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Ketoprofen in cattle with E.coli mastitis

Clinical Scenario

During a visit to one of your dairy farms, you are discussing some recent cases of mastitis with the farmer John Smith. He has had a few cases recently where the cow has been systemically unwell and you both have concerns about  E.coli. The cases have been very difficult to treat and one cow ended up being culled last month.

He has experience of antibiotics and fluid therapy and is unsure if either make a difference and asks you about different treatment options for cases of toxic E.coli mastitis. He specifically asks you about ketoprofen as it was used in one case that did well and wants to know if it works in all cases. You wonder what the advantages are of ketoprofen on clinical recovery of cows with E.coli mastitis...

3-Part Question (PICO)

In [dairy cattle with E.coli mastitis] does [the administration of ketoprofen compared to no anti-inflammatory treatment] [improve clinical recovery]?

Search Strategy and Summary of Evidence

Search Strategy

MEDLINE(R) In-Process & Other Non-Indexed Citations and MEDLINE(R) 1946 to Present using the OVID interface

(cow.mp. OR cows.mp. OR cattle.mp. OR bovine.mp. OR bovines.mp. OR exp Cattle/)

AND

(e coli mastitis.mp. OR escherichia coli mastitis.mp. OR coliform mastitis.mp. OR toxic mastitis.mp. OR systemic mastitis.mp. OR exp Mastitis, Bovine/)

AND

(NSAID.mp. OR NSAIDs.mp. OR non steroidal.mp. OR nonsteroidal.mp. OR ketoprofen.mp. OR ketofen.mp. OR comforion.mp. OR kelaprofen.mp. OR rifen.mp. OR exp Anti-Inflammatory Agents, Non-steroidal/ OR exp Ketoprofen/)

CAB Abstracts 1910 to Present using the OVID interface

(cow.mp. OR cows.mp. OR cattle.mp. OR bovine.mp. OR bovines.mp. Or exp Cattle/ OR exp Dairy cows/)

AND

(e coli mastitis.mp. OR escherichia coli mastitis.mp. OR coliform mastitis.mp. OR toxic mastitis.mp. OR systemic mastitis.mp. OR exp bovine mastitis/)

AND

(NSAID.mp. OR NSAIDs.mp. OR non steroidal.mp. OR nonsteroidal.mp. OR ketoprofen.mp. OR ketofen.mp. OR comforion.mp. OR kelaprofen.mp. OR rifen.mp. OR exp non-steroidal antiinflammatory agents/ OR exp ketoprofen/)

Search Outcome

MEDLINE

  • 53 papers found in MEDLINE search
  • 47 papers excluded as they don't meet the PICO question
  • 0 papers excluded as they are in a foreign language
  • 3 papers excluded as they are review articles/in vitro research/conference proceedings
  • 3 total relevant papers from MEDLINE

CAB Abstracts

  • 97 papers found in CAB search
  • 57 papers excluded as they don't meet the PICO question
  • 0 papers excluded as they are in a foreign language
  • 37 papers excluded as they are review articles/in vitro research/conference proceedings
  • 3 total relevant papers from CAB

Total relevant papers

3 relevant papers from both MEDLINE and CAB Abstracts

Comments

The third relevant paper which is not included in the summary of evidence section below was:

Shpigel et al (1998) Relationship between in vitro sensitivity of coliform pathogens in the udder and the outcome of treatment for clinical mastitis. The Veterinary Record 142: 135-137.

This paper used the same relevant data as the Shpigel et al 1994 paper described below, and was therefore not included.

 

 

Summary of Evidence

Banting et al. (2008) Unclear where the study was conducted

Title:

Efficacy of oral and parenteral ketoprofen in lactating cows with endotoxin-induced acute mastitis

Patient group:

27 cows with experimentally induced acute mastitis (endotoxin infusion)

Study Type:

Controlled clinical trial

Outcomes:
  • Quarter milk production
  • Behaviour of cows (e.g. depressed)
  • Rectal temperature
  • Respiratory rate
  • Ruminal contractions
  • Size of the mammary gland
  • Appearance of the milk
  • Pain in udder
  • Milk thromboxane B2 levels
  • Plasma thromboxane B2 levels
  • Measurements made before challenge then 2,4,6,8,10,24,34,48, 72 hours and 7 days and 14 days post challenge. Milk samples only examined up until 48 hours post challenge.
Key Results:
  • Rectal temperatures were significantly lower in the ketoprofen treated groups compared to the untreated control group at 6, 8 and 10 hours after disease challenge (p<0.05)
  • One cow in the untreated control group had severe clinical signs and was removed from the trial for treatment; 4 of the 8 remaining control cows showed mild clinical signs and 1 out of 9 cows from each of the 2 ketoprofen treated groups showed mild clinical signs (no statistics provided)
  • Respiratory rates were significantly lower throughout the trial in the 2 treated groups compared to the control group (p<0.01)
  • Ruminal contraction rates returned to normal in the treated groups within 24 hours whereas they took 7 days to return to normal in the control group. Overall ruminal contractions were significantly lower in the control group compared to the treated groups for 48 hours post challenge (p<0.001)
  • Pain scores were significantly lower in the treated groups compared to the control group (p<0.01)
  • Udder size was significantly lower in the treated groups at 6,8 and 48 hours post challenge (p<0.05)
  • Milk appearance scores were lower (more normal) in the treated groups compared to the control group for 24 hours post treatment (p<0.05). 
  • There were no significant differences in milk thromboxane levels between the groups
  • Plasma thromboxane levels were significantly lower in the treated groups than the control group at some time points for up to 24 hours after treatment (p<0.05)
Study Weaknesses:
  • Cows in the study had experimentally induced acute mastitis
  • No randomisation of cows to treatment groups
  • No comparison of the treatment groups at baseline for demographic parameters e.g. age, stage of lactation, milk yield
  • Several outcome measures are subjectively scored; no information given as to how many people were assessing the cows and if they received any training to standardise the process
  • No blinding used in the study
  • No ethical approval stated
  • Unclear where the study was conducted
  • No results were reported for quarter milk production although it was stated that it would be measured
  • No sample size justification (n=9 cows per group)
Attachment:
Evidence appraisalEvidence appraisal

