Opiate-induced constipation is frequently encountered by hospitalized patients. As Ben Franklin said, “An ounce of prevention is worth a pound of cure,” therefore an aggressive bowel regiment of stool softeners and laxatives will often prevent this problem from becoming a serious one. Not shockingly conventional bowel regiments sometimes don’t work and clinicians must resort to other treatments. Oral naloxone (Narcan) in escalating doses has been shown to be a successful treatment for opiate-induced constipation and even for post-op ileus in small studies. However its usage is limited by systemic side effects such as return of pain or withdrawal symptoms. Addressing this problem is an interesting blinded trial by Thomas et al. in the NEJM that randomized a study population of 133 patients with advanced illness (terminal cancer or end-stage disease) to receive either methylnaltrexone or placebo. The cool thing about methylnaltrexone is that it’s N-methylation prevents it from crossing the blood-brain barrier, therefore reducing effects on analgesia. Within 4 hours of administration, 48% of patents treated with methylnaltrexone had laxation (defection) vs. 15% in the placebo group (NNT=3). Importantly, both groups had similar pain scores at baseline and these scores minimally changed during the course of the trial. This trial is also unique in that it studies a population of patients in hospice or palliative care, where unfortunately there is a deficiency of evidence-based therapies for this group of very ill and highly-deserving patients.
For a refreshing change this week’s NEJM was focused on gastrointestinal issues as there was another article examining a treatment for chronic constipation. Prucalopride is a selective 5-HT4 receptor agonist which increases colonic motility. In a trial (conducted 9 years ago!) involving 620 patients with chronic constipation, prucalopride 2mg normalized bowel function in 46.6% patients compared to 25.8% patients who received placed (NNT= 5) . Laxatives are a $1.5 billion industry which means constipation is a very common problem and there are a lot of people looking and willing to pay for an effective treatment. Undoubtedly many of these people (as well as the Novartis execs) were disappointed when tegesrod was withdrawn from the US & Canadian markets due to concerns of excessive cardiovascular events in clinical trials. Therefore, while prucalopride was shown to be efficacious in this short, 12 week trial, its long term safety remains to be verified in larger and longer clinical trials. Given that this trial was conducted so long ago, I suspect there isn’t anything very promising in the pipeline. In the interim, patients should still be advised to eat high fiber diets and take a combination of laxatives as needed.
News from our colleagues in the UK: The metabolic syndrome has been sometimes been linked to the development of diabetes mellitus 2 and cardiovascular disease, suggesting the syndrome represents a risk “greater than the sum of its parts.” The syndrome has various definitions, but many have accepted the International Diabetes Foundation’s (IDF) definition; abdominal obesity plus two of the following: triglycerides > 150 mg/dL, HDL < 40, hypertension, and impaired fasting glucose. However there has been considerable debate whether metabolic syndrome truly is a distinct syndrome or just a group of conditions that happen to co-exist. Two prospective studies reported in the Lancet, the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) and the British Regional Heart Study, examined the supposed association of metabolic syndrome with the development of DM2 or CVD. In PROSPER, the metabolic syndrome was not associated with increased risk of cardiovascular disease (HR 1.07, 95% CI 0.86 to 1.32) but was highly associated with a greater risk of diabetes (HR 4.41, 95% CI 3.33 to 5.84). Curiously, neither the metabolic syndrome nor any of its components were significantly associated with the development of CVD in the PROSPER trial. The British Regional Heart Study (n= 2,737 males) did find a small association between metabolic syndrome and CVD (HR 1.27, 95% CI 1.04 to 1.56), but having the syndrome was more strongly predictive of the development of DM2 (HR 7.47, 95% CI 4.90 to 11.46). The new findings therefore show that the metabolic syndrome does not usefully predict a simultaneous risk of DM and CVD. The authors recommend that clinicians should focus on a global assessment of CVD risk based on previously validated criteria (for instance Framingham) rather than chasing down the rather cumbersome diagnosis of metabolic syndrome.
Finally, Neurology published guidelines for the diagnosis and treatment of Benign Positional Paroxysmal Vertigo (BPPV). Essentially it is a systematic review by a group of BPPV experts. Among there findings was there was a lack of standardization of treatment for BPPV. They found that the canalith repositioning procedure (CRP) is safe and effective in the treatment of posterior canal BPPV (the most common variant). There is an alternative procedure called the Semont maneuver that may be “possibly effective.” Postmaneuver activity restriction was not necessary. Regarding surgical options, there was not sufficient evidence to recommend or refute posterior semicircular canal occlusion or singular neurectomy as treatment for BPPV. They also concluded that there was a lack of evidence supporting pharmacologic therapy for BPPV. The online article is very useful because there are online videos demonstrating how to perform these CRPs. So practice your CRP!