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Medication error

Primary Care Corner with Geoffrey Modest MD: Medical Errors, and a Plea For Primary Care

25 May, 16 | by EBM

By Dr. Geoffrey Modest

There was a recent brief article looking at the approximate rate of medical errors leading to death, and suggesting that this was the 3rd leading cause of death in the US (see doi: 10.1136/bmj.i2139).


  • A 1999 Institute of Medicine report, based on the 1984 Harvard Medical Practice Study and the 1992 Utah and Colorado Study, suggested that of the 180,000 reported iatrogenic deaths, 51% were preventable, though the lead Harvard researcher suggested that the number was closer to 78% (i.e. 140,400 preventable deaths). This number was based on a record review of a population-based study of New York Hospitals reported in 1993.Overall there was a 4% incidence of adverse events reported in the hospitalized patients.
  • A 2004 report from the Agency for Healthcare Quality and Research Patient Safety Indicators for the Medicare population estimated 195,000 deaths from medical errors per year (data from 2000-2002). This study found that of 37,000,000 admissions, there was an adverse event rate of 3.1%, a lethal adverse event rate of 0.7%, 389576 preventable deaths over these years, which they extrapolated to 2013 to be 251,454 preventable lethal adverse events.
  • The US Dept of Health and Human Services/Office of Inspector General examined health records of hospital inpatients in 2008, finding 180,000 deaths/year from medical errors in those on Medicare. This study found that of 838 admissions, there was an adverse event rate of 13.5%, a lethal adverse event rate of 1.4%, a 44% rate of preventable deaths, leading to 12 deaths, which they extrapolated to 2013to be 219,579 preventable lethal adverse events.
  • A 2004 study of 3 tertiary care hospitals (2 community-based teaching hospitals, both urban with one in the Mid-west and one Northeast, and one academic hospital in the West) finding that of 795 admissions, there was an adverse event rate of 33.2% (!!!), a lethal adverse event rate of 1.1%, 100% felt to be preventable, leading to 9 deaths, which they extrapolated to 2013 to be 400,201 preventable lethal adverse events
  • A 2002-7 study of 10 hospitals in North Carolina, finding that of 2341 admissions, there was an adverse event rate of 18.1%, a lethal adverse event rate of 0.6%, 63% felt to be preventable, leading to 14 deaths, which they extrapolated to 2013 to be 134,581 preventable lethal adverse events
  • The summary findings were the same as those of the AHRQ/Medicare study, since its 37M admissions so dwarfs the other studies in the weighted average. (So, estimated number of preventable deaths was set at 251,454 for 2013)
  • And, none of these studies included deaths at home, or in nursing homes, or in an ambulatory setting (which is an issue, both in terms of hospitalized patients who may have been discharged from the hospital but may have died relatively shortly thereafter from a hospital-related error, and because some patients undoubtedly die because of errors in medical care in the non-hospital setting itself).

So, there are certainly several issues here:

