Article

Efficacy of intranasal naloxone as a needleless alternative for treatment of opioid overdose in the prehospital setting

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

Prehospital providers are at increased risk for blood-borne exposure and disease due to the nature of their environment. The use if intranasal (i.n.) medications in high-risk populations may limit this risk of exposure. To determine the efficacy of i.n. naloxone in the treatment of suspected opiate overdose patients in the prehospital setting, a prospective, nonrandomized trial of administering i.n. naloxone by paramedics to patients with suspected opiate overdoses over a 6-month period was performed. All adult patients encountered in the prehospital setting as suspected opiate overdose (OD), found down (FD), or with altered mental status (AMS) who met the criteria for naloxone administration were included in the study. i.n. naloxone (2 mg) was administered immediately upon patient contact and before i.v. insertion and administration of i.v. naloxone (2 mg). Patients were then treated by EMS protocol. The main outcome measures were: time of i.n. naloxone administration, time of i.v. naloxone administration, time of appropriate patient response as reported by paramedics. Ninety-five patients received i.n. naloxone and were included in the study. A total of 52 patients responded to naloxone by either i.n. or i.v., with 43 (83%) responding to i.n. naloxone alone. Seven patients (16%) in this group required further doses of i.v. naloxone. In conclusion, i.n. naloxone is a novel alternative method for drug administration in high-risk patients in the prehospital setting with good overall effectiveness. The use of this route is further discussed in relation to efficacy of treatment and minimizing the risk of blood-borne exposures to EMS personnel.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... Vermehrte mukosale Schleimproduktion oder Blut in der Nase kann möglicherweise die Resorptionsrate der Medikamente verändern [13,14]. Da insbe- ...
... Emergency medicine · Seizures · Pain therapy · Pharmacotherapy · Pharmacokinetics sondere Kinder häufig unter Atemwegsinfekten leiden, kann dies ein wesentlicher Einflussfaktor für eine unzureichende Medikamentenwirkung sein. Als weitere Faktoren für eine unsichere Resorption wurden frische Mittelgesichtstraumata und Veränderungen der normalen Nasenanatomie identifiziert [14]. ...
... Erste vielversprechende Ergebnisse mit intranasalem Naloxon im Rettungsdienst wurden 2002 und 2005 aus Denver publiziert [14,40]. Intranasales Naloxon erwies sich in Studien als gleichwertig im Vergleich zur i. v.-Applikation [41] und zeigte eine durchschnittliche Anschlagszeit von rund 3 min [40]. ...
Article
Die intranasale Applikation von Medikamenten zur Erzielung eines relevanten systemischen Plasmaspiegels wurde bereits vor rund 20 Jahren beschrieben. Die intranasale Medikamentenapplikation ist insbesondere durch eine geringe Invasivität bei gleichzeitig günstiger Pharmakokinetik gekennzeichnet und kann vor allem bei Kindern und bei Patienten mit schwierigen Venenverhältnissen eine sinnvolle Alternative zur intravenösen oder intraossären Medikamentengabe in der Notfallmedizin darstellen. Die intranasale Medikamentengabe findet außerdem eine hohe Akzeptanz bei medizinischem Personal. In den letzten Jahren wurden verschiedene Medikamente auf ihre Eignung zur intranasalen Applikation überprüft. Insbesondere die Möglichkeit der Initialtherapie zerebraler Krampfanfälle, der Analgosedierung sowie die intranasale Therapie der Opiatüberdosierung sind dabei attraktiv.
... 10,11 Studies have highlighted the possibility of intranasal (IN) delivery of naloxone to reverse the effects of opioid overdose in the prehospital setting. [12][13][14][15][16][17] These prior studies have largely focused on naloxone delivery administered by paramedics with specialized training serving as Advanced Life Support (ALS) providers. In 2006, in response to the increase in opioid-related overdoses, Boston EMS (the city's ambulance provider) obtained a Commonwealth of Massachusetts Office of Emergency Medical Services Special Project Waiver for the administration of intranasal naloxone by Basic Life Support (BLS) providers. ...
... 27 Barton and colleagues have demonstrated the safety of nasal naloxone by pre-hospital providers. 12,13 They discovered that >80% of patients responded to nasal naloxone, which had the further benefit of reducing the risk of blood-borne exposure and disease that can occur with needle-based administration of the antidote. Davis and colleagues conducted a national systematic legal review of naloxone policies for EMS in the prehospital setting. ...
... 17 However, several subsequent studies have demonstrated that it is safe, that rates of response are within 10 minutes are similar to the IM or IV route, and that there was no difference in mean response time. [11][12][13][14][15] Supplemental naloxone may need to be given more frequently after the IN route (compared to IM), 16 but there is likely minimal harm incurred by giving a second dose of naloxone, and since the IN route works in the vast majority of cases, it can decrease time to antidote. ...
Article
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.
... Early medical intervention may change the course of the poisoning by reducing drug absorption or counteracting the effects of a toxic agent. The prehospital use of naloxone for the treatment of opioid overdose is one typical example of such early medical intervention, with an 83% discharge rate just after its administration as an antidote [9]. ...
... This highlights the need for evaluation of the effectiveness and benefit-risk ratios of specific toxicological treatments in the prehospital setting. The effectiveness of naloxone in the management of opioid poisoning has been well demonstrated [9], however this is not the case for other types of antidote or poisoning. Another issue that remains to be resolved is the role of antidotes or decontamination therapy and the most appropriate person for their administration (paramedic or physician). ...
Article
Emergency management of deliberate self-poisoning (DSP) by drug overdose is common in emergency medicine. There is a paucity of data about the prehospital care of these patients. The principal aim was to describe the intensity of care received by patients with DSP who were managed by prehospital emergency medical service (EMS) physicians. A 48-h cross-sectional study was conducted in 319 EMS and emergency units in France. Patient and poisoning characteristics and treatments administered were recorded. Complications of poisoning, hospitalization, intensive care unit admission and death were recorded until day 30. The primary endpoint was the probability of receiving prehospital intensive care, including fluid resuscitation, vasopressor therapy, invasive ventilation, or antidotal treatments, depending whether prehospital treatment was carried out by an EMS physician or not. Data from 703 patients (median age was 43 [30–52] years, 288 (40%) men) were analyzed. One hundred and fifteen (16%) patients were attended by an EMS physician. Patients attended by EMS physicians were more likely to receive intensive treatment in the prehospital setting [odds ratio (OR) 7.4, 95% confidence interval 4.3–12.9]. These patients had more severe poisoning as suggested mainly by a lower Glasgow Coma Score (13 [8–15] vs. 15 [15–15]; p < 0.001) and a higher rate of admission to an intensive care unit [29 (25%) vs. 15 (2%), p < 0.001]. Patients with DSP attended by prehospital EMS physicians frequently received intensive care. The level of care seemed appropriate for the severity of the poisoning.
... Eventually, six studies were included in the study, including four clinical trials and two cohort studies. The studies contained data on 965 patients suspected of opioid overdose (4,(21)(22)(23)(24)(25). All of these patients had been treated with naloxone. ...
... All of these patients had been treated with naloxone. In the control groups, the patients were treated with intravenous (21,(23)(24)(25) or intramuscular (4,22) naloxone. In the treatment groups, intranasal naloxone was administered to the patients. ...
Article
Full-text available
Context: The present systematic review and meta-analysis aims to perform an extensive search in databases to compare the efficacy of the intranasal administration of naloxone with its intramuscular/intravenous administration in the pre-hospital management of opioid overdose. Evidence acquisition: This meta-analysis included controlled trials conducted on the efficacy of naloxone administration in the pre-hospital management of opioid overdose. A search was carried out in electronic databases on relevant articles published by the end of 2018. After data collection, analyses were performed in STATA 14.0 software and the efficacy and side-effects of the two administration routes of naloxone, i.e. intranasal and intramuscular/intravenous, were compared. An overall effect size with 95% confidence interval (95% CI) was provided for each section. Results: Eventually, data from six studies were included in this meta-analysis. The success rate of the intranasal and intramuscular/intravenous administration of naloxone in the management of opioid overdose in pre-hospital settings was 82.54% (95% CI: 57.97 to 97.89%) and 80.39% (95% CI: 57.38 to 96.04%), respectively. There was no difference between injectable (intramuscular/intravenous) naloxone and intranasal naloxone in the pre-hospital management of opioid overdose (Odds Ratio=1.01; 95% CI: 0.42 to 2.43; P=0.98). The onset of action of intranasal naloxone, however, was slightly longer than injectable naloxone (Standardized Mean Difference=0.63; 95% CI: 0.07 to 1.19; P=0.03). Additionally, the odds of needing a rescue dose was 2.17 times higher for intranasal naloxone than intramuscular/intravenous naloxone (OR=2.17; 95% CI: 1.53 to 3.09; P<0.0001). The prevalence of major side-effects was non-significant for both intranasal (0.00%) and intramuscular/intravenous (0.05%) routes of naloxone administration and there was no difference in the prevalence of major (OR=1.18; 95% CI: 0.38 to 3.69; P=0.777) and minor (OR=0.64; 95% CI: 0.17 to 2.34; P=0.497) side-effects between the two routes. Conclusion: The present meta-analysis demonstrated that intranasal naloxone is as effective as injectable naloxone in the pre-hospital management of opioid overdose complications. Consequently, intranasal naloxone may be an appropriate alternative to injectable naloxone.
... For a patient with suspected opioid overdose who has a definite pulse but no normal breathing or only gasping (ie, a respiratory arrest), in addition to providing standard pediatric BLS or ALS care, it is reasonable for responders to administer intramuscular or intranasal naloxone (Class 2a, LOE B-NR). [136][137][138][139][140][141][142][143][144][145][146][147][148][149] Empirical administration of intramuscular or intranasal naloxone to all unresponsive opioid-associated life-threatening emergency patients may be reasonable as an adjunct to standard first aid and non-healthcare provider BLS protocols (Class 2b, LOE C-EO). [137][138][139][140][141][142][143][144][145][147][148][149][150] New opioid-associated emergency algorithms for lay rescuers and healthcare professionals are provided. ...
... [136][137][138][139][140][141][142][143][144][145][146][147][148][149] Empirical administration of intramuscular or intranasal naloxone to all unresponsive opioid-associated life-threatening emergency patients may be reasonable as an adjunct to standard first aid and non-healthcare provider BLS protocols (Class 2b, LOE C-EO). [137][138][139][140][141][142][143][144][145][147][148][149][150] New opioid-associated emergency algorithms for lay rescuers and healthcare professionals are provided. ...
... Subsequently, Barton et al 39 reported the results of an extension of the foregoing nonrandomized prospective trial in which patients suspected of opioid overdose received IN naloxone. 38 Of the 52 patients who responded to naloxone by either IN or IV administration, 83% responded to 2 mg IN naloxone, although 7 (16%) of these responders were subsequently given IV naloxone due to declining response. ...
... There are two main intended user populations for IN naloxone products: lay responders (e.g., a parent, friend, or other family member of a known or suspected opioid overdose victim) who would be responsible for administering naloxone to the patient, and authorized first responders (e.g., firefighters, paramedics, emergency medical technicians, or police officers) who would be responsible for administering naloxone if no one had been able to do so at the time the first responders arrive at the scene. Although the studies of naloxone use by EMS first responders discussed above [37][38][39][40][41][42][43][44] focus on the comparative pharmacologic effectiveness of IN naloxone, studies of lay responder use, as discussed below, have more of a health services research focus, emphasizing the distribution and take-home delivery of naloxone. ...
