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  • 1.
    Brorsson, Camilla
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nilsson, Leif
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Saliva stimulation with glycerine and citric acid does not affect salivary cortisol levels2014In: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 81, no 2, p. 244-248Article in journal (Refereed)
    Abstract [en]

    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.

  • 2.
    Brorsson, Camilla
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nilsson, Leif
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Thunberg, Johan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Sylvan, Anders
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Adrenal response after trauma is affected by time after trauma and sedative/analgesic drugs2014In: Injury, ISSN 0020-1383, E-ISSN 1879-0267, Vol. 45, no 8, p. 1149-1155Article in journal (Refereed)
    Abstract [en]

    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.

  • 3.
    Brorsson, Camilla
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Rodling-Wahlström, Marie
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Olivecrona, Magnus
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Koskinen, Lars-Owe
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Severe traumatic brain injury: consequences of early adverse events2011In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 55, no 8, p. 944-951Article in journal (Refereed)
    Abstract [en]

    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.

  • 4.
    Fjellström, Mona
    et al.
    Umeå University, Faculty of Arts, Centre for Teaching and Learning (UPC).
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Sawert, Bertil
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation.
    Johnson, Owe
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    En bro mellan högre utbildning och profession: Utbildning för kliniska handledare i läkarutbildning2012In: Nu 2012 Göteborg 17-19 oktober 2012: Gränslöst lärande, Göteborg, 2012, p. 131-132Conference paper (Refereed)
    Abstract [sv]

    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.

  • 5. Grände, P. O.
    et al.
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Clinical studies in severe traumatic brain injury: a controversial issue2002Other (Other (popular science, discussion, etc.))
  • 6. Grände, P-O
    et al.
    Koskinen, L-O
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Naredi, S
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Reinstrup, P
    Romner, B
    Conventional treatments for severe head injury: are they effective, ineffective, or even harmful?2007In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 51, no 10, p. 1294-1296Article in journal (Other academic)
  • 7.
    Koskinen, L. O.
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Olivecrona, M.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Rodling-Wahlstrom, M.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Naredi, S.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Prostacyclin treatment normalises the MCA flow velocity in nimodipine-resistant cerebral vasospasm after aneurysmal subarachnoid haemorrhage: a pilot study2009In: Acta Neurochir (Wien), Vol. 151, no 6, p. 595-9; discussion 599Article in journal (Refereed)
    Abstract [en]

    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.

  • 8.
    Kralova, Ivana
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Winsö, Ola
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Olivecrona, Magnus
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Non-traumatic subarachnoid hemorrhage is associated with subnormal blood creatinine levels2010In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 70, no 6, p. 438-446Article in journal (Refereed)
    Abstract [en]

    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.

  • 9. Lambert, G.
    et al.
    Naredi, S.
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Eden, E.
    Rydenhag, B.
    Friberg, P.
    Monoamine metabolism and sympathetic nervous activation following subarachnoid haemorrhage: influence of gender and hydrocephalus2002In: Brain Res Bull, Vol. 58, no 1, p. 77-82Article in journal (Refereed)
    Abstract [en]

    Subarachnoid haemorrhage is a serious condition, often accompanied by cerebral vasospasm and hydrocephalus, which may result in delayed cerebral ischaemia and neurological deterioration. While the mechanisms responsible remain unknown, activation of the sympathetic nervous system, leading to elevated levels of circulating catecholamines is, at least in part, implicated. In this study, we sought to examine the importance of sympathetic nervous activation and its relation to brain monoaminergic neurotransmission in 25 patients following subarachnoid haemorrhage by examining plasma and cerebrospinal fluid levels of the catecholamines noradrenaline, adrenaline and dopamine, and their metabolites. Total body sympathetic activity was concurrently assessed using isotope dilution methodology. In the early phase following subarachnoid haemorrhage patients exhibited markedly elevated rates of spillover of noradrenaline to plasma (9.11 +/- 1.12 vs. 3.39 +/- 0.26 nmol/min, p < 0.01), with rates being higher in those patients in whom hydrocephalus developed (11.15 +/- 1.40 vs. 7.90 +/- 1.41 nmol/min, p = 0.05). The degree of sympathetic nervous activation tended to be higher in females compared with males. Lower cerebral perfusion pressures were observed in those patients in whom cerebrospinal fluid concentrations of noradrenaline and dopamine metabolites were high. A marked sympathetic nervous activation, more pronounced in women and in those with hydrocephalus, occurs following subarachnoid haemorrhage. The diminished cerebral perfusion seen following subarachnoid bleeding may occur as a result of activation of central catecholaminergic neurones.

