Vasopressin and methylprednisolone and hemodynamics after in-hospital cardiac arrest - A post hoc analysis of the VAM-IHCA trial.

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.

Effect of vasopressin and methylprednisolone vs. placebo on long-term outcomes in patients with in-hospital cardiac arrest a randomized clinical trial.

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.

First description of Onchocerca flexuosa infections in Danish red deer (Cervus elaphus).

The prevalence of Onchocerca infection in wild cervids from Denmark was studied in 119 fallow deer (Dama dama), 123 red deer (Cervus elaphus), 51 roe deer (Capreolus capreolus) and eight sika deer (Cervus Nippon) shot during the hunting season from October 2017 to January 2018 from 18 geographical locations across Denmark. The carcasses were macroscopic checked for nodules, and skin samples were examined for microfilaria. All roe deer, fallow deer and sika deer were negative for Onchocerca, while 30.9% red deer were positive for either microfilaria, nodules or both. Significantly more adult red deer (50.8%; 37.6-62.4; p < 0.0001) were infected with Onchocerca than juveniles <1 year (7.8%; 2.1-18.5), while there was an insignificant (p = 0.075) difference in prevalence observed between males (17.4%; 7.8-31.4) and females (41.7%; 30.2-53.9). Onchocerca-positive red deer were observed from 91.7% (11/12) of the sampled geographical locations. Species identification was done on adult worms from nodules taken from the lumbar region of 20 red deer of different geographical origin by sequencing the mitochondrial 12S, 16S and nad5 gene fragments. The sequences matched with previously published sequences for Onchocerca flexuosa. The high prevalence of Onchocerca infection caused by O. flexuosa in red deer in Denmark shows that Denmark has favourable vector conditions and a suitable environment for the maintenance of the parasite. To our knowledge, this is the first systematic study of Onchocerca in wild-living cervids in Denmark.

Effect of Vasopressin and Methylprednisolone vs Placebo on Return of Spontaneous Circulation in Patients With In-Hospital Cardiac Arrest: A Randomized Clinical Trial.

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.

Vasopressin and methylprednisolone for in-hospital cardiac arrest - Protocol for a randomized, double-blind, placebo-controlled trial.

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.

Diagnostic value of prehospital arterial blood gas measurements - a randomised controlled trial.

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.

Prevalence of Capillaria plica in Danish wild carnivores.

Capillaria plica is a parasitic nematode belonging to the family Capillariidae. The adult parasites reside in the urinary tract of wild and domestic canines. The infection is most often asymptomatic, but can cause a wide range of symptoms including urinary bladder inflammation, pollacisuria, dysuria and hematuria. Canines acquire the infection by ingesting the intermediate host, the earthworm (Lumbricidae). Epidemiological studies on C. plica infection in wildlife are few and only one previous Danish study examined the prevalence in red foxes, while studies on prevalence in other animals are limited. We examined the urine sediment or urinary bladder from 375 Raccoon dogs (Nyctereutes procyonoides), 247 red foxes (Vulpes vulpes), 20 beech martens (Martes foina), 16 wild mink (Neovison vison), 14 otters (Lutra lutra), nine European polecats (Mustela putorius), three European badgers (Meles meles) and one golden jackal (Canis aureus) received as a part of Danish wildlife surveillance. Capillaria plica was detected in 73.7% of red foxes, 20.0% of beech martens, 0.5% of raccoon dogs, and in the Golden jackal. Red foxes originating from all 5 regions of Denmark were infected, although with a significantly higher prevalence in the three regions in Jutland compared to Region Zealand.

Evaluating the Feasibility of DNA Methylation Analyses Using Long-Term Archived Brain Formalin-Fixed Paraffin-Embedded Samples.

We here characterize the usability of archival formalin-fixed paraffin-embedded (FFPE) brain tissue as a resource for genetic and DNA methylation analyses with potential relevance for brain-manifested diseases. We analyzed FFPE samples from The Brain Collection, Aarhus University Hospital Risskov, Denmark (AUBC), constituting 9479 formalin-fixated brains making it one of the largest collections worldwide. DNA extracted from brain FFPE tissue blocks was interrogated for quality and usability in genetic and DNA methylation analyses by different molecular techniques. Overall, we found that DNA quality was inversely correlated with storage time and DNA quality was insufficient for Illumina methylation arrays; data from methylated DNA immunoprecipitation, clonal bisulfite sequencing, and pyrosequencing of BDNF and ST6GALNAC1 suggested that the original methylation pattern is indeed preserved. Proof-of-principle experiments predicting sex based on the methylation status of the X-inactivated SLC9A7 gene, or genotype differences of the Y and X chromosomes, showed consistency between predicted and actual sex for a subset of FFPE samples. In conclusion, even though DNA from FFPE samples is of low quality and technically challenging, it is likely that a subset of samples can provide reliable data given that the methodology used is designed for small DNA fragments. We propose that simple PCR-based quality control experiments at the genetic and DNA methylation level, carried out at the beginning of any given project, can be used to enrich for the best-performing FFPE samples. The apparent preservation of genetic and DNA methylation patterns in archival FFPE samples may bring along new perspectives for the identification of genetic and epigenetic changes associated with brain-manifested diseases.

