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Introduction: The Advanced Trauma Life Support guidelines (ATLS; 2018, 10th ed.) recommend an early and liberal supplemental oxygen for all severely injured trauma patients to prevent hypoxaemia. As of 2024, these guidelines remain the most current. This may lead to hyperoxaemia, which has been associated with increased mortality and respiratory complications. We aimed to investigate the attitudes among clinicians, defined as physicians and prehospital personnel, towards the use of supplemental oxygen in trauma cases., Materials and Methods: A European, web-based, cross-sectional survey was conducted consisting of 23 questions. The primary outcome was the question: "In your opinion, should all severely injured trauma patients always be given supplemental oxygen, regardless of arterial oxygen saturation measured by pulse oximetry?"., Results: The survey was answered by 707 respondents, which corresponded to a response rate of 52 %. The respondents were predominantly male (76 %), with the largest representation from Denmark (82 %), and primarily educated as physicians (62 %). A majority of respondents (73 % [95 % CI: 70 to 76 %]) did not support that supplemental oxygen should always be provided to all severely injured trauma patients without consideration of their arterial oxygen saturation as measured by pulse oximetry (SpO 2 ), with no significant difference between physicians and non-physicians (p = 0.08). Based on the respondents' preferred dosages, the median initial administered dosage of supplemental oxygen for spontaneously breathing trauma patients with a normal SpO 2 in the first few hours after trauma was 0 (interquartile range [IQR] 0-3) litres per minute, with 58 % of respondents opting not to provide any supplemental oxygen. The lowest acceptable SpO 2 goal in the first few hours after trauma was 94 % (IQR 92-95). In clinical scenarios with TBI, higher dosage of supplemental oxygen and fraction of inspired oxygen (FiO 2 ) were preferred, as well as targeting partial pressure of oxygen in arterial blood as opposed to adjusting the FiO 2 directly, compared to no TBI., Conclusion: Almost three out of four clinicians did not support the administration of supplemental oxygen to all severely injured trauma patients, regardless of SpO 2 . This corresponds to a more restrictive approach than recommended in the current ATLS (2018, 10th ed.) guidelines., Competing Interests: Declaration of competing interest None of the authors have any conflicts of interest to declare regarding the present manuscript. For conflicts of interests related to any entity the past 36 months not related to the present manuscript, these authors have the following to declare: Tobias Arleth received funding for a biomarker Copenhagen sub-trial of TRAUMOX2 from the Holger and Ruth Hesses Memorial Foundation and Danish Air Ambulance, and received funding for three months of research PhD programme exchange from Knud Højgaard's Foundation, the William Demant Foundation, Christian and Ottilia Brorson's Travel Scholarships, the Medical Science Faculty Foundation of Copenhagen University, and the Consultant Dr. Med. Edgar Schnohr and wife Gilberte Schnohrs Foundation. Josefine Baekgaard received funding for the TRAUMOX2 trial from the Novo Nordisk Foundation and was awarded with the prize for “talented young researcher” by The Lundbeck Foundation, of which 47.000€ was allocated to research. Stine T. Zwisler attended a Secma ultrasound course, and is an IDMC consultant for the GA Targets Trial; the author or the author's affiliation did not receive any payments in this regard. Wolf. E. Hautz received funding from the Swiss National Science Foundation and the European Union. Wolf E. Hautz received consulting fees and honorarias from the AO Foundation Zurich, and Mundipharma Switzerland gave him support for attending meetings, alongside participating in a DMSC for MDI Australia. Jacob Steinmetz receives funding of his professorship from the Norwegian Air Ambulance Foundation where payments are made to his organization, and he received funding for the TRAUMOX2 trial from the Novo Nordisk Foundation. The rest of the authors have nothing to declare., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Importance: Early administration of supplemental oxygen for all severely injured trauma patients is recommended, but liberal oxygen treatment has been associated with increased risk of death and respiratory complications., Objective: To determine whether an early 8-hour restrictive oxygen strategy compared with a liberal oxygen strategy in adult trauma patients would reduce death and/or major respiratory complications., Design, Setting, and Participants: This randomized controlled trial enrolled adult trauma patients transferred directly to hospitals, triggering a full trauma team activation with an anticipated hospital stay of a minimum of 24 hours from December 7, 2021, to September 12, 2023. This multicenter trial was conducted at 15 prehospital bases and 5 major trauma centers in Denmark, the Netherlands, and Switzerland. The 30-day follow-up period ended on October 12, 2023. The primary outcome was assessed by medical specialists in anesthesia and intensive care medicine blinded to the randomization., Interventions: In the prehospital setting or on trauma center admission, patients were randomly assigned 1:1 to a restrictive oxygen strategy (arterial oxygen saturation target of 94%) (n = 733) or liberal oxygen strategy (12-15 L of oxygen per minute or fraction of inspired oxygen of 0.6-1.0) (n = 724) for 8 hours., Main Outcomes and Measures: The primary outcome was a composite of death and/or major respiratory complications within 30 days. The 2 key secondary outcomes, death and major respiratory complications within 30 days, were assessed individually., Results: Among 1979 randomized patients, 1508 completed the trial (median [IQR] age, 50 [31-65] years; 73% male; and median Injury Severity Score was 14 [9-22]). Death and/or major respiratory complications within 30 days occurred in 118 of 733 patients (16.1%) in the restrictive oxygen group and 121 of 724 patients (16.7%) in the liberal oxygen group (odds ratio, 1.01 [95% CI, 0.75 to 1.37]; P = .94; absolute difference, 0.56 percentage points [95% CI, -2.70 to 3.82]). No significant differences were found between groups for each component of the composite outcome. Adverse and serious adverse events were similar across groups, with the exception of atelectasis, which was less common in the restrictive oxygen group compared with the liberal oxygen group (27.6% vs 34.7%, respectively)., Conclusions and Relevance: In adult trauma patients, an early restrictive oxygen strategy compared with a liberal oxygen strategy initiated in the prehospital setting or on trauma center admission for 8 hours did not significantly reduce death and/or major respiratory complications within 30 days., Trial Registration: ClinicalTrials.gov Identifier: NCT05146700.

