Saturday, August 30, 2014

Reefer Madness part two

Medical marijuana has its boosters and detractors.  I have rarely seen a topic in medicine so polarized.

The following points have been raised by one side or the other.

From the medical establishment.

There is no evidence of the efficacy of medical marijuana

Actually there is considerable evidence of the efficicacy of cannabinoids in both pain and spasm both in human and animal studies.  Cannabinoids have in fact been thoroughly studied, possibly more than many classes of drugs.  The mechanism of action is quite well understood.  There has only been one study comparing smoked marijuana with placebo but this is a reflection of the difficulty of studying a drug which is illegal in most of the world.  This study was by the way positive in favour of smoked marijuana.  

The percived lack of evidence is more of a sad reflection on the academic pain community and the pharmaceutical industry who have had 13 years to test marijuana for pain but have with a few exceptions sat around twiddling their thumbs or pontificating.

Further if we look critically at the evidence for many conventional treatments they too are quite weak.  Even the best treatments for pain have a NNT of 3 or higher which simplistically means that they don't work in over 2/3 of patients.  Then we have to look at the large number of drugs that are used off label for which no studies have been done, the drugs that are used in pediatric patients and the drugs that are used in the frail elderly; neither children or frail elderly get included in clinical trials.  And of course we have to look at the treatments which have never been tested because, well, we've always done it that way.

The potency of medical marijuana is variable and unpredictable.

This would almost be a valid argument if conventional drugs had pharmacokinetics and dynamics which were constant from person to person.  But we all know that isn't true.  If we for example give 10 mg of morphine IV to a group of similar 70 kg individuals we know that we can expect a variety of responses.  Some people will get sleepy, some nauseated, some itchy.  Some will get good analgesia, some will get no analgesia.  This applies to most drugs which is why when things are critical we measure blood levels as we do with antibiotics, digoxin and many anticonvulsants.  Further as we all know and practise in anaesthesia, we titrate to effect.  

This also assumes that bioavailable is constant for the same drug.  We also know this isn't true, there are huge differences in bioavailability between generic and brand name drugs.  This is of course a major problem with drugs like Coumadin and Digoxin.  

The current requirement to obtain drug from a registered supplier also means that patients can get marijuana of known potency.  Not that I like to praise any policy derived by our Canadian Tea Party.

Smoking is harmful

Hard to argue with this one.  Except.

As every anaesthesiologist knows one of the best ways to deliver drugs is through the lungs.  A lot more drugs would probably be administered by this route if a reliable delivery system could be devised.    Smoking while harmful does deliver vapour to the lungs.

It is also possible to purchase a vapourizer to vapourize the marijuana.  This may or may not be safer than smoking.

Patients who smoke marijuana for pain typically smoke way less than do recreational users.  Many patients will only take one or two puffs and typically less than 2 grams a day are necessary.  Interestingly enough our government allows patients to have up to 5 grams a day.

It is possible to take marijuana by the oral route as well.  Because of the reduced bioavailability higher doses are necessary which can be a problem with a drug which is controlled tightly and now fairly expensive.  There is an interesting book, "Cooking with Cannabis" available for free download on the internet.

We have many good treatments for pain, marijuana should not be necessary

Except we don't.  Most of the drugs we have either don't work or are not tolerated in large proportions of patients (this also applies by the way to marijuana).  Some like opioids are extremely controversial.  Multi-disciplinary pain clinics have long wait lists, are expensive and quite frankly really aren't that efficacious.  (At a seminar I gave to a group of pain physicians years ago, I asked if anybody had ever seen somebody benefit from a rehab program.  Only one person had.)  Interventional treatments are great for the interventionalist's bank account but are of limited benefit for patients.  

Further marijuana or any treatment should not be a stand alone treatment but should ideally be a part of an inter-disciplinary approach to pain involving many modalites, focused on the patient.  I also believe in the Easter Bunny.

Marijuana can cause psychosis.

This is based on a retrospective observational study looking at the developement of schizophrenia in teenagers using marijuana.  Funny how observational studies are okay when they justify somebody's agenda.  The saying correlation does not imply causation applies here, and it is quite likely that teenagers with the early symptoms of schizophrenia might be tempted to try marijuana, easily available in most high schools to relieve these symptoms.  Notwithstanding this, I will not authorize it for teenagers (easy for me because I only see adults).  

