The incidence of psychoactive substances and alcohol among impaired drivers in Denmark in 2015-2019.

This study examines the presence of psychoactive drugs and alcohol in blood from apprehended drivers driving under the influence of drugs (DUID) and alcohol in Denmark in a five-year period from 2015 to 2019. Data were analysed with respect to gender, age, substances with concentrations above the Danish legal limit, arresting time of day and repeat arrest. By request of the police, the blood samples were subjected to analysis for alcohol and/or tetrahydrocannabinol (THC) alone, for "other drugs" (covering all drugs including new psychoactive substances (NPS), except THC, listed in the Danish list of narcotic drugs) or for both THC and other drugs. About the same number of alcohol traffic cases (37,960) and drug traffic cases (37,818) were submitted for analysis for the five-year period. The number of drug traffic cases per year increased from 5660 cases in 2015 to 9505 cases in 2019, while the number of alcohol traffic cases per year (average, 7600) was unchanged. Ethanol (89.2%) was the overall most frequent single substance, followed by THC (68.2%). CNS stimulants (46.8%) were the second most prevalent group of non-alcoholic drugs. Cocaine (23.8%) and amphetamine (22.9%) were the most frequent CNS stimulants. The proportion of CNS-stimulant positive drivers more than doubled in ten years. Benzodiazepines/z-hypnotics (12.7%) were the third most prevalent drug group detected, with clonazepam (8%) as the most frequent drug. Opioids were above the legal limit in 9.8% of the cases. NPS was above the legal limit in 128 cases (0.6%). Poly-drug use occurred in 40% of the DUID cases in the requested groups: other drug or other drug/THC. Young males dominated the DUID cases (median age 26). Drink-drivers (median age 39) were also mainly men, but the age distribution was equally spread over the age groups. Re-arrest occurred more often in DUID drivers (18-29%) than in drinking drivers (6-12%). DUID was evenly spread over the week, while drink-driving was most frequent on weekends. This study is an important supplement to the knowledge of drug use in Denmark. It was the well-known psychoactive substances that were detected. Only a few NPS occurred. However, the abuse pattern has changed, and CNS stimulants now account for a much higher proportion than earlier. Our results indicate a drug use problem among DUID drivers. This gives rise to concern because of a risk of traffic accidents. Treating the underlying abuse problem is therefore recommended, rather than focusing solely on prosecuting.

Higher vs lower doses of dexamethasone in patients with COVID-19 and severe hypoxia (COVID STEROID 2) trial: Protocol and statistical analysis plan.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has resulted in millions of deaths and overburdened healthcare systems worldwide. Systemic low-dose corticosteroids have proven clinical benefit in patients with severe COVID-19. Higher doses of corticosteroids are used in other inflammatory lung diseases and may offer additional clinical benefits in COVID-19. At present, the balance between benefits and harms of higher vs. lower doses of corticosteroids for patients with COVID-19 is unclear. METHODS: The COVID STEROID 2 trial is an investigator-initiated, international, parallel-grouped, blinded, centrally randomised and stratified clinical trial assessing higher (12 mg) vs. lower (6 mg) doses of dexamethasone for adults with COVID-19 and severe hypoxia. We plan to enrol 1,000 patients in Denmark, Sweden, Switzerland and India. The primary outcome is days alive without life support (invasive mechanical ventilation, circulatory support or renal replacement therapy) at day 28. Secondary outcomes include serious adverse reactions at day 28; all-cause mortality at day 28, 90 and 180; days alive without life support at day 90; days alive and out of hospital at day 90; and health-related quality of life at day 180. The primary outcome will be analysed using the Kryger Jensen and Lange test adjusted for stratification variables and reported as adjusted mean differences and median differences. The full statistical analysis plan is outlined in this protocol. DISCUSSION: The COVID STEROID 2 trial will provide evidence on the optimal dosing of systemic corticosteroids for COVID-19 patients with severe hypoxia with important implications for patients, their relatives and society.

