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Dyhrfort, P., Svedung-Wettervik, T., Clausen, F., Enblad, P., Hillered, L. & Lewén, A. (2023). A Dedicated 21-Plex Proximity Extension Assay Panel for High-Sensitivity Protein Biomarker Detection Using Microdialysis in Severe Traumatic Brain Injury: The Next Step in Precision Medicine?. NEUROTRAUMA REPORTS, 4(1), 25-40
Open this publication in new window or tab >>A Dedicated 21-Plex Proximity Extension Assay Panel for High-Sensitivity Protein Biomarker Detection Using Microdialysis in Severe Traumatic Brain Injury: The Next Step in Precision Medicine?
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2023 (English)In: NEUROTRAUMA REPORTS, ISSN 2689-288X, Vol. 4, no 1, p. 25-40Article in journal (Refereed) Published
Abstract [en]

Cerebral protein profiling in traumatic brain injury (TBI) is needed to better comprehend secondary injury pathways. Cerebral microdialysis (CMD), in combination with the proximity extension assay (PEA) technique, has great potential in this field. By using PEA, we have previously screened >500 proteins from CMD samples collected from TBI patients. In this study, we customized a PEA panel prototype of 21 selected candidate protein biomarkers, involved in inflammation (13), neuroplasticity/-repair (six), and axonal injury (two). The aim was to study their temporal dynamics and relation to age, structural injury, and clinical outcome. Ten patients with severe TBI and CMD monitoring, who were treated in the Neurointensive Care Unit, Uppsala University Hospital, Sweden, were included. Hourly CMD samples were collected for up to 7 days after trauma and analyzed with the 21-plex PEA panel. Seventeen of the 21 proteins from the CMD sample analyses showed significantly different mean levels between days. Early peaks (within 48 h) were noted with interleukin (IL)-1 beta, IL-6, IL-8, granulocyte colony-stimulating factor, transforming growth factor alpha, brevican, junctional adhesion molecule B, and neurocan. C-X-C motif chemokine ligand 10 peaked after 3 days. Late peaks (>5 days) were noted with interleukin-1 receptor antagonist (IL-1ra), monocyte chemoattractant protein (MCP)-2, MCP-3, urokinase-type plasminogen activator, Dickkopf-related protein 1, and DRAXIN. IL-8, neurofilament heavy chain, and TAU were biphasic. Age (above/below 22 years) interacted with the temporal dynamics of IL-6, IL-1ra, vascular endothelial growth factor, MCP-3, and TAU. There was no association between radiological injury (Marshall grade) or clinical outcome (Extended Glasgow Outcome Scale) with the protein expression pattern. The PEA method is a highly sensitive molecular tool for protein profiling from cerebral tissue in TBI. The novel TBI dedicated 21-plex panel showed marked regulation of proteins belonging to the inflammation, plasticity/repair, and axonal injury families. The method may enable important insights into complex injury processes on a molecular level that may be of value in future efforts to tailor pharmacological TBI trials to better address specific disease processes and optimize timing of treatments.

Place, publisher, year, edition, pages
Mary Ann Liebert, 2023
Keywords
biomarker, cerebral microdialysis, neurointensive care, proximity extension assay, traumatic brain injury
National Category
Neurology Neurosciences
Identifiers
urn:nbn:se:uu:diva-497708 (URN)10.1089/neur.2022.0067 (DOI)000915436800001 ()36726870 (PubMedID)
Note

De tre första författarna delar förstaförfattarskapet.

De två sista författarna delar sistaförfattarskapet.

