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1.	Brorsson, Camilla, et al. (författare) Liver resection is not associated with decreased cortisol levels. Annan publikation (övrigt vetenskapligt/konstnärligt)abstract Background: Adrenal hormones are synthesized from cholesterol, produced and stored in the liver. Liver failure has been reported to be associated with adrenal insufficiency. A possible mechanism could be a limited supply of substrate for cortisol synthesis. The aims of this study was to evaluate the occurrence of total serum cortisol <200 nmol/L after major liver resection (≥ 30%) and other major surgery (hemicolectomy) and to assess associations between cholesterol and cortisol levels after liver resection.Methods: Prospective, observational study. 40 patients were included (major liver resection n=15, hemicolectomy n=25). Serum and salivary cortisol were followed from morning before surgery up to five days postoperatively. Sulphated dehydroepiandrosterone (DHEAS) and lipids (cholesterol, low density lipoproteins, high density lipoproteins and triglycerides) were obtained in liver resection patients.Results: 8/25 (32%, hemicolectomy patients), and 3/15 (20%, liver resection patients) had serum cortisol <200 nmol/L. Neither hemicolectomy nor liver resection was significantly associated with serum cortisol <200 nmol/L, p=0.49. Serum cortisol <200 nmol/L was not significantly associated with lipids below normal limits, (cholesterol; p=1.0 day 1, p=0.46 day 4, LDL; p=0.56 day 1, p=1.0 day 4, and HDL; p=0.27 day 1, p=1.0 day 4). Serum and salivary cortisol correlated significantly (rs=0.83, p<0.0001, hemicolectomy, rs=0.80, p<0.0001, liver resection).Conclusion: Serum cortisol levels <200 nmol/L was found in 32% (hemicolectomy) and 20% (liver resection) postoperatively. Compared to after hemicolectomy, serum cortisol <200 nmol/L was not significantly more common after liver resection. Lipids below normal limits were not associated with serum cortisol <200 nmol/L after liver resection.
2.	Bjerkne Wenneberg, Sandra, et al. (författare) Association between inflammatory response and outcome after subarachnoid haemorrhage. 2021 Ingår i: Acta neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 143:2, s. 195-205 Tidskriftsartikel (refereegranskat)abstract 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).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 10days.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.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.
3.	Bjerkne Wenneberg, Sandra, et al. (författare) Heart rate variability monitoring for the detection of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. 2020 Ingår i: Acta anaesthesiologica Scandinavica. - : Wiley. - 1399-6576 .- 0001-5172. ; 64:7, s. 945-952 Tidskriftsartikel (refereegranskat)abstract 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 preced DCI could be detected.Sixty-four patients with aSAHwere included. HRV data were collected for up to 10 days and analyzed off-line.Correlationwith clinical status and/or radiologic findings was investigated. A linear mixed model was used for the evaluation of HRVparameters over time in patients with and without DCI. Extended Glascow outcome scale score was assessed after 1 year.In 55 patients HRV data could be analysed. Fifteen patients developed DCI. No changes in HRV parameters were observed 24 h before onset of DCI. Mean of the HRV parameters in the first 48 h did not correlate with the development of DCI. Low/high frequency (LF/HF) ratio increased more in patients developing DCI (β -0.07 (95% confidence interval,0.12-0.01);p=0.012). Lower STRDRR (standard deviation of RR intervals), RMSSD (root mean square of the successive differences between adjacent RR intervals),and total power(p=0.003, p=0.007 and p=0.004respectively) in the first 48 h was seen in patients who died within 1 year.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.
4.	Bjerkne Wenneberg, Sandra, et al. (författare) Long-term outcomes after aneurysmal subarachnoid hemorrhage: A prospective observational cohort study 2022 Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 146:5, s. 525-536 Tidskriftsartikel (refereegranskat)abstract 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.
5.	Block, Linda, et al. (författare) Age, SAPS 3 and female sex are associated with decisions to withdraw or withhold intensive care 2019 Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 63:9, s. 1210-1215 Tidskriftsartikel (refereegranskat)abstract 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 97095 cases, 47.1% were 61-80 years old, 41.9% were women and 58.1% men. 14996 (15.4%) were allocated to the WW group and 82149 (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. © 2019 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd
6.	Block, Linda, et al. (författare) Cerebral ischemia detection using artificial intelligence (CIDAI)-A study protocol 2020 Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 64:9, s. 1335-1342 Tidskriftsartikel (refereegranskat)abstract 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.
7.	Brorsson, Camilla, et al. (författare) Adrenal response after trauma is affected by time after trauma and sedative/analgesic drugs 2014 Ingår i: Injury. - : Elsevier. - 0020-1383 .- 1879-0267. ; 45:8, s. 1149-1155 Tidskriftsartikel (refereegranskat)abstract 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.
8.	Brorsson, Camilla, et al. (författare) Saliva stimulation with glycerine and citric acid does not affect salivary cortisol levels 2014 Ingår i: Clinical Endocrinology. - : Wiley. - 0300-0664 .- 1365-2265. ; 81:2, s. 244-248 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE:In critically ill patients with hypotension, who respond poorly to fluids and vasoactive drugs, cortisol insufficiency may be suspected. In serum over 90% of cortisol is protein-bound, thus routine measures of total serum cortisol may yield 'false lows' due to hypoproteinaemia. Thus, the occurrence of cortisol insufficiency could be overestimated in critically ill patients. Salivary cortisol can be used as a surrogate for free serum cortisol, but in critically ill patients saliva production is decreased, and insufficient volume of saliva for analysis is a common problem. The aim of this study was to investigate if a cotton-tipped applicator with glycerine and citric acid could be used for saliva stimulation without affecting salivary cortisol levels.DESIGN:Prospective, observational study.PARTICIPANTS:Thirty-six volunteers (six males, 30 females), age 49 ± 9 years, without known oral mucus membrane rupture in the mouth.MEASUREMENTS:Forty-two pairs of saliva samples (22 paired morning samples, 20 paired evening samples) were obtained before and after saliva stimulation with glycerine and citric acid. Salivary cortisol was analysed using Spectria Cortisol RIA (Orion Diagnostica, Finland).RESULTS:The paired samples correlated significantly (P < 0·0001) and there was no significant difference between un-stimulated and stimulated salivary cortisol levels.CONCLUSIONS:Saliva stimulation with a cotton-tipped applicator containing glycerine and citric acid did not significantly influence salivary cortisol levels in healthy volunteers. This indicates that salivary cortisol measurement after saliva stimulation may be a useful complement when evaluating cortisol status in critically ill patients.
