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Coma is a medical and socioeconomic emergency. Although underfunded, research on coma and disorders of consciousness has made impressive progress. Lesion-network-mapping studies have delineated the precise brainstem regions that consistently produce coma when damaged. Functional neuroimaging has revealed how mechanisms like "communication through coherence" and "inhibition by gating" work in synergy to enable cortico-cortical processing and how this information transfer is disrupted in brain injury. On the cellular level, break-down of intracellular communication between the layer 5 pyramidal cell soma and the apical dendritic part impairs dendritic information integration, with up-stream effects on microcircuits in local neuronal populations and on large-scale fronto-parietal networks, which correlates with loss of consciousness. A breakthrough in clinical concepts occurred when fMRI, and later EEG, studies revealed that 15% of clinically unresponsive patients in acute and chronic settings are in fact awake and aware, as shown by their command following abilities revealed by brain activation during motor and locomotion imagery tasks. This condition is now termed "cognitive motor dissociation." Furthermore, epidemiological data on coma were literally non-existent until recently because of difficulties related to case ascertainment with traditional methods, but crowdsourcing of family observations enabled the first estimates of how frequent coma is in the general population (pooled annual incidence of 201 coma cases per 100,000 population in the UK and the USA). Diagnostic guidelines on coma and disorders of consciousness by the American Academy of Neurology and the European Academy of Neurology provide ambitious clinical frameworks to accommodate these achievements. As for therapy, a broad range of medical and non-medical treatment options is now being tested in increasingly larger trials; in particular, amantadine and transcranial direct current stimulation appear promising in this regard. Major international initiatives like the Curing Coma Campaign aim to raise awareness for coma and disorders of consciousness in the public, with the ultimate goal to make more brain-injured patients recover consciousness after a coma. To highlight all these accomplishments, this paper provides a comprehensive overview of recent progress and future challenges related to understanding, detecting, and stimulating consciousness recovery in the ICU.

Coated activated charcoal haemoperfusion (CAC-HP) is a well-known treatment modality. Case reports have revealed conflicting results about the efficacy of CAC-HP in the treatment of amitriptyline (AT) poisoning, and no randomized clinical trials have been identified in the literature. This study aimed at quantifying the efficacy of modern CAC-HP as an adjunctive treatment of AT intoxication compared with standard care alone. Fourteen female Danish landrace pigs were randomized to either standard care or standard care plus 4 hr of CAC-HP. The pigs were anaesthetized, and vital parameters were continuously recorded. Amitriptyline infusion (7.5 mg/kg) was completed in 20 min. Thirty minutes after AT infusion, activated charcoal was instilled orally in both groups. In the intervention group, CAC-HP was initiated 60 min. after AT infusion. Blood and urine samples were collected as were vital parameters at specific time intervals. The protocol was approved by the Danish Experimental Animal Expectorate and complied with the NIH guide for care and use of laboratory animals. Data were managed according to the ARRIVE guidelines. No statistical significant differences between intervention and control groups were found when analysing for differences in AT levels in plasma at any time-point. Furthermore, significant differences between the control and intervention groups in regard to vital parameters could not be found either. In our animal model, the addition of CAC-HP did not improve the clearance of AT compared with standard treatment alone. We suggest that the effect of modern CAC-HP as a treatment modality in AT-poisoned human patients may be inadequate.

Amitriptyline poisoning (AT) is a common poisoning, and AT possess the ability to promote life-threatening complications by its main action on the central nervous and cardiovascular systems. The pharmacokinetic properties might be altered at toxic levels compared to therapeutic levels. The effect of coated activated charcoal hemoperfusion (CAC-HP) on the accumulation of AT and its active metabolite nortriptyline (NT) in various tissues was studied in a non-blinded randomized controlled animal trial including 14 female Danish Land Race piglets. All piglets were poisoned with amitriptyline 7.5 mg/kg infused in 20 min, followed by orally instilled activated charcoal at 30 min after infusion cessation. The intervention group received 4 h of CAC-HP followed by a 1-h redistribution phase. At study cessation, the piglets were euthanized, and within 20 min, vitreous fluid, liver tissue, ventricle and septum of the heart, diaphragm and lipoic and brain tissues were collected. AT and NT tissue concentrations were quantified by UHPLC-MS/MS. A 4-h treatment with CAC-HP did not affect the tissue accumulation of AT in the selected organs when tested by Mann-Whitney U test (p values between 0.44 and 0.73). For NT concentrations, p values were between 0.13 and 1.00. Although not significant, an interesting finding was that data showed a tendency of increased tissue accumulation of AT and NT in the CAC-HP group compared with the control group. Coated activated charcoal hemoperfusion does not significantly alter the tissue concentration of AT and NT in the AT-poisoned piglet.