Conventional drugs are not innocuous either.  NSAIDs cause GI bleeding and renal failure with prolonged use.  Acetaminophen cause liver and kidney disease.  Anti-depressants cause weight gain.  Opioids cause endocrine abnormalities and have been shown to produce loss of grey matter.  I could go on.  

Cannabinoids may be effective but we should wait until more research is done and until the pharmaceutical industry comes up with a pharmaceutical product.

Again, how much more research do we need?  Marijuana has been sort of legal in Canada for medical uses since 2001 and have we seen any new products?  (Oh I forgot, we don't do pharmaceutical research in Canada.)    The only recent cannabis derived product to come out is Sativex which was developed in Britain.  Some pharmaceuticals may have something in the pipe as it were.   While most of Big Pharma is inherently evil, most of use would welcome the opportunity to be able to prescribe something made by Pfizer or Eli Lilly.

Doctors are being forced......

No they are not.  If they chose to write a prescription, they can if they don't they can refuse, just like they can refuse any service which is not life or limb threatening.  This applies by the way to other requests that may be made by patients.  It is the failure of physicians to act as responsible gatekeepers which helps to maintain the ongoing crisis in healthcare.

And from the advocates of medical marijuana:

Marijuana is a natural medicine.

Actually the marijuana smoked today bears very little resemblance to that smoked 100 or even 30 years ago.  Todays marijuana is the product of breeding and cloning to maximize the amount of THC.  It is for the most part grown hydroponically using who knows how many chemicals.  If you want to consider that natural, go ahead.

Marijuana was widely used as a medicine prior to being made illegal.

Not really a great endorsement.  Strychnine, arsenic and mercury were also widely used as medicines.  Marijuana based preparations were used in the 19th and early 20th century.  They didn't persist largely because they didn't work that well.  Further they were not used in Western medicine prior to their introduction from India in the mid 19th century. 

Marijuana is a wonder drug, a panacea

When I used to give talks on chronic pain management, the first thing I would tell the audience is that there are no panaceas.  This applies to marijuana.

In closing

We don't have a lot of good treatments for chronic pain and most of us in the business welcome any addition to our tool box.  Most of us don't like the way medical marijuana came about, by a court decision, we would rather the government had shown some leadership there.  We are stuck with a bad process and those of us who have chosen to authorize or prescribe are trying to do what is best for our patients.  

It would certainly be refreshing to get a dialogue free of hyperbole because this is not going away.

Reefer madness part 1

Early on in my career trying to treat people with chronic pain, people would tell me that the only thing that worked for their pain was smoked marijuana.  Of course people told me lots of other things that were the only thing that worked for their pain including alcohol, cocaine, injectable Demerol and 30 percocet a day.  I of course told them sorry I couldn't comply with their request.  Marijuana was illegal but as I told patients, if you believe it helps your pain, do it discretely.

Marijuana is still illegal in Canada.  The law is enforced with a certain lack of vigour and consistancy across the country.  Despite this Canada spends between $500 million and $1 billion dollars a year, arresting, proscuting and punishing people for possession of marijuana.

In 2001, courts in Canada decided that it was unconstitional to bar patients from using marijuana for their pain and the government of Canada was forced to design a process by which patients could receive medical marijuana.  This initially involved the signatures of 2 specialists and allowed the patient to grow his own supply, designate a supplier or buy from the government.  

One day in 2001 I got a phone call from the Public Relations department of the hospital.  "Would you like to be interviewed by the CBC?", they asked.  "You cannot however mention the hospital".  The interview was as I should have suspected on medical marijuana.  The regulations had at that time not been finalized, I had never actually prescribed marijuana to any patient and my only knowledge was what I had read or seen at meetings but I figured any publicity is good publicity and so I was interviewed live on the afternoon radio show at 1700 hours.  End of story?

Not really.  On Monday my wife phoned me at work,  "Your interview is on the CBC national radio news".  I was subsequently interviewed by both local papers and got to have my second 15 minutes of fame.  

Keep in mind that I still had not prescribed marijuana to any patient.