9.	Brorsson, Camilla, et al. (författare) Severe traumatic brain injury : consequences of early adverse events 2011 Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley-Blackwell. - 0001-5172 .- 1399-6576. ; 55:8, s. 944-951 Tidskriftsartikel (refereegranskat)abstract Background: Several factors associated with an unfavourable outcome after severe traumatic brain injury (TBI) have been described: prolonged pre-hospital time, secondary referral to a level 1 trauma centre, the occurrence of secondary insults such as hypoxia, hypotension or low end-tidal carbon dioxide (ETCO(2)). To determine whether adverse events were linked to outcome, patients with severe TBI were studied before arrival at a level 1 trauma centre.Methods: Prospective, observational study design. Patients with severe TBI (n = 48), admitted to Umea University Hospital between January 2002 to December 2005 were included. All medical records from the site of the accident to arrival at the level 1 trauma centre were collected and evaluated.Results: A pre-hospital time of >60 min, secondary referral to a level 1 trauma centre, documented hypoxia (oxygen saturation <95%), hypotension (systolic blood pressure <90 mmHg), hyperventilation (ETCO(2) <4.5 kPa) or tachycardia (heart rate >100 beats/min) at any time before arrival at a level 1 trauma centre were not significantly related to an unfavourable outcome (Glasgow Outcome Scale 1-3).Conclusion: Early adverse events before arrival at a level 1 trauma centre were without significance for outcome after severe TBI in the trauma system studied.
10.	Brorsson, Camilla, 1967- (författare) Trauma - logistics and stress response 2014 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Background: Trauma is a major cause of death and disability. Adverse events, such as prolonged prehospital time, hypoxia, hypotension and/or hyperventilation have been reported to correlate to poor outcome.Adequate cortisol levels are essential for survival after major trauma. In hypotensive critically ill patients, lack of sufficient amount of cortisol can be suspected, and a concept of critical illness related corticosteroid insufficiency has been proposed. Corticosteroid therapy has many adverse effects in critically ill patients and should only be given if life-saving. Correct measurement of serum cortisol levels is important but difficult in critically ill patients with capillary leakage. Estimation of the free and biologically active cortisol is preferable. In serum less than 10% of cortisol is free and biologically active and not possible to measure with routine laboratory methods. Salivary cortisol can be used as a surrogate for free cortisol, but salivary production is reduced in critically ill patients. Liver resection could reduce cortisol levels due to substrate deficiency.Aims: 1. Evaluate the occurrence of early adverse events in patients with traumatic brain injury and relate them to outcome. 2. Assess cortisol levels over time after trauma and correlate to severity of trauma, sedative/analgesic drugs and cardiovascular function. 3. Evaluate if saliva stimulation could be performed without interfering with salivary cortisol levels. 4. Assess cortisol levels over time after liver resection in comparison to other major surgery.Results: There was no significant correlation between prehospital time ³60 minutes, hypoxia (saturation <95%), hypotension (systolic blood pressure <90 mmHg), or hyperventilation (ETCO2 <4.5 kPa) and a poor outcome (Glasgow Outcome Scale 1-3) in patients with traumatic brain injury. Cortisol levels decreased significantly over time after trauma, but there was no correlation between low (<200 nmol/L) serum cortisol levels and severity of trauma.Infusion of sedative/analgesic drugs was the strongest predictor for a low (<200 nmol/L) serum cortisol. The odds ratio for low serum cortisol levels (<200 nmol/L) was 8.0 for patients receiving continuous infusion of sedative/analgesic drugs. There was no significant difference between unstimulated and stimulated salivary cortisol levels (p=0.06) in healthy volunteers. Liver resection was not associated with significantly lower cortisol levels compared to other major surgery.Conclusion: There was no significant correlation between early adverse events and outcome in patients with traumatic brain injury. Cortisol levels decreased significantly over time in trauma patients. Low cortisol levels (<200 nmol/L) were significantly correlated to continuous infusion of sedative/analgesic drugs. Saliva stimulation could be performed without interfering with salivary cortisol levels. Liver resection was not associated with low cortisol levels compared to other major surgery.
11.	Cederwall, Carl-Johan, et al. (författare) Care practices for patients requiring mechanical ventilation more than seven days in Swedish intensive care units: A national survey. 2023 Ingår i: Intensive & critical care nursing. - : Elsevier BV. - 0964-3397 .- 1532-4036. ; 74 Tidskriftsartikel (refereegranskat)abstract To identify care practices in Swedish intensive care units specific to patients requiring mechanical ventilation for >7days.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.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.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.
12.	Cederwall, Carl-Johan, et al. (författare) Prevalence and Intensive Care Bed Use in Subjects on Prolonged Mechanical Ventilation in Swedish ICUs 2021 Ingår i: Respiratory Care. - : Daedalus Enterprises. - 0020-1324 .- 1943-3654. ; 66:2, s. 300-306 Tidskriftsartikel (refereegranskat)abstract 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.
13.	Cederwall, Carl-Johan, et al. (författare) Use of person-centred care during weaning from prolonged mechanical ventilation - an interview study 2017 Ingår i: EfCCNa Conference, Belfast, Oral paper. Konferensbidrag (övrigt vetenskapligt/konstnärligt)
14.	Dalla, Keti, 1975, et al. (författare) Speckle tracking-vs conventional echocardiography for the detection of myocardial injury-A study on patients with subarachnoid haemorrhage. 2019 Ingår i: Acta anaesthesiologica Scandinavica. - : Wiley. - 1399-6576 .- 0001-5172. ; 63:3, s. 365-372 Tidskriftsartikel (refereegranskat)abstract 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.Seventy-one unselected patients with verified SAH were included. Echocardiography was performed within 48hours after admission. hsTnT was followed daily up to 3days 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 ≥90ng/L.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.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.
