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Clinical Studies in the Acute Phase of Subarachnoid Haemorrhage
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
2010 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

Patients admitted in similar clinical condition after spontaneous SAH can develop very different clinical courses. This could depend on the severity of the initial global ischemic brain injury at ictus. In the present study, we explored relations between clinical and radiological parameters at admission that indicate a more severe initial impact, and the following days hormone levels and brain metabolism.

Early global cerebral oedema (GCE) on computed tomography occurred in 57 % of SAH patients and was associated with a more severe clinical condition. The brain’s glucose metabolism, measured with intracerebral microdialysis (MD), changed the first days. MD-glucose was initially high and MD-pyruvate low. MD-glucose gradually decreased and MD-pyruvate and MD-lactate increased, suggesting a transition to a hyperglycolytic state. This was more pronounced in patients with GCE. Similar patterns were seen for interstitial non-transmitter amino acids. From initial low concentrations, they gradually increased in parallel with MD-pyruvate. The amino acid concentrations were higher for patients admitted in better clinical condition. Insulin lowered MD-glucose and MD-pyruvate even when plasma glucose values remained high. P-ACTH and S-cortisol were elevated early after SAH. GCE was associated with higher S-cortisol acutely. Urine cortisol excretion, indicating levels of free cortisol, were higher in patients in a better clinical condition. Suppressed P-ACTH occurred in periods of brain ischemia.

We suggest that GCE on the first CT scan is a warning sign indicating increased vulnerability if the patient is exposed to compromised energy supply or increased energy demand. Reduction of blood glucose after SAH should be done with caution. The temporal change of the glucose metabolism and the amino acid concentrations probably reflect activated repair mechanisms. This should be considered in the intensive care treatment of SAH patients. Finally, our results support earlier observations that the response of the hypothalamic-pituitary-adrenal system is important in critical care.

sted, utgiver, år, opplag, sider
Uppsala: Acta Universitatis Upsalaliensis , 2010. , s. 97
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 582
Emneord [en]
Subarachnoid haemorrhage, microdialysis, brain energy metabolism, brain glucose, pyruvate, amino acids, cerebral oedema, ACTH, cortisol
HSV kategori
Forskningsprogram
Neurokirurgi
Identifikatorer
URN: urn:nbn:se:uu:diva-129160ISBN: 978-91-554-7859-9 (tryckt)OAI: oai:DiVA.org:uu-129160DiVA, id: diva2:343048
Disputas
2010-09-24, Grönwallssalen, Akademiska Sjukhuset, Uppsala, 09:15 (svensk)
Opponent
Veileder
Tilgjengelig fra: 2010-09-02 Laget: 2010-08-05 Sist oppdatert: 2010-09-02bibliografisk kontrollert
Delarbeid
1. Brain energy metabolism in patients with spontaneous subarachnoid hemorrhage and global cerebral edema
Åpne denne publikasjonen i ny fane eller vindu >>Brain energy metabolism in patients with spontaneous subarachnoid hemorrhage and global cerebral edema
Vise andre…
2010 (engelsk)Inngår i: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 66, nr 6, s. 1102-1110Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

BACKGROUND: Previous studies of spontaneous subarachnoid hemorrhage (SAH) have shown that global cerebral edema on the first computed tomography scan is associated with a more severe initial injury and is an independent predictor of poor outcome. Effects of secondary ischemic events also influence outcome after SAH. OBJECTIVE: This study demonstrates that early global edema is related to markers of an increased cerebral energy metabolism as measured with intracerebral microdialysis, which could increase vulnerability to adverse events. METHODS: Fifty-two patients with microdialysis monitoring after spontaneous SAH were stratified according to the occurrence of global cerebral edema on the first computed tomography scan taken a median of 2 hours after the initial bleed. Microdialysis levels of glucose, lactate, and pyruvate were compared between the global edema (n = 31) and no global edema (n = 21) groups. Clinical outcome was assessed with the Glasgow Outcome Scale score at >/= 6 months. RESULTS: Patients with global edema showed significantly elevated lactate and pyruvate levels 70 to 79 hours after SAH and marginally significantly higher levels of lactate 60 to 69 hours and 80 to 89 hours after SAH. There was a trend toward worse outcome in the edema group. CONCLUSION: Patients with global cerebral edema have higher interstitial levels of lactate and pyruvate. The edema group may have developed a cerebral hypermetabolism to meet the increased energy demand in the recovery phase after SAH. This stress would make the brain more vulnerable to secondary insults, increasing the likelihood of energy failure.

