3-9, 2013 is Patient Safety Awareness Week
The National Patient Safety Foundation is sponsoring Patient Safety Awareness Week March 3-9, 2013. Visit the NPSF website for tools to use at your organization to promote patient safety awareness.
Our What’s New in the Patient Safety World column for September 2012 “FDA Warning on Codeine Use in Children Following Tonsillectomy” described cases of death and serious adverse effects in children treated with codeine following adenotonsillectomy for obstructive sleep apnea. Those cases led to the FDA issuing a safety alert (FDA 2012).
The FDA has now identified additional cases and announced that it will be requiring a black box warning for products containing codeine (FDA 2013). The announcement states “A new Boxed Warning, FDA’s strongest warning, will be added to the drug label of codeine-containing products about the risk of codeine in post-operative pain management in children following tonsillectomy and/or adenoidectomy. A Contraindication, which is a formal means for FDA to make a strong recommendation against use of a drug in certain patients, will be added to restrict codeine from being used in this setting. The Warnings/Precautions, Pediatric Use, and Patient Counseling Information sections of the drug label will also be updated.”
The original FDA alert was issued after reviewing reports in the literature of 3 deaths and one near-miss case of respiratory depression in young children (ages 2-5) following tonsillectomy and/or adenoidectomy for obstructive sleep apnea (Ciszkowski 2009, Kelly 2012). The most interesting facet is the data presented on unusual metabolism of codeine as a root cause. Ingested codeine is converted into morphine in the liver by cytochrome P450 2D6 (CYP2D6). It turns out there are genetic variations that cause some people to be “ultra-rapid metabolizers” which leads to higher concentrations of morphine earlier. Apparently all the children in the above reports were “ultra-rapid metabolizers”.
The FDA identified 13 cases from its Adverse Event Reporting System (AERS) database between 1969 and 2012, seven of which had been reported in the literature. Eleven of the 13 had tonsillectomy/adenoidectomy (n=8) or respiratory infection (n=3). In most cases the prescribed dose of codeine was not considered to be unusual. However, in most cases it was suspected the children were either “ultra-rapid metabolizers” or “extensive metabolizers”. And from a survey conducted by the American Academy of Otolaryngology-Head and Neck Surgery they identified 2 further deaths following adenotonsillectomy, both of whom were suspected to be “ultra-rapid metabolizers”.
The new information for patients/families and healthcare providers states that codeine should not be used in children following tonsillectomy/adenoidectomy. But it also states that it should be used with caution for other types of pain in children. It emphasizes that when codeine is required it should never be used in children on a scheduled basis but rather only when the child requires the drug. When used, it should be in the lowest effective dose for the minimum amount of time needed. The information also warns parents to call 911 if their child displays unusual sleepiness, confusion, or difficult or noisy breathing since these may be signs of a narcotic overdose.
The original FDA alert (FDA 2012) estimates the number of “ultra-rapid metabolizers” as generally 1 to 7 per 100 people, but may be as high as 28 per 100 people in some ethnic groups (the FDA site has a table of these rates by ethnic group).
FDA. FDA Drug Safety Communication: Codeine use in certain children after tonsillectomy and/or adenoidectomy may lead to rare, but life-threatening adverse events or death. 8/15/12
FDA. FDA Drug Safety Communication: Safety review update of codeine use in children; new Boxed Warning and Contraindication on use after tonsillectomy and/or adenoidectomy. Update February 20, 2013
Ciszkowski C, Madadi P, Phillips MS, Lauwers AE, Koren G. Codeine, ultrarapid-metabolism genotype, and postoperative death. N Engl J Med 2009; 361(8): 827-828
Kelly LE, Rieder M, van den Anker J, Malkin B, Ross C, Neely MN, et al. More codeine fatalities after tonsillectomy in North American children. Pediatrics 2012; 129:5 e1343-e1347; published ahead of print April 9, 2012
One of the diagnostic errors we’ve talked about most frequently is the missed diagnosis due to failure to follow up on test results. But is that the most frequent type of error seen in primary care? If the source of statistics about diagnostic error is primarily malpractice claims and settlements it might be the most frequent type of error. But such data sources may be somewhat misleading. In fact, a new study (Singh 2013) suggests it is not the most common diagnostic error in primary care.
