Doses Of Naloxone Research Articles

The application of combining low dose naloxone with ropivacaine in supraclavicular brachial plexus block

Objective: To observe the effect of low dose naloxone combinewith ropivacaine for supraclavicular brachial plexus block. Methods: Seventy patients undergoing elective upper limb surgery were randomly divided into two groups, ropivacaine group (Group R, n=35) and naloxone group (Group N, n=35). An ultrasound guided technique was used in both two groups.The onset and duration time of sensory and motor blockade, visual analog score(VAS)of 3, 6, 12, 18, 24 h postoperatively, time of first request fordezocine, total amount of dezocine needed, incidence of nausea and vomiting postoperatively(PONV) and patients' satisfaction score for analgesia in 24 h after surgery were measured.At the same time, blood samples were taken before anesthesia, 6 h, 24 h after operation for inspecting the concentration of β-endorphin(β-EP)in plasma. Results: The duration of sensory and motor blockade, time of first request for dezocine in Group N were 736.0(713.5, 836.5), 514.5(491.3, 572.8), 708.5(683.2, 877.0)min, which were all prolonged compared to Group R(522.0(469.5, 606.5), 401.0(370.0, 458.5), 570.0(435.0, 618.5)min)(Z=-6.844, -6.758, -6.700, all P<0.01). The 6, 12, 18 h postoperatively VAS of Group N were 0, 5.0(3.0, 5.8), 5.0(5.0, 6.0)point. Among which the 6, 12 h postoperatively VAS of Group N were lower than that of Group R(1.0(1.0, 3.5), 6.0(6.0, 7.0)point)(Z=-6.596, -4.864, all P<0.01), while the 18 h postoperatively VAS was higher than that of Group R (5.0(4.0, 5.0)point)(Z=-2.603, P<0.01). Total amount of dezocine needed in Group N in 24 h after surgery was 7.5(5.0, 10.0)mg, which was lower than that of Group R(10.0(10.0, 15.0)mg)(Z=-3.449, P<0.01). The incidence of PONV after surgery in Group N was 21.9%, which was lower than that of Group R(45.5%)(χ(2)=4.034, P<0.05). Ptients' satisfaction score for analgesia in 24 h after surgery in Group N was 8.0(7.0, 8.0)point, which was higher than that of Group R(7.0(6.0, 7.0)point)(Z=-3.509, P<0.01). At 6 h postoperatively , the concentration of plasma β-EP in Group N was(113.34±12.36)μg/L, lower than that of Group R((147.14±11.65)μg/L)(t=-7.694, P<0.01). Conclusion: Low dose naloxone combine with ropivacaine for supraclavicular brachial plexus block, prolong the duration of sensory and motor blockade without affecting the onset time.

Naloxone dosage for opioid reversal: current evidence and clinical implications.

Opioid-related mortality is a growing problem in the United States, and in 2015 there were over 33,000 opioid-related deaths. To combat this mortality trend, naloxone is increasingly being utilized in a pre-hospital setting by emergency personnel and prescribed to laypersons for out-of-hospital administration. With increased utilization of naloxone there has been a subsequent reduction in mortality following an opioid overdose. Reversal of opioid toxicity may precipitate an opioid-withdrawal syndrome. At the same time, there is a risk of inadequate response or re-narcotization after the administration of a single dose of naloxone in patients who have taken large doses or long-acting opioid formulations, as the duration of effect of naloxone is shorter than that of many opioid agonists. As out-of-hospital use of this medication is growing, so too is concern about effective but safe dosing.

Management of Suspected Opioid Overdose With Naloxone in Out-of-Hospital Settings: A Systematic Review.