15.	Fjellström, Mona, 1958-, et al. (författare) En bro mellan högre utbildning och profession : Utbildning för kliniska handledare i läkarutbildning 2012 Ingår i: Nu 2012 Göteborg 17-19 oktober 2012. - Göteborg. ; , s. 131-132 Konferensbidrag (refereegranskat)abstract I samband med att läkarutbildningen vid Umeå universitet skulle regionaliseras togs beslut om att samtliga kliniska handledare, varav flertalet är landstingsanställda läkare, i regionen (Västerbotten, Norrbotten, Jämtland och Västernorrland) skulle erbjudas handledarutbildning. Utbildningen skulle stärka kopplingen mellan de högskoleförlagda och de verksamhetsförlagda delarna av utbildningen samt stödja en handledarroll starkt utmanad av sjukvårdens verksamhetskrav. Läkarutbildningen har utökats kraftigt de senaste femton åren samtidigt som kraven ökat på produktivitet inom hälso- och sjukvården. Resultatet har blivit många studenter ute i klinisk verksamhet med kliniska handledare som ofta varken har en tydlig rolldefinition som handledare, aktuell kunskap om vilka mål som skall uppnås eller redskap för hur handledning skall genomföras i en splittrad och tidspressad vardag. För studenterna har problemen yttrat sig i form av brist på tid med, eller avsaknad av, handledare och sämre möjligheter att fullfölja praktiska utbildningsmoment (Läkartidningen, 2008:38; MSF Handledningsenkät 2011). Socialstyrelsen har också uppmärksammat behovet av handledarutbildning genom att ställa krav på handledarutbildning för handledare i specialiseringstjänstgöring (ST) för läkare (SOSFS 2008:17, 3 kap).Fokus för handledarutbildningen blev att utveckla de kliniska handledarnas kunskaper om och förmåga att handleda i kliniska situationer samt att stimulera ett reflekterande och prövande förhållningssätt till studenternas lärande och den egna handledarrollen. Teman som ingår är: Mål och regelverk för läkarprogrammet, planering av klinisk handledning, att stödja ett reflekterat och handlingsinriktat lärande, att handleda, samtal, feedback och bedömning samt den professionella handledaren. Utbildningen, som genomförs som ett samarbete mellan universitetet och de fyra landstingen, omfattar tre dagar med ett eget arbete som genomförs av deltagarna mellan kursdag 2 och 3. Sedan 2009 har 177 kliniska handledare utbildats. Utvärderingar genomförda i samband med kursens genomförande har visat att de kliniska handledarna genomgående är mycket positiva till utbildningen. Det som särskilt lyfts fram är möjligheten till egen reflektion, praktisk problemlösning tillsammans med andra handledare samt en starkare koppling till utbildningsuppdraget genom den ökade kunskapen om lärande och högskolans regelverk.Under den period som handledarutbildningen genomförts har intresset väckts för att handledarutbildning för kliniska handledare skall genomföras i två steg. Ett inledande steg fokuserat på grundläggande handledarkunskap och handledning inom läkarprogrammet som skulle genomföras under läkares specialiseringstjänstgöring. Dessutom ett senare steg, riktat till färdiga specialistkompetenta läkare, som fokuserar på den mer långsiktiga och individnära handledning som genomförs under specialisttjänstgöringen. Idag för läkarprogrammet vid Umeå universitet samtal med två landsting i regionen om möjligheten att bedriva den grundläggande handledarutbildningen.
16.	Grände, PO, et al. (författare) Clinical studies in severe traumatic brain injury:a controversial issue .Editorial. 2002 Ingår i: Intensive Care Medicine. - 0342-4642 .- 1432-1238. ; 28, s. 529-531 Forskningsöversikt (refereegranskat)
17.	Grände, P. O., et al. (författare) Clinical studies in severe traumatic brain injury : a controversial issue 2002 Annan publikation (populärvet., debatt m.m.)
18.	Grände, Per-Olof, et al. (författare) Clinical studies in severe traumatic brain injury: a controversial issue. 2002 Ingår i: Intensive care medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 28:5, s. 529-31 Tidskriftsartikel (refereegranskat)
19.	Koskinen, L. O., et al. (författare) Prostacyclin treatment normalises the MCA flow velocity in nimodipine-resistant cerebral vasospasm after aneurysmal subarachnoid haemorrhage : a pilot study 2009 Ingår i: Acta Neurochirurgica. - : Springer. - 0001-6268 .- 0942-0940. ; 151:6, s. 595-599 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Cerebral vasospasm triggered by subarachnoid haemorrhage is one of the major causes of post-haemorrhage morbidity and mortality. Several treatment modalities have been proposed, and none of them are fully effective.METHODS: In this study we treated five patients with prostacyclin suffering vasospasm after a ruptured aneurysm not responding to high i.v. doses of nimodipine. All patients were severely ill, unconscious and in need of intensive care.FINDINGS: A low dose of prostacyclin i.v. infusion for 72 h reversed the vasospasm as measured by transcranial Doppler technique. The mean MCA blood flow velocity decreased from 199 +/- 31 cm/s to 92 +/- 6 cm/s within 72 h after the start of the prostacyclin infusion.CONCLUSIONS: We suggest that low-dose prostacyclin treatment, an old treatment strategy, can be a treatment option in patients with vasospasm not responding to ordinary measures.
20.	Koskinen, Lars-owe, et al. (författare) Ten-year follow-up of patients in a double blinded randomized study on prostacyclin treatment in severe traumatic brain injury 2017 Ingår i: Brain Injury. - : TAYLOR & FRANCIS INC. - 0269-9052 .- 1362-301X. ; 31:6-7, s. 770-771 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
21.	Kralova, Ivana, et al. (författare) Non-traumatic subarachnoid hemorrhage is associated with subnormal blood creatinine levels 2010 Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Taylor & Francis Group. - 0036-5513 .- 1502-7686. ; 70:6, s. 438-446 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: The aim of this study was to examine the hypothesis that patients with non-traumatic subarachnoid hemorrhage (SAH) have statistically significant subnormal creatinine levels and that the creatinine levels are associated with severity of disease.MATERIALS AND METHODS: This was a retrospective observational study over 2 years (2005-2006) in which the SAH patients were divided into patients with severe symptoms and patients with mild/moderate symptoms, and were compared to patients with; traumatic brain injury, trauma without brain injury and patients undergoing elective knee surgery. Blood creatinine levels (day 1-3, and day 7) were recorded.RESULTS: Compared to a normal distribution, SAH patients had statistically significant subnormal creatinine levels day one through seven. SAH patients with severe symptoms had statistically significant subnormal creatinine levels already on day one, in contrast to patients with mild/moderate symptoms. Women with severe symptoms had statistically significant subnormal creatinine levels throughout the study period in contrast to men with severe symptoms who had a normal distribution of creatinine at admission. Women with mild/moderate symptoms had a normal distribution of creatinine only at admission in contrast to men who had a normal distribution of creatinine throughout the study period. Male patients with traumatic brain injury, all trauma patients without brain injury and all patients undergoing elective knee surgery had a normal distribution of creatinine on all studied days.CONCLUSIONS: SAH is associated with subnormal serum creatinine levels. This finding is more pronounced in patients with severe symptoms and in women.
22.	Lambert, G, et al. (författare) Sympathetic nervous activation following subarachnoid hemorrhage: Influence of intravenous clonidine. 2002 Ingår i: Acta anaesthesiologica Scandinavica. - 0001-5172. ; 46:2, s. 160-5 Tidskriftsartikel (refereegranskat)abstract Subarachnoid hemorrhage is often accompanied by systemic complications and cerebral vasospasm. Elevated levels of circulating catecholamines may be involved in the pathophysiology behind these events. The alpha-2-agonist clonidine inhibits sympathetic outflow by a central mechanism. Unrestricted sympathoexcitation may be detrimental and administration of clonidine may be beneficial in these patients.
