Paramedic Norwegian Acute Stroke Prehospital Project (ParaNASPP) study protocol: a stepped wedge randomised trial of stroke screening using the National Institutes of Health Stroke Scale in the ambulance

Background Less than 50% of stroke patients in Norway reach hospital within 4 h of symptom onset. Early prehospital identification of stroke and triage to the right level of care may result in more patients receiving acute treatment. Quality of communication between paramedics and the stroke centre directly affects prehospital on-scene time, emphasising this as a key factor to reduce prehospital delay. Prehospital stroke scales are developed for quick and easy identification of stroke, but have poor sensitivity and specificity compared to an in-hospital assessment with the National Institutes of Health Stroke Scale (NIHSS). The aim of the Paramedic Norwegian Acute Stroke Prehospital Project (ParaNASPP) is to assess whether a structured learning program, prehospital NIHSS and a mobile application facilitating communication with the stroke physician may improve triage of acute stroke patients. Methods A stepped wedge cluster randomised controlled intervention design will be used in this trial in Oslo, Norway. Paramedics at five ambulance stations will enrol adult patients with suspected stroke within 24 h of symptom onset. All paramedics will begin in a control phase with standard procedures. Through an e-learning program and practical training, a random and sequential switch to the intervention phase takes place. A mobile application for NIHSS scoring, including vital patient information for treatment decisions, transferring data from paramedics to the on-call stroke physician at the Stroke Unit at Oslo University Hospital, will be provided for the intervention. The primary outcome measure is positive predictive value (PPV) for prehospital identification of patients with acute stroke defined as the proportion of patients accepted for stroke evaluation and discharged with a final stroke diagnosis. One thousand three hundred patients provide a 50% surplus to the 808 patients needed for 80% power to detect a 10% increase in PPV. Discussion Structured and digital communication using a common scale like NIHSS may result in increased probability for better identification of stroke patients and less stroke mimics delivered to a stroke team for acute diagnostics and treatment in our population.publishedVersio

Interhospital transport of critically ill patients: experiences and challenges, a qualitative study

Background No consensus based national standard for interhospital transports of critically ill patients exists in Norway. The local hospitals are responsible for funding, organizing and performing these transports, resulting in potentially different level of care for the critically ill patients depending on local hospital resources and not the level of severity in the patient’s condition. The aim of this study was to examine how these transports are executed and to discover challenges during transports and potentials of improvement. Methods A qualitative study with 20 semi-structured interviews of doctors, nurses and ambulance personnel representing a wide range in experience and formal education, reflecting the different compositions of crews performing interhospital transports was conducted. A systematic text condensation of the interviews was performed to describe personal experiences and values. Results Few interviewees reported special adverse events when asked. Instead they chose to describe more general characteristics of the working environment, their own positive emotions or fears and the strengths and weaknesses of the organizational system. The prehospital working environment was described as different from the in-hospital environment. The personnel experienced being on their own during transports, lack of procedures and checklists and often no systematic education or demanded preparedness for participating. The resident doctors described pressure from elderly colleagues to participate in the transports. At the same time, all interviewees reported a self-interest in participating in these transports. Conclusions Safe interhospital transports of the critically ill patients are challenged by the characteristics of the out of hospital environment. The transports are described as potentially unsafe for both patients and personnel. Systematic education is warranted, highlighting the use of checklists and special educational programs in prehospital critical care medicine. The strong personal interest to participate in these transports may serve as a barrier against changing todays system. To ensure the right level of competence and safety for each unique patient, it is imperative to standardize the interhospital transports on a national level, built on consensus from experienced prehospital personnel. Trial registration The trial is approved and registered by the local representative for the Norwegian Data Protection Authority as trial 13–7751

Ambulance-attended opioid overdoses: An examination into overdose locations and the role of a safe injection facility