Perspectives on the fellowship training in cardiac, thoracic, and vascular anesthesia and critical care in Europe from program directors and educational leads around europe

ABSTRACT:This article reviews fellowship training in adult cardiac, thoracic, and vascular anesthesia and critical care from the perspective of European program initiators and educational leaders in these subspecialties together with current training fellows. Currently, the European Association of Cardiothoracic Anaesthesiology (EACTA) network has 20 certified fellowship positions each year in 10 hosting centers within 7 European countries, with 2 positions outside Europe (São Paulo, Brazil). Since 2009, 42 fellows have completed the fellowship training. The aim of this article is to provide an overview of the rationale, requirements, and contributions of the fellows, in the context of the developmental progression of the EACTA fellowship in adult cardiac, thoracic, and vascular anesthesia and critical care from inception to present. A summary of the program structure, accreditation of host centers, requirements to join the program, teaching and assessment tools, certification, and training requirements in transesophageal electrocardiography is outlined. In addition, a description of the current state of EACTA fellowships across Europe, and a perspective for future steps and challenges to the educational program, is provided. (AU)

Intensive care doctors' preferences for arterial oxygen tension levels in mechanically ventilated patients.

BACKGROUND: Oxygen is liberally administered in intensive care units (ICUs). Nevertheless, ICU doctors' preferences for supplementing oxygen are inadequately described. The aim was to identify ICU doctors' preferences for arterial oxygenation levels in mechanically ventilated adult ICU patients. METHODS: In April to August 2016, an online multiple-choice 17-part-questionnaire was distributed to 1080 ICU doctors in seven Northern European countries. Repeated reminder e-mails were sent. The study ended in October 2016. RESULTS: The response rate was 63%. When evaluating oxygenation 52% of respondents rated arterial oxygen tension (PaO2 ) the most important parameter; 24% a combination of PaO2 and arterial oxygen saturation (SaO2 ); and 23% preferred SaO2 . Increasing, decreasing or not changing a default fraction of inspired oxygen of 0.50 showed preferences for a PaO2 around 8 kPa in patients with chronic obstructive pulmonary disease, a PaO2 around 10 kPa in patients with healthy lungs, acute respiratory distress syndrome or sepsis, and a PaO2 around 12 kPa in patients with cardiac or cerebral ischaemia. Eighty per cent would accept a PaO2 of 8 kPa or lower and 77% would accept a PaO2 of 12 kPa or higher in a clinical trial of oxygenation targets. CONCLUSION: Intensive care unit doctors preferred PaO2 to SaO2 in monitoring oxygen treatment when peripheral oxygen saturation was not included in the question. The identification of PaO2 as the preferred target and the thorough clarification of preferences are important when ascertaining optimal oxygenation targets. In particular when designing future clinical trials of higher vs lower oxygenation targets in ICU patients.

Oxygen supplementation for critically ill patients-A protocol for a systematic review.

BACKGROUND: In critically ill patients, hypoxaemia is a common clinical manifestation of inadequate gas exchange in the lungs. Supplemental oxygen is therefore given to all critically ill patients. This can result in hyperoxaemia, and some observational studies have identified harms with hyperoxia. The objective of this systematic review is to critically assess the evidence of randomised clinical trials on the effects of higher versus lower inspiratory oxygen fractions or targets of arterial oxygenation in critically ill adult patients. METHODS: We will search for randomised clinical trials in major international databases. Two authors will independently screen and select references for inclusion using Covidence, extract data and assess the methodological quality of the included randomised clinical trials using the Cochrane risk of bias tool. Any disagreement will be resolved by consensus. We will analyse the extracted data using Review Manager and Trial Sequential Analysis. To assess the quality of the evidence, we will create a 'Summary of Findings' table containing our primary and secondary outcomes using the GRADE assessment. DISCUSSION: Supplemental oxygen administration is widely recommended in international guidelines despite lack of robust evidence of its effectiveness. To our knowledge, no systematic review of randomised clinical trials has investigated the effects of oxygen supplementation in critically ill patients. This systematic review will provide reliable evidence to better inform future trialists and decision-makers on clinical practice on supplemental oxygen administration in critically ill patients.

