As someone with an interest in neonatal abstinence (NAS) I am surprised that I missed this study back in May.\u00a0 Anyone who says they aren’t interested in NAS research must be turning a blind eye to the North American epidemic of patients filling neonatal units or postpartum wards in need of treatment for the same.\u00a0 News feeds such as CNN have covered this story many times with concerning articles such as this published “Opioid Crisis Fast Facts”<\/a> even the Trump White House has\u00a0 officially declared it as an emergency at this point<\/a>.\u00a0 With NICU resources stretched and care providers fatigue levels wearing thin (these patients are typically very challenging to take care of due to the crying and agitation with neurological excitability that is at the core of the symptoms, something needs to be done. The vast majority of neonatal care providers treat such patients with an approach that promotes first non pharmacologic strategies such as keeping mom and baby together when possible, breast feeding and disturbing these infants as little as possible to name a few points.\u00a0 For those patients though who require pharmacologic support though, the mainstay has been oral morphine.\u00a0 At least in our units though once a patient is admitted and undergoes treatment we are still looking at anywhere from 3-4 weeks on average that they will occupy a hospital bed.\u00a0 If only there was a better way.<\/p>\n While morphine is widely used to treat NAS symptoms unresponsive to other non pharmacologic methods of control, buprenorphine has a similar profile as an opioid but has less risk of respiratory depression as a partial agonist. A small but important trial has been published directly comparing the use of morphine to buprenorphine for treatment of NAS symptoms with the primary outcome being days of treatment and the second important point being length of stay.\u00a0 The trial, Buprenorphine for the Treatment of the Neonatal Abstinence Syndrome.<\/a>by Kraft WK et al was entitled the BBORN trial for short.\u00a0 This was a single centre trial in which a double blind\/double dummy approach was used.\u00a0 By double dummy this meant that after randomization those babies randomized to morphine received morphine plus a buprenorphine placebo and the other arm received a buprenorphine dose and a morphine placebo.\u00a0 In total 33 infants were randomized to buprenorphine and 30 to morphine (hence my comment about this being a small study).\u00a0 Their power calculation had called for 40 infants per arm to detect a 28% difference in the primary end point of duration of treatment but in the end that didn’t matter so much as they found a significant difference exceeding their estimate anyway.\u00a0 A lack of power would have become important mind you had they not found a difference as they wouldn’t have actually had the numbers to do so.<\/p>\n A strength of the study up front was that all care providers scored NAS symptoms the same way (need to take into account there is some subjectivity in scoring altogether though) and escalations and decreases of medication were done following a strict protocol both ways.\u00a0 In both arms, once a maximal dose of 60 mcg\/kg of body weight for\u00a0 buprenorphine and 1.2 mg\/kg for morphine was reached phenobarbital was added.\u00a0 When comparing the two groups at the outset there were no significant differences in characteristics so two generally similar populations of infants were being treated.<\/p>\n Before launching into the table, there were 21 babies in both groups that were bottle fed and 12 in the burprenorphine group and 9 in the morphine group that breastfed.<\/p>\nCould Buprenorphine do the trick?<\/h3>\n
The Results Were Indeed Impressive<\/h3>\n
| Outcome<\/td>\n | Buprenorphine<\/td>\n | Morphine<\/td>\n | p<\/td>\n<\/tr>\n |
| Median days of treatment<\/td>\n | 15 (3-67)<\/td>\n | 28 (13-67)<\/td>\n | <0.001<\/td>\n<\/tr>\n |
| Bottle feeding<\/td>\n | 15 (3-67)<\/td>\n | 28 (13-67)<\/td>\n | <\/td>\n<\/tr>\n |
| Breast feeding<\/td>\n | 20 (3-55)<\/td>\n | 28 (16-52)<\/td>\n | <\/td>\n<\/tr>\n |
| <\/td>\n | <\/td>\n | <\/td>\n | <\/td>\n<\/tr>\n |
| Hospital stay in days<\/td>\n | 21 (7-71)<\/td>\n | 33 (18-70)<\/td>\n | <0.001<\/td>\n<\/tr>\n |
