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February 24, 2015
More Risks with Long-Acting Opioids
For quite some time now we have highlighted the dangers of long-acting and/or extended-release opioids (see our Patient Safety Tips of the Week for June 28, 2011 “Long-Acting and Extended-Release Opioid Dangers” and July 24, 2012 “FDA and Extended-Release/Long-Acting Opioids”). Unintentional overdoses with prescription opioids have escalated over the past two decades as prescriptions for all types of opioids have increased. Undoubtedly the development and marketing of multiple opioid preparations has contributed to the increase in prescribing of opioids.
A 2013 CDC report (CDC 2013) showed that fatal overdoses of prescription opioids more than quadrupled between 1999 and 2010 and now exceed fatal overdoses of illicit drugs like heroin and cocaine.
Now a new study further emphasizes the dangers of long-acting opioids in producing unintentional overdoses. Miller and colleagues (Miller 2015) analyzed clinical and pharmacy data from a large VA population over a 10-year period. They identified those patients with non-cancer chronic pain who were newly begun on opioids (having received no opioids for at least the preceding 6 months) and created a propensity-matched cohort for comparison. After adjustment for multiple variables, those patients on long-acting opioids were more than twice as likely to suffer an unintentional overdose than those taking short-acting opioids (hazard ratio 2.33). The risk was especially high during the first two weeks of therapy, where those taking long-acting opioids were more than 5 times more likely to suffer an unintentional overdose. After the first two weeks the risk for unintentional overdose remained twice as high in the group on long-acting opioids. These findings also likely represent an underestimate of the actual occurrence of unintentional overdose.
Opioids in the long-acting group included sustained-release oral morphine sulfate, methadone hydrochloride, controlled-release oxycodone hydrochloride, levorphanol tartrate, and fentanyl patches (they excluded liquid methadone hydrochloride because that is typically used in the VA system for treating opioid addiction).
Though the study had limitations (retrospective design, use of claims database, predominantly male veteran population, inability to exclude unidentified confounders) it nevertheless drives home several important points.
First and foremost is that these long-acting and extended-release opioid formulations are not intended for use as first-line agents in opioid-naïve patients. The newer opiate formulations are either more potent or designed to produce a longer peak action, two characteristics that lead to some of the greatest dangers that have been popping up. We are referring to the long-acting and extended-release forms of opiates. These have been designed to be used in patients who are opioid-tolerant and have pain of a chronic nature that has not been controlled with more conventional opiates. They were not intended to be used for treatment of acute pain nor to be used as first line agents in patients with pain. But in practice they are often being (mis)used in that way.
A second significant factor related to the association between long-acting opioids and overdoses is dosage. The amount of morphine equivalents in these preparations is higher than that found in most short-acting formulations and many prescribers are not appreciative of this. Of course, the issue of dose is not unique to the long-acting opioids. We’ve highlighted the same problem with HYDROmorphone in our September 21, 2010 Patient Safety Tip of the Week “Dilaudid Dangers” and the other columns on HYDROmorphone safety issues listed below. It is also problematic that when switching from short-acting opioids to long-acting or extended-release opioids it is very common to see misunderstandings of the relative potencies of the various opiate preparations.
A third important factor is use of concomitant medications. In the Miller study those patients in the long-acting group were more likely to be also taking benzodiazepines and antidepressants. The increased risk for the long-acting group held up even after adjustments for such variables. However, multiple studies have shown that opioid overdoses, particularly fatal ones, often involve drugs in addition to the opioids. A study of fatal overdoses (Jones 2013) showed many cases had concomitant use of benzodiazepines, antidepressants, antiepileptic agents, antiparkinsonism agents, and antipsychotic or neuroleptic medications. Conversely, fatal overdoses primarily due to these other medications also commonly involved opioids.
Note that long-acting opioid formulations are also now frequent causes of accidental overdoses, including those for whom they were not prescribed such as children and pets (see our September 13, 2011 Patient Safety Tip of the Week “Do You Use Fentanyl Transdermal Patches Safely?” and our May 2012 What’s New in the Patient Safety World column “Another Fentanyl Patch Warning from FDA”).
CPOE (computerized physician order entry) and electronic prescribing probably have the greatest potential to reduce the inappropriate prescribing of long-acting or extended-release opioids. Alerts during CPOE can help prevent their use in opioid-naïve patients and ensure there is a legitimate indication for use of such agents. Similarly, clinical decision support tools during CPOE can help physicians better understand the dosing equivalency issues for each opioid formulation. But we also need to be aware that we do not unintentionally encourage use of such drugs during CPOE. We have seen standardized order sets that have included these formulations as options for pain management for some conditions.
