The Other Opioid Crisis: Hospital Shortages Lead To Patient Pain, Medical Error

I came across this public-accesss story, and wanted to share the perspective:


Even as opioids flood American communities and fuel widespread addiction, hospitals are facing a dangerous shortage of the powerful painkillers needed by patients in acute pain, according to doctors, pharmacists and a coalition of health groups.

The shortage, though more significant in some places than others, has left many hospitals and surgical centers scrambling to find enough injectable morphine, Dilaudid and fentanyl — drugs given to patients undergoing surgery, fighting cancer or suffering traumatic injuries. The shortfall, which has intensified since last summer, was triggered by manufacturing setbacks and a government effort to reduce addiction by restricting drug production.

As a result, hospital pharmacists are working long hours to find alternatives, forcing nurses to administer second-choice drugs or deliver standard drugs differently. That raises the risk of mistakes — and already has led to at least a few instances in which patients received potentially harmful doses, according to the nonprofit Institute for Safe Medication Practices, which works with health care providers to promote patient safety.
In the institute’s survey of hospital pharmacists last year, one provider reported that a patient received five times the appropriate amount of morphine when a smaller-dose vial was out of stock. In another case, a patient was mistakenly given too much sufentanil, which can be up to 10 times more powerful than fentanyl, the ideal medication for that situation.
In response to the shortages, doctors in states as far-flung as California, Illinois and Alabama are improvising the best they can. Some patients are receiving less potent medications like acetaminophen or muscle relaxants as hospitals direct their scant supplies to higher-priority cases. Other patients are languishing in pain because preferred, more powerful medications aren’t available, or because they have to wait for substitute oral drugs to kick in.

The American Society of Anesthesiologists confirmed that some elective surgeries, which can include gall bladder removal and hernia repair, have been postponed.

Even as opioids flood American communities and fuel widespread addiction, hospitals are facing a dangerous shortage of the powerful painkillers needed by patients in acute pain, according to doctors, pharmacists and a coalition of health groups.

The shortage, though more significant in some places than others, has left many hospitals and surgical centers scrambling to find enough injectable morphine, Dilaudid and fentanyl — drugs given to patients undergoing surgery, fighting cancer or suffering traumatic injuries. The shortfall, which has intensified since last summer, was triggered by manufacturing setbacks and a government effort to reduce addiction by restricting drug production.

As a result, hospital pharmacists are working long hours to find alternatives, forcing nurses to administer second-choice drugs or deliver standard drugs differently. That raises the risk of mistakes — and already has led to at least a few instances in which patients received potentially harmful doses, according to the nonprofit Institute for Safe Medication Practices, which works with health care providers to promote patient safety.
In the institute’s survey of hospital pharmacists last year, one provider reported that a patient received five times the appropriate amount of morphine when a smaller-dose vial was out of stock. In another case, a patient was mistakenly given too much sufentanil, which can be up to 10 times more powerful than fentanyl, the ideal medication for that situation.
In response to the shortages, doctors in states as far-flung as California, Illinois and Alabama are improvising the best they can. Some patients are receiving less potent medications like acetaminophen or muscle relaxants as hospitals direct their scant supplies to higher-priority cases. Other patients are languishing in pain because preferred, more powerful medications aren’t available, or because they have to wait for substitute oral drugs to kick in.

The American Society of Anesthesiologists confirmed that some elective surgeries, which can include gall bladder removal and hernia repair, have been postponed.

In a Feb. 27 letter to the U.S. Drug Enforcement Administration, a coalition of professional medical groups — including the American Hospital Association, the American Society of Clinical Oncology and the American Society of Health-System Pharmacists — said the shortages “increase the risk of medical errors” and are “potentially life-threatening.”

In addition, “having diminished supply of these critical drugs, or no supply at all, can cause suboptimal pain control or sedation for patients,” the group wrote.

The shortages involve prefilled syringes of these drugs, as well as small ampules and vials of liquid medication that can be added to bags of intravenous fluids.

Drug shortages are common, especially of certain injectable drugs, because few companies make them. But experts say opioid shortages carry a higher risk than other medications.