Available from: 2023-03-09 Created: 2023-03-09 Last updated: 2023-03-09Bibliographically approved
von Seth, M., Hillered, L., Otterbeck, A., Hanslin, K., Larsson, A., Sjölin, J. & Lipcsey, M. (2023). Early decreased respiratory chain capacity in resuscitated experimental sepsis is a major contributor to lactate production. Shock, 60(3), 461-468
Open this publication in new window or tab >>Early decreased respiratory chain capacity in resuscitated experimental sepsis is a major contributor to lactate production
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2023 (English)In: Shock, ISSN 1073-2322, E-ISSN 1540-0514, Vol. 60, no 3, p. 461-468Article in journal (Refereed) Published
Abstract [en]

Background: Increased plasma lactate levels in patients with sepsis may be due to insufficient oxygen delivery, but mitochondrial dysfunction or accelerated glycolysis may also contribute. We studied the effect of the latter on muscle metabolism by using microdialysis in a sepsis model with sustained oxygen delivery and decreased energy consumption or mitochondrial blockade.

Methods: Pigs were subjected to continuous Escherichia coli infusion (sepsis group, n = 12) or saline infusion (sham group, n = 4) for 3 h. Protocolized interventions were applied to normalize the oxygen delivery and blood pressure. Microdialysis catheters were used to monitor muscle metabolism (naïve). The same catheters were used to block the electron transport chain with cyanide or the Na+/K+-ATPase inhibitor, ouabain locally.

Results: All pigs in the sepsis group had positive blood cultures and a Sequential Organ Failure Assessment score increase by at least 2, fulfilling the sepsis criteria. Plasma lactate was higher in the sepsis group than in the sham group (P < 0.001), whereas muscle glucose was lower in the sepsis group (P < 0.01). There were no changes in muscle lactate levels over time but lactate to pyruvate ratio (LPR) was elevated in the sepsis versus the sham group (P < 0.05). Muscle lactate, LPR, and glutamate levels were higher in the sepsis group than in the sham group in the cyanide catheters (P < 0.001, all comparisons) and did not normalize in the former group.

Conclusions: In this experimental study on resuscitated sepsis, we observed increased aerobic metabolism and preserved mitochondrial function. Sepsis and electron transport chain inhibition led to increased LPR, suggesting a decreased mitochondrial reserve capacity in early sepsis.

Place, publisher, year, edition, pages
Wolters Kluwer, 2023
Keywords
Sepsis, mitochondria, multiple organ failure, lactic acid, models, animal, escherichia coli, microdialysis, cyanides, ouabain
National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-509046 (URN)10.1097/SHK.0000000000002190 (DOI)001081847700017 ()37548644 (PubMedID)
Available from: 2023-08-14 Created: 2023-08-14 Last updated: 2023-11-08Bibliographically approved
Vlachogiannis, P., Hillered, L., Enblad, P. & Ronne-Engström, E. (2023). Elevated levels of several chemokines in the cerebrospinal fluid of patients with subarachnoid hemorrhage are associated with worse clinical outcome. PLOS ONE, 18(3), Article ID e0282424.
Open this publication in new window or tab >>Elevated levels of several chemokines in the cerebrospinal fluid of patients with subarachnoid hemorrhage are associated with worse clinical outcome
2023 (English)In: PLOS ONE, E-ISSN 1932-6203, Vol. 18, no 3, article id e0282424Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Chemokines are small cytokines that exert chemotactic actions on immune cells and are involved in many inflammatory processes. The present study aims to provide insight in the role of this relatively unexplored family of proteins in the inflammatory pathophysiology of subarachnoid hemorrhage (SAH).

MATERIALS AND METHODS: Cerebrospinal fluid of 29 patients (17 female; mean age 57 years) was collected at days 1, 4 and 10 after SAH, centrifuged and frozen at -70°C. Analysis of 92 inflammation-related proteins was performed using Target 96 Inflammation ® assay (Olink Proteomics, Uppsala, Sweden) based on Proximity Extension Assay technology. The panel included 20 chemokines (CCL2 (or MCP-1), CCL3, CCL4, CCL7 (or MCP-3), CCL8 (or MCP-2), CCL11 (or Eotaxin), CCL13 (or MCP-4), CCL19, CCL20, CCL23, CCL25, CCL28, CXCL1, CXCL5, CXCL6, CXCL8 (or IL-8), CXCL9, CXCL10, CXCL11 and CX3CL1 (or Fractalkine)) that were analyzed for their temporal patterns of expression and compared in dichotomized clinical groups based on World Federation of Neurosurgical Societies (WFNS) admission score and amount of blood on admission CT based on Fisher scale; presence of delayed cerebral ischemia(DCI)/delayed ischemic neurological deficit (DIND); and clinical outcome based on Glasgow Outcome Scale. Protein expression levels were provided in output unit Normalized Protein Expression (NPX). ANOVA models were used for statistical analyses.

