b | < .001 | < .001 | < .001 |
| (2.58–2.66) | (2.47–2.55) | (2.43–2.52) | (2.43–2.51) | ||||
| Magnesium | 0.70a | 0.66ab | 0.65b | 0.66ab | .02 | < .001 | < .001 |
| (0.67–0.72) | (0.64–0.68) | (0.63–0.67) | (0.63–0.68) | ||||
| Albumin | 0.04 | 0.038 | 0.038 | 0.038 | .06 | < .001 | < .001 |
| (0.038–0.042) | (0.036–0.039) | (0.036–0.039) | (0.036–0.039) | ||||
| Globulin | 0.021 | 0.023 | 0.02 | 0.021 | .52 | .001 | .8 |
| (0.02–0.023) | (0.022–0.024) | (0.019–0.021) | (0.02–0.022) | ||||
| Total protein | 0.062 | 0.061 | 0.058 | 0.059 | .07 | < .001 | < .001 |
| (0.059–0.064) | (0.058–0.063) | (0.055–0.061) | (0.057–0.062) | ||||
Different superscripted letters within a row indicate treatment group differences (P value < .05) after controlling for pairwise least square mean comparisons with the Tukey post hoc procedure.
Tx = Treatment.
Blood metabolites: LSM and 95% CI for ANOVA of sodium (A), chloride (B), potassium (C), magnesium (D), calcium (E), phosphate (F), and glucose (G) concentrations in plasma. The groups were Con-Health, Con-IV, ELE, and MILK. Treatment group differences (P < .05) after controlling for pairwise LSM comparisons with the Tukey post hoc procedure are indicated with an asterisk.
Citation: Journal of the American Veterinary Medical Association 2025; 10.2460/javma.24.11.0700
The fluctuations in BUN, creatinine, albumin, globulin, and total protein from the time of enrollment until 168 hours after treatment are shown in Figure 4. The BUN was lower in the Con-IV, ELE, and MILK groups compared with the Con-Health group during the first 24 hours after treatment. Moreover, calves in the MILK group had a lower albumin concentration at 48 hours (P = .07) and 96 hours (P = .04) after treatment compared with the Con-Health group.
Blood metabolites: LSM and 95% CI for ANOVA of BUN (A), creatinine (B), albumin (C), globulin (D), total protein (E), anion gap (F), and bicarbonate (G) concentrations in plasma. The groups were Con-Health, Con-IV, ELE, and MILK. Treatment group differences (P < .05) after controlling for pairwise LSM comparisons with the Tukey post hoc procedure are indicated with an asterisk.
Citation: Journal of the American Veterinary Medical Association 2025; 10.2460/javma.24.11.0700
Figure 4 shows the bicarbonate and anion gap changes in time from enrollment until 168 hours after treatment. Bicarbonate concentrations in the Con-IV group returned to normal levels following treatment. Moreover, the bicarbonate concentrations were lowest in the MILK group with a value of 18.1 mM (16.2 to 20.2 mM; P = .01). Bicarbonate levels at 168 hours were 23.9 mM (21.4 to 26.7 mM), 23.9 mM (21.4 to 26.7 mM), 22.8 mM (20.4 to 25.6 mM), and 20.9 mM (18.6 to 23.5 mM) for the Con-Health, Con-IV, ELE, and MILK groups, respectively. The anion gap was greatest in the MILK group and peaked after 12 hours after treatment with a value of 22.0 mM (20.4 to 24.0 mM; P = .01).
Treatment counts and mortality
There were no differences in mortality between the treatment and control groups. The LSM mortality for the Con-Health, Con-IV, ELE, and MILK groups was 5.31% (2.4% to 11.36%), 13.91% (8.68% to 21.56%), 10.43% (6.0% to 17.52%), and 11.3% (6.66% to 18.54%), respectively (P = .21). Unfortunately, the farm records the research study received were not accurate in identifying the causes of death of the calves.
Among the different treatment groups, the relative risk (RR) of requiring additional IV treatments for dehydration was 1.5 (1.2 to 1.8), 1.3 (1.1 to 1.6), and 2.1 (1.8 to 2.4) for the Con-IV, ELE, and MILK groups, respectively (P < .001). The Con-IV group had a 27% lower RR of requiring subsequent IV fluid treatments for dehydration compared to the MILK group (P = .01). Moreover, the ELE had a 34% lower RR of requiring subsequent IV fluid treatments for dehydration compared to the MILK group (P = .001). There was no difference in the RR of subsequent IV fluid treatments between the Con-IV and ELE groups (P = .44).