Giving the wrong dose of morphine, for example, “can lead to severe harm or fatalities,” explained Mike Ganio, a medication safety expert at the American Society of Health-System Pharmacists.

Marchelle Bernell (Courtesy of Marchelle Bernell)
Calculating dosages can be difficult and seemingly small mistakes by pharmacists, doctors or nurses can make a big difference, experts said.
Marchelle Bernell, a nurse at St. Louis University Hospital in Missouri, said it would be easy for medical mistakes to occur during a shortage. For instance, in a fast-paced environment, a nurse could forget to program an electronic pump for the appropriate dose when given a mix of intravenous fluids and medication to which she was unaccustomed.

“The system has been set up safely for the drugs and the care processes that we ordinarily use,” said Dr. Beverly Philip, a Harvard University professor of anesthesiology who practices at Brigham and Women’s Hospital in Boston. “You change those drugs, and you change those care processes, and the safety that we had built in is just not there anymore.”

Dr. Beverly Philip (Courtesy of the American Society of Anesthesiologists)
Chicago-based Marti Smith, a nurse and spokeswoman for the National Nurses United union, offered an example.

“If your drug comes in a prefilled syringe and at 1 milligram, and you need to give 1 milligram, it’s easy,” she said. “But if you have to pull it out of a 25-milligram vial, you know, it’s not that we’re not smart enough to figure it out, it just adds another layer of possible error.”

During the last major opioid shortage in 2010, two patients died from overdoses when a more powerful opioid was mistakenly prescribed, according to the institute. Other patients had to be revived after receiving inaccurate doses.

The shortage of the three medications, which is being tracked by the FDA, became critical last year as a result of manufacturing problems at Pfizer, which controls at least 60 percent of the market of injectable opioids, said Erin Fox, a drug shortage expert at the University of Utah.

A Pfizer spokesman, Steve Danehy, said its shortage started in June 2017 when the company cut back production while upgrading its plant in McPherson, Kan. The company is not currently distributing prefilled syringes “to ensure patient safety,” it said, because of problems with a third-party supplier it declined to name.

That followed a February 2017 report by the U.S. Food and Drug Administration that found significant violations at the McPherson plant. The agency cited “visible particulates” floating in the liquid medications and a “significant loss of control in your manufacturing process [that] represents a severe risk of harm to patients.” Pfizer said, however, that the FDA report wasn’t the impetus for the factory upgrades.

Other liquid-opioid manufacturers, including West-Ward Pharmaceuticals and Fresenius Kabi, are deluged with back orders, Fox said. Importing these heavily regulated narcotics from other countries is unprecedented and unlikely, she added, in part because it would require federal approval.
At the same time, in an attempt to reduce the misuse of opioid painkillers, the Drug Enforcement Administration called for a 25 percent reduction of all opioid manufacturing last year, and an additional 20 percent this year.
“DEA must balance the production of what is needed for legitimate use against the production of an excessive amount of these potentially harmful substances,” the agency said in August.

When the coalition of health groups penned its letter to the DEA last month, it asked the agency to loosen the restrictions for liquid opioids to ease the strain on hospitals.

The shortages are not being felt evenly across all hospitals. Dr. Melissa Dillmon, medical oncologist at the Harbin Clinic in Rome, Ga., said that by shopping around for other suppliers and using pill forms of the painkillers, her cancer patients are getting the pain relief they need.

Dr. Shalini Shah, the head of pain medicine at the University of California-Irvine health system, pulled together a team of 20 people in January to figure out how to meet patients’ needs. The group meets for an hour twice a week.

Dr. Shalini Shah (Courtesy of University of California-Irvine)
The group has established workarounds, such as giving tablet forms of the opioids to patients who can swallow, using local anesthetics like nerve blocks and substituting opiates with acetaminophen, ketamine and muscle relaxants.

“We essentially have to ration to patients that are most vulnerable,” Shah said.

Two other California hospital systems, Kaiser Permanente and Dignity Health in Sacramento, confirmed they’re experiencing shortages, and that staff are being judicious with their supplies and using alternative medications when necessary. (Kaiser Health News, which produces California Healthline, is not affiliated with Kaiser Permanente.)
At Helen Keller Hospital’s emergency department in Sheffield, Ala., earlier this month, a 20-year-old showed up with second-degree burns. Dr. Hamad Husainy said he didn’t have what he needed to keep her out of pain.
Sometime in January, the hospital ran out of Dilaudid, a drug seven times more potent than morphine, and has been low on other injectable opioids, he said.