Introduction: The Vasopressin and Methylprednisolone for In-Hospital Cardiac Arrest (VAM-IHCA) trial demonstrated a significant improvement in return of spontaneous circulation (ROSC) with no clear effect on long-term outcomes. The objective of the current manuscript was to evaluate the hemodynamic effects of intra-cardiac arrest vasopressin and methylprednisolone during the first 24 hours after ROSC., Methods: The VAM-IHCA trial randomized patients with in-hospital cardiac arrest to a combination of vasopressin and methylprednisolone or placebo during the cardiac arrest. This study is a post hoc analysis focused on the hemodynamic effects of the intervention after ROSC. Post-ROSC data on the administration of glucocorticoids, mean arterial blood pressure, heart rate, blood gases, vasopressor and inotropic therapy, and sedation were collected. Total vasopressor dose between the two groups was calculated based on noradrenaline-equivalent doses for adrenaline, phenylephrine, terlipressin, and vasopressin., Results: The present study included all 186 patients who achieved ROSC in the VAM IHCA-trial of which 100 patients received vasopressin and methylprednisolone and 86 received placebo. The number of patients receiving glucocorticoids during the first 24 hours was 22/86 (26%) in the placebo group and 14/100 (14%) in the methylprednisolone group with no difference in the cumulative hydrocortisone-equivalent dose. There was no significant difference between the groups in the mean cumulative noradrenaline-equivalent dose (vasopressin and methylprednisolone: 603 ug/kg [95CI% 227; 979] vs. placebo: 651 ug/kg [95CI% 296; 1007], mean difference -48 ug/kg [95CI% -140; 42.9], p = 0.30), mean arterial blood pressure, or lactate levels. There was no difference between groups in arterial blood gas values and vital signs., Conclusion: Treatment with vasopressin and methylprednisolone during cardiac arrest caused no difference in mean arterial blood pressure, vasopressor use, or arterial blood gases within the first 24 hours after ROSC when compared to placebo., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: AG: DSMB member Noorik Biopharmaceuticals and consultant NMD pharma, outside the submitted work. JK: Grant from the Novo Nordisk Foundation (NNF17OC0028706 and NNF22OC0079649) outside the current work. The remaining authors report no conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Supplemental oxygen is commonly used in trauma patients, although it may lead to hyperoxaemia that has been associated with pulmonary complications and increased mortality. The primary objective of this trial, TRAUMOX2, is to compare a restrictive versus liberal oxygen strategy the first 8 hours following trauma., Methods and Analysis: TRAUMOX2 is an investigator-initiated, international, parallel-grouped, superiority, outcome assessor-blinded and analyst-blinded, randomised, controlled, clinical trial.Adult patients with suspected major trauma are randomised to eight hours of a restrictive or liberal oxygen strategy. The restrictive group receives the lowest dosage of oxygen ( > 21%) that ensures an SpO 2 of 94%. The liberal group receives 12-15 L O 2 /min or FiO 2 =0.6-1.0.The primary outcome is a composite of 30-day mortality and/or development of major respiratory complications (pneumonia and/or acute respiratory distress syndrome).With 710 participants in each arm, we will be able to detect a 33% risk reduction with a restrictive oxygen strategy if the incidence of our primary outcome is 15% in the liberal group., Ethics and Dissemination: TRAUMOX2 is carried out in accordance with the Helsinki II Declaration. It has been approved by the Danish Committee on Health Research Ethics for the Capital Region (H-21018062) and The Danish Medicines Agency, as well as the Dutch Medical Research Ethics Committee Erasmus MS (NL79921.078.21 and MEC-2021-0932). A website (www.traumox2.org) is available for updates and study results will be published in an international peer-reviewed scientific journal., Trial Registration Numbers: EudraCT 2021-000556-19; NCT05146700., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The primary results from the Vasopressin and Methylprednisolone for In-Hospital Cardiac Arrest (VAM-IHCA) trial have previously been reported. The objective of the current manuscript is to report long-term outcomes., Methods: The VAM-IHCA trial was a multicenter, randomized, double-blind, placebo-controlled trial conducted at ten hospitals in Denmark. Adult patients (age ≥ 18 years) were eligible for the trial if they had an in-hospital cardiac arrest and received at least one dose of epinephrine during resuscitation. The trial drugs consisted of 40 mg methylprednisolone (Solu-Medrol®, Pfizer) and 20 IU of vasopressin (Empressin®, Amomed Pharma GmbH) given as soon as possible after the first dose of epinephrine. This manuscript report outcomes at 6 months and 1 year including survival, survival with favorable neurological outcome, and health-related quality of life., Results: 501 patients were included in the analysis. At 1 year, 15 patients (6.3%) in the intervention group and 22 patients (8.3%) in the placebo group were alive corresponding to a risk ratio of 0.76 (95% CI, 0.41-1.41). A favorable neurologic outcome at 1 year, based on the Cerebral Performance Category score, was observed in 14 patients (5.9%) in the intervention group and 20 patients (7.6%) in the placebo group (risk ratio, 0.78 [95% CI, 0.41-1.49]. No differences existed between groups for favorable neurological outcome and health-related quality of life at either 6 months or 1 year., Conclusions: Administration of vasopressin and methylprednisolone, compared with placebo, in patients with in-hospital cardiac arrest did not improve long-term outcomes in this trial., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Importance: Previous trials have suggested that vasopressin and methylprednisolone administered during in-hospital cardiac arrest might improve outcomes., Objective: To determine whether the combination of vasopressin and methylprednisolone administered during in-hospital cardiac arrest improves return of spontaneous circulation., Design, Setting, and Participants: Multicenter, randomized, double-blind, placebo-controlled trial conducted at 10 hospitals in Denmark. A total of 512 adult patients with in-hospital cardiac arrest were included between October 15, 2018, and January 21, 2021. The last 90-day follow-up was on April 21, 2021., Intervention: Patients were randomized to receive a combination of vasopressin and methylprednisolone (n = 245) or placebo (n = 267). The first dose of vasopressin (20 IU) and methylprednisolone (40 mg), or corresponding placebo, was administered after the first dose of epinephrine. Additional doses of vasopressin or corresponding placebo were administered after each additional dose of epinephrine for a maximum of 4 doses., Main Outcomes and Measures: The primary outcome was return of spontaneous circulation. Secondary outcomes included survival and favorable neurologic outcome at 30 days (Cerebral Performance Category score of 1 or 2)., Results: Among 512 patients who were randomized, 501 met all inclusion and no exclusion criteria and were included in the analysis (mean [SD] age, 71 [13] years; 322 men [64%]). One hundred of 237 patients (42%) in the vasopressin and methylprednisolone group and 86 of 264 patients (33%) in the placebo group achieved return of spontaneous circulation (risk ratio, 1.30 [95% CI, 1.03-1.63]; risk difference, 9.6% [95% CI, 1.1%-18.0%]; P = .03). At 30 days, 23 patients (9.7%) in the intervention group and 31 patients (12%) in the placebo group were alive (risk ratio, 0.83 [95% CI, 0.50-1.37]; risk difference: -2.0% [95% CI, -7.5% to 3.5%]; P = .48). A favorable neurologic outcome was observed in 18 patients (7.6%) in the intervention group and 20 patients (7.6%) in the placebo group at 30 days (risk ratio, 1.00 [95% CI, 0.55-1.83]; risk difference, 0.0% [95% CI, -4.7% to 4.9%]; P > .99). In patients with return of spontaneous circulation, hyperglycemia occurred in 77 (77%) in the intervention group and 63 (73%) in the placebo group. Hypernatremia occurred in 28 (28%) and 27 (31%), in the intervention and placebo groups, respectively., Conclusions and Relevance: Among patients with in-hospital cardiac arrest, administration of vasopressin and methylprednisolone, compared with placebo, significantly increased the likelihood of return of spontaneous circulation. However, there is uncertainty whether this treatment results in benefit or harm for long-term survival., Trial Registration: ClinicalTrials.gov Identifier: NCT03640949.

