Introduction
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Do commonly measured CMD analytes display an association with patient functional outcome?
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Are these analytes associated with specific neurophysiologic changes seen during NICU care?
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Are these analytes associated with tissue outcome on imaging (such as acute ischemia/infarct, or atrophy long term)?
Methods
Search question, population, inclusion and exclusion criteria
Functional outcome – outcome measures and primary/secondary outcomes
Neuro-physiologic measures – outcome measures and primary/secondary outcomes
Tissue outcome – outcome measures and primary/secondary outcomes
General inclusion/exclusion criteria
Search strategy
Study selection
Data collection
Bias assessment
Quality of evidence assessment
Statistical analysis
Results
Search strategy results
Patient/study demographics
Functional outcome studies
Reference | Number of patients | Study type | Article location | Mean age (years) | Patient characteristics | Primary and secondary goal of study |
---|---|---|---|---|---|---|
Positive association studies | ||||||
Alessandri et al. [2] | 54 | Unknown | Meeting abstract | Unknown | Severe TBI |
Primary: Determine the relationship between glutamate and lactate; determine link to patient outcome
Secondary: None stated |
Badenes et al. [6] | 30 | Prospective RCT | Meeting abstract | Unknown | Severe TBI; RCT comparing intensive glycemic control |
Primary: Evaluate CMD-based changes with intensive glycemic control
Secondary: Association of CMD markers with patient outcome |
Belli et al. [8] | 19 | Prospective observational | Manuscript | 41.5 years (range, 16–69) | Severe TBI |
Primary: To determine the relationship between NAA, lactate, pyruvate, glycerol, and glutamate to outcome
Secondary: Correlations between NAA and ICP/CPP/PbtO2; Correlations between various CMD markers |
Bidot et al. [9] | 12 | Unknown | Meeting abstract | 38 years (range, 18–70) | Severe TBI |
Primary: Determine the link between CMD measures and neurological outcome
Secondary: None mentioned |
Bolcha et al. [10] | 20 | Prospective observational | Meeting abstract | Unknown | Severe TBI |
Primary: Determine association between PbtO2 and CMD to patient outcome
Secondary: None mentioned |
Bullock et al. [12] | 80 | Prospective observational | Manuscript | Unknown | Severe TBI |
Primary: Determine association of EAA and clinical outcomes (i.e., ischemic events, ICP/CPP, patient outcome)
Secondary: None mentioned |
Chamoun et al. [13] | 135 | Prospective observational | Manuscript | 36.6 years (range, 16–91) | Severe TBI |
Primary: Determine the association between CMD glutamate and prognosis
Secondary: Correlation between glutamate and MABP/ICP/PbtO2/SjvO2
|
Chan et al. [14] | 36 | Unknown | Meeting abstract | Unknown | Severe TBI |
Primary: To determine if the Pearson correlation between Glutamate/CPP correlated to outcome
Secondary: None mentioned |
Clausen et al. [17] | 76 | Prospective observational | Manuscript | Unknown | Severe TBI |
Primary: Determine association between CMD glycerol and patient outcome
Secondary: Determine association between CMD glycerol and monitoring (CPP/PbtO2) |
Clausen et al. [18] | 151 | Prospective observational | Manuscript | 35.5 years (range, unknown) | Severe TBI |
Primary: Determine the association of brain pH, PCO2, lactate to patient outcome
Secondary: Determine the association of above to CPP, PbtO2
|
Dizdarevic et al. [20] | 30 | Prospective RCT | Manuscript | 45.8 years (range, 16–68) | Severe TBI |
Primary: Determine impact of modified Lund therapy vs. standard CPP therapy in severe TBI
Secondary: Determine the difference in CMD characteristics between the two therapies with regard to patient outcome |
Figaji et al. [21] | 5 | Prospective observational | Meeting abstract | Unknown (children) | Severe TBI |