Linking electronic prescribing to prescription databases maintained by state health departments also has great potential to prevent overdoses related to prescription opioids. A study done in Tennessee identified significant risk factors for opioid-related overdose deaths (Gwira Baumblatt 2014). Those risk factors included receiving opioid prescriptions from 4 or more providers, using 4 or more pharmacies, and having a total dose of more than 100 morphine milligram equivalents per day. The authors estimate that about half of the patients could have been identified using these criteria before their deaths.
Our October 2013 What’s New in the Patient Safety World column “Opioid Safety Actions and Resources” provided links to some valuable resources from the FDA, ISMP Canada, SAMHSA, and some state health department resources to help prevent prescription opioid overdoses. The SAMHSA Opioid Overdose Prevention Toolkit includes not only recommendations for physicians regarding opioid prescribing and management but also resources for patients and families, first responders, and community members. It even has resources for survivors of opioid overdose and family members. It has good discussions about recognizing signs and symptoms of opioid overdose and treating overdoses. It also discusses consideration of prescribing a naloxone kit (for emergency treatment of overdose) at the time the opioid prescription is made.
You are probably aware that many communities have begun providing education and naloxone kits to emergency response personnel (eg. police). An observational study in Massachusetts showed that death rates from opioid overdose were reduced in communities where overdose education and naloxone distribution was implemented compared with not implemented (Walley 2013).
The decision to prescribe opioids should not be made without careful consideration of potential risks and benefits and individual patient circumstances. The decision to prescribe long-acting or extended-release opioids requires consideration of even more detailed factors and should not be undertaken lightly.
Our prior articles pertaining to long-acting and/or extended release preparations of opioids:
Our prior columns on patient safety issues related to Dilaudid/HYDROmorphone:
CDC. Addressing prescription drug abuse in the United States: current activities and future opportunities. Atlanta: Centers for Disease Control and Prevention, 2013
Miller M, Barber CW, Leatherman S, et al. Prescription Opioid Duration of Action and the Risk of Unintentional Overdose Among Patients Receiving Opioid Therapy. JAMA Intern Med 2015; Published online February 16, 2015
Jones CM, Mack KA, Paulozzi LJ. Pharmaceutical overdose deaths, United States, 2010. JAMA 2013; 309: 657-659
Gwira Baumblatt JA, Wiedeman C, Dunn JR, et al. High-risk use by patients prescribed opioids for pain and its role in overdose deaths. JAMA Intern Med 2014; 174(5): 796-801
SAMHSA (Substance Abuse & Mental Health Services Administration).
Opioid Overdose Prevention Toolkit. Updated 2014
Walley AY, Xuan Z, Hackman HH, et al. Opioid overdose rates and implementation of overdose education and nasal naloxone distribution in Massachusetts: interrupted time series analysis. BMJ 2013; 346 doi: http://dx.doi.org/10.1136/bmj.f174 (Published 31 January 2013)
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March 8-14, 2015 is Patient Safety Awareness Week
The National Patient Safety Foundation is sponsoring Patient Safety Awareness Week March 8-14, 2015. Visit the NPSF website for tools to use at your organization to promote patient safety awareness.
We’re always amazed at the varied circumstances in which hospitalized patients may suffer iatrogenic burns. While we’ve mentioned heat from light sources such as fiberoptic light as a potential heat source for OR fires (see our December 4, 2007 Patient Safety Tip of the Week “Surgical Fires”), we have not discussed light sources in other iatrogenic burns.
Now halogen lights have been identified as the cause for burns of multiple patients in operating rooms at an Oregon hospital (Wozniacka 2015). The report says that about 10 patients, possibly more, suffered burns over a period of several months. The hospital director of quality and risk services was quoted as saying the hospital initially “looked at more common culprits: solutions used to prep skin before surgery, bandages or dressings used after surgery, and cautery devices used to stop bleeding during surgery”. It was only later that a surgery team member recalled maintenance had been done on the OR lights. Apparently halogen lamps require filters for UV light and those were not changed at the time of maintenance. Subsequently, the hospital has switched to light-emitting diodes (LED’s) and it has changed procedures for medical equipment maintenance, requiring the engineering department or the equipment's vendor to do any kind of maintenance.
Sometimes causes for unusual events are not readily apparent. But it sure helps to disseminate such lessons so another facility won’t need months to solve the problem.