I soon started getting phone calls from patients desperate to get the authorization forms filled out yesterday.  I explained that they would need to have a referral from another doctor and that I had a wait list.  After about a year, I started noticing a certain type of new patient showing up.  These were usually men, men with pony-tails under leather ball caps.  They usually had some vague pain complaint, had not really tried anything else for their pain except marijuana which I could usually smell on them.  I patiently explained, that the regulations as I understood them only allowed medical marijuana after other treatments had been trialled and failed and offered to start these treatments.  That was usually the last I saw of them.  

At that time I practised at the Centre of Excellence in a an academic pain clinic with 3 other doctors.  Shortly after the new regulations came into effect, The Professor at a staff meeting sternly forbode us to sign any authorizations.  I felt that this was curious as he professed to be all about research and this was virgin research territory plus the publicity for the clinic but I kept my mouth shut lest I be verbally castrated which was (and still is) how he dealt with differences in opinion.

For the next year or so, I politely explained to all patients, legitimate or not that I could not fill out the authorization.  That was until a patient I had seen years ago came to see me.  He had what we called failed back syndrome after back surgery with quite severe pain and spasms.  He had been using marijuana which he grew in his house which had lead to his arrest.  He had not really had any treatments since the epidurals I had tried years earlier and so I explained that we actually had lots of great treatments now and that he should try them.  Not surprisingly the first two gave him severe side effects and no relief which sadly is true of most of the wonder drugs in chronic pain.  At that point, I just said shag it and signed the damn forms.  

At that time I had an out in that I worked in another clinic so I just directed the patients to that clinic away from the scrutiny of The Professor.  And I continued there in a small way.  I started doing talks on cannabinoids for Valeant which markets nabilone (Cesamet) in Canada.  I was very cautious with patients, I treated them like any other consult, I listened to their story, examined them and if there were treatments they hadn't tried, I suggested that they try them.  Wherever possible I tried to get them to try nabilone a cannabinoid which is available by prescription and covered under our provincial drug paln or Sativex which is not reimbursed.

A few doctors saw business opportunities in medical marijuana and set up clinics specifically for the authorization of medical marijuana.  Most of these clinics charged $400 for completion of the paperwork, some even allowed you to be interviewed by Skype.

Patients came in a variety of presentations.  Many were sketchy but had a legitimate problem, quite a few were straight-laced folks with intractable pain who had tried somebody's marijuana out of desperation and some were just plain crazy.

In the interim, the Canadian Tea Pary came into office and the idea of people smoking marijuana recreationally or otherwise gave them dyspepsia.  Their hands were tied however by the court decision and so they had to keep the program.  They did however find a way to modify it in a way to make medical marijuana less available as well as reward well connected businessmen.  Effective last April, patients can no longer grow their own or designate a supplier but must buy from a Government registered supplier of which there are about 10.  Doctors rather than fill out the paperwork, must now write a "prescription" which the patient can they send to one of the companies who will then courier the week.  This has upset many long term medical marijuana users who previously grew their supply but now have to spend money with one of the suppliers.  The suppliers are for the most part slick operators with nice glossy brochures, they now sponsor pain meetings and I met my first detail man the week before last.

The change in regulations also sparked responses from both the medical societies and regulatory bodies.  From a physician point of view, the new regulations are actually better.  The "prescription" which I now write is a lot shorter and less complicated than the form I used to have to fill out.  Further just as doctors chose in the past whether or not to fill out an authorization, doctors can now chose whether or not to "prescribe" medical marijuana.  This didn't stop our College (Medical Board) from publishing regulations and demanding that doctors register with them; something they hadn't done between 2001 and 2014.  The Canadian Medical Association or at least the miniscule fraction of the profession that attends its annual meeting condemned the smoking of any plant material.

As someone who has been in the Medical Marijuana trenches for over a decade opinions are extreme on both sides and I wish to comment on and maybe refute some of the myths in my next post.

Friday, August 22, 2014

Dangerous medications or how I saved the 5 cc fentanyl

Hospitals, as we know, are dangerous places and most of us know of ways that we at least think would make things safer.  The problem is that most of these would involve spending money or would interfere with somebody's agenda.  So instead our hospital like most hospital focuses instead on creating solutions for things that aren't really problems.  This is not unique to hospitals, governments do this as well.

A significant source of badness in hospitals is when somebody injects the wrong drug.  This can range from innocuous to catastrophic. Another variation is when a more potent concentration of a drug or electrolyte is injected by somebody thinking they are injecting the lower concentration (often unaware that the higher concentration exists).

