Adequacy of antidote stocking in British Columbia hospitals: The 2005 Antidote Stocking Study

EM Advances

CJEM 2006;8(6):409-416

Abstract

Résumé

Background

Inadequate hospital stocking and the unavailability of essential antidotes is a worldwide problem with potentially disastrous repercussions for poisoned patients.1-7 In most cases of drug overdose, gastric decontamination and supportive care are adequate; however, in some patients the timely administration of an appropriate antidote can be a life-saving intervention. Since this problem was identified in the mid-1980s,1 subsequent research indicates minimal progress has been made in both urban and rural hospitals.2-18

In 2000, the first US consensus guidelines were published, providing direction for hospitals regarding which antidotes were necessary to stock and the quantity recommended.19 Shortly thereafter, investigators in British Columbia, Quebec and Ontario evaluated the adequacy of antidote stocking in Canadian hospitals.7,16,18 Although they applied different criteria, all 3 studies reported gross inadequacies in antidote stocking. In BC, no hospital adequately stocked all 14 evaluated antidotes and 59% adequately stocked fewer than 5 antidotes.7 Ontario hospitals stocked an average of 4.8 antidotes and only 1 hospital (0.6%) stocked all 10 evaluated antidotes,16 while Quebec hospitals stocked an average of 5.9 of 13 antidotes deemed essential.18,20

In 2003 the British Columbia Drug and Poison Information Centre (BC DPIC) developed antidote stocking guidelines for acute care hospitals in BC.21 These guidelines sought to improve availability by providing minimum stocking recommendations and also through implementation of strategic stocking of expensive and infrequently used antidotes. The BC DPIC guidelines provide recommendations for minimum antidote stocking levels of 32 agents based on characteristics such as frequency of use, cost, and transport time from regionally designated "depot" hospitals. This depot model relies on strategic antidote stocking and assumes cooperative development of inventory sharing agreements between health care facilities. Depot hospitals are designated at the discretion of each regional health authority; however, each hospital is ultimately responsible for ensuring that an adequate supply of antidotes is available.

Guidelines were developed based on the following assumptions; (i) regardless of size and location, all acute care hospitals with an emergency department (ED) should stock a core supply of 19 common antidotes required on an urgent basis ("basic stock" items); (ii) strategic stocking of high cost, infrequently used antidotes ("target" items) can reduce inventory costs and minimize wastage of expired stock while still ensuring good patient care; and (iii) hospital pharmacies will work cooperatively to ensure that minimum antidote stocks are maintained. Hospitals in proximity to a depot require sufficient antidote supply to provide treatment until a back-up supply is accessed or patient transfer can be arranged. Back-up supplies may be obtained from the main depot or another nearby health care facility. Stocking recommendations assume use of routine transport (e.g., regular hospital courier, commercial bus service or commercial overnight courier service) for most stock replacement needs. The use of emergency transport (e.g., ground or air ambulance, police) is limited to high-cost antidotes and life-threatening poisoning. Minimum stocking levels in the BC guidelines are based upon the supply required for the initial treatment of one 70-kg patient. Hospitals are expected to adjust stocking level according to hospital size, population served and local special requirements. Hospitals are advised not to decrease their inventory to match the minimum-stocking list if past experience indicates that a larger inventory is required. The quantities are based on the combined inventory of all hospital departments (e.g., pharmacy, ED, night cupboard).

Antidote stocking levels in BC hospitals have not been evaluated since the development of the 2003 provincial guidelines, and thus the impact of these guidelines is unknown. The objectives of this study were to evaluate hospital compliance with antidote stocking guidelines and to determine factors associated with inadequate supply.

Methods

Design and study population

We conducted a prospective observational study in all BC acute care hospitals. The BC Ministry of Health provided a listing of all potentially eligible hospitals.22 Eligible hospitals were defined as any hospital that had inpatient beds and could be required to treat an acutely poisoned patient. Extended care hospitals, diagnostic and treatment centres, cancer agencies, military hospitals, and Red Cross outposts were excluded.