Objective: To describe the clinical trial "Vasopressin and Methylprednisolone for In-Hospital Cardiac Arrest" (VAM-IHCA)., Methods: The VAM-IHCA trial is an investigator-initiated, multicenter, randomized, placebo-controlled, parallel group, double-blind, superiority trial of vasopressin and methylprednisolone during adult in-hospital cardiac arrest. The study drugs consist of 40 mg methylprednisolone and 20 IU of vasopressin given as soon as possible after the first dose of adrenaline. Additional doses of vasopressin (20 IU) will be administered after each adrenaline dose for a maximum of four doses (80 IU).The primary outcome is return of spontaneous circulation and key secondary outcomes include survival and survival with a favorable neurological outcome at 30 days. 492 patients will be enrolled. The trial was registered at the EU Clinical Trials Register (EudraCT Number: 2017-004773-13) on Jan. 25, 2018 and ClinicalTrials.gov (Identifier: NCT03640949) on Aug. 21, 2018., Results: The trial started in October 2018 and the last patient is anticipated to be included in January 2021. The primary results will be reported after 3-months follow-up and are, therefore, anticipated in mid-2021., Conclusion: The current article describes the design of the VAM-IHCA trial. The results from this trial will help clarify whether the combination of vasopressin and methylprednisolone when administered during in-hospital cardiac arrest improves outcomes., (© 2021 Published by Elsevier B.V.)