Primary: Determine association of inflammatory cytokines and other CMD markers/patient outcome
Secondary: None mentioned |
Goodman et al. [25] | 126 | Prospective observational | Manuscript | 34.4 years (range, unknown) | Severe TBI |
Primary: Determine association between CMD lactate and glucose to ICP/CPP/PbtO2/SjvO2/rCBF
Secondary: Clinical outcome |
Gopinath et al. [27] | 86 | Unknown | Meeting abstract | Unknown | Severe TBI |
Primary: Determine association between glutamate/aspartate and patient outcome
Secondary: None mentioned |
Gupta et al. [29] | 25 | Prospective observational | Manuscript | 31.8 (range, 18–64) | Severe TBI with DC |
Primary: Determine association between CMD/serum glucose measures pre- and post-DC and outcome |
Gupta et al. [28] | 41 | Unknown | Meeting abstract | Unknown (over 18) | Severe TBI |
Primary: Determine association between CMD glycerol and LPR with CPP and patient outcome
Secondary: None mentioned |
Hejcl et al. [34] | 20 | Prospective observational | Meeting abstract | Unknown | Severe TBI |
Primary: Determine association between CMD/ICP/CPP/PbtO2 and patient outcome
Secondary: None mentioned |
Hutchinson et al. [38] | 21 | Prospective observational | Meeting abstract | Unknown | Severe TBI |
Primary: Determine association of CMD measures and patient outcome
Secondary: Not mentioned |
Igarashi et al. [42] | 19 | Unknown | Meeting abstract | 61.3 years (range, unknown) | Severe TBI with aSDH |
Primary: Determine association between CMD measures and patient outcome |
Johnston et al. [44] | 11 | Prospective single arm | Manuscript | 32 years (range, unknown) | Severe TBI |
Primary: To evaluate the relationship between 15O PET, PbtO2 and CMD to CPP augmentation in TBI
Secondary: Determine association to outcome |
Karathanou et al. [45] | 33 | Unknown | Meeting abstract | Unknown | Severe TBI |
Primary: Determine association between CMD measures and patient outcome
Secondary: None mentioned |
Koura et al. [47] | 83 | Unknown | Meeting abstract | Unknown | Severe TBI |
Primary: Determine association between CMD measures and CPP/ICP/patient outcome
Secondary: None mentioned |
Kurtz et al. [48] | 46 | Retrospective case series | Manuscript | 55 years (range, unknown) | Severe TBI |
Primary: Determine association between CMD/serum glucose and patient outcome
Secondary: Association with CMD markers of metabolic stress |
Li et al. [51] | 53 | Retrospective case series | Manuscript | 42 years (range, 15–60) | Severe TBI |
Primary: Determine association between CMD glycerol and ICP/CPP and patient outcome |
Marcoux et al. [53] | 15 | Retrospective case series | Manuscript | 30.1 years (range, 18–58) | Severe TBI |
Primary: Determine association between CMD-based metabolic dysfunction and long-term tissue atrophy
Secondary: Determine association with long-term outcome |
Mazzeo et al. [54] | 172 | Retrospective case series | Manuscript | 35.6 years (range, unknown) | Severe TBI |
Primary: To validate a proposed ischemia score on outcome prediction in a retrospective cohort
Secondary: Compare the ischemia score and CMD/PbtO2/CBF measurements |
Mellergard et al. [55] | 69 | Retrospective case series | Manuscript | 45.9 years (range, unknown) | Severe TBI |
Primary: Determine potential age-related difference in CMD-based metabolic and inflammatory markers
Secondary: CMD marker association to patient outcome |
Nordstrom et al. [62] | 213 | Retrospective case series | Manuscript | 40 years (range, 19–63) | Severe TBI |
Primary: Determine correlation between CMD markers and injury patterns/patient outcome
Secondary: None mentioned |
Oddo et al. [64] | 20 | Retrospective case series | Manuscript | 59 years (range, 36–76) | Severe TBI |
Primary: To determine the impact of tight glycemic control on CMD markers
Secondary: To determine the impact on patient outcome |
Olivecrona et al. [65] | 48 | Prospective RCT | Manuscript | 35.5 years (range, unknown) | Severe TBI – RCT comparing epoprostenol to placebo |