RESULTS: Four temporal patterns of expression were observed (i.e., early, middle, late peak and no peak). Significantly higher day 10 mean NPX values were observed in patients with poor outcome (GOS 1-3) for chemokines CCL2, CCL4, CCL7, CCL11, CCL13, CCL19, CCL20, CXCL1, CXCL5, CXCL6 and CXCL8. In the WFNS 4-5 group, CCL11 showed significantly higher day 4 and day 10 mean NPX values and CCL25 significantly higher day 4 values. In patients with SAH Fisher 4, CCL11 showed significantly higher mean NPX values on days 1, 4 and 10. Finally, patients with DCI/DIND had significantly higher day 4 mean NPX values of CXCL5.

CONCLUSION: Higher levels of multiple chemokines at the late stage of SAH seemed to correlate with worse clinical outcome. A few chemokines correlated with WFNS score, Fisher score and occurrence of DCI/DIND. Chemokines may be useful as biomarkers for describing the pathophysiology and prognosis of SAH. Further studies are needed to better understand their exact mechanism of action in the inflammatory cascade.

Place, publisher, year, edition, pages
Public Library of Science (PLoS), 2023
National Category
Neurology
Research subject
Neurosurgery
Identifiers
urn:nbn:se:uu:diva-498218 (URN)10.1371/journal.pone.0282424 (DOI)000949067800064 ()36893189 (PubMedID)
Available from: 2023-03-11 Created: 2023-03-11 Last updated: 2023-05-02Bibliographically approved
Vlachogiannis, P., Hillered, L., Enblad, P. & Ronne-Engström, E. (2022). Temporal patterns of inflammation-related proteins measured in the cerebrospinal fluid of patients with aneurysmal subarachnoid hemorrhage using multiplex Proximity Extension Assay technology. PLOS ONE, 17(3), Article ID e0263460.
Open this publication in new window or tab >>Temporal patterns of inflammation-related proteins measured in the cerebrospinal fluid of patients with aneurysmal subarachnoid hemorrhage using multiplex Proximity Extension Assay technology
2022 (English)In: PLOS ONE, E-ISSN 1932-6203, Vol. 17, no 3, article id e0263460Article in journal (Refereed) Published
Abstract [en]

Background The complexity of the inflammatory response post subarachnoid hemorrhage (SAH) may require temporal analysis of multiple protein biomarkers simultaneously to be more accurately described. Methods Ventricular cerebrospinal fluid was collected at days 1, 4 and 10 after SAH in 29 patients. Levels of 92 inflammation-related proteins were simultaneously measured using Target 96 Inflammation (R) assay (Olink Proteomics, Uppsala, Sweden) based on Proximity Extension Assay (PEA) technology. Twenty-eight proteins were excluded from further analysis due to lack of > 50% of measurable values. Temporal patterns of the remaining 64 proteins were analyzed. Repeated measures ANOVA and its nonparametric equivalent Friedman's ANOVA were used for comparisons of means between time points. Results Four different patterns (Groups A-D) were visually observed with an early peak and gradually decreasing trend (11 proteins), a middle peak (10 proteins), a late peak after a gradually increasing trend (30 proteins) and no specific pattern (13 proteins). Statistically significant early peaks defined as Day 1 > Day 4 values were noticed in 4 proteins; no significant decreasing trends defined as Day 1 > Day 4 > Day 10 values were observed. Two proteins showed significant middle peaks (i.e. Day 1 < Day 4 > Day 10 values). Statistically significant late peaks (i.e. Day 4 < Day 10 values) and increasing trends (i.e. Day 1 < Day 4 < Day 10 values) were observed in 14 and 10 proteins, respectively. Four of Group D proteins showed biphasic peaks and the rest showed stable levels during the observation period. Conclusion The comprehensive data set provided in this explorative study may act as an illustration of an inflammatory profile of the acute phase of SAH showing groups of potential protein biomarkers with similar temporal patterns of activation, thus facilitating further research on their role in the pathophysiology of the disease.

