Clinical supervisors' experience of a first-time application of entrustable professional activities in clinical supervision of medical students: findings from a Swedish pilot study.

BACKGROUND: Recently, all medical universities in Sweden jointly developed a framework for Entrustable Professional Activities (EPAs) for work-based training and assessment. This framework is now being introduced nationally in the new 6-year undergraduate medical programme that directly lead to a licence to practise. When EPAs are introduced, it is of central importance to gain clinical supervisors' acceptance to apply the framework in their supervision of students. The aim of this study was therefore to investigate how clinical supervisors, not familiar with EPAs, experience clinical supervision using the framework for EPAs. METHODS: We used a purposive sampling to recruit clinical supervisors. They were given written information on EPAs with a selection of suitable EPAs and the Swedish observation rating scale for assessment of autonomy, and they were offered to attend a 30-minute introductory web course. The participants were informed that EPAs were to be tested, and the students were asked to participate. After the study period the clinical supervisors participated in semi-structured interviews. Inductive qualitative content analysis was used to analyse the transcribed interviews. RESULTS: Three general themes emerged in the qualitative analysis: Promoting Feedback, Trusting Assessments and Engaging Stakeholders. The participants described benefits from using EPAs, but pointed out a need for preparation and adaptation to facilitate implementation. The structure was perceived to provide structured support for feedback, student involvement, entrustment decisions, enabling supervisors to allow the students to do more things independently, although some expressed caution to rely on others' assessments. Another concern was whether assessments of EPAs would be perceived as a form of examination, steeling focus from formative feedback. To understand the concept of EPA, the short web-based course and written information was regarded as sufficient. However, concern was expressed whether EPA could be applied by all clinical supervisors. Involvement and adaption of the workplace was pointed out as important since more frequent observation and feedback, with documentation requirements, increase the time required for supervision. CONCLUSIONS: EPAs were accepted as beneficial, promoting structured feedback and assessments of the students' autonomy. Preparation of supervisors and students as well as involvement and adaptation of the workplace was pointed out as important.

Physicians' self-perceived preparedness for clinical supervision of medical students at university and non-university hospitals -results from a Swedish survey.

BACKGROUND: The need for clinical placements outside traditional teaching hospitals for medical students is growing, both due to a decrease in hospital beds and the expansion of medical students. In this survey, distributed to supervisors at university and non-university hospitals, we investigated supervisors' self-perceived preparedness for the training assignment and searched for factors associated with self-perceived pedagogical knowledge and familiarity with the students' learning objectives. METHODS: A pilot survey was developed using results from qualitative studies regarding clinical supervision of medical students and included questions on the supervisors' education and preparation, if they were familiar with the students' learning objectives, self-perceived pedagogical knowledge, and characteristics of the learning environment. The pilot survey was tested on a smaller group of supervisors. The results from the pilot survey were used to develop an e-survey that was distributed to all hospital employed physicians in Region Västra Götaland. RESULTS: The survey was completed by 1732 physicians (response rate 43%). Among 517 respondents at the university hospital who reported activity as supervisor, 240 (46%) had attended preparatory supervisor training, 423 (82%) perceived enough pedagogical knowledge for the teaching assignment, and 391 (76%) reported familiarity with the learning objectives. The corresponding proportions at non-university hospitals were 159/485 (33%), 363/485 (75%), and 298/485 (61%), respectively (p ≤ .007 all through, compared to the university hospital). Perceiving that goal description and written information from the course management was sufficient for being able to complete the training assignment showed strong association with both self-perceived pedagogical knowledge and familiarity with the students' learning objectives. CONCLUSIONS: We found consistent differences between university and non-university hospitals with respect to the supervisors' self-perceived preparedness for the training assignment. Efforts to convey the learning objectives and support to clinical supervisors are crucial for supervision of students at non-university hospitals.

Care practices for patients requiring mechanical ventilation more than seven days in Swedish intensive care units: A national survey.