Discussion
Our study aimed to measure how different combinations of fluid therapies for diarrheic calves impact calf health and survival on the basis of blood metabolite concentrations. Despite the common use of fecal scoring to measure the fluidity of feces, it is viewed as a subjective measure21 and a more quantitative measure such as FDM% is warranted. For this reason, fecal water losses were analyzed quantitatively by measuring the dry matter component of fecal samples taken from the control and treatment groups.23 The results of this analysis validated that calves were appropriately assigned into control and treatment groups, as indicated by the significant difference in FDM at enrollment between healthy calves in the control groups and the calves affected by diarrhea in the treatment groups. Furthermore, our results indicate that calves in the treatment groups returned to a normal FDM% of around 23% to 24% at 96 hours after enrollment independent of the treatment.
While the FDM data offer insight into the extent of fluid loss in diarrheic calves, blood metabolite concentrations are a way to quantitatively estimate the effect of fluid therapy on electrolyte recovery, acid-base balance correction, and nutritional support. The Con-IV group returning to normal bicarbonate blood concentration range within 1 hour following treatment infers that this treatment may be effective in correcting acid-base balance disruption (Figure 4). In previous studies, calves subjected to induced metabolic acidosis through force-fed ororuminal milk required a minimum of 48 hours to return to a nonacidotic status.17 Moreover, a recent study24 showed that milk-based oral rehydration solutions pass through the abomasum slower than water-based rehydration solutions, such as the solution used in the ELE treatment group. Milk-based solutions that are used to rehydrate calves may increase bacteria-related acid production and delay correcting acid-base status in calves.24
Additionally, 2 processes continue during episodes of diarrhea in calves, exacerbating metabolic acidosis: (1) the ongoing loss of bicarbonate ions and (2) the production of D-lactate by bacteria breaking down undigested milk or milk replacer.25–27 The calves in the MILK group had a lower FDM% among the treatment groups at 120, 144, and 168 hours after treatment. In addition, the only treatment group that did not return to normal levels of bicarbonate (22 to 30 mM) was the MILK group. This finding may indicate that calves in the MILK group experienced the greatest disruption to their acid-base balance among the treatment groups.
The anion gap in MILK calves being the greatest following treatment reinforces the hypothesis that this treatment may be detrimental to acid-base balance, as an increase in the anion gap may result from increased concentrations of strong anions in the blood. In calves with diarrhea, this is mostly explained by increased D-lactate concentrations.28 Diarrheic calves may indeed need milk to fulfill their energy and protein requirements. Despite being a good source of energy and protein, as indicated by calves in the MILK group having the greatest blood concentration of glucose, this treatment lacks an alkalinizing ability.29
The use of ororuminal tubes to force-feed milk may have adverse effects in diarrheic and dehydrated calves. Our study showed some of the adverse effects of force-feeding milk replacer to calves even once, which was consistent with a previous study17 in which calves developed metabolic acidosis after being fed milk through an ororuminal tube 3 times daily over multiple days. Diarrheic and/or dehydrated calves require milk to meet maintenance requirements and support recovery. Allowing dehydrated and/or diarrheic calves to drink smaller volumes of milk on their own may be more beneficial than force-feeding large volumes of milk or milk replacer via an ororuminal tube.
Although mortality rates did not differ significantly among treatment groups, there were significant differences in the number of additional IV fluid treatments required for rehydration. Calves in the Con-IV and ELE groups had a significantly lower RR of requiring subsequent IV fluid treatments compared to those in the MILK group. It is likely that the previously discussed negative consequences of force-feeding milk replacer to calves with the use of ororuminal tubes is the reason why full rehydration and recovery were prolonged in the MILK group.
Unfortunately, during this study, we did not measure pH or D-lactate in blood to thoroughly understand the effects of the IV and oral treatments on severely dehydrated calves. Pathogen identification was not performed in this study, and that may have affected some of the outcomes observed in this study. Also, < 50% of the calves were tested for failure of passive immunity transfer and we did not include these data in the current manuscript. However, the calves with failure of passive immunity transfer were evenly distributed among the Con-Health, Con-IV, ELE, and MILK groups. We did not analyze the use of antimicrobials in the study population. Moreover, it is possible that the sample size was not enough to detect a statistical difference in mortality among the treatments.
Early and effective fluid therapy is the primary treatment option for reducing mortality caused by diarrhea. We conclude that treatment with ororuminal milk may be detrimental to the acid balance of dehydrated calves. Treatment with lactated Ringer solution IV fluids combined with sodium bicarbonate alone or with oral electrolytes was the most effective at addressing anion gap disruption due to dehydration, as well as rehydrating dehydrated calves in this study.
Supplementary Materials
Supplementary materials are posted online at the journal website: avmajournals.avma.org.
Acknowledgments
The authors thank the participating calf ranch and associated personnel for their invaluable assistance with this project.
Disclosures
The authors have nothing to disclose. No AI-assisted technologies were used in the composition of this manuscript.
Funding
Financial support was provided through the Washington State University College of Veterinary Medicine Summer Research Scholars Fellowship.
ORCID
F. A. Leal Yepes https://orcid.org/0000-0002-7531-5133
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