Place, publisher, year, edition, pages
Public Library of Science (PLoS), 2022
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-473649 (URN)10.1371/journal.pone.0263460 (DOI)000780951300010 ()35324941 (PubMedID)
Available from: 2022-05-03 Created: 2022-05-03 Last updated: 2023-03-23Bibliographically approved
Svedung Wettervik, T., Engquist, H., Howells, T., Lenell, S., Rostami, E., Hillered, L., . . . Lewén, A. (2021). Arterial Oxygenation in Traumatic Brain Injury: Relation to Cerebral Energy Metabolism, Autoregulation, and Clinical Outcome. Journal of Intensive Care Medicine, 36(9), 1075-1083
Open this publication in new window or tab >>Arterial Oxygenation in Traumatic Brain Injury: Relation to Cerebral Energy Metabolism, Autoregulation, and Clinical Outcome
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2021 (English)In: Journal of Intensive Care Medicine, ISSN 0885-0666, E-ISSN 1525-1489, Vol. 36, no 9, p. 1075-1083Article in journal (Refereed) Published
Abstract [en]

Background:

Ischemic and hypoxic secondary brain insults are common and detrimental in traumatic brain injury (TBI). Treatment aims to maintain an adequate cerebral blood flow with sufficient arterial oxygen content. It has been suggested that arterial hyperoxia may be beneficial to the injured brain to compensate for cerebral ischemia, overcome diffusion barriers, and improve mitochondrial function. In this study, we investigated the relation between arterial oxygen levels and cerebral energy metabolism, pressure autoregulation, and clinical outcome.

Methods:

This retrospective study was based on 115 patients with severe TBI treated in the neurointensive care unit, Uppsala university hospital, Sweden, 2008 to 2018. Data from cerebral microdialysis (MD), arterial blood gases, hemodynamics, and intracranial pressure were analyzed the first 10 days post-injury. The first day post-injury was studied in particular.

Results:

Arterial oxygen levels were higher and with greater variability on the first day post-injury, whereas it was more stable the following 9 days. Normal-to-high mean pO2 was significantly associated with better pressure autoregulation/lower pressure reactivity index (P = .02) and lower cerebral MD-lactate (P = .04) on day 1. Patients with limited cerebral energy metabolic substrate supply (MD-pyruvate below 120 µM) and metabolic disturbances with MD-lactate-/pyruvate ratio (LPR) above 25 had significantly lower arterial oxygen levels than those with limited MD-pyruvate supply and normal MD-LPR (P = .001) this day. Arterial oxygenation was not associated with clinical outcome.

Conclusions:

Maintaining a pO2 above 12 kPa and higher may improve oxidative cerebral energy metabolism and pressure autoregulation, particularly in cases of limited energy substrate supply in the early phase of TBI. Evaluating the cerebral energy metabolic profile could yield a better patient selection for hyperoxic treatment in future trials.