Because Husainy’s patient was a former opioid user, she had a higher tolerance to the drugs. She needed something strong like Dilaudid to keep her out of pain during a two-hour ride to a burn center, he said.
“It really posed a problem,” said Husainy, who was certain she was in pain even after giving her several doses of the less potent morphine. “We did what we could, the best that we could,” he said.

Bernell, the St. Louis nurse, said some trauma patients have had to wait 30 minutes before getting pain relief because of the shortages.
Dr. Howie Mell (Courtesy of Howie Mell)

“That’s too long,” said Bernell, a former intensive care nurse who now works in radiology.

Dr. Howie Mell, an emergency physician in Chicago, said his large hospital system, which he declined to name, hasn’t had Dilaudid since January. Morphine is being set aside for patients who need surgery, he said, and the facility has about a week’s supply of fentanyl.

Mell, who is also a spokesman for the American College of Emergency Physicians, said some emergency departments are considering using nitrous oxide, or “laughing gas,” to manage patient pain, he said.
When Mell first heard about the shortage six months ago, he thought a nationwide scarcity of the widely used drugs would force policymakers to “come up with a solution” before it became dire.

“But they didn’t,” he said.

Ten Gripes of Buprenorphine Doctors

I recently gave a lecture to medical students about opioid dependence and medication assisted treatment using buprenorphine, methadone, or naltrexone. I was happy to see their interest in the topic, in contrast to the utter lack of interest in learning about buprenorphine shown by practicing physicians. In case someone from the latter group comes across this page, I’ll list a few things to do or to avoid when caring for someone on buprenorphine (e.g. Suboxone).

1. Buprenorphine does NOT treat acute pain, so don’t assume that it will. Patients are fully tolerant to the mu-opioid effects of buprenorphine, so they do not walk around in a state of constant analgesia. Acute pain that you would typically treat with opioids should be treated with opioids in buprenorphine patients. Patients on buprenorphine need higher doses of agonist, usually 2-3 times greater than other patients. Reduce risk of overuse/overdose by providing multiple scripts with ‘fill after’ dates. For example if someone needs opioid analgesia for 6 days, use three prescriptions that each cover two days, each with the notation ‘fill on or after’ the date each will be needed.

2. Don’t say ‘since you’re an opioid addict I can’t give you anything’. There are ways to provide analgesia safely. If you do not provide analgesia when indicated, your patient will only crave opioids more, and may seek out illicit opioids for relief. Unfortunately nobody will criticize you for leaving your patient in pain, but they should!

3. Don’t blame the lack of pain control on laws that don’t exist, for example “I’d like to help you but the law won’t let me.” Patients deserve honesty, even when the truth makes us uncomfortable. We get paid ‘the big bucks’ for tolerating the discomfort that sometimes comes from frank discussions with our patients.

4. Don’t assume your patient can or cannot control pain medications. If a patient has been stable on buprenorphine for years, he/she may have a partner or family member who you can trust to control pain medications. Some patients stable on buprenorphine can control agonists used for acute pain, but I wouldn’t stake my life, or theirs, on that ability. A useful compromise is to prescribe enough pain medication to cover 1-2 days of analgesia on each of several prescriptions, each with a ‘fill after’ date, to reduce the amount of agonist controlled by the patient at one time.

5. Don’t tell your patients that ‘opioids don’t work for chronic pain.’ I see stories on such great medical sources as the ‘Huffington Post’ explaining that ‘opioids never help chronic pain’. In reality, your patients know that opioids DO treat chronic pain, so they will consider you a liar or an idiot if you clam they don’t. The challenge is explaining the risk/reward equation to your patients, and explaining why treating chronic pain with opioids often leads to greater problems, as the risk/benefit equation is changed by tolerance.

