July 3, 2012
Recycling an Old Column: Dilaudid Dangers
We had planned to be on vacation this week and next week. But a safety bulletin just put out by ISMP Canada on HYDROmorphone (ISMP Canada 2012a) suggested to us that we might recycle one of our most popular previous columns (September 21, 2010 Patient Safety Tip of the Week “Dilaudid Dangers”).
ISMP Canada had done a nationwide survey on knowledge about a variety of things related to HYDROmorphone because that drug was one of the top 3 drugs reported to ISMP Canada as causing harm. Their analysis of those reports strongly suggested gaps in provider knowledge, particularly in relation to dose potency compared to morphine and other opioids.
There were almost 3500 respondents to the survey (nurses, pharmacists, and physicians). The findings are summarized in the ISMP Canada Safety Bulletin (ISMP Canada 2012a) and the full survey results with questions, actual responses, and correct answers also provides additional analysis (ISMP Canada 2012b). While 88% of respondents correctly identified the relative potency of HYDROmorphone compared to morphine, those responses may have been influenced by an associated webinar that presented such information. There were especially knowledge gaps on differences in potencies of HYDROmorphone in various preparations (eg. oral vs. parenteral vs. subcutaneous) and gaps regarding the various slow-release forms.
Some gaps in knowledge were also noted regarding the concepts of patients being either opioid-naive or opioid-tolerant.
The biggest gaps in knowledge about HYDROmorphone appeared to be related to the pharmacological aspects. In particular, knowledge appeared to be limited regarding the duration of action of the various forms of HYDROmorphone and their relationship to the duration of action of naloxone. That, of course, is relevant to the phenomenon of “renarcotization” in which the reversal effect of the narcotic antagonist disappears while there is still substantial opioid on board.
Also, there were gaps in knowledge regarding dosing of HYDROmorphone in patients with various comorbidities. Many respondents incorrectly thought that higher doses were needed in obese patients. Many also did not understand that lower doses should be used in patients with COPD, obstructive sleep apnea, the elderly, and those taking benzodiazepines.
They also identified knowledge gaps related to the HYDROmorphone medication use process, particularly related to the proper steps for verifying orders, doing dose calculations, and programming IV pumps.
ISMP Canada. Identifying Knowledge Deficits Related to HYDROmorphone. ISMP Canada Safety Bulletin 2012; 12(7): 1-4 June 27, 2012
ISMP Canada. Report to Health Canada. Hydromorphone Knowledge Assessment
Survey Results. April 2012
Also recall that the FDA recently recommended altered labeling for HYDROmorphone (see our November 2011 What’s New in the Patient Safety World column “FDA Changes on Dilaudid/HYDROmorphone”). The new labeling has some changes in format designed to bring to the attention of the prescriber some important aspects of using HYDROmorphone. But probably the two most important changes have to do with specific dosing issues:
1) The recommended intravenous starting dose is reduced to 0.2-1 mg (previously it was 1-2 mg)
2) A bolded warning notes that morphine and HYDROmorphone are not milligram-to-milligram conversion equivalents and they provide a conversion table for converting doses of other opioids to HYDROmorphone
So we hope you’ll read the 2 ISMP Canada documents. Take time to read all the questions and correct answers in the full survey document. We learned a lot from them. Then read our previous column:
September 21, 2010 Dilaudid Dangers
One of the topics we seem to keep returning to is respiratory depression due to intravenous opioids. Our most recent column was our July 13, 2010 Patient Safety Tip of the Week “Postoperative Opioid-Induced Respiratory Depression”, in which we highlighted the inherent difficulties in monitoring patients on intravenous opioids.
While all opioids may cause respiratory depression, we have always been surprised that Dilaudid (HYDROmorphone) seems to pop up as a cause in a disproportionate number of cases. We’re not the only ones! Some recent published reports seem to have come to that same conclusion. About a year ago The Doctors Company (Marcus 2009) published several cases from their claims database that highlighted some of the lessons learned in cases of Dilaudid-induced respiratory depression. And the Pennsylvania Patient Safety Authority (PPSA 2010) just highlighted issues with hydromorphone in their most recent Patient Safety Advisory.
But problems with Dilaudid are not new. ISMP Canada (ISMP Canada 2006) noted that Dilaudid ranked third on their list of drugs most frequently reported as causing harm. They found that 9.3% of all their reported cases of medications causing harm or death were attributed to Dilaudid.