23.	Lindgren, Cecilia, 1958-, et al. (författare) ADMA Levels and Arginine/ADMA Ratios Reflect Severity of Disease and Extent of Inflammation After Subarachnoid Hemorrhage 2014 Ingår i: Neurocritical Care. - : Springer Science and Business Media LLC. - 1541-6933 .- 1556-0961. ; 21:1, s. 91-101 Tidskriftsartikel (refereegranskat)abstract Subarachnoid hemorrhage (SAH) is characterized by an inflammatory response that might induce endothelial dysfunction. The aim of this study was to evaluate if ADMA and arginine/ADMA ratios after SAH (indicators of endothelial dysfunction) are related to clinical parameters, inflammatory response, and outcome. Prospective observational study. ADMA, arginine, C-reactive protein (CRP), and cytokines were obtained 0-240 h (h) after SAH. Definition of severe clinical condition was Hunt&Hess (H&H) 3-5 and less severe clinical condition H&H 1-2. Impaired cerebral circulation was assessed by clinical examination, transcranial doppler, CT-scan, and angiography. Glasgow outcome scale (GOS) evaluated the outcome. Compared to admission, 0-48 h after SAH, the following was observed 49-240 h after SAH; (a) ADMA was significantly increased at 97-240 h (highest 217-240 h), (b) CRP was significantly increased at 49-240 h (highest 73-96 h), (c) interleukin-6 (IL-6) was significantly lower at 97-240 h (highest 49-96 h), p < 0.05. ADMA, CRP, and IL-6 were significantly lower and peak arginine/ADMA ratio was significantly higher in patients with H&H 1-2 compared to patients with H&H 3-5, p < 0.05. The peak ADMA or the nadir arginine/ADMA ratio did not differ significantly between patients with (55 %) or without (45 %) signs of impaired cerebral circulation. The peak ADMA or the nadir arginine/ADMA ratio did not differ significantly between patients with GOS 1-3 and patients with GOS 4-5. ADMA increased significantly after SAH, and the increase in ADMA started after the pro-inflammatory markers (CRP and IL-6) had peaked. This might indicate that endothelial dysfunction, with ADMA as a marker, is induced by a systemic inflammation.
24.	Lindgren, Cecilia, et al. (författare) Cerebrospinal fluid lactate and neurological outcome after subarachnoid haemorrhage 2019 Ingår i: Journal of Clinical Neuroscience. - : Elsevier BV. - 0967-5868 .- 1532-2653. ; 60, s. 63-67 Tidskriftsartikel (refereegranskat)abstract 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 Umea 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. (C) 2018 Published by Elsevier Ltd.
25.	Lindgren, Cecilia, et al. (författare) Cortisol levels are influenced by sedation in the acute phase after subarachnoid haemorrhage 2013 Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 57:4, s. 452-460 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Subarachnoid haemorrhage (SAH) is a life-threatening condition that may be aggravated by acute pituitary damage and cortisol insufficiency. Robust diagnostic criteria for critical illness-related corticosteroid insufficiency (CIRCI) are lacking. The aim of this study was to assess the frequency of CIRCI in the acute phase (0-240 h) after SAH and to evaluate associations between cortisol levels and clinical parameters (sedation, circulatory failure, gender, age, severity of disease, treatment). CIRCI was defined as a single morning serum cortisol (mSC) < 200 nmol/L. The lower limit for calculated free cortisol (cFC) was set at < 22 nmol/L, and for saliva cortisol at < 7.7 nmol/L.METHODS: Fifty patients were included. Serum/saliva cortisol and corticosteroid-binding globulin were obtained every second morning. A logistic regression model was used for multivariate analysis comparing cortisol levels with clinical parameters.RESULTS: Of the patients, 21/50 (42%) had an mSC < 200 nmol/L and 30/50 (60%) had a cFC < 22 nmol/L. In patients with continuous intravenous sedation, the odds ratio for a mSC to be < 200 nmol/L was 18 times higher (95% confidence interval 4.2-85.0, P < 0.001), and the odds ratio for a cFC to be < 22 nmol/L was 2.4 times higher (95% confidence interval 1.2-4.7, P < 0.05) compared with patients with no continuous intravenous sedation.CONCLUSIONS: Continuous intravenous sedation was significantly associated with cortisol values under defined limits (mSC < 200, cFC < 22 nmol/L). The possibility that sedating drugs per se may influence cortisol levels should be taken into consideration before CIRCI is diagnosed.
26.	Lindgren, Cecilia, et al. (författare) Frequency of non-convulsive Seizures and non-convulsive status Epilepticus in Subarachnoid Hemorrhage patients in need of controlled ventilation and sedation 2012 Ingår i: Neurocritical Care. - : Springer. - 1541-6933 .- 1556-0961. ; 17:3, s. 367-373 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Non-convulsive seizures (NCSZ) can be more prevalent than previously recognized among comatose neuro-intensive care patients. The aim of this study was to evaluate the frequency of NCSZ and non-convulsive status epilepticus (NCSE) in sedated and ventilated subarachnoid hemorrhage (SAH) patients.METHODS: Retrospective study at a university hospital neuro-intensive care unit, from January 2008 until June 2010. Patients were treated according to a local protocol, and were initially sedated with midazolam or propofol or combinations of these sedative agents. Thiopental was added for treatment of intracranial hypertension. No wake-up tests were performed. Using NicoletOne((R)) equipment (VIASYS Healthcare Inc., USA), continuous EEG recordings based on four electrodes and a reference electrode was inspected at full length both in a two electrode bipolar and a four-channel referential montage.RESULTS: Approximately 5,500 h of continuous EEG were registered in 28 SAH patients (33 % of the patients eligible for inclusion). The median Glasgow Coma scale was 8 (range 3-14) and the median Hunt and Hess score was 4 (range 1-4). During EEG registration, no clinical seizures were observed. In none of the patients inter ictal epileptiform activity was seen. EEG seizures were recorded only in 2/28 (7 %) patients. One of the patients experienced 4 min of an NCSZ and one had a 5 h episode of an NCSE.CONCLUSION: Continuous EEG monitoring is important in detecting NCSZ in sedated patients. Continuous sedation, without wake-up tests, was associated with a low frequency of subclinical seizures in SAH patients in need of controlled ventilation.
27.	Lindgren, Cecilia, et al. (författare) Leptin levels after subarachnoid haemorrhage are gender dependent 2016 Ingår i: Springerplus. - : Springer Science and Business Media LLC. - 2193-1801. ; 5 Tidskriftsartikel (refereegranskat)abstract 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.
