title: Towards rationalisation of antivenom use in funnel-web spider envenoming: enzyme immunoassays for venom concentrations.
abstract: BACKGROUND
  Funnel-web spider (Atrax and Hadronyche spp.) envenoming is rare but causes severe neuromuscular, autonomic, and cardiac effects. A rabbit-derived IgG antivenom is available, but venom detection in patients has not been reported.
  
  
  OBJECTIVE
  To use serial venom and antivenom concentrations to better define envenoming and antivenom effectiveness.
  
  
  METHODS
  Serum was collected from nine patients with suspected funnel-web spider bites and clinical effects were recorded. Venom-specific enzyme immunoassays were developed to measure funnel-web spider venom and antivenom concentrations. Goat anti-rabbit whole serum was coupled to UltraLink resin and added to samples to remove bound venom and measure free venom. Antivenom efficacy was defined as antivenom binding all free venom and antivenom effectiveness as resolution of clinical features.
  
  
  RESULTS
  Venom was detectable in samples from six of nine patients. In three patients without venom detected, there were only moderate effects, which did not completely respond to antivenom in all cases and no spider was identified. In five of six cases, a male Atrax spp. (Sydney funnel-web) spider was identified. Three patients had moderate envenoming which responded to antivenom. Three patients had severe envenoming and developed catecholamine-induced myocarditis and acute pulmonary oedema. Although cholinergic and non-specific clinical features appeared to respond to antivenom, myocarditis and pulmonary oedema lasted 2-4 days. Median venom concentration pre-antivenom in five patients with samples was 5.6 ng/ml (3-35 ng/ml), and immediately post-antivenom decreased to a median of 0 ng/ml (0-1.8 ng/ml). Post-antivenom venom concentrations decreased when bound venom was removed; median, 0 ng/ml (0-0.9 ng/ml), indicating that most venom detected post-antivenom was bound. There was recurrence of venom and clinical features in one patient when a pressure bandage was removed.
  
  
  CONCLUSIONS
  Detection of venom in suspected funnel-web spider bites identified definite cases with characteristic envenoming and a spider was identified. Measurement of venom concentrations pre- and post-antivenom demonstrated that venom was bound by antivenom, but in severe cases cardiac toxicity was not reversed.
authors.affiliation: a Emergency Department , John Hunter Hospital , Newcastle , NSW , Australia ;
authors.forename: Mark
authors.initials: M
authors.lastname: Miller
authors.affiliation: b Clinical Toxicology Research Group , University of Newcastle , Newcastle , NSW , Australia ;
authors.forename: Margaret A
authors.initials: MA
authors.lastname: O'Leary
authors.affiliation: b Clinical Toxicology Research Group , University of Newcastle , Newcastle , NSW , Australia ;|c Department of Clinical Toxicology and Pharmacology , Calvary Mater Hospital , Newcastle , NSW , Australia.
authors.forename: Geoffrey K
authors.initials: GK
authors.lastname: Isbister
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000997:Antivenins / Q000032:analysis*; D001342:Autonomic Nervous System Diseases / Q000139:chemically induced / Q000188:drug therapy; D002675:Child, Preschool; D005260:Female; D006041:Goats / Q000276:immunology; D006801:Humans; D007124:Immunoenzyme Techniques; D007074:Immunoglobulin G / Q000032:analysis; D057230:Limit of Detection; D008297:Male; D008875:Middle Aged; D009205:Myocarditis / Q000139:chemically induced / Q000188:drug therapy; D011654:Pulmonary Edema / Q000139:chemically induced / Q000188:drug therapy; D011817:Rabbits; D012008:Recurrence; D001098:Spider Bites / Q000188:drug therapy*; D013111:Spider Venoms / Q000032:analysis* / Q000037:antagonists & inhibitors*; D055815:Young Adult
chemical_list: D000997:Antivenins; D007074:Immunoglobulin G; D013111:Spider Venoms
keywords: Catecholamine excess; spider bite; toxins