Background: Arterial blood gas analysis is an important diagnostic tool in managing critically ill patients within the hospital. Whether prehospital application of this diagnostic modality contributes to more exact diagnoses and treatments in critically ill prehospital patients is unknown. The aim of this study was to establish whether access to arterial blood gas analysis increased the prehospital diagnostic accuracy of prehospital anaesthesiologists. Furthermore, we investigated whether prehospital blood gas analysis resulted in therapeutic interventions that would not have been carried out if the arterial blood gas analyser had not been available., Methods: In a prospective randomised study, two groups of prehospital adult patients with acute critical illness were compared. All patients received standard prehospital care. In the intervention group, an arterial blood gas sample was analysed prehospitally. The primary outcome was the impact of blood gas analysis on the accuracy of prehospital diagnoses. Furthermore, we registered any therapeutic interventions that were carried out as a direct result of the blood gas analysis., Results: A total of 310 patients were included in the study. Eighty-eight of these patients were subsequently excluded, primarily due to difficulties in obtaining post hoc consent or venous sampling or other technical difficulties. A total of 102 patients was analysed in the arterial blood gas group (ABG group), while 120 patients were analysed in the standard care group (noABG group). In 78 of the 102 patients in the ABG group, the prehospital physician reported that ABG analysis increased their perceived diagnostic precision. In 81 cases in the noABG group, the lack of arterial blood gas analysis was perceived to have decreased diagnostic accuracy. The claim that ABG analysis increased diagnostic accuracy could, however, not be substantiated as there was no difference in the number of un-specific diagnoses between the groups. Blood gas analysis increased the probability of targeting specific prehospital therapeutic interventions and led to 159 interventions, including intubation, ventilation and/or upgrading the level of urgency, in 71 ABG-group patients (p < 0.001)., Conclusion: Although prehospital arterial blood gas analysis did not improve the accuracy of the prehospital diagnoses assigned to patients, it significantly increased the quality of treatment provided to patients with acute critical illness., Trial Registration: ClinicalTrials.gov, NCT03006692 , retrospectively registered six months after first patient entry.