Naloxone is effective for reversing opioid overdose, but optimal strategies for out-of-hospital use are uncertain. To synthesize evidence on 1) the effects of naloxone route of administration and dosing for suspected opioid overdose in out-of-hospital settings on mortality, reversal of overdose, and harms, and 2) the need for transport to a health care facility after reversal of overdose with naloxone. Ovid MEDLINE (1946 through September 2017), PsycINFO, Cochrane Central Register of Controlled Trials, CINAHL, U.S. Food and Drug Administration (FDA) materials, and reference lists. English-language cohort studies and randomized trials that compared different doses of naloxone, administration routes, or transport versus nontransport after reversal of overdose with naloxone. Main outcomes were mortality, reversal of overdose, recurrence of overdose, and harms. Dual extraction and quality assessment of individual studies; consensus assessment of overall strength of evidence (SOE). Of 13 eligible studies, 3 randomized controlled trials and 4 cohort studies compared different administration routes. At the same dose (2 mg), 1 trial found similar efficacy between higher-concentration intranasal naloxone (2 mg/mL) and intramuscular naloxone, and 1 trial found that lower-concentration intranasal naloxone (2 mg/5 mL) was less effective than intramuscular naloxone but was associated with decreased risk for agitation (low SOE). Evidence was insufficient to evaluate other comparisons of route of administration. Six uncontrolled studies reported low rates of death and serious adverse events (0% to 1.25%) in nontransported patients after successful naloxone treatment. There were few studies, all had methodological limitations, and none evaluated FDA-approved autoinjectors or highly concentrated intranasal formulations. Higher-concentration intranasal naloxone (2 mg/mL) seems to have efficacy similar to that of intramuscular naloxone for reversal of opioid overdose, with no difference in adverse events. Nontransport after reversal of overdose with naloxone seems to be associated with a low rate of serious harms, but no study evaluated risks of transport versus nontransport. Agency for Healthcare Research and Quality. (PROSPERO: CRD42016053891).

Pediatric patients receiving naloxone within 48 h of anesthesia: a case–control study

Excessive narcotization in pediatric surgical patients has not been well characterized. This report describes the use of postoperative naloxone in pediatric patients. Pediatric surgical patients from January 1, 2010, through June 30, 2016, who underwent general anesthesia and received naloxone within 48h postoperatively were identified and matched 1:1 with controls by age, sex, and procedure. Cases and controls underwent retrospective chart review. Forty-seven patients received naloxone, with a rate of 2.0 (95% CI 1.5-2.7) per 1000 anesthetics. Indications were respiratory depression (n = 19), facilitating extubation (n = 15), and reversing sedation (n = 13), and 44 cases received naloxone in a monitored environment. The median (interquartile range) naloxone dose was 4.0 (2.0-23.5) mcg/kg, and five patients (11%) later required subsequent naloxone treatments. Their characteristics were similar to controls, including opioid medications, except cases that had signs of respiratory depression before naloxone administration. The outcomes were similar, although more cases were admitted to the intensive care unit before naloxone administration. One patient died 13 days postoperatively of unrelated causes. Postoperative naloxone administration in pediatric patients is rare. The observation that most administrations occurred in a monitored setting implies that at-risk patients had been appropriately identified and kept under closer surveillance.

Insights on efficacious doses of PAMORAs for patients on chronic opioid therapy or opioid-naïve patients.

Opioid-induced constipation (OIC) is a major side effect of opioid use. Centrally acting antagonists result in opioid withdrawal or worsening of pain and lead to use of peripherally acting mu-opioid receptor antagonists (PAMORAs). The required doses of the PAMORAs, methylnaltrexone and naloxegol, in the treatment of OIC are well established in chronic opioid users. OIC may occur after short duration of opioid treatment; the required doses of naloxone, naltrexone, and PAMORAs in opioid-naïve subjects (with no opioid use for at least 3months) are unclear. The aim of this review was to evaluate the PAMORA dose required for opioid-naïve subjects to achieve similar beneficial effects on symptoms or valid surrogates to those observed in chronic opioid users. A PubMed search of μ-opioid antagonists to counter μ-opioid effects included terms: naloxone, naltrexone, methylnaltrexone, alvimopan, and naloxegol, as well as OIC and colonic transit. The approved dose of methylnaltrexone in chronic opioid users, 0.3mg/kg subcutaneous (SQ), did not affect motility in opioid-naïve subjects. Trials investigating the required dose of alvimopan showed 0.5-1mg dose was efficacious in treating OIC; a 10-fold higher dose (12mg) of alvimopan is needed to block effects of codeine on small bowel and colonic transit in opioid-naïve subjects compared to chronic opioid users. Opioid-naïve users need 125mg of naloxegol to reverse the effects of opioids on transit; this is in contrast to the 12.5 to 25mg needed to treat OIC in chronic opioid users. Opioid-naïve subjects require a higher dose of PAMORA than chronic opioid users to achieve μ-opioid antagonist effect.

