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Medication Safety in Anesthesia

Epidemiology, Causes, and Lessons Learned in Achieving Reliable Patient Outcomes

Cooper, R. Lebron MD, FASA*; Fogarty-Mack, Patricia MD; Kroll, Henry R. MD; Barach, Paul MD, MPH§

International Anesthesiology Clinics: Summer 2019 - Volume 57 - Issue 3 - p 78–95
doi: 10.1097/AIA.0000000000000232
Review Articles
Free

*Department of Anesthesiology, Indiana University Health Arnett Hospital, Lafayette, Indiana

Department of Anesthesiology, Weill Cornell Medicine, New York, New York

Department of Anesthesiology, Henry Ford Health System, Detroit, Michigan

§Department of Anesthesiology, Children’s Hospital of Michigan, Wayne State University, Detroit, Michigan

The authors declare that they have nothing to disclose.

Address Correspondence to: R. Lebron Cooper, MD, FASA, Department of Anesthesiology, Indiana University Health Arnett Hospital, 5165 McCarty Lane, Lafayette, IN 47905. E-mail: lebroncooper@mac.com

Patients continue to suffer from medication harm despite 40 years of research; anesthesia providers have been slow to recognize the implications and acknowledge the extent of the problem. Research efforts to define the incidence, causes, and associated human factors, after a slow start in the 1980s and 1990s, have taken off. The Anesthesia Patient Safety Foundation (APSF), under Dr Ellison “Jeep” Pierce,1 along with the American Society of Health-System Pharmacists (ASHP), the Institute of Safe Medication Practices (ISMP), and other national and international professional societies, support an emerging literature that has become more difficult to ignore or refute. In a recent literature review, Abrishami et al2 reported that the number of studies reporting medication errors has increased exponentially over the past 2 decades. The American Society of Anesthesiologists is actively working to educate the anesthesia community in finding new ways to prevent errors from reaching or harming patients.3

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History and Epidemiology

Research in anesthesia medication errors has somewhat paralleled research on the epidemiology of medical errors. Three studies in the 1980s and 1990s reported anesthesia mishaps and adverse events. None of these retrospective studies looked specifically for medication errors. Craig and Wilson4 reported that the rate of any mishap was 0.14% or 1 in 694 anesthetics. Human error was the most frequent cause. Nine years later, Chopra et al5 found that the failure to check, lack of vigilance, inattention, and carelessness were the main causes of anesthesia complications, incidentally finding the rate of drug error to be only 0.012%, and acknowledging that minor medication errors were probably missed because of the study design. Wilson et al6 found drug error to be the fourth most common adverse event, resulting in permanent disability and death (17% and 8% respectively), with 51% deemed preventable.

The 1999 landmark article from the Institute of Medicine (IHI), “To Err is Human,” found that 7% of hospital admissions experience a serious medication error.7 In the first prospective study based on voluntary reporting, Webster et al8 found the incidence of medication error in anesthesia to be 1 in 133 anesthetics. This incidence was significantly higher than reported previously and suggested that many more errors were not being reported or recognized. In a retrospective review, Yamamoto et al9 found the incidence of medication errors to be 1 in 450 anesthetics, noting limitations that included the retrospective study design, lack of comprehensive education about how to report, no active encouragement to report, and unreported minor drug errors. Llewellyn et al,10 in a prospective design based on voluntary reporting similar to the earlier Webster study, found the incidence to be 1 in 274 anesthetics. The first report in the United States also used a prospective design based on voluntary reporting, and found the incidence to be 1 in 203 anesthetics.11

A recent publication by Nanji and colleagues attempted to define the incidence using a mixed-methods, human factors ethnographic study. The authors used trained observers backed by a detailed chart review of almost 3700 individual drug administrations, and found 193 errors (5.3%), equating to one in every other anesthetic.12 79.3% of errors were considered preventable, of which 64.7% were considered serious and 3% as life threatening. Although the authors defined medication errors differently, this incidence is markedly higher than that found in any previous studies on the basis of voluntary reporting. Table 1 summarizes these studies.

Table 1

Table 1

Four studies carried in the 1970s-1990s specifically attempted to define adverse events or which human factors play a role in medication errors.4–6,13 From New Zealand in 2001, Webster et al8 reported a failure to check, misread syringe/vial, and “syringe swaps” as the most common human factors leading to error. These were closely followed by distraction, inattention, and pressure to proceed. Cooper et al11 found identical results 11 years later in an entirely different culture and environment. Considering that the human factors involved have remained essentially unchanged between 1978 and today, these should be addressed if new strategies for reducing medication errors are going to be implemented effectively.