  • 10. Lambert, G.
    et al.
    Naredi, S.
    Eden, E.
    Rydenhag, B.
    Friberg, P.
    Sympathetic nervous activation following subarachnoid hemorrhage: Influence of intravenous clonidine2002In: Acta Anaesthesiol Scand, Vol. 46, no 2, p. 160-5Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: 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. METHODS: Using isotope dilution methodology, norepinephrine kinetic determinations, comprising determination of arterial norepinephrine concentration and rates of norepinephrine spillover to and removal, or clearance, from plasma, were performed on three occasions during the first week after subarachnoid hemorrhage in 25 patients. Eleven of these patients received clonidine (continuous i.v. infusion 5.8 +/- 0.7 microg x kg(-1) x 24 h(-1)) and the remainder, standard therapy. Initial results were compared with 17 healthy age-matched subjects and eight patients suffering from severe traumatic brain injury without traumatic subarachnoid hemorrhage. RESULTS: Subarachnoid hemorrhage patients exhibited markedly elevated arterial plasma norepinephrine concentrations [3.74 +/- 0.48, P < 0.001 vs. healthy subjects (1.59 +/- 0.11 nmol/L) and P < 0.05 vs. head trauma patients (1.94 +/- 0.29 nmol/L)]. The rate of clearance of norepinephrine from plasma in the subarachnoid patients was also significantly greater than that observed in the healthy subjects (2.66 +/- 0.15 vs. 2.14 +/- 0.15 L/min, P < 0.05) and the head trauma patients (2.00 +/- 0.12 L/min, P < 0.05). Compared with both control groups, on admission the rate of spillover of norepinephrine to plasma following subarachnoid hemorrhage was markedly elevated (9.11 +/- 1.12, P < 0.001). Clonidine treatment (continuous i.v. infusion 5.8 +/- 0.7 microg x kg(-1) x 24 h(-1)) did not reduce the increased rate of spillover of norepinephrine to plasma following subarachnoid hemorrhage. CONCLUSION: Sympathetic nervous activity is markedly elevated following subarachnoid bleeding. Clonidine had no effect on the rate of norepinephrine spillover to, or clearance from, plasma in these patients. Clearly, further studies are required to elucidate the mechanisms responsible for generating sympathetic nervous activation following subarachnoid hemorrhage.

  • 11.
    Lindgren, Cecilia
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lindvall, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Nilsson, Leif
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Koskinen, Lars-Owe
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Cortisol levels are influenced by sedation in the acute phase after subarachnoid haemorrhage2013In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 57, no 4, p. 452-460Article in journal (Refereed)
    Abstract [en]

    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.

  • 12.
    Lindgren, Cecilia
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Hultin, Magnus
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Koskinen, Lars-Owe D
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Lindvall, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Borota, Ljubisa
    Department of Radiology, Oncology and Radiation Science, Uppsala University, Sweden .
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    ADMA levels and arginine/ADMA ratios reflect severity of disease and extent of inflammation after subarachnoid hemorraghe2014In: Neurocritical Care, ISSN 1541-6933, E-ISSN 1556-0961, Vol. 21, no 1, p. 91-101Article in journal (Refereed)
    Abstract [en]

    Background: 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.

    Methods: 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.

    Results: 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.

    Conclusions: 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.

  • 13.
    Lindgren, Cecilia
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Hultin, Magnus
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Koskinen, Lars-Owe
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Edvardsson, Ludwig
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology. Göteborgs universitet.
    Long term survivors of subarachnoid haemorrhage have an increased risk of death due to cerebrovascular causesManuscript (preprint) (Other academic)
  • 14.
    Lindgren, Cecilia
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Nordh, Erik
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Olivecrona, Magnus
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Frequency of non-convulsive Seizures and non-convulsive status Epilepticus in Subarachnoid Hemorrhage patients in need of controlled ventilation and sedation2012In: Neurocritical Care, ISSN 1541-6933, E-ISSN 1556-0961, Vol. 17, no 3, p. 367-373Article in journal (Refereed)
    Abstract [en]

    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.