Risk of respiratory depression with opioids and concomitant gabapentinoids.

IntroductionThe combination of opioids and central nervous system depressants such as benzodiazepines and barbiturates has an additive effect on the frequency of oversedation and respiratory depression requiring naloxone use in hospitalized patients. Gabapentinoids (gabapentin and pregabalin) are frequently prescribed with opioids for their opioid-sparing and adjuvant analgesic effects. There is limited literature on the risk of respiratory depression due to the combination of opioids and gabapentinoids requiring naloxone administration.MethodsThis retrospective study evaluated patients who were prescribed opioids and at least one dose of naloxone between March 1, 2014 and September 30, 2016. The primary objective of this study was to compare the frequency of respiratory depression among patients who received naloxone and opioids (non-gabapentinoid group) with those who received naloxone, opioids, and gabapentinoids (gabapentinoid group). Secondary objectives included comparing the association of oversedation, using the Pasero Opioid-induced Sedation Scale, and various risk factors with those in the gabapentinoid group.ResultsA total of 153 patient episodes of naloxone administration (102 in the non-gabapentinoid and 51 in the gabapentinoid groups) in 125 unique patients were included in the study. For the primary objective, there were 33 episodes of respiratory depression associated with the non-gabapentinoid group (33/102=32.4%) versus 17 episodes of respiratory depression with the gabapentinoid group (17/51=33.3%) (p=0.128). Secondary objectives showed a significant association between respiratory depression and surgery in the previous 24 hours (p=0.036) as well as respiratory depression and age >65 years (p=0.031) for patients in the non-gabapentinoid group compared to the gabapentinoid group.ConclusionThere was no significant association of respiratory depression in the gabapentinoid group versus the non-gabapentinoid group. There was an increased risk of respiratory depression in the gabapentinoid group, specifically in patients who had surgery within the previous 24 hours.

Opioid Overdose Outbreak - West Virginia, August 2016.

On August 15, 2016, the Mayor's Office of Drug Control Policy in Huntington, West Virginia, notified the Cabell-Huntington Health Department (CHHD) of multiple calls regarding opioid overdose received by the emergency medical system (EMS) during 3 p.m.-8 p.m. that day. A public health investigation and response conducted by the West Virginia Bureau for Public Health (BPH) and CHHD identified 20 opioid overdose cases within a 53-hour period in Cabell County; all cases included emergency department (ED) encounters. EMS personnel, other first responders, and ED providers administered the opioid antidote naloxone to 16 (80%) patients, six of whom were administered multiple doses, suggesting exposure to a highly potent opioid. No patients received referral for recovery support services. In addition to the public health investigation, a public safety investigation was conducted; comprehensive opioid toxicology testing of clinical specimens identified the synthetic opioid fentanyl* and novel fentanyl analogs, including carfentanil,† which had been used by patients who overdosed in Huntington. Results of these two investigations highlight the importance of collaboration between public health and public safety agencies to provide in-depth surveillance data from opioid overdose outbreaks that involve high-potency fentanyl analogs. These data facilitated a public health response through increased awareness of powerful opioid substances requiring multiple naloxone doses for reversal, and improved patient linkage to recovery support services and a harm reduction program from the ED after opioid overdose.

A Case of a Contraband Body Packer Requiring High-Dose Naloxone

Background:Body packers occasionally refer to the Emergency Department (ED), after leakage of package contents within intestinal lumen, resulting in life-threatening toxicities, depending upon the nature of the chemical product. Case Presentation: We present a case report of a patient presented with sudden onset of drowsiness while he was on board a flight. He was brought in by the airport security staff. On arrival to the ED, his Glasgow Coma Scale (GCS) was 3/15 and pupils were pinpoint bilaterally. He was empirically treated with Naloxone on clinical suspicion of narcotic overdose. He required a cumulative dose of 12 mg of Naloxone for reversal of respiratory depression and coma. On subsequent investigation in the ED, he was identified to be a body packer. Discussion: This case represents a rare clinical example of narcotic overdose which resulted in a life-threatening opioid toxicity due to leakage of the package contents into his bowels. In this case, a dosage greater than 10 mg of the maximum recommended dose of Naloxone is required for reversal of toxicity. Conclusion:It is imperative to have a high level of suspicion for managing possible opioid intoxication as immediate treatment can be diagnostic and lifesaving. Our case required more than the recommended dosage of Naloxone, highlighting the possible suggestion of further studies to look into the maximum threshold of this reversal agent.