Data collection and analysis

Data were collected using a 2-part survey instrument. Part 1 captured demographics including hospital size, presence of an ED (and ED hours of operation), pharmacy hours and the availability of on-call pharmacy services. Part 2 captured dosage form, strength and quantity of all 32 antidotes outlined in the BC DPIC guidelines.

All surveys were sent by mail on Sept. 2, 2005. A second mailing was sent to nonresponders on Oct. 3, 2005. A third and final contact attempt with nonresponders was conducted by telephone between Nov. 1, 2005, and Dec. 9, 2005. Any responses obtained after Dec. 9, 2005, were excluded from the analysis. Responses were accepted by fax (preferred method), mail, email or telephone.

Outcomes

The primary outcome was the number and proportion of the 21 essential antidotes appropriately stocked by the surveyed hospitals. All hospitals regardless of size or location are expected to carry on-site an adequate supply of all 19 basic items in addition to 5 targeted items, which are outlined in Table 1. For toxic ingestions where 2 different antidotes could be used (e.g., ethyl alcohol or fomepizole; calcium gluconate or calcium chloride; and the cyanide antidote kit or sodium thiosulfate) an adequate supply of either antidote was deemed sufficient. Other targeted and specialty antidotes included in the survey were excluded from the analysis, as they are either optional by current guidelines or only required in certain geographic or industrial settings.21

In a secondary analysis, we assessed factors potentially associated with inadequate stocking. These factors, defined a priori, included hospital size, geographic location (degree of isolation) and referral population. Hospital size was categorized as small (<50 beds), medium (50-250 beds) and large (>250).16 Isolation was defined by distance to the nearest eligible hospital; a distance of >100 km, or the necessity to utilize ferry transport to reach the nearest hospital was categorized as isolated.7 Urban hospitals were defined as those serving populations of >20 000.7,23

Statistical analysis

Data were entered into an Excel 2000 (Microsoft, Redmond, Wash.) database and imported to SPSS (ver. 11.0 Macintosh) and STATA (ver. 5.0 Macintosh) for analysis. Standard descriptive statistics were reported including means and standard deviations. The adequacy of antidote supply for each hospital was reported as a raw number and proportion of essential antidotes stocked. The overall proportion of hospitals stocking an adequate supply of each individual antidote was also determined. Overall comparison of the mean number of antidotes stocked between various hospital sizes was performed using a one-way analysis of variance (ANOVA) with a p value for statistical significance of 0.05. Two-group comparisons of the mean number of antidotes available between 2 a priori-defined hospital categories were made using a 2-tailed student's t test. No adjustments were made for multiple comparisons.

Results

Ninety-three potentially eligible hospitals were identified and invited to participate. Following the initial mailing, 14 hospitals were excluded because they did not have inpatient beds. All 79 eligible hospitals (100%) responded before the enrollment deadline and were included in the final analysis. Hospital characteristics are outlined in Table 2.

Primary outcomes

Table 3 summarizes stocking adequacy for each essential antidote. BC hospitals adequately stocked a mean of 15.6 ± 4.9 antidotes. Only 7 (8.9%) hospitals adequately stocked all 21 essential antidotes. Over 90% of hospitals had adequate stocks of N-acetylcysteine, activated charcoal, naloxone, calcium salts, flumazenil, and vitamin K; >70%-90% had adequate ethyl alcohol/fomepizole, polyethylene glycol electrolyte solution, protamine sulfate, cyanide antidotes, and dextrose 50% in water (D₅₀W); >50%-70% had adequate folic acid, glucagon, methylene blue, atropine, pralidoxime, leucovorin, pyridoxine, and deferoxamine; and <50% had adequate isoproterenol and digoxin immune F_ab.