Article
Full-text available
Deaths due to prescription and illicit opioid overdose have been rising at an alarming rate, particularly in the USA. Although naloxone injection is a safe and effective treatment for opioid overdose, it is frequently unavailable in a timely manner due to legal and practical restrictions on its use by laypeople. As a result, an effort spanning decades has resulted in the development of strategies to make naloxone available for layperson or “take-home” use. This has included the development of naloxone formulations that are easier to administer for nonmedical users, such as intranasal and autoinjector intramuscular delivery systems, efforts to distribute naloxone to potentially high-impact categories of nonmedical users, as well as efforts to reduce regulatory barriers to more widespread distribution and use. Here we review the historical and current literature on the efficacy and safety of naloxone for use by nonmedical persons, provide an evidence-based discussion of the controversies regarding the safety and efficacy of different formulations of take-home naloxone, and assess the status of current efforts to increase its public distribution. Take-home naloxone is safe and effective for the treatment of opioid overdose when administered by laypeople in a community setting, shortening the time to reversal of opioid toxicity and reducing opioid-related deaths. Complementary strategies have together shown promise for increased dissemination of take-home naloxone, including 1) provision of education and training; 2) distribution to critical populations such as persons with opioid addiction, family members, and first responders; 3) reduction of prescribing barriers to access; and 4) reduction of legal recrimination fears as barriers to use. Although there has been considerable progress in decreasing the regulatory and legal barriers to effective implementation of community naloxone programs, significant barriers still exist, and much work remains to be done to integrate these programs into efforts to provide effective treatment of opioid use disorders.
... Unapproved intranasal kits contain an injectable formulation of naloxone (e.g., prefilled syringe); to enable intranasal administration, the user must first attach an atomizer (manufactured by another company but provided in the kit) to the syringe [14]. Such kits have been increasingly available for public use [14] and have been employed successfully by first responders (e.g., emergency medical service personnel, police officers and bystanders) to reverse opioid overdose [15][16][17][18][19][20]. Although these products are FDA approved as injectables, they are not FDA approved for intranasal administration when included in a kit with an atomizer. ...
... Although comparative efficacy studies of naloxone formulations in the community-use setting are not feasible, the use of unapproved intranasal naloxone spray in a prehospital setting has been shown to be effective in reversing opioid overdose in retrospective studies [17,19], prospective nonrandomized studies [15,18,20] and in a randomized controlled study with im. naloxone as a comparator treatment arm [16]. ...
Article
Aim: To assess the pharmacokinetic properties of community-use formulations of naloxone for emergency treatment of opioid overdose. Methods: Systematic literature review based on searches of established databases and congress archives. Results: Seven studies met inclusion criteria: two of US FDA-approved intramuscular (im.)/subcutaneous (sc.) auto-injectors, one of an FDA-approved intranasal spray, two of unapproved intranasal kits (syringe with atomizer attachment) and two of intranasal products in development. Conclusion: The pharmacokinetics of im./sc. auto-injector 2 mg and approved intranasal spray (2 and 4 mg) demonstrated rapid uptake and naloxone exposure exceeding that of the historic benchmark (0.4 mg im.), indicating that naloxone exposure was adequate for reversal of opioid overdose.
... 12 In recent years, IN naloxone has become a popular choice for EMS because of its ease of use in a prehospital setting, with successful reversal rates 66-83% of the time, similar to other routes of administration. [13][14][15][16][17] Although the majority of the literature suggests that IN naloxone is effective, some research has shown that the clinical response time was slower and that more administrations were required to achieve the same effect as IV. 16 It has also been noted that that the change in respiratory rate is slightly less rapid for IN. 17 Dowling et al., found that a combination of IN and IM naloxone produced the best long-lasting reversal effect. ...
... The National EMS data for 2012 show that 95,012 patients were administered naloxone, of whom 13 A comparison of expected MNA and observed MNA by US Census region shows that the South had a lower MNA (n = 9,954) than what would be expected (n = 13,991) (Chi Squared = 1,164.7, p<0.01; see Figure 2). ...
Article
Background: Opioid overdoses are at epidemic levels in the United States. Emergency Medical Service (EMS) providers may administer naloxone to restore patient breathing and prevent respiratory arrest. There was a need for contemporary data to examine the number of naloxone administrations in an EMS encounter. Methods: Using data from the National Emergency Medical Services Information System, we examined data from 2012-5 to determine trends in patients receiving multiple naloxone administrations (MNAs). Logistic regression including demographic, clinical, and operational information was used to examine factors associated with MNA. Results: Among all events where naloxone was administered only 16.7% of the 911 calls specifically identified the medical emergency as a drug ingestion or poisoning event. The percentage of patients receiving MNA increased from 14.5% in 2012 to 18.2% in 2015, which represents a 26% increase in MNA in 4 years. Patients aged 20-29 had the highest percentage of MNA (21.1%). Patients in the Northeast and the Midwest had the highest relative MNA (Chi Squared = 539.5, p < 0.01 and Chi Squared = 351.2, p < 0.01, respectively). The logistic regression model showed that the adjusted odds ratios (aOR) for MNA were greatest among people who live in the Northeast (aOR = 1.18, 95% CI = 1.13-1.22) and for men (aOR = 1.13, 95% CI = 1.10-1.16), but lower for suburban and rural areas (aOR = 0.76, 95% CI = 0.72-0.80 and aOR = 0.85, 95% CI = 0.80-0.89) and lowest for wilderness areas (aOR = 0.76, 95% CI = 0.68-0.84). Higher adjusted odds of MNA occurred when an advanced life support (ALS 2) level of service was provided compared to basic life support (BLS) ambulances (aOR = 2.15, 95% CI = 1.45-3.16) and when the dispatch complaint indicated there was a drug poisoning event (aOR = 1.12, 95% CI = 1.09-1.16). Reported layperson naloxone administration prior to EMS arrival was rare (1%). Conclusion: This study shows that frequency of MNA is growing over time and is regionally dependent. MNA may be a barometer of the potency of the opioid involved in the overdose. The increase in MNA provides support for a dosage review. Better identification of opioid related events in the dispatch system could lead to a better match of services with patient needs.
... Despite the poor bioavailability of standard concentration (0.4-1 mg/ml) IN naloxone, there are numerous reports of its clinical efficacy being equal to or surpassing that of IV administration.134,[172][173][174] Barton and colleagues evaluated the pre-hospital administration of IN followed by IV naloxone to patients suspected of opioid overdose.175 Among 52 patients that responded to either IV or IN naloxone, 83% responded to an Administration of naloxone in a community setting by non-medical personnel.AMA, against medical advice; ED, emergency department; EMS, emergency medical services; GCS, Glasgow Coma Scale; HR, heart rate; NR, not reported; OD, overdose; RR, respiratory rate; HA, headache. ...
Article
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.
... Naloxone is a competitive antagonist of the μ opioid receptor, which has been used clinically for many years to reverse the effects of opioids. Several clinical studies suggest its efficacy when INas administered [40]. ...
Article
Full-text available
Opioids are essential for the treatment of pain, which is a serious symptom for children and adolescents affected by cancer. Intranasal opioids may be very useful for the treatment of breakthrough pain in children and adolescents with cancer, for their little invasiveness, ease of administration, rapid onset of action, and high bioavailability. Intranasal drug delivery may be influenced by anatomical and physiological factors (nasal mucosa absorption area, mucociliary clearance, enzymatic activity, anatomical anomalies, chronic or inflammatory alterations of nasal mucosa), drug-related factors (molecular weight, solubility), and delivery device. Fentanyl is a lipophilic opioid commonly proposed for intranasal use among pediatric patients, but no studies have been conducted yet about intranasal use of other available opioids for management of pediatric cancer pain. In this review, we analyze several elements which may influence absorption of intranasal opioids in children and adolescents, with a focus on pharmacokinetics and therapeutic aspects of each opioid currently available for intranasal use.
... Darüber hinaus können Veränderungen der nasalen Anatomie (etwa bei einer Mittelgesichtsfraktur), Blut oder Sekret in den Nasengängen oder eine Änderung der mukosalen Durchblutung möglicherweise die Resorption von Medikamenten verändern bzw. einschränken [2,5]. Die Nasenhöhle sollte daher vor der Medikamentengabe inspiziert und größere Mengen an Blut oder Sekretwenn möglichvorsichtig abgesaugt werden. ...
... The acute effects and potential lethality of opioids can be reversed by the timely administration of naloxone, which is a nonselective competitive opioid antagonist at the opioid receptors that inhibits all pharmacologic effects of opioids (39,40). Naloxone may be quickly, safely, and effectively administered intranasal by first responders, with low overall risk (41,42). However, in order for it to be effective, one must first have the clinical suspicion that an opioid overdose may have occurred and also have naloxone readily available for administration in a timely fashion (43). ...
Article
In recent years, there has been a substantial increase in opioid use and abuse, and in opioid-related fatal overdoses. The increase in opioid use has resulted at least in part from individuals transitioning from prescribed opioids to heroin and fentanyl, which can cause significant respiratory depression that can progress to apnea and death. Heroin and fentanyl may be used individually, together, or in combination with other substances such as ethanol, benzodiazepines, or other drugs that can have additional deleterious effects on respiration. Suspicion that a death is drug-related begins with the decedent's medical and social history, and scene investigation, where drugs and drug paraphernalia may be encountered, and examination of the decedent, which may reveal needle punctures and needle track marks. At autopsy, the most significant internal finding that is reflective of opioid toxicity is pulmonary edema and congestion, and frothy watery fluid is often present in the airways. Various medical ailments such as heart and lung disease and obesity may limit an individual's physiologic reserve, rendering them more susceptible to the toxic effects of opioids and other drugs. Although many opioids will be detected on routine toxicology testing, more specialized testing may be warranted for opioid analogs, or other uncommon, synthetic, or semisynthetic drugs.
... 85 IN naloxone is statistically as effective as IV and IM naloxone, causes improvement and withdrawal effects almost as rapidly as IV, but requires rescue doses more often. [86][87][88][89] IN naloxone was shown to be faster, easier to administer and perceived as safer in those trained. 90 This evidence suggests that IN is the preferred route, with IV and IM as alternative routes. ...
Article
Full-text available
Introduction In the United States emergency medical services (EMS) protocols vary widely across jurisdictions. We sought to develop evidence-based recommendations for the prehospital evaluation and treatment of a patient with an acute change in mental status and to compare these recommendations against the current protocols used by the 33 EMS agencies in the State of California. Methods We performed a literature review of the current evidence in the prehospital treatment of a patient with altered mental status (AMS) and augmented this review with guidelines from various national and international societies to create our evidence-based recommendations. We then compared the AMS protocols of each of the 33 EMS agencies for consistency with these recommendations. The specific protocol components that we analyzed were patient assessment, point-of-care tests, supplemental oxygen, use of standardized scoring, evaluating for causes of AMS, blood glucose evaluation, toxicological treatment, and pediatric evaluation and management. Results Protocols across 33 EMS agencies in California varied widely. All protocols call for a blood glucose check, 21 (64%) suggest treating adults at <60mg/dL, and half allow for the use of dextrose 10%. All the protocols recommend naloxone for signs of opioid overdose, but only 13 (39%) give specific parameters. Half the agencies (52%) recommend considering other toxicological causes of AMS, often by using the mnemonic AEIOU TIPS. Eight (24%) recommend a 12-lead electrocardiogram; others simply suggest cardiac monitoring. Fourteen (42%) advise supplemental oxygen as needed; only seven (21%) give specific parameters. In terms of considering various etiologies of AMS, 25 (76%) give instructions to consider trauma, 20 (61%) to consider stroke, and 18 (55%) to consider seizure. Twenty-three (70%) of the agencies have separate pediatric AMS protocols; others include pediatric considerations within the adult protocol. Conclusion Protocols for patients with AMS vary widely across the State of California. The evidence-based recommendations that we present for the prehospital diagnosis and treatment of this condition may be useful for EMS medical directors tasked with creating and revising these protocols.
... Naloxon bei Opiatüberdosierung kann trotz häufig schwieriger Venenverhältnisse intranasal zügig appliziert werden. Hierbei ist zu beachten, dass mit die in Deutschland verbreiteten Ampullen mit 0,4 mg/ml bei Verteilung von je 1 ml pro Nasenloch eine maximale Dosierung von 0,8 mg erlauben [2]. ...
... An intranasal device was chosen carefully by the Norwegian Directorate of health, given its demonstrated effectiveness (Barton et al., 2005;Kerr et al., 2009;Lobmaier et al., 2011;Robertson et al., 2009) and user-friendly administration. However, at the time, an ideal pre-assembled registered intranasal preparation was unavailable. ...
