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Hyperketonemia
treatment at the individual
cow and herd level
Jessica McArt, DVM, PhD
jmcart@cornell.edu
Overview ▪ Physiology
▪ BHB cut-points
▪ Individual animal treatment
▪ Herd-level testing and
treatment
Negative Energy Balance (NEB)
• Dairy cows enter a state of NEB during the
transition period
• Increased energy demand in early lactation
Energy (NEL) Requirements
2 days before versus 2 days after calving
1,600-lb Cow 1,250-lb Heifer
Function Pre Post Pre Post
Maintenance 11.2 10.1 9.3 8.5
Pregnancy 3.3 --- 2.8 ---
Growth --- --- 1.9 1.7
Milk production --- 18.7 --- 14.9
Total (Mcal) 14.5 28.8 14.0 25.1
Calculated from NRC (2001). Assumes milk production of 55 lb/d for cow and 44 lb/d for
heifer, each containing 4% fat.
Courtesy of J. K. Drackley
Dry Matter Intake
kg
Ospina et al., 2013, VCNA
Ketosis
▪ Ketosis is the elevation of ketone bodies:
▪ Acetone
▪ Acetoacetate
▪ β-hydroxybutyrate (BHB)
▪ Clinical manifestation:
▪ Decrease in appetite
▪ Weight loss
▪ Decrease in milk production
 Subclinical disease
>80% of cases
Nomenclature ▪ Ketosis
▪ Subclinical ketosis
▪ Blood BHB 1.2 – 2.9 mmol/L
▪ Clinical ketosis
▪ Blood BHB ≥ 3.0 mmol/L
▪ Hyperketonemia (HYK)
▪ Blood BHB ≥ 1.2 mmol/L
Types of Hyperketonemia
▪ Type I andType II: human-based distinction
▪ Inability to adapt to early lactation NEB
▪ Early in lactation, 3-21 DIM
▪ Excessive NEB just before or after calving
▪ Energy intake limited
▪ 3 to 6 weeks in milk
▪ Lack of energy substrates for level of milk production
Periparturient Blood BHB Concentration
0.0
0.2
0.4
0.6
0.8
1.0
1.2
-21 -18 -15 -12 -9 -6 -3 0 3 6 9 12 15 18 21
BHB,mmoL/L
Day relative to calving
Adapted from McCarthy et al., 2015, JDS
How much is “normal”?
▪ Incidence:
▪ Follow a group of animal through time
▪ Number of new cases/number of animals tested
▪ 25% - 85%, average ~ 45%
▪ Prevalence:
▪ Snapshot in time
▪ Number of new and existing cases/number of
animals tested
▪ 0% - 70%, average ~ 20%
Incidence ~2-2.2 x prevalence
Additional Info on Blood BHBTesting
▪ Time of sampling
▪ Not important in ad libTMR fed herds
▪ Otherwise highest ~ 4 to 5 hours after feeding
▪ Location of sampling
▪ Tail vessels = jugular vein
▪ Milk vein ~ 0.3 mmol/L lower
Blood BHB Cut-Points
▪ ≥ 1.2 to 1.4 mmol/L
▪ Based on health and production outcomes
▪ ≥ 3.0 mmol/L = more severe hyperketonemia
▪ Remember:
▪ If you your cut-point, sensitivity and specificity
▪ You correctly identify more ketotic cows but treat
more non-ketotic cows
Applications of HyperketonemiaTesting
▪ Identifying individual hyperketonemic cows
▪ Cow-side test for treatment decisions
▪ How intensive should we be?
▪ Identifying herds with hyperketonemia problems
▪ Herd-level testing for management decisions
Individual Consequences of HYK
▪ Higher risk for adverse health events
▪ Metritis
▪ Displaced abomasum
▪ Mastitis
▪ Culling
▪ Decrease milk yield in early lactation
▪ Poorer reproduction
When do we test?
0
5
10
15
20
25
30
35
3 4 5 6 7 8 9 10 11 12 13 14 15 16
BloodBHB≥1.2mmol/L(%)
Days in Milk
Prevalence
Adapted from McArt et al., 2012, JDS
▪ Hyperketonemia
▪ BHB ≥ 1.2 mmol/L
▪ Severe hyperketonemia
▪ BHB ≥ 3.0 mmol/L
Hyperketonemia
Treatment
HYKTreatment (BHB ≥1.2 mmol/L)
▪ Propylene glycol
▪ Vitamin B12
▪ Glucocorticoids - ?