  • The quality of the data: the list of causes of death, per the CDC, is based on ICD coding, and there are no codes for diagnostic errors, poor judgment, inadequate skills, or, in general, either human or systems errors that could lead to death. And, accurate numbers still assume that the people or the institution involved is willing to acknowledge that a preventable cause of death occurred.
  • It is pretty striking that the number of adverse events was so variable (why was the Medicare one in the 3% range, yet up to 33% in the 3 tertiary care hospitals? Is it how adverse events are classified? Is it that Medicare just wasn’t looking hard enough?), but still, finding up to 1% of admissions were associated with preventable deaths is shocking….
  • There are many methodological concerns with the data in this report:
    • How accurate are the data collected (and how do they define a death as preventable )?
    • How extrapolatable are the data from a survey of 3 or 10 hospitals, or even the Medicare data, to the general population, in teaching and nonteaching hospitals, in small and large hospitals, in urban and rural hospitals, in hospitals with a slew of specialists and not, etc.
    • How extrapolatable is the preventable death rate from 2002 or 2008 to 2013? Lots has changed. Part is that the degree of illness of admitted patients may have changed. Or the intensity of testing. Or doing higher risk procedures. and the extrapolation of preventable deaths to 2013 as done in the above study is based only on the number of admissions in 2013 vs the number in the year studied
  • But, the bottom line is that there are a huge number of potentially preventable deaths, that the number is probably in the general ballpark of what they report, and that as such a huge issue, we should be devoting large amounts of resources to deal with this (i.e., one might think that prioritizing this issue makes sense, perhaps over developing/using another orphan drug for a rare disease, or devoting large amounts of resources to providing very expensive care to a terminal cancer patient where the benefit is on the order of a few months of additional life or less)
  • One very related issue to me is the remarkably backward nature of our health care system. It seems to me that the primary way to avoid preventable hospital-related deaths is to prevent hospitalization. Which for many of my patients in the 80-100 year old range, means preventing their going to the ER unless really necessary. Which means redesigning the orientation and reimbursement of the health care system to value primary care, move away from the 10-20 minute appointments (which, in the era of electronic medical records, translates to 5-10 minutes actually spent with the patient during which time we take care of their diabetes, hypertension, depression, domestic violence/other social issues, and their preventive care issues, etc.). And giving us the time and associated reimbursement to allow us to really take care of the patients’ problems, be accessible to avoid unnecessary ER visits and thereby decrease unnecessary hospitalizations. My experience is that when one of my frail patients goes to the ER for a likely minor problem, they are usually admitted (and I do not blame the ER physicians, since they see a frail person, do not know them, are not sure they will get outpatient follow-up, and feel that it is better to be safe than sorry. Though I almost never get a phone call to see if we can see the person the next morning. And the reality is that about 50% of my elderly patients admitted do not need admission, they often stay longer than they should, they decondition after 2 days, then they go to a rehab facility to recondition……and, in many cases, they become delirious and are put on unnecessary medications which lead to significant morbidity.
  • Of note, the April 30 issue of Lancet had a brief article and relevant editorial supporting a fundamental reworking of primary care for the NHS in the UK, with a large program to increase primary care recruitment, support primary care, streamline bureaucracy and improve reimbursement (see for a 5 year plan). There is also a report Primary Care by the House of Commons Health Committee “which emphasizes the need for increased funding of general practice to improve access to care and services for patients, such as extending the traditional 10 minute appointment time” — though I was unable to locate that report. And this is in the UK, which already has a universal, reasonably coherent/connected, accessible system of care (i.e., already much beyond us)…

Primary Care Corner with Geoffrey Modest MD: Medication errors with liquid meds in kids

11 Sep, 14 | by EBM

Medication adherence issues are one of the most pervasive primary care conundrums. I must admit that I always cringe a bit whenever I write for liquid meds for kids, hoping that the pharmacist can appropriately explain how to take the meds and give the appropriate measuring device. (There are other types of educational issues gone awry, evidenced by parents instilling the oral liquid antibiotics directly into the ear, or people taking suppositories by mouth….). So, in this light, there was a study done in New York assessing medication errors and the potential utility of “advanced counseling” in decreasing these errors (see 10.1016/j.acap.2014.01.003).


No clear marking to allow dose titration


Several studies have found that 40% of caregivers make errors in giving kids liquid meds. More if low levels of health literacy, or limited English proficiency. The language used in the instructions can also be confusion (writing “5ml” instead of “1 teaspoon” may be difficult for some parents; or using kitchen teaspoons instead of measuring spoons leads to dosing errors). Use of “advanced counseling skills” can help, eg asking the parent to describe how they will give the med, provider demonstration esp coupled with patient demonstration, use of pictures/drawings do help… but are underutilized.