Singh and colleagues have just published a remarkable study on diagnostic errors in primary care that is very enlightening. They used a trigger tool methodology (See our Patient Safety Tips of the Week for October 30, 2007 “Using IHI's Global Trigger Tool” and April 15, 2008 “Computerizing Trigger Tools” and our What’s New in the Patient Safety World columns for January 2011 “No Improvement in Patient Safety: Why Not?” and May 2011 “Just How Frequent Are Hospital Medical Errors?” on using the trigger tool methodology). The triggers they used to identify cases for manual review were: (1) a primary care index visit followed within 14 days by an unplanned hospital admission and (2) a primary care index visit followed within 14 days by one or more primary care visits, emergency department visits or urgent care visits. Cases identified by these triggers were then manually reviewed by trained experienced clinical reviewers for the occurrence of diagnostic errors. They found diagnostic errors in 20.9% of cases identified by the first trigger and 5.4% identified by the second trigger, compared to 2.1% in control cases.
They found that patients involved in cases with diagnostic errors were slightly older (66.5 years on average compared to 62.7 years). That should not be particularly surprising. We know that, in general, medical errors tend to occur more often in older patients probably as a result of a number of factors, including more comorbidities, more medications, and other variables.
The diagnoses that were “missed” were not “zebras” or relatively uncommon or complex diagnoses but rather very common diagnoses and conditions (eg. pneumonia, decompensated CHF, acute renal failure, cancer, UTI, etc.). That is similar to results of another study on diagnostic errors in primary care (Ely 2012) that we discussed in our May 15, 2012 Patient Safety Tip of the Week “Diagnostic Error Chapter 3”. The nature of the presenting symptoms was not particularly remarkable with the exception that a significant number of patients did not have a specific presenting complaint (eg. those presenting for followup of their chronic conditions or those having a first visit to establish ongoing care).
While breakdowns were seen in all dimensions of the diagnostic process (and often involved more than one dimension) breakdowns most often occurred during the patient-practitioner clinical encounter and most often involved cognitive errors in data-gathering or synthesis. These included items related to medical history, physical exam, ordering diagnostic tests or failure to review prior documentation. Interestingly, there was no documentation of differential diagnosis in over 80% of cases with diagnostic errors. And another unintended consequence of technology: they found that copying and pasting previous progress notes was frequently associated with errors.
They also did find errors related to referrals, failure to follow up on diagnostic tests and interpretation of diagnostic tests.
The authors note that their methodology, specifically the short time frame for the trigger tools, likely biased the resulting types of errors toward more acute conditions rather than more chronic conditions. Nevertheless, the study really shows that diagnostic errors are very common in primary care visits and occur across the broad spectrum of conditions seen in primary care practices.
The accompanying editorial by Newman-Toker and Makary (Newman-Toker 2013) uses the statistics from the Singh study plus those from autopsy-related studies on diagnostic errors to suggest that more than 150,000 patients per year in the US might have suffered misdiagnosis-related harm.
Singh and colleagues make several salient points about interventions to prevent diagnostic errors. First, given the wide variety of conditions and presenting symptoms they found in their study it is very unlikely that focusing solely on specific presentations will be successful in reducing overall errors. They note that most of the breakdowns occurred in the clinical encounter, perhaps with time pressures and short encounters contributing to inadequate decision making. Further yet they note that the trend toward team care and the patient-centered medical home may not result in the level of cognitive support needed for complex decision making. And the current levels of technological decision support for diagnosis are not readily available in most of today’s electronic medical records.
This is a really good study that highlights both the frequency and breadth of the problem of diagnostic error in primary care. It clearly points out how much needs to be done going forward.