Forced fluid removal in intensive care patients with acute kidney injury: The randomised FFAKI feasibility trial.

BACKGROUND: Accumulation of fluids is frequent in intensive care unit (ICU) patients with acute kidney injury and may be associated with increased mortality and decreased renal recovery. We present the results of a pilot trial assessing the feasibility of forced fluid removal in ICU patients with acute kidney injury and fluid accumulation of more than 10% ideal bodyweight. METHODS: The FFAKI-trial was a pilot trial of forced fluid removal vs standard care in adult ICU patients with moderate to high risk acute kidney injury and 10% fluid accumulation. Fluid removal was done with furosemide and/or continuous renal replacement therapy aiming at net negative fluid balance > 1 mL/kg ideal body weight/hour until cumulative fluid balance calculated from ICU admission reached less than 1000 mL. RESULTS: After 20 months, we stopped the trial prematurely due to a low inclusion rate with 23 (2%) included patients out of the 1144 screened. Despite the reduced sample size, we observed a marked reduction in cumulative fluid balance 5 days after randomisation (mean difference -5814 mL, 95% CI -2063 to -9565, P = .003) with forced fluid removal compared to standard care. While the trial was underpowered for clinical endpoints, no point estimates suggested harm from forced fluid removal. CONCLUSIONS: Forced fluid removal aiming at 1 mL/kg ideal body weight/hour may be an effective treatment of fluid accumulation in ICU patients with acute kidney injury. A definitive trial using our inclusion criteria seems less feasible based on our inclusion rate of only 2%.

Effects of fluid restriction on measures of circulatory efficacy in adults with septic shock.

BACKGROUND: The haemodynamic consequences of fluid resuscitation in septic shock have not been fully elucidated. Therefore, we assessed circulatory effects in the first 24 h of restriction of resuscitation fluid as compared to standard care in intensive care unit (ICU) patients with septic shock. METHODS: This was a post-hoc analysis of the multicentre CLASSIC randomised trial in which patients with septic shock, who had received the initial fluid resuscitation, were randomised to a protocol restricting resuscitation fluid or a standard care protocol in nine ICUs. The highest plasma lactate, highest dose of noradrenaline, and the urinary output were recorded in five time frames in the first 24 h after randomisation. We used multiple linear mixed effects models to compare the two groups. RESULTS: We included all 151 randomised patients; the cumulated fluid resuscitation volume in the first 24 h after randomisation was median 500 ml (Interquartile range (IQR) 0-1500) and 1250 ml (500-2500) in the fluid restriction group and standard care group, respectively. The estimated differences in the fluid restriction group vs. the standard care group were 0.1 mM (95% confidence interval -0.7 to 0.9; P = 0.86) for lactate, 0.01 µg/kg/min (-0.02 to 0.05; P = 0.48) for dose of noradrenaline, and -0.1 ml/kg/h (-0.3 to 0.2; P = 0.70) for urinary output during the first 24 h after randomisation. CONCLUSIONS: We observed no indications of worsening of measures of circulatory efficacy in the first 24 h of restriction of resuscitation fluid as compared with standard care in adults with septic shock who had received initial resuscitation.

Extracorporeal shockwave therapy in the treatment of chronic diabetic foot ulcers: a prospective randomised trial.

OBJECTIVE: To investigate the efficacy of extracorporeal shockwave therapy (ESWT) on healing chronic diabetic foot ulcers (DFU). METHOD: Patients with chronic DFUs were randomised (1:1) to receive a series of six ESWT treatments over 3 weeks in combination with standard care or standard care alone. ESWT was performed on DFUs using 250 shocks/cm2 and 500 shocks on arterial beds supplying the ulcer location. RESULTS: We recruited 23 patients, 11 in the intervention group and 12 in the control. Transcutaneous oxygen tension was significantly increased in patients treated with ESWT compared with those receiving standard care alone at 3 weeks (p=0.044). Ulcer area reduction was 34.5% in the intervention group versus 5.6% in the control group at 7 weeks (p=0.387). Within-group analysis revealed a significant reduction of ulcer area in the intervention group (p<0.01), while healing was not demonstrated in the control group (p>0.05) (data tested for trend). CONCLUSION: This randomised study indicates a potential beneficial effect of ESWT on ulcer healing as well as tissue oxygenation. Owing to weaknesses of the study and the fact that ulcer healing was not significantly improved in the intervention group compared with the control group, a larger randomised trial with blinded design is suggested.