6. I know this will cause heads to explode, but don’t assume that chronic pain is always less severe than acute pain. What if your patient’s chronic pain is worse than the typical pain after cholecystectomy or ACL repair? Most doctors would gasp at the idea of recovering from major surgery without opioids. What if the pain from failed back syndrome is worse?! I have had a few patients who, I’m certain, experience a great deal of suffering, and have gone so far as to have brain or spinal cord implants to get relief. I’m not arguing that we treat chronic pain in the same way as acute pain. But we shouldn’t jump to the conclusion that chronic pain isn’t severe enough to warrant opioids in order to dismiss those complaints more easily.

7. Don’t tell your patient to stop taking buprenorphine unless you’ve talked with the doctor who is prescribing that medication, and realize that the doctor you are calling knows more about buprenorphine and addiction than you do.

8. Don’t ask patients ‘how long are you going to take that stuff’ or criticize patients’ use of buprenorphine medications. Likewise psychiatrists shouldn’t tell patients scheduled for knee arthroscopy that the procedure is controversial, or talk patients out of hernia surgery.

9. Don’t assume that the doctor prescribing buprenorphine knows what YOU are doing. Too often patients will tell me about surgery that they failed to discuss in advance, even calling about pain hours after getting home from a procedure they failed to mention. Some people seem to believe that doctors regularly collaborate on their care, even though the opposite is closer to the truth.

10. Don’t assume that unusual or atypical symptoms come fromo buprenorphine. One truism of medicine is that doctors tend to blame unexplained symptoms on whatever medication they know the least about. Fevers of unknown origin, mental status changes, or double vision are not ‘from the buprenorphine!’

Those are the gripes at the top of my list. Did I miss one of yours? Or for patients, have you suffered from breakdowns in the system?

Addendum: 11. When treating post-surgical pain in buprenorphine patients, choose one opioid and stick with it. What often happens is that doctors will use one opioid, say morphine… and when nurses call a few hours later to say the patient is still screaming, they change to a different opioid, then another after that. As a result, the patient is placed on insufficient doses of several opioids, rather than an adequate dose of one medication.

There are two critical issues in treating such patients effectively. First, providing pain relief comes down to competition at the mu receptor. A certain concentration of agonist in the brain and spinal fluid will out-compete buprenorphine and provide analgesia. You cannot get there by adding other opioids together. If you use oxycodone for an hour and then change to dilaudid, you are starting over. Instead, choose one drug, preferably something that can be given intravenously, and stick with it. Morphine is not a good option btw, because of the low potency and histamine releasing properties of that drug.

Second, remember that analgesia and respiratory depression travel together, both mediated by the mu receptor. Anesthesiologists know this principle well… opioid medication can be titrated to respiratory rate, providing that the medication is given IM or IV. If a patient is breathing 28 times per minute, he/she is in pain. If the patient is breathing 6 times per minute, pain is not a problem, and the patient should be monitored for respiratory depression and possible overdose. When treating pain, doctors should aim for a respiratory rate of 14-18 breaths per minute, making sure that the medication is actually getting into the bloodstream (the risk comes when patients are given SQ injections or oral doses of narcotic that enter the bloodstream later, causing toxic blood levels).

Opioid Analgesia Without Addiction

I don’t have pull with the addiction-related organizations out there. I’m never been a joiner, and I tend to notice the problems caused by medical societies over the good things that they supposedly accomplish. For example PROP, or ‘Physicians for Responsible Opioid Prescribing’, have a specific mission. Once a group has a mission, any considerations about individual patients go out the window. PROP has propagated the message that opioids are NEVER beneficial for patients with chronic pain.

Legislators with no knowledge of clinical medicine hear that message, and respond by passing draconian laws that interfere with any considerations of individual patients. I would guess that the people of PROP pat themselves on the back for encouraging laws that remove physician autonomy. I’m sure they figure that they are smarter than all the family practice docs out there. But in reality, they are only destroying the control of doctors over patient care, and handing that care over to politicians. Way to go, PROP.

In the same way, the societies that hold meetings about meetings, that elect Secretaries who become Vice Presidents who become Presidents, get to publish the articles that describe clinical protocols. The doc who spends every day talking with patients has no access to these sources, and little ability to influence those protocols. Sometimes the societies and organizations get things right… and sometimes they get things wrong. The latter is the case with post-op pain control in patients on buprenorphine products.