Keywords
autoregulation, energy metabolism, hyperoxia, neurointensive care, traumatic brain injury
National Category
Surgery Neurology
Research subject
Neurosurgery
Identifiers
urn:nbn:se:uu:diva-421611 (URN)10.1177/0885066620944097 (DOI)000553082200001 ()32715850 (PubMedID)
Funder
Swedish Research Council
Available from: 2020-10-11 Created: 2020-10-11 Last updated: 2021-10-01Bibliographically approved
Svedung-Wettervik, T., Howells, T., Hillered, L., Rostami, E., Lewén, A. & Enblad, P. (2021). Autoregulatory or Fixed Cerebral Perfusion Pressure Targets in Traumatic Brain Injury: Determining Which Is Better in an Energy Metabolic Perspective. Journal of Neurotrauma, 38(14), 1969-1978
Open this publication in new window or tab >>Autoregulatory or Fixed Cerebral Perfusion Pressure Targets in Traumatic Brain Injury: Determining Which Is Better in an Energy Metabolic Perspective
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2021 (English)In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 38, no 14, p. 1969-1978Article in journal (Refereed) Published
Abstract [en]

Current guidelines in traumatic brain injury (TBI) recommend a cerebral perfusion pressure (CPP) within the fixed interval of 60-70 mm Hg. However, the autoregulatory, optimal CPP target (CPPopt) might yield better cerebral blood flow (CBF) regulation. In this study, we investigated fixed versus autoregulatory CPP targets in relation to cerebral energy metabolism and clinical outcome after TBI. Ninety-eight non-craniectomized patients with severe TBI treated in the neurointensive care unit, Uppsala University Hospital, Sweden, 2008-2018, were included. Data from cerebral microdialysis (MD), intracranial pressure (ICP), pressure autoregulation, CPP and CPPopt55-15 (a variant of CPPopt based on filtered slow waves from 15-55 sec range) were analyzed the first 10 days. The good monitoring time (GMT %) below/within/above the fixed and autoregulatory CPP targets were calculated. CPPopt55-15 was >70 mm Hg 74% of the time the first 10 days. Higher GMT (%) Delta CPPopt55-15 +/- 10 mm Hg correlated with lower lactate/pyruvate ratio (LPR) on day 1 and lower cerebral glycerol on days 6-10, and predicted favorable clinical outcome. Higher GMT (%) CPP within 60-70 mm Hg correlated with lower cerebral glucose on days 2-10 and higher LPR on days 6-10, but predicted favorable clinical outcome. Higher GMT (%) CPP >70 mm Hg had the opposite associations; that is, with higher cerebral glucose and lower LPR, but unfavorable clinical outcome. Autoregulatory CPP targets may be beneficial, because patients with CPP values close to the optimal CPP had both better cerebral energy metabolism and better clinical outcome, but this needs to be evaluated in randomized trials.

Place, publisher, year, edition, pages
Mary Ann LiebertMary Ann Liebert Inc, 2021
Keywords
cerebral microdialysis, neurointensive care, optimal cerebral perfusion pressure, pressure autoregulation, traumatic brain injury
National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-454104 (URN)10.1089/neu.2020.7290 (DOI)000624602200001 ()33504257 (PubMedID)
Available from: 2021-09-29 Created: 2021-09-29 Last updated: 2024-01-15Bibliographically approved
Engquist, H., Lewén, A., Hillered, L., Ronne-Engström, E., Nilsson, P., Enblad, P. & Rostami, E. (2021). CBF changes and cerebral energy metabolism during hypervolemia, hemodilution, and hypertension therapy in patients with poor-grade subarachnoid hemorrhage. Journal of Neurosurgery, 134(2), 555-564
Open this publication in new window or tab >>CBF changes and cerebral energy metabolism during hypervolemia, hemodilution, and hypertension therapy in patients with poor-grade subarachnoid hemorrhage
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2021 (English)In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 134, no 2, p. 555-564Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: Despite the multifactorial pathogenesis of delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH), augmentation of cerebral blood flow (CBF) is still considered essential in the clinical management of DCI. The aim of this prospective observational study was to investigate cerebral metabolic changes in relation to CBF during therapeutic hypervolemia, hemodilution, and hypertension (HHH) therapy in poor-grade SAH patients with DCI.