Gordon et al., 2013, VCNA
Propylene Glycol
▪ Two modes of action:
▪ Increased supply of propionate = glucogenic
▪ Reduced insulin sensitivity = decreased glucose
demand by peripheral tissues
▪ Oral drenching preferred over mixing in feed
▪ No benefit with additional glycerol
Propylene Glycol
▪ Speeds resolution of ketosis
▪ Prevents progression to severe
ketosis
▪ Increases early lactation milk yield
▪ Reduces risk of DA and culling
▪ 300 mL, orally once a day for 5 days
~$1/dose
Administration of Propylene Glycol
▪ The stuff tastes horrible …
Dosing gun
Homemade pump
20 oz. soda bottle & speculum
Vitamin B12
▪ Synthesized in rumen
▪ Methylmalonyl-CoA mutase
▪ Coverts propionate to succinyl-CoA
▪ Vitamin B12 dependent
▪ Some supporting evidence
▪ 1 dose 25 mL Catosal (0.05 mg B12
and 100 mg butaphosphan/mL)
Propionate
Vitamin B12
Glucocorticoids
▪ Examples:
▪ Dexamethasone (Azium)
▪ Isoflupredone (Predef)
▪ Lack of efficacy
▪ Possible adverse side effects
HYKTreatment (BHB ≥3.0 mmol/L)
▪ Dextrose
▪ ½ - 1 bottle IV
▪ No randomized, controlled trials ever done on
efficacy of dextrose!
▪ Propylene glycol
▪ Vitamin B12
▪ Corticosteroids - ?
▪ Resent study shows 20mg dexamethasone may be
detrimental to cows with BHB >2.0 mmol/L
Gordon et al., 2013, VCNA
▪ BHB ≥1.2 mmol/L
▪ Excellent
▪ BHB ≥3.0 mmol/L
▪ Fair to good
▪ Monitor for subsequent
diseases
▪ Severe fatty liver
▪ Poor – intensive therapy and
$$$
Prognosis of
Hyperketonemia
Applications of HyperketonemiaTesting
▪ Identifying individual hyperketonemic cows
▪ Cow-side test for treatment decisions
▪ How intensive should we be?
▪ Identifying herds with hyperketonemia problems
▪ Herd-level testing for management decisions
Incidence vs. PrevalenceTesting
▪ Incidence = new cases
▪ Difficult to measure
▪ Prevalence = new and existing cases
▪ Easier to measure
▪ First take a prevalence sample
▪ Sample at least 20 cows between 3 to 14 DIM
▪ A larger sample size will result in a more precise
estimate
Sample Size
▪ The more cows you test, the more precise the
prevalence estimate.
▪ 35 animals between 3-14 DIM:
▪ Bleed 14 cows, 3 ketotic
▪ 75% confident the prevalence is between 11-31%
▪ Bleed 25 cows, 5 ketotic
▪ 75% confident the prevalence is between 15-25%
▪ Bleed 33 cows, 7 ketotic
▪ 95% confident the prevalence is between 15-25%
TestAccuracy
▪ Ketone tests with poor sensitivity falsely
decrease prevalence estimate.
▪ Use cow-side blood BHB meters!
Which cows to sample?
▪ All cows in DIM range are eligible
▪ Most really sick cows will not be hyperketonemic
▪ Random sample
▪ Systematic sample – every kth animal
≤ 15%
(e.g. ≤ 3/20, + cows)
Estimate Herd Level Prevalence:
Sample ~20 cows that are 3 to 14 DIM
Positive cows have BHB ≥ 1.2 mmol/L
> 15% to 40%
(e.g. 4 to 8/20, + cows)
≥ 40%
(e.g. ≥ 9/20, + cows)
≤ 15%
Monitor herd level
prevalence monthly.
Sample ~20 cows once
monthly. More frequently
when there are changes,
e.g. diet formulation.
Monitor
≥ 40%
Give 300 mL of propylene
glycol once daily for 5
days starting at 3 DIM to
all cows.
Recheck prevalence in
one month.
Treat all cows
Monitoring and Action Recommendations
Ospina et al.,
2013, VCNA
>15% to 40%
Monitor incidence of SCK.
Sample cows 3 to 9 DIM
twice a week, e.g.,
Tuesday and Friday.
Test and treat
Relevance?