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The Cause for the Large Variation

There are several reasons for the wide variation in the reported incidence of medication errors in anesthesia. Early research efforts on anesthesia mishaps only incidentally found the error rate. Differences found between 2001 and 2017 were based mainly on study design. Three prospective studies with similar designs found similar results. The 2016 Nanji study adopted a different methodology, and found a much higher rate.12,15 As stated by Grigg and Roesler, “the anesthesia approach to medication errors in primitive, fragmented, and cavalier.”16 Although several studies have attempted to define the true incidence, many questions remain as to the true incidence and the disparate research findings. There is some disagreement as to what should be reported and what actually constitutes a medication error. Use of commonly accepted definitions of medication error and medication harm will help resolve some of the variance in future studies.

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Definitions of Medication Error, Adverse Drug Events (ADEs), and Adverse Drug Reactions (ADRs)

When a patient experiences a drug-related event under anesthesia, one wonders whether this is an expected outcome or a known hazard that could have been prevented. Should this be defined as a medication error, adverse medication event, near miss, or simply a reflection of the patient’s underlying illness? The field of pharmacovigilance is devoted to understanding the full range of expected physiological responses of humans exposed to medicinal substances with powerful properties. The terms adverse drug event (ADE) and adverse drug reaction (ADR) are useful markers to help anesthesiologists assess and understand why patients react in certain ways.17 The International Conference on Registration of Pharmaceuticals defines medication error as “any preventable event that may cause or lead to inappropriate medication use or patient harm while the medication is in the control of the health care professional, patient, or consumer.”18 An ADE is defined as an injury resulting from the use of a drug.19 This definition includes ADRs and includes events due of treatment failures and medication errors20 (Table 2).

Table 2

Table 2

Understanding ADRs requires careful event analysis to help rule out other potential causes that might have contributed to the patient’s response.21,22 Pharmacovigilance addresses the time intervals between the drug administration and the adverse event, pathophysiology and competing causes for the event, response to dechallenge (eg, stopping vasopressor infusion or a drug dose reduction), and the response to rechallenge (ie, protamine readministration). Table 3 describes the causal criteria to gauge the likelihood that a drug contributed to an adverse event. A drug has likely contributed to an adverse event if, when administered, clear and consistent effects are seen, and if, when the drug is not administered, the symptoms and signs would not have occurred or would be considerably different in severity.23

Table 3

Table 3

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Types and Mechanics of Reporting Errors

Differing methodologies lead to variances in reported incidence. Observation studies and other review methods have consistently found higher rates of error than those relying on voluntary reporting. Cohen,26 in an editorial, stated that voluntary reporting underestimates the actual incidence of medication error by many fold, but may be the most effective method of reporting. In an observational study, Cullen et al27 reported that retrospective chart review found at least a 5-fold incidence of errors compared with voluntary reporting. Classen and colleagues compared the IHI “Global Trigger Tool” (GTT) to voluntary reporting and the Agency for Healthcare Research and Quality’s Patient Safety Indicators chart review. The authors found that both fared poorly in comparison with the GTT and missed 90% of adverse events.28 The IHI GTT found at least 10 times more confirmed and serious events.

Voluntary reporting assumes that the person making the error recognizes that an error was made and will be honest, take the time, and report the error.30 It also assumes that the practitioner knows the definition of medication error and what should be reported. There may be a rational fear of retaliation, adverse legal action, or reports made to the National Practitioner Data Bank or medical/nursing boards, leading to a hesitation to report.