Background: Little is known regarding paediatric medical emergency calls to Danish Emergency Medical Dispatch Centres (EMDC). This study aimed to investigate these calls, specifically the medical issues leading to them and the pre-hospital units dispatched to the paediatric emergencies., Methods: We performed a retrospective, observational study on paediatric medical emergency calls managed by the EMDC in the Region of Southern Denmark in February 2016. We reviewed audio recordings of emergency calls and ambulance records to identify calls concerning patients ≤ 15 years. We examined EMDC dispatch records to establish how the medical issues leading to these calls were classified and which pre-hospital units were dispatched to the paediatric emergencies. We analysed the data using descriptive statistics., Results: Of a total of 7052 emergency calls in February 2016, 485 (6.9%) concerned patients ≤ 15 years. We excluded 19 and analysed the remaining 466. The reported medical issues were commonly classified as: "seizures" (22.1%), "sick child" (18.9%) and "unclear problem" (12.9%). The overall most common pre-hospital response was immediate dispatch of an ambulance with sirens and lights with a supporting physician-manned mobile emergency care unit (56.4%). The classification of medical issues and the dispatched pre-hospital units varied with patient age., Discussion: We believe our results might help focus the paediatric training received by emergency medical dispatch staff on commonly encountered medical issues, such as the symptoms and conditions pertaining to the symptom categories "seizures" and "sick child". Furthermore, the results could prove useful in hypothesis generation for future studies examining paediatric medical emergency calls., Conclusion: Almost 7% of all calls concerned patients ≤ 15 years. Medical issues pertaining to the symptom categories "seizures", "sick child" and "unclear problem" were common and the calls commonly resulted in urgent pre-hospital responses.

Introduction: When general practitioners (GPs) order an ambulance, their calls are handled by staff at the emergency medical dispatch centre (EMDC) who then select an appropriate response. There are currently no data evaluating this mode of communication between the GPs and the staff at the EMDC. 
METHODS: A retrospective study was performed based on evaluation of calls during which GPs requested a rapid response ambulance. Over a period of three months of 2014, 1,334 calls were included for evaluation according to specific parameters including a transactional analysis of the communication. 
RESULTS: We found problematic communication in less than 2% (n = 25) of the evaluated calls. In 68% of the 25 problematic cases transactional analysis showed that the staff at the EMDC initiated the problematic communication. In 4% (n = 51) of the calls, the GP delegated the call to a secretary or nurse, and we found that these calls were more likely to contain problematic communication (odds ratio = 5.1). In 18% (n = 236) of the cases, there was not sufficient information to assess if the physician-manned mobile emergency care unit (MECU) should have been dispatched along with the ambulance. 
CONCLUSIONS: Problematic communication is rare, occurring in less than 2% of the calls. Problems are more frequent when the GP delegates the call. Furthermore, we established that the communicative problems were more likely to be initiated by the staff at the EMDC than by the GP. In addition, we found that there was insufficient information to assess if the MECU should be dispatched in nearly 20% of all calls.
 FUNDING: none.
 TRIAL REGISTRATION: The study was approved by the Danish Data Protection Agency (ref. no. 2008-58-0035). Informed consent from individual patients or ethics committee approval was not required since it was a register-based study solely and no person-identifiable data were used., (Articles published in the DMJ are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.)

Objective: Necrotizing fasciitis is a difficult diagnosis with a very high mortality. However, thermal imaging has the potential to identify increasing skin temperature and rapid progression., Materials and Methods: We used repeat photographs taken with a thermal camera to visualize changes in skin temperature over time., Results: An unstable male patient presented at the emergency department. Thermal imaging showed increased skin temperature of his left foot with a rapid increase and progression in extent within 1 hour. Necrotizing fasciitis was suspected and later confirmed., Conclusions: We believe thermal imaging could be an important adjunct for the diagnosis of suspected necrotizing fasciitis., Learning Points: Necrotizing fasciitis is a difficult diagnosis to make.Thermal imaging can visualize skin temperature and thus show increased temperature and extent.Rapid identification of necrotizing fasciitis is vital for patient survival., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interests.

Long-distance athletes are at risk of serious fluid and electrolyte disturbances, such as hypernatraemia (dehydration). Recently, cases of serious morbidity have been reported, due to acute exercise-associated hyponatraemia, which can advance to encephalopathy. An arterial blood gas analysis (ABG) was drawn from collapsed athletes at the championship of full-distance triathlon 2015, and different electrolyte imbalances were found. Our findings show that prehospital ABG can assist in differentiating the cause of collapse, and presumably, targeted treatment can be initiated already on scene.