–287 patients <9 yo from 2 urban New York public hospital ERs prescribed liquid meds. Parents were asked about the quality of counseling they received and/or a dosing instrument. Primary endpoint was observed dosing error, defined as >20% deviation from what was prescribed. Variables controlled for include: parent age, language, country, ethnicity, socioeconomic status, education, health literacy as assessed by Short Test of Functional Health Literacy in Adults, child age and their chronic disease status. cross-sectional analysis.

–41.1% of parents made dosing errors (81.4% underdosed, and 18.6% overdosed the med). Advanced counseling was provided to 33.1%, measuring instruments provided to 19.2%.

–97.6% of parents received some counseling in ER or pharmacy. 15% received both advanced counseling and medication instrument; 4.2% instrument only, 18.1% advanced counseling only, 62.7% neither

–Advanced counseling associated with decreased errors (30.5% vs 46.4%); instrument provision also associated with decreased errors (21.8% vs 45.7%)

–Combo of advanced counseling and instrument provision decreased odds of error, as compared to neither (20.9% vs 47.8%), with adjusted odds ratio of 0.3.

–Subgroup analysis did find that the combo strategy was significant only for those who spoke English, and those with adequate health literacy (there were essentially the same odds ratios of benefit for each of these interventions individually but were not statistically significant, perhaps because of small sample sizes)

Evidence shows that advanced counseling strategies work and have the support of the AMA and other professional organizations. However, most patients/parents in this study (and, i would imagine, in most practices) do not receive such counseling regularly. Pharmacists, at least in Massachusetts, are supposed to instruct parents in detail and provide measuring instruments, though unclear what the actual details or quality of that input really is.  The current study is limited, based on patients self-report and with likely biases, but it does highlight a very important problem inherent in outpatient medications — medication non-adherence is responsible for a huge amount of morbidity/mortality (eg, many hypertension studies find about 50% non-adherence rates) and the complexity of the medication regimens leads to more errors and non-adherence. Kids prescribed liquid meds have even more complex regimes than simply taking pills.



Primary Care Corner with Geoffrey Modest MD: varenicline, combo Rx and use in mental illness

21 Jan, 14 | by EBM

there were a few important articles in the jan 8th JAMA on smoking — i will highlight 2 of them on varenicline, a partial agonist which binds with high affinity as well as specificity to neuronal acetylcholine receptors. smoking cessation in smokers is the most significant single intervention to decrease mortality, and 62% of deaths in female smokers/60% of deaths in male smokers are attributable to smoking.


1. i had postedt a general smoking cessation article about one year ago from JAMA which referenced some small study finding benefit of combining varenicline with bupropion. the current study (see  doi:10.1001/jama.2013.283185) was a 12-month multi-center RCT comparing varenicline with bupropion vs varenicline with placebo, with both medications dosed as is generally recommended.  results:


–500 patients (mean age 42, 94% white, 45% women, 78% completed at least some college — study done at Mayo clinic and univ minnesota), though only 62% completed the study (dropout rates similar in both groups)

–of those completing study:

–at 12 weeks: 53% in combo group achieved smoking abstinence and 56% 7-day point-prevalence smoking abstinence (ie, self-reported tobacco cessation for previous 7 days, confirmed by carbon monoxide level), vs 43% and 49% with varenicline alone

–at 26 weeks: 37% with prolonged and 38% with 7-day point prevalence abstinence in combo and 28% and 32% with varenicline alone

–at 52 weeks: 31% with prolonged and 37% with 7-day point prevalence abstinence in combo and 25% and 29% with varenicline alone

–adverse effects: combo with more anxiety (7% vs 3%) and depressive sx (4% vs 1%) — a bit surprising since the combo group had bupropion, a pretty potent anti-depressant….

–of the above, the only findings reaching statistical significance were: smoking abstinence at 12 and 26 weeks. no significance at 52 weeks, or any of the measures of 7-day point prevalence.