A qualitative study of the key factors in implementing telemedical monitoring of diabetic foot ulcer patients.

INTRODUCTION: The implementation of telemedicine often introduces major organizational changes in the affected healthcare sector. The objective of this study was to examine the organizational changes through the perception of the healthcare professionals regarding the implementation of a telemedical intervention. We posed the following research question: What are the key organizational factors in the implementation of telemedicine in wound care? METHODS: In connection with a randomized controlled trial of telemedical intervention for patients with diabetic foot ulcers in the region of Southern Denmark, we conducted an organizational analysis. The trial was designed as a multidisciplinary assessment of outcomes using the Model of ASsessment of Telemedicine (MAST). We conducted eight semi-structured interviews including individual interviews with leaders, and an IT specialist as well as focus group interviews with the clinical staff. A qualitative data analysis of the interviews was performed in order to analyze the healthcare professionals and leaders perception of the organizational changes caused by the implementation of the intervention. RESULTS: The telemedical setup enhanced confidence among collaborators and improved the wound care skills of the visiting nurses from the municipality. The effect was related to the direct communication between visiting nurses and specialist doctors. Focus on the training of the visiting nurses was highlighted as a key factor in the success to securing implementation. Concerns regarding lack of multidisciplinary wound care teams, patient responsibility and lack of patient interaction with the physician were raised. Furthermore, the need for clinical guidelines in future implementation was underlined. CONCLUSIONS: Several influential factors were demonstrated in the analysis including visiting nurses wound care training, focus on management, economy, periods with absence from work and clinical care. However, the technology used here could provide an additional option to offer patients after an individual assessment of their health condition.

Variability in targeted arterial oxygenation levels in patients with severe sepsis or septic shock.

BACKGROUND: Supplemental oxygen therapy is used for intensive care (ICU) patients with severe sepsis, but with no general guidelines and few safety data. The aim of this observational study was to describe the variability in oxygen administration as well as the association between partial pressure of arterial oxygen (PaO2 ) and mortality. METHODS: We extracted data from two Scandinavian clinical trials of ICU patients with severe sepsis or septic shock. We calculated average PaO2 and fraction of inspired oxygen (FiO2 ) from trial inclusion and the following 5 days, and assessed the association between PaO2 and 90-day mortality. RESULTS: The median PaO2 was 9.8 kPa [5-95% range 6.4-19.9] and FiO2 was 0.51 [5-95% range 0.27-1.00], respectively. Eight hundred and five of 1,770 patients (45%) died. The relative risk of mortality was 1.43 [95% CI: 1.19-1.65] in patients with average PaO2 < 8 kPa and 1.29 [95% CI: 0.84-1.68] in patients with average PaO2 ≥ 16 kPa, as compared to patients with average PaO2 10-12 kPa. The relative risk of mortality was 1.38 [95% CI: 1.17-1.58] in patients with an average FiO2 0.60-0.80 and 2.10 [95% CI: 1.88-2.23] in patients with an average FiO2  ≥ 0.80 as compared to patients with an average FiO2  ≤ 0.40. CONCLUSION: Administration of oxygen in patients with severe sepsis resulted in a wide range of PaO2 . Significantly higher mortality was observed in patients with an average PaO2 < 8 kPa and FiO2 ≥ 0.60. The results do not imply causation and the associations between average PaO2 and adverse outcomes have to be assessed further.

Validation of a new imaging device for telemedical ulcer monitoring.

