PubMed Update March/April 2014

Better late than never, right? 24 papers over two months.

1) Overdose rescues by trained and untrained participants and change in opioid use among substance-using participants in overdose education and naloxone distribution programs: a retrospective cohort study.

Doe-Simkins M, Quinn E, Xuan Z, Sorensen-Alawad A, Hackman H, Ozonoff A, Walley AY.

BMC Public Health. 2014 Apr 1;14(1):297. [Epub ahead of print]

Comments: Sometimes naloxone is used by bystanders who have not been formally educated (or “trained”) in administering naloxone. This innovative analysis suggests that the untrained witness does a good job in lay naloxone administration.

2) Easy-to-use overdose antidote earns fast-track approval.

Kuehn BM.

JAMA. 2014 Apr 23-30;311(16):1600. doi: 10.1001/jama.2014.4483. No abstract available.

Comments: The naloxone auto-injector – Evzio – has been approved and is expected to be available this summer.

3) Research gaps on methadone harms and comparative harms: findings from a review of the evidence for an american pain society and college on problems of drug dependence clinical practice guideline.

Weimer MB, Chou R.

J Pain. 2014 Apr;15(4):366-76. doi: 10.1016/j.jpain.2014.01.496.

Comments: Basic summary is that it’s not entirely clear why there was such a surge in methadone-related deaths in the early part of the 2000s. It’s important to remember that the surge came after a surge in oxycontin-related deaths, when many payers shifted their preferred agent from oxycontin to methadone. Mortality data seems to follow the trend of the most prescribed agent.

4) Paramedic-supplied 'Take Home' Naloxone: protocol for cluster randomised feasibility study.

Moore C, Lloyd G, Oretti R, Russell I, Snooks H.

BMJ Open. 2014 Mar 20;4(3):e004712. doi: 10.1136/bmjopen-2013-004712.

Comments: Outstanding, innovative design to reach those at very high risk of future overdose events. I anxiously await results.

5) Intranasal naloxone for treatment of opioid overdose.

[No authors listed]

Med Lett Drugs Ther. 2014 Mar 17;56(1438):21-4. No abstract available.

Comments: Can’t access.

6) Long-term opioids and naloxone administration in a district general hospital.

Facey C, Brooks D.

BMJ Support Palliat Care. 2014 Mar;4 Suppl 1:A103. doi: 10.1136/bmjspcare-2014-000654.297.

Comments: All I see is an abstract here that suggests naloxone is being over-administered to patients on long-acting opioids in the inpatient setting. This is hard to assess without more details, including the context of the facility, but I am somewhat skeptical of the authors stark conclusions. The authors state that the only reason to administer naloxone is respiratory depression. There are flaws with this – providers often don’t document respiratory rate or use default parameters and don’t actually measure the rate; oxygenation is often a far better parameter; and there are other reasons to administer naloxone in a monitored setting, such as hypotension which is often caused by opioids and may be somewhat improved with naloxone.

7) Management of opioid addiction with buprenorphine: French history and current management.

Poloméni P, Schwan R.

Int J Gen Med. 2014 Mar 3;7:143-8. doi: 10.2147/IJGM.S53170. eCollection 2014.

Comments: A history and update on opioid use disorder management in France, including summary of the remarkable impact of buprenorphine on overdose mortality in that country.

8) Methadone overdose and cardiac arrhythmia potential: findings from a review of the evidence for an american pain society and college on problems of drug dependence clinical practice guideline.

Chou R, Weimer MB, Dana T.

J Pain. 2014 Apr;15(4):338-65. doi: 10.1016/j.jpain.2014.01.495.

Comments: Methadone has a long history of potential issues with the QT phase of the cardiac cycle (we’ve discussed this before on this blog so I won’t include a nifty cardiac cycle picture again here). One question with the surge in methadone deaths was if it was related to the lengthening of the QT interval. The basic summary is that there’s no data to support that at this time.

9) Methadone safety: a clinical practice guideline from the american pain society and college on problems of drug dependence, in collaboration with the heart rhythm society.

Chou R, Cruciani RA, Fiellin DA, Compton P, Farrar JT, Haigney MC, Inturrisi C, Knight JR, Otis-Green S, Marcus SM, Mehta D, Meyer MC, Portenoy R, Savage S, Strain E, Walsh S, Zeltzer L.

J Pain. 2014 Apr;15(4):321-37. doi: 10.1016/j.jpain.2014.01.494.

Comments: No recommendations were based on high-quality data.

10) Methadone Overdose and Withdrawal in a Tetraplegic Patient: A Case Report.

Connelly P, Wu H.

PM R. 2014 Mar 2. pii: S1934-1482(14)00098-7. doi: 10.1016/j.pmrj.2014.02.012. [Epub ahead of print] No abstract available.

Comments: Methadone is metabolized by enzymes in the liver that are also affected by other common drugs. In this case ciprofloxacin and phenytoin messed up the metabolism and caused overdose, then withdrawal. This is also a reminder that overdose isn’t always evidence of a substance use disorder – it is a risk of ‘risky medications’ not necessarily ‘risky patients.’

11) High-Risk Use by Patients Prescribed Opioids for Pain and Its Role in Overdose Deaths.