Secondary outcomes

Table 4 shows that urban hospitals adequately stocked an average of 17.6 ± 3.5 (83.8%) antidotes versus 13.3 ± 5.3 (63.3%) for rural centres (p < 0.0001). Table 5 shows that isolated hospitals adequately stocked an average of 13.7 ± 5.4 (65.2%) antidotes versus 16.6 ± 4.3 (79.0%) in non-isolated hospitals (p = 0.0111). Small, medium, and large hospitals adequately stocked 13.4 ± 5.2 (63.8%), 18.5 ± 1.8 (88.1%), and 19.2 ± 1.9 (91.4%) antidotes, respectively (p < 0.0001) (Table 6).

Discussion

This study indicates that, despite improvements since the development of the BC antidote stocking guidelines, BC acute care hospitals still have substantial deficiencies in the stocking of several essential antidotes. Several factors are associated with adequacy of antidote stocking. Specifically, inadequate stocking was more common in smaller (<50 beds) hospitals and in rural hospitals. These findings are consistent with previous studies. Our study captured information on all 79 eligible hospitals in BC, which allows confidence that the results provide an accurate assessment of stocking adequacy.

Barriers to antidote stocking

High costs of antidote stocking and supply maintenance have been cited as barriers to adequate stocking.4,5,13,20 The initial cost of purchasing an adequate supply of antidotes in Canada has been estimated at $9250 for suburban hospitals and $10 190 for remote hospitals, with stock maintenance costing an additional $2130 to $5410 annually.24 Expenditures of this magnitude may not be feasible or efficient for many rural hospitals that serve small populations and only occasionally treat acute poisoning.

Although cost has been cited as a barrier to adequate antidote supply, we found that several inexpensive antidotes were poorly stocked. Folic acid, leucovorin and isoproterenol, which cost a combined total of less than $125 to purchase, were only adequately stocked in 70%, 62% and 49%, respectively. More expensive antidotes such as glucagon, atropine and cyanide kit/sodium thiosulfate were also poorly stocked. Even with the replacement cost of digoxin immune F_ab completely covered by a BC DPIC antidote stock replacement program, digoxin immune F_ab, was the most poorly stocked antidote. Table 1 shows that it would cost $3849 to purchase all 21 antidotes outlined in this study.

Antidote availability is a commonly cited barrier to stocking; however, during the course of the study all but 3 antidotes were readily available for purchase and thus stocking of most antidotes was not affected by availability. There were persistent shortages of pyridoxine and pralidoxime before and during the study period. Inadequate stocking of these 2 antidotes may reflect this shortage. The 3-drug cyanide antidote kit (sodium thiosulfate, sodium nitrite, amyl nitrite) is not available on the Canadian market and must be obtained through the Health Canada Special Access Program; however, sodium thiosulfate can be readily purchased as a single agent.

Limitations

Although it appears that the adequacy of antidote stocks has improved since the 2000 BC antidote survey, several limitations preclude a comprehensive comparative evaluation of this issue. First, the current study was not designed to compare stocking levels between 2000 and 2005. In addition, the minimum requirements used during the previous study were based on US consensus guidelines rather than BC guidelines. The BC guidelines differ from the US guidelines in several ways, including a minimum supply definition based on the ability to treat one rather than two 70-kg patients for some antidotes, and incorporation of the depot model for expensive and infrequently used antidotes. Finally, some agents that were deemed essential within the US guidelines were not included in the BC guidelines.

Another potential limitation is that our results are based upon on a reporting of antidote supply, rather than direct observation. It is conceivable that those completing the survey may have been more likely to overestimate rather than underestimate supplies at their location, thus improving the likelihood of their hospital meeting the minimum standards. Second, although there are several factors that may contribute to inadequate antidote supply, our study was not designed to thoroughly investigate the reasons for inadequate antidote supply. Finally, our study was not designed to evaluate any potential relationship between antidote stocking and patient outcome.

Conclusion

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. Future research focusing on the implication of inadequate antidote stocking on actual patient outcomes would facilitate the future development and implementation of evidence-based guidelines.

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