Month: March 2016

Ketamine For Anger Management

From the land of “we still have droperidol”, this case series details the use of ketamine as “rescue” treatment for “agitated delirium”.  In lay terms, the situation they’re describing is the utterly bonkers patient being physically restrained by law enforcement for whom nothing else has worked.

In this case series, which represented only 49 of 1,296 patients with acute agitation, intramuscular ketamine was used as second- or third-line therapy behind droperidol and benzodiazepines.  Target dosing was 4-6 mg/kg, similar to procedural sedation.  Of the 49 requiring rescue ketamine, 44 were effectively sedated within 120 minutes – with a median time to sedation of 20 minutes.  The patients who were not adequately sedated with their initial dose of ketamine almost all received deliberate underdosing out of concern for potential respiratory impairment.

Three patients suffered adverse effects – two with vomiting, and one with desaturation 40 minutes after ketamine.  As with any observational series without a control, particularly a small one, little can be conclusively stated regarding the safety.  However, it is reasonable to consider any potential harms from such large doses of ketamine in the context of the harms of alternative sedating agents or injuries from continued agitation.

It may even be worth trying on the big green guy.

“Ketamine as Rescue Treatment for Difficult-to-Sedate Severe Acute Behavioral Disturbance in the Emergency Department”
http://www.ncbi.nlm.nih.gov/pubmed/26899459

ClinicalTrials.gov Registration & Cleaning Up Primary Outcomes

It is an oft-repeated pseudoaxiom that half of your medical knowledge is wrong – we just don’t yet know which half.  This hyperbole is founded, in part, in the work of Ioannidis and examinations of refutations of clinical trials.  This study represents another log to toss onto our conflagaration of uncertainty.

These authors noted a recent analysis of large clinical trials funded by the National Heart, Lung, and Blood Institute showed these trials had mostly neutral results.  Neutral trials, of course, are still valuable – they frequently help inform efforts to prevent unnecessary or low-value care.  However, the prior analysis only evaluated studies published after year 2000, the year trials began being registered in ClinicalTrials.gov.  This new analysis extended the review window back to 1975, to see if this trend of predominantly null outcomes was a historical trend, or whether the requirement to publicly pre-specify a primary outcome might have had some effect.

Not terribly surprisingly, there is a relatively clear difference in the frequency of null outcomes in the post-ClinicalTrials.gov period compared with prior:

The authors’ quite reasonable conclusion: prior trials, not having the requirement to pre-specify a primary outcome, were probably more likely to retroactively promote a positive outcome as the primary outcome of a study.

Should all these primary outcomes prior to 2000 be re-tested?  Considering all these prehistoric trials noted ties to industry, it’s probably a fair suggestion – and, certainly, it fuels our further skeptical re-examination of established medical practices.

“Likelihood of Null Effects of Large NHLBI Clinical Trials Has Increased over Time”
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0132382