Adapted from Ospina et al., 2010, JDS
Postpartum BHBA
40% of herds above herd alarm level
Summary ▪ High prevalence of HYK
▪ Use an accurate test
▪ Treatment is cost-effective
▪ Regular herd monitoring is
important
Questions?
jmcart@cornell.edu

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Hyperketonemia Treatment at the Individual Cow and Herd Level

  • 1. Hyperketonemia treatment at the individual cow and herd level Jessica McArt, DVM, PhD jmcart@cornell.edu
  • 2. Overview ▪ Physiology ▪ BHB cut-points ▪ Individual animal treatment ▪ Herd-level testing and treatment
  • 3. Negative Energy Balance (NEB) • Dairy cows enter a state of NEB during the transition period • Increased energy demand in early lactation
  • 4. Energy (NEL) Requirements 2 days before versus 2 days after calving 1,600-lb Cow 1,250-lb Heifer Function Pre Post Pre Post Maintenance 11.2 10.1 9.3 8.5 Pregnancy 3.3 --- 2.8 --- Growth --- --- 1.9 1.7 Milk production --- 18.7 --- 14.9 Total (Mcal) 14.5 28.8 14.0 25.1 Calculated from NRC (2001). Assumes milk production of 55 lb/d for cow and 44 lb/d for heifer, each containing 4% fat. Courtesy of J. K. Drackley
  • 6. Ospina et al., 2013, VCNA
  • 7. Ketosis ▪ Ketosis is the elevation of ketone bodies: ▪ Acetone ▪ Acetoacetate ▪ β-hydroxybutyrate (BHB) ▪ Clinical manifestation: ▪ Decrease in appetite ▪ Weight loss ▪ Decrease in milk production  Subclinical disease >80% of cases
  • 8. Nomenclature ▪ Ketosis ▪ Subclinical ketosis ▪ Blood BHB 1.2 – 2.9 mmol/L ▪ Clinical ketosis ▪ Blood BHB ≥ 3.0 mmol/L ▪ Hyperketonemia (HYK) ▪ Blood BHB ≥ 1.2 mmol/L
  • 9. Types of Hyperketonemia ▪ Type I andType II: human-based distinction ▪ Inability to adapt to early lactation NEB ▪ Early in lactation, 3-21 DIM ▪ Excessive NEB just before or after calving ▪ Energy intake limited ▪ 3 to 6 weeks in milk ▪ Lack of energy substrates for level of milk production
  • 10. Periparturient Blood BHB Concentration 0.0 0.2 0.4 0.6 0.8 1.0 1.2 -21 -18 -15 -12 -9 -6 -3 0 3 6 9 12 15 18 21 BHB,mmoL/L Day relative to calving Adapted from McCarthy et al., 2015, JDS
  • 11. How much is “normal”? ▪ Incidence: ▪ Follow a group of animal through time ▪ Number of new cases/number of animals tested ▪ 25% - 85%, average ~ 45% ▪ Prevalence: ▪ Snapshot in time ▪ Number of new and existing cases/number of animals tested ▪ 0% - 70%, average ~ 20% Incidence ~2-2.2 x prevalence
  • 12. Additional Info on Blood BHBTesting ▪ Time of sampling ▪ Not important in ad libTMR fed herds ▪ Otherwise highest ~ 4 to 5 hours after feeding ▪ Location of sampling ▪ Tail vessels = jugular vein ▪ Milk vein ~ 0.3 mmol/L lower
  • 13. Blood BHB Cut-Points ▪ ≥ 1.2 to 1.4 mmol/L ▪ Based on health and production outcomes ▪ ≥ 3.0 mmol/L = more severe hyperketonemia ▪ Remember: ▪ If you your cut-point, sensitivity and specificity ▪ You correctly identify more ketotic cows but treat more non-ketotic cows
  • 14. Applications of HyperketonemiaTesting ▪ Identifying individual hyperketonemic cows ▪ Cow-side test for treatment decisions ▪ How intensive should we be? ▪ Identifying herds with hyperketonemia problems ▪ Herd-level testing for management decisions
  • 15. Individual Consequences of HYK ▪ Higher risk for adverse health events ▪ Metritis ▪ Displaced abomasum ▪ Mastitis ▪ Culling ▪ Decrease milk yield in early lactation ▪ Poorer reproduction
  • 16. When do we test? 0 5 10 15 20 25 30 35 3 4 5 6 7 8 9 10 11 12 13 14 15 16 BloodBHB≥1.2mmol/L(%) Days in Milk Prevalence Adapted from McArt et al., 2012, JDS
  • 17. ▪ Hyperketonemia ▪ BHB ≥ 1.2 mmol/L ▪ Severe hyperketonemia ▪ BHB ≥ 3.0 mmol/L Hyperketonemia Treatment