Background: Although the United States and numerous other countries are amidst an opioid overdose crisis, access to safe injection facilities remains limited. Methods: We used prospective data from ambulance journals in Oslo, Norway, to describe the patterns, severity, and outcomes of opioid overdoses and compared these characteristics among various overdose locations. We also examined what role a safe injection facility may have had on these overdoses. Results: Based on 48,825 ambulance calls, 1054 were for opioid overdoses from 465 individuals during 2014 and 2015. The rate of calls for overdoses was 1 out of 48 of the total ambulance calls. Males made up the majority of the sample (n = 368, 79%), and the median age was 35 (range: 18–96). Overdoses occurred in public locations (n = 530, 50.3%), the safe injection facility (n = 353, 33.5%), in private homes (n = 83, 7.9%), and other locations (n = 88, 8.3%). Patients from the safe injection facility and private homes had similarly severe initial clinical symptoms (Glasgow Coma Scale median =3 and respiratory frequency median =4 breaths per minute) when compared with other locations, yet the majority from the safe injection facility did not require further ambulance transport to the hospital (n = 302, 85.6%). Those overdosed in public locations (odds ratio [OR] = 1.66, 95% confidence interval [CI] = 1.17–2.35), and when the safe injection facility was closed (OR =1.4, 95% CI =1.04–1.89), were more likely to receive transport for further treatment. Conclusions: Our findings suggest that the opening hours at the safe injection facility and the overdose location may impact the likelihood of ambulance transport for further treatment

NTNU intranasal naloxone trial (NINA-1) study protocol for a double-blind, double-dummy, non-inferiority randomised controlled trial comparing intranasal 1.4 mg to intramuscular 0.8 mg naloxone for prehospital use

Abstract Introduction Intranasal naloxone is widely used to treat opioid overdoses. The advantage of nasal administration compared to injection lies in its suitability for administration by lay people as it is needless. Approved formulations of nasal naloxone with bioavailability of approximately 50% have only undergone trials in healthy volunteers, while off-label nasal sprays with low bioavailability have been studied in patients. Randomised clinical trials are needed to investigate efficacy and safety of approved intranasal naloxone in patients suffering overdose. This study investigates whether the administration of 1.4 mg naloxone in 0.1 millilitres per dose is non- inferior to 0.8 mg intramuscular injection in patients treated for opioid overdose. Methods and analysis Sponsor is the Norwegian University of Science and Technology. The study has been developed in collaboration with user representatives. The primary endpoint is the restoration of spontaneous respiration ≥10 breaths/minute based on a sample of 200 opioid overdose cases. Double-dummy design ensures blinding, which will be maintained until the database is locked. Ethics and dissemination The study was approved by the Norwegian Medicines Agency and Regional Ethics Committees (REC: 2016/2000). It adheres to the Good Clinical Practice guidelines as set out by The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. Informed consent will be sought through a differentiated model. This allows for deferred consent after inclusion for patients who have regained the ability to consent. Patients who are unable to consent prior to discharge by emergency services are given written information and can withdraw at a later date in line with user recommendations. Metadata will be published in the NTNU Open repository. De-identified individual participant data will be made available to recipients conditional of data processor agreement being entered. Trial registrations: EudraCT number: 2016-004072-22 and Clinicaltrials.gov NCT0351802

NTNU intranasal naloxone trial (NINA-1) study protocol for a double-blind, double-dummy, non-inferiority randomised controlled trial comparing intranasal 1.4 mg to intramuscular 0.8 mg naloxone for prehospital use

