Opioid Toxicity Recurrence After an Initial Response to Naloxone

Abstract

Objective: To determine the frequency and potential predictors of opioid toxicity recurrence after a response to naloxone in adult Emergency Department patients. Methods: A retrospective case-control study of naloxone-treated patients with opioid toxicity over an 8-year period. Both the patient response to naloxone and recurrence of opioid toxicity was determined by an expert Delphi Panel. The frequency of opioid toxicity recurrence was compared by the duration of opioid effect, the route of opioid exposure, and the presence of other CNS depressant drugs. Results: Ninety of 221 (41%) cases with a discharge diagnosis of opioid toxicity were treated with naloxone; six patients were excluded because of a lack of toxicity. There was a response to naloxone in 50% of the 84 cases, and recurrence of toxicity in 31% (95% CI 17–45%) of naloxone responders. The most common opioids were codeine, heroin, propoxyphene, and oxycodone/hydrocodone. Recurrence of toxicity was more common with long-acting opioids (p = 0.04), and was not associated with the route of opioid exposure (p = 0.42), or presence of ethanol and other CNS depressants (p ± 0.87). Conclusion: Opioid toxicity recurrence after a response to naloxone occurred in approximately 1/3 of adult Emergency Department opioid overdose cases. Recurrence was more common with long-acting opioids and was not associated with the route of opioid exposure. Other clinically useful predictors of toxicity recurrence were not identified.     

Implementing Harm Reduction Strategies to Reduce Opioid Overdoses

Nurse practitioners play a pivotal role in ensuring patients’ access to naloxone to reduce the number of opioid overdoses. A quality improvement project was developed to determine if or to what degree the implementation of the Opioid Overdose Prevention Toolkit would impact patient access to naloxone in a pain management practice. Clinically, the significance is in changing prescribing practice related to naloxone. Use of the toolkit is a feasible method to offer nurse practitioners education on how to identify patients at risk of an opioid overdose and the recommendation to coprescribe naloxone.     

Measuring a Crisis: Questioning the Use of Naloxone Administrations as a Marker for Opioid Overdoses in a Large U.S. EMS System

Objective: The United States is currently experiencing a public health crisis of opioid overdoses. To determine where resources may be most needed, many public health officials utilize naloxone administration by EMS as an easily-measured surrogate marker for opioid overdoses in a community. Our objective was to evaluate whether naloxone administration by EMS accurately represents EMS calls for opioid overdose. We hypothesize that naloxone administration underestimates opioid overdose. Methods: We conducted a chart review of suspected overdose patients and any patients administered naloxone in Wake County, North Carolina, from January 2013 to December 2015. Patient care report narratives and other relevant data were extracted from electronic patient care records and the resultant database was analyzed by two EMS physicians. Cases were divided into categories including “known opioid use,” “presumed opioid use,” “no known opioid,” “altered mental status,” “cardiac arrest with known opioid use,” “cardiac arrest with no known opioid use,” or “suspected alcohol intoxication,” and then further separated based on whether naloxone was administered. Patient categories were compared by patient demographics and incident year. Using the chart review classification as the gold standard, we calculated the sensitivity and positive predictive value (PPV) of naloxone administration for opioid overdose. Results: A total of 4,758 overdose cases from years 2013–15 were identified. During the same period, 1,351 patients were administered naloxone. Of the 1,431 patients with known or presumed opioid use, 57% (810 patients) received naloxone and 43% (621 patients) did not. The sensitivity of naloxone administration for the identification of patients with known or presumed opioid use was 57% (95% CI: 54%–59%) and the PPV was 60% (95% CI: 57%–63%). Conclusion: Among patients receiving care in this large urban EMS system in the United States, the overall sensitivity and positive predictive value for naloxone administration for identifying opioid overdoses was low. Better methods of identifying opioid overdose trends are needed to accurately characterize the burden of opioid overdose within and among communities.     