I’ve written about this before, as regular readers know. Over the past 8 years I’ve had dozens, if not hundreds, of patients on buprenorphine undergo surgery. The surgeries include coronary bypass, thoracotomy, rotator cuff repair, C-section, nephrectomy, total knee or hip replacement… and a host of minor surgeries with scopes and lasers. I’ve treated these patients in a number of ways, in part because hospitals that provide emergency care have different ways of dealing with post-op analgesia. I rarely have control over what they do acutely– but I almost-always take over pain control when patients are discharged.

In the past few months there have been several ‘articles’ stating that the best way to handle surgery, in people on buprenorphine products, is to stop the buprenorphine before surgery, and treat pain using opioid agonists. This opinion is not supported by any data. It is someone’s opinion– usually someone who has a title, i.e. someone who spends at least some of his/her time in society meetings. That time is removed from the amount of time that could be spent treating and speaking with patients. Frankly, the ‘higher’ a doctor is in society circles, the less time they spend in patient care. That comment will anger the docs who it applies to. I can hear them now– saying I’m only full of ‘sour grapes’. But maybe those same docs should look in the mirror, and wonder how they ended up as ‘President’ of a society.

I’ve used the approach claimed as best practice in the society journals– i.e stopping buprenorphine before surgery– and the same thing always happens. Tolerance to opioid agonists rises very rapidly in the post-op period. Patients are discharged on huge doses of opioid agonists. And at some point, agonists must be discontinued for 24 hours to allow for re-induction with buprenorphine agents. I’ve had several recent patients go through this exact process– and my frustration motivates this post. One guy shot himself in the femur, and the bullet also passed through his lower leg. He needed fasciotomy to avoid losing the leg. His Suboxone was discontinued at admission, and ten days later he was discharged on 30 mg of oxycodone every 2-3 hours– i.e. over 200 mg per day. The other person was in a serious car accident, and had multiple fractures— femur, pelvis, ribs, wrist– as well as internal injuries. After 3 weeks he was released on over 300 mg of oxycodone per day!

On the other hand, I’ve had many patients go through the surgeries listed earlier while maintained on buprenorphine, 4-8 mg per day. In ALL cases, they had excellent analgesia with lower doses of oxycodone than in the people who stopped buprenorphine. Most patients did well on 15 mg of oxycodone every 3-4 hours– a max of 120 mg of oxycodone per day. In a few cases– i.e. in the most painful operations, in the most sensitive patients– I had to use 30 mg of oxycodone every 4 hours.

The most amazing thing about the combination of buprenorphine and opioid agonists is the absence of tolerance to agonists, when buprenorphine is present. I’ve had patients with recurrent injuries that required repeated surgeries, including a woman who tore her rotator cuff and the surgical repair THREE times over three months. She took the same amount of opioid agonist for three months, with no noticeable decrease in efficacy. After the final operation, after three months on significant amounts of opioid agonist, she simply stopped the agonist and resumed her full dose (16 mg) of buprenorphine. She had no withdrawal, and not other complications. She simply stopped the agonist and resumed buprenorphine treatment.

I’ve come to realize that buprenorphine effectively ‘anchors’ tolerance when patients take opioid agonists, as long as the buprenorphine is continued. Patients always say the same thing: that the pain was reduced by the agonist, but that it didn’t ‘feel’ like the agonist they used to take. In fact, patients who could never control pain pills found that they COULD control agonists if they stayed on buprenorphine.

A couple years ago I presented these findings at an annual meeting of ASAM. The slides can be found here. I believe that some day, combinations of buprenorphine and opioid agonists will be the standard approach to pain treatment. The combination allows for opioid analgesia without tolerance, without euphoria, and with little or no risk of addiction. If THAT doesn’t piqué your interest, you have no business reading about opioid dependence!

I picture combinations of buprenorphine and fentanyl… especially since both are now FDA-approved as transdermal patches. Or perhaps a combination of fentanyl lozenges and sublingual buprenorphine. The possibilities are endless. Throughout history, the miracle of opioid analgesia has been cursed by the attachment to tolerance, dependence, and addiction.