Shpigel et al. (1994) Jerusalem

Title:

Anti-inflammatory ketoprofen in the treatment of field cases of bovine mastitis

Patient group:

385 Israeli-Holstein cows with naturally occurring clinical mastitis defined by the diagnosis of typical acute, local and systemic abnormal changes in the body, the udder and the milk, and a concurrent drop of at least 25% in the daily milk production.

Study Type:

Controlled clinical trial

Outcomes:
  • Recovery rate of cases. Outcome of each case defined as:
    • Recovered (cows that returned to at least 75% of the pre-mastitis daily milk production)
    • Blind quarter (cows in which lactation ceased in the affected quarters for the duration of the present lactation)
    • Culled (cows that died, were salvage slaughtered, culled or did not return to at least 75% of premastitis daily milk production)

    Recovered cows = treatment success, blind quarters/culled = treatment failures

Key Results:
  • In cases where gram negative organisms were cultured, the recovery rates in the ketoprofen groups were higher than in the non ketoprofen treated groups (ketoprofen recovery rates were 93.5% (group 2) and 92% (group 4) compared to 84% (group 1), 81.5% (group 3) and 63.6% (group 5) in the non ketoprofen treated groups).

  • For all cases of clinical mastitis (i.e. not gram negative only) the recovery rates in the ketoprofen groups were higher than in the non ketoprofen treated groups (ketoprofen recovery rates were 94.7% (group 2) and 92.3% (group 4) compared to 81% (group 1), 83.7% (group 3) and 70.7% (group 5) in the non ketoprofen treated groups).

  • In the blinded part of the study (all cases included, i.e. not gram negative only), the odds of recovery was higher for the ketoprofen treated cows compared to the non ketoprofen treated cows (odds ratio = 6.75, p<0.01).

  • In the non blinded part of the study, the odds ratio for recovery of ketoprofen treated cows compared to non ketoprofen treated cows was not significantly different.
Study Weaknesses:
  • Experiments not all conducted concurrently, some controls were historical
  • Some parts of the study were blinded but others were not
  • Allocation of cows to treatment groups was predictable and not truly randomised which could introduce bias
  • Not all cow and affected quarter numbers add up in the results section
  • Statistical significance levels not defined in the methods
  • No sample size calculation performed
  • No comparison of the treatment groups at baseline for demographic parameters e.g. age, stage of lactation, milk yield
  • No ethical approval stated
Attachment:
Evidence appraisalEvidence appraisal

Comments

The primary aim of the Banting et al study was not to assess the efficacy of ketoprofen in cows with acute mastitis but rather to compare the efficacy of orally and parenterally administered ketoprofen, however there was an untreated control group which allows us to make a comparison.

The Banting et al trial used a model of acute mastitis where inflammation was created by the intramammary infusion of E.coli endotoxin. Most cows in this trial only displayed mild clinical signs and ketoprofen treatment was initiated 2 hours after endotoxin challenge; the results of the trial may therefore not be applicable to field cases of acute mastitis.  In contrast, the larger Shpigel et al study is more representative of field cases of acute mastitis.

Both trials have a high risk of bias due to the lack of complete randomisation and blinding and further randomised trials under field conditions would be beneficial to address this question.

Bottom line

Ketoprofen improves the clinical recovery in dairy cattle with acute mastitis compared to no anti inflammatory treatment.

Disclaimer

The BETs on this website are a summary of the evidence found on a topic and are not clinical guidelines. It is the responsibility of the individual veterinary surgeon to ensure appropriate decisions are made based on the specific circumstances of patients under their care, taking into account other factors such as local licensing regulations. Read small print

References

Banting A, Banting S, Heinonen K, Mustonen K, (2008). Efficacy of oral and parenteral ketoprofen in lactating cows with endotoxin-induced acute mastitis. Veterinary Record 163: 506-509.

Shpigel NY, Chen R, Winkler M, Saran A, Ziv G, Longo F, (1994). Anti-inflammatory ketoprofen in the treatment of field cases of bovine mastitis. Research in Veterinary Science 56: 62-68.

About this BET

First author:
Kathryn Wareham
Second author:
Rachel Dean
Institution:

CEVM, University of Nottingham

Search last performed:
2016-05-16 20:14:52
Original publication date:
2016-09-30 20:14:52
Last updated:
2016-09-27 20:14:52
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