–subgroup analysis: for heavy smokers (>20 cigs/day), combo therapy assoc with statistically significant prolonged smoking abstinence at 12 weeks (50% vs 36%), 26 weeks (35% vs 19%) and 52 weeks (32% vs 17%), with similar numbers for those with high levels of nicotine dependence.

–less weight gain in combo group than in varenicline alone (1.1 vs 2.5kg at 12 weeks, 3.4 vs 3.8kg at 26 weeks, and 4.9 vs 6.1kg at 52 weeks)


this trial confirms the concept of combination therapy and extends it to varenicline plus bupropion. other studies have found improved abstinence rates with combo of bupropion and nicotine replacement therapy (NRT), and with using combo NRTs (eg patch for maintenance nicotine levels, with inhaler or lozenge for times of increased urge to smoke).  this study, though small numbers of patients and pretty high dropout rate, does suggest that the combo of bupropion and varenicline is effective, esp in those who are heavy smokers.


there are minimal studies of electronic cigarettes, as per a prior blog. mostly short-term (eg 12 weeks: 14% abstinence with e-cigarettes vs 4% with nicotine-free device; another study for 6 months found no statistical difference between e-cigarettes, nicotine patch or placebo). of note, the FDA has found important carcinogenic contaminants in 2 brands of e-cigarettes: polycyclic aromatic hydrocarbons and nitrosamines. (though my experience in a relatively small number of smokers is that the e-cigs did help them quit, and cigarettes have many more dangerous additives. however, i and others are concerned that e-cigarettes may change the rather pervasive anti-smoking ethic developed in this country over many years and make tobacco more acceptable and even chic for young people).


2. the above study excluded patients with major medical or psych illnesses, and there is concern that varenicline could exacerbate psych problems. in addition, the baseline smoking rates are significantly higher in people with mental illness (25% vs 19%, in 2011). not surprisingly, those with mental illness who received mental health treatment quit smoking at a higher rate than those who did not receive treatment (37% vs 33%). another JAMA article looked at patients with schizophrenia or bipolar disease who had quit smoking on varenicline and then were put on maintenance of varenicline plus cognitive behavioral therapy (CBT) vs CBT alone (see  doi:10.1001/jama.2013.285113), as follows:


–of 203 smokers (60% smoking more than 20 cigs/d) with medically-treated and stable schizophrenia or bipolar dz, then treated with varenicline in a 12-week open trial, 87 had at least 14 days of continuous abstinence by the end of this period (88% had schizophrenia, 12% bipolar)

–these 87 abstinent patients were randomized to continued varenicline to complete 52 weeks, along with tapering CBT sessions (median of 26 sessions), vs  placebo and CBT (24 sessions)

–at the end of the varenicline intervention (52 weeks), point prevalence abstinence rate of 60% with varenicline vs 19% placebo

–at the end of the study (76 weeks — ie, 24 weeks after stopping intervention), abstinence rates of 30% vs 11% (pretty impressive!!)

–and, perhaps most noteworthy, no difference in adverse events with varenicline in the open-label part of the study, and there were actually fewer reports of agitation or excitement with the maintenance varenicline than placebo (though more headaches)


so, small study, but does suggest that we can use varenicline in patients with schizophrenia or bipolar disease, which i think many of us were wary about.



Primary care corner with Dr Geoffrey Modest: Adverse statin effects

25 Nov, 13 | by EBM

There have been a slew of articles in the literature in the past year on the harmful effects of statins. A recent study-level network meta-analysis was reported, incorporating 135 randomized controlled trials with 250K participants to assess the reported adverse effects (note that some of these effects could have been under-reported, such as myalgias, given the relative frequency of such in many of our clinical practices but their low numbers) — see  DOI: 10.1161/CIRCOUTCOMES.111.000071.

The findings:

–no difference between individual statins and controls for: myalgias (subjective muscle pain), creatine kinase elevations (varied in studies from 3x to 10x more than baseline), cancer, or discontinuations because of adverse events. Likelihood of rhabdomyolysis small and no diff from controls.