Primary: 1. Determine the impact of epoprostenol on LPR, 2. Compare CMD between epoprostenol vs. placebo, 3. Correlate LPR to GOS at 3 months
Secondary: None mentioned |
Omerhodzic et al. [66] | 33 | Prospective observational | Manuscript | Unknown | Severe TBI |
Primary: Determine the correlation between CMD markers and patient outcome
Secondary: None mentioned |
Paraforou et al. [69] | 34 | Prospective observational | Manuscript | 43.6 years (range, unknown) | Severe TBI |
Primary: Determine relationship between CPP/ICP/CMD and patient outcome
Secondary: None mentioned |
Peerdeman et al. [70] | 15 | Prospective observational | Manuscript | 39.5 years (range, 18–69) | Severe TBI |
Primary: Determine the association between secondary events (elevated ICP, low CPP, elevated temp) to CMD and outcome
Secondary: None mentioned |
Petzold et al. [71] | 10 | Prospective observational | Manuscript | 39 years (range, 20–68) | Severe TBI |
Primary: To correlate CMD measured neurofilament protein to injury pattern, physiologic measures, and outcome
Secondary: Assess other CMD measures’ relationships to outcome |
Reinert et al. [73] | 20 | Prospective observational | Manuscript | 40.1 years (range, 21–70) | Severe TBI |
Primary: Determine the correlation between autoregulation (PRx) and CPP/PbtO2/CMD and patient outcome
Secondary: None mentioned |
Reinert et al. [74] | 85 | Prospective observational | Manuscript | Unknown | Severe TBI |
Primary: Determine the relationship between CMD potassium and ICP/CBF/other CMD substrates and patient outcome
Secondary: None mentioned |
Richards et al. [75] | 9 | Prospective observational | Manuscript | 8 years (range, 3–14) | Severe TBI |
Primary: Determine the association between glutamate and clinical outcome; also determine if an “excitotoxic index” (glutamate:glutamine) correlated to outcome
Secondary: None mentioned |
Robertson et al. [76] | 79 | Unknown | Meeting abstract | Unknown | Severe TBI |
Primary: Determine the association between CMD glutamine/aspartate and patient outcome and PbtO2/CBF (TCD)
Secondary: None mentioned |
Sanchez-Porras et al. [81] | 29 | Retrospective case series | Manuscript | 37.2 years (range, unknown) | Severe TBI |
Primary: To evaluate long PRx and its relationship to patient outcome
Secondary: To correlate PRx to other monitoring (i.e., CMD) |
Sanchez et al. [80] | 12 | Unknown | Meeting abstract | Unknown | Severe TBI |
Primary: Determine correlation between CDM measures and patient outcome
Secondary: None mentioned |
Singla et al. [86] | 41 | Unknown | Meeting abstract | Unknown | Severe TBI |
Primary: Determine relationship between CPP/CMD to patient outcome
Secondary: None mentioned |
Stein et al. [88] | 89 | Prospective observational | Manuscript | 46.4 years (range, 26–62) | Severe TBI |
Primary: Determine the relationship between “metabolic crisis” (low glucose and elevated LPR) with outcome
Secondary: None mentioned |
Stiefel et al. [91] | 27 | Retrospective case series | Meeting abstract | Unknown | Severe TBI |
Primary: Determine relationship between ICP/CPP/PbtO2/CMD and outcome
Secondary: Determine if “metabolic compromise” (LPR > 25) or “metabolic crisis” (LPR > 40) is associated to outcome |
Timofeev et al. [93] | 223 | Retrospective case series | Manuscript | Unknown | Severe TBI |
Primary: Determine the relationship between CMD markers and neurological outcome
Secondary: Association between CMD markers and ICP/Mx |
Vespa et al. [99] | 30 | Prospective observational | Manuscript | 34.4 years (range, unknown) | Severe TBI |
Primary: To describe the trend of CMD glucose after TBI
Secondary: Evaluate the lactate response to low CMD glucose; also assess FDG-PET response |
Wang et al. [103] | 18 | Unknown | Meeting abstract | Unknown | Severe TBI – all post-DC |
Primary: To evaluate CMD measures during medical ICP therapy, post-DC