Emneord
Cerebral edema, Energy metabolism, Microdialysis, SAH
HSV kategori
Forskningsprogram
Neurokirurgi
Identifikatorer
urn:nbn:se:uu:diva-128973 (URN)10.1227/01.NEU.0000370893.04586.73 (DOI)000278006200030 ()20495425 (PubMedID)
Tilgjengelig fra: 2010-08-05 Laget: 2010-08-05 Sist oppdatert: 2017-12-12bibliografisk kontrollert
2. Early global brain oedema in relation to clinical admission parameters and outcome in patients with aneurysmal subarachnoid haemorrhage
Åpne denne publikasjonen i ny fane eller vindu >>Early global brain oedema in relation to clinical admission parameters and outcome in patients with aneurysmal subarachnoid haemorrhage
2010 (engelsk)Inngår i: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 152, nr 9, s. 1527-1533Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

BACKGROUND: Previous studies on spontaneous aneurysmal subarachnoid haemorrhage (SAH) treatment have found the presence of global cerebral oedema on the first CT scan to be a predictor of poor outcome. We have reviewed our own experience with SAH in order to evaluate the relation of global cerebral oedema to clinical parameters at admission and to functional outcome. METHODS: One hundred ninety patients with spontaneous aneurysmal SAH were included in the study. The first CT scan for each patient was evaluated for signs of global cerebral oedema. Clinical status on admission was assessed according to the Hunt & Hess score and the World Federation of Neurosurgical Societies (WFNS) grade and functional outcome using the Glasgow Outcome Scale (GOS). Clinical condition at admission was dichotomised as 'better' (Hunt & Hess 1-2, WFNS 1-2) or 'worse' (Hunt & Hess 3-5, WFNS 3-5) and outcome as 'favourable' (GOS 4-5) or 'poor' (GOS 1-3). The amount of blood on the CT scan was assessed using the Fisher scale. Comparisons were made between patients with and without global cerebral oedema on the first CT regarding clinical condition, age, gender, mode of aneurysm treatment, outcome, 6-month mortality, amount of blood on the CT scan and time lag to the first CT scan. RESULTS: Global cerebral oedema was observed in 57% of patients admitted with aneurysmal SAH, which is a much higher frequency than has been reported previously. Patients with oedema were admitted in a worse clinical status, but there was no difference between patients with and without oedema regarding other clinical parameters or outcome. The median time between the haemorrhage and the first CT scan was short compared to earlier studies, 2.5 h for those with oedema and 3.4 for those without. This difference was significant, suggesting that global cerebral oedema can be a very early phenomenon after SAH, and may be missed in later CT scans. Early global brain oedema, occurring within a few hours of bleeding, may be more common than previously thought. In aneurysmal SAH patients, the presence of global cerebral oedema was associated with a worse clinical condition at admission which in turn could indicate a more severe initial injury. The clinical significance of early oedema may differ from that of late oedema, which may explain the lack of an association between global oedema and poor outcome in this study. However, the nature of the oedema as well as its relation to the clinical course has to be further studied in separate studies.