OBJECTIVE: To identify care practices in Swedish intensive care units specific to patients requiring mechanical ventilation for >7 days. RESEARCH METHODOLOGY: We conducted a national cross-sectional survey inviting all adult Swedish ICUs (n = 79). Nurse managers were invited by email to complete a questionnaire by telephone. The questionnaire included seven domains: ventilator weaning, mobilisation, communication, nutrition, symptom assessment, psychosocial support and organisational characteristics. RESULTS: We received responses from 77 units (response rate, 97%). Weaning protocols were available in 42 (55%) units, 52 (68%) used individualised weaning strategies and 50 (65%) involved physicians and nurses in collaborative decision making. In 48 units (62%), early mobilisation was prioritised using bed cycling but only 26 (34%) units had mobilisation protocols. Most of the intensive care units (74, 96%) had nutrition protocols but only 2 (3%) had dedicated dieticians. Delirium screening tools were available in 49 (64%) ICUs, 3 (4%) assessed anxiety and none assessed dyspnoea. Nineteen (25%) units employed a primary nursing model and 11 (14%) indicated person-centred care policies. Regular case conferences, including family participation, were held by 39 (51%) units. CONCLUSION: We found that an individualised approach to ventilator weaning, decided by physicians and nurses in collaboration, was the predominant approach, although weaning protocols were available in some intensive care units. Most units prioritised early mobilisation, though few used protocols. Nutritional protocols were widely adopted, as few units had a dedicated dietician.

Long-term outcomes after aneurysmal subarachnoid hemorrhage: A prospective observational cohort study.

OBJECTIVES: The survival rates for patients affected by aneurysmal subarachnoid hemorrhage (aSAH) have increased in recent years; however, many patients continue to develop cognitive dysfunctions that affect their quality of life. The commonly used outcome measures often fail to identify these cognitive dysfunctions. This study aimed to evaluate the long-term outcomes at 1 and 3 years after aSAH to assess changes over time and relate outcomes to patient characteristics and events during the acute phase. MATERIALS AND METHODS: This prospective observational study included patients that experienced aSAH. Patients were assessed according to the extended Glasgow Outcome Scale, Life Satisfaction Questionnaire, Mayo-Portland Adaptability inventory-4, and Mental Fatigue scale. RESULTS: Patients were assessed after 1 year (n = 62) and 3 years (n = 54). At 3 years, the extended Glasgow Outcome Scale score improved in 15% and worsened in 12% of the patients. Mental fatigue was observed in 57% of the patients at 1 year. Patients <60 years of age at the time of aSAH had more self-assessed problems, including pain/headache (p < .01), than patients >60 years of age. Patients with delayed cerebral ischemia during the acute phase reported more dissatisfaction at 3 years, whereas no significant result was seen at 1 year. CONCLUSIONS: Cognitive dysfunction, especially mental fatigue, is common in patients with aSAH, which affects quality of life and recovery. Patient outcome is a dynamic process developing throughout years after aSAH, involving both improvement and deterioration. This study indicates the importance of longer follow-up periods with broad outcome assessments.

Machine learning analysis of heart rate variability to detect delayed cerebral ischemia in subarachnoid hemorrhage.

OBJECTIVES: Approximately 30% of patients with aneurysmal subarachnoid hemorrhage (aSAH) develop delayed cerebral ischemia (DCI). DCI is associated with increased mortality and persistent neurological deficits. This study aimed to analyze heart rate variability (HRV) data from patients with aSAH using machine learning to evaluate whether specific patterns could be found in patients developing DCI. MATERIAL & METHODS: This is an extended, in-depth analysis of all HRV data from a previous study wherein HRV data were collected prospectively from a cohort of 64 patients with aSAH admitted to Sahlgrenska University Hospital, Gothenburg, Sweden, from 2015 to 2016. The method used for analyzing HRV is based on several data processing steps combined with the random forest supervised machine learning algorithm. RESULTS: HRV data were available in 55 patients, but since data quality was significantly low in 19 patients, these were excluded. Twelve patients developed DCI. The machine learning process identified 71% of all DCI cases. However, the results also demonstrated a tendency to identify DCI in non-DCI patients, resulting in a specificity of 57%. CONCLUSIONS: These data suggest that machine learning applied to HRV data might help identify patients with DCI in the future; however, whereas the sensitivity in the present study was acceptable, the specificity was low. Possible confounders such as severity of illness and therapy may have affected the result. Future studies should focus on developing a robust method for detecting DCI using real-time HRV data and explore the limits of this technology in terms of its reliability and accuracy.

Prevalence and Intensive Care Bed Use in Subjects on Prolonged Mechanical Ventilation in Swedish ICUs.