I went to a meeting a few months ago.  We were discussing what were called high alert medications and opioids were on the table which is why I attended.  There were a number of highly placed nursing administrators and a few pharmacists present and like most people who actually don't have to work for a living they were very pleasant and friendly; maybe a little surprised that a doctor showed up (if only because they had scheduled the meeting in the middle of the day, just for that purpose).  Specifically the 50 mg per ml morphine, the 10 mg per ml hydromorphone and incongruously the 5 cc fentanyl ampoule were on the chopping block.  Somebody high up in administration for various reasons wanted these medications gone except in various situations.

The first two are pretty much no brainers.  Obviously injection of 50 mg of morphine or 10 cc of hydromorphone could be catastrophic.  On the other hand many cancer patients are getting injectable narcotics by clysis requiring these highly concentrated solutions.  So either restrict them to palliative care units or keep them in pharmacy until they are needed.  Nice idea except that cancer patients also show up on medical or surgical wards and they are often admitted after hours when the hospital pharmacist is tucked into his bed.  We weighed this for most of an hour and I'm not sure what we actually decided.  The high concentration morphine and hydromorphone typically come in large bottles while regular strength comes in single dose ampoules which should alert all but the most brain dead nurse or physician.  Logically suggesting that people actually read the labels before they draw up medications makes sense but we all know about human factors analysis and not giving people a change to screw up.  I suggested why not put some harmless dye in the high potency narcotics like we do with 4% lidocaine.  Nobody thought that was a good idea although in about two years somebody will take credit for it.

We then went to the 5 cc fentanyl.  I don't use fentanyl much but some people do and like most doctors I don't like being told that a medication that has been used for at least 30 years can't be used anymore. Fentanyl is almost exclusively given by anaesthesiologists in the OR, by emergency room nurses or doctors and by ICU nurses usually to intubated or at least closely monitored patients.   First they kept on called this a high potency formulation.  Calmly and politely I explained that, no,  the 5 cc fentanyl has the same concentration as the 2 cc fentanyl.   I can see that giving 250 mcg of fentanyl when you only wanted 100 mcg could cause a problem for the patient, but unless you are someone who believes that the correct dose of any drug is one ampoule, this is unlikely to happen.  I then explained that we frequently use more than 100 mcg of fentanyl to induce anaesthesia and that while we could break open multiple ampoules of 100 mcg, this could lead to drug errors, injury to staff and problems with counts.  They then asked me what safeguards I proposed so that we could use the 5 cc fentanyl.

What I should have said was:  we go to medical school and then do 5 years of post graduate training, and we understand the pharmacology of fentanyl.  Further we are of moderate intelligence and can tell the difference between a 5 cc ampoule and a 2 cc ampoule.  I really should have said this but atypically for me I didn't take this obvious set-up.  Instead I mumbled the obvious that these patients were always monitored, that they was always an anaesthesiologist present and that the patients were usually intubated and ventilated shortly after the fentanyl was given.  

This went over well and the pharmacist filled out the appropriate exemption form.  I left the room thinking I had saved the 5 cc fentanyl.

About a week later, I came home late in the evening and did something I should have learned never to do.  I checked my email.  There was a form from our "quality" department which stated that our request for the exemption for the 5 cc fentanyl had been rejected because they did not have sufficient details about how we actually administered the fentanyl.  It has signed by the Head Stasi of Quality, (HSQ)  a lady I know all too well.

I had a fit.  I tossed and turned all night.  

What really pissed me off was that HSQ who signed the rejection had spent half a day in the OR with me because she wanted to see how we handled medications in the OR.

So first thing in the morning I wrote a letter.  I reminded the HSQ that she had spent a morning in the OR with me and had she not notice that I, not the nurses, the surgeon or porters,  injected all the medications.  I pointed out a lot of other stuff too.  I was maybe a little rude and condescending but in a controlled and logical fashion.  I then actually sat on the letter for about 3 hours, read it again decided everything was perfectly true and widely broadcast it by email.  

About an hour later I got a call from the head of Pharmacy who was apologetic.  Half and hour later, the Chief of Staff, a surgeon called me. "Why didn't you go through me, " he asked, "Don't you think I could have helped you?"  "Actually, " I said, "no I don't think you could have helped me."