Thesis
Full-text available
Naloxone is the antidote to an opioid overdose, and has long been used by health personnel to reverse overdoses. More recently, non-medical bystanders have also been equipped to recognize and respond to an overdose with naloxone. In 2014 the National Overdose Prevention Strategy included the provision of naloxone to bystanders, becoming one of the first government-supported naloxone programs. The aims of this thesis were to describe characteristics of opioid overdoses occurring in Bergen, Norway, and to evaluate the introduction and implementation of a widespread take-home naloxone program in Norway. This was done using ambulance records, a pre-test post-test analysis, and questionnaires from participants trained to use naloxone. Participants were mostly opioid users, and nearly all had previously witnessed or experienced an overdose. Distribution goals were met within the first 18 months, demonstrating that that the use multiple existing facilities achieved rapid, high volume distribution of naloxone to an at-risk group. Together the findings support the appropriateness and feasibility of implementing a widespread naloxone distribution program.
... In another a prospective nonrandomized trial among all patients who presented with potential opiate drug intoxication, paramedics administered 2 mg of IN naloxone upon patient contact [17]. Of the 52 patients treated, 83% responded to IN naloxone alone and 16% were unresponsive to IN naloxone and required further doses of IV naloxone. ...
Article
Full-text available
Purpose of Review Rising opioid overdoses are a nationwide problem. This review aims to educate health care professionals on the various naloxone nasal formulations that are available. Recent Findings National data confirms a significant increase in opioid overdoses and a need for all health care professionals to recognize the importance of dispensing naloxone when indicated. With four options available (two intranasal and two intramuscular), naloxone may be dispensed with or without a prescription in many states. Summary Being aware of the current formulations and offering naloxone prescriptions to patients at risk are among the current recommendations for providers to impact addictive behaviors, thus, reducing the risk of overdose.
... The usual route in overdose is i.v., but the intranasal route has proved to be effective in a community setting, where it will most likely be administered by nonmedically trained individuals. 17 ...
... The FDA approved the first commercial IN naloxone kit (Narcan®, 4 mg/0.1 mL) in 2015 (U.S. retail price of approximately $130 for two IN kits) [95]. The concentrated formulation was intended to improve the clinical reversal rate of the non-FDA approved kits, which had an 18% to 27% non-response rate [86,93,97]. The Narcan IN device delivers misted naloxone through a single nostril. ...
Article
Full-text available
Introduction: There has been an exponential increase in overdose fatalities as illicitly manufactured fentanyl and its analogs (IMF) are becoming more prevalent in the illicit drug supply. In response, overdose education and naloxone distribution (OEND) programs have been implemented throughout the United States as a harm reduction strategy. However, there are increasing reports that higher naloxone doses or repeat administration might be required for overdose victims involving IMF. Areas covered: In this article, we provide a comprehensive review of the epidemiology, public health impact, and pharmacologic properties of IMF. The pharmacokinetic properties of currently available take-home naloxone (THN) kits, the role of THN as a harm reduction strategy and available data on its clinical use are discussed. Implications of occupational IMF exposure for first responders are also described. Expert opinion: THN administration by a bystander is an effective harm reduction intervention. However, there is growing evidence that higher dose or multiple administrations of naloxone are required to fully reverse IMF related toxicity. Recently, the US Food and Drug Administration approved THN kits with a concentrated naloxone dose that produce high bioavailability. However, limited presence of OEND programs and cost of these new devices impede their accessibility to the general public.
... Several clinical studies have evaluated the potential of nasal naloxone. The common issue in these studies was the same as that for the THN-programs; in the use of formulations not optimized for nasal administration [25][26][27], and in the few randomized controlled trials conducted, the need for naloxone rescue was 13% higher in the IN group compared to that in IM administrations [7,8] confirming that the dose delivered systemically may have been too small, as expected from the biological considerations above. ...
Article
Full-text available
Purpose: Nasal naloxone is wanted for bystander administration in opioid overdose and as a needle-free alternative for emergency medical personnel. Epidemiologic studies have indicated a therapeutic effect of bystander administration of low-concentration/high-volume formulations. The objective for this study was to describe the nasal pharmacokinetics of a new high-concentration/low-volume nasal formulation of naloxone. Methods: This was an open, randomized triple crossover trial in healthy, human volunteers (n = 12) where two doses of nasal naloxone (0.8 and 1.6 mg) and one intravenous dose (1.0 mg) were compared. Fifteen serum samples were collected before and until 6 h after naloxone administration. Quantification of naloxone was performed by a validated liquid chromatography-tandem mass spectrometry method. Results: Bioavailability was 0.54 (0.45-0.63) for the 0.8 mg and 0.52 (0.37-0.67) for the 1.6 mg nasal naloxone formulation. Maximum concentration levels (C max) were 1.45 ng/ml (1.07-1.84) for 0.8 mg and 2.57 ng/ml (1.49-3.66) for the 1.6 mg. Time to maximum concentrations (T max) were reached at 17.9 min (11.4-24.5) and 18.6 min (14.4-22.9) for the 0.8 mg and the 1.6 mg doses, respectively. Conclusion: This nasal naloxone formulation had a rapid, systemic uptake and higher bioavailability than naloxone formulations not designed for IN use. This indicates that an optimized high-concentration/low-volume nasal spray formulation may deliver a therapeutic dose. The 1.6 mg nasal dose provided serum concentrations that surpassed those of 1.0 mg IV after 15-20 min and stayed above for the rest of the study period. FULL TEXT: http://rdcu.be/oW0B
... Naloxone has a rapid onset of action, reaching maximal serum concentration within 2 minutes after IV administration, 10 minutes after IM, and [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30]. Naloxone distributes to the central nervous system and equilibrates with the plasma within minutes ( 15 ). ...
Article
Full-text available
The opioid crisis is a growing concern for Americans, and it has become the leading cause of injury-related death in the United States (¹). An adjunct to respiratory support that can reduce this high mortality rate is the administration of naloxone by Emergency Medical Services (EMS) practitioners for patients with suspected opioid overdose. However, clear evidence-based guidelines to direct EMS use of naloxone for opioid overdose have not been developed. Leveraging the recent Agency for Healthcare Research and Quality (AHRQ) systematic review on the EMS administration of naloxone for opioid poisonings, federal partners determined the need for a clinical practice guideline for EMS practitioners faced with suspected opioid poisoning (²). Project funding was provided by the National Highway Traffic Safety Administration, Office of EMS, (NHTSA OEMS) and the Health Resources and Services Administration, Maternal and Child Health Bureau’s EMS for Children Program (EMSC). The objectives of this project were to develop and disseminate an evidence-based guideline and model protocol for administration of naloxone by EMS practitioners to persons with suspected opioid overdose. We have four recommendations relating to route of administration, all conditional, and all supported by low or very low certainty of evidence. We recommend the intravenous route of administration to facilitate titration of dose, and disfavor the intramuscular route due to difficulty with titration, slower time to clinical effect, and potential exposure to needles. We equally recommend the intranasal and intravenous routes of administration, while noting there are variables which will determine which route is best for each patient. Where we are unable to make recommendations due to evidence limitations (dosing, titration, timing, and transport) we offer technical remarks. Limitations of our work include the introduction of novel synthetic opioids after many of the reviewed papers were produced, which may affect the dose of naloxone required for effect, high risk of bias and imprecision in the reviewed papers, and the introduction of new naloxone administration devices since many of the reviewed papers were published. Future research should be conducted to evaluate new devices and address the introduction of synthetic opioids.
... Historically, the intravenous administration of naloxone has been the preferred route due to its rapid onset of action. However, several studies in the out-of-hospital setting have demonstrated the effectiveness of alternative routes of administration [6][7][8][9][10][11]. ...
Article
Introduction Patient-specific discrepancies in prehospital naloxone administration have been documented. As the opioid epidemic continues to evolve, further evaluation of prehospital naloxone administration practices is needed. The objective of this study was to compare patients who received prehospital naloxone and received an emergency department (ED) diagnosis of opioid overdose with patients who received prehospital naloxone and received an alternative ED diagnosis. Methods This was a retrospective, multicenter chart review of patients who received naloxone by prehospital personnel for suspected opioid overdose between October 1, 2016, and October 31, 2017. Patients were excluded if age was less than 18 years, naloxone was administered by non-emergency medical service (EMS) personnel, not transported, or if prehospital records could not be linked with ED records. Demographic information and several prehospital clinical findings, including unresponsiveness, apnea, and miosis, were compared between patients diagnosed with opioid overdoses versus an alternative ED diagnosis. Descriptive statistics were utilized. Results A total of 837 patients had complete data available and were included in the analysis. Overall, 402 (48%) of patients received an ED diagnosis of opioid overdose, and 435 (52%) of patients received an alternative ED diagnosis. Patients in the alternative diagnosis group were older, had less known drug use, were more likely to be admitted, and had lower incidences of apnea, unresponsiveness, and miosis. In the opioid overdose group, there was a higher proportion of previous drug use, apnea, unresponsiveness, and miosis in the EMS setting, whereas there was a higher proportion of previous overdose, previous suicide attempts, and neurological deficits in the ED setting. Conclusions In this retrospective review evaluating patients who received prehospital naloxone, several demographic and clinical differences were noted between the two groups. Further elucidation of the safety and efficacy of prehospital naloxone in alternative diagnoses is needed.
... 20 In a study of [ 14 C] labeled NLX, peak radioactivity was detected at 15 min, with 82% of the radioactivity reduced after 30 min, after 10 mg kg −1 sc dose, showing the rapid metabolism and elimination of NLX, demonstrating its short duration of action. 39 Recent studies have shown that NLX is clinically effective for the reversal of opioid intoxication in an emergency setting 40 and can be safely administered in prehospital and hospital environments. 24,25 Intranasal route of administration has the advantage of rapid onset of action, bypassing the first-pass metabolism through the direct transport to the central nervous system via nasal mucosa. ...
Article
Full-text available
Overdose is the main cause of mortality among heroin users. Many of these overdose-induced deaths can be prevented through the timely administration of naloxone (NLX), a nonselective mu (μ)-, kappa (κ)-, and delta (δ)-opioid receptor antagonist. NLX competitively inhibits opioid-overdose-induced respiratory depression without eliciting any narcotic effect itself. The aim of this study was to investigate the antagonistic action of NLX by comparing its distribution to that of 6-monacetylmorphine (6-MAM), heroin’s major metabolite, in a rodent model using mass spectrometric imaging (MSI) in combination with liquid chromatography–tandem mass spectrometry (LC–MS/MS). Male Sprague–Dawley rats (n = 5) received heroin (10 mg kg–1) intraperitoneally, NLX (10 mg kg–1) intranasally, and NLX injected intranasally 5 min after heroin administration. The animals were sacrificed 15 min after dose and brain tissues were harvested. The MSI image analysis showed a region-specific distribution of 6-MAM in the brain regions including the corpus callosum, hippocampal formation, cerebral cortex, corticospinal tracts, caudate putamen, thalamus, globus pallidus, hypothalamus, and basal forebrain regions of the brain. The antagonist had a similar biodistribution throughout the brain in both groups of animals that received NLX or NLX after heroin administration. The MSI analysis demonstrated that the intensity of 6-MAM in these brain regions was reduced following NLX treatment. The decrease in 6-MAM intensity was caused by its displacement by the antagonist and its binding to these receptors in these specific brain regions, consequently enhancing the opioid elimination. These findings will contribute to the evaluation of other narcotic antagonists that might be considered for use in the treatment of drug overdose via MSI.
... A follow-up study found that using a more concentrated form of naloxone at the same dose resulted in no difference in the latency of IN and IM naloxone to restore respiration (Kerr et al., 2009). Barton et al. compared naloxone IV (1-2 mg) or IN (2 mg) for opioid overdose in humans, and found that both produced clinically significant recovery within 3 minutes (Barton et al., 2005). However, the paramedic subjectively determined the choice of which route to use, the initial dose of drug IV, and the presence or absence of clinically ...