BACKGROUND: The number of patients requiring prolonged mechanical ventilation (PMV) is predicted to escalate due to an aging population. International studies on prevalence and resource utilization of this patient group exist, but data are lacking from Scandinavian ICUs, where there is a relatively low number of ICU beds in relation to population. The primary aim was to identify prevalence of admissions requiring mechanical ventilation ≥ 7-21 d and PMV > 21 d, and their use of ICU bed days in Sweden. Secondary aims were to describe patient characteristics and outcomes. METHODS: We obtained data from the Swedish Intensive Care Registry on admissions age ≥ 18 y mechanically ventilated ≥ 7 d and used open source registry data to calculate the prevalence and use of bed days of admissions ventilated ≥ 7-21 d and PMV > 21 d. RESULTS: Of the 39,510 ICU admissions to Swedish ICUs in 2017, those mechanically ventilated ≥ 7-21 d accounted for 1,643 (4%) admissions, and those with PMV > 21 d accounted for 307 (0.8%) admissions. Of the 109,457 ICU bed days, 22% were consumed by admissions ventilated ≥ 7-21 d and 10% by those with PMV > 21 d. The ICU mortality of both groups was 21%. Admissions with mechanical ventilation ≥ 7 d had a median age of 65 y and were predominantly male (64%). CONCLUSIONS: Admissions to Swedish ICUs who required mechanical ventilation ≥ 7-21 d and PMV > 21 d form a relatively small proportion of all ICU admissions, but consume a significant proportion of ICU beds days. Prevalence of admissions, ICU bed days, and ICU mortality were lower than reports from other countries, but the admissions were predominantly elderly and male, in accordance with other reports.

Association between inflammatory response and outcome after subarachnoid haemorrhage.

OBJECTIVES: Recent reports suggest an association between the inflammatory response after aneurysmal subarachnoid haemorrhage (aSAH) and patients' outcome. The primary aim of this study was to identify a potential association between the inflammatory response after aSAH and 1-year outcome. The secondary aim was to investigate whether the inflammatory response after aSAH could predict the development of delayed cerebral ischaemia (DCI). MATERIALS AND METHODS: This prospective observational pilot study included patients with an aSAH admitted to Sahlgrenska University Hospital, Gothenburg, Sweden, between May 2015 and October 2016. The patients were stratified according to the extended Glasgow Outcome Scale (GOSE) as having an unfavourable (score: 1-4) or favourable outcome (score: 5-8). Furthermore, patients were stratified depending on development of DCI or not. Patient data and blood samples were collected and analysed at admission and after 10 days. RESULTS: Elevated serum concentrations of inflammatory markers such as tumour necrosis factor-α and interleukin (IL)-6, IL-1Ra, C-reactive protein and intercellular adhesion molecule-1 were detected in patients with unfavourable outcome. When adjustments for Glasgow coma scale were made, only IL-1Ra remained significantly associated with poor outcome (p = 0.012). The inflammatory response after aSAH was not predictive of the development of DCI. CONCLUSION: Elevated serum concentrations of inflammatory markers were associated with poor neurological outcome 1-year after aSAH. However, inflammatory markers are affected by many clinical events, and when adjustments were made, only IL-1Ra remained significantly associated with poor outcome. The robustness of these results needs to be tested in a larger trial.

Cerebral ischemia detection using artificial intelligence (CIDAI)-A study protocol.

BACKGROUND: The onset of cerebral ischemia is difficult to predict in patients with altered consciousness using the methods available. We hypothesize that changes in Heart Rate Variability (HRV), Near-Infrared Spectroscopy (NIRS), and Electroencephalography (EEG) correlated with clinical data and processed by artificial intelligence (AI) can indicate the development of imminent cerebral ischemia and reperfusion, respectively. This study aimed to develop a method that enables detection of imminent cerebral ischemia in unconscious patients, noninvasively and with the support of AI. METHODS: This prospective observational study will include patients undergoing elective surgery for carotid endarterectomy and patients undergoing acute endovascular embolectomy for cerebral arterial embolism. HRV, NIRS, and EEG measurements and clinical information on patient status will be collected and processed using machine learning. The study will take place at Sahlgrenska University Hospital, Gothenburg, Sweden. Inclusion will start in September 2020, and patients will be included until a robust model can be constructed. By analyzing changes in HRV, EEG, and NIRS measurements in conjunction with cerebral ischemia or cerebral reperfusion, it should be possible to train artificial neural networks to detect patterns of impending cerebral ischemia. The analysis will be performed using machine learning with long short-term memory artificial neural networks combined with convolutional layers to identify patterns consistent with cerebral ischemia and reperfusion. DISCUSSION: Early signs of cerebral ischemia could be detected more rapidly by identifying patterns in integrated, continuously collected physiological data processed by AI. Clinicians could then be alerted, and appropriate actions could be taken to improve patient outcomes.