Anyway we still have the 5 cc fentanyl.  And the HSQ was moved off the narcotic file so I at least temporarily no longer have to deal with her. 

We have now  turned to other "high alert" medications.

First came hypertonic saline.  About 10 years ago at other hospital a patient died of hyponatremia after a prolonged TURP.  It probably would not have made a difference but because it was the evening, there was nobody in pharmacy to get any hypertonic saline.  Consequently all OR's that do TURPs have hypertonic saline in their Pyxis.  How quickly people forget.  Our safety Stasi wanted to make hypertonic saline a patient specific medications meaning we would have to have to write an order and call pharmacy if we wanted hypertonic saline.  This required multiple exemption forms (one for the OR  and one for recovery room) to be filled out.  I realize all the bad things that can happen if you inject hypertonic saline by mistake, which is why I don't want it in my cart but keeping it in the Pyxis makes sense.  Anyway I filled out the form explaining that hyponatremia was a severe condition, the treatment of which was time sensitive, that we know what we are doing (I didn't actually say that) etc, etc.

They have also moved on the Magnesium Sulphate 5 g per 10 cc.  Some of my colleagues and I like to give 2-5 g and Mg to patients in the OR.  We believe it is analgesic and there is some evidence to this.  It is also a good anti-hypertensive and anti-arrhythmic.  Further I use it in the Pain Clinic on a completely non-evidence based basis.   Pharmacy who cite over-work whenever you ask to them to do something were proposing to put Magnesium into 100 cc mini-bags.  Another exemption form to be filled out.

Calcium Chloride/Gluconate had also been deemed dangerous.  Calcium disappeared from ACLS years ago although it is still on the crash cart.  We do use in in massive transfusion which I had to remind them we usually can't predict plus it is a pretty good inotrope in a pinch.  (It will also reverse the hypotension you get with  Magnesium if you inject it by mistake)  Pharmacy's solution was to draw up Calcium into syringes which would be stored in Pyxis. It is of course as easy to inject a pre-filled syringe (possibly easier) by mistake as it is to draw up a drug from a bottle and inject it and I could have pointed this out but they were on a mission and I can live with this one.

The euthanasia size bottles of Potassium Chloride disappeared years ago, now we have 10 MEq of KCl in 100 cc.

While I was writing this, I was reminded of something which happened about 10 years ago.  In an emergency room to the south of us, a nurse gave a patient 10 mg of hydromorphone instead of 10 mg of morphine leading to the patient's death on the way home from hospital.  When you think of it, this involved drawing up 5 cc instead of 1 cc, except that there is a 2 mg per ml morphine so one can sort of see the confusion.  (I am wondering if some well meaning administrator figured that the 10 mg morphine was dangerous and replaced it with 2 mg)  Our medical protective association, whom I (mostly my government actually) pay thousands of dollars a year to, came out with an atypically idiotic statement that hydromorphone was a dangerous drug.  Another physician and I had to write them a letter stating that hydromorphone doesn't kill patients, people kill patients (or something to that effect).

Tuesday, August 12, 2014

Yes ma'am I really am a doctor.

I was doing my penance in the pre-assessment clinic today.  A patient came in who was booked for a stone removal at the end of the week.  I introduced myself as Dr. BH from anaesthesia.

"Oh," she said, "you're just anaesthesia, I thought I was going to see a doctor."

"Actually", I said, "I am a doctor."  And what little bedside manner I have evaporated.  It was a frosty visit.

This is of course a problem in the US where nurses can give anaesthesia as my blogging colleague Great Zs has pointed out. 

I also loved the scene in "Deadwood" where a lady had to have a D+C for her miscarriage and one of the prostitutes, Trixie administered the ether.  This is a picture of her relaxing in the OR lounge after a tough case.

In Canada and in most of the British Commonwealth, anaesthesia has been the exclusive purview of physicians since the 19th century.  This didn't however stop our hospital from recently trying to buy an information pamphlet on surgery, which informed the patient that their anaesthesiologist could be a physician or a nurse.  I pointed out the flaw and I hope it disappeared.

I should be used to this now, I have been in the business for 24 years, not counting residency.  Sometimes I can even joke about it.  Like the time a patient in the OR about to go to sleep asked me if I had to go to medical school.  "No just Grade 11," I said, injecting the propofol.