Thesis
There are two general approaches for improving pain control with opioids: identifying novel analgesics without μ-opioid receptor side effects, and developing strategies to optimize clinically used opioids. This thesis investigates a novel target for pain control (the nociceptin/orphanin FQ (NOPr) receptor), as well as the potential for improving current and future opioid medications by utilizing the intranasal (IN) route of delivery. In rhesus monkeys, NOPr agonists have been shown to produce analgesia in the absence of unwanted μ-receptor mediated effects. Other behaviors produced through NOP receptors have not been characterized. This thesis established for the first time in monkeys that the NOPr agonist Ro 64-6198 produced discriminative stimulus effects that were behaviorally and pharmacologically distinct from other opioid receptors, but were similar to the benzodiazepine, diazepam. In contrast to previous work, Ro 64-6198 did not produce antinociception in the monkey tail withdrawal assay, suggesting that this effect may be more variable than previously thought. IN drug administration offers several benefits for developing and administering therapeutics. Despite the favorable profile, IN delivery is employed less frequently than other parenteral routes, and functional animal models for IN delivery are not well established. This thesis reports the first model to measure the analgesic effects of intranasally administered opioids in rhesus monkeys. The effects of IN fentanyl and buprenorphine were found to be dose-dependent; a comparison to intramuscular (IM) administration suggested that IN delivery may result in a faster onset of action, and produce greater analgesia at lower doses. The translational aspects of this model were further explored by studying the actions of IN naloxone (NLX), a drug that is routinely used to reverse opioid toxicity, and where some questions remain about its potency and effectiveness relative to other routes. IN and IV NLX were found to be equipotent in reversing fentanyl-induced antinociception, however there was a trend for IV administration to produce larger decreases. Data obtained from PET images showed a similar trend for receptor occupancy. Overall, this thesis expanded the behavioral profile of NOPr agonists in monkeys, and provided a framework to investigate the IN delivery of novel and clinically used opioids.
... 25 In another study from the same time period, 16% required more than the 4 mg dose to be revived. 26 In a retrospective review of suspected opioid overdose in California, significantly more patients responded to combined routes of administration (intranasal followed by intravenous) than they did to one route alone. 27 And because of the short half-life of naloxone and other factors, revival from opioid-induced respiratory depression may be transient. ...
Article
What is known and Objective Food and Drug Administration (FDA) risk evaluation and mitigation strategies (REMs) encourage emergency responders, paramedics, law enforcement agents, and even laypeople to be trained in the administration of naloxone with the intent of rescuing individuals from a known or suspected opioid overdose. Comment Although naloxone is generally safe and effective at reversing respiratory depression caused by a conventional opioid such as morphine or heroin by competing with the opioid and displacing it from the μ-opioid receptor, questions increasingly are arising as to whether naloxone can adequately reverse opioid overdoses that may involve the potent opioids fentanyl and its analogues (F/FAs). In other words, as more and more opioid overdoses involve F/FAs, can naloxone keep up? What is new and Conclusion As a competitive antagonist at μ-opioid receptors, naloxone is often a life-saving agent in cases of overdose caused by conventional opioids, but it may not be versatile or powerful enough to combat the rising tide of overdoses due to fentanyl and its illicit analogues, or in cases of overdose involving combinations of opioids and non-opioids.
... Intranasal (IN) naloxone gained fast-track FDA approval in November 2015, although it had long been used as an improvised kit involving an atomizer and injectable naloxone [6]. It has proven to be a safe, effective, and easy-to-use method of reducing heroin and opiate overdose mortality [7][8][9]. ...
Article
Full-text available
Introduction: The opioid crisis continues to claim lives at historically unprecedented levels and shows few signs of abating. One means of mitigating the harm from opioid abuse and unintentional overdose is training and equipping police officers to administer intranasal (IN) naloxone as part of a broader public health response. While an increasing number of state and local agencies have implemented law enforcement officer (LEO) naloxone training programs, due to the novelty of these programs, the evidence of program efficacy is limited. This study describes the implementation and evaluation of a LEO training program in opioid overdose recognition, management, and administration of IN naloxone. Methods: This evaluation consisted of a secondary analysis of de-identified administrative quality assurance data. Police officers in Howard County, Maryland (n=281) underwent an IN naloxone training program between June and July 2015. The training program entailed a 30-minute online component, a 45-minute in-service session, and a 15-question post-test (n=228). The success of the training program was evaluated via an opioid overdose knowledge survey administered at 30 days (n=207) and 6 months (n=182) after training. Results: The 30-day and 6-month scores for all knowledge outcomes indicated that officers retained the contents of the training program well over time. After six months, 100% of respondents correctly identified the physiological effects of naloxone administration, and 95.6% correctly identified the opioid-containing drugs that may result in overdose. At the six-month mark, 74.59% correctly identified the initial signs of opioid overdose, and 60.99% correctly identified the time required for IN to begin working. Conclusion: LEOs exhibit the ability to retain the contents of IN training over 30-day and 6-month periods and express confidence in their ability to assist suspected opioid overdose victims. Further research is necessary to determine the degree to which further knowledge decay might occur, the sustained ability to implement this knowledge under real-world conditions, and the subsequent effects on overdose victim survival.
... Subsequently, intranasal administration was suggested as a safe and efficient alternative to the use of needles. Injectable naloxone has been used offlabel for intranasal administration throughout several years by prehospital staff [54][55][56][57][58][59][60], emergency medical services [61] and in the emergency department [62] with satisfactory clinical effect, compared to IV or IM administration [59,60,63]. Approved by the FDA in November 2015 [63], pharmacokinetic studies comparing the new intranasal to intra muscular administration, have shown satisfying results [64][65][66][67]. ...
Article
Full-text available
Background: Continuously high rates of overdose deaths in Sweden led to the decision by the Skåne County to initiate the first regional take-home naloxone program in Sweden. The project aims to study the effect of overdose prevention education and naloxone distribution on overdose mortality in Skåne County. Secondary outcome measures include non-fatal overdoses and overdose-related harm in the general population, as well as cohort-specific effects in study participants regarding overdoses, mortality and retention in naloxone program. Methods: Implementation of a multi-site train-the-trainer cascade model was launched in June 2018. Twenty four facilities, including opioid substitution treatment units, needle exchange programs and in-patient addiction units were included for the first line of start-up, aspiring to reach a majority of individuals at-risk within the first 6 months. Serving as self-sufficient naloxone hubs, these units provide training, naloxone distribution and study recruitment. During 3 years, questionnaires are obtained from initial training, follow up, every sixth month, and upon refill. Estimated sample size is 2000 subjects. Naloxone distribution rates are reported, by each unit, every 6 months. Medical diagnoses, toxicological raw data and data on mortality and cause of death will be collected from national and regional registers, both for included naloxone recipients and for the general population. Data on vital status and treatment needs will be collected from registers of emergency and prehospital care. Discussion: Despite a growing body of literature on naloxone distribution, studies on population effect on mortality are scarce. Most previous studies and reports have been uncontrolled, thus not being able to link naloxone distribution to survival, in relation to a comparison period. As Swedish registers present the opportunity to monitor individuals and entire populations over time, conditions for conducting systematic follow-ups in the Swedish population are good, serving the opportunity to study the impact of large scale overdose prevention education and naloxone distribution and thus fill the knowledge gap. Trial registration: Naloxone Treatment in Skåne County - Effect on Drug-related Mortality and Overdose-related Complications, NCT03570099, registered on 26 June 2018.
... In addition, the use of this needleless route is effective in the treatment and minimizing the risk of blood-borne exposures to EMS personnel, mainly in addicted patients (16,17). ...
Article
Introduction: The administration of the opioid antagonist naloxone in the community is a measure to prevent death from opioid overdose. Approved nasal naloxone sprays deliver initial doses of 0.9 to 8 mg. The level of the initial community dose is controversial, as the scientific base is weak. Areas covered: In this review knowledge of the pharmacokinetics of nasal, both approved and improvised nasal sprays, and intramuscular naloxone will be utilized to evaluate dose-effect relationships in previous studies of opioid overdose outcomes.The aim was to present scientifically based considerations on the initial nasal naloxone doses currently available, which reasonably balances the effect and adverse outcomes, given that at least two doses are at hand. Also included in these considerations is the challenge by illicitly manufactured fentanyl and analogs.This paper is based on both peer-reviewed and grey literature identified by several searches, of such as naloxone pharmacokinetics/formulations/outcomes/emergency medical services, in PubMed and Embase. Expert opinion: There is little scientific evidence that supports the use of initial systemic dosing that exceed 0.8 mg in the community. Higher doses increase the risk of withdrawal symptoms feared in people who use opioids. Many obstacles may reduce the potential of community-administered naloxone.
Article
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.
Article
Background: As drug-related morbidity and mortality continue to surge, police officers are on the front lines of the North American overdose (OD) crisis. Drug law enforcement shapes health risks among people who use drugs (PWUD), while also impacting the occupational health and wellness of officers. Effective interventions to align law enforcement practices with public health and occupational safety goals remain underresearched. Objective: The Opioids and Police Safety Study (OPS) aims to shift police practices relating to PWUD. It adapts and evaluates the relative effectiveness of a curriculum that bundles content on public health promotion with occupational risk reduction (ORR) to supplement a web-based OD response and naloxone training platform (GetNaloxoneNow.org, or GNN). This novel approach has the potential to improve public health and occupational safety practices, including using naloxone to reverse ODs, referring PWUD to treatment and other supportive services, and avoiding syringe confiscation. Methods: This longitudinal study uses a randomized pragmatic trial design. A sample of 300 active-duty police officers from select counties in Pennsylvania, Vermont, and New Hampshire with high OD fatality rates will be randomized (n=150 each) to either the experimental arm (GNN + OPS) or the control arm (GNN + COVID-19 ORR). A pre- and posttraining survey will be administered to all 300 officers, after which they will be administered quarterly surveys for 12 months. A subsample of police officers will also be qualitatively followed in a simultaneous embedded mixed-methods approach. Research ethics approval was obtained from the New York University Institutional Review Board. Results: Results will provide an understanding of the experiences, knowledge, and perceptions of this sample of law enforcement personnel. Generalized linear models will be used to analyze differences in key behavioral outcomes between the participants in each of the 2 study arms and across multiple time points (anticipated minimum effect size to be detected, d=0.50). Findings will be disseminated widely, and the training products will be available nationally once the study is completed. Conclusions: The OPS is the first study to longitudinally assess the impact of a web-based opioid-related ORR intervention for law enforcement in the U.S. Our randomized pragmatic clinical trial aims to remove barriers to life-saving police engagement with PWUD/people who inject drugs by focusing both on the safety of law enforcement and evidence-based and best practices for working with persons at risk of an opioid OD. Our simultaneous embedded mixed-methods approach will provide empirical evaluation of the diffusion of the naloxone-based response among law enforcement. Trial registration: ClinicalTrail.gov NCT05008523; https://clinicaltrials.gov/show/NCT05008523. International registered report identifier (irrid): DERR1-10.2196/33451.
Chapter
The prehospital patient with altered mental status (AMS) presents a challenge to EMS clinicians, who must rapidly and thoroughly assess and stabilize vital functions in an undifferentiated patient. Reversible causes must be evaluated and treated, and life-threatening conditions recognized. EMS clinicians are better able to effectively manage AMS patients when they understand the breadth of potentially concomitant causes of the condition. An organized approach to assessment and management of the AMS patient is important as a broad differential diagnosis is considered and an appropriate treatment pathway is pursued.
