Methanol toxicity is a serious poisoning that has high morbidity and mortality, which typically occurs in outbreaks in the community through ingestion of homemade or illegally produced alcoholic drinks. Despite that, the world health organization’s global report on health outcomes related to alcohol describes that methanol toxicity only accounted for less than 1% of all alcohol-attributable deaths (WHO, 2014). A study in the United States reported that the inpatient prevalence of methanol toxicity was 6.4 cases per 1,000,000 admissions. Nevertheless, these outbreaks are tragic events as methanol poisoning if not rapidly treated, causes retinal injury and eventually permanent blindness, as well as ischemic or hemorrhagic injury to the basal ganglia, renal failure, respiratory failure, and death (Kaewput et al., 2021).

In September 2020, we identified our first case of methanol toxicity which turned into a series of cases that came to be recognized as a national methanol outbreak, as other cases were reported at other hospitals. All these cases were linked to one source of poorly adulterated alcoholic beverages, distributed illegally. Familiarity with methanol toxicity is not common in our region. A retrospective review of methanol toxicity cases received over the past decade using data from our pharmacy showed that only 15 vials of fomepizole were dispensed over 10 years, with a zero consumption over the past 3 years ahead of this outbreak, compared to 95 vials utilized since the outbreak.

A literature search of methanol toxicity cases in Saudi Arabia (SA) revealed only four cases (Algahtani et al., 2018; Althwanay et al., 2020; Owolabi et al., 2020). However, Galvez-Ruiz et al. described outcomes of optic disk cupping following methanol poisoning in a series of 50 cases presenting at two large hospitals in Riyadh between 2008 and 2014, possibly indicating a higher incidence of methanol toxicity than perceived (Galvez-Ruiz et al., 2015). A recent study that used the United States National Inpatient Sample database reported 6.4 cases per 1,000,000 inpatient prevalence of methanol toxicity (Kaewput et al., 2021).

Insufficient stocking and availability of antidotes have been reported as a worldwide problem (Dart et al., 1996; Al-Sohaim et al., 2012; Gasco et al., 2013; Thanacoody et al., 2013). The Institute of Safe Medication Practice (ISMP-Canada) in a safety bulletin recognized the inaccessibility to antidotes and availability of information resources to guide timely use as main vulnerabilities in dealing with toxicity cases (Ismp-canada, 2018).

This paper aims to share a learning experience as we describe the incidence of delay in allocation and treatment with the antidote fomepizole in the first cases of methanol toxicity presented at our facility. We also describe the root cause analysis (RCA) of the incidence and the measures taken to ensure patient safety and prevent a recurrence.

No patient or case details are described in this paper, the aim is to share barriers to proper medication management of antidotes to promote patient safety.

In 2020, around the beginning of the autumn season and just as COVID-19 lockdown and restrictions on gatherings were eased in SA, the first case in a series of cases of methanol toxicity presented to the emergency room (ER) during the weekend. With classic signs and symptoms of methanol toxicity including metabolic acidosis and changes in the level of consciousness. The diagnosis was confirmed with methanol blood levels. At this point, dialysis and intravenous (IV) fomepizole were ordered.

The order for fomepizole was entered in the computerized physician order entry (CPOE) as a STAT order, which was verified by the ER satellite pharmacy within 2 mins; however, no stocks of fomepizole were available in the ER satellite pharmacy. The pharmacy technician proceeded to check the pharmacy’s electronic inventory system, which indicated that stocks were available in the pharmacy warehouse. The technician called and paged the on-call pharmacist in charge of the pharmacy main store but no one answered.

The pharmacy technician also called the intensive care unit (ICU) satellite pharmacy in another attempt to locate stocks of fomepizole, as satellite pharmacy stocks are not linked to the electronic inventory system, and thus, stocks need to be checked manually. Over the phone, the pharmacist misheard fomepizole IV as omeprazole IV, which is not a formulary item at the hospital, and therefore, the pharmacist provided a negative response, replying that no stocks are available. The technician also contacted the IV room pharmacy but they also had no stock.