| Bottle feeding<\/td>\n | 21 (7-71)<\/td>\n | 33 (18-70)<\/td>\n | <\/td>\n<\/tr>\n |
| Breast feeding<\/td>\n | 26 (7-58)<\/td>\n | 32 (20-58)<\/td>\n | <\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n No difference was seen in those who needed phenobarbital.\u00a0 Looking at the table, a couple things really stand out to me.\u00a0 They were looking for a 28% reduction in days of treatment.\u00a0 The results came in far excess of that at a 46% reduction.\u00a0 Curiously, breastfeeding which has classically been associated with a reduction in scores and therefore faster weaning due to less symptoms seemed to have the opposite effect here.\u00a0 Does this imply that breastfeeding slows down both duration of treatment and length of stay as a result?\u00a0 With a study this small it is difficult to say with so few breastfed babies but if I had to guess I would suggest those mothers that worked at breastfeeding may have had longer stays.<\/p>\n Should we all jump on the buprenorphine train?<\/h3>\nFor now I would give this a big maybe.\u00a0 One of the concerns about burprenorphine is that it comes as a solution of 30% alcohol.\u00a0 Giving multiple doses (3 per day in this study) of such a solution could in part contribute to these results of lower NAS symptoms.\u00a0 Is giving alcohol to reduce symptoms a good idea here?\u00a0 Not sure if there are any long term effects and moreover if the cumulative dose of this medication would be of a concern.\u00a0 Definitely something to check with your local pharmacist before rolling this out.\u00a0 On the other hand if the dose of alcohol provided was truly significant I might have expected the burprenorphine group to be poorer feeders due to intoxication which we certainly did not see.<\/p>\n With increasing volumes of newborns afflicted with symptoms of NAS we do need to find a way to stem the tide.\u00a0 Ideally, primary preventative strategies would be best but until that solution is found could burprenorphine be the next step in tackling this epidemic?<\/p>\n","protected":false},"excerpt":{"rendered":" As someone with an interest in neonatal abstinence (NAS) I am surprised that I missed this study back in May.\u00a0 Anyone who says they aren’t interested in NAS research must be turning a blind eye to the North American epidemic of patients filling neonatal units or postpartum wards in need of treatment for the same.\u00a0 […]<\/p>\n","protected":false},"author":2,"featured_media":4784,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_et_pb_use_builder":"","_et_pb_old_content":"","_et_gb_content_width":"","jetpack_post_was_ever_published":false,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":"","jetpack_publicize_message":"","jetpack_publicize_feature_enabled":true,"jetpack_social_post_already_shared":true,"jetpack_social_options":{"image_generator_settings":{"template":"highway","enabled":false}}},"categories":[225,66,96],"tags":[232,233],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"https:\/\/allthingsneonatal.com\/wp-content\/uploads\/2017\/09\/6091832360_c140db4ca7_b.jpg","jetpack_sharing_enabled":true,"jetpack_shortlink":"https:\/\/wp.me\/p91QDZ-1f5","jetpack_likes_enabled":true,"jetpack-related-posts":[],"_links":{"self":[{"href":"https:\/\/allthingsneonatal.com\/wp-json\/wp\/v2\/posts\/4779"}],"collection":[{"href":"https:\/\/allthingsneonatal.com\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/allthingsneonatal.com\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/allthingsneonatal.com\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/allthingsneonatal.com\/wp-json\/wp\/v2\/comments?post=4779"}],"version-history":[{"count":3,"href":"https:\/\/allthingsneonatal.com\/wp-json\/wp\/v2\/posts\/4779\/revisions"}],"predecessor-version":[{"id":6212,"href":"https:\/\/allthingsneonatal.com\/wp-json\/wp\/v2\/posts\/4779\/revisions\/6212"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/allthingsneonatal.com\/wp-json\/wp\/v2\/media\/4784"}],"wp:attachment":[{"href":"https:\/\/allthingsneonatal.com\/wp-json\/wp\/v2\/media?parent=4779"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/allthingsneonatal.com\/wp-json\/wp\/v2\/categories?post=4779"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/allthingsneonatal.com\/wp-json\/wp\/v2\/tags?post=4779"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}} |