William H Richardson

Publications of William H Richardson

• Unified treatment algorithm for the management of crotaline snakebite in the United States: results of an evidence-informed consensus workshop.

  Authors: Eric J Lavonas, Anne-Michelle Ruha, William Banner, Vikhyat Bebarta, Jeffrey N Bernstein, Sean P Bush, William P Kerns, William H Richardson, Steven A Seifert, David A Tanen, Steve C Curry, Richard C Dart

  BMC emergency medicine. 01/2011; 11:2.

  Envenomation by crotaline snakes (rattlesnake, cottonmouth, copperhead) is a complex, potentially lethal condition affecting thousands of people in the United States each year. Treatment of crotalineEnvenomation by crotaline snakes (rattlesnake, cottonmouth, copperhead) is a complex, potentially lethal condition affecting thousands of people in the United States each year. Treatment of crotaline envenomation is not standardized, and significant variation in practice exists. A geographically diverse panel of experts was convened for the purpose of deriving an evidence-informed unified treatment algorithm. Research staff analyzed the extant medical literature and performed targeted analyses of existing databases to inform specific clinical decisions. A trained external facilitator used modified Delphi and structured consensus methodology to achieve consensus on the final treatment algorithm. A unified treatment algorithm was produced and endorsed by all nine expert panel members. This algorithm provides guidance about clinical and laboratory observations, indications for and dosing of antivenom, adjunctive therapies, post-stabilization care, and management of complications from envenomation and therapy. Clinical manifestations and ideal treatment of crotaline snakebite differ greatly, and can result in severe complications. Using a modified Delphi method, we provide evidence-informed treatment guidelines in an attempt to reduce variation in care and possibly improve clinical outcomes.

• In reply.

  Authors: Steven R Offerman, J David Barry, William H Richardson, David A Tanen, Richard F Clark

  Clinical toxicology (Philadelphia, Pa.). 07/2009;

• Cost-benefit analysis of a regional poison center.

  Authors: Joseph Charles Blizzard, Jill E Michels, William H Richardson, Clairborne E Reeder, Richard M Schulz, Christopher P Holstege

  Clinical toxicology (Philadelphia, Pa.). 07/2008; 46(5):450-6.

  BACKGROUND: Funding poison center (PC) operations has become a major challenge nationwide. Increasingly, state and federal budget cuts have resulted in diminished funding to PCs. OBJECTIVES: In anBACKGROUND: Funding poison center (PC) operations has become a major challenge nationwide. Increasingly, state and federal budget cuts have resulted in diminished funding to PCs. OBJECTIVES: In an effort to demonstrate the value of current PC phone services, a cost-benefit analysis of a regional center was completed. METHODS: A telephone survey was used to collect data from PC callers during an 8-week period in 2004. Callers with human exposure poisonings determined by the PC to be of minimal or no risk were asked to complete the phone survey. Callers were asked their alternative plan if the PC staff had not been available to assist them. Benefits were measured as healthcare charges potentially avoided. RESULTS: A total of 652 caller surveys were completed. The benefit-to-cost ratio was 7.67 (95% C.I. 6.83, 8.50). CONCLUSION: In addition to non-monetary benefits, the operation of a regional poison center provides significant positive return on investment.

• Comparative treatment of alpha-amanitin poisoning with N-acetylcysteine, benzylpenicillin, cimetidine, thioctic acid, and silybin in a murine model.

  Authors: Tri C Tong, Mark Hernandez, William H Richardson, David P Betten, Michael Favata, Robert H Riffenburgh, Richard F Clark, David A Tanen

  Annals of emergency medicine. 10/2007; 50(3):282-8.