28.	Lindgren, Cecilia, et al. (författare) Long-term subarachnoid haemorrhage survivors still die due to cerebrovascular causes 2015 Ingår i: Acta Neurologica Scandinavica. - : John Wiley & Sons. - 0001-6314 .- 1600-0404. ; 132:6, s. 410-416 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: Subarachnoid haemorrhage (SAH) is associated with sympathetic nervous activation and inflammation. SAH could therefore theoretically be a risk factor for development of cardiovascular disease. The aim of this study was to investigate whether long-term (>/=1 year) SAH survivors had an increased risk of death due to cardiovascular causes. MATERIAL & METHODS: SAH patients >/=18 years treated at Umea University Hospital between 1986 and 2006 were eligible for inclusion. Deceased patients were identified in the Swedish population register. Death certificates from long-term SAH survivors and causes of death in the general population were obtained from the National Board of Health and Welfare, Sweden. The prevalence of comorbidities at the time of SAH was compared with the distribution of cardiovascular risk factors in the northern Sweden MONICA (Multinational Monitoring of Trends and Determinants in Cardiovascular Disease) health survey. Analyses were stratified for age and sex. RESULTS: In the SAH patients, the median year of SAH was 1992 and the median year of death was 2001. The MONICA survey in 1994 and the distribution of deaths in the general population in 2001 were used for comparison. Long-term SAH survivors had, compared to the general population, a significantly increased risk for death due to cerebrovascular disease (P < 0.0001), but not for death due to cardiovascular disease. Hypertension was more common in SAH patients compared to survey participants (P < 0.01). CONCLUSION: Cerebrovascular causes of death were significantly more common in long-term survivors after SAH compared to the general population.
29.	Lindgren, Cecilia, 1958-, et al. (författare) Long term survivors of subarachnoid haemorrhage have an increased risk of death due to cerebrovascular causes Annan publikation (övrigt vetenskapligt/konstnärligt)
30.	Lindgren, Cecilia, 1958- (författare) Subarachnoid haemorrhage : clinical and epidemiological studies 2014 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Background: Subarachnoid haemorrhage (SAH) is a severe stroke that in 85% of all cases is caused by the rupture of a cerebral aneurysm. The median age at onset is 50-55 years and the overall mortality is approximately 45%.Sufficient cortisol levels are important for survival. After SAH hypothalamic/pituitary blood flow may be hampered this could result in inadequate secretion of cortisol. SAH is also associated with a substantial inflammatory response. Asymmetric dimethyl arginine (ADMA), an endogenous inhibitor of nitric oxide synthase, mediates vasoconstriction and increased ADMA levels may be involved in inflammation and endothelial dysfunction. Continuous electroencephalogram (EEG) monitoring can be used to detect non-convulsive seizures, leading to ischemic insults in sedated SAH patients. Elevated ADMA levels are risk factors for vascular diseases. Vascular disease has been linked to stress, inflammation and endothelial dysfunction. SAH possesses all those clinical features and theoretically SAH could thus induce vascular disease.Aims: 1. Assess cortisol levels after SAH, and evaluate associations between cortisol and clinical parameters. 2. Assess ADMA levels and arginine/ADMA ratios after SAH and evaluate associations between ADMA levels and arginine/ADMA ratios with severity of disease, co-morbidities, sex, age and clinical parameters. 3. Investigate occurrence of subclinical seizures in sedated SAH patients. 4. Evaluate if patients that survive a SAH ≥ one year have an increased risk of vascular causes of death compared to a normal population.Results: Continuous infusion of sedative drugs was the strongest predictor for a low (<200 nmol/L) serum cortisol. The odds ratio for a sedated patient to have a serum cortisol < 200 nmol/L was 18.0 times higher compared to an un-sedated patient (p < 0.001). Compared to admission values, 0-48 hours after SAH, CRP increased significantly already in the time-interval 49-72 hours (p<0.05), peaked in the time-interval 97-120 hours after SAH and thereafter decreased. ADMA started to increase in the time-interval 97-120 hours (p<0.05). ADMA and CRP levels were significantly higher, and arginine/ADMA ratios were significantly lower in patients with a more severe condition (p<0.05). Epileptic seizure activity, in sedated SAH patients, was recorded in 2/28 (7.1%) patients during 5/5468 (0.09%) hours of continuous EEG monitoring. Cerebrovascular disease was significantly more common as a cause of death in patients that had survived a SAH ≥ one year, compared to the population from the same area (p<0.0001).Conclusions: Continuous infusion of sedative drugs was associated with low (<200 nmol/L) cortisol levels. ADMA increased significantly after SAH, after CRP had peaked, indicating that endothelial dysfunction, with ADMA as a marker, is induced by a systemic inflammation. Patients with a more severe condition had significantly higher ADMA and CRP levels, and significantly lower arginine/ADMA ratio. Continuous sedation in sedated SAH patients seems to be beneficial in protecting from subclinical seizures. Cerebrovascular causes of death are more common in SAH survivors.
31.	Lindvall, Peter, et al. (författare) Reducing intracranial pressure may increase survival among patients with bacterial meningitis 2004 Ingår i: Clinical Infectious Diseases. - Chicago : Univ. of Chicago Press. - 1058-4838 .- 1537-6591. ; 38:3, s. 384-390 Tidskriftsartikel (refereegranskat)abstract We reported findings concerning continuous intracranial pressure (ICP) and cerebral perfusion pressure (CPP) measurements and mortality in patients with severe bacterial meningitis treated on the basis of an ICP-targeted approach. Eighteen patients with severe bacterial meningitis were admitted for neurointensive care at Umeå University Hospital (Umeå, Sweden). In 15 patients, ICP was measured continuously through an ICP measuring device. During care, all patients but one developed intracranial hypertension with an ICP of ⩾15 mm Hg (14 [93%] of 15 patients). Ten (67%) of 15 patients survived and were discharged, and 5 patients (33%) died. Mean ICP was significantly higher and CPP was markedly decreased in nonsurvivors, compared with survivors. Among the survivors, ICP was gradually reduced. Treatment of patients with severe bacterial meningitis should include neurointensive care and continuous ICP measurement. Increased ICP may be reduced by using the ICP-targeted therapy that closely resembles the “Lund concept.”
32.	Malm, J., et al. (författare) The Swedish Malignant Middle cerebral artery Infarction Study : long-term results from a prospective study of hemicraniectomy combined with standardized neurointensive care 2006 Ingår i: Acta Neurologica Scandinavica. - Copenhagen : Munksgaard. - 0001-6314 .- 1600-0404. ; 113:1, s. 25-30 Tidskriftsartikel (refereegranskat)abstract Objectives: Hemicraniectomy in patients with malignant middle cerebral artery (mMCA) infarct may be life-saving. The long-term prognosis is unknown.Methods: Patients with mMCA infarct treated with hemicraniectomy between 1998 and 2002 at three hospitals were included. The criterion for surgical intervention was if the patients deteriorated from awake to being responding to painful stimuli only. All patients were followed for at least 1 year. Outcome was defined as alive/dead, walkers/non-walkers or modified Rankin Scale (mRS) score ≤2.Results: Thirty patients were included (median age at stroke onset 49 years, range 17–67 years). Fourteen patients had mMCA infarct on the left side and 16 patients on the right side. Fourteen patients had pupil dilatation before surgery. Hemicraniectomy was performed at a median of 52 h (range 13–235 h) after stroke onset. Nine patients died within 1 month after surgery because of cerebral herniation (n = 6), myocardial infarction (n = 1) or intensive care complications (n = 2). No further deaths occurred during follow-up, which was at median 3.4 years after surgery. Status for the 21 survivors at the last follow-up was: mRS 2 or less (n = 6) and mRS 3–5 (n = 15). The oldest patient with mRS 2 or less was 53 years at stroke onset. Thirteen patients (43%) could walk without substantial aid.Conclusion: The long-term survival after mMCA infarction treated with hemicraniectomy seems to be favourable if the patient survives the acute phase. The outcome as measured with mRS may be better among younger patients.