Opioid crisis at the Jersey Shore—special report

The USA is experiencing an epidemic of drug overdoses and deaths with a 200% increase in overdose deaths involving opioids including heroin. Legislation since 2013 has created paths to reduce opioid overdose deaths and since, basic life support (BLS) and police agencies have been administering naloxone to patients with suspected opioid overdoses as part of standard treatment protocols. Charts were reviewed from 1 January 2016 to 15 April 2016 on the de-identified electronic medical records of patients in a two-county system comprising the 'Jersey Shore' who received naloxone to determine the number of naloxone administrations and heroin overdoses. Additionally, narratives were examined for evidence of heroin use. Of the 312 patients, 213 received a first dose of naloxone by a family member or bystander, police, or by BLS; 99 received a first dose by a paramedic (ALS). About 233 were initially unresponsive or had altered mental status that improved after naloxone administration. About210 (67.3%) charts illustrated obvious opioid use. Of the note, 282 patients arrived to an emergency department alive. About 30 patients were pronounced dead. From 1 February 2016 to 31 March 2016, the number of opioid overdoses increased and the subsequent use of naloxone has increased by 176%.

Naloxone’s Effect on Activity-Induced Phase Shifts of Circadian Rhythms

Vigorous running in a novel exercise wheel by hamsters during the subjective day results in large (about 3 hr) phase advances of their circadian rhythms. We administered the opiate receptor antagonist naloxone at 10 mg/kg and 20 mg/kg (i.p.) and found that at 20 mg/kg it significantly reduced phase shifts. This dose of naloxone also reduced the amount of running shown by hamsters in the novel wheel. At the 20 mg/kg dose, the reduced amount of running resulted in smaller phase shifts. The results are consistent with the hypothesis that nonphotic phase shifts are linked to exercise and arousal in hamsters. However, because high amounts of running were accompanied by phase shifting in animals whose opiate receptors were blocked, the results provide no evidence that the rewarding nature of running in rodents is an important causal factor in nonphotic phase shifting beyond its role in promoting running.

Suspected Methadone Toxicity: from Hospital to Autopsy Bed.

High mortality rates have been reported for methadone in both adults and children. We aimed to determine the pattern of toxicity, possible underlying diseases and treatment challenges in patients referred to our centre with early diagnosis of methadone toxicity and who later died. Medical files of all methadone-poisoned patients who had been admitted to a referral centre of toxicology between March 2011 and March 2016, died during the hospital stay and sent for autopsy to Legal Medicine Organization were retrospectively evaluated. In a total of 94 patients, autopsy findings and laboratory evaluations showed that cause of death was pure methadone toxicity in 57 (60.6%). Other causes of death were ischaemic heart disease in ten, co-ingestions (toxicities including methadone) in eight, brain haemorrhage, multi-organ failure and pneumosepsis (each in four), meningitis/encephalitis in three and head trauma and other toxicities (other than methadone but including an opioid, each in two) patients. Time of cardiopulmonary arrest was significantly different between those with pure methadone toxicity and those who died due to other causes (p = 0.01). Patients who had died due to co-ingestions and other toxicities were younger (p = 0.029) and took more bolus doses of naloxone (p = 0.042). In methadone users, especially in older ages and those with trivial response to naloxone administration, loss of consciousness should not be strictly attributed to methadone toxicity. In such patients, thorough evaluation for other possible causes of loss of consciousness is mandatory.