  STUDY OBJECTIVE: The foraging of wild mushrooms can be complicated by toxicity from several mushroom types. Amatoxin, a peptide contained in several mushroom species, accounts for the majority ofSTUDY OBJECTIVE: The foraging of wild mushrooms can be complicated by toxicity from several mushroom types. Amatoxin, a peptide contained in several mushroom species, accounts for the majority of severe mushroom poisonings by binding to RNA polymerase II irreversibly, leading to severe hepatonecrosis. There is no effective antidote for severe amatoxin poisoning. We compare the effectiveness of 5 potential antidotal therapies in limiting the degree of hepatonecrosis in a randomized, controlled, murine model of amatoxin-induced hepatotoxicity. METHODS: One hundred eighty male Institute of Cancer Research mice were randomized into 6 equal groups. Within each group, 21 mice were intraperitoneally injected with 0.6 mg/kg of alpha-amanitin (amatoxin); the remaining 9 were injected with 0.9% normal saline solution. Four hours postinjection, each group of 30 mice was randomized to 1 of 5 intraperitoneal treatments (N-acetylcysteine, benzylpenicillin, cimetidine, thioctic acid, or silybin) or normal saline solution. Repeated dosing was administered intraperitoneally every 4 to 6 hours for 48 hours. After 48 hours of treatment, each subject was killed, cardiac blood was aspirated for hepatic aminotransferase measurements (alanine transaminase and aspartate transaminase), and liver specimens were harvested to evaluate the extent of hepatonecrosis. The degree of hepatonecrosis was determined by a pathologist blinded to the treatment group and divided into 5 categories according to percentage of hepatonecrosis. RESULTS: Amanitin significantly increased aspartate transaminase in treated mice compared with normal saline solution-treated controls (mean [SD] 2,441 [2,818] IU/L versus 310 [252]; P=.03). None of the antidotal therapies were found to significantly decrease the increase in aminotransferases compared with controls. Further, none of the antidotal therapies demonstrated an important decrease in hepatonecrosis compared with controls when a histologic grading scale was used. CONCLUSION: In this murine model, N-acetylcysteine, benzylpenicillin, cimetidine, thioctic acid, and silybin were not effective in limiting hepatic injury after alpha-amanitin poisoning. Increases of aminotransferases and degrees of histologic hepatonecrosis were not attenuated by these antidotal therapies.

• Herbal drugs of abuse: an emerging problem.

  Authors: William H Richardson, Cheryl M Slone, Jill E Michels

  Emergency medicine clinics of North America. 06/2007; 25(2):435-57; abstract ix.

  Some herbal products are emerging as popular drugs for recreational abuse. Plant and herbal supplements used recreationally can have a wide spectrum of clinical effects ranging from euphoric andSome herbal products are emerging as popular drugs for recreational abuse. Plant and herbal supplements used recreationally can have a wide spectrum of clinical effects ranging from euphoric and stimulant effects to hallucinogenic experiences. Despite the potential for abuse, addiction, and serious adverse effects, there may be a false perception that these products are all safe, legal, and organic. These perceptions and the ease of accessibility to herbal products could result in greater potential for recreational abuse and subsequent complications presenting to emergency departments. Health care professionals must be cognizant of this emerging problem as increased media coverage and marketing have made these products accessible and recognizable to many young adults and teenagers.

• A pilot study of mechanical stimulation and cardiac dysrhythmias in a porcine model of induced hypothermia.

  Authors: James Grueskin, David A Tanen, Pamela Harvey, Frank Dos Santos, William H Richardson, Robert H Riffenburgh

  Wilderness & environmental medicine. 01/2007; 18(2):133-7.

  BACKGROUND: Hypothermia is a frequent complication of cold weather exposure and/or wilderness injuries. Anecdotal reports have postulated that patients suffering from acute hypothermia are atBACKGROUND: Hypothermia is a frequent complication of cold weather exposure and/or wilderness injuries. Anecdotal reports have postulated that patients suffering from acute hypothermia are at significantly increased risk of developing lethal cardiac dysrhythmias secondary to the physical stimulation from moving and transporting patients. OBJECTIVE: To develop a model to attempt to determine if rough handling and sudden movement can induce lethal cardiac dysrhythmias in a controlled animal study of mild to severe hypothermia. METHODS: Ten anesthetized swine had continuous cardiac and invasive blood pressure (BP) monitoring. Core body temperature (CBT) was measured with an esophageal probe. Animals were secured to a backboard in a supine position for the duration of the study and their CBT was serially lowered by external cooling measures. At preset intervals (every 3 degrees C lowered from the baseline CBT of 38 degrees C), the animals were lifted via the backboard and rolled 90 degrees to the left and held for 5 seconds and then rolled to the right and held for 5 seconds. After rolling, the swine were lifted via the backboard 6 inches off the surgical table and dropped back onto the table, and after 15 seconds this was repeated at 12 inches. If no signs of dysrhythmia were noted, external cooling was continued. Data were analyzed by tests of proportion on mortality associated with hypothermia and mechanical stimulation. To determine whether hypothermia and mechanical stimulation were independent effects, a one-sided McNemar's test of matched pairs was employed. RESULTS: No animal developed a dysrhythmia at a CBT > 25 degrees C with or without stimulation. Fifty percent of the animals developed fatal dysrhythmias (3 ventricular fibrillation, 2 asystole) with no stimulation but at CBT <or= 25 degrees C (average CBT 22.7 degrees C). Twenty percent (2/10) developed fatal dysrhythmias (ventricular fibrillation) during mechanical stimulation. For hypothermia, a binomial test of the observed proportion 0.70 (fatality during hypothermia) against a hypothetical proportion of 0 (no fatality in the absence of hypothermia) yielded P < .001 with power = 1.00. For mechanical stimulation, a binomial test of the observed proportion 0.20 (fatality from mechanical stimulation); against a hypothetical proportion of 0 yielded P < .001 with power = 1.00. The test of matched pairs yielded P < .037, indicating that the variables of mechanical stimulation and hypothermia jointly caused mortality. CONCLUSION: Profound hypothermia induces fatal dysrhythmias both with and without mechanical stimulation in a swine model.