Heart rate variability monitoring for the detection of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

BACKGROUND: Delayed cerebral ischemia (DCI) is a major cause of impaired outcome after aneurysmal subarachnoidal hemorrhage (aSAH). In this observational cohort study we investigated whether changes in heart rate variability (HRV) that precede DCI could be detected. METHODS: Sixty-four patients with aSAH were included. HRV data were collected for up to 10 days and analyzed offline. Correlation with clinical status and/or radiologic findings was investigated. A linear mixed model was used for the evaluation of HRV parameters over time in patients with and without DCI. Extended Glasgow outcome scale score was assessed after 1 year. RESULTS: In 55 patients HRV data could be analyzed. Fifteen patients developed DCI. No changes in HRV parameters were observed 24 hours before onset of DCI. Mean of the HRV parameters in the first 48 hours did not correlate with the development of DCI. Low/high frequency (LF/HF) ratio increased more in patients developing DCI (ß -0.07 (95% confidence interval, 0.12-0.01); P = .012). Lower STDRR (standard deviation of RR intervals), RMSSD (root mean square of the successive differences between adjacent RR intervals), and total power (P = .003, P = .007 and P = .004 respectively) in the first 48 hours were seen in patients who died within 1 year. CONCLUSION: Impaired HRV correlated with 1-year mortality and LF/HF ratio increased more in patients developing DCI. Even though DCI could not be detected by the intermittent analysis of HRV used in this study, continuous HRV monitoring may have potential in the detection of DCI after aSAH using different methods of analysis.

Swedish intensivists' experiences and attitudes regarding end-of-life decisions.

BACKGROUND: To make end-of-life (EOL) decisions is a complex and challenging task for intensive care physicians and a substantial variability in this process has been previously reported. However, a deeper understanding of intensivists' experiences and attitudes regarding the decision-making process is still, to a large extent, lacking. The primary aim of this study was to address Swedish intensivists' experiences, beliefs and attitudes regarding decision-making pertaining to EOL decisions. Second, we aimed to identify underlying factors that may contribute to variability in the decision-making process. METHOD: This is a descriptive, qualitative study. Semi-structured interviews with nineteen intensivists from five different Swedish hospitals, with different ICU levels, were performed from 1 February 2017 to 31 May 2017. RESULTS: Intensivists strive to make end-of-life decisions that are well-grounded, based on sufficient information. Consensus with the patient, family and other physicians is important. Concurrently, decisions that are made with scarce information or uncertain medical prognosis, decisions made during on-call hours and without support from senior consultants cause concern for many intensivists. Underlying factors that contribute to the variability in decision-making are lack of continuity among senior intensivists, lack of needed support during on-call hours and disagreements with physicians from other specialties. There is also an individual variability primarily depending on the intensivist's personality. CONCLUSION: Swedish intensivists' wish to make end-of-life decisions based on sufficient information, medically certain prognosis and consensus with the patient, family, staff and other physicians. Swedish intensivists' experience a variability in end-of-life decisions, which is generally accepted and not questioned.

Age, SAPS 3 and female sex are associated with decisions to withdraw or withhold intensive care.

BACKGROUND: Intensive care treat critically ill patients. When intensive care is not considered beneficial for the patient, decisions to withdraw or withhold treatments are made. We aimed to identify independent patient variables that increase the odds for receiving a decision to withdraw or withhold intensive care. METHODS: Registry study using data from the Swedish Intensive Care Registry (SIR) 2014-2016. Age, condition at admission, including co-morbidities (Simplified Acute Physiology Score version 3, SAPS 3), diagnosis, sex, and decisions on treatment limitations were extracted. Patient data were divided into a full care (FC) group, and a withhold or withdraw (WW) treatment group. RESULTS: Of all 97 095 cases, 47.1% were 61-80 years old, 41.9% were women and 58.1% men. 14 996 (15.4%) were allocated to the WW group and 82 149 (84.6%) to the FC group. The WW group, compared with the FC group, was older (P < 0.001), had higher SAPS 3 (P < 0.001) and were predominantly female (P < 0.001). Compared to patients 16-20 years old, patients >81 years old had 11 times higher odds of being allocated to the WW group. Higher SAPS 3 (continuous) increased the odds of being allocated to the WW group by odds ratio [OR] 1.085, (CI 1.084-1.087). Female sex increased the odds of being allocated to the WW group by 18% (1.18; CI 1.13- 1.23). CONCLUSION: Older age, higher SAPS 3 at admission and female sex were found to be independent variables that increased the odds to receive a decision to withdraw or withhold intensive care.