See our many prior Patient Safety Tips of the Week on diagnostic error:
· September 28, 2010 “Diagnostic Error”
· November 29, 2011 “More on Diagnostic Error”
· May 15, 2012 “Diagnostic Error Chapter 3”
· May 29, 2008 “If You Do RCA’s or Design Healthcare Processes…Read Gary Klein’s Work”)
· August 12, 2008 “Jerome Groopman’s “How Doctors Think”)
· August 10, 2010 “ ”
· January 24, 2012 “Patient Safety in Ambulatory Care”
· October 9, 2012 “Call for Focus on Diagnostic Errors”
Singh H, Giardina TD, Meyer AND, et al. Types and Origins of Diagnostic Errors in Primary Care Settings. JAMA Intern Med 2013; published online February 25, 2013
Ely JW, Kaldjian LC, D’Alessandro DM. Diagnostic Errors in Primary Care: Lessons Learned. J Am Board Fam Med 2012; 25: 87–97
Newman-Toker DE, Makary MA. Measuring Diagnostic Errors in Primary Care. Comment on “Types and Origins of Diagnostic Errors in Primary Care Settings”. JAMA Intern Med 2013; published online February 25, 2013
We’ve tried for years, with varying degrees of success, to get physicians to use sedative/hypnotic drugs less frequently in hospitalized patients. We’ve long recommended that routine “prn” orders for such not be included on standard order sets (see our August 2009 What’s New in the Patient Safety World column “Bold Experiment: Hospitals Saying No to Sleep Meds”). ISMP has echoed that approach (see our March 23, 2010 Patient Safety Tip of the Week “ISMP Guidelines for Standard Order Sets”). In our May 2012 What’s New in the Patient Safety World column “Safety of Hypnotic Drugs” we discussed many of the safety issues related to sedative/hypnotic drugs. They frequently are contributing factors to patient falls, delirium, and opioid-related respiratory depression. Sometimes we’ll see withdrawal syndromes in patients who have been receiving such drugs chronically. They may also play a role in predisposing some patients to aspiration. And they are a frequent contributor to events occurring in patients with sleep apnea. They appear on Beers’ List or other lists of drugs potentially contraindicated in the elderly. In 2 columns (May 2012 “Safety of Hypnotic Drugs” and November 2012 “More on Safety of Sleep Meds”) we we also discussed the possible link between such drugs and mortality. In the latter column we also noted a study linking hypnotic use with hip fractures in nursing home patients (Berry 2012). This study found that nursing home residents taking the newer non-benzodiazepine hypnotics were 70% more likely to suffer hip fractures.
Of the sedative/hypnotic agents, zolpidem is the most widely prescribed in the US. Now a new study shows that zolpidem is associated with over a 4-fold increased risk of falls in inpatients (Kolla 2013). They looked at fall rates in a large database of inpatients and were able to compare patients who received zolpidem with those in whom zolpidem had been prescribed but not administered and those in whom it had not been prescribed. They found that zolpidem use had an odds ratio of 4.37 for being associated with falls in inpatients, a finding that held up strongly even after adjustment for a whole host of other clinical and demographic variables. The number needed to harm (NNH) was calculated to be 55 and the risk appeared to be beyond that attributable to other medications.
Also in January 2013 zolpidem was the subject of an FDA drug safety communication (FDA 2013). That communication recommended lower doses of certain drugs containing zolpidem because of the potential increased risk of next-morning impairment for activities requiring mental alertness, such as driving. Though women may be more at risk than men the FDA recommended lower doses in both women and men. They recommended the dose of zolpidem be lowered from 10 mg to 5 mg for immediate release products (Ambien, Edluar, and Zolpimist) and from 12.5 mg to 6.25 mg for extended-release products (Ambien-CR). Note that there was no dose change recommendation for Intermezzo, the lower dose zolpidem approved in November 2011 for middle-of-the-night awakenings. The label for that drug already included a recommended lower dose for women. That safety communication includes both the safety data leading to the new recommendations plus multiple practical recommendations for both patients and healthcare providers regarding use of zolpidem products.
Prescribing sleep meds, whether for inpatients or outpatients, is often done without much thought. All too often they are thought of as being relatively harmless. Knowing the downside is an important first step. But putting in place various system fixes (eg. removing them from standardized order sets, using clinical decision support tools, etc.) may play a more important role.
Berry S, et al "Risk of hip fracture associated with non-benzodiazepine hypnotics in subgroups of nursing home residents" American Society for Bone and Mineral Research ASBMR 2012; Abstract 1056 as reported by Walsh N. Hip Fractures High with Newer Sleeping Pills. MedPage Today 2012; October 15, 2012
Kolla BP, Lovely JK, Mansukhani MP, Morgenthaler TI. Zolpidem Is Independently Associated With Increased Risk of Inpatient Falls. Journal of Hospital Medicine 2013; 8(1): 1-6
FDA. FDA Drug Safety Communication: Risk of next-morning impairment after use of insomnia drugs; FDA requires lower recommended doses for certain drugs containing zolpidem (Ambien, Ambien CR, Edluar, and Zolpimist). January 10, 2013
Wanna see something scary? Try googling “fentanyl accidents”. You’ll never order fentanyl again! When you search on that term you get page after page after page of websites for malpractice lawyers. Most of them deal with fentanyl patches and motor vehicle accidents. But a variety of other adverse events related to fentanyl pop up, too.