Emneord
Subarachnoidal haemorrhage, Aneurysm, CT scan, Global brain oedema, Outcome
HSV kategori
Forskningsprogram
Neurokirurgi
Identifikatorer
urn:nbn:se:uu:diva-128972 (URN)10.1007/s00701-010-0684-8 (DOI)000281246500011 ()20495834 (PubMedID)
Tilgjengelig fra: 2010-08-05 Laget: 2010-08-05 Sist oppdatert: 2017-12-12bibliografisk kontrollert
3. Cortisol and ACTH dynamics in the acute phase of subarachnoid haemorrhage
Åpne denne publikasjonen i ny fane eller vindu >>Cortisol and ACTH dynamics in the acute phase of subarachnoid haemorrhage
Vise andre…
(engelsk)Inngår i: British Journal of Neurosurgery, ISSN 0268-8697, E-ISSN 1360-046XArtikkel i tidsskrift (Fagfellevurdert) Submitted
Abstract [en]

Objective: An adequate response of hypothalamic-pituitary-adrenal (HPA) axis is important for survival and recovery after a severe disease. The hypothalamus and the pituitary glands are at risk of damage after subarachnoid haemorrhage (SAH). A better understanding of the hormonal changes would be valuable for optimizing care in the acute phase of SAH.

Patients: 55 patients with spontaneous SAH were evaluated regarding morning levels of S-Cortisol and P-ACTH seven days after the bleeding. In a subgroup of 20 patients the diurnal changes of S-Cortisol and P-ACTH levels were studied and U-Cortisol measured. The relations of hormone levels to clinical and radiological parameters and to outcome were assessed.

Results: S-Cortisol and P-ACTH were elevated the day of SAH. S-Cortisol levels below reference range were uncommon. Early global cerebral oedema was associated with higher S-Cortisol concentrations at admission and a worse WFNS and RLS85 grade. Patients in better WFNS grade had higher U-Cortisol levels. All patients showed diurnal variations of S-Cortisol and P-ACTH. A reversed diurnal variation of S-Cortisol was more frequently seen in mechanically ventilated patients. Periods of suppressed P-ACTH associated with S-Cortisol peaks occurred especially in periods of secondary brain ischemia.

Conclusion: There is a HPA response acutely after SAH with an increase of P-ACTH and S-Cortisol levels. Higher U-Cortisol levels in patients in a better clinical grade may indicate a more robust response of the HPA system. Global cerebral oedema was associated with higher S-Cortisol levels at admission and may be the result of the stress response initiated by the brain injury. Periods of suppressed P-ACTH occurred particularly in periods of brain ischemia, indicating a possibly connection between brain ischemia and ACTH suppression. These two novel findings should be evaluated in further studies.

Emneord
Subarachnoid haemorrhage, Cortisol, ACTH, Diurnal variation, Cerebral oedema
HSV kategori
Forskningsprogram
Neurokirurgi
Identifikatorer
urn:nbn:se:uu:diva-128968 (URN)
Tilgjengelig fra: 2010-08-04 Laget: 2010-08-04 Sist oppdatert: 2017-12-12bibliografisk kontrollert
4. Temporal patterns of interstitial pyruvate and amino acids after subarachnoid haemorrhage are related to the level of consciousness: a clinical microdialysis study
Åpne denne publikasjonen i ny fane eller vindu >>Temporal patterns of interstitial pyruvate and amino acids after subarachnoid haemorrhage are related to the level of consciousness: a clinical microdialysis study
Vise andre…
2009 (engelsk)Inngår i: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 151, nr 7, s. 771-780Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