33.	Naredi, Silvana, 1953, et al. (författare) A standardized neurosurgical neurointensive therapy directed toward vasogenic edema after severe traumatic brain injury: clinical results. 1998 Ingår i: Intensive care medicine. - 0342-4642. ; 24:5, s. 446-51 Tidskriftsartikel (refereegranskat)abstract Analysis of a standardized therapy focusing on prevention and treatment of vasogenic edema in patients suffering severe traumatic brain injury (TBI).
34.	Naredi, Silvana, 1953 (författare) Cerebral circulation and the sympathetic nervous system in patients with traumatic brain injury or subarachnoid hemorrhage 2000 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Maintenance of adequate cerebral microcirculation is necessary to avoid cerebral ischemia after severe traumatic brain injury and non-traumatic subarachnoid hemorrhage. After severe traumatic brain injury the blood-brain-barrier is disrupted and transcapillary leakage will contribute to the development of vasogenic brain edema. The edema causes a compromised microcirculation.Systemic complications and cerebral vasospasm observed after non-traumatic subarachnoid hemorrhage may be associated with an activated sympathetic nervous system. Although in-creased concentrations of plasma and urinary norepinephrine are found in patients following subarachnoid hemorrhage, this does not necessarily indicate an activated sympathetic nervous system. To adequately assess an activation of the sympathetic nervous system both release and removal processes of norepinephrine must be considered.A therapy focused on physiological principles for volume regulation and preserved microcir-culation following traumatic brain injury was evaluated in two clinical studies. Prostacyclin may improve cerebral microcirculation after severe traumatic brain injury due to its inhibition of platelet/leukocyte aggregation and adhesion to endothe-lium. Safety profile and outcome after prostacyclin administration was evaluated in the sec-ond study. With an isotope dilution technique the duration and magnitude of the sympathetic nervous activation in patients following subarachnoid hemorrhage was measured and the presumed inhibitory effect of clonidine on sympathetic nervous activation was tested.Favorable outcome after severe traumatic brain injury was 71% in both studies and the mor-tality rate was 13% and 3% respectively. Prostacyclin did not cause any severe side effects. Patients following subarachnoid hemorrhage exhibited an extreme elevation in sympathetic nervous system activity that persisted for at least one week after the insult. Contrary to what would be expected, clonidine did not reduce sympathetic nervous activation in patients fol-lowing subarachnoid hemorrhage.
35.	Naredi, Silvana, 1953, et al. (författare) Increased sympathetic nervous activity in patients with nontraumatic subarachnoid hemorrhage. 2000 Ingår i: Stroke; a journal of cerebral circulation. - 0039-2499. ; 31:4, s. 901-6 Tidskriftsartikel (refereegranskat)abstract Activation of the sympathetic nervous system, which leads to elevation of circulating catecholamines, is implicated in the genesis of cerebral vasospasm and cardiac aberrations after subarachnoid hemorrhage. To this juncture, sympathetic nervous testing has relied on indirect methods only.
36.	Naredi, Silvana, 1953, et al. (författare) Sympathetic activation and inflammatory response in patients with subarachnoid haemorrhage 2006 Ingår i: Intensive Care Med. - 0342-4642. ; 32:12, s. 1955-61 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: The aim of this study was to evaluate the correlation between sympathetic nervous activation and the immune response in patients following subarachnoid haemorrhage (SAH). DESIGN AND SETTING: Clinical study in a neurosurgical intensive care unit. PATIENTS AND PARTICIPANTS: Fourteen patients with acute non-traumatic SAH were included. Fifteen healthy, age-matched volunteers served as controls for measurement of catecholamine spillover. INTERVENTION: Blood sampling for C3a, C5b-9, IL-6, IL-8 and norepinephrine kinetic determination was made within 48 h, at 72 h and on the 7th-10th day after the SAH. MEASUREMENTS AND RESULTS: SAH patients exhibited a profound increase in the rate of norepinephrine spillover to plasma at 48 h, 72 h and 7-10 days after the insult, 3-4 times that in healthy individuals. The plasma levels of C3a, IL-6 and C5b-9 were significantly elevated at 48 h, at 72 h and 7-10 days after the SAH, but the plasma level of IL-6 decreased significantly 7-10 days after the SAH. There was no relationship between the magnitude of sympathetic activation and the levels of inflammatory markers. CONCLUSIONS: Following SAH a pronounced activation of the sympathetic nervous system and the inflammatory system occurs. The lack of significant association between the rate of spillover of norepinephrine to plasma and the plasma levels of inflammatory markers indicates that the two processes, sympathetic activation and the immune response, following SAH are not quantitatively linked. In spite of a persistent high level of sympathetic activation the plasma level of IL-6 decreased significantly one week after SAH.
37.	Naredi, Silvana, 1953, et al. (författare) Treatment of traumatic head injury--U.S./European guidelines or the Lund concept. 2003 Ingår i: Critical care medicine. - 0090-3493 .- 1530-0293. ; 31:11, s. 2713-4 Tidskriftsartikel (refereegranskat)
38.	Naredi, Silvana, 1953, et al. (författare) Vasogenic edema and brain trauma. 1999 Ingår i: Intensive Care Medicine. - 0342-4642 .- 1432-1238. ; 25, s. 244-245 Forskningsöversikt (refereegranskat)
39.	Nordenskjöld Syrous, Anna, et al. (författare) Swedish intensivists' experiences and attitudes regarding end-of-life decisions 2020 Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 64:5, s. 656-62 Tidskriftsartikel (refereegranskat)abstract 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.