• North American coral snake antivenin for the neutralization of non-native elapid venoms in a murine model.

  Authors: William H Richardson, David A Tanen, Tri C Tong, David P Betten, Shaun D Carstairs, Saralyn R Williams, Frank L Cantrell, Richard F Clark

  Academic emergency medicine : official journal of the Society for Academic Emergency Medicine. 02/2006; 13(2):121-6.

  OBJECTIVES: North American coral snake antivenin (CSAV; Wyeth Antivenin [Micrurus fulvius], equine origin) is approved for the treatment of coral snake envenomations in the United States. The coralOBJECTIVES: North American coral snake antivenin (CSAV; Wyeth Antivenin [Micrurus fulvius], equine origin) is approved for the treatment of coral snake envenomations in the United States. The coral snake is the only elapid that is native to North America, but envenomations from non-native elapids are occurring more commonly in this country. This study was designed to evaluate the efficacy of CSAV in the neutralization of two exotic elapid envenomations: Naja naja (Indian cobra) and Dendroaspis polylepsis (black mamba). METHODS: A randomized, blinded, placebo-controlled murine model of intraperitoneal venom injection was employed. Venom potency was determined in preliminary dosing studies. Study animals then were divided into five groups: 1) N. naja venom + CSAV, 2) N. naja venom + 0.9% normal saline (NS), 3) D. polylepsis venom + CSAV, 4) D. polylepsis venom + NS, and 5) CSAV + NS. The venom dose was chosen to be twice the estimated LD50. The amount of CSAV injected was ten times the amount necessary for neutralization of a 2 x LD50 dose of M. f. fulvius venom in a murine model. Statistical analysis included Fisher's exact and log-rank testing to compare survival rates and times. RESULTS: Preliminary studies estimated the venom LD50 to be 2.58 mg/kg and 0.45 mg/kg, respectively, for the N. naja and D. polylepsis. A significant difference was shown in comparison of survival times between CSAV-venom groups and normal saline-venom groups despite all animals in both treatment and control arms dying. Animals receiving CSAV and N. naja venom survived (mean +/- SD) 24.4 +/- 3.0 minutes, versus 17.8 +/- 1.3 minutes in the control group (p < 0.001), whereas those receiving CSAV and D. polylepsis venom survived 203.8 +/- 37.0 minutes versus 130.0 +/- 42.6 minutes in the control group (p < 0.001). All animals in the CSAV + NS group survived to the conclusion of the study. CONCLUSIONS: When premixed with venom, CSAV increased survival time in a murine model of intraperitoneal N. naja and D. polylepsis venom injection. The clinical implications of this are unclear, given unchanged mortality rates.

• Massive honey bee envenomation-induced rhabdomyolysis in an adolescent.

  Authors: David P Betten, William H Richardson, Tri C Tong, Richard F Clark

  Pediatrics. 02/2006; 117(1):231-5.