Our prior columns on iatrogenic burns:
Wozniacka G. The Associated Press. Oregon hospital patients burned by lights in operating rooms. CTV News. Published Thursday, January 22, 2015
Our readers might get the erroneous impression that we are not advocates of CPOE from reading our many columns outlining some of the untoward consequences and other problems with CPOE and healthcare IT in general. Nothing could be further from the truth. We remain huge supporters of CPOE and clinical decision support and IT applications in healthcare. However, once again, we find ourselves commenting on yet another example of problematic CPOE.
In the new study, researchers culled the MEDMARX database for medication errors which included some indication that CPOE may have played a role (Schiff 2015). They then developed a taxonomy and coding for the types of errors, why they occurred, and what preventive strategies might be employed. From their list they then developed multiple scenarios and tested on a representative sample of CPOE systems at multiple facilities whether these error-prone scenarios might pass through.
From over 1 million reports available in MEDMARX they found 6.1% reported as CPOE-related. The reviewers actually found only about half of these were truly CPOE-related. The taxonomy was then developed on a sample of these reports and 21 scenarios were developed for vulnerability testing on representative systems.
Overall, 79.5% of the erroneous order scenarios were able to be placed (28% “easily” placed with no additional steps or warnings and 28.3% placed with only “minor workarounds”). Specific computer-generated warnings occurred for 26.6% of the erroneous orders but the vast majority of these (69%) were passive alerts and another 29% required workarounds that could be done. Interestingly, they encountered one system in which no alerts were triggered at all. It was found that alerts in that system had been turned off several months earlier during an upgrade and were never turned back on!
This process, of course, is quite similar in concept to that developed and used by The Leapfrog Group to simulate problematic medication orders (see our previous columns for July 27, 2010 “EMR’s Still Have a Long Way to Go” and June 2012 “Leapfrog CPOE Simulation: Improvement But Still Shortfalls”). That tool was to be used by hospitals to assess the vulnerabilities of their CPOE systems to medication errors. Voluntary testing at over 200 hospitals (Leapfrog 2010) then revealed that about half of errors on “routine” medication orders were missed and almost a third of potentially fatal medication errors were also missed. Those hospitals adjusted their CPOE systems and protocols and nearly all showed improvement when retested. A similar test was conducted in 2011 by over 250 hospitals (Leapfrog 2012). The rate of missed potentially fatal errors dropped to just over 1% but the rate of missed “routine” medication errors was still on average about one third.
Tools like these to identify potential vulnerabilities are really needed to help prevent such errors from occurring elsewhere. Just like the problems we identify in our RCA’s and other case reviews, issues that occur at one facility or organization are likely to also occur at others. It is only through sharing experiences and lessons learned that we are likely to make progress in reducing errors and their consequences.
This is good work. Schiff and colleagues are to be commended for this considerable undertaking.
See some of our other Patient Safety Tip of the Week columns dealing with unintended consequences of technology and other healthcare IT issues:
Schiff GD, Amato MG, Eguale T, et al. Computerised physician order entry-related medication errors: analysis of reported errors and vulnerability testing of current systems. BMJ Qual Saf 2015; Published Online First 16 January 2015
The Leapfrog Group. Leapfrog Group Report on CPOE Evaluation Tool Results
June 2008 to January 2010. June 2010
The Leapfrog Group. Lack of Testing and Monitoring of Health IT by Hospitals and Vendors Potentially Jeopardizes Patients -- Hospital Performance Is Improving, but More Must Be Done. PR Newswire April 27, 2012
We all know that sometimes our patient safety interventions may have unintended consequences. In fact, sometimes they may paradoxically worsen the condition for which we implemented them. For example, in our What’s New in the Patient Safety World columns for June 2010 “Seeing Clearly a Common Sense Intervention” and June 2014 “New Glasses and Fall Risk” we noted that sometimes new glasses may paradoxically result in increased falls even though impaired vision is a risk factor for falls.
Now another paradox has been reported: devices designed to aid walking may produce an increase in falls! Researchers looked at 43 elderly patients living in residential aged care facilities and compared 22 patients who used walking aids (predominantly walkers) to 21 who did not use walking aids (Roman de Mettelinge 2015). Those who used them were slightly older, more likely to report fear of falling, and more likely to be taking psychotropic medications. They also fell more frequently. 68% of those using walking aids had at least one fall during the one year of followup, compared to 35% for those not using walking aids. Those using a walking aid demonstrated a significantly different gait pattern than those not using them. They walked slower and took shorter steps, greater step times, and fewer steps per minute.
We need to be careful in interpreting the results of this study. It does show an association between use of an assistive device for walking and future falls. However, the study was based upon a small population. More importantly, the association does not necessarily imply a cause-and-effect relationship, a point readily acknowledged by the authors. It is almost impossible to exclude selection bias in such studies (i.e. those patients using walking aids may have been doing so because they were already at greater risk of falls than those not using them). Indeed, the group using walking aids did have more risk factors for falls, such as more use of psychotropic medications.