Five hours from the initial order the on-call pharmacist in charge of the pharmacy main store answered, but replied that no stocks are available in the pharmacy warehouse.

The patient was then transferred to the ICU where a new order for fomepizole was made. The ICU pharmacy technician was also unable to locate the stock of fomepizole, but a senior pharmacy technician was aware of its presence. The first dose of fomepizole was finally administered to the patient 6 hours after the initial order.

During that time, the pharmacy director and director of pharmaceutical planning who were off-duty were informed by hospital staff about the unavailability of fomepizole and began efforts in borrowing stocks from other hospitals. The director of pharmaceutical planning requested from one of his off-duty staff to physically check the pharmacy warehouse for stocks of fomepizole, which were available and delivered to the ICU-satellite pharmacy within 7 hours from the initial fomepizole order for the index case. Figure 1 outlines the pharmaceutical distribution process at our institution.

The toxicologists overseeing the patient had also inquired the pharmacy about the availability of ethanol (an alternative antidote for methanol toxicity), which was unfortunately not listed as a formulary item and was only stocked in the narcotic pharmacy in small quantities for other uses, and pharmacy staff were not aware of its availability. Figure 2 outlines the timeline and sequence of the event.

The event was deemed preventable by the task force evaluating the incidence. The family was disclosed about the event.

The RCA elucidated the fundamental error in this event to be the failure to locate the available stocks of fomepizole within the hospital by pharmacy staff, resulting in a 6-hours delay in the administration of the antidote. On further analysis, this error of medication administration delay was attributed to the following three root causes:

Planning pharmaceutical inventory can be extremely challenging in such a dynamic setting of disease trends, drug discovery, and new clinical research, adding to these, the rarity of some indications and their therapeutic utilization makes it more challenging.

The outbreak of COVID-19 in 2020 and the shutdown of major pharmaceutical plants around the world added to the challenge of a well-planned secured drug supply in many healthcare settings (Abu Esba et al., 2020).

Poisoning cases vary in epidemiology and often lack good evidence on incidence, in addition to geographical differences in types and frequencies of occurrences. This makes local assessment and decisions on antidote stocking crucial (Azab et al., 2016; Sandilands and Bateman, 2016).

A national survey of antidote stocking in the United Kingdom revealed that atropine, calcium gluconate, and flumazenil were the only antidotes available in adequate stocks in all hospitals. They also reported that only (24.3%) of the hospitals held all antidotes that were recommended to be available immediately, which only improved to (47.9%) after auditing and introducing a national guideline. They concluded that more efforts are required to ensure timely access to other antidotes (Bailey et al., 2016).

This RCA triggered a holistic review of our antidote preparedness and identified areas of weakness in stocking and access that were important to be reassessed and modified to be prepared for any further poisoning cases presenting. Similar efforts have been shared by the Nova Scotia antidote program which demonstrated that adequate stocking is achievable through ongoing surveillance and maintenance by a multidisciplinary team (Murphy et al., 2019).

Pharmacists working in poison centers should be able to provide information on the appropriate use of antidotes including method of preparation, dosing, and monitoring in addition to advice on procurement and stocking of antidotes suitable to the size and area of their served community.

Cultural aspects and difference also unique to our setting was the unavailability of ethanol, which in other countries is readily available. Therefore, antidote stocking and planning should be tailored to address these differences.

Whatever the reasons for inadequate stocking of antidotes, be it cost, availability, infrequent use, or lack of awareness, institutions should make all efforts to regularly review and audit their antidote stocks.

Management of antidotes in large healthcare systems requires a team effort to ensure appropriate and timely availability in emergency poisoning cases. This RCA identified important areas for improvement that could be insightful to other institutions in preventing similar vulnerabilities. It provides details on operational level modifications that are needed to ensure safe access to antidotes when needed. The implemented measures require future analysis and assessment of their success in improving access to antidotes.