http://annals.org/article.aspx?articleid=2089370
One large, fair-quality retrospective cohort study (
n = 9940) found that, compared with nonuse, recent opioid use was associated with an increased risk for any overdose events (adjusted hazard ratio
, 5.2 [CI, 2.1 to 12.5]) and serious overdose events (adjusted HR, 8.4 [CI, 2.5 to 28]) (
Appendix Table 2) (
42). The annual overdose rate was 256 per 100 000 person-years among patients who had recently received prescribed opioids versus 36 per 100 000 person-years among those who had not. Higher doses were associated with increased risk. Compared with an MED of 1 to 19 mg/d, the adjusted HRs for overdose ranged from 1.44 (CI, 0.57 to 3.62) for an MED of 20 to 49 mg/d to 8.87 (CI, 3.99 to 19.72) for an MED of at least 100 mg/d. A similar pattern was observed for serious overdose.
If we're getting to where zero mg is the safest dose, which it is, then let's go there now. Let's not waste our time pretending 90mg or any other arbitrarily chosen cutoff is magically safe, as if one mg higher is deadly and 1 mg below is without risk. It's like the frickin' 5 blade razor. It's perfect and no one can imagine anything better, until some dweeb comes along and shocks the world with a six blade razor claiming its radically better.
I'm aware of all these studies and I think they're very valuable studies. They show dose dependent risk for opiates. They show that ZERO mg is the safest dose, not 90mg daily morphine. My point was, what studies show that 90 mg is somehow the magic number?
This study doesn't show that. The highlest category is "at least 100mg/d." That category would include patients at 100mg/day, 120mg/day and 1,000mg per day.
You can't possibly believe that the overdose risk of 1,000 mg/day is no greater than 120mg, can you?
My point: Whatever cutoff you choose, be it 100mg/day like this study, or 120mg or 150mg, or whatever, that category will include doses up to infinity. Therefore, the dose just under the cutoff will appear to be the "safe dose." But still not safer than something even lower.
The other categories are very narrow and share roughly the same risk. But a category of "greater than" some number creates a very, very large risk ratio because it would necessarily include doses way off the scale. Then, if you take the dose just under that cutoff, it's going to look like that's the magic number. If they had made that category ">120mg/d" or ">200mg/day" that would still be the highest risk group, in fact it would be higher since you've left out some low dose people. Then you could conclude:
"190mg per day is the safest dose!"
Also, since it's a dose dependent risk, anyone who has any dose limit in their practice, for example, 40mg/d, I can go to them and say, "30 mg is safer!"
Here's where it's a big deal to me. I've made a point have a dose limit in my practice of 120mg/day, though I prefer no to start if they're on none, and not to dose escalate if they're on less than 120mg/d. It took some very difficult work to get every single one of my patients to at or below that threshold. The numbers over it was not many, and all were started on those doses by someone else. All in all it's worked out great. I have what is consider a very low dose Pain practice with many patients on zero mg, or low to moderate doses. Only a few patients deemed low risk and proper candidates, monitored very closely are on 120mg/day, and none over that limit.
But what do we do now, now that someone came along and arbitrarily picked 90mg as a threshold? Do we break the backs of our compliant, controlled, non-addict, non-diverting patients, because someone else picked this dose which actually isn't the safest dose, because 80mg is safer than that, 70mg safer than that and zero safer than all?
Then when they come along next year and say "Nope, 40 mg is the threshold, 40 is safer"? Because 40 mg is less risk than 120mg, or 90 mg or 60 mg?
So if what we're getting at, is that the only safe dose is zero mg per day, then let's just get right to zero mg per day. Let's not play these silly games of every year, some resident that wants to do a research project, "See! 80 mg/day is safer than 90mg! Over 80 is deadly!" then "70mg is safer! Over 70mg is deadly!"
Because the only risk free dose is zero.
Ultimately it has to do with the patient, more than the dose. The most dangerous
patients shop around for the highest doses. A little old lady on 200mg morphine per day maybe be infinitely lower risk than a 29 yr old addict that walks out the door with a prescription for 80mg/day (MS ER 40mg #60 pills) or even 20 mg/day intent on injecting the whole bottle tonight. This data applies to populations much better than individual patients. We cannot forget that.