[Prehospital arterial blood gas analysis after collapse connected to triathlon participation].

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.

Single-molecule detection of dihydroazulene photo-thermal reaction using break junction technique.

Charge transport by tunnelling is one of the most ubiquitous elementary processes in nature. Small structural changes in a molecular junction can lead to significant difference in the single-molecule electronic properties, offering a tremendous opportunity to examine a reaction on the single-molecule scale by monitoring the conductance changes. Here, we explore the potential of the single-molecule break junction technique in the detection of photo-thermal reaction processes of a photochromic dihydroazulene/vinylheptafulvene system. Statistical analysis of the break junction experiments provides a quantitative approach for probing the reaction kinetics and reversibility, including the occurrence of isomerization during the reaction. The product ratios observed when switching the system in the junction does not follow those observed in solution studies (both experiment and theory), suggesting that the junction environment was perturbing the process significantly. This study opens the possibility of using nano-structured environments like molecular junctions to tailor product ratios in chemical reactions.

A Study of Electrocyclic Reactions in a Molecular Junction: Mechanistic and Energetic Requirements for Switching in the Coulomb Blockade Regime.

Molecular photoswitches incorporated in molecular junctions yield the possibility of light-controlled switching of conductance due to the electronic difference of the photoisomers. Another isomerization mechanism, dark photoswitching, promoted by a voltage stimulus rather than by light, can be operative in the Coulomb blockade regime for a specific charge state of the molecule. Here we elucidate theoretically the mechanistic and thermodynamic restrictions for this dark photoswitching for donor-acceptor substituted 4n and 4n+2 π-electron open-chain oligoenes (1,3-butadiene and 1,3,5-hexatriene) by considering the molecular energies and orbitals of the molecules placed in a junction. For an electrocyclic ring closure reaction to occur for these compounds, we put forward two requirements: a) the closed stereoisomer (cis or trans form) must be of lower energy than the open form, and b) the reaction pathway must be in accordance to the orbital symmetry rules expressed by the Woodward-Hoffmann rules (when the electrodes do not significantly alter the molecular orbital appearances). We find these two requirements to be valid for the dianion of (1E,3Z,5E)-hexa-1,3,5-triene-1,6-diamine, and the Coulomb blockade diamonds were therefore modeled for this compound to elucidate how a dark photoswitching event would manifest itself in the stability plot. From this modeling of conductance as a function of gate and bias potentials, we predict a collapse in Coulomb diamond size, that is, a decrease in the height of the island of zero conductance.

Predicting transport regime and local electrostatic environment from Coulomb blockade diamond sizes.

Electron transport through a molecule is often described in one of the two regimes: the coherent tunnelling regime or the Coulomb blockade regime. The twilight zone of the two regimes still possesses many unsolved questions. A theoretical analysis of the oligophenylenevinylene OPV3 experiments by Bjørnholm and co-workers is performed. The experiments showed how two OPV3 derivatives performed very differently despite the strong similarity of the molecular structure, hence the experimental data showed two different transport mechanisms. The different transport mechanisms of the two OPV3 derivatives are explained from quantum mechanical calculations of the molecular redox energies and from the experimentally accessible window size.

Theoretical Investigation of Substituent Effects on the Dihydroazulene/Vinylheptafulvene Photoswitch: Increasing the Energy Storage Capacity.

We have investigated the effects of substituents on the properties of the dihydroazulene/vinylheptafulvene photoswitch. The focus is on the changes of the thermochemical properties by placing electron withdrawing and donating groups on the monocyano and dicyano structures of the parent dihydroazulene and vinylheptafulvene compounds. We wish to increase the energy storage capacity, that is, the energy difference between the dihydroazulene and vinylheptafulvene isomers, of the photoswitch by computational molecular design and have performed over 9000 electronic structure calculations using density functional theory. Based on these calculations, we obtain design rules for how to increase the energy storage capacity of the photoswitch. Furthermore, we have investigated how the activation energy for the thermally induced vinylheptafulvene to dihydroazulene conversion depends on the substitution pattern, and based on these results, we have outlined molecular design considerations for obtaining new desired target structures exhibiting long energy storage times. Selected candidate systems have also been investigated in terms of optical properties to elucidate how sensitive the absorption maxima are to the functionalizations.