Objective: To elucidate pain treatment with analgesics in a prehospital trauma population., Design: Retrospective database study., Setting: Prehospital data from the anesthesiologist-manned Mobile Emergency Care Unit (MECU) in Odense, Denmark, were extracted and subjected to analysis., Patients: During the period of January 1, 2013 to December 31, 2014, patients with the diagnoses "unspecified multiple injuries," "examination and observation following traffic accident," "examination and observation following other accident," and "commotio cerebri" were included in the analysis., Main Outcome Measures: Evaluation of the application of the pain scale Numeric Rating Scale (NRS). Furthermore, the authors performed a characterization of the patients with mild pain and severe pain according to specific parameters such as pharmacological interventions, opioid consumption, intubation, and others., Results: Nine hundred eighty-five cases were analyzed. NRS was documented only in one case. In all, 787 patients experienced no pain or mild pain (no pain, n = 242; mild pain, n = 545) and 168 patients severe pain or worse (severe pain, n = 155; intolerable pain, n = 13). In the severe pain group, 138 were treated with opioid analgesics or S-ketamine, while no pharmacological intervention was documented in 30 cases. Eight of the 138 cases with severe pain needed endotracheal intubation, whereas nine cases in the patients with mild or no pain needed endotracheal intubation; odds ratio (OR) 4.3 (p = 0.003)., Conclusions: Effect was only documented in one patient after administering opioids in a patient with trauma population, where approximately 17 percent of patients experienced severe pain. Severe pain was correlated to male gender, respiratory intervention, opioid administration, and the diagnosis unspecified multiple injuries.

Objective: To describe the legal use of opioids in adult patients before and after high-energy trauma., Design: The study was a retrospective database study., Setting: Clinical care outside hospitals., Patients: All patients who suffered high-energy trauma and were brought to Odense University Hospital (OUH), Denmark, in 2007 and 2008 were retrieved from the trauma database. These patients were linked with data on opioid use from the regional prescription database. In all, 938 patients were included., Main Outcome Measure: Redemption of opioid prescription during the 6 months prior to a multitrauma or redemption of two or more prescriptions for opioids 6 months or later after a multitrauma., Results: Of the 938 patients brought to OUH with severe trauma within the study period, 61 patients died (7 percent) and six of these had redeemed prescriptions for opioids within 6 months prior to the trauma (10 percent) compared to 65 patients of the 877 survivors (7 percent) (odds ratio 1.4, nonsignificant). In all, 62 patients (7 percent) redeemed opioid prescriptions later than 6 months after their trauma and in a multivariable analysis, severe injury itself and severe injuries of the lower extremities were associated with redemption of opioid prescription after the trauma., Conclusions: The authors did not find any correlation between death by trauma and redemption of opioid prescriptions within the 6 months before the trauma. More severe traumas and especially severe traumas to the lower extremities were associated with redemption of opioid prescriptions after multitrauma.

Background: Prehospital care provided by specially trained, physician-based emergency services (P-EMS) is an integrated part of the emergency medical systems in many developed countries. To what extent P-EMS increases survival and favourable outcomes is still unclear. The aim of the study was thus to investigate ambulance runs initially assigned 'life-saving missions' with emphasis on long-term outcome in patients treated by the Mobile Emergency Care Unit (MECU) in Odense, Denmark, Methods: All MECU runs are registered in a database by the attending physician, stating, among other parameters, the treatment given, outcome of the treatment and the patient's diagnosis. Over a period of 80 months from May 1 2006 to December 31 2012, all missions in which the outcome of the treatment was registered as 'life saving' were scrutinised. Initial outcome, level of competence of the caretaker and diagnosis of each patient were manually established in each case in a combined audit of the prehospital database, the discharge summary of the MECU and the medical records from the hospital. Outcome parameters were final outcome, the aetiology of the life-threatening condition and the level of competences necessary to treat the patient., Results: Of 25 647 patients treated by the MECU, 701 (2.7%) received prehospital 'life saving treatment'. In 596 (2.3%) patients this treatment exceeded the competences of the attending emergency medical technician or paramedic. Of these patients, 225 (0.9%) were ultimately discharged to their own home., Conclusions: The present study demonstrates that anaesthesiologist administrated prehospital therapy increases the level of treatment modalities leading to an increased survival in relation to a prehospital system consisting of emergency medical technicians and paramedics alone and thus supports the concept of applying specialists in anaesthesiology in the prehospital setting especially when treating patients with cardiac arrest, patients in need of respiratory support and trauma patients., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Purpose: The aim of the study was to search for an association between the single-nucleotide polymorphisms A118G in OPRM1 and C3435T and G2677T/A in ABCB1 and the analgesic effect of intravenous oxycodone in postoperative pain., Methods: There were 268 patients with postoperative pain after, primarily, thyroidectomy. At given times during the first 24 hours postoperatively, their pain was rated at rest and during activity according to a numeric rating scale (0 = no pain, 10 = worst possible pain) and calculated as pain time area under the curve0-24 hours . A negative answer in a final questionnaire and/or the use of rescue medication categorized a patient as a nonresponder., Results: For OPRM1, there was no difference found between the wild type and the variant allele in the percentages of nonresponders (118AA = 16.4% vs 118AG/118GG = 17.0%, P = 1.0) or in the pain ratings. For ABCB1, no difference was found between the wild type and the variant alleles for single-nucleotide polymorphism tested as percentages of nonresponders (3435CC = 17.5% vs 3435CT/3435TT = 15.8%, P = .85; 2677GG = 17.8% vs 2677GT/2677TT = 15.8%, P = .74) or pain ratings., Conclusion: No association was found between the tested single-nucleotide polymorphisms in OPRM1 and ABCB1 and changes in the analgesic effect of oxycodone., (2012 American College of Clinical Pharmacology.)