Mental fatigue assessment may add information after aneurysmal subarachnoid hemorrhage.

BACKGROUND: Mental fatigue, as part of cognitive dysfunction, has been reported to be common after subarachnoid hemorrhage and it significantly affects quality of life. AIMS OF THE STUDY: The aim of this study was to assess mental fatigue one year after an aneurysmal subarachnoid hemorrhage and to correlate the degree of mental fatigue to functional outcome assessed with the Extended Glasgow Outcome Scale (GOSE). METHODS: One year after an aneurysmal subarachnoid hemorrhage, the GOSE was assessed and a questionnaire for self-assessment of mental fatigue, the Mental Fatigue Scale, was distributed to all included patients. The maximum score is 42 and a score of ≥10.5 indicates mental fatigue. RESULTS: All patients with GOSE 8, indicating full recovery, had a mental fatigue score of <10.5. A linear correlation between the GOSE and the mental fatigue score was observed (p < 0.0001). CONCLUSIONS: Patients with a favorable outcome and GOSE 5-7 could benefit from the assessments of mental fatigue in order to receive satisfactory rehabilitation.

Cerebrospinal fluid lactate and neurological outcome after subarachnoid haemorrhage.

BACKGROUND: Increased lactate in cerebrospinal fluid (CSF) has been regarded as a marker for cerebral ischemia and damage in the central nervous system. The aim of this study was to evaluate if CSF-lactate was associated with; impaired cerebral circulation, outcome, sex, age, clinical condition or treatment after subarachnoid haemorrhage (SAH). METHODS: This study consists of 33 patients (22 females, 11 males) with aneurysmal SAH treated at Umeå university hospital 2008-2009. Samples were obtained from external ventricular catheters 0-240 h after SAH. Normal CFS-lactate was defined as 1.2-2-1 mmol/L. Hunt & Hess scale assessed clinical condition. Impaired cerebral circulation was evaluated by clinical examination, transcranial doppler, CT-scan, and cerebral angiography. Glasgow outcome scale (GOS) evaluated outcome. RESULTS: Seventy-nine CSF-lactate samples were analysed. CSF-lactate >2.1 mmol/L was found in 25/33 (76%) patients and in 50/79 (63%) samples. No difference in CSF-lactate levels was found over time. No association was found between patients with CSF-lactate >2.1 mmol/L and; sex, severity of clinical condition, impaired cerebral circulation or outcome. CSF-lactate >2.1 mmol/L was more common in patients ≥61 years of age (p = 0.04) and in patients treated with endovascular coiling compared to surgical clipping (p = 0.0001). CONCLUSION: In patients with SAH, no association was found between increased CSF-lactate (>2.1 mmol/L) and severe clinical condition, impaired cerebral circulation or unfavourable outcome. Endovascular coiling and age ≥61 years was associated with CSF-lactate above >2.1 mmol/L.

Speckle tracking-vs conventional echocardiography for the detection of myocardial injury-A study on patients with subarachnoid haemorrhage.