METHODS: CBF was assessed by bedside xenon-enhanced CT at days 0–3, 4–7, and 8–12, and the cerebral metabolic state by cerebral microdialysis (CMD), analyzing glucose, lactate, pyruvate, and glutamate hourly. At clinical suspicion of DCI, HHH therapy was instituted for 5 days. CBF measurements and CMD data at baseline and during HHH therapy were required for study inclusion. Non-DCI patients with measurements in corresponding time windows were included as a reference group.

RESULTS: In DCI patients receiving HHH therapy (n = 12), global cortical CBF increased from 30.4 ml/100 g/min (IQR 25.1–33.8 ml/100 g/min) to 38.4 ml/100 g/min (IQR 34.2–46.1 ml/100 g/min; p = 0.006). The energy metabolic CMD parameters stayed statistically unchanged with a lactate/pyruvate (L/P) ratio of 26.9 (IQR 22.9–48.5) at baseline and 31.6 (IQR 22.4–35.7) during HHH. Categorized by energy metabolic patterns during HHH, no patient had severe ischemia, 8 showed derangement corresponding to mitochondrial dysfunction, and 4 were normal. The reference group of non-DCI patients (n = 11) had higher CBF and lower L/P ratios at baseline with no change over time, and the metabolic pattern was normal in all these patients.

CONCLUSIONS: Global and regional CBF improved and the cerebral energy metabolic CMD parameters stayed statistically unchanged during HHH therapy in DCI patients. None of the patients developed metabolic signs of severe ischemia, but a disturbed energy metabolic pattern was a common occurrence, possibly explained by mitochondrial dysfunction despite improved microcirculation.

Place, publisher, year, edition, pages
Journal of Neurosurgery Publishing Group (JNSPG), 2021
Keywords
subarachnoid hemorrhage, cerebral blood flow, delayed cerebral ischemia, xenon CT, XeCT
National Category
Neurology Surgery
Research subject
Neurosurgery
Identifiers
urn:nbn:se:uu:diva-400694 (URN)10.3171/2019.11.JNS192759 (DOI)000646414300007 ()
Available from: 2020-01-02 Created: 2020-01-02 Last updated: 2022-11-17Bibliographically approved
Engquist, H., Hillered, L., Enblad, P. & Rostami, E. (2021). Hyperglycolysis as a common cause for elevated lactate in subarachnoid hemorrhage: Response [Letter to the editor]. Journal of Neurosurgery, 134(2), 682-682
Open this publication in new window or tab >>Hyperglycolysis as a common cause for elevated lactate in subarachnoid hemorrhage: Response
2021 (English)In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 134, no 2, p. 682-682Article in journal, Letter (Other academic) Published
Place, publisher, year, edition, pages
AMER ASSOC NEUROLOGICAL SURGEONS, 2021
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-442912 (URN)10.3171/2020.2.JNS20246 (DOI)000646417500010 ()
Available from: 2021-05-21 Created: 2021-05-21 Last updated: 2021-05-21Bibliographically approved
Lindblom, R., Tovedal, T., Norlin, B., Hillered, L., Englund, E. & Thelin, S. (2021). Mechanical Reperfusion Following Prolonged Global Cerebral Ischemia Attenuates Brain Injury. Journal of Cardiovascular Translational Research, 14, 338-347
Open this publication in new window or tab >>Mechanical Reperfusion Following Prolonged Global Cerebral Ischemia Attenuates Brain Injury
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2021 (English)In: Journal of Cardiovascular Translational Research, ISSN 1937-5387, E-ISSN 1937-5395, Vol. 14, p. 338-347Article in journal (Refereed) Published
Abstract [en]

Previous experiments demonstrated improved outcome following prolonged cerebral ischemia given controlled brain reperfusion using extracorporeal circulation. The current study further investigates this. Young adult pigs were exposed to 30 min of global normothermic cerebral ischemia, achieved through intrathoracic clamping of cerebral arteries, followed by 20 min of isolated mechanical brain reperfusion. Leukocyte-filtered blood was delivered by a roller-pump at fixed pressure and flow. One experimental group additionally had a custom-made buffer solution delivered at 1:8 ratio with the blood. Hemodynamics including intracranial pressure were monitored. Blood gases were from peripheral arteries and the sagittal sinus, and intraparenchymal brain microdialysis was performed. The brains were examined by a neuropathologist. The group with the added buffer showed lower intracranial pressure as well as decreased intraparenchymal glycerol and less signs of excitotoxicity and ischemia, although histology revealed similar degrees of injury. A customized mechanical reperfusion improves multiple parameters after prolonged normothermic global cerebral ischemia.

