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Administration of flunixin in addition to antibiotics in calves with pneumonia

Clinical Scenario

Matt Brown, one of your beef clients, purchases large numbers of weaned suckler calves in the autumn and rears them through to finishing weight. Despite his best efforts to prevent the disease, pneumonia remains a significant problem in the calves on his unit. He normally treats the affected calves with antibiotics (tulathromycin) but he sometimes has calves that don’t seem to respond and take a long time to recover. You have previously been out to see some of the sick calves and administered flunixin which Matt says definitely improves their clinical condition in the short term. He asks you if he treats all calves routinely with flunixin from the start when he gives the antibiotics, would this shorten their overall time to clinical recovery. You wonder if flunixin would help in this way.....

3-Part Question (PICO)

In [calves with pneumonia] does [the administration of flunixinin in combination with antibiotics compared to antibiotics alone] [shorten the time to clinical recovery from the disease]?

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

calf.mp. OR calves.mp. OR cattle.mp. OR bovine.mp. OR bovines.mp. OR bos.mp. OR exp Cattle/

AND

pneumonia.mp. OR respiratory infection.mp. OR respiratory diseases.mp. OR respiratory infections.mp. OR respiratory disease.mp. OR pneumonic.mp. OR exp Pneumonia/ OR exp Respiratory Tract Infections/ OR exp Respiratory Tract Diseases/

AND

antibacterial.mp. or antibacterials.mp. OR antibiotic.mp. OR antibiotics.mp. OR antimicrobial.mp. OR antimicrobials.mp. OR exp Anti-Bacterial Agents/ OR exp Anti-Infective Agents/

AND

NSAID.mp. OR NSAIDs.mp. OR nonsteroidal.mp. OR non steroidal.mp. OR exp Anti-Inflammatory Agents, Non-Steroidal/ OR flunixin.mp. OR finadyne.mp. OR Banamine.mp. OR Meflosil.mp. OR Resflor.mp. OR Cronyxin.mp.

CAB Abstracts 1910 to Present using the OVID interface

calf.mp. OR calves.mp. OR cattle.mp. OR bovine.mp. OR bovines.mp. OR bos.mp. OR exp cattle/ OR exp calves/

AND

pneumonic.mp. OR pneumonia.mp. OR respiratory infection.mp. OR respiratory diseases.mp. OR respiratory infections.mp. OR respiratory disease.mp. OR exp pneumonia/ OR exp respiratory diseases/

AND

antibacterial.mp. OR antibacterials.mp. OR antibiotic.mp. OR antibiotics.mp. OR antimicrobial.mp. OR antimicrobials.mp. OR exp antibacterial agents/ OR exp antibiotics/ OR exp antiinfective agents/

AND

NSAID.mp. OR NSAIDS.mp. OR nonsteroidal.mp. OR non steroidal.mp. OR finadyne.mp. OR flunixin.mp. OR Banamine.mp. OR Meflosil.mp. OR Resflor.mp. OR Cronyxin.mp. OR exp flunixin/ OR exp non-steroidal antiinflammatory agents/

Search Outcome

MEDLINE

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

CAB Abstracts

  • 92 papers found in CAB search
  • 71 papers excluded as they don't meet the PICO question
  • 4 papers excluded as they are in a foreign language
  • 11 papers excluded as they are review articles/in vitro research/conference proceedings
  • 7 total relevant papers from CAB

Total relevant papers

7 relevant papers from both MEDLINE and CAB Abstracts

Comments

There were a number of papers found in the search that addressed this treatment comparison with experimentally induced respiratory disease or undifferentiated fever but it was felt this did not answer the PICO question. 