PURPOSE: To clarify whether a new portable imaging device (PID) providing 3D images for telemedical use constitutes a more correct expression of the clinical situation compared to standard telemedical equipment in this case iPhone 4s. METHOD: We investigated intra- and interindividual variability between the new portable camera and the iPhone images vs. clinical assessment as the 'gold standard'. The study included 36 foot ulcers. Four specialists rated the ulcers and filled out a questionnaire, which formed the basis of the evaluation. RESULTS: We found fair to very good intra-rater agreement for the new PID and iPhone, respectively. The gold standard was evaluated by assessing the ulcer twice by two different specialists. Kappa values were moderate to very good with respect to inter-rater agreement except for two variables. The agreement between standard and new equipment compared to the gold standard showed highest agreement with the new PID. CONCLUSION: The new PID is more in accordance with the clinical assessment compared to standard images. It opens for the possibility of using more advanced techniques in a telemedical approach to ulcer treatment and care, including volume measurements.

Mortality in elderly ICU patients: a cohort study.

BACKGROUND: The population is aging. We examined changes in the proportion of elderly (≥ 80 years) intensive care unit (ICU) patients during 2005-2011 and the association between age and mortality controlling for preexisting morbidity. METHODS: Through the Danish National Patient Registry, we identified a cohort of 49,938 ICU admissions (47,596 patients) in Northern Denmark from 2005 to 2011. Patients were subdivided in age groups (15-49, 50-64, 65-79 and ≥ 80 years) and calendar year. We estimated 30-day and 31-365-day mortality and mortality rate ratios (MRRs), stratified by admission type (medical and elective/acute surgical patients). Mortality was compared between age groups adjusting for sex and preexisting morbidity using 50-64-year-olds as reference. RESULTS: The proportion of elderly patients increased from 11.7% of all ICU patients in 2005 to 13.8% in 2011. Among the elderly, the 30-day mortality was 43.7% in medical, 39.6% in acute surgical, and 11.6% in elective surgical ICU patients. The corresponding adjusted 30-day MRRs compared with the 50-64-year-olds were 2.7 [95% confidence interval (CI) 2.5-3.0] in medical, 2.7 (95% CI 2.4-3.0) in acute surgical, and 5.2 (95% CI 4.1-6.6) in elective surgical ICU patients. The 31-365-day mortality among elderly patients was 25.4% in medical, 26.9% in acute, and 11.9% in elective surgical ICU patients, corresponding to adjusted MRRs of 2.5 (95% CI 2.1-2.9), 2.2 (95% CI 1.9-2.5), and 1.9 (95% CI 1.6-2.3), respectively. CONCLUSIONS: During 2005-2011, there was an 18% increase in the proportion of elderly ICU patients. Advancing age is associated with increased mortality even after controlling for preexisting morbidity.

Employment status 1 year after out-of-hospital cardiac arrest in comatose patients treated with therapeutic hypothermia.

BACKGROUND: Therapeutic hypothermia for comatose survivors of out-of-hospital cardiac arrest (OHCA) has improved survival and neurologic outcome. This study focused on return to work 1 year after therapeutic hypothermia. METHODS: From June 2004 to June 2009, patients between 18 and 65 years of age with OHCA, who were treated with hypothermia from two regions, representing one third of the national population, were identified from the Danish National Patient Registry, and from hospital and ambulance records. The patients' employment status was obtained from the Danish Ministry of Employment. RESULTS: One hundred thirty-three comatose patients after OHCA treated with hypothermia were identified. One hundred and four (78%) patients were employed, or able to work, at the time of cardiac arrest. This particular group of patients showed significant lower in-hospital mortality compared to the group of patients who were not able to work before cardiac arrest; 13% vs. 48%, respectively (P < 0.001). The workable group had a lower Charlson comorbidity score (P = 0.004), a higher incidence of witnessed cardiac arrest (P = 0.004) and a higher incidence of shockable heart rhythm (P < 0.001). Eighty-seven patients (84%), who were able to work prior to cardiac arrest, survived, and 55 (65%) of these patients were employed or able to work at 1 year follow-up. CONCLUSION: The majority of patients employed, or able to work prior to OHCA, had returned to work at one year follow-up. Predictors of return to work in comatose patients treated with hypothermia have to be identified in a larger-scale study.