  Massive envenomations by honey bees are capable of causing multiorgan dysfunction as a result of the direct toxic effects of the large venom load received. Although all varieties of honey bee haveMassive envenomations by honey bees are capable of causing multiorgan dysfunction as a result of the direct toxic effects of the large venom load received. Although all varieties of honey bee have the potential for these attacks, the Africanized honey bee (Apis mellifera scutellata) is the most commonly implicated subspecies. In the United States, the Africanized strain is found primarily in the southwestern states and is known for its highly defensive behavior if disturbed. Mechanisms behind the multiorgan dysfunction produced by these mass envenomations are not clearly understood. We present a case of a 13-year-old male who was stung by approximately 700 honey bees and developed progressive upper-body swelling and systemic manifestations of mass envenomation including rhabdomyolysis, renal insufficiency, and a transient transaminase elevation.

• Crotalidae polyvalent immune Fab (ovine) antivenom is effective in the neutralization of South American viperidae venoms in a murine model.

  Authors: William H Richardson, David A Tanen, Tri C Tong, David P Betten, Shaun D Carstairs, Saralyn R Williams, Frank L Cantrell, Richard F Clark

  Annals of emergency medicine. 07/2005; 45(6):595-602.

  STUDY OBJECTIVE: Crotalidae polyvalent immune Fab (ovine) (CroFab; FabAV) is used in the treatment of symptomatic crotaline envenomations in North America. Unlike Antivenin (Crotalidae) Polyvalent,STUDY OBJECTIVE: Crotalidae polyvalent immune Fab (ovine) (CroFab; FabAV) is used in the treatment of symptomatic crotaline envenomations in North America. Unlike Antivenin (Crotalidae) Polyvalent, which is approved for treatment of crotaline envenomation in North and South America, FabAV is manufactured using only venoms from crotaline snakes native to the United States. This study was designed to evaluate the efficacy of FabAV in the neutralization of venom from 2 South American crotaline snakes: Crotalus durissus terrificus (tropical rattlesnake) and Bothrops atrox (fer-de-lance). METHODS: A randomized, blinded, placebo-controlled murine model of intraperitoneal venom injection was used. Venom potency was determined in preliminary median lethal dose (LD 50) dosing studies. Study animals were then divided into 7 groups: (1) C durissus terrificus venom (Sigma-Aldrich Co.)+FabAV, (2) C durissus terrificus venom (Sigma-Aldrich Co.)+0.9% normal saline solution, (3) C durissus terrificus venom (Biotoxins Inc.)+FabAV, (4) C durissus terrificus venom (Biotoxins Inc.)+normal saline solution, (5) B atrox venom+FabAV, (6) B atrox venom+normal saline solution, and (7) FabAV+normal saline solution. Twice the estimated LD 50 was the chosen venom dose, and the amount of FabAV injected was 10 times the amount needed for venom neutralization. Statistical analysis included Fisher's exact test and log-rank testing to compare survival rates and times. RESULTS: The venom LD 50 was found in preliminary studies to be 0.9 mg/kg and 1.35 mg/kg for the C durissus terrificus venom obtained from Sigma-Aldrich Co. and Biotoxins Inc., respectively. The LD 50 for B atrox venom was 5.0 mg/kg. All animals receiving venom only and saline solution died. Animals receiving FabAV together with either venom survived to the end of the 24-hour observation period ( P <.001). Comparison of survival times between groups demonstrated a significant difference in time to death between venom-only control groups and the FabAV+venom groups (P <.001). All animals in the FabAV+normal saline solution group survived to the conclusion of the study. CONCLUSION: FabAV, when premixed with venom, decreases lethality in a murine model of intraperitoneal venom injection of the South American pit vipers, C durissus terrificus and B atrox .

• Rattlesnake envenomation to the face of an infant.

  Authors: William H Richardson, James D Barry, Tri C Tong, Saralyn R Williams, Richard F Clark

  Pediatric emergency care. 04/2005; 21(3):173-6.