Summary of Evidence

Wilson et al, 2015, USA

Title:

Evaluation of multiple ancillary therapies used in combination with an antimicrobial in newly received high-risk calves treated for bovine respiratory disease

Patient group:

320 Calves (bodyweight 217 +/- 20kg) split into 4 groups: Antibiotics and flunixin (N=80), Antibiotics and intranasal vaccine (N=80), Antibiotics and vitamin C (N=80), Antibiotics alone (N=80)

Study Type:

Randomised controlled trial

Outcomes:
  • Rectal temperature
  • Clinical Severity Score 
  • Body weight
  • Average daily weight gain
  • Re-treatment with antibiotics
  • Removal from the group
  • Finishing performance
Key Results:
  • At the time of the 2nd antimicrobial treatment the antibiotic only treatment group had a significantly lower (better) clinical score than the group receiving flunixin (P<0.01).
  • At the time of the 3rd treatment, calves receiving antibiotics only had significantly lower (better) clinical severity scores than calves in the other 3 groups(P < 0.01).
  • By the 3rd antimicrobial treatment those on antibiotics only were significantly heavier than those receiving any ancillary treatment (p=0.01, the antibiotics only group lost 0.13kg/d whereas the other groups lost 12.54kg/d)
  • Average daily gain was significantly more in the antibiotics only group compared to the groups receiving ancillary treatments (P<0.01)
  • No significant difference in mortality  or removals between groups
  • No significant difference in performance or efficiency parameters between groups
  • No significant difference in finishing performance between groups
Study Weaknesses:
  • Method of randomisation not stated
  • Limited data given about the groups prior to randomisation but body weight was not different between groups of calves at the start of the study and all calves met the inclusion criteria
  • It was not stated if the person administering the treatments was blinded
  • Subjective clinical scoring system used, unclear if it was fully validated
  • No sample size calculation reported
  • Basic data not described in enough detail
  • Side effects not reported
  • No information on who funded the study
Attachment:
Evidence appraisalEvidence appraisal

Thiry et al, 2014, France, Spain, Belgium

Title:

Treatment of naturally occurring bovine respiratory disease in juvenile calves with a single administration of a florfenicol plus flunixin meglumine formulation

Patient group:

210 pre-ruminating calves (bodyweight 31-78.6kg, age 12-41 days) of  a number of beef breeds split into 2 groups: Antibiotics and flunixin (N=106), Antibiotics alone (N=104)

Study Type:

Randomised controlled trial

Outcomes:
  • Rectal temperature at 6 hours
  • Treatment success (depress score = 0, respiratory score > 2, rectal temperature < 40 degrees Celsius)
  • Treatment failure (depression score >1, respiratory score > 2, rectal temperature > 40 degress Celsius)
Key Results:
  • The means of change in rectal temperature from time 0 hour to time six hours was−1.36°C in the florfenicol-flunixin group and −0.6°C in the florfenicol group. The means of relative change (%) in rectal temperature (±SD) between groups was significantly different (P<0.0001).
  • By 6 hours, a decrease in the severity of depression was observed in both treatment groups with a significantly greater improvement observed in the florfenicol-flunixin group than in the florfenicol group (P<0.0001).
  • By day 4, florfenicol-flunixin group had 99 successes (93.4%) and the florfenicol group had 93 successes (90.3%). Hence the florfenicol-flunixin formulation was significantly non-inferior to florfenicol for the initial treatment success on day four.
  • By day 10 florfenicol-flunixin group had 71 successes (67%) and the florfenicol group had 62 successes (60.2%). Hence the florfenicol-flunixin formulation was significantly non-inferior to florfenicol for the cumulative treatment success on day 10.
  • The incidence of injection site reactions for florfenicol-flunixin group was 16.8% and 15.5% for the florfenicol group.
Study Weaknesses:
  • Not clear if the people administering treatments were blinded or not, but they were different from the people making the assesments.
  • Minimal data provided about the groups prior to intervention but they all met the inclusion criteria
  • A subjective clinical scoring system as used.
  • The basic data was not given in enough detail to reproduce the results.
  • Two of the authors were funded by the company who made the product tested.
Attachment:
Evidence appraisalEvidence appraisal

Bednarek et al, 2013, Poland

Title:

The effect of the combined use of a long-acting antibiotic with NSAID on
the clinical status and cellular immune response in calves affected with
bovine respiratory disease

Patient group:

90 Black and White Lowland breed dairy calves of mean body weight 147 +6.5 kg, aged between 2 and 4 months showing typical clinical signs of bovine respiratory disease (BRD) (fever over 40°C, cough, with a nasal discharge from mucoid, mucopurulent to purulent, dyspnea, anorexia and lethargy).