The Doctors Company paper cites several cases of fatalities or serious neurological damage in patients where Dilaudid contributed to respiratory depression. They cite a number of reasons for this adverse consequence. First and foremost is the issue of improper dosage. Most physicians and nurses don’t realize how potent Dilaudid is on a mg to mg basis compared to morphine sulfate. While estimates of equipotency vary considerably in the literature, most now agree that 1 mg. of Dilaudid is probably the equivalent of 7 mg. of morphine. Chang and colleagues (Chang 2010) had noted several years ago that emergency room physicians and nurses who were hesitant to administer 7 to 10 mg. of morphine were not reluctant to administer 1 to 1.5 mg. of Dilaudid. They point out this is an illusion that less narcotic is being used with that Dilaudid dose.
Ironically, Dilaudid’s problems may be an unintended consequence of a patient safety initiative taken by most facilities. Demerol (meperidine) was removed from many formularies a number of years ago because a toxic metabolite was causing significant untoward effects. It was replaced in most cases by Dilaudid and most healthcare workers were much less familiar with Dilaudid.
The look-alike/sound-alike (LASA) issue obviously also pops up, in which hydromorphone and morphine are mixed up. In fact, this is said to be one of the most frequent drug pairs involved in LASA errors. Use of tall man lettering (HYDROmorphone) is advised but, frankly, many healthcare workers still mistakenly assume that HYDROmorphone is an equipotent form of morphine. An outstanding published RCA (root cause analysis) done by ISMP Canada on a fatal Dilaudid overdose highlighted not only the fact that hydromorphone sounds like morphine but at that time also came in packaging that looked similar to that for morphine. Note that even the tall man lettering standard for Dilaudid has been controversial. At one time hydromorPHONE was used. But in response to an ISMP survey done in 2007, the standard was changed to the currently used HYDROmorphone.
The recent Pennsylvania Patient Safety Advisory noted over 1600 reports of medication errors related to hydromorphone in a period of less than two years (PPSA 2010). Of these, 1.8% resulted in patient harm. They highlighted wrong dose errors, wrong drug errors, and monitoring errors and noted problems in the prescribing, dispensing and administration phases of medication safety. They offer numerous recommendations to improve safety when using hydromorphone.
In many of the cases in the Doctors Company paper the patients also received other agents (sedative/hypnotic drugs) capable of potentiating the respiratory depressant effects of Dilaudid. And beware when using supplemental oxygen in such patients. Not only does supplemental oxygen render pulse oximetry less reliable in detecting early respiratory depression but it may also contribute to depression of respiration in patients prone to hypercapnia (see our Patient Safety Tips of the Week for April 8, 2008 “Oxygen as a Medication”, June 10, 2008 “Monitoring the Postoperative COPD Patient”, and January 27, 2009 “Oxygen Therapy: Everything You Wanted to Know and More!”). In such patients who are at risk for hypercapnia, using lower oxygen saturation targets may be indicated.
The ISMP Canada study noted that mixups between hydromorphone and morphine were the most common “substitution errors” in their analysis. They especially noted that availability of higher-concentration vials of hydromorphone (10 mg/mL) seemed to increase the likelihood of confusion with morphine. And while they noted that unfamiliarity with appropriate dosages of hydromorphone were the most common reason for incorrect doses, they also cited poor communication of orders (eg. verbal, telephone or written), lack of a preceding “0” before decimal points, and cognitive lapses as contributing factors. Errors in programming infusion pumps were frequent causes of harm. And they noted that the monitoring protocols typically used are often inadequate in high risk patients. We will focus on that latter point later because the problems we have encountered with Dilaudid have occurred most frequently in such high risk patients (eg. those with morbid obesity and /or sleep apnea).
Double checks are often recommended when we are dealing with administration of high-risk medications. Even though we have emphasized that double checks are a relatively weak intervention (we know from all industries that the error rate when a supervisor checks someone else’s work may be 10% or higher), the literature supports a medication error reduction of about 30% when using a double check system (see our July 15, 2008 Patient Safety Tip of the Week “Publicly Released RCA’s: Everyone Learns from Them” for a description of independent double checks). Another nice article on independent double checks in preventing medication errors (ISMP Canada 2005) describes the independent double check process and calculates that independent double checks would reduce the error rate of a process having an error rate of 5% all the way down to 1 in 400.”). Also, for any high-risk medications you need to do truly independent double checks (see our March 30, 2010 Patient Safety Tip of the Week “
A large number of claims and settlements in anesthesiology cases involving postoperative care had respiratory depression secondary to opioid analgesics as a central issue (Bird 2001). Many of the reported cases have occurred in patients with known sleep apnea or with suspected sleep apnea and morbid obesity. Sleep apnea patients are vulnerable to the respiratory depressant effects of opioids and there often seems to be a disproportionate effect on respiration compared to depression of the level of arousal.