Abstract Introduction Intranasal naloxone is widely used to treat opioid overdoses. The advantage of nasal administration compared to injection lies in its suitability for administration by lay people as it is needless. Approved formulations of nasal naloxone with bioavailability of approximately 50% have only undergone trials in healthy volunteers, while off-label nasal sprays with low bioavailability have been studied in patients. Randomised clinical trials are needed to investigate efficacy and safety of approved intranasal naloxone in patients suffering overdose. This study investigates whether the administration of 1.4 mg naloxone in 0.1 millilitres per dose is non- inferior to 0.8 mg intramuscular injection in patients treated for opioid overdose. Methods and analysis Sponsor is the Norwegian University of Science and Technology. The study has been developed in collaboration with user representatives. The primary endpoint is the restoration of spontaneous respiration ≥10 breaths/minute based on a sample of 200 opioid overdose cases. Double-dummy design ensures blinding, which will be maintained until the database is locked. Ethics and dissemination The study was approved by the Norwegian Medicines Agency and Regional Ethics Committees (REC: 2016/2000). It adheres to the Good Clinical Practice guidelines as set out by The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. Informed consent will be sought through a differentiated model. This allows for deferred consent after inclusion for patients who have regained the ability to consent. Patients who are unable to consent prior to discharge by emergency services are given written information and can withdraw at a later date in line with user recommendations. Metadata will be published in the NTNU Open repository. De-identified individual participant data will be made available to recipients conditional of data processor agreement being entered. Trial registrations: EudraCT number: 2016-004072-22 and Clinicaltrials.gov NCT0351802

Ambulance-attended opioid overdoses: An examination into overdose locations and the role of a safe injection facility

Background: Although the United States and numerous other countries are amidst an opioid overdose crisis, access to safe injection facilities remains limited. Methods: We used prospective data from ambulance journals in Oslo, Norway, to describe the patterns, severity, and outcomes of opioid overdoses and compared these characteristics among various overdose locations. We also examined what role a safe injection facility may have had on these overdoses. Results: Based on 48,825 ambulance calls, 1054 were for opioid overdoses from 465 individuals during 2014 and 2015. The rate of calls for overdoses was 1 out of 48 of the total ambulance calls. Males made up the majority of the sample (n = 368, 79%), and the median age was 35 (range: 18–96). Overdoses occurred in public locations (n = 530, 50.3%), the safe injection facility (n = 353, 33.5%), in private homes (n = 83, 7.9%), and other locations (n = 88, 8.3%). Patients from the safe injection facility and private homes had similarly severe initial clinical symptoms (Glasgow Coma Scale median =3 and respiratory frequency median =4 breaths per minute) when compared with other locations, yet the majority from the safe injection facility did not require further ambulance transport to the hospital (n = 302, 85.6%). Those overdosed in public locations (odds ratio [OR] = 1.66, 95% confidence interval [CI] = 1.17–2.35), and when the safe injection facility was closed (OR =1.4, 95% CI =1.04–1.89), were more likely to receive transport for further treatment. Conclusions: Our findings suggest that the opening hours at the safe injection facility and the overdose location may impact the likelihood of ambulance transport for further treatment

Prehospital naloxone administration – what influences choice of dose and route of administration?

Background Amidst the ongoing opioid crisis there are debates regarding the optimal route of administration and dosages of naloxone. This applies both for lay people administration and emergency medical services, and in the development of new naloxone products. We examined the characteristics of naloxone administration, including predictors of dosages and multiple doses during patient treatment by emergency medical service staff in order to enlighten this debate. Methods This was a prospective observational study of patients administered naloxone by the Oslo City Center emergency medical service, Norway (2014–2018). Cases were linked to The National Cause of Death Registry. We investigated the route of administration and dosage of naloxone, clinical and demographic variables relating to initial naloxone dose and use of multiple naloxone doses and one-week mortality. Results Overall, 2215 cases were included, and the majority (91.9%) were administered intramuscular naloxone. Initial doses were 0.4 or 0.8 mg, and 15% of patients received multiple dosages. Unconscious patients or those in respiratory arrest were more likely to be treated with 0.8 mg naloxone and to receive multiple doses. The one-week mortality from drug-related deaths was 4.1 per 1000 episodes, with no deaths due to rebound opioid toxicity. Conclusions Intramuscular naloxone doses of 0.4 and 0.8 mg were effective and safe in the treatment of opioid overdose in the prehospital setting. Emergency medical staff appear to titrate naloxone based on clinical presentation

Comparison of intranasal and intramuscular naloxone in opioid overdoses managed by ambulance staff: a double-dummy, randomised, controlled trial.