Secondary: None mentioned |
Yokobori et al. [105] | 25 | Prospective observational | Manuscript | 58.2 years (range, unknown) | Severe TBI |
Primary: To determine the association between CMD markers and PRx within the first 7 days of injury
Secondary: Determine association between CMD markers and patient outcome |
Zauner et al. [107] | 20 | Unknown | Meeting abstract | Unknown | Severe TBI |
Primary: To compare CMD markers, PbtO2, and CPP to patient outcome
Secondary: None mentioned |
Zauner et al. [108] | 24 | Prospective observational | Manuscript | Unknown | Severe TBI |
Primary: To evaluate the association between PbtO2 and outcome
Secondary: To evaluate the association between CMD markers and outcome |
Nil association studies | ||||||
Alessandri et al. [3] | 34 | Unknown | Meeting abstract | Unknown | Severe TBI |
Primary: To determine the association between CMD sodium and glutamate to outcome and ICP
Secondary: None mentioned |
Chen et al. [16] | 20 | Retrospective case series | Meeting abstract | Unknown (range, 18–90) | Severe TBI |
Primary: To determine the association between CMD LPR/glucose with ICP/CPP in young and old patients
Secondary: To determine the association between CMD markers and outcome |
Nelson et al. [60] | 26 | Retrospective case series | Manuscript | 52.2 years (range, 15–77) | Severe TBI |
Primary: To determine patterns between CMD measures and ICP/CPP
Secondary: Determine association between CMD markers and outcome |
Nelson et al. [61] | 90 | Retrospective case series | Manuscript | 48.9 years (range, 17–77) | Severe TBI |
Primary: To determine the relationship between CMD measures and ICP/CPP
Secondary: Determine association to outcome |
Papanikolaou et al. [68] | 30 | Unknown | Meeting abstract | Unknown | Severe TBI |
Primary: To determine the correlation between glycerol and other CMD measures to outcome and ICP/CPP
Secondary: None mentioned |
Thelin et al. [92] | 14 | Prospective observational | Manuscript | 43.2 years (range, 20–62) | Severe TBI |
Primary: To assess the relationship between CSF CMD and conventional brain parenchymal CMD
Secondary: Determine association with outcome |
Neuro-physiologic measures studies
Reference | Number of patients | Study type | Article location | Mean age (years) | Patient characteristics | Primary and secondary goal of study |
---|---|---|---|---|---|---|
ICP/CPP positive association studies | ||||||
Adamides et al. [1] | 14 | Prospective observational | Manuscript | 40 years (range, 19–66) | Severe TBI |
Primary: To evaluate the temporal relationship between CMD measures and ICP/CPP
Secondary: None mentioned |
Belli et al. [7] | 25 | Prospective observational | Manuscript | 41.8 years (range, 16–78) | Severe TBI |
Primary: To evaluate the relationship between CMD measures and ICP
Secondary: None mentioned |
Bolcha et al. [10] | 20 | Prospective observational | Meeting abstract | Unknown | Severe TBI |
Primary: Determine association between ICP/PbtO2 and CMD to patient outcome
Secondary: None mentioned |
Bullock et al. [12] | 80 | Prospective observational | Manuscript | Unknown | Severe TBI |
Primary: Determine association of EAA and clinical outcomes (i.e., ischemic events, ICP/CPP, patient outcome)
Secondary: None mentioned |
Clausen et al. [17] | 76 | Prospective observational | Manuscript | Unknown | Severe TBI |
Primary: Determine association between CMD glycerol and patient outcome
Secondary: Determine association between CMD glycerol and monitoring (CPP/PbtO2) |
Clausen et al. [18] | 151 | Prospective observational | Manuscript | 35.5 years (range, unknown) | Severe TBI |
Primary: Determine the association of brain pH, PCO2, lactate to patient outcome
Secondary: Determine the association of above to CPP, PbtO2
|
Goodman et al. [26] | 7 | Retrospective case series | Manuscript | 34.6 years (range, 19–48) | Severe TBI on barbiturate therapy |
Primary: To evaluate the impact of barbiturate sedation on CMD measures and ICP in severe TBI