Article
Context: The United States is in the midst of an opioid overdose epidemic. Opioids killed more than 28 000 people in 2014, more than any year on record. One approach to addressing this growing epidemic is Opioid Overdose Education and Naloxone Distribution (OEND) training. Little is known about these programs' participants and their effectiveness across different demographic groups. Objectives: To examine (1) whether knowledge and attitudes improved over the course of the training programs; (2) whether training outcomes differ by demographics; and (3) what overdose experiences do attendees have, and whether those experiences influence their knowledge and attitudes. Design: A pre- and posttest survey was used to collect data on participants' demographics, overdose experiences, and opioid overdose knowledge and attitudes. Setting: Surveys that took place at community-wide OEND programs were offered throughout Erie County, New York, during October and November 2015. Participants: Community members who elected to attend the training programs, were at least 18 years of age, spoke English, and were willing and able to participate were included in the sample (N = 198). Intervention: N/A. Main outcome measure: The Opioid Overdose Knowledge and Attitudes Scale. Results: Knowledge and attitude scores significantly improved from pre- to posttest assessments, increasing by 23.1% and 15.4%, respectively (Ps < .001). There were significant demographic differences in knowledge and attitudes at the pretest assessment, but these differences were ameliorated by the OEND program and did not persist at posttest assessment. In addition, 62.9% of participants had never experienced, witnessed, or known someone who had overdosed. Conclusion: Results indicate that OEND programs are effective at improving knowledge and attitudes toward opioid overdose. These results indicate that OEND programs are not reaching the highest risk individuals but are instead attracting concerned family and significant others. Future programs should focus on reaching current opioid users, overdose victims, and their families to ensure OEND programs are reaching the target audiences.
Article
The intranasal route for medication administration is increasingly popular in the emergency department and out-of-hospital setting because such administration is simple and fast, and can be used for patients without intravenous access and in situations in which obtaining an intravenous line is difficult or time intensive (eg, for patients who are seizing or combative). Several small studies (mostly pediatric) have shown midazolam to be effective for procedural sedation, anxiolysis, and seizures. Intranasal fentanyl demonstrates both safety and efficacy for the management of acute pain. The intranasal route appears to be an effective alternative for naloxone in opioid overdose. The literature is less clear on roles for intranasal ketamine and dexmedetomidine.
Article
Objective: To examine the impact of full-time equivalent employee (FTEE) allocation to academic detailers on naloxone prescribing at the U.S. Veterans Health Administration (VA). Design: Longitudinal nonequivalent control group posttest-only design using a random effects model. Setting and participants: Closed cohort of primary care providers exposed to academic detailing between September 1, 2016, and September 20, 2018, at VA. Outcome measures: Previous analysis identified a cutoff of 0.40 FTEE was associated with a greater return on investment. We evaluated whether this level of FTEE allocation was associated with increases in naloxone prescribing rates and compared providers who had an interaction with an academic detailer allocated 0.4 FTEE or greater (high FTEE) to providers who interacted with an academic detailer allocated less than 0.4 FTEE (low FTEE). Results: Among VA primary care providers who received academic detailing, 1770 (68%) had interactions with a high FTEE academic detailer. There were no differences in demographics between providers who interacted with high FTEE and low FTEE academic detailers except for the distribution of provider classes (P = 0.004) and geographic districts (P < 0.001). Providers who interacted with high FTEE academic detailers had a greater average monthly number of naloxone prescriptions prescribed compared with low FTEE academic detailers (0.60 vs. 0.53; P = 0.005). In the random effects model, there was a 65% greater increase in the average monthly number of naloxone prescriptions prescribed among providers who interacted with a high FTEE academic detailer compared with providers who interacted with low FTEE academic detailers (P = 0.027). We also observed a dose-dependent relationship between the number of naloxone prescribed and the amount of FTEE allocated. Conclusion: This observational study highlights the potential benefits (e.g., increased naloxone prescribing) of academic detailers having more FTEE allocated. Hence, implementation of academic detailing needs to consider the amount of dedicated time for academic detailers, given competing VA priorities.
Article
Background: Fatalities from opioid overdose have risen by 117% over the past 10 years. Increasing access to the opioid antagonist, naloxone can combat this trend and saves lives. This study investigates the various routes of naloxone administration for opioid reversal in the prehospital setting. Methods: PubMed, Ovid, and Google Scholar were searched for references that included the words naloxone and prehospital. Inclusion criteria were peer reviewed publications after 1995, English language, studies conducted in an outpatient setting, and intramuscular, intranasal, intravenous, or subcutaneous formulations; exclusion criteria were review articles or editorials. Results: 8 articles met the inclusion criteria: intramuscular, intranasal, intravenous, and subcutaneous dosage forms of naloxone were analyzed to compare their time to administration, time to efficacy, financial impact, administrator safety, and administrator preference. Conclusion: There is little consensus on the optimal route of naloxone administration in the prehospital setting. Little training is required for proper administration of the intramuscular auto-injector; however, the high price of this device is a barrier to access. Intranasal naloxone appears to be the optimal dosage form when considering cost, effectiveness, and administrator safety. Pharmacists must be aware of trends in naloxone use, dosage forms, and administration when caring for patients and their communities.
Article
Background. Opioids contribute tomore than 60 000 deaths annually in North America. While the expansion of overdose education and naloxone distribution (OEND) programs has been recommended in response to the opioid crisis, their effectiveness remains unclear. Objectives. To conduct an umbrella review of systematic reviews to provide a broad-based conceptual scheme of the effect and feasibility of OEND and to identify areas for possible optimization. Search Methods. We conducted the umbrella review of systematic reviews by searching PubMed, Embase, PsycINFO, Epistemonikos, the Cochrane Database of Systematic Reviews, and the reference lists of relevant articles. Briefly, an academic librarian used a 2-concept search, which included opioid subject headings and relevant keywords with a modified PubMed systematic review filter. Selection Criteria. Eligible systematic reviews described comprehensive search strategies and inclusion and exclusion criteria, evaluated the quality or risk of bias of included studies, were published in English or French, and reported data relevant to either the safety or effectiveness of OEND programs, or optimal strategies for the management of opioid overdose with naloxone in out-of-hospital settings. Data Collection and Analysis. Two reviewers independently extracted study characteristics and the quality of included reviews was assessed in duplicate with AMSTAR-2, a critical appraisal tool for systematic reviews. Review quality was rated critically low, low, moderate, or high based on 7 domains: protocol registration, literature search adequacy, exclusion criteria, risk of bias assessment, meta-analytical methods, result interpretation, and presence of publication bias. Summary tables were constructed, and confidence ratings were provided for each outcome by using a previously modified version of the Royal College of General Practitioners’ clinical guidelines. Main Results. Six systematic reviews containing 87 unique studies were included.We found that OEND programs produce long-term knowledge improvement regarding opioid overdose, improve participants’ attitudes toward naloxone, provide sufficient training for participants to safely and effectivelymanage overdoses, and effectively reduce opioid-relatedmortality. High-concentration intranasal naloxone (.2mg/mL) was as effective as intramuscular naloxone at the same dose, whereas lower-concentration intranasal naloxone was less effective. Evidence was limited for other naloxone formulations, as well as the need for hospital transport after overdose reversal. The preponderance of evidence pertained persons who use heroin. Author's Conclusions. Evidence suggests that OEND programs are effective for reducing opioid-related mortality; however, additional high-quality research is required to optimize program delivery. Public Health Implications. Community-based OEND programs should be implemented widely in high-risk populations. (Am J Public Health. Published online ahead of print July 2, 2021: e1–e12. https://doi.org/10.2105/AJPH.2021.306306 )
Article
Background Patients with opioid use disorder (OUD) are at high risk of overdose. To minimize that risk, a program offering intranasal naloxone rescue kits was piloted at a Veterans Administration Hospital. The purpose of this study was to characterize the veterans who accepted these potentially lifesaving kits. Methods Retrospective medical chart review of 158 veterans with OUD receiving treatment on either the inpatient psychiatry detoxification units or outpatient methadone maintenance setting who were offered overdose education and naloxone rescue (OEND) kits. Results 110 of 158 veterans (70%) accepted OEND. Overall, they had a mean age of 39.1 years and averaged 12.7 years of opioid use. In the prior month, they averaged 14.3 days of heroin use; they used alone 48.5% of the time. They estimated an average of 2.8 accidental overdoses over their lifetimes. There were few differences between those who accepted and those who declined with regards to demographic and clinical variables. However, significantly higher percentages of outpatients accepted OEND compared to the inpatients (89% versus 63%, p = .003, chi-square); the odds of acceptance were increased four-fold when offered to outpatients. Outpatients were nearly a decade older, with more years of opioid use (19.0 versus 11.0), but with less utilization of inpatient services in the prior year (all p<.05). Conclusions The main finding was that 70% of veterans accepted OEND, but significantly higher proportions of outpatients were more receptive than inpatients [89% versus 63%, p = .003]. Efforts to increase OEND acceptance in all settings are encouraged.
Article
Objective: Overdose mortality from illicit and prescription opioids has reached epidemic proportions in the United States, especially in rural areas. Naloxone is a safe and effective agent that has been shown to successfully reverse the effects of opioid overdose in the prehospital setting. The National EMS Scope of Practice Model currently only recommends advanced life support (ALS) providers to administer naloxone; however, some individual states have expanded this scope of practice to include intranasal (IN) administration of naloxone by basic life support (BLS) providers, including the Northern New England states. This study compares the effectiveness and appropriateness of naloxone administration between BLS and ALS providers. Methods: All Vermont, New Hampshire, and Maine EMS patient encounters between April 1, 2014 and December 31, 2016 where naloxone was administered were examined and 3,219 patients were identified. The proportion of successful reversals of opioid overdose, based on improvement in the Glasgow Coma Scale (GCS), respiratory rate (RR), and provider global assessment (GA) of response to medication was compared between BLS and ALS providers using a Chi-Squared statistic, Fisher's exact or Wilcoxon rank-sum test. Results: There was no significant difference in the percent improvement in GCS between BLS and ALS (64% and 64% P = 0.94). There was no significant difference in the percentage of improvement in RR between BLS and ALS (45% and 48% P = 0.43). There was a significant difference in the percentage of improvement of GA between BLS and ALS (80% and 67% P < 0.001). There was no significant difference in determining appropriate cases to administer naloxone where RR < 12 and GCS < 15 between BLS and ALS (42% and 43% P = 0.94). Conclusions: BLS providers were as effective as ALS providers in improving patient outcome measures after naloxone administration and in identifying patients for whom administration of naloxone is appropriate. These findings support expanding the National EMS Scope of Practice Model to include BLS administration of intranasal naloxone for suspected opioid overdoses.
Article
Full-text available
Background: While misuse of prescription opioids has reached epidemic proportions, pharmacy-based preventive services to combat this epidemic are limited. The aims of this study were to identify barriers and facilitators to the dispensing of intranasal naloxone (INN) by pharmacists in New Mexico. Methods: For this mixed methods study, a qualitative component (focus group) informed the development of a quantitative component (electronic survey) distributed to all pharmacists registered with the New Mexico Board of Pharmacy and practicing in the state. A 46-item survey included questions about pharmacists' concerns regarding dispensing INN, barriers and facilitators to dispensing INN, efforts needed to increase availability and utilization of pharmacist-dispensed INN, and characteristics of respondents and their pharmacies. Results: Pharmacists from all geographical regions and all types of pharmacy settings were represented in the sample (final n = 390, participation rate 23.5%, including a subset of 182 community pharmacists). The main barriers identified were: 1) out-of-pocket costs for patients; 2) time constraints for pharmacists; and 3) inadequate reimbursement for pharmacists. The main facilitators were: 1) increased awareness among opioid-using patients and family members about the need for INN; 2) additional education to the general public; and 3) additional training for pharmacists on how to initiate discussions about INN with high-risk patients. Some community pharmacists were concerned that INN dispensing would promote opioid abuse (16.5%) and attract undersirable clientele (14.3%). In a multivariable logistic regression analysis of a community pharmacy subset, a higher number of concerns about INN (OR = 0.87; 95% CI: 0.82-0.93), and a pharmacy setting in a chain grocery or a 'big box' store (OR = 0.38; 95% CI: 0.16; 0.92) were associated with decreased odds of dispensing INN. Conclusions: Effective intervention strategies for increasing dispensing of intranasal naloxone by pharmacists should focus on pharmacist concerns, include education to multiple audiences, and address provider-level, system-level, and society-level barriers.