AIMS: To measure and evaluate clinical response to nasal naloxone in opioid overdoses in the pre‐hospital environment. DESIGN: Randomised, controlled, double‐dummy, blinded, non‐inferiority trial, and conducted at two centres. SETTING: Participants were included by ambulance staff in Oslo and Trondheim, Norway, and treated at the place where the overdose occurred. PARTICIPANTS: Men and women age above 18 years with miosis, rate of respiration ≤8/min, and Glasgow Coma Score <12/15 were included. Informed consent was obtained through a deferred‐consent procedure. INTERVENTION AND COMPARATOR: A commercially available 1.4 mg/0.1 mL intranasal naloxone was compared with 0.8 mg/2 mL naloxone administered intramuscularly. MEASUREMENTS: The primary end‐point was restoration of spontaneous respiration of ≥10 breaths/min within 10 minutes. Secondary outcomes included time to restoration of spontaneous respiration, recurrence of overdose within 12 hours and adverse events. FINDINGS: In total, 201 participants were analysed in the per‐protocol population. Heroin was suspected in 196 cases. With 82% of the participants being men, 105 (97.2%) in the intramuscular group and 74 (79.6%) in the intranasal group returned to adequate spontaneous respiration within 10 minutes after one dose. The estimated risk difference was 17.5% (95% CI, 8.9%–26.1%) in favour of the intramuscular group. The risk of receiving additional naloxone was 19.4% (95% CI, 9.0%–29.7%) higher in the intranasal group. Adverse reactions were evenly distributed, except for drug withdrawal reactions, where the estimated risk difference was 6.8% (95% CI, 0.2%–13%) in favour of the intranasal group in a post hoc analysis. CONCLUSION: Intranasal naloxone (1.4 mg/0.1 mL) was less efficient than 0.8 mg intramuscular naloxone for return to spontaneous breathing within 10 minutes in overdose patients in the pre‐hospital environment when compared head‐to‐head. Intranasal naloxone at 1.4 mg/0.1 mL restored breathing in 80% of participants after one dose and had few mild adverse reactions

Paramedic Norwegian Acute Stroke Prehospital Project (ParaNASPP) study protocol: a stepped wedge randomised trial of stroke screening using the National Institutes of Health Stroke Scale in the ambulance

Background: Less than 50% of stroke patients in Norway reach hospital within 4 h of symptom onset. Early prehospital identification of stroke and triage to the right level of care may result in more patients receiving acute treatment. Quality of communication between paramedics and the stroke centre directly affects prehospital on-scene time, emphasising this as a key factor to reduce prehospital delay. Prehospital stroke scales are developed for quick and easy identification of stroke, but have poor sensitivity and specificity compared to an in-hospital assessment with the National Institutes of Health Stroke Scale (NIHSS). The aim of the Paramedic Norwegian Acute Stroke Prehospital Project (ParaNASPP) is to assess whether a structured learning program, prehospital NIHSS and a mobile application facilitating communication with the stroke physician may improve triage of acute stroke patients. Methods: A stepped wedge cluster randomised controlled intervention design will be used in this trial in Oslo, Norway. Paramedics at five ambulance stations will enrol adult patients with suspected stroke within 24 h of symptom onset. All paramedics will begin in a control phase with standard procedures. Through an e-learning program and practical training, a random and sequential switch to the intervention phase takes place. A mobile application for NIHSS scoring, including vital patient information for treatment decisions, transferring data from paramedics to the on-call stroke physician at the Stroke Unit at Oslo University Hospital, will be provided for the intervention. The primary outcome measure is positive predictive value (PPV) for prehospital identification of patients with acute stroke defined as the proportion of patients accepted for stroke evaluation and discharged with a final stroke diagnosis. One thousand three hundred patients provide a 50% surplus to the 808 patients needed for 80% power to detect a 10% increase in PPV. Discussion: Structured and digital communication using a common scale like NIHSS may result in increased probability for better identification of stroke patients and less stroke mimics delivered to a stroke team for acute diagnostics and treatment in our population