  BACKGROUND: Mortality from rattlesnake envenomation in the United States is rare. Despite approximately 8000 crotaline (pit vipers) bites annually, it is estimated that only 10 to 15 deaths occur.BACKGROUND: Mortality from rattlesnake envenomation in the United States is rare. Despite approximately 8000 crotaline (pit vipers) bites annually, it is estimated that only 10 to 15 deaths occur. Besides direct intravascular envenomation and anaphylaxis, bites to the head and neck may account for some of these rare fatalities. We report a pediatric case of severe facial envenomation requiring emergent intubation and antivenom administration. CASE REPORT: A 14-month-old female toddler was envenomated by a Southern Pacific rattlesnake (Crotalus viridis helleri) above the right upper lip while playing in her backyard. Rapid swelling and ecchymosis developed, and the patient was airlifted to a pediatric tertiary care hospital. Within 3 hours, stridorous respirations complicated by significant facial and oropharyngeal edema necessitated emergent orotracheal intubation. A total of 16 vials of FabAV [Crotalidae Polyvalent Immune Fab (ovine) antivenom] were administered over the next 24 hours. The child gradually improved and was successfully extubated 5 days later. A 3-month follow-up demonstrated no significant cosmetic facial abnormalities. CONCLUSION: Crotaline bites to the head and neck have the potential for significant swelling and airway compromise. Facial bites, anaphylaxis, and rare intravascular envenomation may account for many of the fatalities from rattlesnake envenomation. Early intubation may be required to maintain airway patency.

• A picturesque reversal of antimuscarinic delirium.

  Authors: William H Richardson, Saralyn R Williams, Shaun D Carstairs

  The Journal of emergency medicine. 06/2004; 26(4):463.

• A case of type F botulism in southern California.

  Authors: William H Richardson, Shermane S Frei, Saralyn R Williams

  Journal of toxicology. Clinical toxicology. 02/2004; 42(4):383-7.

  BACKGROUND: Botulism caused by type F botulinum toxin accounts for less than 0.1% of all human botulism cases and is rarely reported in the literature. CASE REPORT: A 45-year-old woman presented toBACKGROUND: Botulism caused by type F botulinum toxin accounts for less than 0.1% of all human botulism cases and is rarely reported in the literature. CASE REPORT: A 45-year-old woman presented to an emergency department complaining of blurred vision, difficulty focusing, and dysphagia. The treating physician initially considered the possibility of paralytic shellfish poisoning due to a report of shellfish ingestion, which was later determined to be frozen shrimp and a can of tuna, but no gastroenteritis or paresthesias were present. During the emergency department observation, the patient developed respiratory distress with hypercapnea and required intubation and mechanical ventilation. Within hours, ptosis, mydriasis, and weakness in the arms and legs developed. Bivalent (A, B) botulinum antitoxin was administered approximately 24 h from the onset of initial symptoms, but over the next two days complete paralysis progressed to the upper and lower extremities. Shortly thereafter a stool toxin assay demonstrated the presence of type F botulinum toxin. The patient subsequently received an experimental heptavalent botulinum antitoxin on hospital day 7 but paralysis was already complete. Her three-week hospital course was complicated by nosocomial pneumonia and a urinary tract infection, but she gradually improved and was discharged to a rehabilitation facility. Anaerobic cultures and toxin assays have yet to elucidate the source of exposure. CONCLUSION: We report a rare case of type F botulism believed to be foodborne in etiology. Administration of bivalent botulinum antitoxin did not halt progression of paralysis.

• Molecular orbital calculations of ring opening of the isoelectronic cyclopropylcarbinyl radical, cyclopropoxy radical, and cyclopropylaminium radical cation series of radical clocks.

  Authors: Andrew L Cooksy, Harry F King, William H Richardson

  The Journal of organic chemistry. 12/2003; 68(24):9441-52.