Incidence of Naloxone Redosing in the Age of the New Opioid Epidemic

Study Objective: Naloxone, an opioid-antagonist deliverable by an intra-nasal route, has become widely available and utilized by law enforcement officers as well as basic life support (BLS) providers in the prehospital setting. This study aimed to determine the frequency of repeat naloxone dosing in suspected narcotic overdose (OD) patients and identify patient characteristics. Methods: A retrospective chart review of patients over 17 years of age with suspected opioid overdose, treated with an initial intranasal (IN) dose of naloxone and subsequently managed by paramedics, was performed from April 2014 to June 2016. Demographic data was analyzed using descriptive statistics to identify those aspects of the history, physical exam findings. Results: A sample size of 2166 patients with suspected opioid OD received naloxone from first responders. No patients who achieved GCS 15 after treatment required redosing; 195 (9%) received two doses and 53 patients received three doses of naloxone by advanced life support. Patients were primarily male (75.4%), Caucasian (88.2%), with a mean age of 36.4 years. A total of 76.7% of patients were found in the home, 23.1% had a suspected mixed ingestion, and 27.2% had a previous OD. Two percent of all patients required a third dose of naloxone. Conclusion: In this prehospital study, we confirmed that intranasal naloxone is effective in reversing suspected opioid toxicity. Nine percent of patients required two or more doses of naloxone to achieve clinical reversal of suspected opioid toxicity. Two percent of patients received a third dose of naloxone.

Misuse of Novel Synthetic Opioids: A Deadly New Trend.

Novel synthetic opioids (NSOs) include various analogs of fentanyl and newly emerging non-fentanyl compounds. Together with illicitly manufactured fentanyl (IMF), these drugs have caused a recent spike in overdose deaths, whereas deaths from prescription opioids have stabilized. NSOs are used as stand-alone products, as adulterants in heroin, or as constituents of counterfeit prescription medications. During 2015 alone, there were 9580 deaths from synthetic opioids other than methadone. Most of these fatalities were associated with IMF rather than diverted pharmaceutical fentanyl. In opioid overdose cases, where the presence of fentanyl analogs was examined, analogs were implicated in 17% of fatalities. Recent data from law enforcement sources show increasing confiscation of acetylfentanyl, butyrylfentanyl, and furanylfentanyl, in addition to non-fentanyl compounds such as U-47700. Since 2013, deaths from NSOs in the United States were 52 for acetylfentanyl, 40 for butyrylfentanyl, 128 for furanylfentanyl, and 46 for U-47700. All of these substances induce a classic opioid toxidrome, which can be reversed with the competitive antagonist naloxone. However, due to the putative high potency of NSOs and their growing prevalence, it is recommended to forgo the 0.4 mg initial dose of naloxone and start with 2 mg. Because NSOs offer enormous profit potential, and there is strong demand for their use, these drugs are being trafficked by organized crime. NSOs present major challenges for medical professionals, law enforcement agencies, and policymakers. Resources must be distributed equitably to enhance harm reduction though public education, medication-assisted therapies, and improved access to naloxone.

Opioid receptors mediate the acquisition, but not the expression of mitragynine-induced conditioned place preference in rats.

Mitragynine is the main psychoactive ingredient of the herbal drug preparation Kratom (Ketum), derived from the plant Mitragyna speciosa. Kratom is a widely abused drug in Southeast Asian and has a psychostimulant profile at low-medium doses, while high doses have opioidergic effects. Mitragynine was shown to possess opiate receptor affinity. However, its role in the behavioural effects of mitragynine is unclear. Here we asked whether the reinforcing effects of mitragynine are mediated by opiate receptors using a conditioned place preference (CPP) paradigm in rats. In the first experiment we tested the effects of the opiate receptor antagonist naloxone (0.1, 0.3 and 1.0mg/kg) on the acquisition of mitragynine (10mg/kg)-induced CPP. In the second experiment, we tested the involvement of opiate receptors in the expression of mitragynine-induced CPP in rats. We found that naloxone suppresses the acquisition of mitragynine-induced CPP. This effect was already evident at a dose of naloxone (0.1mg/kg) which, by itself, had no conditioned place aversion (CPA) effect. Higher doses of naloxone induced a CPA and blocked mitragynine-induced CPP. In contrast, naloxone had no effect on the expression of mitragynine-induced CPP. These findings suggest that the acquisition, but not the expression of the reinforcing effects of mitragynine is mediated by opiate receptors.