  • 18. HYKTreatment (BHB ≥1.2 mmol/L) ▪ Propylene glycol ▪ Vitamin B12 ▪ Glucocorticoids - ? Gordon et al., 2013, VCNA
  • 19. Propylene Glycol ▪ Two modes of action: ▪ Increased supply of propionate = glucogenic ▪ Reduced insulin sensitivity = decreased glucose demand by peripheral tissues ▪ Oral drenching preferred over mixing in feed ▪ No benefit with additional glycerol
  • 20. Propylene Glycol ▪ Speeds resolution of ketosis ▪ Prevents progression to severe ketosis ▪ Increases early lactation milk yield ▪ Reduces risk of DA and culling ▪ 300 mL, orally once a day for 5 days ~$1/dose
  • 21. Administration of Propylene Glycol ▪ The stuff tastes horrible … Dosing gun Homemade pump 20 oz. soda bottle & speculum
  • 22. Vitamin B12 ▪ Synthesized in rumen ▪ Methylmalonyl-CoA mutase ▪ Coverts propionate to succinyl-CoA ▪ Vitamin B12 dependent ▪ Some supporting evidence ▪ 1 dose 25 mL Catosal (0.05 mg B12 and 100 mg butaphosphan/mL) Propionate Vitamin B12
  • 23. Glucocorticoids ▪ Examples: ▪ Dexamethasone (Azium) ▪ Isoflupredone (Predef) ▪ Lack of efficacy ▪ Possible adverse side effects
  • 24. HYKTreatment (BHB ≥3.0 mmol/L) ▪ Dextrose ▪ ½ - 1 bottle IV ▪ No randomized, controlled trials ever done on efficacy of dextrose! ▪ Propylene glycol ▪ Vitamin B12 ▪ Corticosteroids - ? ▪ Resent study shows 20mg dexamethasone may be detrimental to cows with BHB >2.0 mmol/L Gordon et al., 2013, VCNA
  • 25. ▪ BHB ≥1.2 mmol/L ▪ Excellent ▪ BHB ≥3.0 mmol/L ▪ Fair to good ▪ Monitor for subsequent diseases ▪ Severe fatty liver ▪ Poor – intensive therapy and $$$ Prognosis of Hyperketonemia
  • 26. Applications of HyperketonemiaTesting ▪ Identifying individual hyperketonemic cows ▪ Cow-side test for treatment decisions ▪ How intensive should we be? ▪ Identifying herds with hyperketonemia problems ▪ Herd-level testing for management decisions
  • 27. Incidence vs. PrevalenceTesting ▪ Incidence = new cases ▪ Difficult to measure ▪ Prevalence = new and existing cases ▪ Easier to measure ▪ First take a prevalence sample ▪ Sample at least 20 cows between 3 to 14 DIM ▪ A larger sample size will result in a more precise estimate
  • 28. Sample Size ▪ The more cows you test, the more precise the prevalence estimate. ▪ 35 animals between 3-14 DIM: ▪ Bleed 14 cows, 3 ketotic ▪ 75% confident the prevalence is between 11-31% ▪ Bleed 25 cows, 5 ketotic ▪ 75% confident the prevalence is between 15-25% ▪ Bleed 33 cows, 7 ketotic ▪ 95% confident the prevalence is between 15-25%
  • 29. TestAccuracy ▪ Ketone tests with poor sensitivity falsely decrease prevalence estimate. ▪ Use cow-side blood BHB meters!
  • 30. Which cows to sample? ▪ All cows in DIM range are eligible ▪ Most really sick cows will not be hyperketonemic ▪ Random sample ▪ Systematic sample – every kth animal
  • 31. ≤ 15% (e.g. ≤ 3/20, + cows) Estimate Herd Level Prevalence: Sample ~20 cows that are 3 to 14 DIM Positive cows have BHB ≥ 1.2 mmol/L > 15% to 40% (e.g. 4 to 8/20, + cows) ≥ 40% (e.g. ≥ 9/20, + cows) ≤ 15% Monitor herd level prevalence monthly. Sample ~20 cows once monthly. More frequently when there are changes, e.g. diet formulation. Monitor ≥ 40% Give 300 mL of propylene glycol once daily for 5 days starting at 3 DIM to all cows. Recheck prevalence in one month. Treat all cows Monitoring and Action Recommendations Ospina et al., 2013, VCNA >15% to 40% Monitor incidence of SCK. Sample cows 3 to 9 DIM twice a week, e.g., Tuesday and Friday. Test and treat
  • 32. Relevance? Adapted from Ospina et al., 2010, JDS Postpartum BHBA 40% of herds above herd alarm level
  • 33. Summary ▪ High prevalence of HYK ▪ Use an accurate test ▪ Treatment is cost-effective ▪ Regular herd monitoring is important