  Detailed molecular orbital calculations were directed to the cyclopropylcarbinyl radical (1), the cyclopropoxy radical (2), and the cyclopropylaminium radical cation (3) as well as their ring-openedDetailed molecular orbital calculations were directed to the cyclopropylcarbinyl radical (1), the cyclopropoxy radical (2), and the cyclopropylaminium radical cation (3) as well as their ring-opened products. Since a considerable amount of data are published about cyclopropylcarbinyl radicals, calculations were made for this species and related ring-opened products as a reference for 2 and 3 and their reactions. Radicals 1-3 have practical utility as "radical clocks" that can be used to time other radical reactions. Radical 3 is of further interest in photoelectron-transfer processes where the back-electron-transfer process may be suppressed by rapid ring opening. Calculations have been carried out at the UHF/6-31G*, MP4//MP2/6-31G*, DFT B3LYP/6-31G*, and CCSD(T)/cc-pVTZ//QCISD/cc-pVDZ levels. Energies are corrected to 298 K, and the barriers between species are reported in terms of Arrhenius E(a) and log A values along with differences in enthalpies, free energies, and entropies. The CCSD(T)-calculated energy barrier for ring opening of 1 is E(a) = 9.70, DeltaG* = 8.49 kcal/mol, which compares favorably to the previously calculated value of E(a) = 9.53 kcal/mol by the G2 method, but is higher than an experimental value of 7.05 kcal/mol. Our CCSD(T)-calculated E(a) value is also higher by 1.8 kcal/mol than a previously reported CBS-RAD//B3LYP/6-31G* calculation. The cyclopropoxy radical has a very small barrier to ring opening (CCSD(T), E(a) = 0.64 kcal/mol) and should be a very sensitive time clock. Of the three series studied, the cyclopropylaminium radical cation is most complex. In agreement with experimental data, bisected cyclopropylaminium radical cation is not found, but instead a ring-opened species is found. A perpendicular cyclopropylaminium radical cation (4) was found as a transition-state structure. Rotation of the 2p orbital in 4 to the bisected array results in ring opening. The minimum onset energy of photoionization of cyclopropylamine was calculated to be 201.5 kcal/mol (CCSD(T)) compared to experimental values of between about 201 and 204 kcal/mol. Calculations were made on the closely related cyclopropylcarbinyl and bicyclobutonium cations. Stabilization of the bisected cyclopropylcarbinyl conformer relative to the perpendicular species is much greater for the cations (29.1 kcal/ mol, QCISD) compared to the radicals (3.10 kcal/mol, QCISD). A search was made for analogues to the bicyclobutonium cation in the radical series 1 and 2 and the radical cation series 3. No comparable species were found. A rationale was made for some conflicting calculations involving the cyclopropylcarbinyl and bicyclobutonium cations. The order of stability of the cyclopropyl-X radicals was calculated to be X = CH2 >> X = O > X = NH2+, where the latter species has no barrier for ring opening. The relative rate of ring opening for cyclopropyl-X radicals X = CH2 to X = O was calculated to be 3.1 x 10(6) s(-1) at 298 K (QCISD).

• Another hazard of college drinking: the black light concoction.

  Authors: William H Richardson, Richard F Clark, William C Gerard

  Annals of emergency medicine. 07/2003; 41(6):890-91.

• Rattlesnake envenomation with neurotoxicity refractory to treatment with crotaline Fab antivenom.

  Authors: William H Richardson, Collin S Goto, David J Gutglass, Saralyn R Williams, Richard F Clark

  Clinical toxicology (Philadelphia, Pa.). 45(5):472-5.

  INTRODUCTION: Neurotoxicity following rattlesnake envenomation is reported with certain crotaline species. In some instances, crotaline Fab antivenom therapy that effectively halts progression ofINTRODUCTION: Neurotoxicity following rattlesnake envenomation is reported with certain crotaline species. In some instances, crotaline Fab antivenom therapy that effectively halts progression of local tissue edema and hemotoxicity fails to reverse neurologic venom effects. CASE SERIES: A 50-year-old man presented following a rattlesnake envenomation to the left ring finger. He had swelling and pain in the affected hand and complained of dyspnea and dysphonia. Significant fasciculations were seen in the face, tongue, neck, trunk, and arms. The patient received crotaline Fab antivenom but continued to develop worsening respiratory distress. His respiratory insufficiency requiring ventilatory support appeared related to respiratory muscle incoordination as extremity motor function remained intact. Initial control of local edema progression and hematologic parameters was achieved with antivenom, but diffuse fasciculations involving the entire body worsened despite aggressive antivenom treatment. In another case, a 9-year-old boy was envenomated by a rattlesnake on the left thenar eminence. He presented with pain and swelling up to the forearm and fasciculations of the tongue, face, and upper extremities. The progression of edema was halted at the mid-bicep level and hematologic parameters normalized with crotaline Fab antivenom. However, fasciculations continued for two days despite antivenom treatment. CONCLUSION: We describe two cases of neurotoxicity following rattlesnake envenomation in which treatment with crotaline Fab antivenom adequately obtained initial control of local swelling and hematologic effects, but neurotoxic venom effects remained refractory to antivenom therapy. This phenomenon is anecdotally recognized following certain crotaline species envenomations.