How the errors are reported may be a challenge. In the current health care climate, production pressure leaves little time between cases to report.31 Computerized risk management software programs exist in most hospitals, and yet many are cumbersome and require extensive data entry.30 The 3 prospective studies referenced above used a simple piece of paper included with each anesthesia record, facilitating voluntary reporting and preventing the need to spend time on the computer. In the era of electronic medical records (EMR), paper systems have mostly fallen by the wayside. A potential solution is an electronic error report, ergonomically designed to mitigate the workload on clinicians, with dropdown menus linking directly into a secure and confidential database facilitating ease of reporting, analysis, and feedback to the clinician.32

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Causes of Medication Errors

Cooper et al13 first described “syringe swaps” in 1978 as one of the top 3 causes of preventable anesthesia mishaps. The authors identified human factors associated with these types of medication errors, including haste, inattention/carelessness, fatigue, distraction, and poor labeling and failure to check or read the label, among others. Although progress has been made to address these human factors, in some ways, they have not gone away and their impact may even be more prevalent, given the organizational emphasis on productivity above all and the surge of new and poorly designed technologies and EMR contributing to more work and stress to providers.33

The most common medication errors in one of the largest prospective studies were wrong dose, labeling, and failure to deliver correct medication.12 The most common medications associated with errors in the operating room (OR) were propofol, phenylephrine, and fentanyl; neuromuscular-blocking agents and opioids have also been documented as common offending agents.34

The causes of these socio-technical system safety failures are many and are embedded in professional, cultural, and organizational norms,35 including rampant normalized deviance,36 in which unacceptable actions or professional violations are ignored, ignoring human factors, lack of data and outcomes transparency, and organizational secrecy.37 Poorly designed medication dispensing systems/carts, labels and fonts, vial sizes, and unaddressed embedded human factors constraints, including the existence of confusing drug names and look-alike/sound alike dissimilar drugs, are the most common causes of medication errors worldwide.38 The anesthesiologist working alone to draw up, dilute, label, and administer medications with little or no oversight is clearly a contributory factor.39

While labeling may now be more standardized, with ASTM color-coded syringe standards and computer-generated labels being readily available, we still rely on the “read the label” exhortation.40 Prefilled syringes are available with barcoded labels, and yet in the United States, there is no commercial anesthesia computer system that will seamlessly read the labels and integrate them into the EMR.41 There are no auditory or visual alerts to help anesthetists avoid administering the wrong medication or the wrong dose. Fewer than one in 10 physicians routinely read drug labels, despite their clear and accepted warnings.42 This is particularly challenging with anesthesia outside the OR, where drug or syringe mix-ups can often be difficult to recognize and manage quickly. A manual independent risk-reduction strategy of double-checking high-alert medications that has been a strategy widely promoted by nurses and pharmacists has long been disputed and ridiculed by anesthesia providers.43 The ability of independent double checks to detect up to 95% of errors has been demonstrated in numerous studies.44,45 This may be impractical in the daily practice of anesthesia, but deserves a deeper consideration.

The most important organizational barrier to medication safety is the prevalent risk culture. A culture of safety is created when an organization endorses medication reporting and where physicians, nurses, and pharmacists feel psychologically safe to speak up and report errors or other improvement opportunities.46 Staff can report dangerous or inadequate processes or outcomes and will not be censured or suffer reprisal unless their actions were malicious or deemed to have intent to cause patient harm.47 Careful investigation of these ADE leads to thoughtful and meaningful steps that make sense to clinicians and are likely to endure. This type of environment has been described as a learning environment, and in conjunction with concrete learning processes and practices, is the first step toward creating a learning organization.48 Conversely, a blame culture instigated by the department head or hospital leadership can lead to staff fear and a marked reduction in reported medication incidents.49

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Challenges With Labeling and Drug Shortages

The US Food and Drug Administration (FDA) has estimated that 20% of medication errors may be related to suboptimal packaging or labeling.50 Packaging and labeling are important means of differentiating high-risk/high-acuity medications. Human factors research has shown that pattern recognition is important in performing time-sensitive tasks in high-stress situations and the ASA supports the ASTM color-coding for anesthesiologist use in procedure areas.51,52 Commercial compounding pharmacies that prepare bulk prefilled syringes also utilize ASTM color-coding. The FDA and ISMP have cautioned, however, that color-coding may actually lead to more errors, such as the lavender background on ephedrine and epinephrine. The alternative recommended by ISMP and the FDA in most situations is to have all labels as white with black-block lettering of the medication name and concentration.53 This should force clinicians to verify the name and dosage of the medication.

