Fridtjof Heyerdahl

Effects of COX inhibition on experimental pain and hyperalgesia during and after remifentanil infusion in humans

&NA; Opioids may enhance pain sensitivity resulting in opioid‐induced hyperalgesia (OIH). Activation of spinal cyclooxygenase may play a role in the development of OIH. The aim of this study was to demonstrate remifentanil‐induced postinfusion hyperalgesia in an electrical pain and a cold pain model, and to investigate whether COX‐2 (parecoxib) or COX‐1 (ketorolac) inhibition could prevent hyperalgesia after remifentanil infusion. Sixteen healthy males were enrolled in this randomized, double‐blind, placebo‐controlled crossover study. Each subject went through 4 sessions: control, remifentanil, parecoxib + remifentanil, and ketorolac + remifentanil. Transcutaneous electrical stimulation induced acute pain and areas of pinprick hyperalgesia. The areas of pinprick hyperalgesia were assessed before, during, and after a 30‐minute infusion of either remifentanil or saline. The cold‐pressor test (CPT) was performed before, at the end of, and 1 hour after the infusions. The subjects received a bolus of either saline, 40 mg parecoxib, or 30 mg ketorolac intravenously after the first CPT. The areas of pinprick hyperalgesia and CPT pain after the end of remifentanil infusion increased significantly compared to control (P < 0.001 and P = 0.005, respectively). Pretreatment with parecoxib or ketorolac reduced the postinfusion area of pinprick hyperalgesia (P < 0.001 and P = 0.001, respectively), compared to the remifentanil group. Parecoxib reduced the area significantly more than ketorolac (P = 0.009). In the CPT, pretreatment with parecoxib or ketorolac did not prevent postinfusion hyperalgesia. These results demonstrated OIH in both models, and may suggest that COX‐2 inhibition is more important than COX‐1 inhibition in reducing hyperalgesia. Remifentanil‐induced hyperalgesia was demonstrated for both electrically induced pain and cold‐pressor pain. Both parecoxib and ketorolac prevented hyperalgesia in the electrical model, parecoxib to a larger extent.

Acute recreational drug and new psychoactive substance toxicity in Europe: 12 months data collection from the European Drug Emergencies Network (Euro-DEN).

Context. Despite the potential for recreational drugs and new psychoactive substances (NPSs) to cause significant morbidity and mortality, there is limited collection of systematic data on acute drug/NPS toxicity in Europe. Objective. To report data on acute drug/NPS toxicity collected by a network of sentinel centres across Europe with a specialist clinical and research interest in the acute toxicity of recreational drugs and NPS to address this knowledge gap. Methods. Sixteen sentinel centres in 10 European countries (Denmark, Estonia, France, Germany, Ireland, Norway, Poland, Spain, Switzerland and the UK) collected data on all acute drug toxicity presentations to their Emergency Rooms (ERs) for 12 months (October 2013–September 2014); information on the drug(s) involved in the presentations was on the basis of patient self-reporting. Results. Data were collected on a total of 5529 presentations involving 8709 drugs (median (interquartile range [IQR]): 1 (1–2) drugs per presentation), a median of 0.3% of all ER attendances. Classical recreational drugs were most common (64.6%) followed by prescription drugs (26.5%) and NPS (5.6%). The ‘top five’ drugs recorded were heroin (1345 reports), cocaine (957), cannabis (904), GHB/GBL (711) and amphetamine (593). 69.5% of individuals went to hospital by ambulance (peak time between 19:00 and 02:00 at weekends); the median (IQR) age was 31 (24–39) years and 75.4% were male. Although serious clinical features were not seen in most presentations and 56.9% were medically discharged from the ER (median length of stay: 4.6 hours), a significant number (26.5%) was agitated, in 10.5% the GCS was 8 or less and 35 presented in cardiac arrest. There were 27 fatalities with opioids implicated in 13. Conclusion. The Euro-DEN dataset provides a unique insight into the drugs involved in and clinical pattern of toxicity/outcome of acute recreational drug toxicity presentations to hospitals around Europe. This is complimentary to other indicators of drug-related harm and helps to build a fuller picture of the public health implications of drug use in Europe.