In a well-done FMEA on PCA therapy, Moss (Moss 2010) also highlighted some of the problems noted above. She noted that, as in most facilities, Dilaudid had replaced Demerol in the formularies but that most physicians and nurses and pharmacists had much less experience with Dilaudid than with Demerol. That group then made use of standardized order sets to help reduce the errors. A second key vulnerability point they identified was patient selection. Patients using PCA must have both cognitive and physical capabilities to operate the pumps. However, at-risk patients (for PCA using any opioid) are those at the extremes of age, those with COPD, end-stage renal disease, and especially obesity and sleep apnea. They emphasized the need for careful monitoring with pulse oximetry and capnography if PCA is to be used in such patients.
The Anesthesia Patient Safety Foundation (APSF) in 2006 held a workshop focusing on postoperative opioid therapy and respiratory depression (Weinger 2007). They emphasized the risk of respiratory depression occurs with patient controlled analgesia (PCA), neuraxial opioid anesthesia, and intermittent dosing of opioids. And their findings and recommendations obviously apply not to just postoperative settings but to any time such opioid therapy is being used. While they recognize that current fiscal realities and limitations of monitoring technologies might limit special monitoring to high risk patients, they readily point out that you cannot always identify high risk patients (eg. many OSA patients are undiagnosed) and that even young healthy patients may suffer respiratory depression from opioid therapy. Their recommendations therefore are for continuous monitoring of patients on such opioid therapy, using continuous pulse oximetry plus capnography or other advanced technologies. But they also emphasize the importance of having a system that leads to timely responses to changes detected by such monitoring systems so that a healthcare professional capable of appropriate management is summoned to the bedside rapidly.
In our experience, monitoring patients on intravenous opioids has been the most problematic area. Others have also noted that monitoring is critical to preventing patient harm. Studies looking at malpractice claims noted that over half of respiratory events in patients on central neuraxial narcotics and almost three-quarters of those on PCA were potentially preventable using better monitoring (Weinger 2007). All such patients need to be monitored both for efficacy of pain treatment and for dangerous side effects. As such, in addition to the typical visual analog scale pain measurement (1 to 10) patients should also have their level of arousal assessed by a validated tool such as the Richmond Agitation Sedation Scale (RASS) or equivalent. And, of course, they need their vital signs monitored, including continuous monitoring of oxygen saturation by pulse oximetry. Keep in mind that pulse oximetry may provide a false sense of security, particularly when patients are on supplemental oxygen. You can have significant hypercapnia when your saO2 is still in the normal range. For high risk patients we therefore also recommend capnography.
There are several caveats about monitoring. Most importantly, when you arouse a patient who is oversedated with opioids they may, in fact, appear to be breathing at a normal rate and be able to respond appropriately to questions. Therefore, observing the patient before you stimulate them is extremely important. Anecdotally, there are also many reports of patients having respiratory depression at times when their level of arousal appears to be reasonably normal. And respiratory rate is a notoriously poor predictor of opioid-induced respiratory depression. The respiratory rate may be normal despite significant hypoventilation. Also mentioned anecdotally (Weinger 2007) is that changes in patient status may take place very rapidly and not be detected by conventional monitoring techniques used in most settings today.
Just as important is having in place a system to ensure the monitoring actually takes place. While your nursing plans of care may include all the above elements in a pain management module, you’d be surprised at how often various elements are omitted. We therefore recommend that you use some sort of forcing function to ensure they are done. For example, you could program your bedside medication verification (barcoding) system to require input of the RASS before a opioid medication may be given. Or you could require the RASS score be entered into your automated dispensing cabinet (ADC) before a nurse can take the opioid out of the ADC. You should also periodically audit compliance with your pain management monitoring.
Then clearly tie your monitoring process to the administration of opioid doses. You need clearcut instructions on withholding doses or contacting the physician when the RASS score is above certain levels or when monitoring of vital signs or saO2 or capnography demonstrates abnormalities or trends. In our June 10, 2008 Patient Safety Tip of the Week “Monitoring the Postoperative COPD Patient” we noted a simple system used by our colleagues in the field of pain management. (Pasero and McCaffery 2002):
S = Sleep, easy to arouse (acceptable; no action necessary)
1 = Awake and alert (acceptable; no action necessary)
2 = Slightly drowsy, easily arousable (acceptable; no action necessary)
3 = Frequently drowsy, arousable, drifts off to sleep during conversation (unacceptable; decrease opioid dose by 25-50%, add an opioid-sparing analgesic, and monitor the patient’s level of sedation and respiratory status closely)
4 = Somnolent, minimal or no response to physical stimulation (unacceptable; stop opioid, consider administering naloxone)
The above stresses assessing the level of arousal before administering the next dose of the opioid. Addressing the level of arousal after a dose may be equally important. One hospital system (Marcus 2009) implemented a system of checking level of arousal 15-30 minutes after a Dilaudid dose.