Baumblatt JA, Wiedeman C, Dunn JR, Schaffner W, Paulozzi LJ, Jones TF.

JAMA Intern Med. 2014 Mar 3. doi: 10.1001/jamainternmed.2013.12711. [Epub ahead of print]

Comments: Risk factors for death were high dose opioid prescription and using multiple providers – 55% of deaths had one of these risk factors. What’s interesting, however, is the other 45%, who did not have any of these risk factors.

12) Take-home naloxone kits preventing overdose deaths.

Eggertson L.

CMAJ. 2014 Jan 7;186(1):17. doi: 10.1503/cmaj.109-4663. Epub 2013 Nov 25. No abstract available.

Comments: A news article in the journal regarding naloxone programs.

13) Opioid prescribing: a systematic review and critical appraisal of guidelines for chronic pain.

Nuckols TK, Anderson L, Popescu I, Diamant AL, Doyle B, Di Capua P, Chou R.

Ann Intern Med. 2014 Jan 7;160(1):38-47. doi: 10.7326/0003-4819-160-1-201401070-00732. Review.

Comments: There are lots of guidelines for reducing risk with opioid prescribing but no data.

14) Heroin use and heroin use risk behaviors among nonmedical users of prescription opioid pain relievers - United States, 2002-2004 and 2008-2010.

Jones CM.

Drug Alcohol Depend. 2013 Sep 1;132(1-2):95-100. doi: 10.1016/j.drugalcdep.2013.01.007. Epub 2013 Feb 12.

Comments: Opioid use precedes heroin use, heroin use is going up.

15) "SALOME gave my dignity back": the role of randomized heroin trials in transforming lives in the Downtown Eastside of Vancouver, Canada.

Jozaghi E.

Int J Qual Stud Health Well-being. 2014 Mar 13;9:23698. doi: 10.3402/qhw.v9.23698. eCollection 2014.

Comments: Personal level experience in heroin treatment programs.

16) 'Lingering' opiate deaths? Concentration of opiates in medulla and femoral blood.

Naso-Kaspar CK, Herndon GW, Wyman JF, Felo JA, Lavins ES, Gilson TP.

J Anal Toxicol. 2013 Oct;37(8):507-11. doi: 10.1093/jat/bkt061. Epub 2013 Jul 18.

Comments: Analysis of opiate levels from femoral and cerebral sources suggesting opiates linger in the brain – authors suggest this may explain low blood opioid levels in overdose deaths but I’m not sure that’s a reasonable conclusion.

17) Is opioid substitution treatment beneficial if injecting behaviour continues?

Gjersing L, Bretteville-Jensen AL.

Drug Alcohol Depend. 2013 Nov 1;133(1):121-6. doi:

Comments: Yes.

18) Medication-Assisted Therapies - Tackling the Opioid-Overdose Epidemic.

Volkow ND, Frieden TR, Hyde PS, Cha SS.

N Engl J Med. 2014 Apr 23. [Epub ahead of print]

Comments: A discussion of methadone, buprenorphine and naltrexone as responses to the opioid overdose epidemic.

19) Poisonings requiring admission to the pediatric intensive care unit: A 5-year review.

Even KM, Armsby CC, Bateman ST.

Clin Toxicol (Phila). 2014 Apr 17. [Epub ahead of print]

Comments: An increasing proportion of pediatric poisonings involve opioids.

20) Opioid-related mortality and filled prescriptions for buprenorphine and methadone.

Wikner BN, Ohman I, Seldén T, Druid H, Brandt L, Kieler H.

Drug Alcohol Rev. 2014 Apr 16. doi: 10.1111/dar.12143. [Epub ahead of print]

Comments: Rarely does methadone or buprenorphine prescribed for maintenance result in death. I can’t access the full article so cannot assess quality.

21) Unexpected variation of the codeine/morphine ratio following fatal heroin overdose.

Gambaro V, Argo A, Cippitelli M, Dell'acqua L, Farè F, Froldi R, Guerrini K, Roda G, Rusconi C, Procaccianti P.

J Anal Toxicol. 2014 Jun;38(5):289-94. doi: 10.1093/jat/bku016. Epub 2014 Apr 11.

Comments: Codeine may accumulate in brain tissue more than morphine (heroin’s major metabolites are codeine, morphine, and 6-monoacetylmorphine).

22) Suboxone versus Methadone for the Treatment of Opioid Dependence: A Review of the Clinical and Cost-effectiveness [Internet].

Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2013 Nov 14.

Comments: They are similar.

23) [No opiates against cannabis hyperemesis syndrome].

Bonnet U, Stratmann U, Isbruch K.

Dtsch Med Wochenschr. 2014 Feb;139(8):375-7. doi: 10.1055/s-0033-1360065. Epub 2014 Feb 11. German.

Comments: An odd case report.

24) Analyzing methadone-related deaths.

Newman RG.

J Addict Med. 2014 Jan-Feb;8(1):73. doi: 10.1097/ADM.0000000000000014. No abstract available.

Comments: A letter responding to “Methadone-related overdose deaths in rural Virginia: 1997 to 2003” – I can’t access.