Repetition of acute poisoning in Oslo: 1-year prospective study.

BACKGROUND The repetition of acute poisoning occurs frequently. The intention may change between episodes and many poisonings are treated outside the hospital setting. Few studies have taken this into account. AIMS To quantify the repetition frequency regardless of the level of health care or the intention behind the poisoning, and to identify possible risk factors for repetition. METHOD A prospective multicentre study of all acute poisonings in Oslo treated in hospital, at an out-patient clinic or by the ambulance service. Repetition was estimated using Kaplan-Meier calculations, and predictive factors were identified using Cox regression analysis. RESULTS The estimated 1-year repetition rate was 30% (95% CI 24-35). Independent predictors of repetition were middle age (30-49 years), poisoning with opiates or sedatives, unemployment or living on social welfare, a previous suicide attempt, and a history of psychiatric treatment. Intention was not a significant predictor. CONCLUSIONS Repetition of acute poisoning is high, irrespective of the level of healthcare and the intention behind the poisoning.

Pre-hospital treatment of acute poisonings in Oslo

BackgroundPoisoned patients are often treated in and discharged from pre-hospital health care settings. Studies of poisonings should therefore not only include hospitalized patients. Aims: To describe the acutely poisoned patients treated by ambulance personnel and in an outpatient clinic; compare patients transferred to a higher treatment level with those discharged without transfer; and study the one-week mortality after pre-hospital discharge.MethodsA one-year multi-centre study with prospective inclusion of all acutely poisoned patients ≥ 16 years of age treated in ambulances, an outpatient clinic, and hospitals in Oslo.ResultsA total of 3757 health service contacts from 2997 poisoning episodes were recorded: 1860 were treated in ambulances, of which 15 died and 750 (40%) were discharged without transfer; 956 were treated in outpatient clinic, of which 801 (84%) were discharged without transfer; and 941 episodes were treated in hospitals. Patients discharged alive after ambulance treatment were mainly poisoned by opiates (70%), were frequently comatose (35%), had respiratory depression (37%), and many received naloxone (49%). The majority of the patients discharged from the outpatient clinic were poisoned by ethanol (55%), fewer were comatose (10%), and they rarely had respiratory depression (4%). Among the hospitalized, pharmaceutical poisonings were most common (58%), 23% were comatose, and 7% had respiratory depression. Male patients comprised 69% of the pre-hospital discharges, but only 46% of the hospitalized patients. Except for one patient, who died of a new heroin overdose two days following discharge from an ambulance, there were no deaths during the first week after the poisonings in the 90% of the pre-hospital discharged patients with known identity.ConclusionMore than half of the poisoned patients treated in pre-hospital treatment settings were discharged without transfer to higher levels. These poisonings were more often caused by drug and alcohol abuse than in those who were hospitalized, and more than two-thirds were males. Almost half of those discharged from ambulances received an antidote. The pre-hospital treatment of these poisonings appears safe regarding short-term mortality.

The European Drug Emergencies Network (Euro-DEN)

1Guy’s and St Thomas’ NHS Foundation Trust and King’s Health Partners, London, UK 2King’s College London, London, UK 3Department of Acute Medicine, The National NBC Centre, Oslo University Hospital, Ullevaal, Oslo, Norway 4Emergency Department and Clinical Toxicology Unit, Hospital Universitari Son Espases, Palma de Mallorca, Spain 5Action on New Drugs and Epidemiology Units, European Monitoring Centre for Drugs and Drug Addiction, Lisbon, Portugal

Acute poisonings treated in hospitals in Oslo: a one-year prospective study (II): clinical outcome.

