Naloxone

The 2016 CDC Opioid Prescribing Guideline was based on a systematic clinical evidence review sponsored by AHRQ on the effectiveness and risks of long-term opioid therapy for chronic pain (47 ,97 ), a CDC update to the AHRQ-sponsored review, and additional contextual questions (56 ,98 ). The systematic review addressed the effectiveness of long-term opioid therapy for outcomes related to pain, function, and quality of life; the comparative effectiveness of different methods for initiating and titrating opioids; the harms and adverse events associated with opioids; and the accuracy of risk prediction instruments and effectiveness of risk mitigation strategies on outcomes related to overdose, opioid use disorder, illicit drug use, and prescription opioid misuse. The CDC update to the AHRQ-sponsored review included literature published during or after 2015 and an additional question on the association between opioid therapy for acute pain and long-term use. The contextual evidence review addressed effectiveness of nonpharmacologic and nonopioid pharmacologic treatments, clinician and patient values and preferences, and information about resource allocation.
For this update to the 2016 CDC Opioid Prescribing Guideline, CDC funded AHRQ in 2018 and 2019 to conduct five systematic reviews (7 –11 ). AHRQ’s Evidence-based Practice Centers completed these reviews, which included new evidence related to the treatment of chronic and acute pain. The AHRQ review of opioids for chronic pain updated and expanded the evidence for the 2016 CDC review; studies were included on short-term (1 to <6 months), intermediate-term (6 to <12 months) and long-term (≥12 months) outcomes of therapy involving opioids, effects of opioid plus nonopioid combination therapy, effects of tramadol, effects of naloxone coprescription, risks of coprescribed benzodiazepines, risks of coprescribed gabapentinoids, and effects of concurrent use of cannabis (7 ). The systematic clinical evidence review on opioids for chronic pain (7 ) also included contextual questions on clinician and patient values and preferences, costs and cost-effectiveness of opioid therapy, and risk mitigation strategies. CDC considered four new complementary AHRQ reviews on the benefits and harms of nonpharmacologic treatments for chronic pain (9 ), nonopioid pharmacologic treatments for chronic pain (8 ), treatments for acute episodic migraine (11 ), and treatments for acute (nonmigraine) pain (10 ). A question on management of acute pain in the systematic clinical evidence review for the 2016 CDC Opioid Prescribing Guideline was included in the new review on therapies for acute pain (10 ). CDC also reviewed AHRQ-sponsored surveillance reports conducted in follow-up to the five systematic reviews for any new evidence that could potentially change systematic review conclusions. To supplement the clinical evidence reviews, CDC sponsored a contextual evidence review on clinician and patient values and preferences and resource allocation (costs) for the areas addressed in the four new reviews (8 –11 ).

BALB/c mice of either sex (n = 6) weighing 18–22g were acclimatized to laboratory conditions one hour before the start of experiment with food and water available ad libitum. Animals were then subjected to pre-testing on hot plat (Havard apparatus) maintained at 55 ± 0.1°C. Animals having latency time greater than 15 s on hot plate during pre-testing were rejected (latency time) [12 ]. All the animals were divided in eight groups each of six mice. Group I was treated with saline (10ml/kg), group II was treated with Tramadol^R (30mg/kg i.p). Group III, IV and V were treated with 100, 200 and 300mg/kg VBME, i.p. respectively. After 30min of treatment the animals were placed on hot plat and the latency time (time for which mouse remains on the hot plate (55 ± 0.1°C) without licking or flicking of hind limb or jumping) was measured in seconds. In order to prevent the tissue damage a cut-off time of 30 s were imposed for all animals. To find out the opiodergic mechanism in the analgesic activity of VBME, Groups VI and VII were treated with naloxone (0.5mg/kg s.c.) and after 10min these groups were treated with VBME (200 and 300mg/kg, i.p), while group VIII was treated with Tramadol^R (30mg/kg i.p.) after 10min of naloxone injection. The latency time for all groups was recorded at 0, 30, 60, 90 and 120min. Percent analgesia was calculated using the following formula:
% Analgesia = (Test latency – control latency)/(Cut – off time – control latency) × 100

A qualitative methodology was adopted to examine individual officer perspectives and behaviors surrounding naloxone administration using semi-structured, in-person interviews. Topics addressed in the interview guide included training received, officer experiences working with PWUD and responding to scenes of suspected overdoses, post-naloxone administration protocols, and knowledge of applicable laws and regulations. Although the initial target was 30 interviews, the research team was able to exceed the target for a total of 38 interviews due to a robust recruitment strategy.