Out-of-hospital Treatment of Opioid Overdoses in an Urban Setting

Objectives : To investigate clinical outcomes in a cohort of opioid overdose patients treated in an out-of-hospital urban setting noted for a high prevalence of IV opioid use. Methods : A retrospective review was performed of presumed opioid overdoses that were managed in 1993 by the emergency medical services (EMS) system in a single-tiered, urban advanced life support (ALS) EMS system. Specifically. all patients administered naloxone by the county paramedics were reviewed. Those patients with at least 3 of 5 objective criteria of an opioid overdose [respiratory rate <6/min, pinpoint pupils, evidence of IV drug use, Glasgow Coma Scale (GCS) score <12, or cyanosis] were included. A response to naloxone was defined as improvement to a GCS 14 and a respiratory rate 10/min within 5 minutes of naloxone administration. ED dispositions of opioid-overdose patients brought to the county hospital were reviewed. All medical examiner's cases deemed to be opioid-overdose-related deaths by postmortem toxicologic levels also were reviewed. Results : There were 726 patients identified with presumed opioid overdoses. Most patients (609/726, 85.4%) had an initial pulse and blood pressure (BP). Most (94%) of this group responded to naloxone and all were transported. Of the remainder, 101 (14%) had obvious signs of death and 16 (2.2%) were in cardiopulmonary arrest without obvious signs of death. Of the patients in full arrest, 2 had return of spontaneous circulation but neither survived. Of the 609 patients who had initial BPs, 487 (80%) received naloxone IM (plus bag-valve-mask ventilation) and 122 (20%) received the drug IV. Responses to naloxone were similar; 94% IM vs 90% IV. Of 443 patients transported to the county hospital, 12 (2.7%) were admitted. The admitted patients had noncardiogenic pulmonary edema (n = 4). pneumonia (n = 2), other infections (n = 2), persistent respiratory depression (n = 2). and persistent alteration in mental status (n = 2). The patients with pulmonary edema were clinically obvious upon ED arrival. Hypotension was never noted and bradycardia was seen in only 2% of our presumed-opioid:overdose population. Conclusions : The majority of the opioid-overdose patients who had initial BPs responded readily to naloxone, with few patients requiring admission. Noncardiogenic pulmonary edema was uncommon and when present, hypoxia was evident upon arrival to the ED. Naloxone administered IM in conjunction with bag-valve-mask ventilation was effective in this patient population. The opioid-overdose patients in cardiopulmonary arrest did not survive.     

Use of Neurofeedback to Enhance Response to Hypnotic Analgesia in Individuals With Multiple Sclerosis

This proof of principle study examined the potential benefits of EEG neurofeedback for increasing responsiveness to self-hypnosis training for chronic pain management. The study comprised 20 individuals with multiple sclerosis (MS) who received 5 sessions of self-hypnosis training—1 face-to-face session and 4 prerecorded sessions. Participants were randomly assigned to have the prerecorded sessions preceded by either (a) EEG biofeedback (neurofeedback) training to increase left anterior theta power (NF-HYP) or (b) a relaxation control condition (RLX-HYP). Eighteen participants completed all treatment sessions and assessments. NF-HYP participants reported greater reductions in pain than RLX-HYP participants. The findings provide support for the potential treatment-enhancing effects of neurofeedback on hypnotic analgesia and also suggest that effective hypnosis treatment can be provided very efficiently.     

Feasibility of Bystander Administration of Public-Access Naloxone for Opioid Overdose

Objective: Pre-stationing naloxone, a competitive antagonist that can reverse the effects of opioid overdose, in public spaces may expedite antidote delivery. Our study aimed to determine the feasibility of bystander-assisted overdose treatment using pre-stationed naloxone. Methods: Convenience sample of bystanders in Cambridge, Massachusetts in April 2017. Subjects assisted a simulated patient described as unconscious. Subjects interacted with simulated EMS dispatch to locate a nearby box, unlock it, and administer naloxone. Results: Fifty participants completed the simulation. Median time from simulated ambulance dispatch to naloxone administration was 189 seconds, and from arrival at patient side to administration 61 seconds. All but one participant (98.0%) correctly administered naloxone. Subjects' comfort with administration and willingness to provide medical care increased from before to after the trial. Comfort in administering naloxone varied significantly with level of previous training prior to, but not following, study participation. Conclusions: Bystanders are willing and able to access pre-stationed naloxone and administer it to a simulated patient in a public space. Public access naloxone stations may be a useful tool to reduce time to naloxone administration, particularly in areas where opioid overdoses are clustered.     

纳洛酮在ICU中的应用

作者在ICU中应用钢治团治疗中毒性休克、败血症、细菌性脑膜炎、一氧化碳中毒、脑梗死共104例，除细菌性脑膜炎病例数过少未作比较外，与对照组相比各指标均有显著性差异（P＜0．05）。结果认为，1．纳洛酮在治疗严重感染性疾息时，通过结抗体内β-内啡肽，稳定细胞微粒体膜阻止其酶的释放而发挥抗炎作用；2．纳洛酮具有催醒和促进神经系统病变恢复的作用；3．纳洛酮具有高效抗休克作用，特别是感染性休克。     

Opioid Abuse in the United States and Department of Health and Human Services Actions to Address Opioid-Drug-Related Overdoses and Deaths

On March 26, 2015, the Office of the Assistant Secretary for Planning and Evaluation of the U.S. Department of Health and Human Services (HSS) published an online Issue Brief that addresses opioid abuse in the United States and (HHS) actions to address opioid-drug-related overdoses and deaths. This report, which contains the full content of the Issue Brief, is adapted from that document.     