–overall 9% higher likelihood of developing diabetes

–51% higher likelihood of developing transaminitis (ALT or AST >3x baseline, though note that this is not a clinical marker only a biochemical one)

–simvastatin and pravastatin best tolerated, higher doses of atorvastatin and rosuvastatin less tolerated

–higher dose simvastatin (>40mg/d) assoc with more marked increase in CK elevations (OR 4.14)

Some specifics:

–myalgias: in the larger analysis of all studies, found in 2% of participants, no diff between statins

–transaminitis: 1% of participants. Atorva the worst in dose-response fashion, with OR 5.25 if >40mg/d.  fluvastatin pretty bad, but no one uses this anymore….

–CK elevations: 0.6% of individuals. Worst with high-dose simva (though interesting that myalgias in this group were not significantly different from controls and actually had a trend to be 28% less than controls…)

–diabetes: overall 9% increased risk, though worse for high-dose rosuvastatin (16%) in the placebo-controlled direct trials, but no individual statin difference in the overall network analysis.

–simva and prava were best in the combined outcomes (includes discontinuations from combo of adverse effects, myalgia, transaminitis and CK elevation)

–pitavastatin recently approved by FDA (have never used it myself), but in general seems to be worse than the others overall.

The background here is that statins are dramatically effective in reducing clinical cardiac/cerebrovascular events, in the elderly, in women, in patients with diabetes, with relative risk reductions in the 25-30% range (even in patients with diabetes felt by their endocrinologists not to need statins  because their cholesterol levels were “okay”). Of course the absolute risk reduction depends on the risk status of the cohort involved,but recent meta-analyses have shown pretty conclusively that statins are beneficial even in primary prevention and even if some cases of diabetes develop) — see Lancet 2012; 380: 565–71 for Jupiter study with rosuvastatin, the worst one in the above meta-analysis, and argument that cardiovasc benefits exceed diabetes risk. Overall, there do seem to be some differences between the statins, with pravastatin and simvastatin having the fewest adverse effects (I was a bit surprised here, since some earlier individual studies found worse problems with simvastatin vs atorvastatin,  which reinforces the utility of these larger analyses).


Primary care corner with Dr. Geoffrey Modest: Chronic pain and opioids 1

25 Nov, 13 | by EBM

caring for patients who have chronic pain can be one of the most challenging issues in primary care. unlike almost any other primary care issue, the use of opioids for chronic pain tends to be the most likely one to pit a provider (or staff) against the patient, the antithesis of developing a strong primary care relationship. background:

–at our health center 20+ years ago, there were at most a handful of patients on opioids for chronic non-cancer pain. currently, most of us have at least a few patients on our schedule every day coming in for opioids for noncancer pain. Similarly, all of the patients addicted to opioids in the past were using illicit drugs (basically heroin and cocaine). now, my health center experience is that pretty much all of the young opioid-addicted patients are addicted to prescribed opioids (the very typical scenario of my young suboxone — ie buprenorphine/naloxone — patients is: they were given prescription opioids for acute pain, liked the feeling, increased their consumption by buying meds on the street, became addicted, had serious problems with life (maintaining job, relationships, etc), then came for suboxone and have mostly done very well).

–a recent study suggested more than 3% of adults receive long-term opioid therapy for chronic non-cancer pain!

–One of the major reasons for this dramatic transformation was within the medical profession: The Institute of Medicine came out with clear guidelines that pain was being underassessed and undertreated, raising the request that pain assessment be a vital sign, checked at every visit.