OBJECTIVES The changing pattern of acute poisoning may affect complications and outcome in these patients. An update study on acute poisonings was therefore performed and compared to similar data from 1980. DESIGN A prospective cross-sectional multi-center study of all adult patients (> or = 16 years) hospitalized in Oslo with a main diagnosis of acute poisoning, irrespective of intention, over a one-year period. RESULTS Of 947 admissions, 222 (23%) were comatose. Complications were observed in 173 (18%), slightly reduced from 1980 (22%). Ten (1.1%) died and six (0.6%) got permanent sequelae, of which seven and five were drug- or alcohol-related, respectively. Seventy-five percent received treatment besides observation; 39% received antidotes, increased from 21% in 1980, most frequently flumazenil (23%) and naloxone (14%). CONCLUSIONS In-hospital mortality in poisoned patients remained low, few patients entailed complications, and most patients survived without permanent sequelae. Drug- and alcohol-abuse related poisonings were most severe.

Fatal poisonings in Oslo: a one-year observational study

BackgroundAcute 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.MethodsFatal 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.ResultsIn 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.ConclusionsThree 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.

Clinical assessment compared to laboratory screening in acutely poisoned patients

Acute poisonings may require identification of the toxic agents. It is impossible for routine laboratories to provide a full spectrum of toxicological analyses, and clinicians should know the reliability of the clinical diagnoses of toxic agents. We performed a 1-year study of hospitalized acute poisonings to determine the agreement between the clinical assessment on admission and serum laboratory tests for eight common toxic agents. Blood samples were drawn in 665 (70%) of the 947 admissions. The total number of laboratory found agents (967) exceeded the clinically suspected (871) by 11%. The agreement between the clinical assessment and laboratory analyses was good for ethanol and paracetamol (κ = 0.70 for both), whereas only moderate or fair for other agents (κ 0.22–0.51). Sensitivities of the clinical assessments compared to the laboratory results were better for common than rare agents, and better for higher than lower serum concentrations. The four most common agents (ethanol, benzodiazepines, paracetamol, and opiates) had overall sensitivity of 82% for higher-than-median serum concentrations, whereas the other agents had sensitivities ranging from 14% to 71% for higher-than-median concentrations. The reliability of the clinical diagnoses varied to such an extent that agents, which are important to recognize for specific treatment, should be tested for.

Current European data collection on emergency department presentations with acute recreational drug toxicity: Gaps and national variations

Abstract Background. The number of new (novel) psychoactive substances (NPS) available in the illegal market is increasing; however, current monitoring of the drug situation in Europe focuses mainly on classical drugs of abuse, with limited emphasis on clinical presentation in the emergency department (ED). The European Drug Emergencies Network (Euro-DEN) is a European Commission-funded project that aims to improve the knowledge of acute drug toxicity of both classical recreational drugs and NPS. As a baseline for this project, we performed a study to establish which data are currently being collected and reported in Europe on ED presentations with acute toxicity related to NPS and classical drugs of abuse. Methods. We used a three-pronged approach to identify any systematic collection of data on NPS toxicity in Europe by i) performing a literature search, ii) utilising an online survey of the European Monitoring Centre for Drugs and Drug Addiction Re seau Europe en d’Information sur les Drogues et les Toxicomanies national focal points and iii) exploiting the knowledge and resources of the Euro-DEN network members. Results. The literature search revealed 21 papers appropriate for assessment, but only one described a systematic collection of clinical data on NPS. Twenty-seven of thirty countries responded to the online survey. More than half of all the countries (52%) did not perform any registration at all of such data, 37% collected systematic clinical data on NPS at a national level, while 44% collected data on classical drugs. A few examples for good practice of systematic collection of clinical data on ED presentations due to acute toxicity were identified. Conclusion. The systematic collection of data on ED presentation of toxicity related to NPS and classical drugs in Europe is scarce; the existing collection is limited to single centres, single countries, groups of patients or not focused on novel drugs; the collection of data is highly variable between the different countries. Euro-DEN, a European Commission funded project, aims at closing some of these gaps.

Acute child poisonings in Oslo: a 2-year prospective study

Aim: To study the current epidemiology, clinical course and outcome of poisonings among children in Oslo and compare findings to a similar study from 1980.