BACKGROUND: Temporal patterns of brain interstitial amino acids after subarachnoid haemorrhage (SAH) were studied in relation to energy metabolite levels and to the severity of the initial global ischaemia as reflected by the level of consciousness at admission. METHOD: Intracerebral microdialysis was used to measure brain interstitial amino acids and the energy metabolites glucose, lactate, and pyruvate during five days in 19 patients. Patients who were conscious (n = 11) were compared to those who were unconscious on admission (n = 8). FINDINGS: Eight non-transmitter amino acids (alanine, asparagine, glutamine, isoleucine, leucine, phenylalanine, serine and tyrosine), as well as glycine and pyruvate showed a pattern of increasing concentrations starting at 60-70 h after the onset of SAH. The conscious patients showed more pronounced elevations of non-transmitter amino acids, glycine, taurine and pyruvate compared to the unconscious patient group. Pyruvate levels were initially critically low for all patients, then normalised in the conscious patients but remained low in the unconscious group. CONCLUSIONS: There was an increase of the cerebral interstitial levels of non-transmitter amino acids and glycine which correlated temporally to pyruvate levels, more pronounced in patients conscious on admission. Pyruvate levels in these patients normalised, but remained reduced in the unconscious patients. The increase of the non-transmitter amino acids and glycine could reflect an increased amino acid turnover in an attempt at repairing the injured brain, which could have been hampered by the lower pyruvate levels. Interstitial pyruvate may be a useful marker of the energy metabolic situation in the acutely injured brain.

Emneord
amino acids, microdialysis, pyruvate, subarachnoid haemorrhage
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-107570 (URN)10.1007/s00701-009-0384-4 (DOI)000267388600007 ()19430719 (PubMedID)
Tilgjengelig fra: 2009-08-17 Laget: 2009-08-17 Sist oppdatert: 2017-12-13bibliografisk kontrollert
5. Relation between brain interstitial and systemic glucose levels after subarachnoid hemorrhage
Åpne denne publikasjonen i ny fane eller vindu >>Relation between brain interstitial and systemic glucose levels after subarachnoid hemorrhage
Vise andre…
(engelsk)Inngår i: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693Artikkel i tidsskrift (Fagfellevurdert) Submitted
Abstract [en]

Objects: The optimal blood glucose level after acute brain injury is not known. The aim of the present investigation was to study the relation between brain interstitial and systemic blood glucose levels during the acute phase after SAH. We also studied the effects of insulin administration on local brain energy metabolism.

Methods: 19 patients with spontaneous SAH were monitored with intracerebral microdialysis (MD). The relation between plasma (P)-glucose and interstitial MD-glucose levels and the temporal pattern of MD-metabolites was studied seven days after SAH. With a target P-glucose of 5-10 mmol/L, the effect of insulin injection on brain energy metabolites (MD-glucose, lactate, pyruvate) and glutamate was evaluated.

Results: The mean correlation coefficient between P-glucose and MD-glucose was 0.27 ± 0.27, (p=0.0005) with a high degree of individual variation. MD-glucose, MD/P-glucose ratio and MD-glutamate levels decreased in parallel with a gradual increase in MD-pyruvate and MD-lactate levels. There were no significant changes of MD-L/P ratio or MD-glycerol. Insulin administration induced a statistically significant decrease in MD-glucose and MD-pyruvate.

Conclusion: After SAH, there was a positive correlation between P-glucose and MD-glucose levels with a high degree of individual variation. A gradual decline of MD-glucose and MD/P-glucose ratio and an increase of MD-pyruvate and MD-lactate levels during the first week after SAH could suggest a transition to a hyperglycolytic state with increased cerebral glucose consumption. Administration of insulin was related to lowering of MD-glucose and MD-pyruvate, often to critically low levels even though plasma glucose values remained above 6 mmol/L. Thus, P-glucose should not be low in the acute phase after SAH and administration of insulin should be done with caution, even more crucial when the cerebral glucose metabolism has recovered and an increased energy demand is developing in the injured, repairing brain.

Emneord
Brain glucose, Blood glucose, Insulin, Microdialysis, Subarachnoid hemorrhage
HSV kategori
Forskningsprogram
Neurokirurgi
Identifikatorer
urn:nbn:se:uu:diva-128970 (URN)
Tilgjengelig fra: 2010-08-04 Laget: 2010-08-04 Sist oppdatert: 2017-12-12bibliografisk kontrollert

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