–However, parallel with this dramatic increase of providers’ prescribing opioids, there have been dramatic increases in deaths from opioid poisoning, for example hospitalizations for opioid related overdoses doubled in the 10 year period of 1995 to 2004 in Washington state. The MMWR (see Morbidity and Mortality weekly reports from the CDC Centers for Disease Control in the US MMWR Nov 1, 2011 Vital Signs: overdose of prescription opioid pain relievers –United States 1999-2008) reported that nearly 100 people/day died of drug overdoses in the United States in 2007 (that is  >10x the death rate from asthma, at least as reported in the new york times today).  The 2007 death rate was 3 times that of 1991.  At this point the majority of overdose deaths are from prescribed opioid pain relievers.  A study in Virginia found that the majority of overdoses resulted from drug diversion to others who then OD’d.

–Another recent study (see Ann Intern Med. 2010;152:85-92) looked at the patients themselves, finding that increasing doses of prescribed opioids was associated with increasing likelihood of overdose.  This study was done at a large HMO in Seattle Washington with 10,000 people who received 3 or more opioid prescriptions within 90 days for chronic non-cancer pain between 1997 and 2005.  They found:

–opioids were mostly prescribed for musculoskeletal pains, with two thirds specifically for back or extremity pain.  Mean daily dose was 13.3 mg of morphine equivalents, with 80% of the patients using 1-20 mg per day and only 2% using 100 or more milligrams per day. (pretty low doses compared to what we typically see!)

–There were 51 opioid-related overdoses including 6 deaths

–converting the opioids to morphine equivalents using the CONSORT classification (see the article  Clin J Pain 2008;24:521–527):

–overdose rates were somewhat higher in patients over 65 and in those with a history of depression or treatment of substance abuse

–Using the lowest group (1-20 mg per day) as a reference, those in the 20-50 mg per day had a 19% increase risk of serious overdose, the 50-100 mg per day had a 2 fold increased risk, in those greater than 100 mg per day had a 10 fold increased risk.

–similar numbers were found in a veterans study

Typically use of opioids is the last resort after the patient has failed pain management with non-opioid analgesics or anti-inflammatories, as well as other potential pain modulators (including tricyclic antidepressants; seizure meds such as gabapentin, pregabalin, or other anticonvulsants; muscle relaxants; NMDA receptor antagonist; and topical analgesics). although I suspect that we all have patients who have clearly responded to opioids clinically for non-cancer chronic pain, the actual data is not great:

–The average pain reduction through all of these modalities averages only about a 30% decrease in pain (which may well be important for the patient, but is important for us to realize and communicate to the patient that it is unlikely that they will get full resolution of their pain)

-for neuropathic pain, a 2013 Cochrane review of 31 trials (see DOI: 10.1002/14651858.CD006146.pub2) showed that: for acute pain of less than 24-hour duration (16 studies with 392 participants) — half had less pain with opioids than placebo, and more than a quarter had no difference.  6 studies with 170 participants found that the average pain score with opioids was 15/100 points less than with placebo. 14 studies with 845 participants were of intermediate duration lasting less than 12 weeks (which they comment were small studies, short duration, and potentially inadequate handling of dropouts creating bias of overestimating treatment effects) all demonstrated efficacy for neuropathic pain with at least 33% pain relief found in 57% of those on opioids versus 34% in those receiving placebo. no improvement in many aspects of emotional or physical functioning.  Common adverse effects of constipation, drowsiness, nausea, dizziness, vomiting.  They conclude that “the efficacy of opioids and chronic neuropathic pain is subject to considerable uncertainty”.

–for chronic nociceptive pain, the data are quite mixed for opioids.  Again they are a last resort for therapy.  A systematic review in the annals of internal medicine (Ann Intern Med 2007;146(2):116) of opioid treatment for chronic low back pain analyzed 4 studies comparing opioids with placebo or non-opioid controls found no difference in pain control.  5 studies directly comparing the efficacy of different opioids found a nonsignificant reduction in pain from baseline.  However, the prevalence of lifetime substance use disorders ranged from 36-56%.

–one other very unfortunate trend is that chronic pain clinics used to be multi-disciplinary, involving social workers, psychologists or psychiatrists, neurologists or other pain specialists, anesthesia.  now, these have devolved into just being anesthesiologists giving injections (at least in boston).