40.	Nyberg, Christoffer, 1977- (författare) Metabolic and Endocrine Response in the Acute Stage of Subarachnoid Hemorrhage 2017 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract The rupture of an aneurysm in subarachnoid hemorrhage (SAH) is a dramatic event causing a severe impact on the brain and a transient or permanent ischemic condition. Several types of responses to meet the challenges of SAH have been found in the acute phase, including activation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system, elevated levels of brain natriuretic peptide (BNP), and disturbances in cerebral and systemic metabolism.Cerebral metabolism and the endocrine stress response in the ultra-early phase was investigated in a novel porcine model of SAH in which autologous blood was injected to the anterior skull base. Early activation of the HPA axis was found with rapid elevation of adrenocorticotrophic hormone, cortisol and aldosterone. The peak values of these hormones were early and may be impossible to catch in patients. There were indications of a sympathetic nervous response with excretion of catecholamines in urine as well as plasma chromogranin-A elevation. Cerebral microdialysis suggested immediate substrate failure followed by hypermetabolism of glucose. The animal model seems suited for further studies of aneurysmal SAH.NT-proBNP was investigated in 156 patients with SAH, there was a dynamic course with increasing levels during the first 4 days of the disease. Factors predicting high NT-proBNP load included female sex, high age, high Troponin-I at admission, angiographic finding of an aneurysm and worse clinical condition at admission. High levels of NT-proBNP were correlated to factors indicating a more severe disease, suggesting the initial injury in aneurysmal SAH is an important factor in predicting high NT-proBNP during the acute stage of the disease.Measurements with indirect calorimetry were performed daily during the first week after SAH on 32 patients with SAH. There was a dynamic course with increasing energy expenditure (EE) the first week after SAH. Comparisons with three predictive equations indicated that measured EE generally is higher than predicted, but considerable variation exists within and between patients, indicating that prediction of EE in SAH is difficult.Altogether, the studies demonstrate a complicated response in acute SAH that needs to be further studied to increase possibility of good outcome in SAH patients.
41.	Odenstedt Hergès, Helena, et al. (författare) Machine learning analysis of heart rate variability to detect delayed cerebral ischemia in subarachnoid hemorrhage 2022 Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 145:2, s. 151-159 Tidskriftsartikel (refereegranskat)abstract 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.
42.	Olivecrona, Magnus, et al. (författare) Absence of electroencephalographic seizure activity in patients treated for head injury with an ICP targeted therapy 2009 Ingår i: Journal of Neurosurgery. - : Journal of Neurosurgery Publishing Group (JNSPG). - 0022-3085 .- 1933-0693. ; 110:2, s. 300-305 Tidskriftsartikel (refereegranskat)abstract OBJECT: The authors prospectively studied the occurrence of clinical and nonclinical electroencephalographically verified seizures during treatment with an intracranial pressure (ICP)-targeted protocol in patients with traumatic brain injury (TBI). METHODS: All patients treated for TBI at the Department of Neurosurgery, University Hospital Umea, Sweden, were eligible for the study. The inclusion was consecutive and based on the availability of the electroencephalographic (EEG) monitoring equipment. Patients were included irrespective of pupil size, pupil reaction, or level of consciousness as long as their first measured cerebral perfusion pressure was > 10 mm Hg. The patients were treated in a protocol-guided manner with an ICP-targeted treatment based on the Lund concept. The patients were continuously sedated with midazolam, fentanyl, propofol, or thiopental, or combinations thereof. Five-lead continuous EEG monitoring was performed with the electrodes at F3, F4, P3, P4, and a midline reference. Sensitivity was set at 100 muV per cm and filter settings 0.5-70 Hz. Amplitude-integrated EEG recording and relative band power trends were displayed. The trends were analyzed offline by trained clinical neurophysiologists. RESULTS: Forty-seven patients (mean age 40 years) were studied. Their median Glasgow Coma Scale score at the time of sedation and intubation was 6 (range 3-15). In 8.5% of the patients clinical seizures were observed before sedation and intubation. Continuous EEG monitoring was performed for a total of 7334 hours. During this time neither EEG nor clinical seizures were observed. CONCLUSIONS: Our protocol-guided ICP targeted treatment seems to protect patients with severe TBI from clinical and subclinical seizures and thus reduces the risk of secondary brain injury.
43.	Olivecrona, Magnus, et al. (författare) Effective ICP reduction by decompressive craniectomy in patients with severe traumatic brain injury treated by an ICP-targeted therapy 2007 Ingår i: Journal of Neurotrauma. - 0897-7151 .- 1557-9042. ; 24:6, s. 927-935 Tidskriftsartikel (refereegranskat)abstract Severe traumatic brain injury (TBI) is one of the major causes of death in younger age groups. In Umea, Sweden, an intracranial pressure (ICP) targeted therapy protocol, the Lund concept, has been used in treatment of severe TBI since 1994. Decompressive craniectomy is used as a protocol-guided treatment step. The primary aim of the investigation was to study the effect of craniectomy on ICP changes over time in patients with severe TBI treated by an ICP-targeted protocol. In this retrospective study, all patients treated for severe TBI during 1998-2001 who fulfilled the following inclusion criteria were studied: GCS 10 mm Hg, arrival within 24 h of trauma, and need of intensive care for >72 h. Craniectomy was performed when the ICP could not be controlled by evacuation of hematomas, sedation, ventriculostomy, or low-dose pentothal infusion. Ninety-three patients met the inclusion criteria. Mean age was 37.6 years. Twenty-one patients underwent craniectomy as a treatment step. We found a significant reduction of the ICP directly after craniectomy, from 36.4 mm Hg (range, 18-80 mm Hg) to 12.6 mm Hg (range, 2-51 mm Hg). During the following 72 h, we observed an increase in ICP during the first 8-12 h after craniectomy, reaching approximately 20 mm Hg, and later levelling out at approximately 25 mm Hg. The reduction of ICP was statistically significant during the 72 h. The outcome as measured by Glasgow Outcome Scale (GOS) did not significantly differ between the craniectomized group (DC) and the non-craniectomized group (NDC). The outcome was favorable (GOS 5-4) in 71% in the craniectomized group, and in 61% in the non-craniectomized group. Craniectomy is a useful tool in achieving a significant reduction of ICP overtime in TBI patients with progressive intracranial hypertension refractory to medical therapy. The procedure seems to have a satisfactory effect on the outcome, as demonstrated by a high rate of favorable outcome and low mortality in the craniectomized group, which did not significantly differ compared with the non-craniectomized group.
44.	Olivecrona, Magnus, et al. (författare) Prostacyclin treatment and clinical outcome in severe traumatic brain injury patients managed with an ICP-targeted therapy : A prospective study 2012 Ingår i: Brain Injury. - London : Informa Healthcare. - 0269-9052 .- 1362-301X. ; 26:1, s. 67-75 Tidskriftsartikel (refereegranskat)abstract Objective: To prospectively assess clinical outcome in patients with severe traumatic brain injury (sTBI) managed according to an ICP-targeted programme as well as additional treatment with prostacyclin.Materials and methods: Inclusion criteria were GCS <= 8, age 15-70 years, first recorded cerebral perfusion pressure (CPP)>10mmHg. Exclusion criteria were pregnancy, breastfeeding or penetrating brain injury. The patients were treated using the same ICP-guided protocol, with one group randomized to receive prostacyclin in a low dose (0.5 ng kg(-1) min(-1)). The clinical outcome was prospectively assessed at 3, 6, 12, 18 and 24 months using structured interviews.Results: Forty-eight patients were included, mean age 35.5 years, median GCS 6 (3-8), 69% were multi-traumatized. Mortality at 3 months was 12.5%. Median Glasgow Outcome Scale (GOS) at all follow-up points was 4. Favourable outcome (GOS 4-5) at 3 months was 52%, at 24 months 64%. Favourable outcome increased over time. There was a statistically significant association between GOS, GCS at admission and age. Higher ICP(max) was associated with worse outcome.Conclusion: With this treatment protocol, a low number of deaths and a high number of favourable outcomes in sTBI were observed. Prostacyclin in this low dose does not seem to improve the outcome. ICP(max) is a positive predictor of worse outcome. Higher GCS at admission and lower age are correlated to better outcome.
