Inhaled nitric oxide as temporary respiratory stabilization in patients with COVID-19 related respiratory failure (INOCOV): Study protocol for a randomized controlled trial

Background In March 2020, WHO announced the COVID-19 a pandemic and a major global public health emergency. Mortality from COVID-19 is rapidly increasing globally, with acute respiratory failure as the predominant cause of death. Many patients experience severe hypoxia and life-threatening respiratory failure often requiring mechanical ventilation. To increase safety margins during emergency anaesthesia and rapid sequence intubation (RSI), patients are preoxygenated with a closed facemask with high-flow oxygen and positive end-expiratory pressure (PEEP). Due to the high shunt fraction of deoxygenated blood through the lungs frequently described in COVID-19 however, these measures may be insufficient to avoid harmful hypoxemia. Preoxygenation with inhaled nitric oxide (iNO) potentially reduces the shunt fraction and may thus allow for the necessary margins of safety during RSI. Methods and design The INOCOV protocol describes a phase II pharmacological trial of inhaled nitric oxide (iNO) as an adjunct to standard of care with medical oxygen in initial airway and ventilation management of patients with known or suspected COVID-19 in acute respiratory failure. The trial is parallel two-arm, randomized, controlled, blinded trial. The primary outcome measure is the change in oxygen saturation (SpO2), and the null hypothesis is that there is no difference in the change in SpO2 following initiation of iNO.publishedVersio

Erratum to: Psychosis associated with acute recreational drug toxicity: a European case series

Psychosis can be associated with acute recreational drug and novel psychoactive substance (NPS) toxicity. However, there is limited data available on how common this is and which drugs are most frequently implicated. We describe a European case series of psychosis associated with acute recreational drug toxicity, and estimate the frequency of psychosis for different recreational drugs.; The European Drug Emergencies Network (Euro-DEN) collects data on presentations to Emergency Departments (EDs) with acute recreational drug and NPS toxicity at 16 centres in ten countries. Euro-DEN data from October 2013 through September 2014 was retrospectively searched, and cases with psychosis were included. The proportion of cases with psychosis per drug was calculated in the searched Euro-DEN dataset.; Psychosis was present in 348 (6.3 %) of 5529 cases. The median (interquartile range) age was 29 (24-38) years, 276 (79.3 %) were male and 114 (32.8 %) were admitted to psychiatric ward. The drugs most commonly reported were cannabis in 90 (25.9 %) cases, amphetamine in 87 (25.0 %) and cocaine in 56 (16.1 %). More than one drug was taken in 189 (54.3 %) cases. Psychosis was frequent in those ED presentations involving tryptamines (4/7; 57.1 %), methylenedioxypyrovalerone (MDPV) (6/22; 27.3 %), methylphenidate (6/26; 23.1 %), lysergic acid diethylamide (LSD) (18/86; 20.9 %), psilocybe mushrooms (3/16; 18.8 %), synthetic cannabinoid receptor agonists (4/26; 15.4 %) and amphetamine (87/593; 14.7 %), but less common in those involving mephedrone (14/245; 5.7 %), methylenedioxymethamphetamine (MDMA) (20/461; 4.3 %) and methedrone (3/92; 3.3 %). Amphetamine was the most frequent drug associated with psychosis when only one agent was reported, with psychosis occurring in 32.4 % of these presentations.; The frequency of psychosis in acute recreational drug toxicity varies considerably between drugs, but is a major problem in amphetamine poisoning. In rapidly changing drug markets and patterns of use, the Euro-DEN sentinel network contributes to measuring the scale of drug-related harms in Europe beyond other more established indicators

