Investigating myotoxicity following Australian red-bellied black snake (Pseudechis porphyriacus) envenomation.

<h4>Background</h4>Myotoxicity is one of the common clinical manifestations of red-bellied black snake (Pseudechis porphyriacus) envenomation characterised by elevated creatine kinase (CK) concentrations of greater than 1000 U/L. This study aimed to investigate the occurrence of myotoxic...

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Autores principales:	Suchaya Sanhajariya, Stephen B Duffull, Geoffrey K Isbister
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/07d8bb3a936b41eaa3a7891a02b09df4
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spelling	oai:doaj.org-article:07d8bb3a936b41eaa3a7891a02b09df42021-12-02T20:14:43ZInvestigating myotoxicity following Australian red-bellied black snake (Pseudechis porphyriacus) envenomation.1932-620310.1371/journal.pone.0256653https://doaj.org/article/07d8bb3a936b41eaa3a7891a02b09df42021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0256653https://doaj.org/toc/1932-6203<h4>Background</h4>Myotoxicity is one of the common clinical manifestations of red-bellied black snake (Pseudechis porphyriacus) envenomation characterised by elevated creatine kinase (CK) concentrations of greater than 1000 U/L. This study aimed to investigate the occurrence of myotoxicity in patients following envenomation.<h4>Methods/principal findings</h4>Patient characteristics and serial blood samples (timed venom concentrations and CK concentrations, pre- and post- antivenom) from 114 patients (median age 41, 2-90y; 80 male) were extracted from the Australian Snakebite Project database. Patients were categorised into three groups based on peak CK concentrations [no myotoxicity (<1000 U/L), mild (1000-10,000 U/L) and severe (>10,000 U/L)]. The odds of (mild or severe) myotoxicity was lower in patients that received early antivenom (within 6 hours post-bite) compared to those that received late or no antivenom (odd ratio was 0.186; 95% confidence interval, 0.052-0.664). A population pharmacokinetic-pharmacodynamic (PKPD) model was developed to describe the relationship between the time course of venom (a mixture of toxins) and effect (elevated CK). In addition, a kinetic-pharmacodynamic (KPD) model was developed to describe the relationship between time course of a theoretical toxin and effect. Model development and parameter estimation was performed using NONMEM v7.3. No single set of parameter values from either the PKPD or KPD models were found that could accurately describe the time course of different levels of severity of myotoxicity. The predicted theoretical toxin half-life from the KPD model was 11 ± 3.9 hours compared to the half-life of venom of 5.3 ± 0.36 hours. This indicates that the putative causative toxin's concentration-time profile does not parallel that of venom.<h4>Conclusion</h4>Early antivenom administration reduces the incidence of myotoxicity. The venom concentration profile does not appear to be the driver for myotoxicity following envenomation. Additional factors that affect the sensitivity of the patient to snake venom/toxins must be explored to understand the relationship with myotoxicity.Suchaya SanhajariyaStephen B DuffullGeoffrey K IsbisterPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 9, p e0256653 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Suchaya Sanhajariya Stephen B Duffull Geoffrey K Isbister Investigating myotoxicity following Australian red-bellied black snake (Pseudechis porphyriacus) envenomation.
description	<h4>Background</h4>Myotoxicity is one of the common clinical manifestations of red-bellied black snake (Pseudechis porphyriacus) envenomation characterised by elevated creatine kinase (CK) concentrations of greater than 1000 U/L. This study aimed to investigate the occurrence of myotoxicity in patients following envenomation.<h4>Methods/principal findings</h4>Patient characteristics and serial blood samples (timed venom concentrations and CK concentrations, pre- and post- antivenom) from 114 patients (median age 41, 2-90y; 80 male) were extracted from the Australian Snakebite Project database. Patients were categorised into three groups based on peak CK concentrations [no myotoxicity (<1000 U/L), mild (1000-10,000 U/L) and severe (>10,000 U/L)]. The odds of (mild or severe) myotoxicity was lower in patients that received early antivenom (within 6 hours post-bite) compared to those that received late or no antivenom (odd ratio was 0.186; 95% confidence interval, 0.052-0.664). A population pharmacokinetic-pharmacodynamic (PKPD) model was developed to describe the relationship between the time course of venom (a mixture of toxins) and effect (elevated CK). In addition, a kinetic-pharmacodynamic (KPD) model was developed to describe the relationship between time course of a theoretical toxin and effect. Model development and parameter estimation was performed using NONMEM v7.3. No single set of parameter values from either the PKPD or KPD models were found that could accurately describe the time course of different levels of severity of myotoxicity. The predicted theoretical toxin half-life from the KPD model was 11 ± 3.9 hours compared to the half-life of venom of 5.3 ± 0.36 hours. This indicates that the putative causative toxin's concentration-time profile does not parallel that of venom.<h4>Conclusion</h4>Early antivenom administration reduces the incidence of myotoxicity. The venom concentration profile does not appear to be the driver for myotoxicity following envenomation. Additional factors that affect the sensitivity of the patient to snake venom/toxins must be explored to understand the relationship with myotoxicity.
format	article
author	Suchaya Sanhajariya Stephen B Duffull Geoffrey K Isbister
author_facet	Suchaya Sanhajariya Stephen B Duffull Geoffrey K Isbister
author_sort	Suchaya Sanhajariya
title	Investigating myotoxicity following Australian red-bellied black snake (Pseudechis porphyriacus) envenomation.
title_short	Investigating myotoxicity following Australian red-bellied black snake (Pseudechis porphyriacus) envenomation.
title_full	Investigating myotoxicity following Australian red-bellied black snake (Pseudechis porphyriacus) envenomation.
title_fullStr	Investigating myotoxicity following Australian red-bellied black snake (Pseudechis porphyriacus) envenomation.
title_full_unstemmed	Investigating myotoxicity following Australian red-bellied black snake (Pseudechis porphyriacus) envenomation.
title_sort	investigating myotoxicity following australian red-bellied black snake (pseudechis porphyriacus) envenomation.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/07d8bb3a936b41eaa3a7891a02b09df4
work_keys_str_mv	AT suchayasanhajariya investigatingmyotoxicityfollowingaustralianredbelliedblacksnakepseudechisporphyriacusenvenomation AT stephenbduffull investigatingmyotoxicityfollowingaustralianredbelliedblacksnakepseudechisporphyriacusenvenomation AT geoffreykisbister investigatingmyotoxicityfollowingaustralianredbelliedblacksnakepseudechisporphyriacusenvenomation
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Investigating myotoxicity following Australian red-bellied black snake (Pseudechis porphyriacus) envenomation.

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