Secondary: None mentioned |
Goodman et al. [25] | 126 | Prospective observational | Manuscript | 34.4 years (range, unknown) | Severe TBI |
Primary: Determine association between CMD lactate and glucose to ICP/CPP/PbtO2/SjvO2/rCBF
Secondary: Clinical outcome |
Gupta et al. [28] | 41 | Unknown | Meeting abstract | Unknown (over 18) | Severe TBI |
Primary: Determine association between CMD glycerol and LPR with CPP and patient outcome
Secondary: None mentioned |
Hejcl et al. [34] | 20 | Prospective observational | Meeting abstract | Unknown | Severe TBI |
Primary: Determine association between CMD/ICP/CPP/PbtO2 and patient outcome
Secondary: None mentioned |
Koura et al. [47] | 83 | Unknown | Meeting abstract | Unknown | Severe TBI |
Primary: Determine association between CMD measures and CPP/ICP/patient outcome
Secondary: None mentioned |
Kurtz et al. [48] | 46 | Retrospective case series | Manuscript | 55 years (range, unknown) | Severe TBI |
Primary: Determine association between CMD/serum glucose and patient outcome
Secondary: Association with CMD markers of metabolic stress (CPP and PbtO2) |
Li et al. [51] | 53 | Retrospective case series | Manuscript | 42 years (range, 15–60) | Severe TBI |
Primary: Determine association between CMD glycerol and ICP/CPP and patient outcome
Secondary: None mentioned |
Meixensberger et al. [56] | 9 | Prospective observational | Manuscript | 33.3 years (range, 14–60) | Severe TBI |
Primary: To determine the correlation between CMD measures and ICP/CPP and PbtO2
Secondary: None mentioned |
Nelson et al. [61] | 90 | Retrospective case series | Manuscript | 48.9 years (range, 17–77) | Severe TBI |
Primary: To determine the relationship between CMD measures and ICP/CPP
Secondary: Determine association to outcome |
Nordstrom et al. [62] | 213 | Retrospective case series | Manuscript | 40 years (range, 19–63) | Severe TBI |
Primary: Determine correlation between CMD markers and injury patterns/patient outcome
Secondary: None mentioned |
Papanikolaou et al. [68] | 30 | Unknown | Meeting abstract | Unknown | Severe TBI |
Primary: To determine the correlation between glycerol and other CMD measures to outcome and ICP/CPP
Secondary: None mentioned |
Paraforou et al. [69] | 34 | Prospective observational | Manuscript | 43.6 years (range, unknown) | Severe TBI |
Primary: Determine relationship between CPP/ICP/CMD and patient outcome
Secondary: None mentioned |
Richards et al. [75] | 9 | Prospective observational | Manuscript | 8 years (range, 3–14) | Severe TBI |
Primary: Determine the association between glutamate and clinical outcome; also determine if an “excitotoxic index” (glutamate:glutamine) correlated to outcome
Secondary: Correlation of CMD markers to ICP |
Salci et al. [79] | 10 | Unclear | Manuscript | 45.1 years (range, 19–63) | Severe TBI |
Primary: To determine the relationship between CMD measures and ICP/compliance
Secondary: None mentioned |
Sarrafzadeh et al. [82] | 18 | Unclear | Meeting abstract | 36 years (range, unknown) | Severe TBI |
Primary: To determine the relationship between CMD measures and ICP/SjvO2/PbtO2
Secondary: None mentioned |
Singla et al. [86] | 41 | Unknown | Meeting abstract | Unknown | Severe TBI |
Primary: Determine relationship between CPP/CMD to patient outcome
Secondary: None mentioned |
Stahl et al. [87] | 7 | Retrospective case series | Manuscript | 55.4 years (range, 27–74) | Severe TBI whom died |
Primary: To document CMD measure responses to ICP during end of life
Secondary: None mentioned |
Stein et al. [89] | 117 | Unclear | Meeting abstract | Unknown | Severe TBI |
Primary: To determine the relationship between CMD measured metabolic crisis (LPR > 40) and ICP
Secondary: None mentioned |
Stiefel et al. [91] | 27 | Retrospective case series | Meeting abstract | Unknown | Severe TBI |
Primary: Determine relationship between ICP/CPP/PbtO2/CMD and outcome