Chapter
Intranasal administration is an attractive option for the delivery of many therapeutic agents especially for the treatment of central nervous system (CNS). In contrast to drugs that require delivery by peripheral injection, which requires blood brain barrier permeability of the injected drug for CNS delivery and may cause anxiety and infection, the intranasal route allows drugs to bypass the BBB due to its highly specialized nasal anatomy and the olfactory pathway. Due to its non-invasive nature and easy procedure, intranasal drug delivery is particularly suited for use in children and may be performed by medical staff or family members. This article will review the use of intranasal medications with a focus on their utility in children. We will provide an overview of the nasal anatomy and its impact on drug delivery, the side effects of drugs specific to intranasal delivery, and a list of the medications which are currently administered intranasally. The most common drug classes for intranasal delivery in pediatrics include sedatives and analgesia, drugs for seizure control, opioid antagonists, and antimigraine medications. In summary, intranasal delivery is a versatile method for drug application with a wide range of clinical utility, and especially effective in the pediatric population.
Article
Background: The purpose of this study was to evaluate prehospital and emergency department (ED) interventions and outcomes of patients who received prehospital naloxone for a suspected opioid overdose. Objectives: The primary objective was to evaluate if the individual dose, individual route, total dose, number of prehospital naloxone administrations, or occurrence of a prehospital adverse event (AE) were associated with the occurrence of AEs in the ED. Secondary objectives included a subset analysis of patients who received additional naloxone while in the ED, or were admitted to an intensive care or step-down unit (ICU). Methods: This was a retrospective, observational chart review of adult patients who received prehospital naloxone and were transported by ambulance to a suburban academic tertiary care center between 2014 and 2017. Descriptive, univariate, and multivariate statistics were used, with p < 0.05 indicating significance. Results: There were 513 patients included in the analysis, with a median age of 29 years, and median total prehospital naloxone dose of 2 mg. An increasing number of prehospital naloxone doses, an occurrence of a prehospital AE, and a route of administration other than intranasally for the first dose of prehospital naloxone were significantly associated with an increased likelihood of an ED AE. Patients who received < 2 mg of prehospital naloxone had the least likelihood of being admitted to an ICU, whereas patients who received at least 6 mg had a dramatically increased likelihood of ICU admission. Conclusions: Our results suggest that an increasing number of prehospital naloxone doses was significantly associated with an increased likelihood of an ED adverse event.
Article
A group of noroxymorphone derivatives were subjected to Gewald reaction conditions to prepare their respective aminothieno products. In refluxing piperidine/ethanol, 1a–g reacted with elemental sulfur and malononitrile to produce 2a–g in high yields. Reactions took place in one pot and completed within 4–7 h and products precipitated spontaneously in the reaction mixtures.
Article
Background Take-home naloxone, an opioid antagonist, has become part of a multimodal approach to curbing opioid-related mortality. However, there is little information about the utility of take-home naloxone in pediatric patients. We report a case of opioid toxicity after exposure to methadone in a pediatric patient, which was successfully reversed with take-home naloxone. Case A previously healthy 22-month-old girl ingested an unknown amount of liquid methadone. The child became progressively somnolent. The mother administered intranasal naloxone at home with reversal of somnolence. The patient presented to the emergency department and had recurrence of symptoms. The patient was placed on a naloxone infusion and discharged from a tertiary care facility, uneventfully, 2 days after ingestion. Results To our knowledge, we report the first case of pediatric opioid toxicity reversed by take-home naloxone. In the setting of rising opioid-related mortality, providers and public health officials should consider expanding access of take-home naloxone for children at high risk for opioid overdose.
Article
Full-text available
People with a learning disability are often disadvantaged due to the nature of their disability. Up to a third are likely to have concomitant epilepsy which adds to the health loss experienced by this group. It is important to manage their epilepsy in such a way as to limit the debilitating effects of both the illness and the medication. Rectal diazepam remains the gold standard rescue medication for prolonged, recurrent seizures or seizures associated with hypoxia. Some of the drawbacks are highlighted in this paper and we go on to explore a novel means of treating these seizures. Midazolam, via the intranasal route, has been used extensively in children, mostly as a sedative but also in the treatment of epilepsy. We present two cases, both are adults with a learning disability, who have benefited significantly from the use of intranasal midazolam. Ongoing research into the safe use of this form of treatment, training of staff and carers and the impact on the individual is being conducted.
Article
Full-text available
To compare the safety and efficacy of midazolam given intranasally with diazepam given intravenously in the treatment of children with prolonged febrile seizures. Prospective randomised study. Paediatric emergency department in a general hospital. 47 children aged six months to five years with prolonged febrile seizure (at least 10 minutes) during a 12 month period. Intranasal midazolam (0.2 mg/kg) and intravenous diazepam (0.3 mg/kg). Main outcome measures: Time from arrival at hospital to starting treatment and cessation of seizures. Intranasal midazolam and intravenous diazepam were equally effective. Overall, 23 of 26 seizures were controlled with midazolam and 24 out of 26 with diazepam. The mean time from arrival at hospital to starting treatment was significantly shorter in the midazolam group (3.5 (SD 1.8) minutes, 95% confidence interval 3.3 to 3.7) than the diazepam group (5.5 (2.0), 5.3 to 5.7). The mean time to control of seizures was significantly sooner (6.1 (3.6), 6.3 to 6.7) in the midazolam group than the diazepam group (8.0 (0.5), 7. 9 to 8.3). No significant side effects were observed in either group. Seizures were controlled more quickly with intravenous diazepam than with intranasal midazolam, although midazolam was as safe and effective as diazepam. The overall time to cessation of seizures after arrival at hospital was faster with intranasal midazolam than with intravenous diazepam. The intranasal route can possibly be used not only in medical centres but in general practice and, with appropriate instructions, by families of children with recurrent febrile seizures at home.
Article
Full-text available
The aim of this study was to determine whether intranasal midazolam is a safe and effective rescue medication in adolescent and adult patients with severe epilepsy. This field trial was designed to test the feasibility of the use of intranasal midazolam as an alternative to rectal diazepam in a cohort of patients with severe epilepsy who require rescue medication as part of their treatment. A dose of intranasal midazolam (5 mg if the patient weighed less than 50 kg and 10 mg if the patient weighed over 50 kilograms) was prescribed for those who had previously responded to other rescue medication. Midazolam was prescribed buccally if excessive head movement accompanied seizures. The protocol reverted to the usual rescue medication if there was no response to midazolam within 10 minutes. Vital signs were monitored for half an hour following the administration of the treatment. Twenty-two patients received 84 treatment episodes and 79 of these were considered clinically effective. Five treatment failures were recorded, three due to poor technique in delivering the midazolam. Two patients were successfully retried on midazolam and a third is awaiting a retrial of this drug. The two other treatment failures received the drug buccally. In the first patient the clinical opinion was that this was possibly a psychogenic non-epileptic seizure. The other patient responded initially, but within an hour had another seizure requiring further rescue treatment. No significant adverse effects were reported. Our study shows that intranasal midazolam, when used appropriately, is an effective treatment in those who require rescue treatment. There are clear advantages in the use of midazolam over diazepam in the treatment of acute seizures. These include the favourable pharmacokinetic and pharmacodynamic properties of midazolam as well as the potential of a more acceptable and dignified administration route.
Article
Full-text available
In order to determine the efficiency of intranasal midazolam in prolonged convulsive episodes, we conducted a prospective study in children with various types of seizures. Nine patients (six boys, three girls; age range 6 months to 9 years) with prolonged convulsions lasting more than 10 min were treated with intranasal midazolam, 0.3 mg/kg. The success rate was 100% with only one case requiring a second dose. Estimated duration of seizures was 12-30 min (mean 18.6) while mean time elapsed until cessation of seizures was 139.6 s (range 60-480). No significant adverse effects were noted except for one patient who had seizures secondary to serious CNS infection and respiratory depression after intranasal midazolam.
Conference Paper
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 greater than or equal to 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 greater than or equal to 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 greater than or equal to 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.
Article
• To determine their occupational risk for hepatitis B infection, 59 Seattle paramedics were tested for hepatitis B serum markers. Evidence of antibody to hepatitis B surface antigen (anti-HBs) or antibody to hepatitis B core antigen (anti-HBc) was found in 25%, a rate five times that of a similar Seattle population. Seropositivity did not correlate with age, race, clinical history, or length of service. Of the 15 paramedics with seropositivity to hepatitis B virus, six initially had low titers of either anti-HBs or anti-HBc. Four of the six demonstrated persistent low-grade seropositivity on retesting. Paramedics are at increased risk of hepatitis B infection. The high frequency of low-titer anti-HBs suggests that frequent low-level exposure to hepatitis B virus occurs in this population; hepatitis B vaccine should be strongly considered for paramedics. (Arch Intern Med 1985;145:1976-1977)
Article
Objective: To compare the safety and efficacy of midazolam given intranasally with diazepam given intravenously in the treatment of children with prolonged febrile seizures. Design: Prospective randomised study. Setting: Paediatric emergency department in a general hospital. Subjects: 47 children aged six months to five years with prolonged febrile seizure (at least 10 minutes) during a 12 month period. Interventions: Intranasal midazolam (0.2 mg/kg) and intravenous diazepam (0.3 mg/kg). Main outcome measures: Time from arrival at hospital to starting treatment and cessation of seizures. Results: Intranasal midazolam and intravenous diazepam were equally effective. Overall, 23 of 26 seizures were controlled with midazolam and 24 out of 26 with diazepam. The mean time from arrival at hospital to starting treatment was significantly shorter in the midazolam group (3.5 (SD 1.8) minutes, 95% confidence interval 3.3 to 3.7) than the diazepam group (5.5 (2.0), 5.3 to 5.7). The mean time to control of seizures was significantly sooner (6.1 (3.6), 6.3 to 6.7) in the midazolam group than the diazepam group (8.0 (0.5), 7.9 to 8.3). No significant side effects were observed in either group. Conclusion: Seizures were controlled more quickly with intravenous diazepam than with intranasal midazolam, although midazolam was as safe and effective as diazepam. The overall time to cessation of seizures after arrival at hospital was faster with intranasal midazolam than with intravenous diazepam. The intranasal route can possibly be used not only in medical centres but in general practice and, with appropriate instructions, by families of children with recurrent febrile seizures at home.
Article
The effects of intranasal fentanyl citrate (INFC) were assessed in 12 hospice inpatients with cancer-related breakthrough pain. Patients received 20 μg of fentanyl citrate and were asked to rate their pain using a visual analogue scale (VAS) before INFC, then after 3, 5, 10, 15, 30, 45, and 60 minutes. Eight patients (66%) had reductions in pain scores, four within 5 minutes and seven within 10 minutes of taking INFC. Ratings for INFC were very good (5 = 42%), good (3 = 25%), moderate (1 = 8%), and bad (3 = 25%). In comparison to oral morphine, INFC was better (6 = 50%), the same (3 = 25%), or worse (3 = 25%). Nine patients (75%) said they would continue to use INFC. Of the three patients who did not experience a positive result, two were taking relatively higher baseline opioid doses and one was found to have a fracture. No systemic adverse events were noted; two patients reported nasal itching or discomfort on first use that disappeared with repeated use. Intranasal fentanyl citrate appears safe and well tolerated by these patients. Randomized placebo-controlled and dose-ranging studies are required to confirm these findings.
Article
Objective: To determine whether naloxone administered i.v. to out-of-hospital patients with suspected opioid overdose would have a more rapid therapeutic onset than naloxone given subcutaneously (s.q.). 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 > or =10 breaths/min, and durations of bag-valve-mask ventilation. Subjects received either naloxone 0.4 mg i.v. (n = 74) or naloxone 0.8 mg s.q. (n = 122), for respiratory depression of <10 breaths/min. Results: Mean interval from crew arrival to respiratory rate > or =10 breaths/min was 9.3 +/- 4.2 min for the i.v. group vs 9.6 +/- 4.58 min for the s.q. 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 i.v. group vs 9.1 +/- 4.8 min for the s.q. group. Cost of materials for administering naloxone 0.4 mg i.v. was $12.30/patient, compared with $10.70/patient for naloxone 0.8 mg s.q. Conclusion: There was no clinical difference in the time interval to respiratory rate > or =10 breaths/min between naloxone 0.8 mg s.q. and naloxone 0.4 mg i.v. for the out-of-hospital management of patients with suspected opioid overdose. The slower rate of absorption via the s.q. route was offset by the delay in establishing an i.v.
