In Dogs With a European Adder Bite, Does the Use of Antivenom With Supportive Treatment Compared to Supportive Treatment Alone Improve Time to Recovery?

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Appraisal, application and reflection

The literature search performed by the authors found three papers which partially addressed the PICO question.

The study by Lund et al (2013) reports an improvement in local swelling and mental status in animals that received antivenom within 24 hours of the European adder bite. The group of dogs receiving antivenom also showed decreased proteinuria levels two weeks after the bite. These findings could be considered of interest when answering the PICO question; the study, however, presents some significant limitations which affect the quality of the evidence produced. The dogs recruited for the study had not been randomly assigned to the antivenom or the control group. The choice to administer antivenom was based on the clinician’s subjective assessment of the severity of the clinical signs, the financial situation of the owner and the availability of antivenom. This could have led to the introduction of bias in patient selection. Moreover, the study was not blinded and the subjective improvement noted by the clinicians in swelling and mental status of dogs receiving antivenom cannot be regarded as good quality evidence for the PICO question.

In the Sutton et al (2011) study of cases reported to the VPIS, it was found that in dogs receiving antivenom, oedema lasted an average of 46.8 hours, compared to dogs that did not receive antivenom, where oedema lasted an average of 94.1 hours. This was the most significant finding to the PICO question in this paper but is limited by several factors. Duration of generalised oedema was not reported in all dogs, decreasing the sample size, and objective method of oedema measurement was not given. Statistical analysis of the findings was not reported, so it is not known if the findings are significant. Death occurred in 3% of dogs receiving antivenom and 4.8% of dogs not receiving antivenom, which appears similar, but unfortunately no conclusions can be drawn due to the lack of statistical analysis. The study looked at broad risk factors for envenomation and mortality and the scope of treatment, rather than evaluating the effect of any individual treatment, and this was a common theme among the evidence found.

Turkovic et al (2015) found that antivenom administration did not significantly clinically affect local swelling 24 hours after envenomation, which appears to contrast to the finding from the Lund paper (2013). This paper was another case series studying risk factors, treatments and outcomes, with a very small study size and data relevant to the PICO question was incomplete. Duration of hospitalisation was recorded for dogs receiving and not receiving antivenom but the results were unfortunately not analysed for significance. The use of heparin and antihistamines in treating envenomation were highlighted as future areas of research.

The majority of the studies found by the authors examine risk factors for envenomation, adverse effects of antivenom administration and common treatment choices. Furthermore, most studies were retrospective, considered envenomation by other species or studied the effects of other elements of the treatment regime, such as glucocorticoids. There is wide variation in the combinations of supportive treatment given in the literature; combinations of intravenous fluid therapy (IVFT) with crystalloids, colloids or blood products, analgesia, antibacterial agents, glucocorticoids, antihistamines and heparin (Sutton et al, 2011, Turkovic et al, 2015 and Lund et al, 2013). This lack of a standardised treatment protocol makes direct comparison of the effect of antivenom more difficult to assess. These variations affect the analysis of the impact of antivenom on time to recovery. The best study design to answer this PICO question would directly compare the outcomes when the use of antivenom is the only variable imposed by the study authors.  

The PICO question could be best answered by a prospective, randomised, double-blinded controlled trial, comparing the effects of the addition of antivenom to supportive treatment alone. This could be considered as a research prospect; although a lack of antivenom licensed in dogs and the need to envenomate dogs would render such a study unlikely to pass ethics approval. The relatively small number of dogs envenomated each year in the UK could potentially render such a study financially unviable for antivenom manufacturers. Objective judgement of the clinical effects of antivenom, such as reduction of oedema, also generates difficulties. As such, the proposed clinical trial using ViperaVet may be of interest in revisiting this clinical question in the future; although at the time of writing the study was postponed (VPIS, 2017).

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