Place, publisher, year, edition, pages
SpringerSPRINGER, 2021
Keywords
Global cerebral ischemia, Reperfusion, Mechanical circulation
National Category
Anesthesiology and Intensive Care Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-450612 (URN)10.1007/s12265-020-10058-9 (DOI)000549659000001 ()32681452 (PubMedID)
Available from: 2021-08-17 Created: 2021-08-17 Last updated: 2024-01-15Bibliographically approved
Svedung-Wettervik, T., Engquist, H., Lenell, S., Howells, T., Hillered, L., Rostami, E., . . . Enblad, P. (2021). Systemic Hyperthermia in Traumatic Brain Injury—Relation to Intracranial Pressure Dynamics, Cerebral Energy Metabolism, and Clinical Outcome. Journal of Neurosurgical Anesthesiology, 329-336
Open this publication in new window or tab >>Systemic Hyperthermia in Traumatic Brain Injury—Relation to Intracranial Pressure Dynamics, Cerebral Energy Metabolism, and Clinical Outcome
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2021 (English)In: Journal of Neurosurgical Anesthesiology, ISSN 0898-4921, E-ISSN 1537-1921, p. 329-336Article in journal (Refereed) Published
Abstract [en]

Background: Systemic hyperthermia is common after traumatic brain injury (TBI) and may induce secondary brain injury, although the pathophysiology is not fully understood. In this study, our aim was to determine the incidence and temporal course of hyperthermia after TBI and its relation to intracranial pressure dynamics, cerebral metabolism, and clinical outcomes.

Materials and Methods: This retrospective study included 115 TBI patients. Data from systemic physiology (body temperature, blood pressure, and arterial glucose), intracranial pressure dynamics (intracranial pressure, cerebral perfusion pressure, compliance,and pressure reactivity), and cerebral microdialysis (glucose, pyruvate, lactate, glycerol, glutamate, and urea) were analyzed during the first 10 days after injury.

Results: Overall, 6% of patients did not have hyperthermia (T> 38°C) during the first 10 days after injury, whereas 20% had hyperthermia for > 50% of the time. Hyperthermia increased from 21% (±27%) of monitoring time on day 1 to 36% (± 29%) on days 6 to 10 after injury. In univariate analyses, higher body temperature was not associated with higher intracranial pressure nor lower cerebral perfusion pressure, but was associated with lower cerebral glucose concentration (P= 0.001) and higher percentage of lactate-pyruvate ratio> 25 (P=0.02) on days 6 to 10 after injury. Higher body temperature and lower arterial glucose concentration were associated with lower cerebral glucose in a multiple linear regression analysis (P=0.02 for both). There was no association between hyperthermia and worse clinical outcomes.

Conclusion: Hyperthermia was most common between days 6 and 10 following TBI, and associated with disturbances in cerebral energy metabolism but not worse clinical outcome.

Place, publisher, year, edition, pages
Wolters KluwerOvid Technologies (Wolters Kluwer Health), 2021
National Category
Surgery
Research subject
Neurosurgery
Identifiers
urn:nbn:se:uu:diva-421612 (URN)10.1097/ANA.0000000000000695 (DOI)000696559100008 ()
Available from: 2020-10-11 Created: 2020-10-11 Last updated: 2024-01-15Bibliographically approved
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ORCID iD: ORCID iD iconorcid.org/0000-0002-2808-9292

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