We have actually written about adverse events related to fentanyl on multiple occasions. In fact, when we searched our own website we were surprised to see how often we had written about such events (see the list below). But most of those were also fentanyl patches and long-acting formulations of fentanyl.
But the short-acting formulations of fentanyl are not without risk either. A recent Pennsylvania Patient Safety Advisory (Aseeri 2012) discussed multiple risks associated with IV fentanyl. Because it has a short onset of action and relatively short duration of action, fentanyl has become a preferred analgesic for procedures where a short recovery time is expected. The PPSA advisory identified over 2000 events involving IV fentanyl reported over an 8-year period. Three quarters of the events reached the patient, a third resulted in the need for increased monitoring of patients, and 3.2% of the events resulted in patient harm. Events were distributed across a wide variety of hospital units (ICU’s, pediatric ICU’s, med/surg units, ob/gyn areas, PACU’s, etc.). Wrong dose or overdose was the most common reported event, often attributable to pump programming errors. In other cases errors were related to size of vials or ampules or available concentrations. Mixups between dosage units (mg vs. mcg) were also common. Parenteral fentanyl is 80-100 times more potent than morphine for opioid-naïve patients. Hence the dose is usually prescribed in mcg rather than mg. Wrong drug events also were reported. While we typically use tall-man lettering for fentaNYL to differentiate it from SUFentail the wrong drug events usually involved other drugs. Those confused most often were HYDROmorphone, morphine, midazolam, and combined fentaNYL/bupivacaine. Often the wrong drug errors came from retrieving drugs from automated dispensing cabinets or involved mixups with fentanyl epidural preparations. Other events included respiratory depression and changes in mental status. Particularly when fentanyl is used in conjunction with other sedating agents as part of moderate sedation for procedures the risk of respiratory depression increases.
The PPSA article has multiple suggestions for interventions to reduce the risks of events related to fentanyl. Under constraints, first and foremost is consideration to limiting use of fentanyl in PCA pumps to pain services or providers specifically credentialed and privileged to prescribe it. Where it is used in PCA there should be standardized order sets. They recommend that stores of fentanyl be restricted to areas where it is absolutely needed. Each medication should be stored in a separate lock-lidded bin in the ADC and in the pharmacy drugs in prefilled syringes or vials need to be segregated. They have good recommendations on standardizing, both in pain management protocols and standardized order sets. To avoid confusion with epidural preparations containing fentanyl they recommend clearly identified labels with warnings such as “For Epidural Use Only” and using yellow-lined tubing without injection ports for epidural infusions (and obviously don’t use yellow-lined tubing for anything else). Use of independent double checks by nursing before administration is recommended (including requiring a witness when fentanyl is removed from ADC’s). In addition to the above mentioned practice of privileging providers for prescribing fentanyl, they recommend educational and inservicing programs for staff, annual competency evaluations, and safety bulletins via newsletters and other vehicles.
The PPSA article is very timely and has very practical useful information that all healthcare organizations can use.
Some of our other Patient Safety Tips of the Week regarding fentanyl:
· April 2010 “RCA: Epidural Solution Infused Intravenously”
· July 13, 2010 “Postoperative Opioid-Induced Respiraatory Depression”
· January 18, 2011 “More on Medication Errors in Long Term Care”
· April 12, 2011 “Medication Issues in the Ambulatory Setting”
· June 28, 2011 “Long-Acting and Extended-Release Opioid Dangers”
· September 13, 2011 “Do You Use Fentanyl Transdermal Patches Safely?”
· November 8, 2011 “WHO’s Multi-Professional Patient Safety Curriculum Guide”
· May 2012 “Another Fentanyl Patch Warning from FDA”
· July 24, 2012 “FDA and Extended-Release/Long-Acting Opioids”
· September 2012 “Joint Commission Sentinel Event Alert on Opioids”
Aseeri M, Grissinger M. Analysis of the Multiple Risks Involving the Use of IV FentaNYL. Pa Patient Saf Advis 2012; 9(4): 122-129