Creating simple solutions for safe naloxone use.

e18185 Background: Naloxone is sometimes required to reverse acute intoxication from opioid pain medications. Although clinical guidelines exist, naloxone dosing is variable in practice. Higher doses can cause pain crisis, acute withdrawal, and possibly increased patient risk. We developed a multi-faceted intervention to increase guideline-concordant naloxone dosing. Methods: We surveyed medical staff and retrospectively collected 6 months of naloxone prescribing data to assess knowledge and frequency of guideline-concordant dosing. We reviewed the electronic order for naloxone and interviewed experienced nurses to facilitate mapping of the process of naloxone administration. We then designed 4 interventions aimed at adult inpatients on medical oncology, general medical and ICU services: 1. Simplify wording of naloxone guidelines; 2. Create naloxone kit containing all necessary equipment and instructions; 3. Auto-populate dose into electronic naloxone order; 4. Administer 5-minute educational inservice to staff (RN, NP, PA, MD). To assess rate of guideline concordance, naloxone prescribing data was collected for the pre-intervention (12 months), intervention (6 weeks), and post-intervention (8.5 months) groups. The survey was repeated after the intervention. For analysis, a generalized linear regression with logit link function and a generalized estimating equation method were used. Results: Over the 22-month study period, 137 patients received 148 naloxone doses. Patients were mean age 63.1 y/o, 54.7% female, and 75.9% white. Of the 90 naloxone doses given pre-intervention, only 24.4% were guideline-concordant. The 10 doses of naloxone given during the intervention period were guideline-concordant in 40% of the cases. Of the 48 naloxone doses given post-intervention, 62.5% were guideline-concordant, a significant increase compared to the pre-intervention group (p &lt; 0.001). The improvement was most dramatic in the non-ICU services (26.4% to 73.5%, p &lt; 0.001). Increases were maintained at 8 months (median concordant rate 53.5%/month (range: 33%-100%). Conclusions: A simple, inexpensive intervention can be used to increase guideline-concordant naloxone dosing and potentially avoid adverse effects of naloxone.

Frequency and severity of non-fatal opioid overdoses among clients attending the Sydney Medically Supervised Injecting Centre

BackgroundPharmaceutical opioid overdose rates have increased in recent years. The current study aimed to compare rates per 1000 injections of non-fatal overdose after heroin or oxycodone injection, and their comparative clinical severity. MethodsAnalysis of prospectively collected data from the Sydney Medically Supervised Injecting Centre (MSIC). Severity of overdose was measured using the Glasgow Coma Scale, oxygen saturation levels, and the administration of naloxone. ResultsHeroin overdoses occurred at three times the rate of oxycodone overdoses (12.7 v 4.1 per 1000 injections). Heroin overdoses appeared to be more severe than oxycodone overdoses, with higher levels of compromised consciousness (31 v 18%) and severe respiratory depression (67 v 48%), but there were no differences in naloxone doses (20 v 17%). Concurrent use of other depressants at the time of overdose was also associated with compromised consciousness, and the need for naloxone. ConclusionsHeroin overdoses occurred at a greater rate than oxycodone overdoses, and had more severe clinical indicators.

Pharmacokinetics after a single dose of naloxone administered as a nasal spray in healthy volunteers.

There is increasing interest in the use of intranasal naloxone to reverse adverse opioid effects during management of procedural pain in children and in adults after overdose. There are limited data on the pharmacokinetics of intranasal naloxone so in this study we aimed to detail the pharmacokinetic profile of the commercially marketed injectable solution of naloxone 0.4 mg/ml when administered as an intranasal spray. Twenty healthy volunteers received naloxone as an intranasal spray at a dose of 10 μg/kg. Venous blood sampling was carried out for 90 min after administration to determine the time profile of the plasma concentrations of using tandem mass spectrometry. Pharmacokinetic parameters were calculated using a one-compartment model. Median time to maximum naloxone concentration (Tmax) was 14.5 (95% CI: 9.0-16.5) min, mean maximum naloxone concentration (Cmax) was 1.09 ± 0.56 ng/ml and mean AUC0-90 min was 37.1 ± 15.0 ng*min/ml. Elimination half-life estimated from the median concentration data was 28.2 min. Our results show a faster uptake of intranasal naloxone to maximum concentration compared with previous studies although with a marked variation in maximum concentration. The findings are consistent with our clinical experience of the time profile for reversing the effects of sufentanil sedation in children.

Characteristics of Fentanyl Overdose - Massachusetts, 2014-2016.