45.	Olivecrona, Magnus, 1959-, et al. (författare) Prostacyclin treatment in severe traumatic brain injury : a microdialysis and outcome study 2009 Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert Inc. - 0897-7151 .- 1557-9042. ; 26:8, s. 1251-1262 Tidskriftsartikel (refereegranskat)abstract Prostacyclin (PGI2) is a potent vasodilator, inhibitor of leukocyte adhesion, and platelet aggregation. In trauma the balance between PGI2 and thromboxane A2 (TXA2) is shifted towards TXA2. External provided PGI2 would, from a theoretical and experimental point of view, improve the microcirculation in injured brain tissue. This study is a prospective consecutive double blinded randomised study on the effect of PGI2 versus placebo in severe traumatic brain injury (sTBI). All patients with sTBI were eligible. Inclusion criteria: verified sTBI, Glasgow Coma Score (GCS) at intubation and sedation ≤8, age 15 - 70 years, a first recorded cerebral perfusion pressure (CPP) of ≥ 10mmHg, and arrival within 24h of trauma. All subjects received an intra-cranial pressure (ICP) measuring device, bilateral intracerebral microdialysis catheters, and a microdialysis catheter in the abdominal subcutaneous adipose tissue. Subjects were treated according to an ICP targeted therapy based on the Lund concept. 48 patients, mean age of 35.5 years, and a median GCS 6 (3-8) were included. We found no significant effect of epoprostenol on either the lactate pyruvate ratio (L/P) at 24 hours or the brain glucose levels. There was no significant difference in clinical outcome between the two groups. The median Glasgow Outcome Score (GOS) at 3 months was 4, and mortality was 12.5%. The favourable outcome (GOS 4-5) was 52%. The initial L/P did not prognosticate for outcome. Thus our results indicate that there is no effect of PGI2 at a dose of 0.5 ng/kg/min on brain L/P, brain glucose levels or outcome at 3 months. The treatment seemed to yield a high number of favourable outcome and low mortality
46.	Olivecrona, Magnus, et al. (författare) S-100B and neuron specific enolase are poor outcome predictors in severe traumatic brain injury treated by an intracranial pressure targeted therapy 2009 Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 80:11, s. 1241-1247 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: To prospectively study S-100B and neuron specific enolase (NSE) levels in subjects treated for severe head injury (sTBI), and investigate the prognostic value of these biomarkers. METHODS: Subjects included in a prospective double blind randomised study for sTBI. Inclusion criteria: Glasgow Coma Score (GCS) 10 mm Hg and arrival <24 h after trauma. Subjects were treated with an intracranial pressure (ICP) targeted therapy. Blood samples for S-100B and NSE were drawn immediately after arrival and every 12 h for 5 days. Outcome was evaluated as Glasgow Outcome Scale (GOS) by independent staff at 3 and 12 months. RESULTS: 48 subjects, mean age 35.5 years, and median GCS 6 were included. The first blood sample was drawn at 15.6 (1.4) h after injury. Initial concentration of S-100B was 1.04 (0.21) microg/l and for NSE 18.94 (2.32) microg/l. The biomarkers were significantly higher in subjects with GCS 3 and in those who died compared with those with GCS 4-8 and GOS 2-5, respectively. Receiver operated characteristic curve analyses of the initial S-100B and NSE levels to GOS dichotomised as unfavourable (GOS 1-3) and favourable (GOS 4-5) showed a weak correlation: AUC 0.585 and 0.555, respectively. Using the dichotomisation dead (GOS 1)/alive (GOS 2-5), the AUC values were 0.687 and 0.734, respectively. Furthermore, a correlation was found between the biomarkers themselves and the biomarkers and ICP. CONCLUSION: At 3 and 12 months after trauma, no differences in prognostic values between the markers were apparent nor was there any clinical significant value of the markers as predictors of clinical outcome.
47.	Olivecrona, Magnus, et al. (författare) S-100B and NSE are poor outcome predictors in severe traumatic brain injury treated by an ICP targeted therapy Annan publikation (övrigt vetenskapligt/konstnärligt)
48.	Olofsson, Anders D, et al. (författare) The implementation of distance teaching in the Swedish Regionalized Medical Program - multiple small steps of change for an inert system 2013 Ingår i: Book of Abstracts of the 40th AMEE-conference. - Prague. ; , s. 329-329 Konferensbidrag (refereegranskat)abstract Background: This study examines possibilities and challenges when implementing distance teaching for teaching theoretical content in the Swedish regionalized medical program (RMP). The distance teaching by means of digital technologies and Technology-Enhanced Learning (TEL) is seen as an alternative to the face-to-face teaching in the medical program. Summary of work: A framework built upon the work of Sannino (2008) including the notion of dominant and non-dominant activities, conflicts and transitional actions were used for analysis. Summary of results: In the results a number of conflicts were identified which inhibit medical teachers from adopting especially interactive and communicative elements of distance teaching. Those were for example teachers’ digital literacy, lack of trust in digital teaching tools and willingness to keep to the face-to-face teaching practice. Conclusions: Illustrated by transitional actions it is discussed how the non-dominant distance teaching activity actually functioned as a catalyst for minor but important changes in the medical teachers’ dominant face-to-face teaching practice. Based on the results from this study one can raise the question of what really can be seen as a success or a failure when implementing TEL in medical education. Implementation processes in medical education is a process of interplay between dominant and non-dominant activities. Recognizing such interplay provides possibilities for future educational development. Take-home messages: Implementing distance teaching is not a straightforward process but rather characterized by small steps of change that needs to be continuously supported by the medical program management.
49.	Pålsson, Paul, 1982, et al. (författare) Physicians’ self-perceived preparedness for clinical supervision of medical students at university and non-university hospitals-results from a Swedish survey 2023 Ingår i: BMC Medical Education. - 1472-6920. ; 23:1 Tidskriftsartikel (refereegranskat)abstract 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.
50.	Rodling Wahlström, Marie, et al. (författare) Effects of prostacyclin on the early inflammatory response in patients with traumatic brain injury : a randomised clinical study 2014 Ingår i: SpringerPlus. - : Springer. - 2193-1801. ; 3 Tidskriftsartikel (refereegranskat)abstract 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.

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