45 calves given florfenicol and flunixin meglumine and 45 calves give florfenicol alone

Study Type:

Randomised controlled trial

Outcomes:
  • Clinical Illness Index Score (CIIS) – body temperature, respiratory rate, nasal discharge, coughing, dyspnea, appetite, depression and mortality
  • WBC counts, CD2, CD4, CD8, WC4, Immunophenotyping 
Key Results:
  • The group treated with florfenicol and flunixin meglumine had significantly lower CIIS scores on day 2 and 3 (p<0.05) compared with the group treated with florfenicol alone.
  • By day 5 the CIIS scores in the florfenicol and flunixin meglumine group were lower than the florfenicol only group but this was not significant.
  • The immunological markers were significantly lower in the florfenicol and flunixin meglumine group compared to the florfenicol alone group.
Study Weaknesses:
  • Method of randomisation not stated
  • Limited data given about the groups prior to randomisation but all calves met the inclusion criteria
  • It was not stated if the person administering the treatments were blinded
  • Subjective clinical scoring system used, unclear if it was fully validated
  • It was not stated if the person(s) administering the outcomes was (were) blinded
  • No sample size calculation reported
  • No level of statistical significance reported in the methods
  • Statistical methods very short
  • Basic data not adequately described
  • Side effects not reported
  • No ethical approval reported
  • No information on who funded the study
Attachment:
Evidence appraisalEvidence appraisal

Guzel et al, 2010, Turkey

Title:

Clinical efficacy of diclofenac sodium and flunixin meglumine as
adjuncts to antibacterial treatment of respiratory disease of calves

Patient group:

80 calves (2-5months, 6-155kg) on 3 private farms in Turkey split into 3 groups: Tulathromycin only (N=20), Tulathromycin and diclofenac (N=30) and Tulathromycin  and flunixin (N=30)

Study Type:

Randomised controlled trial

Outcomes:
  • Rectal temperature
  • Respiratory rate
  • Improvement in clinical score at day 7
  • Improvement in clinical score at day 14
Key Results:
  • Rectal temperature, respiratory rate and clinical index score in the NSAIDs groups were all significantly decreased (P < 0.05) in comparison with the tulathromycin group for the first 48 h.
  • There were no statistical differences between treatment groups on day 7.
  • There were no statistical differences between treatment groups on day 14.
Study Weaknesses:
  • Method of randomisation not stated
  • It is not stated explicitly if the people administering treatments or assessing outcomes were  blinded or not, though it says the trial is doubled blinded in the first line of the methods
  • Subjective clinical scoring system used, unclear if it was fully validated
  • No sample size calculation reported
  • No level of statistical significance reported in the methods
  • Statistical methods very short
  • Side effects not reported
  • No ethical approval reported
  • No information on who funded the study
Attachment:
Evidence appraisalEvidence appraisal

Keita et al, 2007, France

Title:

A combination oxytetracycline/flunixin treatment of respiratory infections in cattle

Patient group:

150 pre-ruminant calves, 8-90 days old, with clinical signs of respiratory disease and body temperature of over 39.5oC, split into 3 groups oxytetracycline and flunixin (N=50), oxytetracycline only (N=50) and tilmicosin only (N=50)

Study Type:

Randomised controlled trial

Outcomes:
  • Rectal temperature
  • Respiratory rate
  • Subjective clinical score
  • Retreatment rates
Key Results:
  • Body temperature decreased in all groups and was statistically significant in the oxytetracycline/flunixin group compared to both groups treated with antibiotics alone (P <0.001) at 6 hours.
  • The body temperature was significantly lower in the oxytetracycline/flunixin group compared to the oxytetracycline only group  (P <0.001) at 24 hours.  
  • There was no significant difference in body temperature between treatment groups at 3, 7 and 10 days post treatment (P>0.05).
  • There was no significant difference between groups in terms of respiratory rate, hyperpnoea, respiratory sounds, coughing, demeanor, re-treatment rates and overall clinical scores (P>0.05).
Study Weaknesses:
  • It was not stated if the people administering the treatments were blinded
  • Subjective clinical scoring system used, unclear if it was fully validated
  • No sample size calculation reported
  • Basic data not adequately described
  • Side effects not reported
  • No ethical approval reported
  • No information on who funded the study
Attachment:
Evidence appraisalEvidence appraisal

Lockwood et al, 2003, USA

Title:

Clinical efficacy of flunixin, carprofen and ketoprofen as adjuncts to the antibacterial treatment of bovine respiratory disease

Patient group:

66 mixed breed calves (mean weight 197kg), with dyspnea score of 1 or 2, a clinical illness score of 2 or more and/or a depression score of 2 or 3 and body temperature of at least 40oC, split into 4 groups ceftiofur and flunixin (N=17), ceftiofur and ketoprofen (N=16), ceftiofur and carprofen (N=16), and ceftiofur only (N=17)

Study Type:

Randomised controlled trial

Outcomes:
  • Rectal temperature
  • Respiratory rate
  • Subjective clinical illness score
  • Clinical success
  • Lung consolidation
Key Results:
  • The pyrexia of the calves treated with the three NSAIDs was significantly reduced in comparison with the group treated with antibiotic alone during the first 24 hours (P<0.05).
  • After 48 and 72 hours there was no significant difference in rectal temperature between groups.
  • There was no significant difference between treatment groups in terms of clinical illness score, dyspnea, and clinical success.
  • The use of flunixin in conjunction with ceftiofur resulted in a statistically significant (P=0.003) reduction in the mean extent of lung consolidation compared to other groups (P=0.03).
Study Weaknesses:
  • Limited data given about the groups prior to randomisation but all calves met the inclusion criteria
  • It was not stated if the person administering the treatments was blinded
  • Subjective clinical scoring system used, unclear if it was fully validated
  • No sample size calculation reported
  • No level of statistical significance reported in the methods
  • Basic data not adequately described
  • Side effects not reported
  • No ethical approval reported
  • No information on who funded the study
Attachment:
Evidence appraisalEvidence appraisal

Hellwig et al, 2000, USA

Title:

Flunixin Meglumine as Adjunct Therapy for Bovine Respiratory Disease in Stocker Cattle

Patient group:

96 beef breed calves, body weight 396-526lb, with clinical signs of bovine respiratory disease split into 2 groups tilmicosin and flunixin (N=48) and tilmicosin only (N=48)

Study Type:

Randomised controlled trial

Outcomes:
  • Clinical signs
  • Rectal temperature
  • Treatment success (resolution of clinical signs and body temperature <103oF)
  • Treatment failure (no improvement in clinical signs or reduction in body temperature within 48hours)
  • Treatment relapses
  • Average daily weight gain
  • Cost of gain per pound
Key Results:
  • The number of treatment successes was greater in the flunixin/antibiotic treated (88%) group compared to the group treated with antibiotics alone (61%) (P=0.06).
  • The combined number of treatment failures and relapses of disease was less for the flunixin/antibiotic (5%) treated group than group treated with antibiotics alone (38%) (P < 0.05).
  • The total medication cost per head for the flunixin/antibiotic treated group was less than for group receiving antibiotics alone ($14.66 vs. $18.10) (P = 0.10).
  • The average daily gain over the 35 days feeding period was not different between groups (2.2 vs. 2.4 lb per head/d, P = 0.51).
  • The cost of gain per pound was the same for both groups ($0.37).
Study Weaknesses:
  • Limited data given about the groups prior to randomisation but all calves met the inclusion criteria
  • It was not stated if the people administering the treatments were blinded
  • Subjective clinical scoring system used, unclear if it was fully validated
  • No sample size calculation reported
  • No level of statistical significance reported in the methods and various p values reported in the results, therefore it is unclear what was considered significant. 
  • Basic data not adequately described
  • Side effects not reported
  • No ethical approval reported
  • No information on who funded the study
Attachment:
Evidence appraisalEvidence appraisal