Opioid overdose deaths in Massachusetts increased 150% from 2012 to 2015 (1). The proportion of opioid overdose deaths in the state involving fentanyl, a synthetic, short-acting opioid with 50-100 times the potency of morphine, increased from 32% during 2013-2014 to 74% in the first half of 2016 (1-3). In April 2015, the Drug Enforcement Agency (DEA) and CDC reported an increase in law enforcement fentanyl seizures in Massachusetts, much of which was believed to be illicitly manufactured fentanyl (IMF) (4). To guide overdose prevention and response activities, in April 2016, the Massachusetts Department of Public Health and the Office of the Chief Medical Examiner collaborated with CDC to investigate the characteristics of fentanyl overdose in three Massachusetts counties with high opioid overdose death rates. In these counties, medical examiner charts of opioid overdose decedents who died during October 1, 2014-March 31, 2015 were reviewed, and during April 2016, interviews were conducted with persons who used illicit opioids and witnessed or experienced an opioid overdose. Approximately two thirds of opioid overdose decedents tested positive for fentanyl on postmortem toxicology. Evidence for rapid progression of fentanyl overdose was common among both fatal and nonfatal overdoses. A majority of interview respondents reported successfully using multiple doses of naloxone, the antidote to opioid overdose, to reverse suspected fentanyl overdoses. Expanding and enhancing existing opioid overdose education and prevention programs to include fentanyl-specific messaging and practices could help public health authorities mitigate adverse effects associated with overdoses, especially in communities affected by IMF.

Experimental Research Showing the Reduction of Naloxone-Place Aversion by Oral Zinc Administration in Rats.

Previous studies showed the attenuation of both morphine-dependence and morphine-place preference by zinc. Conditioned place preference and aversion are experimental models frequently used to test the reward-stimulating, respectively the aversive effects induced by different stimuli or substances. Addictive substances usually induce place preference (exhibit reward-stimulating properties), while their antagonists determine place-avoidance (aversion). The present study aimed to assess the effect determined by zinc sulphate oral administration (2 and 4mg/kg/day, 14days, prior to habituation) on the place aversion induced by two naloxone doses (1.5 and 2.5mg/kg/administration). The results show a robust, dose-dependent reduction of the aversion determined by both naloxone doses (the aversion induced by 1.5mg/kg naloxone was reduced with 15%-the lower zinc dose and with 24%-the higher zinc dose; the aversion induced by 2.5mg/kg naloxone was reduced with 16%-the lower zinc dose and with 29%-the higher zinc dose). This represents a new proof of the interactions between zinc and opioidergic system and a further argument for dietary zinc supplementation in patients on opioids for cancer-related chronic pain.

Use of Intranasal Naloxone by Basic Life Support Providers

Study Objectives: Intranasal delivery of naloxone to reverse the effects of opioid overdose by Advanced Life Support (ALS) providers has been studied in several prehospital settings. In 2006, in response to the increase in opioid-related overdoses, a special waiver from the state allowed administration of intranasal naloxone by Basic Life Support (BLS) providers in our city. This study aimed to determine: 1) if patients who received a 2-mg dose of nasal naloxone administered by BLS required repeat dosing while in the emergency department (ED), and 2) the disposition of these patients. Methods: This was a retrospective review of patients transported by an inner-city municipal ambulance service to one of three academic medical centers. We included patients aged 18 and older that were transported by ambulance between 1/1/2006 and 12/12/2012 and who received intranasal naloxone by BLS providers as per a state approved protocol. Site investigators matched EMS run data to patients from each hospital's EMR and performed a chart review to confirm that the patient was correctly identified and to record the outcomes of interest. Descriptive statistics were then generated. Results: A total of 793 patients received nasal naloxone by BLS and were transported to three hospitals. ALS intervened and transported 116 (14.6%) patients, and 11 (1.4%) were intubated in the field. There were 724 (91.3%) patients successfully matched to an ED chart. Hospital A received 336 (46.4%) patients, Hospital B received 210 (29.0%) patients, and Hospital C received 178 (24.6%) patients. Mean age was 36.2 (SD 10.5) years and 522 (72.1%) were male; 702 (97.1%) were reported to have abused heroin while 21 (2.9%) used other opioids. Nasal naloxone had an effect per the prehospital record in 689 (95.2%) patients. An additional naloxone dose was given in the ED to 64 (8.8%) patients. ED dispositions were: 507 (70.0%) discharged, 105 (14.5%) admitted, and 112 (15.5%) other (e.g., left against medical advice, left without being seen, or transferred). Conclusions: Only a small percentage of patients receiving prehospital administration of nasal naloxone by BLS providers required additional doses of naloxone in the ED and the majority of patients were discharged.