Look alike-sound alike (LASA) drugs have been a major contributor to medication errors.54 Information technology solutions can reduce the LASA risk, but the potential for error will remain unless these systems are implemented carefully.55 Tall man lettering, endorsed by the FDA, The Joint Commission, and ISMP, utilizes UPPERCASE letters to highlight dissimilar letters of LASA names to better distinguish between the 2. Medications identified commonly with tall man labeling include ePHREDrine versus EPINEPHrine, DOBUTamine versus DOPamine, and NORepinephrine versus EPINEPHrine.56 Recent meta-analyses and reviews have determined that there are mixed results for the effectiveness of both tall man lettering and color-coding.57,58

The barriers to implementing a barcoding system in the OR include hardware, software, and labeling. Results from the 5 studies in a recent review suggest that barcode medication administration has the potential to reduce nontiming administration, transcription, and total medication errors.59 Barcodes most likely are black on a white background and must not be placed in an area easily damaged.

ISMP, FDA, and United States Pharmacopeia (USP) also have recommendations for the content and design of drug labels. FDA recommends that label fonts use a 12-point minimum sans serif-type font with enough contrast in colors to ensure legibility.60 USP requires that the full contents of a vial or prefilled syringe be the primary dosage content on the label, as opposed to previous standard unit per milliliter (ie, fentanyl 250 mcg/5 mL as opposed to 50 mcg/mL). Pharmacists traditionally purchase medications placed in an anesthesiology drug tray with the intention of avoiding look-alike vials, especially when they would be positioned in close proximity. With the exception of neuromuscular blockers, which are required to have a yellow vial cap stating “WARNING: PARALYTIC AGENT” in black letters, there are no color-specific requirements for vial shape or cap color. Consistent shortages have forced pharmacists to source drugs in any packaging available, increasing the risk of medication errors.

One author of this chapter recently experienced a series of LASA vials/syringes resulting from drug shortages (Fig. 1). Three different types of ondansetron vials were sourced, leading to near misses with look-alike concentrated phenylephrine, sugammadex, and ketorolac. In addition, substitution of rocuronium with different-colored caps led to a near miss with succinylcholine as succinylcholine and rocuronium vials were almost indistinguishable in color, shape, and print font.

Figure 1

Figure 1

The lack of availability of products in standard concentrations leads to substitution in a different concentration, a substitute medication in the same pharmacologic class, or a different medication altogether. Lack of recognition that a concentration has been changed or lack of familiarity with a substitute medication may lead to untoward effects. Respondents to an ISMP national survey of hospital pharmacists found that 21% documented a drug error secondary to drug shortages and 75% stated that treatment had been delayed.61 Examples of various medication errors directly attributed to drug shortages may be found on the ISMP website.62

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Evidence-based Strategies and Multimodal Interventions

Over the last 15 years, significant efforts have been made to develop strategies to prevent drug errors. Jensen et al45 published recommendations to reduce drug administration errors. They proposed, after reviewing 98 publications and reports related to anesthesia IV drug errors, the following: (1) correcting systematic challenges that may lead to decreased medication error rates; (2) reading the label before any drug being drawn up or injected; (3) ensuring legibility and that label details meet agreed-upon standards; (4) always labeling syringes; (5) standardized and organized drug trays/workspaces in as many work locations as possible; and (6) drug labeling should always be confirmed with an additional provider or through a barcode reader. A second verification could have avoided 58% of the errors identified, making it the single most effective drug error prevention strategy.

The APSF hosted a conference on medication safety in 2010, proposing a new paradigm to reduce medication errors in the OR1: high-risk medications should be made available in standardized concentrations that are prepared by the pharmacy in a form that can be used without further dilution, use of smart devices with a preconfigured library of drugs and their most-common delivery rates, and the acquisition of commercially prepared syringes or infusions with barcodes that can be scanned for confirmation before administration and automatic documentation into the EMR. In addition, anesthesia workstation scanners should automatically convey feedback to the provider to assist in patient medication and management choices. The goal is to eliminate compounding and dilution of drugs at the bedside by the provider. This would require dedicated OR clinical pharmacists to be part of the team. Importantly, a “just culture” should be established that allows for reporting of drug errors without fear of blame or retaliation with discussions of lessons learned. APSF concluded that these consensus-based recommendations may result in a marked reduction in the medication error rate and related morbidity and mortality.