BACKGROUND: Myocardial injury with regional wall motion abnormalities (RWMA) is common in subarachnoid haemorrhage (SAH). We hypothesized that the diagnostic performance of left ventricular (LV) global and regional longitudinal strain (GLS and RLS, respectively), assessed with speckle tracking echocardiography is superior to standard echocardiography for the detection of myocardial injury in SAH. METHODS: Seventy-one unselected patients with verified SAH were included. Echocardiography was performed within 48 hours after admission. hsTnT was followed daily up to 3 days post-admission. RWMA, LV ejection fraction (LVEF), GLS and RLS were analysed by two experienced echocardiographists, blinded to the information on plasma hsTnT. A reduced GLS was defined as >-15%. Two cut-off levels were used for the definition of RLS, ie when segmental strain was >-15% (liberal) or >-11% (conservative) in ≥2 adjacent segments. Myocardial injury was defined as a peak hsTnT ≥90 ng/L. RESULTS: The incidence of myocardial injury was 25%. The hsTnT (median, 25% and 75% percentile) in patients with (a) reduced LV ejection fraction (LVEF <50%, n = 10) was 502 (175-718), (b) RWMA (n = 12) was 648 (337-750), (c) reduced GLS (n = 12) was 502 (132-750) and (d) reduced RLS (n = 42) was 40 (10-216), respectively. The specificity/sensitivity for LVEF, RWMA, GLS and RLS to detect myocardial injury 98%/50%, 100%/67%, 96%/56% and 54%/94%, respectively. The intra- and inter-observer variability for assessment of RLS was high. CONCLUSION: The diagnostic performance of GLS by strain imaging is not superior to standard echocardiography for the detection of myocardial injury in SAH. RLS could not reliably detect regional myocardial injury.

Person-centred care during prolonged weaning from mechanical ventilation, nurses' views: an interview study.

OBJECTIVE: To determine: 1) if the three elements of person-centred care (initiating, working and safeguarding the partnership) were present, and 2) to identify evidence of barriers to person-centred care during prolonged weaning from mechanical ventilation. RESEARCH METHODOLOGY: Secondary analysis of semi structured interviews with 19 critical care nurses using theoretical thematic analysis. SETTING: This study was conducted in three Swedish intensive care units, one in a regional hospital and two in a university hospital. FINDINGS: Three themes and nine subthemes related to person-centred care were identified. The three themes included: 1) 'finding a person behind the patient' related to the 'initiating the partnership' phase, 2) 'striving to restore patient́s sense of control' related to 'working the partnership' phase and 3) 'impact of patient involvement' related to 'safeguarding the partnership' phase of person-centred care'. Additionally a further theme 'barriers to person-centred care' was identified. CONCLUSION: We found evidence of all three person-centred care routines. Barriers to person-centred care comprised of lack team collaboration and resources. Facilitating patients to actively participate in decision-making during the weaning process may optimise weaning outcomes and warrants further research.

Leptin levels after subarachnoid haemorrhage are gender dependent.

BACKGROUND: Subarachnoid hemorrhage (SAH) is a neurological disease where the majority of the patients are critically ill. The adipokine leptin has in cerebral emergencies been related to severity of disease and to adverse outcome. The aim of this study was to examine leptin levels over time after SAH and associations to gender, age, body mass index, severity of disease, parenteral lipids, systemic organ failure and outcome. METHODS: Prospective observational study in 56 patients. Leptin was obtained 0-240 h after SAH, in 48 h intervals. Severity of disease was assessed with the Hunt and Hess score, organ failure with the sequential organ failure assessment score, and outcome with Glasgow outcome scale. Leptin levels in the SAH group were compared with controls from the same geographical area. RESULTS: At admission, Leptin was significantly higher in SAH patients compared to controls, both in female (28.6 ± 25.6 vs 13.0 ± 2.3 ng/mL, p = 0.001) and male patients (13.3 ± 8.4 vs 4.3 ± 0.7 ng/mL, p = 0.001). Leptin levels remained stable over time. Female patients had significantly higher leptin levels than male patients, and deceased female patients had higher leptin levels than female survivors (85.5 ± 20.5 vs 50.5 ± 34.6, n = 4/35, p < 0.05). Leptin levels did not differ between male survivors and non-survivors. Leptin levels were not associated with severity of disease, organ failure or parenteral lipids. CONCLUSION: Leptin levels were significantly higher in both male and female patients compared to controls. Higher leptin levels were related to outcome and organ failure in women but not in men. When analysing leptin levels gender-related differences should be considered.

Blood Metabolomic Predictors of 1-Year Outcome in Subarachnoid Hemorrhage.