Where your patients should be monitored is another issue you need to address. The dangers in the postoperative patient on the general medical floors compared to ICU’s have been stressed, noting that preventable cardiopulmonary arrests are 5 times more likely on general medical floors (Overdyk 2010). We recommend that at least for high-risk patients you consider monitoring them in an ICU setting.
We are also advocates of keeping a “cumulative dose” record readily available for opioids administered. Unfortunately, there is no evidence base available to guide how you use such cumulative dose records. However, the mere fact that such would pop up may be an alert that the patient might be at risk of excessive opioid use.
And you need in place protocols whereby nursing may administer narcotic antagonists such as naloxone without having to first call a physician. Keep in mind we have previously seen cases of acute narcotic withdrawal precipitated by administration of Narcan (see our February 26, 2007 Patient Safety Tip of the Week “Unintended Consequences”) but those have usually occurred in patients on long-standing narcotics and, on the whole, the risk of not administering Narcan typically outweighs the very small risk of precipitating withdrawal. Also keep in mind the risk of “renarcotization” that may occur when there are disparities between the half life of the opioid and the half life of naloxone (see our July 13, 2010 Patient Safety Tip of the Week “Postoperative Opioid-Induced Respiratory Depression”). That Tip of the Week also contains a discussion of the nuances of monitoring the patient on IV opioids.
Here are some strategies you should consider to reduce the risk of Dilaudid (and other opioid) adverse events:
And don’t forget these standard medication safety considerations:
We’ve done several other columns on postoperative respiratory depression related to opioid administration (see our Patient Safety Tips of the Week for June 10, 2008 “Monitoring the Postoperative COPD Patient”, May 12, 2009 “Errors With PCA Pumps”, and August 18, 2009 “ ”.).
Opioid analgesics have been very useful in the management of acute pain and postoperative pain and there has been a push in recent years to ensure adequate pain management in all hospitalized patients. Just be wary of the potential complications and be both vigilant for their occurrence and be prepared to deal appropriately with those complications that arise.
Opioids are one of your high-alert medications. How they are used and monitored in your facility is another excellent topic for a FMEA (failure mode and effects analysis).
Other Patient Safety Tips of the Week pertaining to opioid-induced respiratory depression and PCA safety:
Marcus H. Dilaudid-Related Morbidity and Mortality from Respiratory Depression. The Doctors Company. The Doctor’s Advocate. Third Quarter 2009.
Pennsylvania Patient Safety Authority. Adverse Drug Events with HYDROmorphone: How Preventable are They? Pa Patient Saf Advis 2010 Sep;7(3):69-75
ISMP Canada. Shared Learning – Reported Incidents Involving Hydromorphone. ISMP Canada Safety Bulletin. December 28, 2006
Chang AK, Bijur PE, Meyer RH, et al. Safety and Efficacy of Hydromorphone as an Analgesic Alternative to Morphine in Acute Pain: A Randomized Clinical Trial.
Ann Emerg Med 2006; 48: 164-172
ISMP Canada. Event Analysis Report: Hydromorphone/Morphine Event - Red Deer Regional Hospital. Red Deer, Alberta. 2004
ISMP Canada. Lowering the Risk of Medication Errors: Independent Double Checks. ISMP Canada Safety Bulletin. January 2005
Bird M : Acute Pain Management: A New Area of Liability for Anesthesiologist. ASA
Newsletter 71(8), 2007
Moss J. Reducing Errors During Patient-Controlled Analgesia
Therapy Through Failure Mode and Effects Analysis. The Joint Commission Journal
on Quality and Patient Safety 2010; 36(8): 359-364
Weinger MB. Dangers of Postoperative Opioids. APSF Workshop and White Paper Address Prevention of Postoperative Respiratory Complications. APSF Newsletter 2007; 21(4): 61, 63-67
Pasero C, McCaffery M. Monitoring Sedation: It's the key to preventing opioid-induced respiratory depression. American Journal of Nursing. 2002; 102(2):67-69
Overdyk, Frank J. Postoperative Opioids Remain a Serious Patient Safety Threat.
Anesthesiology. 113(1): 259-260, July 2010