Psychoactive substances in seriously injured drivers in Denmark.

This study assesses the presence of a number of psychoactive substances, including alcohol, based on blood samples from 840 seriously injured drivers admitted to five selected hospitals located in five different regions of Denmark. The study was a part of the EU 6th framework program DRUID (Driving Under the Influence of Drugs, Alcohol and Medicines). Blood samples were screened for 30 illegal and legal psychoactive substances and metabolites as well as ethanol. Danish legal limits were used to evaluate the frequency of drivers violating the Danish legislation while limit of quantification (LOQ) was used for monitoring positive drivers. Tramadol is not included in the Danish legislation therefore the general cut off, as decided in the DRUID project was used. Overall, ethanol (18%) was the most frequently identified compound (alone or in combination with other drugs) exceeding the legal limit, which is 0.53g/l in Denmark. The percentage of seriously injured drivers testing positive for medicinal drugs at levels above the Danish legal limit was 6.8%. Benzodiazepines and Z-drugs (6.4%) comprised the majority of this group. One or more illegal drugs (primarily amphetamines and cannabis) were found to be above the Danish legal limit in 4.9% of injured drivers. Young men (median age 31 years) were over-represented among injured drivers who violated Danish law for alcohol and drugs. Diazepam (4.4%), tramadol (3.2%), and clonazepam (3.0%) were the medicinal drugs most frequently detected at levels above LOQ, whereas amphetamines (5.4%) (amphetamine [5.2%] and methamphetamine [1.5%]), tetrahydrocannabinol (3.7%), and cocaine (3.3%), including the metabolite benzoylecgonine, were the most frequently detected illegal drugs. A driver could be positive for more than one substance; therefore, percentages are not mutually exclusive. Poly-drug use was observed in 112 (13%) seriously injured drivers. Tramadol was detected above DRUID cutoffs in 2.1% of seriously injured drivers. This is 3.5 times that observed in a Danish survey of randomly selected drivers. Moreover, illegal and medicinal drug levels above the Danish legal limit were present more than 10 times as frequently as in injured drivers, whereas ethanol was present more than 30 times as frequently than in randomly selected drivers. The results indicate that there is an increased risk in traffic when driving under the influence of psychoactive drugs, especially alcohol in young male drivers.

Presence of psychoactive substances in oral fluid from randomly selected drivers in Denmark.

This roadside study is the Danish part of the EU-project DRUID (Driving under the Influence of Drugs, Alcohol, and Medicines) and included three representative regions in Denmark. Oral fluid samples (n=3002) were collected randomly from drivers using a sampling scheme stratified by time, season, and road type. The oral fluid samples were screened for 29 illegal and legal psychoactive substances and metabolites as well as ethanol. Fourteen (0.5%) drivers were positive for ethanol (alone or in combination with drugs) at concentrations above 0.53g/l, which is the Danish legal limit. The percentage of drivers positive for medicinal drugs above the Danish legal concentration limit was 0.4%; while, 0.3% of the drivers tested positive for one or more illicit drug at concentrations exceeding the Danish legal limit. Tetrahydrocannabinol, cocaine, and amphetamine were the most frequent illicit drugs detected above the limit of quantitation (LOQ); while, codeine, tramadol, zopiclone, and benzodiazepines were the most frequent legal drugs. Middle aged men (median age 47.5 years) dominated the drunk driving group, while the drivers positive for illegal drugs consisted mainly of young men (median age 26 years). Middle aged women (median age 44.5 years) often tested positive for benzodiazepines at concentrations exceeding the legal limits. Interestingly, 0.6% of drivers tested positive for tramadol, at concentrations above the DRUID cut off; although, tramadol is not included in the Danish list of narcotic drugs. It can be concluded that driving under the influence of drugs is as serious a road safety problem as drunk driving.