BACKGROUND: Animal models of serious infection suggest that 24 h of induced hypothermia improves circulatory and respiratory function and reduces mortality. We tested the hypothesis that a reduction of core temperature to 32-34°C attenuates organ dysfunction and reduces mortality in ventilator-dependent patients with septic shock.METHODS: In this randomised, controlled, open-label trial, we recruited patients from ten intensive care units (ICUs) in three countries in Europe and North America. Inclusion criteria for patients with severe sepsis or septic shock were a mean arterial pressure of less than 70 mm Hg, mechanical ventilation in an ICU, age at least 50 years, predicted length of stay in the ICU at least 24 h, and recruitment into the study within 6 h of fulfilling inclusion criteria. Exclusion criteria were uncontrolled bleeding, clinically important bleeding disorder, recent open surgery, pregnancy or breastfeeding, or involuntary psychiatric admission. We randomly allocated patients 1:1 (with variable block sizes ranging from four to eight; stratified by predictors of mortality, age, Acute Physiology and Chronic Health Evaluation II score, and study site) to routine thermal management or 24 h of induced hypothermia (target 32-34°C) followed by 48 h of normothermia (36-38°C). The primary endpoint was 30 day all-cause mortality in the modified intention-to-treat population (all randomly allocated patients except those for whom consent was withdrawn or who were discovered to meet an exclusion criterion after randomisation but before receiving the trial intervention). Patients and health-care professionals giving the intervention were not masked to treatment allocation, but assessors of the primary outcome were. This trial is registered with ClinicalTrials.gov, number NCT01455116.FINDINGS: Between Nov 1, 2011, and Nov 4, 2016, we screened 5695 patients. After recruitment of 436 of the planned 560 participants, the trial was terminated for futility (220 [50%] randomly allocated to hypothermia and 216 [50%] to routine thermal management). In the hypothermia group, 96 (44·2%) of 217 died within 30 days versus 77 (35·8%) of 215 in the routine thermal management group (difference 8·4% [95% CI -0·8 to 17·6]; relative risk 1·2 [1·0-1·6]; p=0·07]).INTERPRETATION: Among patients with septic shock and ventilator-dependent respiratory failure, induced hypothermia does not reduce mortality. Induced hypothermia should not be used in patients with septic shock.FUNDING: Trygfonden, Lundbeckfonden, and the Danish National Research Foundation.

Coated activated charcoal haemoperfusion (CAC-HP) does not reduce the plasma concentration in amitriptyline (AT)-poisoned pigs. The aim of this non-blinded, randomized, controlled animal trial was to determine if CAC-HP reduces the pathological ECG changes caused by AT poisoning. Fourteen female Danish Landrace pigs (mean weight 27.7 kg, range 20-35 kg (CAC-HP) and 24.4 kg, range 18-30 kg (control group, CG), n = 7 in each group) were included. After randomization, the pigs were anaesthetized and intravenously poisoned with AT. The intervention group underwent 4 hr of CAC-HP plus standard care (oral activated charcoal). Intervention was compared to standard care alone. From each pig, a 12-lead ECG and haemodynamic variables were obtained at baseline, at full AT loading dose, before and during CAC-HP. Baseline ECG variables (RR, PR, QRS, QTc, QTp, QTe, TpTe and TpTe/QT) for lead II, v2 and v5 were not significantly different (F = 0.035-0.297, p-values 0.421-0.919). Differences within groups over time and between groups were tested by anova repeated measures. For all variables, the time-plus-group level of significance revealed a p-value > 0.05. Severe cardiovascular arrhythmias occurred in both groups with 3 in the CAC-HP group versus 1 incident with premature death in the CG. The attenuating effect of CAC-HP to orally instilled activated charcoal alone on AT-induced ECG alterations did not differ significantly. We conclude that the use of modern CAC-HP as an adjunctive treatment modality in AT-poisoned pigs is inadequate.

To study the use and misuse (poisonings) of baclofen in the time period of 2007-2012 and to evaluate the severity and clinical symptoms of poisonings including ingested baclofen. The National Patient Register (NPR) was searched for admissions due to baclofen poisonings from 2007 to 2012. The search was conducted with ICD-10 codes for poisoning, self-harm and suicide, and coupled with the baclofen ATC code. All enquiries about baclofen to the Danish Poison Information Centre (DPIC) in the same period were evaluated. Demographic and clinical data were extracted, and the poisonings were classified according to the Poison Severity Score. The number of baclofen poisonings did not increase from 2007 to 2012. Thirty-eight admissions with baclofen poisoning were registered at the NPR; however, only one-third of the reviewed DPIC cases were registered at the NPR with the correct coding. In the group of severely poisoned patients (PSS 3), three patients had only ingested baclofen (mean 2000 mg; SD 500 mg) and eight patients had ingested baclofen together with alcohol or psychotropic drugs (mean 900 mg; SD 641 mg). All patients presented with deep coma and respiratory depression. Additionally, seizures and cardiovascular events (mild hypo- or hypertension and bradycardia) occurred. There is a substantial degree of underreporting of baclofen poisonings in Denmark. Symptoms of baclofen poisoning progress very fast, and toxicity was observed even with doses as low as 150 mg. We therefore recommend that observation and treatment of these patients should be carried out in an intermediate- or intensive care unit. The most important treatment is the maintenance of a protected airway and respiration.