Imagine if that curse was lifted from opioid analgesia. Can you even dare to imagine that world? I’m telling you… it is closer than you think—- and there for the taking.

Short-Timers

Another question from a reader:
The current blog brings up the notion of long term use of Bupe or short term detox. You say you are a fan of long term use, and that is clearly a good thing when the patient is one headed back to a drug culture of life of crime or is obsessed with the drug. But- what about patients like me and I think many others who have zero contact with the drug world, have never taken an illegal drug, and yet have taken Ocy C over the years for pain and find it all but impossible to stop the Ocy C.
The Suboxone helps with the W/D and just getting through with that is all we want. NA meetings and the like are like being on Mars, it makes no sense. There are no drug cravings at all and the goal is just normal. Or rather, the goal is to make it through the W/D which is so harsh with Oxy C as to be dangerous for older people, whose only source of drugs indeed is the doctors Rx for them And now that too is unavailable. This group does not need Suboxone to become a new problem for them. They just want the help. It is not critically important to determine “who” is being treated. The certification training materials seem to brush over this so lightly that there is only one induction method allowed. One that a drug company would love, but not always a patient — pleading, do no harm.
My Thoughts:
I hear you, and watch for those patients. Frankly I wish I had more of them, so that I could get some movement through my practice—- instead of being stuck with 100 chronic patients and a long wait list. The financial motivation for the DOCTOR is to push people through, for that same reason. Of course the drug company gets paid in either case.
The first question is whether buprenorphine even helps in the case you describe. It is easier, in many ways, to taper with methadone than with buprenorphine, as you don’t have to divide such tiny pills. It has been suggested that it is easier to taper off a partial agonist than an agonist—and I believe that to be true, simply because I have seen people do the former and not the latter. But I don’t know HOW much easier it is—or if psychological aspects of the taper were more responsible than the person’s state of misery.
There were several studies a few years ago that showed relapse rates of 100% in people treated with Suboxone for less than a year; those findings, it seems to me, put a damper on the idea that buprenorphine could be useful for short-term detox. But I don’t know where those people would have fallen on the spectrum that you are presenting. I do know that they were people with a primary diagnosis of ADDICTION— NOT chronic pain– so maybe they are not relevant here.
My caveat would be that I HAVE met many people over the years who are convinced that they fall in the pain camp you describe, but who turn out to be just as ‘addicted’ as anyone else. They describe the process in different terms; instead of admitting to ‘relapsing on opioids’, they describe ‘deciding the pain was worse than they expected, and that it was a mistake to go off opioids.’ They will claim to be different…. But an objective observer would see the same growing attachment to opioids, the same gradual dose escalation, the same excitement and activity when opioids are ‘on board’, and the same depression and misery if a day passes without using.
I agree with your thoughts, and get your point. I just don’t know if very many people are as clearly-defined as you describe. One reason is because there are few conditions that cause pain severe enough to require high-dose opioid agonists for an extended period of time– say, a few months– that then go away. Most pain conditions have residual symptoms—- from chronic inflammation, or even from the set-up of central pain circuits. In a sense the pain is remembered, even after the original injury is repaired. The severity of that residual pain is affected by the person’s emotional state, dependency, motivation, genetics….. and the residual pain becomes a expressway back to using opioids— an expressway that is used often by many people.
Thanks for your comments!

Uncoupling of analgesia, tolerance, and euphoria from mu-agonists using buprenorphine

I presented this topic at the Atlanta meeting of ASAM a couple weeks ago. There are too many slides, but the historical stuff was just too fascinating to leave out. I wanted to demonstrate, by lining it up on the side, how time has compressed the most critical discoveries to a very short period of time. In other words, it wasn’t until thousands of years of opium use that the general concept of endorphines and opioid receptors came along. We can only hope that similar understandings of the biological basis of tolerance and withdrawal will be comparatively soon.
My study shows something truly fascinating– that a partial agonist seems to anchor tolerance at a lower level, still allowing for potent analgesia, but preventing euphoria and dose escalation. I have used this combination in people with very major surgeries, that are known to be quite painful– i.e. knee and hip replacements, dental surgeries, gallbladder surgery, and median sternotomy.