  • 15.
    Lindvall, Peter
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Ericsson, Mats
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Gothefors, Leif
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Koskinen, Lars-Owe D
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Reducing intracranial pressure may increase survival among patients with bacterial meningitis2004In: Clinical Infectious Diseases, ISSN 1058-4838, E-ISSN 1537-6591, Vol. 38, no 3, p. 384-390Article in journal (Refereed)
    Abstract [en]

    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.”

  • 16.
    Malm, J.
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Bergenheim, A. T.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Enblad, P.
    Department of Neuroscience/Neurosurgery, University Hospital, Uppsala, Sweden.
    Hårdemark, H.-G.
    Department of Neuroscience/Neurosurgery, University Hospital, Uppsala, Sweden.
    Koskinen, L-O D
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Nordström, C.-H.
    Department of Clinical Sciences, Lund, University Hospital, Lund, Sweden.
    Norrving, B.
    Department of Clinical Sciences, Lund, University Hospital, Lund, Sweden.
    Uhlin, J.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Lindgren, A.
    Department of Clinical Sciences, Lund, University Hospital, Lund, Sweden.
    The Swedish Malignant Middle cerebral artery Infarction Study: long-term results from a prospective study of hemicraniectomy combined with standardized neurointensive care2006In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 113, no 1, p. 25-30Article in journal (Refereed)
    Abstract [en]

    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.

  • 17.
    Naredi, S.
    et al.
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Koskinen, L. O.
    Umeå University, Faculty of Medicine, Pharmacology and Clinical Neuroscience, Neurosurgery.
    Grände, P. O.
    Nordström, C. H.
    Nellgård, B.
    Rydenhag, B.
    Vegfors, M.
    Treatment of traumatic head injury--U.S./European guidelines or the Lund concept2003In: Crit Care Med, Vol. 31, no 11, p. 2713-4Article in journal (Refereed)
  • 18.
    Naredi, S.
    et al.
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Olivecrona, M.
    Lindgren, C.
    Östlund, A. L.
    Grände, P. O.
    Koskinen, L. O.
    An outcome study of severe traumatic head injury using the "Lund therapy" with low-dose prostacyclin2001In: Acta Anaesthesiol Scand, Vol. 45, no 4, p. 402-6Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: There are two independent head injury outcome studies using the "Lund concept", and both showed a mortality rate of about 10%, and a favourable outcome (Glasgow outcome scale, GOS 4 and 5) of about 70%. The Lund concept aims at controlling intracranial pressure, and improving microcirculation around contusions. Intracranial pressure is controlled by maintaining a normal colloid osmotic pressure and reducing the hydrostatic capillary pressure. Microcirculation is improved by ensuring strict normovolaemia and reducing sympathetic discharge. The endogenous substance prostacyclin with its antiaggregatory/antiadhesive effects may further improve microcirculation, which finds support from a microdialysis-based clinical study and an experimental brain trauma study. The present clinical outcome study aims at evaluating whether the previously obtained good outcome with the Lund therapy can be reproduced, and whether the addition of prostacyclin has any adverse side-effects. METHODS: All 31 consecutive patients with severe head injury, Glasgow coma scale (GCS) < or = 8, admitted to the University Hospital of Umea during 1998 were included. The Lund therapy including prostacyclin infusion for the first three days at a dose of 0.5 ng kg(-1) min(-1). Outcome was evaluated according to the GOS >10 months after the injury. RESULTS: One patient died, another suffered vegetative state and 7 severe disability. Of the 22 patients with favourable outcome, 19 showed good recovery and 3 moderate disability. No adverse side-effects of prostacyclin were observed. CONCLUSION: The outcome results from previous studies using the Lund therapy were reproduced, and no adverse side-effects of low-dose prostacyclin were observed.

  • 19.
    Naredi, Silvana
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Lambert, Gavin
    Friberg, Peter
    Zäll, Stefan
    Edén, Elisabeth
    Rydenhag, Bertil
    Tylman, Maria
    Bengtsson, Anders
    Sympathetic activation and inflammatory response in patients with subarachnoid haemorrhage.2006In: Intensive Care Medicine, ISSN 0342-4642, Vol. 32, no 12, p. 1955-61Article in journal (Refereed)
    Abstract [en]

    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.