Fatal poisonings in Oslo: a one-year observational study

<p>Abstract</p> <p>Background</p> <p>Acute poisonings are common and are treated at different levels of the health care system. Since most fatal poisonings occur outside hospital, these must be included when studying characteristics of such deaths. The pattern of toxic agents differs between fatal and non-fatal poisonings. By including all poisoning episodes, cause-fatality rates can be calculated.</p> <p>Methods</p> <p>Fatal and non-fatal acute poisonings in subjects aged ≥16 years in Oslo (428 198 inhabitants) were included consecutively in an observational multi-centre study including the ambulance services, the Oslo Emergency Ward (outpatient clinic), and hospitals, as well as medico-legal autopsies from 1st April 2003 to 31st March 2004. Characteristics of fatal poisonings were examined, and a comparison of toxic agents was made between fatal and non-fatal acute poisoning.</p> <p>Results</p> <p>In Oslo, during the one-year period studied, 103 subjects aged ≥16 years died of acute poisoning. The annual mortality rate was 24 per 100 000. The male-female ratio was 2:1, and the mean age was 44 years (range 19-86 years). In 92 cases (89%), death occurred outside hospital. The main toxic agents were opiates or opioids (65% of cases), followed by ethanol (9%), tricyclic anti-depressants (TCAs) (4%), benzodiazepines (4%), and zopiclone (4%). Seventy-one (69%) were evaluated as accidental deaths and 32 (31%) as suicides. In 70% of all cases, and in 34% of suicides, the deceased was classified as drug or alcohol dependent. When compared with the 2981 non-fatal acute poisonings registered during the study period, the case fatality rate was 3% (95% C.I., 0.03-0.04). Methanol, TCAs, and antihistamines had the highest case fatality rates; 33% (95% C.I., 0.008-0.91), 14% (95% C.I., 0.04-0.33), and 10% (95% C.I., 0.02-0.27), respectively.</p> <p>Conclusions</p> <p>Three per cent of all acute poisonings were fatal, and nine out of ten deaths by acute poisonings occurred outside hospital. Two-thirds were evaluated as accidental deaths. Although case fatality rates were highest for methanol, TCAs, and antihistamines, most deaths were caused by opiates or opioids.</p

Determinants of Admission to Critical Care Following Acute Recreational Drug Toxicity: A Euro-DEN Plus Study

This study aimed to characterize patients admitted to critical care following Emergency Department (ED) presentation with acute recreational drug toxicity and to identify determinants of admission to critical care. A retrospective multicenter matched case-control study was conducted by the European Drug Emergency Network Plus (Euro-DEN Plus) over the period 2014–2021. The cases were ED presentations with acute recreational drug toxicity admitted to critical care, the controls consisted of ED presentations with acute recreational drug toxicity medically discharged directly from the ED. The potential determinants of admission to critical care were assessed through multivariable conditional stepwise logistic regression analysis and multiple imputation was used to account for the missing data. From 2014 to 2021, 3448 Euro-DEN Plus presentations involved patients admitted to critical care (76.9% males; mean age 33.2 years; SD 10.9 years). Patient age ≥35 years (as compared to ≤18 years) was a determinant of admission to critical care following acute recreational drug toxicity (adjusted odds ratio, aOR, 1.51, 95% confidence interval, CI, 1.15–1.99), along with polydrug use (aOR 1.39, 95% CI 1.22–1.59), ethanol co-ingestion (aOR 1.44, 95% CI 1.26–1.64), and the use of gamma-hydroxybutyrate/gamma-butyrolactone (GHB/GBL, aOR 3.08, 95% CI 2.66–3.57). Conversely, lower odds of admission to critical care were associated with the use of cocaine (aOR 0.85, 95% CI 0.74–0.99), cannabis (aOR 0.44, 95% CI 0.37–0.52), heroin (aOR 0.80, 95% CI 0.69–0.93), and amphetamine (aOR 0.65, 95% CI 0.54–0.78), as was the arrival to the ED during the night (8 p.m.–8 a.m., aOR 0.88, 95% CI 0.79–0.98). These findings, which deserve confirmation and further investigation, could contribute to a more complete understanding of the decision-making process underlying the admission to critical care of patients with acute recreational drug toxicity

Acute recreational drug toxicity: Comparison of self-reports and results of immunoassay and additional analytical methods in a multicenter European case series

The aim of the study was to compare self-reported and analytically confirmed substance use in cases of acute recreational drug toxicity.We performed a retrospective analysis of emergency department presentations of acute recreational drug toxicity over 2 years (October 2013 to September 2015) within the European Drug Emergencies Network Plus project.Among the 10,956 cases of acute recreational drug toxicity during the study period, 831 could be included. Between the self-reported substance use and the toxicological results, the highest agreement was found for heroin (86.1%) and cocaine (74.1%), whereas inhalants, poppers, and magic mushrooms were self-reported but not analytically detected. Cathinones and other new psychoactive substances (NPS) could be detected using additional analytical methods. Among cases with both immunoassay (IA) and confirmation with mass spectrometry (MS), the results were consistent for methadone (100%) and cocaine (95.5%) and less consistent for amphetamines (81.8%). In cases with a positive IA for amphetamines (n = 54), MS confirmed the presence of 3,4-methylenedioxymethamphetamine (MDMA), amphetamine, methamphetamine, and NPS in 37, 20, 10, and 6 cases, respectively, also revealing use of more than 1 substance in some cases. MS yielded positive results in 21 cases with a negative IA for amphetamines, including amphetamine, MDMA, methamphetamine, and NPS, in 14, 7, 2, and 2 cases, respectively.In conclusion, the highest agreement was found between self-reports and analytical findings for heroin and cocaine. The diagnosis of NPS use was mainly based on self-report. The IAs accurately identified methadone and cocaine, and MS had advantages for the detection of NPS and amphetamine derivatives

Clinical effects of cannabis compared to synthetic cannabinoid receptor agonists (SCRAs): a retrospective cohort study of presentations with acute toxicity to European hospitals between 2013 and 2020.

