Isoniazid Overdose: A Case Series, Literature Review and Survey of Antidote Availability

Department of Emergency Medicine, The Townsville Hospital, Townsville, Australia
Clinical Drug Investigation (Impact Factor: 1.56). 12/2002; 23(7):479-485.

ABSTRACT Tuberculosis has re-emerged as a significant public health threat over the last decade both globally and within Australia. This is thought to be largely due to the HIV epidemic, a growing itinerant population, and immigration. The antibiotic isoniazid remains an integral part of drug therapy. With the numbers of patients receiving isoniazid remaining high, the number of cases of acute poisoning is expected to be significant. This paper presents a series of two cases of isoniazid poisoning presenting to a tertiary referral centre in North Queensland. Isoniazid toxicity produces a triad of coma, metabolic acidosis and seizures. The seizures are often refractory to traditional antiepileptics. A specific antidote is available (pyridoxine [vitamin B6]) and both patients were administered this as part of their treatment. We also surveyed all hospitals in Australia with an accredited adult Emergency Department to assess the availability of pyridoxine.

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    ABSTRACT: The Bayesian estimation scheme has proved widely useful in providing estimates of inexactly observable parameters and state variables of noisy linear discrete-time systems for the derivation of an optimal control policy. Controllers may be derived which are adaptive and relatively insensitive to system parameter changes. In this paper dual control schemes are developed for a class of discrete-time noisy extremum systems given by the state equations x(t+1) = ¿x(t) + Bu(t) + w(t) (1) z1 (t) = - + v1(t) (2) The optimal control policy is defined as that which minimizes ¿t=0 T-1 E {x(t+1)tx(t+1)} The control scheme is intentionally sub-optimal to reduce computation to a feasible level. The technique is to reduce Equation (2) by a series of approximations to a set of linear equations. A set of control schemes may be set up based on the Bayesian estimation approach and the set of linearized equations. An algorithm for choosing at each time interval which of the control schemes is to be used to calculate the control is developed such that it satisfies certain performance criteria. The results of extensive computer studies of one-and two-dimensional extremum systems are presented.
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    ABSTRACT: Inadequate hospital stocking and the unavailability of essential antidotes is a worldwide problem with potentially disastrous repercussions for poisoned patients. Research indicates minimal progress has been made in the resolution of this issue in both urban and rural hospitals. In response to this issue the British Columbia Drug and Poison Information Centre developed provincial antidote stocking guidelines in 2003. We sought to determine the compliance with antidote stocking in BC hospitals and any factors associated with inadequate supply. A 2-part survey, consisting of hospital demographics and antidote stocking information, was distributed in 2005 to all acute care hospital pharmacy directors in BC. The 32 antidotes examined (21 deemed essential) and the definitions of adequacy were based on the 2003 BC guidelines. Availability was reported as number of antidotes stocked per hospital and proportion of hospitals stocking each antidote. For secondary purposes, we assessed factors potentially associated with inadequate stocking. Surveys were completed for all 79 (100%) hospitals. A mean of 15.6+/-4.9 antidotes were adequately stocked per hospital. Over 90% of hospitals had adequate stocks of N-acetylcysteine, activated charcoal, naloxone, calcium salts, flumazenil and vitamin K; 71%-90% had adequate dextrose 50% in water (D50W), ethyl alcohol or fomepizole, polyethylene glycol electrolyte solution, protamine sulfate, and cyanide antidotes; 51%-70% had adequate folic acid, glucagon, methylene blue, atropine, pralidoxime, leucovorin, pyridoxine, and deferoxamine; and <50% had adequate isoproterenol and digoxin immune Fab. Only 7 (8.9%) hospitals sufficiently stocked all 21 essential antidotes. Factors predicting poor stocking included small hospital size (p < 0.0001), isolation (p = 0.01) and rural location (p < 0.0001). Although antidote stocking has improved since the implementation of the 2003 guidelines, essential antidotes are absent in many BC hospitals. Future research should focus on determining the reasons for this situation and the effects of corrective interventions.
    Canadian Journal of Emergency Medicine 12/2006; 8(6):409-16. · 1.16 Impact Factor
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    ABSTRACT: To determine the sufficiency of stock levels of 13 antidotes in Queensland hospitals. A self-report survey was sent to 128 Queensland hospitals with acute care facilities. The stock level of the following antidotes was determined: acetylcysteine, anti-digoxin Fab antibodies (digibind), atropine, calcium gluconate, cyanokit, desferrioxamine, flumazenil, glucagon, intravenous ethanol, methylene blue, naloxone, pralidoxime and pyridoxine. Other factors sampled were bed capacity, rural, remote and metropolitan areas classification, use of formal stock reviews by pharmacists or nurses, existence of formal borrowing agreements with other facilities for non-stocked antidotes, distance to the nearest referral hospital and time taken to transfer antidotes from another hospital. Pharmacists or nurses responsible for maintaining antidote stocks in Queensland hospitals. Proportions of hospitals with sufficient antidote stock to treat a 70-kg adult for four or more hours using previously published guidelines. Survey response rate was 73.4%. No hospital had sufficient stock of all 13 antidotes. The proportion of hospitals with sufficient stocks varied from 0% (pyridoxine) to 68.1% (acetylcysteine). Larger hospitals had a higher frequency of sufficient antidote stocks. Only 16% of hospitals claimed to be able to acquire an antidote from another facility within 30 min. Most Queensland hospitals stocked some important antidotes, but few had sufficient stock to treat a 70-kg patient or acquire an antidote within the recommended time frame of 30 min. Specific antidote stocking guidelines might be required for Queensland hospitals. A formalised program for stock rotation with rural facilities should be explored.
    Australian Journal of Rural Health 04/2010; 18(2):78-84. DOI:10.1111/j.1440-1584.2010.01129.x · 1.23 Impact Factor
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