Comments

The studies found in this BET all differ slightly in terms of age, breed and weight of the calves and are undertaken at a number of different locations across the world, where animal management systems vary. Therefore it is likely that the disease processes and infectious agents involved in the pathogenesis of the disease in the calves may vary from one study to the next.

The papers found in this study consistently suggest that the administration of flunixin to antibiotics when treating calves with pneumonia will reduce their body temperature signficantly in the first 24-48 hours. Some of the studies also found that the subjective clinical scores also reduced in this time period if flunixin was used. Other studies found it made no difference to the clinical condition of the calves. The difference in the findings may be due to the subjective nature of the assessments used which have uncertain validity or differing pathological processes across the different studies, or some other unmeasured factor.

The welfare of calves suffering from pneumonia is considerably compromised, and whilst it might be unlikely that flunixin confers significant benefits in productivity outcomes, there are likely to be considerable and immediate benefits to animal health and welfare.

Bottom line

Flunixin reduces pyrexia and may reduce some other clinical signs in calves with pneumonia. Whilst an increase in productivity is unlikely, there are likely to be rapid and significant benefits to animal health and welfare.

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

Wilson BK, Step DL, Maxwell CL, Wagner JJ, Richards CJ, Krehbiel CR, (2015). Evaluation of multiple ancillary therapies used in combination with an antimicrobial in newly received high-risk calves treated for bovine respiratory disease. Journal of Animal Science93: 3661-74.

Thiry J, Gonzalez-Martin JV, Elvira L, Pagot E, Voisin F, Lequeux G, Weingarten A, de Haas V, (2014). Treatment of naturally occurring bovine respiratory disease in juvenile calves with a single administration of a florfenicol plus flunixin meglumine formulation. Veterinary Record 174:430. 

Bednarek D, Lutnicki K, Dudek K, Marczuk J, Kurek L, Mordak R, Stewart PA, (2013). The effect of the combined use of a long-acting antibiotic with NSAID on the clinical status and cellular immune response in calves affected with bovine respiratory disease. Cattle Practice 21:91-97. 

Guzel M, Karakurum MC, Durgut R, Mamak N, (2010). Clinical efficacy of diclofenac sodium and flunixin meglumine as adjuncts to antibacterial treatment of respiratory disease of calves. Australian Veterinary Journal 88:236-9. 

Keita A, Pommier P, Pagot E, Couper A, Cromie L, (2007). A combination oxytetracycline/flunixin treatment of respiratory infections in cattle. Revue de Medecine Veterinaire 158:86-91.

Lockwood PW, Johnson JC, Katz TL, (2003). Clinical efficacy of flunixin, carprofen and ketoprofen as adjuncts to the antibacterial treatment of bovine respiratory disease. Veterinary Record. 152:392-4.

Hellwig DH, Kegley EB, Johnson Z, Hunsaker B, (2000). Flunixin meglumine as adjunct therapy for bovine respiratory disease in stocker cattle. Research Series - Arkansas Agricultural Experiment Station 478:10-12. 

About this BET

First author:
Rachel Dean
Second author:
Bobby Hyde
Institution:

CEVM, SVMS

Search last performed:
2018-02-27 11:35:35
Original publication date:
2018-02-28 11:35:35
Last updated:
2018-02-28 11:35:35
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