Nevertheless, there are several factors that may make patients more prone to falls when using a walking aid. They note patients must have sufficient strength, balance, coordination, and attention to master the walking aid. And the environment comes into play as well. Stairs present a challenge to those walking with walkers. Also, the devices may put excessive strain on the patient’s upper limbs. And using such devices may inhibit compensatory grasping that a patient might use to prevent a fall. And incorrect posture while using the devices, particularly walkers, may result in both falls and injuries related to the falls.
Prior studies have had mixed results regarding use of walking aids and risk of falls. But a systematic review and meta-analysis (Deandrea 2013) found that walking aid use was one of the three strongest associations with falls in nursing home residents (the other two being history of falls and moderate disability). Walking aid use roughly doubled the risk of falls.
Several studies have shown high rates of injury with falls related to walking aids, particularly walkers. Stevens and colleagues (Stevens 2009) found an estimated 47,312 older adult fall injuries associated with walking aids were treated annually in U.S. ED’s (87.3% with walkers, 12.3% with canes, and 0.4% with both). Walkers were associated with seven times as many injuries as canes and women's injury rates exceeded those for men. The most prevalent injuries were fractures and contusions or abrasions. Approximately one-third of subjects were hospitalized for their injuries.
A study done in the Netherlands also showed that falls associated with use of four-wheeled walkers in adults 65 and older were at high risk for serious injury (van Riel 2014). The majority of injuries were fractures (60%) with hip fracture (25%) being the most common injury. Contusions and abrasions accounted for 23% of injuries. The lower extremity, including hip, leg and foot, was the most frequently injured body region. As a second most common injury, men injured their head and neck, whereas women more often injured their arm or hand. Nearly half of all four-wheeled walker related injuries required hospitalization, mostly due to hip fractures.
The importance of training the patients on how to correctly use the walking devices is obvious. Many patients first use their device when recovering from surgery or other hospital event and the training may be very brief and never reinforced following discharge.
Roman de Mettelinge T, Cambier D. Understanding the Relationship Between Walking Aids and Falls in Older Adults: A Prospective Cohort Study. Journal of Geriatric Physical Therapy 2015; Published Ahead-of_Print January 15, 2015
Deandrea S, Bravi F, Turati F, Lucenteforte E, La Vecchia C, Negri E. Risk factors for falls in older people in nursing homes and hospitals. A systematic review and meta-analysis. Arch Gerontol Geriatr 2013; 56 (3): 407-415
Stevens JA, Thomas K, Teh L, Greenspan AI. Unintentional fall injuries associated with walkers and canes in older adults treated in U.S. emergency departments. J Am Geriatr Soc 2009; 57(8): 1464-1469
van Riel KMM, Hartholt KA, Panneman MJM, Patka P, van Beeck EF, van der Cammen TJM. Four-wheeled walker related injuries in older adults in the Netherlands. Inj Prev 2014; 20(1): 11-15
Emergency Department visits related to medication issues are very common in adults. In our May 2011 What’s New in the Patient Safety World column “Adverse Drug Events and the ER” we cited a study from Vancouver (Hohl 2011) which found that 12.2% of patients presenting to the emergency room were there because of medication-related issues. Most were for unintended consequences of appropriately prescribed drugs. Compared to patients who did not have such reactions these patients had 50% higher rates of hospitalization, 20% higher outpatient encounters, and almost double the healthcare median monthly costs.
Now another Canadian study found an almost as many pediatric ED visits are due to medication-related issues. Zed and colleagues (Zed 2015) found that medication-related issues accounted for one in every 12 pediatric ED visits and that almost two-thirds of these were potentially preventable. Adverse drug reactions accounted for 26.4%, subtherapeutic dosage 19.0%, and nonadherence. Of these patients, 7.2% required hospitalization and medication-related issues contributed to prolonged lengths of stay.
The most commonly implicated drugs were anti-infective, respiratory, and nervous system agents.
Basically, the study highlights the fact that medication-related events lead to increased utilization of emergency department and inpatient resources not only in adults but in children as well.
Hohl CM, Nosyk B, Kuramoto L, et al. Outcomes of Emergency Department Patients Presenting With Adverse Drug Events. Ann Emerg Med 2011; online ahead of print February 28, 2011
Zed PJ, Black KJL, Fitzpatrick EA. Medication-Related Emergency Department Visits in Pediatrics: a Prospective Observational Study. Pediatrics 2015; Published online February 2, 2015
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