Assessment of acute pain in trauma-A retrospective prehospital evaluation.

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.

Boron Subphthalocyanine Based Molecular Triad Systems for the Capture of Solar Energy.

In this study a number of chromophores based on boron subphthalocyanines are investigated for use in the future design of organic photovoltaic devices based on molecular triad systems. The computational study is performed at the TD-DFT CAM-B3LYP/6-311G(d) level of theory. The absorption spectra of these chromophores are simulated using TD-DFT and compared to experimental results. All investigated chromophores absorb light in the visible range and thus are suitable for absorption of sunlight in solar cell applications. On the basis of energy-level alignments, suitable combinations of moieties for a molecular triad system are proposed. The molecular triads will be used in future work as the functional part of organic photovoltaic devices, where the chromophore will be used both to absorb the incoming solar radiation and to increase the distance between the separated charges on donor and acceptor units to increase the lifetime of the charge-separated state.

First hyperpolarizability of para-aminoaniline induced by a variety of gold nano particles.

Molecules exposed to an electromagnetic field due to the presence of nearby nanoparticles are known to be affected. The nonlinear response of the molecular system, the first hyperpolarizability, is investigated for 4-nitroaniline (PNA) in a variety of different nanoparticle environments. In order to introduce different molecular environments the quantum mechanical-molecular mechanics DFT/MM response method was utilized for calculating the electromagnetic properties of the molecule interacting with the nanoparticles and the frequency dependent electromagnetic fields. We clearly show that the metal nanoparticles are able to influence the first hyperpolarizability of the molecule, and that the influence strongly depends on the chosen molecular environment. It is found that the first hyperpolarizability of the molecule strongly depends on the distance and orientation to the nanoparticles, whereas the size of the nanoparticles is of little importance when a sufficiently sized nanoparticle is used for representing a bulk metal cluster. Especially, the different orientations of the nanoparticles with respect to the molecule show the chemical effect of different functional groups, since the nonlinear response is significantly larger for the electron withdrawing group pointing towards the nanoparticle.

Azulenium chemistry: towards new derivatives of photochromic dihydroazulenes.

Here we present the preparation of a selection of azulenium ions by hydride abstraction from photochromic 1,8a-dihydroazulenes (1,8a-DHAs) incorporating two cyano groups at C-1. The reactivity of the electrophilic tropylium ring of these molecules towards lithium triisopropylsilylacetylide was investigated. The position of attack by the nucleophile depended on the substitution pattern of the azulenium cation but was in general found to occur preferentially at positions C-4, C-5, and C-6, and to a minor extent at positions C-7 and C-8. The outcome was a mixture of non-photochromic, regioisomeric DHAs. One of these compounds containing the ethynyl substituent at position C-4 was partly tautomerized to the photochromic 1,8a-dihydroazulene, which was isolated and its switching properties were investigated by UV-Vis absorption spectroscopy. Upon irradiation, it undergoes a ring-opening reaction to form a vinylheptafulvene (VHF), which in turn returns to the original DHA. The half-life of this reaction was significantly smaller than for a derivative with the alkynyl substituent placed at C-7. This fast switching behavior was according to the calculations explained by an enhancement in the stability of the reactive s-cis conformer of the VHF relative to the, still more stable, s-trans conformer, and by a smaller activation energy for this s-cis conformer to undergo ring-closure.

Tracking molecular resonance forms of donor-acceptor push-pull molecules by single-molecule conductance experiments.

The ability of molecules to change colour on account of changes in solvent polarity is known as solvatochromism and used spectroscopically to characterize charge-transfer transitions in donor-acceptor molecules. Here we report that donor-acceptor-substituted molecular wires also exhibit distinct properties in single-molecule electronics under the influence of a bias voltage, but in absence of solvent. Two oligo(phenyleneethynylene) wires with donor-acceptor substitution on the central ring (cruciform-like) exhibit remarkably broad conductance peaks measured by the mechanically controlled break-junction technique with gold contacts, in contrast to the sharp peak of simpler molecules. From a theoretical analysis, we explain this by different degrees of charge delocalization and hence cross-conjugation at the central ring. Thus, small variations in the local environment promote the quinoid resonance form (off), the linearly conjugated (on) or any form in between. This shows how the conductance of donor-acceptor cruciforms is tuned by small changes in the environment.

Opioid prescriptions before and after high-energy trauma.

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.