  • 20.
    Olivecrona, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Rodling Wahlström, Marie
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Koskinen, Lars-Owe D
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Effective ICP reduction by decompressive craniectomy in patients with severe traumatic brain injury treated by an ICP-targeted therapy2007In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 24, no 6, p. 927-935Article in journal (Refereed)
    Abstract [en]

    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 <or= 8 at intubation and sedation, first recorded cerebral perfusion pressure (CPP) of >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.

  • 21.
    Olivecrona, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Rodling Wahlström, Marie
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Koskinen, Lars-Owe D
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Prostacyclin treatment in severe traumatic brain injury: a microdialysis and outcome study2009In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 26, no 8, p. 1251-1262Article in journal (Refereed)
    Abstract [en]

    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

  • 22.
    Olivecrona, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Rodling-Wahlstrom, Marie
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Koskinen, Lars-Owe D.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Prostacyclin treatment and clinical outcome in severe traumatic brain injury patients managed with an ICP-targeted therapy: A prospective study2012In: Brain Injury, ISSN 0269-9052, E-ISSN 1362-301X, Vol. 26, no 1, p. 67-75Article in journal (Refereed)
    Abstract [en]

    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.

  • 23.
    Olivecrona, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Rodling-Wahlström, Marie
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Koskinen, Lars-Owe
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    S-100B and neuron specific enolase are poor outcome predictors in severe traumatic brain injury treated by an intracranial pressure targeted therapy2009In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 80, no 11, p. 1241-1247Article in journal (Refereed)
    Abstract [en]

    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.

  • 24.
    Olivecrona, Magnus
    et al.
    Umeå University, Faculty of Medicine, Pharmacology and Clinical Neuroscience.
    Rodling-Wahsltröm, Marie
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Koskinen, Lars-Owe D
    Umeå University, Faculty of Medicine, Pharmacology and Clinical Neuroscience, Neurosurgery.
    S-100B and NSE are poor outcome predictors in severe traumatic brain injury treated by an ICP targeted therapyManuscript (Other academic)
  • 25.
    Olivecrona, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Zetterlund, Bo
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neurophysiology.
    Rodling-Wahlström, Marie
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Koskinen, Lars-Owe D
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Absence of electroencephalographic seizure activity in patients treated for head injury with an ICP targeted therapy2009In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 110, no 2, p. 300-305Article in journal (Refereed)
    Abstract [en]

    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.

  • 26.
    Olofsson, Anders D
    et al.
    Umeå University, Faculty of Social Sciences, Department of Education.
    Pettersson, Fanny
    Umeå University, Faculty of Social Sciences, Department of Education.
    Ljungberg, Christina
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Hultin, Magnus
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    The implementation of distance teaching in the Swedish Regionalized Medical Program - multiple small steps of change for an inert system2013In: Book of Abstracts of the 40th AMEE-conference: Colouring outside the lines / [ed] AMEE, Prague, 2013, p. 329-329Conference paper (Refereed)
    Abstract [en]

    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.

  • 27.
    Rodling Wahlström, Marie
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Olivecrona, Magnus
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Bengtsson, Anders
    The Sahlgrenska Academy, University of Gothenburg.
    Koskinen, Lars-Owe D
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Hultin, Magnus
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Effects of prostacyclin on the early inflammatory response in patients with traumatic brain injury: a randomised clinical study2014In: SpringerPlus, E-ISSN 2193-1801, Vol. 3, article id 98Article in journal (Refereed)
    Abstract [en]

    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.

  • 28.
    Rodling Wahlström, Marie
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Olivecrona, Magnus
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Bengtsson, Anders
    Anestesi och intensivvård, Sahlgrenska Universitetssjukhuset, Göteborg.
    Koskinen, Lars-Owe
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Prostacyclin modulates the systemic inflammatory response in traumatic brain injury: a randomised clinical studyIn: Article in journal (Other academic)
    Abstract [en]

    Purpose:

    Systemic inflammatory response is common in patients with severe traumatic brain injury (TBI), and may contribute to a less favourable outcome. The aim was to evaluate the effect of prostacyclin on systemic inflammation.

    Methods:

    This study is part of a prospective, randomised, clinical trial on the effect of prosta­cyclin (epoprostenol, Flolan®) in patients with severe TBI. Epoprostenol/placebo was given during 72 hours and then de-escalated. Interleukin-6, interleukin-8, soluble intracellular adhesion molecules-1 (sICAM-1) and C-reactive protein (CRP) were sampled daily.