So, what does this mean in clinical practice when we see a patient in chronic pain who is not responding well to non-opioid therapies? My guess is that most of us see patients like this pretty often and find that often they do respond to opioids, though sometimes pretty high doses. However, the data suggest that this it is pretty uncommon in placebo-controlled trials (though were the trials constructed well?? with high enough doses of opioids??), and we know that there may be significant harms to the patient (esp if on large doses, as the studies above found) and to the community (with increasing availability of opioids on the street and associated overdoses, and we do see that in our community). Part of the answer is to follow people closely, have pain contracts/urine testing/etc, though this does tend to undercut the provider-patient relationship. What about the patient who comes into the practice on high doses of opioids? One of our residents just saw a person with trigeminal neuralgia on 60 mg of methadone and 180 mg of oxycodone a day (if you whip out your opioid conversion table, that is 450 morphine equivalents!!!). the patient states he is stable on this dose and needs to continue. His urine tox screens are appropriate. We ultimately decided to decrease his dosage in part because he may well be diverting meds (2 nieces who are reputed to be “drug addicts”) and we felt uncomfortable continuing with this high a dose for the patient’s own safety. But it’s hard to know what the right answer is…


Primary Care Corner with Geoffrey Modest MD: Chronic pain/opioid guidelines

25 Nov, 13 | by EBM

in the flurry of recent articles on opioid prescribing for chronic pain, the annals of intl med came out with a systematic review and assessment of the 13 identified guidelines, evaluating them using 2 tools: AGREE II (appraisal of guidelines for research and evaluation II) and AMSTAR (a measurement tool to assess systematic reviews). for article, see doi:10.7326/0003-4819-160-1-201401070-00732. they basically found that the only 2 guidelines which received high ratings were the Am Pain Society one (doi:10.1016/j.jpain.2008.10.008) and the Canadian National Opioid Use Guideline Group one. overall, they were quite impressed at the level of agreement in the differing guidelines. major points:

–these guideline evaluators assessed many aspects of the formulation of the guidelines, including input from providers /patients, how evidence was selected, strengths/limitations of the evidence, how recommendations formulated, external reviews prior to publication, implementation recommendations, measures to ensure editorial independence…

–a recent workers’ comp study (2012) found that 8-30% of pts with noncancer pain were on opioids, with average daily doses from 13-128 mg morphine equivalents

–nearly half of fatal overdoses were assoc with concommitant use of sedative-hypnotics, esp benzos. and esp an issue in the elderly

–leading risk factor for overdose or misuse of opioids is personal or family hx of substance abuse or psych issues

–there was general agreement that we should use extreme caution if doses greater than 90-200 mg of morphine equivalents per day. 5 guidelines published before 2012 felt that doses >200 mg morphine equiv conferred high risk, and observational studies found that the risk increased dramatically with doses over 100-200 mg.  in washington state, they began requiring workers’ comp cases get a pain management referral if pt receiving more than 120 mg/d.  no data on pain control (unfortunately) but assoc signif decrease in opioid overdoses.

–if you are considering changing opioids because you are prescribing really high dose and want to see if other opioid is more effective, you should reduce the morphine equivalent dose by 25-50% (to avoid too much opioid in what may be a more potent drug for the patient)

–be careful with methadone (long QTc, respiratory suppression due to long half-life — half-life typically 15-60 hrs, can be as high as 120 hrs) and follow more closely than other long-acting drugs (check drug-drug interactions, care with other drugs which prolong QTc).  also be careful with fentanyl patches “including limiting use to opioid-tolerant patients and being aware that unpredictable absorption can occur with fever, exercise or exposure to heat”

–important to use opioid risk assessment tools (eg appendix 4 or 5 in the am pain society paper), written treatment agreements, urine drug testing (guidelines differ a bit on frequency, but most suggest at baseline, and random thereafter, esp if risk is high).



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