BACKGROUND: Delayed neurological deficit (DND) is the most important cause of morbidity and mortality in patients with subarachnoid hemorrhage (SAH) whose aneurysms have been secured. However, the methods currently used to predict the development of DND, such as trans-cranial Doppler or levels biochemical markers in blood and cerebrospinal fluid are not very accurate. METHOD: Venous blood was drawn from 50 patients with SAH, admitted to the neurosurgical department Umeå University Hospital, at day 1-3 and day 7 after the bleed. The clinical status of the patients was followed up approximately 1 year after this episode and classified according to the Glasgow Outcome Score (GOS). RESULTS: Results showed considerable differences in blood metabolomic patterns between day 1-3 and 7 after the hemorrhage. Fifty-six out of 98 metabolites could be identified from our in-house library and 17 of these metabolites changed significantly from day 1-3 to 7 after the bleed. One of these, myo-inositol, was predictive of clinical outcome even after correction for multiple testing. An estimation of the diagnostic accuracy of high levels of this substance in predicting good outcome (GOS 4-5) yielded a sensitivity of .763 and a specificity of .5 at the optimal cut off point. CONCLUSIONS: SAH is an event with a profound effect on blood metabolomics profiles. Myo-inositol might be an interesting compound for future study to focus on in the search for metabolic markers in venous blood of delayed neurological deterioration in SAH patients.

Adrenal response after trauma is affected by time after trauma and sedative/analgesic drugs.

BACKGROUND: The adrenal response in critically ill patients, including trauma victims, has been debated over the last decade. The aim of this study was to assess the early adrenal response after trauma. METHODS: Prospective, observational study of 50 trauma patients admitted to a level-1-trauma centre. Serum and saliva cortisol were followed from the accident site up to five days after trauma. Corticosteroid binding globulin (CBG), dehydroepiandrosterone (DHEA) and sulphated dehydroepiandrosterone (DHEAS) were obtained twice during the first five days after trauma. The effect of time and associations between cortisol levels and; severity of trauma, infusion of sedative/analgesic drugs, cardiovascular dysfunction and other adrenocorticotropic hormone (ACTH) dependent hormones (DHEA/DHEAS) were studied. RESULTS: There was a significant decrease over time in serum cortisol both during the initial 24 h, and from the 2nd to the 5th morning after trauma. A significant decrease over time was also observed in calculated free cortisol, DHEA, and DHEAS. No significant association was found between an injury severity score ≥ 16 (severe injury) and a low (< 200 nmol/L) serum cortisol at any time during the study period. The odds for a serum cortisol < 200 nmol/L was eight times higher in patients with continuous infusion of sedative/analgesic drugs compared to patients with no continuous infusion of sedative/analgesic drugs. CONCLUSION: Total serum cortisol, calculated free cortisol, DHEA and DHEAS decreased significantly over time after trauma. Continuous infusion of sedative/analgesic drugs was independently associated with serum cortisol < 200 nmol/L.

Effects of prostacyclin on the early inflammatory response in patients with traumatic brain injury-a randomised clinical study.

OBJECTIVE AND DESIGN: A prospective, randomised, double-blinded, clinical trial was performed at a level 1 trauma centre to determine if a prostacyclin analogue, epoprostenol (Flolan®), could attenuate systemic inflammatory response in patients with severe traumatic brain injury (TBI). SUBJECTS: 46 patients with severe TBI, randomised to epoprostenol (n = 23) or placebo (n = 23). TREATMENT: Epoprostenol, 0.5 ng · kg(-1) · min(-1), or placebo (saline) was given intravenously for 72 hours and then tapered off over the next 24 hours. METHODS: Interleukin-6 (IL-6), interleukin-8 (IL-8), soluble intracellular adhesion molecule-1 (sICAM-1), C-reactive protein (CRP), and asymmetric dimethylarginine (ADMA) levels were measured over five days. Measurements were made at 24 h intervals ≤24 h after TBI to 97-120 h after TBI. RESULTS: A significantly lower CRP level was detected in the epoprostenol group compared to the placebo group within 73-96 h (p = 0.04) and within 97-120 h (p = 0.008) after trauma. IL-6 within 73-96 h after TBI was significantly lower in the epoprostenol group compared to the placebo group (p = 0.04). ADMA was significantly increased within 49-72 h and remained elevated, but there was no effect of epoprostenol on ADMA levels. No significant differences between the epoprostenol and placebo groups were detected for IL-8 or sICAM-1. CONCLUSIONS: Administration of the prostacyclin analogue epoprostenol significantly decreased CRP and, to some extent, IL-6 levels in patients with severe TBI compared to placebo. These findings indicate an interesting option for treatment of TBI and warrants future larger studies. TRIAL REGISTRATION: ClinicalTrials.gov Identifier, NCT01363583.