Article
The nasal administration of naloxone (30 μg/rat) and buprenorphine (135 μg/rat) was studied in male rats following single doses and compared with intravenous and intraduodenal administration of the two drugs. The nasal bioavailabilities calculated from the ratio of the AUC (nasal/intravenous × 100) was 101% for naloxone and 95% for buprenorphine. The intraduodenal bioavailability for naloxone was only 1.5% of the intravenous bioavailability. These studies showed that the nasal route for the administration of these two drugs can be considered as effective as the parenteral route.
Article
To investigate the time of onset and incidence of complications in patients presenting to the emergency department with an IV heroin overdose and the need for routine admission of such patients. A retrospective chart review of hospital and emergency medical service records of 124 patient visits involving IV heroin overdose over a five-month period. We also reviewed the death certificates of 115 persons having succumbed to a narcotic overdose over a 44-month period and compared these with our hospital records. Urban county hospital. Patients presenting to the ED with an IV heroin overdose. There were five deaths in the ED, 12 hospital admissions, and 107 patients who were discharged home. Neither delayed onset of pulmonary edema nor recurrence of respiratory depression was observed. Of the 115 persons having succumbed to a narcotic overdose, eight had been seen previously at our hospital for a heroin overdose. There is no evidence that any of these eight deaths would have been prevented by a 24-hour hospital observation period. Complications arising from an IV overdose of heroin are usually evident on arrival in the ED or shortly thereafter. On retrospective review we have found no evidence that admission to the hospital and 24 hours of observation are of benefit to patients who are awake, alert, and lacking evidence of pulmonary complications after an IV heroin overdose.
Article
In clinical trials, nasally applied naloxone was used to identify opiate dependence in humans for the first time. Withdrawal distress was recorded, and pupillary response, pulse rate and blood pressure measured. A significant increase in withdrawal distress and pupillary dilation was observed after nasal administration of 1mg (1mg/400 microliters) naloxone in all subjects who also showed opiate-positive urine samples. In control subjects, no reaction to naloxone was observed. It may be concluded that the nasal route for naloxone administration is as effective as the parenteral route. This test is sensitive enough to identify the physically-dependent opiate user and might have a role in emergency medicine and withdrawal treatment.
Article
The kinetics and systemic bioavailability of intranasally administered buprenorphine have been investigated in 9 healthy volunteers in an intranasal/intravenous cross-over study. Each subject received a nominal 0.3 mg dose of buprenorphine intranasally followed one week later by a matched dose intravenously. For the intranasal administration mean tmax and mean Cmax were 30.6 min and 1.77 ng mL-1, respectively. Mean intranasal bioavailability was 48.2 +/- 8.35% (mean +/- s.e.m.) of the intravenous value. Intranasal administration may represent a valuable new delivery route for buprenorphine.
Article
An octapeptide and a protein, of molecular weights 800 and 34,000, respectively, were found to have nasal bioavailabilities of 73 and 0.6%, respectively, in the rat. This data, combined with reported values for 23 other compounds, indicated good availability without adjuvants for all molecules up to 1000 molecular weight (mean 70%, SD between compounds 26%, n = 15) with a decline in availability above this value. The relationship between absorption and molecular weight was modeled assuming competition between constant clearance from the nasal cavity and molecular weight-dependent transport through the mucosa. Deviations of absorption from values predicted by this model did not correlate with factors such as charge, hydrophobicity, or susceptibility to aminopeptidases, but the relative absorption of cyclic and cross-linked peptides and proteins was significantly greater than that of linear peptides. It is argued that the most likely route for transport is through junctions between cells and that surface-active adjuvants (MW 6000) which markedly enhance insulin uptake may act by rendering hydrophobic areas of contact of the junctional proteins temporarily hydrophilic. The nasal route is suitable for efficient, rapid delivery of many molecules of molecular weight less than 1000. With the use of adjuvants, this limit can be extended to at least 6000 and possibly much higher.
Article
To evaluate nasally administered sufentanil, 1.5-4.5 micrograms/kg, for pre-induction (i.e., pre-medication/induction) of anesthesia in pediatric patients, the authors studied ASA PS 1 or 2 patients scheduled for elective surgery. Eighty children, ages 6 months to 7 yr, were randomized to receive sufentanil (1.5, 3.0, or 4.5 micrograms/kg) or placebo (normal saline, 0.03 ml/kg) nasally over 15-20 s. Induction of anesthesia was completed with 5% halothane and O2 via facemask. After tracheal intubation, anesthesia was maintained with N2O (60-70%) and halothane, as clinically indicated. A blinded observer remained with the child from prior to drug administration until discharge from the recovery room. Patients given sufentanil were more likely to separate willingly from their parents and be judged as calm at or before 10 min compared to those given saline. Ventilatory compliance during induction of anesthesia decreased markedly in 25% of subjects given sufentanil, 4.5 micrograms/kg. Subjects given sufentanil moved or coughed less during tracheal intubation and required less halothane compared to those given placebo. During recovery, patients given sufentanil cried less and fewer needed analgesics; recovery times were similar for all groups. However, patients given sufentanil, 4.5 micrograms/kg, had a higher incidence of vomiting in the recovery room and during the first postoperative day. The authors conclude that nasally administered sufentanil, 1.5 or 3.0 micrograms/kg, facilitates separation of children from parents, has minimal side effects, may improve intubating conditions, and can provide postoperative analgesia.
Article
Plasma concentrations of nasally inhaled ipratropium bromide were analyzed in eight healthy volunteers by using a sensitive radioreceptor assay (RRA). The rate of saliva secretion, heart rate and changes in visual accommodation were quantitated in order to measure possible systemic anticholinergic drug effects. 240 micrograms of ipratropium bromide (40 micrograms each nostril, repeated twice at 15 min intervals) were inhaled nasally in a double blind, randomized, placebo-controlled experiment. Ipratropium bromide absorbed fast, and peak plasma concentrations of the drug (257 +/- 55 pg/ml) were detected as soon as 5 min after the last inhalation (at 35 min from the beginning). The plasma levels of ipratropium bromide decreased rapidly, being only 86 +/- 7 pg/ml one hour after the last inhalation. These low concentrations of ipratropium bromide indicate that only a small portion of it absorbs after nasal application, which is consistent with the lack of any systemic anticholinergic drug effects in our subjects. It is concluded that nasally applied ipratropium bromide is not likely to cause systemic anticholinergic side-effects, even in doses exceeding the therapeutic recommendations.
Article
Houston has large groups of people known to be at high risk for hepatitis B virus (HBV) infection. Emergency medical services (EMS) personnel are continuously exposed to blood from these high-risk individuals. We sought to determine the prevalence of HBV infection in the city's EMS personnel. Of the 350 Houston firefighters assigned to EMS, 344 were surveyed by questionnaire and a blood specimen was obtained. Each sample was assayed by radio-immunoassay or enzyme-linked immunoassay for hepatitis A antibody (anti-HAV), hepatitis B surface antigen (HBsAg), and antibodies to HBsAg (anti-HBs) and hepatitis B core antigen (anti-HBc). A history of hepatitis was reported by 19 persons, 17 of whom had serologic evidence of infection with HAV (56%), HBV (26%), or both diseases (11%). The anti-HAV prevalence was 16% (12% in whites and 35% in nonwhites; P less than .001). No correlation was observed with years of occupational exposure. Of the 338 personnel evaluated for HBV seromarkers (six HBsAg-vaccinated subjects were excluded), 13% were positive; 0.6% had an active infection as determined by the presence of both HBsAg and anti-HBc; 6.8% were both anti-HBs and anti-HBc positive; 0.9% were positive for anti-HBc alone; and 4.7% of the sera contained only anti-HBs (all with geometric mean antibody levels of less than or equal to 13 mlU/mL). The 28 individuals (8.3%) whose sera contained anti-HBc were classified as cases of previous or concurrent HBV infection. A strong correlation (P less than .004) was observed between HBV infection and years of work exposure in EMS regardless of job description (paramedic versus emergency medical technician).(ABSTRACT TRUNCATED AT 250 WORDS)
Article
To determine their occupational risk for hepatitis B infection, 59 Seattle paramedics were tested for hepatitis B serum markers. Evidence of antibody to hepatitis B surface antigen (anti-HBs) or antibody to hepatitis B core antigen (anti-HBc) was found in 25%, a rate five times that of a similar Seattle population. Seropositivity did not correlate with age, race, clinical history, or length of service. Of the 15 paramedics with seropositivity to hepatitis B virus six initially had low titers of either anti-HBs or anti-HBc. Four of the six demonstrated persistent low-grade seropositivity on retesting. Paramedics are at increased risk of hepatitis B infection. The high frequency of low-titer anti-HBs suggests that frequent low-level exposure to hepatitis B virus occurs in this population; hepatitis B vaccine should be strongly considered for paramedics.
Article
To assess the nature and frequency of blood contact (BC) among emergency medical service (EMS) workers. During an 8-month period, we interviewed EMS workers returning from emergency transport calls on a sample of shifts. We simultaneously conducted an HIV seroprevalence survey among EMS-transported patients at receiving hospitals served by these workers. Three US cities with high AIDS incidence. EMS workers. During 165 shifts, 2,472 patients were attended. Sixty-two BCs (1 needlestick and 61 skin contacts) were reported. Individual EMS workers had a mean of 1.25 BCs, including .02 percutaneous exposures, per 100 patients attended. The estimated annual frequency of BC for an EMS worker at the study sites was 12.3, including .2 percutaneous exposures. For 93.5% of the BCs, the HIV serostatus of the source patients was unknown to the EMS worker. HIV seroprevalences among EMS-transported patients at the three receiving hospital emergency departments were 8.3, 7.7, and 4.1 per 100 patients; the highest rates were among male patients 15 to 44 years old who presented with pneumonia. EMS personnel regularly experience BCs, most of which are skin contacts. Because the HIV serostatus of the patient is usually unknown, EMS workers should practice universal precautions. Postexposure management should include a mechanism for voluntary HIV counseling and testing of the patient after transport and transmittal of the results to the EMS.
Article
Naloxone is used intravenously in opiate addiction in emergency cases, in rapid opiate detoxification, and as a diagnostic tool. This is a study comparing the efficacy of intranasal naloxone to other routes (intravenous/intramuscular) in 17 opiate-dependent patients. The nasal drug administration of naloxone was found to be as effective as the intravenous route. The nasal drug application offers a wide margin of safety for patients and medical staff, especially in emergency situations in regard to infection risks associated with vessel puncture.
Article
The kinetics and bioavailability of a new formulation of metoclopramide (CAS 364-62-5) nasal spray (MTC NS) were assessed in two separate studies versus the same drug administered intravenously (MTC IV) according to a balanced-block design where each study subject served as his own control. The first study involved 10 healthy subjects, each receiving metoclopramide NS 20 mg (one 10-mg puff per nostril) and metoclopramide IV 20 mg on two trial days separated by a 7-day washout period. On both occasions, blood samples were obtained at time 0 and at 20, 40, 60, 120, 150, 210, 280 and 360 min of dosing. Metoclopramide concentrations were assayed in plasma by HPLC. The second study involved 10 patients of oncologic domain, scheduled to receive mildly emetic chemotherapy regimes. The experimental design was similar to the one above except that blood was sampled at 0, 20, 40 and 60 min and again at 2, 3, 4, 6, and 8 h of dosing. All healthy subjects completed the trial without experiencing any adverse or untoward events; in the group of cancer patients, one subject dropped out after the nose spray treatment when he was removed to another department. This patient was replaced by another, and included in final data analysis only for the segment of treatment actually received. Metoclopramide kinetics after intravenous dosing were in good agreement with known data for the active substance, with no meaningful differences between healthy subjects and cancer patients. With MTC NS administration there was only a slight but significant difference of Cmax, being lower in the cancer patient group (p < 005).(ABSTRACT TRUNCATED AT 250 WORDS)
Article
Education and universal precautions alone may be insufficient to ameliorate the potential crisis situation brought about by fear of occupational exposure to blood or body fluids. The authors discuss typical initial reactions to exposure and propose specific steps to be taken in this initial period prior to the introduction of medical exam and counseling.