The aim of this study was to search for a possible association between the variant allele of the single nucleotide polymorphisms A118G in the OPRM1 gene and C3435T and G2677T/A in the ABCB1 gene and altered antinociceptive effect and adverse drug reactions of oxycodone. Thirty-three healthy subjects exposed to experimental pain including electrical stimulation and the cold pressor test were included. A118G: We found that the variant G allele was associated with reduced antinociceptive effect as measured by pain tolerance thresholds to single electrical nerve stimulation (8% increase vs. 25% for the wild-type carriers, P = 0.007). C3435T: The carriers of the variant T allele generally had less adverse drug reactions on oxycodone than the carriers of the wild-type genotype. G2677T/A: The carriers of the variant T allele had a better antinociceptive effect of oxycodone than the carriers of the wild-type genotype in the cold pressor test (25% reduction vs. 15%, P = 0.015 in the discomfort rating and 25% reduction vs. 12%, P = 0.007 in the pain time AUC) and less adverse drug reactions. The combined wild-type genotype 3435CC-2677GG was associated with less antinociceptive effect of oxycodone in the discomfort rating of the cold pressor test (13% reduction vs. 23%, P = 0.019) and more severe adverse drug reactions than the carriers of the variant alleles. We found a moderate association between less antinociceptive effect of oxycodone and the variant allele of A118G. There was strong association between less adverse drug reactions of oxycodone and the variant alleles of C3435T and G2677T/A.

Background The antidepressant drugs imipramine and venlafaxine relieve clinical neuropathic pain and have been shown to increase pain thresholds in healthy volunteers during repetitive electrical sural nerve stimulation causing temporal pain summation, whereas pain during the cold pressor test is unaltered by these drugs. If this pattern of effect in experimental pain models reflects potential efficacy in clinical neuropathic pain, the pain summation model may potentially be used to identify new drugs for such pain conditions. Gabapentinoids are evidence-based treatments of clinical neuropathic pain and could contribute with additional knowledge of the usefulness of the pain summation model. The aim of this study To test the analgesic effect of the gabapentinoid gabapentin in a sural nerve stimulation pain model including temporal pain summation and the cold pressor test. Method 18 healthy volunteers completed a randomized, double-blind, cross-over trial with medication of 600 mg gabapentin orally dosed 3 times over 24 h against placebo. Pain tests were performed before and 24 h after medication including pain detection and tolerance to single sural nerve stimulation and pain summation threshold to repetitive stimulation (3 Hz). Peak pain intensity and discomfort were rated during a cold pressor test. Results Compared to placebo, gabapentin had a highly significant effect on the threshold of pain summation to repetitive electrical sural nerve stimulation (P = 0.009). Gabapentin significantly increased the pain tolerance threshold to single electrical sural nerve stimulation (P = 0.04), whereas the pain detection threshold to single electrical sural nerve stimulation tended to be increased (P = 0.06). No significant differences were found on pain ratings during the cold pressor test. Conclusion Gabapentin had a selective hypoalgesic effect in a human experimental pain model of temporal pain summation and the results lend further support to the usefulness of the pain summation model to identify drugs for neuropathic pain.

Background: Oxycodone is a semi-synthetic opioid with a mu-receptor agonist-mediated effect in several pain conditions, including post-operative pain. Oxycodone is metabolized to its active metabolite oxymorphone by O-demethylation via the polymorphic CYP2D6. The aim of this study was to investigate whether CYP2D6 poor metabolizers (PMs) yield the same analgesia post-operatively from intravenous oxycodone as extensive metabolizers (EMs)., Methods: Two hundred and seventy patients undergoing primarily thyroid surgery or hysterectomy were included and followed for 24 h post-operatively. The CYP2D6 genotype was blinded until study procedures had been completed for all patients. All patients received intravenous oxycodone as pain treatment for 24 h post-operatively and morphine 5 mg was used as escape medication. A responder was characterized as a patient without the need for escape medication and a positive evaluation in a questionnaire 24 h post-operatively., Results: Twenty-four patients were PM (8.9%) and 246 were EM (91.1%). One PM (4.17%, CI=0.1-21.1) was a non-responder and 42 EM (17.07%, CI=12.6-22.4) were non-responders. The non-responder rate did not differ between the two genotypes (P=0.14). There was no difference in the total consumption of oxycodone between the two genotypes (EM=14.7 mg, CI=13.0-16.4 and PM=13.0 mg, CI=8.9-17.0, P=0.42). The mean oxymorphone/oxycodone ratios were 0.0031 and 0.00081 in the EMs and PMs, respectively (P<0.0001)., Conclusion: This study showed for the first time in patients that the oxymorphone formation depends on CYP2D6, but we found no difference in the post-operative analgesic effect of intravenous oxycodone between the two CYP2D6 genotypes.