    Results:

    46 patients were included and randomised to 23 of each group (epopros­tenol/placebo). Interleukin-6 was statistically lower within 96 hours (p = 0.04), and CRP within 96 and 120 hours (p = 0.04 and p = 0.008 respectively) after trauma in the epoprostenol group compared to the placebo group. No significant differences were detected between the groups in the levels of interleukin-8 and sICAM-1 or in outcome.

    Conclusions:

    Administration of the prostacyclin analogue epoprostenol, compared to placebo significantly decreased interleukin-6 and CRP levels in patients with severe TBI. The beneficial effect of this decrease is further to investigate.

  • 29.
    Rodling Wahlström, Marie
    et al.
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Olivecrona, Magnus
    Umeå University, Faculty of Medicine, Pharmacology and Clinical Neuroscience, Neurosurgery.
    Koskinen, Lars-Owe
    Umeå University, Faculty of Medicine, Pharmacology and Clinical Neuroscience, Neurosurgery.
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Hultin, Magnus
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Subarachnoid haemorrhage induces a long-lasting increase of asymmetric dimethylarginine, ADMA, in serumArticle in journal (Other academic)
    Abstract [en]

    Background and Purpose: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase (NOS), inhibiting nitric oxide (NO) production and thus induces vasoconstriction and endothelial dysfunction. ADMA might therefore be involved in the cerebral vasospasm and cardiovascular complications observed after subarachnoid haemorrhage (SAH). The aim of this study was to evaluate whether ADMA was increased in subjects during the acute phase (first week) and non-acute phase (three months later) after SAH.

    Methods: Prospective clinical study of 20 subjects with SAH. ADMA in serum (ADMA/s) at admission was compared to sex and age matched controls. ADMA/s and ADMA in cerebrospinal fluid (ADMA/csf, from subjects with ventriculostomy) were determined by HPLC-based separation and detection.

    Results: There was no significant difference in ADMA/s the day after SAH (day 2) between SAH subjects and controls (0.22±0.10 vs. 0.25±0.12 µmol/L). ADMA/s increased by 68% during the first week after SAH (day 2; 0.22±0.10 vs. day 7; 0.37±0.34 µmol/L, p<0.05) and remained elevated at a three-month follow-up (0.36±0.10 µmol/L). ADMA/csf was significantly lower than ADMA/s throughout the study period.

    Conclusion; ADMA/s in SAH subjects increased significantly during the first week after SAH and remained elevated at a three-month follow-up. This might indicate that reduction of the available NO is involved in long-term effects after SAH.

  • 30.
    Rodling Wahlström, Marie
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Olivecrona, Magnus
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Koskinen, Lars-Owe
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Hultin, Magnus
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Subarachnoid haemorrhage induces an inflammatory response followed by a delayed persisting increase in asymmetric dimethylarginine2012In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 72, no 6, p. 484-489Article in journal (Refereed)
    Abstract [en]

    Object: Subarachnoid haemorrhage (SAH) is associated with an inflammatory systemic response and cardiovascular complications. Asymmetric dimethyl arginine (ADMA), an endogenous inhibitor of nitric oxide synthase, mediates vasoconstriction and might contribute to cerebral vasoconstriction and cardiovascular complications after SAH. ADMA is also involved in inflammation and induces endo­thelial dysfunction.

    The aim of this study was to evaluate whether and how CRP (marker for systemic inflammation) and ADMA increased in patients during the acute phase (first week) after SAH. The ADMA level was also assessed in the patients in a non-acute phase (three months), and in healthy controls.

    Methods: Prospective study of 20 patients with aneurysmal SAH. ADMA and CRP were followed daily during the first week after SAH and a follow up sample for ADMA was obtained three months later. A single blood sample for ADMA was collected from age and sex matched healthy controls (n=40, 2 for each case).

    Results: CRP increased significantly from day 2; 16  (Confidence interval (CI) 10-23) mg/L to day 4; 84 (CI 47-120) mg/L, (p<0.01). ADMA increased significantly from day 2; 0.22 (CI 0.17-0.27) µmol/L, to day 7; 0.37 (CI 0.21-0.54) µmol/L, p<0.01. ADMA remained elevated at a three-month follow-up 0.36 (CI 0.31-0.42) µmol/L.