We present a rare case of subacute fat-embolism-like syndrome (FES-like) following intravascular injection of mineral oil-steroid solution with delayed diagnosis, acute onset of pulmonary distress, and transient clinical deterioration.A 40-year-old man was admitted following as a pedestrian being hit by a car. Examinations revealed sternum fracture and lung contusion. The patient was discharged with oral analgesics. Seven days later he returned presenting with coughing, hemoptysis, elevated leucocytes, and increased C-reactive protein. Chest radiograph revealed basal infiltrations. Suspecting pneumonia, the patient was discharged with antibiotics. Unknown to the clinicians, the patient had self-administered a mineral oil with added anabolic steroids by intramuscular injections for cosmetic purposes. The patient had observed blood on aspiration, and then relocated the needle before injecting 140 ml in his biceps muscle. Shortly after, the patient described near fainting and hemoptysis suggesting an accidental intravascular injection. Over the next 3 days the patient experienced increasing shortness of breath and hemoptysis. Examinations confirmed the diagnosis and the patient was treated with organ-specific supportive measures, tranexamic acid, and prednisolone and discharged after 11 days in the hospital.Subacute FES-like was associated with injection of body filler in muscle tissue. FES-like can mimic pneumonia, posttraumatic lung injury, and other more frequent causes to respiratory failure.

This article describes the structure of the research training module, as a part of the education programme for anaesthesiologists in the eastern region of Denmark. The module consists of courses, independent work on a project, guidance and evaluation. In a period of about four years a total of 56 anaesthesiologists have completed the programme. A questionnaire revealed that 59% felt their abilities to read and interpret research had been improved and 30% reported an increasing interest in research. 40% had presented their project at scientific meetings and 25% had published their project.

We aimed to evaluate the feasibility and safety of using Nitrox 50 as breathing gas during attendance in a multiplace hyperbaric chamber.Paper logs between Jan.-Dec. 2011 were reviewed to analyze nitrogen gas-loading, actual bottom time, total bottom time and surface interval time. With the use of the Norwegian Diving Tables nitrogen gas-loading was converted to Repetitive Group Letters. Symptoms of decompression sickness and health problems related to hyperbaric exposures were registered at weekly staff meetings. The chamber personnel breathed chamber air or Nitrox 50.1,207 hyperbaric exposures were distributed to five chamber attendants and technicians, 14 doctors, and six nurses. Nitrox 50 was inhaled on 978 occasions (81.0%). Median nitrogen gas-loading after first pressurization complied with Repetitive Group Letter A (range A-E), second to C (range A-F), third to D (range A-F), fourth to E (range C-H), fifth to F (range C-H), and sixth to E (range B-G). No symptoms of decompression sickness were reported (95% CI 0.00-0.33%).Breathing Nitrox 50 during repetitive hyperbaric sessions seems to be feasible and safe while meeting high demands in number of treatment sessions and patient flow and with fewer people employed in the hyperbaric unit.

The ability of transversus abdominis plane (TAP) blocks to anesthetize the upper abdomen remains debatable. We aimed to describe the local anesthetic distribution following ultrasound-guided TAP blocks with repeated magnetic resonance imaging investigations and to relate this to the resulting dermatomal anesthesia.Eight volunteers were included in a randomized, observer-blinded study. Sixty milliliters of ropivacaine 0.375% was administered: 1 injection of 30 mL as a lateral classic TAP block, followed by a sham upper intercostal TAP block, and on the contralateral side, 2 separate 15-mL injections at the upper intercostal and lateral classic TAP plexuses, respectively. The primary outcome measure was magnetic resonance imaging-assessed area expansion of all injectates over a 6-hr period. Dermatomal anesthesia and sequential serum ropivacaine levels were recorded at the same time intervals.All injectate areas expanded in a statistically significant manner in the anterior abdominal wall. Lateral classic TAP blocks with 30-mL injectates did not extend into the upper intercostal TAP plexus. The dual 15-mL injectates on the other hemiabdomen remained within the upper intercostal and lateral classic TAP compartments and resulted in significantly (P0.018) more widespread dermatomal anesthesia. Measured serum ropivacaine concentrations were below the potential level of toxicity.Magnetic resonance imaging analysis revealed a significant time-dependent expansion of injectates. Magnetic resonance imaging and the degree of dermatomal anesthesia confirmed that the upper and lateral TAP compartments do not appear to communicate. Separate injections at the upper intercostal and lateral classic TAP plexuses are necessary to block the entire abdominal wall.

Twice a young man was admitted to hospital upon having taken baclofen overdoses by intention. The ingested dose was 1,850 mg at the first episode and up to 2,500 mg at the second. In both cases the patient had severe overdose symptoms and scored 4-5 on the Glascow Coma Scale and was admitted to intensive care. Continuous venovenous hemodiafiltration (CVVHDF) was initiated. The elimination pharmacokinetics and toxicokinetics for baclofen is not fully known. During the second submission a shorter elimination half-life time was observed and it might be due to either compartmental distribution of baclofen, or more likely caused by an advantageous effect of the CVVHDF.