Merry et al63 reported a multifaceted attempt to reduce errors on the basis of systems design and incorporating the psychology behind human factors that may contribute to error. The system included organized anesthesia workspaces, barcoded syringes with colored labels, automated anesthesia records, electronic documentation, and automatic visual and auditory computer feedback before each drug administration. This resulted in a 35% reduction in drug administration errors compared with their previous traditional system.64 These researchers subsequently reported a prospective, randomized study to determine the impact on errors in recording and administration of drugs and on vigilance and workload.65 They found that use of the new system led to a 21% reduction in documentation errors, and the system did not add to the work of clinicians; however, there was no significant impact on the incidence of drug administration errors.

Wahr et al66 performed an extensive literature review, identifying recommendations suggested by the literature, expert opinion, and national societies. Of 138 recommendations found, 35 recommendations were determined to be significant. They posit that these recommendations may serve as a tool for developing programs toward improving medication safety and assessing weaknesses within an institution.

Grigg et al67 prospectively assessed the impact of an anesthesia medication template on medication errors during anesthesia. This tool was created to systematically standardize and arrange workstations to assist in choosing the appropriate and intended medication. This novel system of syringe selection is aided by the physical characteristics of the syringe (shape, size, color) and its location on the template. The hypothesis was that this template would decrease both inaccurate drug administration and save time in finding the sought-after syringe. After implementation, the mean monthly drug errors reaching patients decreased from 1.24 to 0.65 per 1000 anesthetics. The greatest decreases in the incidence of error were those targeted specifically by using the anesthesia medication template system: a decrease from 0.97 to 0.35 errors per 1000 anesthetics. Surprisingly, the rate of drug errors resulting in patient harm did not change with the use of the template, although only 10 serious safety events were reported.

In 2018, Grigg and Roesler16 identified numerous weaknesses in the present culture that makes tackling the anesthesia medication error problem so difficult. The true number of medication errors in the OR is hampered by retrospective self-reporting; most errors go unreported or unnoticed. There is an entrenched cultural resistance to standardization of medication handling and arranging medications in the individual anesthesia workspace. They identified dangerous myths in our specialty including the following: “(1) removing colors from labels will force providers to read labels more carefully, (2) hand-written labels are reliable in high-stress environments, and (3) prefilled syringes have questionable safety benefits.” Currently, there are no alarms for bolus medications, which limits error detection. Nothing prevents a provider from attaching a potentially lethal dose of local anesthetic intended for an epidural catheter to an IV line or administering a lethal dose of any drug through IV.

Although high-quality evidence is limited in terms of effective strategies to prevent medication errors, international anesthesia societies have promulgated specific recommendations for safe medication practice.68–70 In its 2018 Year in Review, ISMP states that “for medication error-prevention efforts to be effective, they must be a priority.”71 ISMP has identified safety issues that are readily applicable to the practice of anesthesia. Color-coded injectables by drug class can be dangerous; thus, vials containing drugs in the same class should not be stored next to each other, distinguishing labels to differentiate drugs should be used, and color-coding by drug class is not recommended for commercial vial caps and labels. ASHP is leading an FDA-funded “Standardize 4 Safety” program to develop and implement national standardized concentrations for continuous IV medications as an error-reducing strategy, especially during vulnerable periods, such as when transferring patients between patient care areas within and between hospitals.24,72

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Conclusions

There is substantial potential for reducing medication-related harm, and there are many opportunities to improve safety in the perioperative setting. Anesthesiologists are the reason why patients can undergo surgery safety while receiving dozens of drugs. Widespread efforts are needed to rethink the design of medication administration workflow and support implementing specific actions to prevent adverse medication safety in the perioperative setting. That we are talking about it so openly now, we would argue, is a strength of the field and the leadership of anesthesiology in implementing the patient safety agenda.

However, little prevents anesthetists from making simple and harmful medication errors. There are few checks and balances, at odds with all other high-risk industries where safety records are multiple-fold better than medication safety in anesthesia. We believe that, despite all we know about preventing harm because of medication errors, their persistence may be related to 3 important drivers. First, most medication errors are near misses; that is, there is no patient harm and thus may not be considered important to report or prevent. Second, the anesthetist who makes an error must realize that he or she made the error and third, he or she must report the error. Observational studies have consistently shown that physicians under-report the majority of their medication errors.

The pursuit of applied human factors and appreciating how they can encourage or mitigate harm, while implementing systematic changes, rather than focusing on individual personnel failures is vital to reducing medication adverse events. Truth telling and data transparency in terms of the prevalence and causes of medical errors and medication adverse events are essential if trust is to be enabled, leading to a culture of safety.

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