Evaluating the effect of equine tetanus antitoxin on mortality rates of dogs affected by tetanus

PICO Question
In dogs with tetanus, does administering the equine tetanus antitoxin compared to not administering the antitoxin reduce mortality rates?
 
Clinical bottom line
Category of research
Treatment.
Number and type of study designs reviewed
Three studies were reviewed for this Knowledge Summary, all of which were retrospective case-control studies.
Strength of evidence 
Weak.
Outcomes reported
There was no difference in survival to discharge between dogs treated and dogs not treated with equine tetanus antitoxin.
Conclusion
The current literature suggests that administering the equine tetanus antitoxin to dogs affected by tetanus had no positive or negative effect on mortality rates, though the level of evidence amongst the literature is weak.
 
How to apply this evidence in practice
The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources.
Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.

The current literature suggests that administering the equine tetanus antitoxin to dogs affected by tetanus had no positive or negative effect on mortality rates, though the level of evidence amongst the literature is weak.
The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient's circumstances and owners' values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources.
Knowledge Summaries are a resource to help reinforce or inform decision-making.They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.

PICO question
In dogs with tetanus, does administering the equine tetanus antitoxin compared to not administering the antitoxin reduce mortality rates?

Clinical scenario
A 10-month-old female neutered Golden Retriever is presented to you with a 2 day history of having a 'strange' facial expression and generalised muscle stiffness.Upon presentation, the dog is exhibiting risus sardonicus, characteristic of tetanus.The use of the equine tetanus antitoxin has been described in the management of tetanus, but is there any evidence to suggest any benefits between dogs that do receive the equine tetanus antitoxin compared to those that do not?

The evidence
A search of the literature revealed three studies relevant to this PICO, all of which were retrospective case-control studies.The strength of evidence for each paper is considered weak due to the lack of prospective systematic reviews or meta-analyses for this Knowledge Summary.

Main findings (relevant to PICO question)
Dogs with characteristic clinical signs and treated for tetanus, without evidence of other neuromuscular disease.20 dogs.

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A total of 16 dogs received the equine tetanus antitoxin (200 IU/ kg, intravenously [IV]), 12 of which also received an intradermal test dose of 0.1 ml prior to the IV dose.Amongst the 16 dogs, six dogs were found to have wounds or lacerations and received an additional 1000 IU equine tetanus antitoxin after exploration and lavage.• A total of four dogs did not receive the antitoxin.

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All dogs received IV fluid and nutritional support.
Retrospective case-control study.
• Survival -this was defined as survival to discharge.Each case was described as 'survived', 'died' or 'euthanised'.• Severity -there was no mention as to how this was specifically measured, though the following was recorded and presumed to be taken into account with respect to assessing severity: clinical signs and complications measured as number of cases affected respectively; and duration of hospitalisation for survivors, first sign of improvement of clinical signs, and time to complete recovery, all of which were measured as a median value and a range respectively.• Duration -this was defined as time to complete recovery amongst dogs that survived their respective treatment protocol, and measured as a median value and a range.
• There was no difference in survival to discharge between dogs treated and dogs not treated with antitoxin.• Survival -50% (2/4) dogs that did not receive the antitoxin survived, and 50% (8/16) dogs that received the antitoxin survived.

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The researchers also reported no difference in severity or duration of clinical signs between dogs treated and not treated with antitoxin.This is difficult to verify given the lack of clarity with respect to specific measurement of severity, and specific comparison of time to complete recovery for dogs treated with antitoxin and those that were not.

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No power calculation was used, nor was there any form of randomisation.• Small sample size.

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Variable treatment protocols in each case as well as advances in nursing care over the 16 year duration of the study make it difficult to extrapolate reliable conclusions.

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The study mentions a Chi-square analysis was used but no such data was presented.

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Information bias associated with retrospective nature.
Dogs with typical clinical signs of tetanus, excluding those with incomplete medical records, hypocalcaemia, and confirmed neurotoxicoses or myositis.
A canine tetanus severity classification system was developed prior to identifying dogs eligible for inclusion into the study.
The system was based on the human classification system, information gathered from veterinary textbooks and case reports, and the researchers' experience.The dogs were then grouped into the following classes:

Appraisal, application and reflection
Three studies were reviewed for this Knowledge Summary, all of which were retrospective case-control studies that aimed to evaluate the clinical courses and outcomes of dogs affected by tetanus.The main finding reported was that there was no positive or negative effect on the survival of dogs affected by tetanus who received the equine tetanus antitoxin (Bandt et al., 2007;Burkitt et al., 2007;and Zitzl et al., 2022).
There were an insufficient number of cases in the studies reviewed, as demonstrated by the relatively small sample sizes.Two of the studies appraised are relatively old being published at least 15 years ago, and therefore advances in intensive care management and general nursing care since would play a part in affecting the mortality rate of dogs affected by tetanus, questioning the applicability of these studies' findings.Furthermore, referral populations were assessed and therefore findings may not necessarily represent those found with other subpopulations.Variable treatment protocols for each case associated with the retrospective nature of the studies is a large confounding factor but this was acknowledged in their respective discussions.Given the broad aim of the studies, direct comparison of outcomes on the basis of clinical treatment choice, or specifically on the basis of administration of the antitoxin in this case, was not always clear to avoid confounding by indication as mentioned in Burkitt et al. (2007).In other words, an accurate and reliable association between the use of the equine tetanus antitoxin and mortality rates cannot be deduced based on these retrospective studies owing to the fact that more severely affected dogs were potentially more likely to receive earlier, higher frequency of treatments and interventions.As a result, alternative associations between the multiple different treatments and interventions used, as well as the indications of their use and the mortality rates of the dogs affected by tetanus, cannot be ruled out.
Cases of tetanus in dogs are relatively uncommon.The small sample sizes of the studies reviewed may be explained by the fact that dogs are relatively resistant to tetanus due to poor tetanospasmin penetration of neural tissue compared to that in humans (Greene, 2006).Moreover, the antitoxin acts by binding to any unbound toxin.Considering this, its administration would likely be useful during the peracute stage of the disease which may well be prior to presentation.Future large, randomised, prospective studies assessing for optimal timing and dosing of equine tetanus antitoxin administration, complication rates, and duration of hospitalisation or time to recovery in survivors are indicated to determine whether the findings of these three studies reviewed are supported or refuted.

Methodology
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