Should blood flow during cardiopulmonary bypass be individualized more than to body surface area?

Blood flow during cardiopulmonary bypass (CPB) is calculated on body surface area (BSA). Increasing comorbidity, age and weight of today's cardiac patients question this calculation as it may not reflect individual metabolic requirement. The hypothesis was that a measured cardiac index (CI) prior to normothermic CPB is a better estimate. A cross-over study, with random allocation to CPB blood flow for 20 minutes based on either a calculation (2.4 L/min/m(2)) or on CI, with a switch to the opposite flow for another 20 minutes, was performed. Twenty-two elective cardiac surgery patients with normal ventricular function were included. Effect parameters were cerebral oxygenation, mixed venous saturation and arterial lactate. CI varied from 1.9 to 3.1 L/min/m(2) (median 2.4 L/min/m(2)). No differences in effect parameters were seen. In conclusion, a CPB blood flow based on an individual estimate did not improve cerebral and systemic oxygenation compared to a blood flow based on BSA.

Oxygenation and release of inflammatory mediators after off-pump compared with after on-pump coronary artery bypass surgery.

BACKGROUND: In a previous study, we showed that oxygenation was impaired for up to 5 day after conventional coronary artery bypass grafting (CABG). As cardiopulmonary bypass (CPB) may have a detrimental effect on pulmonary function, we hypothesized that coronary revascularization grafting without the use of CPB (OPCAB) would affect post-operative oxygenation and release of inflammatory mediators less compared with CABG. METHODS: Low-risk patients scheduled for elective coronary revascularization were randomly assigned to one of two groups (CABG, n = 17 or OPCAB, n = 18). Two parameters of oxygenation, shunt (%) and ventilation-perfusions mismatch, described as DeltaPO(2) (kPa), were estimated for up to 5 days post-operatively. Systemic release of interleukin (IL)-6, -8 and -10, C-reactive protein (CRP) and neutrophils were measured in peripheral blood samples for up to 3 days post-operatively. The lungs participation in the cytokine response was evaluated from mixed venous blood samples taken within the first 16 h post-operatively. RESULTS: OPCAB was followed by a higher shunt (P = 0.047), with no difference (P = 0.47) in the deterioration of DeltaPO(2) between the groups. OPCAB was followed by an attenuated systemic release of IL-8 (P = 0.041) and IL-10 (P = 0.006), while the release of IL-6 (P = 0.94), CRP (P = 0.121) and neutrophils (P = 0.078) did not differ between the groups. Indications of an uptake of cytokines in the lungs were found after OPCAB. CONCLUSIONS: When comparing OPCAB with CABG, oxygenation was more affected and only part of the systemic inflammatory response was attenuated.

Oxygenation within the first 120 h following coronary artery bypass grafting. Influence of systemic hypothermia (32 degrees C) or normothermia (36 degrees C) during the cardiopulmonary bypass: a randomized clinical trial.

BACKGROUND: Lung function is often impaired after cardiac surgery performed under cardiopulmonary bypass (CPB). Normothermic CPB has become more common, but it remains unknown whether it reduces post-operative lung function compared with hypothermic CPB. The aim of this study was to investigate oxygenation within the first 120 h after systemic hypothermia and normothermia under CPB. METHODS: Thirty patients undergoing coronary artery bypass grafting (CABG) were randomized to either hypothermic (32 degrees C) or normothermic (36 degrees C) CPB. Oxygenation was studied by a simple method for the estimation of intrapulmonary shunt and ventilation-perfusion (V/Q) mismatch pre-operatively and 4, 48 and 120 h post-operatively by changing Fio2 in four to six steps. V/Q mismatch was described with DeltaPo2 (normal values, 0-2.38 kPa). RESULTS: Shunt and V/Q mismatch (DeltaPo2) increased post-operatively in both groups (P<0.01), with no differences between the groups, and with the nadir values 48 h after surgery, i.e. shunt of 15% (5.8-25%) and DeltaPo2 of 3.0 kPa (0.8-14 kPa) [values given as median (range)]. CONCLUSIONS: Impaired oxygenation is prevalent and prolonged following CABG, with equal intensity after hypothermic and normothermic CPB.