Tramadol is O-demethylated to the active metabolite (+)-O-desmethyltramadol ((+)-M1) via CYP2D6, an enzyme that is weakly inhibited by escitalopram. We investigated the possibility of a pharmacokinetic (PK) and pharmacodynamic (PD) effect of escitalopram on tramadol metabolism. Fifteen healthy subjects completed this randomized, double-blind, three-phase, crossover trial. Combinations of escitalopram 20 mg/day or placebo together with tramadol 150 mg or placebo were used. Blood samples for pharmacokinetics were drawn at 0-24 h after medication. The analgesic effect of (+)-M was assessed by the cold pressor test (CPT) (area under effect curve, 1-12 h after medication (AUEC(1-12))). The median area under plasma concentration-time curve extrapolated to infinity (AUC(0-infinity)) of (+)-M1 was 2.75 micromol/l.h after placebo pretreatment compared with 1.95 micromol/l.h after escitalopram (P = 0.0027). The mean AUEC(1-12) of CPT were 4,140 and 4,388 cm.s after placebo and escitalopram, respectively (P = 0.71). Although escitalopram is a weak inhibitor of CYP2D6, it does not impair the analgesic effect of tramadol.

Purpose: To investigate the impact of cytochrome P450 2C19 (CYP2C19) phenotypes on escitalopram metabolism and to evaluate pupillometry as a serotonergic biomarker., Methods: This was a double-blind, crossover design study with single and multiple doses of 10 mg escitalopram and placebo in panels of CYP2C19 extensive (EM) and poor metabolisers (PM). Pupillometry was measured by a NeurOptics Pupillometer-PLR., Results: Five PM and eight EM completed the study. The CYP2C19 phenotype significantly affected the metabolism of escitalopram. The area under the time-plasma concentration curve (AUC(0-24)) was 1.8-fold higher in PM than in EM after both single and multiple doses. Escitalopram treatment did not affect the maximum pupil size, but it did statistically significantly decrease the relative amplitude of the pupil light reflex compared to the placebo; this effect was equal in both phenotype groups., Conclusions: The CYP2C19 polymorphism affects escitalopram metabolism, but the difference does not justify dose adjustment. The puzzling results from pupillometry can be due to interplay between a central and a local serotonergic effect. Based on these results, pupillometry can not be recommended as a serotonergic biomarker.

Oxycodone is O-demethylated by CYP2D6 to oxymorphone which is a potent micro-receptor agonist. The CYP2D6 oxidation polymorphism divides the Caucasian population in two phenotypes: approximately 8% with no enzyme activity, poor metabolizers (PM) and the remainder with preserved CYP2D6 activity, extensive metabolizers (EM). The objective of the study was to determine if the analgesic effect of oxycodone in human experimental pain depends on its metabolism to oxymorphone. The analgesic effect of oxycodone was evaluated in a randomized, placebo-controlled, double-blinded, crossover experiment including 33 (16 EM and 17 PM) healthy volunteers. Pain tests were performed before and 1, 2, 3 and 4 hr after medication and included pain detection and tolerance thresholds to single electrical sural nerve stimulation, pain summation threshold to repetitive electrical sural nerve stimulation and the cold pressor test with rating of discomfort and pain-time area under curve (AUC(0-2 min.)). For single sural nerve stimulation, there was a less pronounced increase in thresholds on oxycodone in pain detection (9% vs. 20%, P = 0.02, a difference of 11%, CI: 2%-20%) and pain tolerance thresholds (15% vs. 26%, P = 0.037, a difference of 10%, CI: 1%-20%) for PM compared with EM. In the cold pressor test, there was less reduction in pain AUC on oxycodone for PM compared with EM (14% vs. 26%, P = 0.012, a difference of 12%, CI: 3%-22%). The plasma oxymorphone/oxycodone ratio was significantly lower in PM compared with EM (P < 0.001). Oxycodone analgesia seems to depend both on oxycodone itself and its metabolite oxymorphone.