Article
To estimate (1) the prevalence of human immunodeficiency virus (HIV) infection in emergency department (ED) patients, (2) the frequency of blood contact (BC) in ED workers (EDWs), (3) the efficacy of gloves in preventing BC, and (4) the risk of HIV infection in EDWs due to BC. We conducted an 8-month study in three pairs of inner-city and suburban hospital EDs in high AIDS incidence areas in the United States. At each hospital, blood specimens from approximately 3,400 ED patients were tested for HIV antibody. Observers monitored BC and glove use by EDWs. HIV seroprevalence was 4.1 to 8.9 per 100 patient visits in the 3 inner-city EDs, 6.1 in 1 suburban ED, and 0.2 and 0.7 in the other 2 suburban EDs. The HIV infection status of 69% of the infected patients was unknown to ED staff. Seroprevalence rates were highest among patients aged 15 to 44 years, males, blacks and Hispanics, and patients with pneumonia. BC was observed in 379 (3.9%) of 9,793 procedures; 362 (95%) of the BCs were on skin, 11 (3%) were on mucous membranes, and 6 (2%) were percutaneous. Overall procedure-adjusted skin BC rates were 11.2 BCs per 100 procedures for ungloved workers and 1.3 for gloved EDWs (relative risk = 8.8; 95% confidence interval = 7.3 to 10.3). In the high HIV seroprevalence EDs studied, 1 in every 40 full-time ED physicians or nurses can expect an HIV-positive percutaneous BC annually; in the low HIV seroprevalence EDs studied, 1 in every 575. The annual occupational risk of HIV infection for an individual ED physician or nurse from performing procedures observed in this study is estimated as 0.008% to 0.026% (1 in 13,100 to 1 in 3,800) in a high HIV seroprevalence area and 0.0005% to 0.002% (1 in 187,000 to 1 in 55,000) in a low HIV seroprevalence area. In both inner-city and suburban EDs, patient HIV seroprevalence varies with patient demographics and clinical presentation; the infection status of most HIV-positive patients is unknown to ED staff. The risk to an EDW of occupationally acquiring HIV infection varies by ED location and the nature and frequency of BC; this risk can be reduced by adherence to universal precautions.
Article
To evaluate the safety and efficacy of intranasal diamorphine as an analgesic for use in children in accident and emergency (A&E). A prospective, randomised clinical trial with consecutive recruitment of patients aged between 3 and 16 years with clinically suspected limb fractures. One group received 0.1 mg/kg intranasal diamorphine, and the other group received 0.2 mg/kg intramuscular morphine. At 0, 5, 10, 20, and 30 minutes pain scores, Glasgow coma score, and peripheral oxygen saturations were recorded; parental acceptability was assessed at 30 minutes. 58 children were recruited, with complete data collection in 51 (88%); the median summed decrease in pain score was better for intranasal diamorphine than intramuscular morphine (9 v 8), though this was not significant (P = 0.4, Mann-Whitney U test). The episode was recorded as "acceptable" in all parents whose child received intranasal diamorphine, compared with only 55% of parents in the intramuscular morphine group (P < 0.0001, Fisher's exact test). There was no incidence of decreased peripheral oxygen saturation or depression in the level of consciousness in any patient. Intranasal diamorphine is an effective, safe, and acceptable method of analgesia for children requiring opiates in the A & E department.
Article
Our investigation was carried out in subjects intoxicated with heroin or heroin mixtures to find out the time interval during which delayed life-threatening complications become manifest, such as pulmonary oedema or relapse into respiratory depression or coma after naloxone treatment. We studied prospectively all drug intoxications between 1991 and 1992. Of the 538 intoxications, we assessed in detail 160 outpatients who lived within the catchment area of our hospital. The outcome variables studied were (1) rehospitalization for pulmonary oedema, (2) relapse into coma, and/or (3) death and cause within 24 h after release from hospital. Deaths occurring outside our hospital have to be reported, as decreed by law, to the Institute for Forensic Medicine. The results of our investigation showed no rehospitalization owing to pulmonary oedema or coma, but one death, outside the hospital, owing to delayed pulmonary oedema. This delayed complication had an incidence of 0.6% (95% confidence interval 0-3.8%). A reintoxication could be excluded in this patient. Based on reliable report, the pulmonary oedema occurred between approximately 2 1/4 and 8 1/4 hours after intoxication. In the literature, only two cases of delayed pulmonary oedema have been reported with reliable time statements (4 and 6 h after hospitalization). We therefore conclude that surveillance for at least 8 h is essential after successful treatment to exclude delayed pulmonary oedema in patients intoxicated with heroin or heroin mixtures.
Article
Naloxone is frequently used by prehospital care providers to treat suspected heroin and opioid overdoses. The authors' EMS system has operated a policy of allowing these patients, once successfully treated, to sign out against medical advice (AMA) in the field. This study was performed to evaluate the safety of this practice. The authors retrospectively reviewed all 1996 San Diego County Medical Examiner's (ME's) cases in which opioid overdoses contributed to the cause of death. The records of all patients who were found dead in public or private residences or died in emergency departments of reasons other than natural causes or progression of disease, are forwarded to the ME office. ME cases associated with opiate use as a cause of death were cross-compared with all patients who received naloxone by field paramedics and then refused transport. The charts were reviewed by dates, times, age, sex, location, and, when available, ethnicity. There were 117 ME cases of opiate overdose deaths and 317 prehospital patients who received naloxone and refused further treatment. When compared by age, time, date, sex, location, and ethnicity, there was no case in which a patient was treated by paramedics with naloxone within 12 hours of being found dead of an opiate overdose. Giving naloxone to heroin overdoses in the field and then allowing the patients to sign out AMA resulted in no death in the one-year period studied. This study did not evaluate for return visits by paramedics nor whether patients were later taken to hospitals by private vehicles.
Article
The purpose of this study was to investigate both the in vitro and in vivo release of apomorphine from mucoadhesive powder formulations of Carbopol 971P and polycarbophil. The in vitro drug release from the mucoadhesive formulations was studied using a modified USP XXII rotating basket. The pharmacokinetics of apomorphine given as a solution was determined after subcutaneous and intranasal administrations to rabbits. The animals also received intranasally the mucoadhesive dosage forms and immediate release lactose powder mixture. Comparisons were made between the salient pharmacokinetic parameters of the different dosage forms. Sustained in vitro drug release was obtained from the mucoadhesive formulations. Apomorphine was absorbed more rapidly in rabbits when administered intranasally than as a subcutaneous injection. The mucoadhesive formulations both gave sustained plasma drug concentrations and bioavailabilities comparable to subcutaneous injections. The times taken to achieve peak plasma drug concentrations from these mucoadhesive formulations were more than three-fold that of lactose. With these mucoadhesive formulations apomorphine lasted longer in the blood. It could be detected for up to 6-8 h compared to approximately 3 h for the other forms of administration. The nasal bioavailability of powders is higher than that of solutions. Drug release from the mucoadhesive powders was sustained and there was no significant difference between Carbopol 971P and polycarbophil.
Article
A study of HIV post-exposure prophylaxis in 28 recipients showed that indinavir-containing regimens were poorly tolerated. This finding has implications for compliance and efficacy of the currently recommended combinations.
Article
The effects of intranasal fentanyl citrate (INFC) were assessed in 12 hospice inpatients with cancer-related breakthrough pain. Patients received 20 microg of fentanyl citrate and were asked to rate their pain using a visual analogue scale (VAS) before INFC, then after 3, 5, 10, 15, 30, 45, and 60 minutes. Eight patients (66%) had reductions in pain scores, four within 5 minutes and seven within 10 minutes of taking INFC. Ratings for INFC were very good (5 = 42%), good (3 = 25%), moderate (1 = 8%), and bad (3 = 25%). In comparison to oral morphine, INFC was better (6 = 50%), the same (3 = 25%), or worse (3 = 25%). Nine patients (75%) said they would continue to use INFC. Of the three patients who did not experience a positive result, two were taking relatively higher baseline opioid doses and one was found to have a fracture. No systemic adverse events were noted; two patients reported nasal itching or discomfort on first use that disappeared with repeated use. Intranasal fentanyl citrate appears safe and well tolerated by these patients. Randomized placebo-controlled and dose-ranging studies are required to confirm these findings.
Article
Naloxone is a medication that is frequently administered in the field by paramedics for suspected opioid overdoses. Most prehospital protocols, however, require this medication to be given to patients intravenously (i.v.) or intramuscularly (i.m.). Unfortunately, intravenous line placement may be problematic and time-consuming in chronic i.v. drug users. There may also be a delay in patient response to opioid reversal with i.m. absorption of naloxone. Additionally, routine use of needles in high-risk populations poses an increased risk of occupational blood exposures to paramedics. To prospectively test the effectiveness of intranasal (i.n.) naloxone administration by paramedics. This preliminary report summarizes the first month's experience in the city of Denver. Naloxone was first administered to patients found unconscious in the field using a nasal mucosal atomizer device (MAD). Patients were then treated using standard prehospital protocols, which included i.v. line placement and medications, if they did not immediately respond to i.n. naloxone. Time to patient response was recorded. A total of 30 patients received i.n. naloxone in the field over a one-month period. Of these, 11 patients responded to either i.n. or i.v. naloxone. Ten (91%) patients responded to i.n. naloxone alone, with an average response time of 3.4 minutes. Seven patients (64%) did not require an i.v. in the field after response to i.n. naloxone. Intranasal naloxone may provide a safe, rapid, effective way to manage suspected opioid overdoses in the field. Use of this route may decrease paramedic exposures to blood-borne diseases. The addition of i.n. naloxone administration to prehospital protocols should be considered as an initial therapy for suspected opioid abusers.
Article
In this study, the effects and side effects of rectal diazepam and intranasal midazolam were compared in the treatment of acute convulsions in children to develop a practical and safe treatment protocol. In the diazepam group, the seizures of 13 (60%) patients terminated in 10 minutes; however, 9 (40%) patients did not respond. In the midazolam group, 20 (87%) patients responded in 10 minutes, but 3 (13%) patients did not respond. Regarding the anticonvulsant effect, midazolam was found to be more effective than diazepam, and the difference was statistically significant (P < .05). The necessity of a second drug for the seizures that did not stop with the first drug was higher in the diazepam group than the midazolam group, and the difference was statistically significant (P < .05). We conclude that as an antiepileptic agent, intranasal midazolam is more effective than rectal diazepam. After administration, we did not observe any serious complications. Further investigations are necessary; however, intranasal administration is easy, so if the nasal drop and spray forms used in some European countries and the United States are available worldwide, it will be very useful for physicians in the emergency room.
Official Protocol No. 40 A-R. Available at: http://www.ci.slc.ut.us/fire/EmsPro-40.htm
  • Salt
  • Lake
  • District
Salt Lake EMS District Protocols. Official Protocol No. 40 A-R. Available at: http://www.ci.slc.ut.us/fire/EmsPro-40.htm. Accessed June 3, 2003. Prehospital Intranasal Naloxone 271
Anatomy and physiology of the nose
  • Chien
  • Yw
  • Su
  • Kse
  • Chang
  • Sf
Chien YW, Su KSE, Chang SF. Anatomy and physiology of the nose. In: Chien YW, Su KSE, Chang SF, eds. Nasal systemic drug delivery. New York: Dekker; 1989:1–26.
Official Protocol No. 40 A-R. Available at
  • Salt Lake
Salt Lake EMS District Protocols. Official Protocol No. 40 A-R. Available at: http://www.ci.slc.ut.us/fire/EmsPro-40.htm. Accessed June 3, 2003. Prehospital Intranasal Naloxone
Occupational exposure to bloodborne pathogens; needlesticks and other sharps injuries; final rule
Occupational exposure to bloodborne pathogens; needlesticks and other sharps injuries; final rule. Fed Regist 2001;66:5318 –25.
Anatomy and physiology of the nose
  • Chien
Midazolam via the intranasal route
  • Scheepers