Myocardial structure as a determinant of pre- and postoperative ventricular function and long-term prognosis after valve replacement for aortic stenosis.

BACKGROUND: Long-term results after aortic value replacement for aortic stenosis can be correlated to a cardiac-related pre-operative risk profile. This predictability indicates that there is a common basis in subtle or overt structural abnormalities of left ventricular myocardium. METHODS AND RESULTS: Forty-nine patients aged 24-82 (mean 61) years, with aortic stenosis had a full wall thickness transmural biopsy of the left ventricular antero-lateral free wall during aortic valve replacement. Echocardiography and radionuclide ventriculography were performed prior to, and 18 months (n = 41) after, the operation. Postoperative follow-up to a maximum of 7.7 years was 100% complete. Pre-operatively, all patients had an increase in both the left ventricular mass index (202 +/- 67 g.m-2) and the muscle cell diameter (41 +/- 8 microns); other morphological data included a muscle cell nucleus volume of 752 +/- 192 microns3, a muscle cell mass index of 163 +/- 54.m-2, and a fibrous tissue mass index of 39 +/- 16 g.m-2. Patients with a pre-operative episode of clinical left ventricular failure (n = 19) had significantly greater morphological variables than those without. Pre-operative ejection fraction and other measures of systolic function correlated inversely with the morphological data, except for the fibrous tissue mass index; diastolic function indices correlated inversely with all the morphological variables. At the 18-month re-study, the same general picture was noted, but with an underlying strengthening, especially of the muscle cell mass index. Overall, the mass index dropped to 152 +/- 51 g.m-2 (P < 0.0001), but in 17% of the patients it became normal; the mass index at 18 months was directly correlated to morphological variables. A high muscle cell nucleus volume was identified as an independent predictor of early and late mortality. CONCLUSIONS: Abnormalities of the hypertrophied left ventricular muscle cell and the degree of muscle hypertrophy are, to some degree, underlying determinants of pre-operative symptomatology, pre- and postoperative ventricular function, and early and late mortality after valve replacement for aortic stenosis. Incomplete hypertrophy impaired results, was related to pre-operative myocardial structural abnormalities.

[Mortality and worsening of prognosis for patients with aortic stenosis while on the waiting list]. / Mortalitet og prognoseforringelse for patienter med aortastenose på kirurgisk venteliste.

In a prospective study, 99 consecutive patients with an operative indication due to severe aortic stenosis (AS) were put on a surgical waiting list. The waiting time to aortic valve replacement (AVR) averaged 6.3 months (0.5-19 months). There were 58 men and 41 women with a mean age of 61 years (21-82 years). The patients were divided into three groups: group 1 (N = 81) with an uneventful stay on the waiting list; group 2 (N = 11) with significant worsening of a prognostic index; and group 3 (N = 7) with patients who died during the waiting time. The waiting list death rate was 13.5%/patient-year compared with a post-AVR death rate of 4.9% patient-year (p < 0.05) with a mean post-AVR follow-up of 5.7 years. According to a prognostic index (Cox regression model) at inclusion, group 2 patients had a predicted 7-year post-AVR survival probability of 72%, but only of 61% according to their prognostic index immediately preoperatively; their observed 7-year post-AVR survival was 60%. Logistic regression analysis identified high age, short duration of symptoms, signs of severe hypertrophy and strain in the ECG, female gender, and deranged left ventricular diastolic function (related to severely increased left ventricular muscle mass) as independent predictors of prognostic worsening and death while on the waiting list. The predictive models did not allow sufficiently accurate identification of the patients at risk during the waiting period. The consequences of a surgical waiting period averaging 6 months are serious for AS patients. The death rate is high and a subgroup worsens its prognostic profile with a significantly reduced post-AVR long-term survival as the result.