Intravenous vs Subcutaneous Naloxone for Out-of-hospital Management of Presumed Opioid Overdose

Objective : To determine whether naloxone administered IV to out-of-hospital patients with suspected opioid overdose would have a more rapid therapeutic onset than naloxone given subcutaneously (SQ).
Methods : A prospective, sequential, observational cohort study of 196 consecutive patients with suspected opioid overdose was conducted in an urban out-of-hospital setting, comparing time intervals from arrival at the patient's side to development of a respiratory rate ≥10 breaths/min, and durations of bag-valve-mask ventilation. Subjects received either naloxone 0.4 mg IV ( n = 74) or naloxone 0.8 mg SQ ( n = 122), for respiratory depression of <10 breaths/min.
Results : Mean interval from crew arrival to respiratory rate ≥ 10 breaths/min was 9.3 ± 4.2 min for the IV group vs 9.6 ± 4.58 min for the SQ group (95% CI of the difference -1.55, 1.00). Mean duration of bag-valve-mask ventilation was 8.1 ± 6.0 min for the IV group vs 9.1 ± 4.8 min for the SQ group. Cost of materials for administering naloxone 0.4 mg IV was $12.30/patient, compared with $10.70/patient for naloxone 0.8 mg SQ.
Conclusion : There was no clinical difference in the time interval to respiratory rate ≥10 breaths/min between naloxone 0.8 mg SQ and naloxone 0.4 mg IV for the out-of-hospital management of patients with suspected opioid overdose. The slower rate of absorption via the SQ route was offset by the delay in establishing an IV.     

Appropriate Use of Naloxone in the Clinical Setting

Naloxone is an opioid antagonist that competitively binds to opioid receptors and reverses all of their effects. The indication for use is respiratory depression as a result of known or suspected opioid overdose. Clinicians involved in patient care must use the drug appropriately, rather than as a diagnostic tool, such as to determine the etiology of a change in mental status. This article reviews the pharmacokinetics and pharmacodynamics of naloxone. In addition, the appropriate administration is reviewed using a case study approach.     

Patient-Reported Outcomes and Opioid Use by Outpatient Cancer Patients

The Memorial Sloan Kettering Pain Registry contains patient characteristics, treatments, and outcomes for a prospective cohort of 1,534 chronic pain cancer patients who were seen at outpatient pain service clinics. Average pain intensity (Brief Pain Inventory) was reported as mild by 24.6% of patients, moderate by 41.5%, and severe by 33.9%. The patient's report of average percent pain relief and health state (EuroQOL 5 dimensions) was inversely related to average pain intensity category, whereas measures of pain interference, number of worst pain locations, and physical and psychological distress were directly related to pain intensity category. Eighty-six percent of patients received an opioid at 1 or more clinic encounters. Regression analysis revealed that male sex or being younger (65 years of age or younger) was associated with a greater likelihood of an opioid ordered. Male sex nearly doubled the likelihood of a higher dose being ordered than female sex. Bivariate analysis found that patients receiving opioids reported significantly more pain relief than no-opioid patients. However, patients receiving opioids had higher pain interference scores, lower index of health state, and more physical distress than no-opioid patients Our results identify the need to consider opioid use and dosage when attempting to understand patient-reported outcomes (PROs) and factors affecting pain management.

Development of the Revised Opioid Risk Tool to Predict Opioid Use Disorder in Patients with Chronic Nonmalignant Pain

The Opioid Risk Tool (ORT) is a commonly used measure of risk of aberrant drug-related behaviors in patients with chronic pain prescribed opioid therapy. In this study, the discriminant predictive validity of the ORT was evaluated in a unique cohort of patients with chronic nonmalignant pain (CNMP) on long-term opioid therapy who displayed no evidence of developing an opioid use disorder (OUD) and a sample of patients with CNMP who developed an OUD after commencing opioid therapy. Results revealed that the original ORT was able to discriminate between patients with and without OUDs (odds ratio = 1.624; 95% confidence interval [CI] = 1.539–1.715, P < .001). A weighted ORT eliminating the gender-specific history of preadolescent sexual abuse item revealed comparable results (odds ratio = 1.648, 95% CI = 1.539–1.742, P < .001). A revised unweighted ORT removing the history of preadolescent sexual abuse item was notably superior in predicting the development of OUD in patients with CNMP on long-term opioid therapy (odds ratio = 3.085; 95% CI = 2.725–3.493; P < .001) with high specificity (.851; 95% CI = .811–.885), sensitivity (.854; 95% CI = .799–.898), positive predictive value (.757; 95% CI = .709–.799), and negative predictive value (.914; 95% CI = .885–.937).Perspective: The revised ORT is the first tool developed on a unique cohort to predict the risk of developing an OUD in patients with CNMP receiving opioid therapy, as opposed to aberrant drug-related behaviors that can reflect a number of other issues. The revised ORT has clinical usefulness in providing clinicians a simple, validated method to rapidly screen for the risk of developing OUD in patients on or being considered for opioid therapy.