    ADMA in the first sample from the patients (day 1-3); 0.25 (CI 0.19-0.30) µmol/L, was not different from ADMA in matched healthy controls; 0.25 (CI 0.20-0.31), p>0.05.

    Conclusion: After SAH, CRP and ADMA in serum increased significantly during the first week and ADMA remained elevated three months later.

  • 31.
    Rodling Wahlström, Marie
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Olivecrona, Magnus
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Nyström, Fredrik
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Koskinen, Lars-Owe
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Fluid therapy and the use of albumin in the treatment of severe traumatic brain injury2009In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 53, p. 18-25Article in journal (Refereed)
    Abstract [en]

    Background: Evidence-based guidelines for severe traumatic brain injury (TBI) do not include strategies for fluid administration. The protocol used in this study includes albumin administration to maintain normal colloid osmotic pressure and advocates a neutral to slightly negative fluid balance. The aim of this study was to analyze the occurrence of organ failure and the mortality in patients with severe TBI treated by a protocol that includes defined strategies for fluid therapy.

    Methods: Ninety-three patients with severe TBI and Glasgow Coma Score ≤ 8 were included during 1998–2001. Medical records of the first 10 days were retrieved. Organ dysfunction was evaluated with the Sequential Organ Failure Assessment (SOFA) score. Mortality was assessed after 10 and 28 days, 6 and 18 months.

    Results: The total fluid balance was positive on days 1–3, and negative on days 4–10. The crystalloid balance was negative from day 2. The mean serum albumin was 38 ± 6 g/l. Colloids constituted 40–60% of the total fluids given per day. Furosemide was administered to 94% of all patients. Severe organ failure defined as SOFA ≥ 3 was evident only for respiratory failure, which was observed in 29%. None developed renal failure. After 28 days, mortality was 11% and, after 18 months, it was 14%.

    Conclusions: A protocol including albumin administration in combination with a neutral to a slightly negative fluid balance was associated with low mortality in patients with severe TBI in spite of a relatively high frequency (29%) of respiratory failure, assessed with the SOFA score.

  • 32.
    Sjöberg, Rickard L.
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Bergenheim, Tommy
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Mörén, Lina
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Antti, Henrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Lindgren, Cecilia
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Lindvall, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Blood Metabolomic Predictors of 1-Year Outcome in Subarachnoid Hemorrhage2015In: Neurocritical Care, ISSN 1541-6933, E-ISSN 1556-0961, Vol. 23, no 2, p. 225-232Article in journal (Refereed)
    Abstract [en]

    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. Venous blood was drawn from 50 patients with SAH, admitted to the neurosurgical department UmeAyen 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 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. 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.

  • 33.
    Wahlström, Marie Rodling
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Olivecrona, Magnus
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Koskinen, Lars-Owe D
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Rydenhag, Bertil
    Department of Neurosurgery, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Naredi, Silvana
    Department of Anesthesia and Intensive Care, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Severe traumatic brain injury in pediatric patients: treatment and outcome using an intracranial pressure targeted therapy–the Lund concept2005In: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 31, no 6, p. 832-839Article in journal (Refereed)
    Abstract [en]

    Objective: This study evaluated the outcome of treatment according to the Lund concept in children with severe traumatic brain injury and investigated whether the preset goals of the protocol were achieved.

    Design and setting: A two-center retrospective study in neurointensive care units at university hospitals.

    Patients: Forty-one children with severe traumatic brain injury from blunt trauma and arriving at hospital within 24 h after injury. Median age was 8.8 years (range 3 months–14.2 years), Glasgow Coma Scale 7 (3–8), and Injury Severity Score 25 (16–75). All children had pathological findings on initial computed tomography. All developed intracranial hypertension, and survivors required intensive care longer than 72 h.

    Interventions: Treatment according to the principles of the Lund concept.

    Measurements and results: Neurosurgery was required in 46% of the children. Survival rate was 93% and favorable outcome (Glasgow Outcome Score 4 or 5) was 80% at long-term follow-up (median 12 months postinjury, range 2.5–26). The preset physiological and biochemical goals were achieved in over 90% of observations.

    Conclusions: Treating pediatric patients with severe traumatic brain injury, according to the Lund concept, results in a favorable outcome when the protocol is followed.

1 - 33 of 33
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