INTRODUCTION Cannabis is the most common recreational drug worldwide and synthetic cannabinoid receptor agonists are currently the largest group of new psychoactive substances. The aim of this study was to compare the clinical features and outcomes of lone acute cannabis toxicity with lone acute synthetic cannabinoid receptor agonist toxicity in a large series of presentations to European emergency departments between 2013-2020. METHODS Self-reported drug exposure, clinical, and outcome data were extracted from the European Drug Emergencies Network Plus which is a surveillance network that records data on drug-related emergency department presentations to 36 centres in 24 European countries. Cannabis exposure was considered the control in all analyses. To compare the lone cannabis and lone synthetic cannabinoid receptor agonist groups, univariate analysis using chi squared testing was used for categorical variables and non-parametric Mann-Whitney U- testing for continuous variables. Statistical significance was defined as a P value of < 0.05. RESULTS Between 2013-2020 there were 54,314 drug related presentations of which 2,657 were lone cannabis exposures and 503 lone synthetic cannabinoid receptor agonist exposures. Synthetic cannabinoid receptor agonist presentations had statistically significantly higher rates of drowsiness, coma, agitation, seizures and bradycardia at the time of presentation. Cannabis presentations were significantly more likely to have palpitations, chest pain, hypertension, tachycardia, anxiety, vomiting and headache. DISCUSSION Emergency department presentations involving lone synthetic cannabinoid receptor agonist exposures were more likely to have neuropsychiatric features and be admitted to a psychiatric ward, and lone cannabis exposures were more likely to have cardiovascular features. Previous studies have shown variability in the acute toxicity of synthetic cannabinoid receptor agonists compared with cannabis but there is little comparative data available on lone exposures. There is limited direct comparison in the current literature between lone synthetic cannabinoid receptor agonist and lone cannabis exposure, with only two previous poison centre series and two clinical series. Whilst this study is limited by self-report being used to identify the drug(s) involved in the presentations, previous studies have demonstrated that self-report is reliable in emergency department presentations with acute drug toxicity. CONCLUSION This study directly compares presentations with acute drug toxicity related to the lone use of cannabis or synthetic cannabinoid receptor agonists. It supports previous findings of increased neuropsychiatric toxicity from synthetic cannabinoid receptor agonists compared to cannabis and provides further data on cardiovascular toxicity in lone cannabis use

Pain Management with Inhalation of Methoxyflurane Administrated by Non-Medical Ski Patrol: A Quality Assessment Study

Abstract Introduction Pain management can be challenging, especially in remote locations where first responders are not certified health care personnel. In these settings, traditional intravenous administration of analgesics is not feasible. In this study, we explore the feasibility of using methoxyflurane as a first-line analgesic in ski-related traumas, administered by the ski patrol, acting as the municipality physician’s aiding personnel. Methods This is a quality assessment of a project aimed at improving pain management in trauma patients at the largest ski resort in Norway. Members of the ski patrol were trained and delegated administration of methoxyflurane on behalf of the municipality physician. Patients > 18 years with ski-related trauma and pain Numeric Rating Scale (NRS) of 6 or more were included. The patients received inhalational methoxyflurane on site, with continued administration during transport. Data were collected by the ski patrol and entered into a quality register. Results In total, 53 patients (18 to 76 years, 32 (60%) males) accepted to be registered. The injuries were fractures in 35 (66%), joint luxation in seven (13%), combination of fracture and luxation in seven (13%), and blunt soft tissue damage in four (8%) cases. Median NRS before administration of methoxyflurane was 8 decreasing to median NRS 5 after 5–10 min. The median NRS reduction of 3 (25–75% percentiles 2–5) was significant, p < 0.001. Patients rated the perceived effect as good in 40 (80%) moderate in nine (18%) and no effect in 1 (2%). Side effects were mild: Six patients (11%) experienced dizziness, one patient (2%) was considered drowsy. Conclusions Methoxyflurane is feasible as a first-line analgesic administered by a non-medical ski patrol in a responsibly organized system. Early pain management with inhalation of methoxyflurane provides good perceived effect with mild adverse events and can be of great value in settings where few alternatives for pain management are available