Secondary: Determine is “metabolic compromise” (LPR > 25) or “metabolic crisis” (LPR > 40) is associated to outcome |
Timofeev et al. [93] | 223 | Retrospective case series | Manuscript | Unknown | Severe TBI |
Primary: Determine the relationship between CMD markers and neurological outcome
Secondary: Association between CMD markers and ICP/PRx |
Timofeev et al. [94] | 97 | Prospective observational | Manuscript | Unknown | Severe TBI |
Primary: To determine the relationship between CMD measures and PRx, ICP/CPP, PbtO2
Secondary: None mentioned |
Vespa et al. [98] | 17 | Prospective observational | Manuscript | 39.4 years (range, unknown) | Severe TBI |
Primary: To determine the extent and duration of CMD glutamate changes post-TBI
Secondary: To determine the correlation between glutamate and CPP |
PbtO2/SjvO2 positive association studies | ||||||
Chan et al. [15] | 25 | Unknown | Meeting abstract | Unknown | Severe TBI |
Primary: To determine SjvO2 correlated to CMD measures in TBI
Secondary: None mentioned |
Figaji et al. [21] | 5 | Prospective observational | Meeting abstract | Unknown (children) | Severe TBI |
Primary: Determine association of inflammatory cytokines and other CMD markers/patient outcome
Secondary: None mentioned |
Menzel et al. [57] | 24 | Prospective Non-randomized | Manuscript | 34.4 years (range, 20–74) | Severe TBI Non-randomized to high FiO2
|
Primary: To determine the impact of increased FiO2 on CMD measures and PbtO2
Secondary: None mentioned |
Menzel et al. [58] | 14 | Prospective single arm | Manuscript | Unknown (adults) | Severe TBI |
Primary: To determine the change in CMD markers, CBF, and PbtO2 to induced hyperoxia
Secondary: None mentioned |
Nortje et al. [63] | 11 | Prospective single arm | Manuscript | 42 years (range, 17–64) | Severe TBI |
Primary: To determine if normobaric hyperoxia leads to changes in 15O PET, CMD and PbtO2
Secondary: None mentioned |
Purins et al. [72] | 23 | Prospective observational | Manuscript | Unknown | Severe TBI |
Primary: To determine the relationship between PbtO2 and CMD measures
Secondary: None mentioned |
Robertson et al. [76] | 79 | Unknown | Meeting abstract | Unknown | Severe TBI |
Primary: Determine the association between CMD glutamine/aspartate and patient outcome and PbtO2/CBF (TCD)
Secondary: None mentioned |
Sarrafzadeh et al. [83] | 35 | Retrospective case series | Manuscript | Unknown | Severe TBI |
Primary: To determine the relationship between CMD and PbtO2
Secondary: None mentioned |
Sarrafzadeh et al. [84] | 24 | Unknown | Meeting abstract | Unknown | Severe TBI |
Primary: To determine the relationship between CMD and PbtO2
Secondary: None mentioned |
Timofeev et al. [95] | 56 | Prospective observational | Manuscript | 38.5 years (range, 25–52) | Severe TBI |
Primary: To compare brain pH to disturbances in PbtO2 and CMD
Secondary: None mentioned |
Valdaka et al. [96] | 5 | Prospective observational | Manuscript | Unknown | Severe TBI during herniation and death |
Primary: To evaluate the correlation between CMD and PbtO2 in fatal TBI
Secondary: None mentioned |
Vilalta et al. [101] | 30 | Prospective single arm | Manuscript | 27 years (range, 17–59) | Severe TBI - Normobaric hyperoxic challenge |
Primary: To determine the impact of normbaric hyperoxia on CMD and PbtO2 in TBI
Secondary: Determine the impact on outcome |
Autoregulation - positive association studies | ||||||
Asgari et al. [4] | 19 | Prospective observational | Manuscript | 41.9 years (range, unknown) | Severe TBI |
Primary: To evaluate the relationship between MOCAIP ICP waveform-based autoregulation measurements and CMD measures
Secondary: None mentioned |
Asgari et al. [5] | 30 | Prospective observational | Manuscript | 46 years (unknown) | Severe TBI |
Primary: To determine the relationship between CMD measures and PMTM ICP waveform analysis of vasoconstriction/vasodilation
Secondary: None mentioned |
Yokobori et al. [105] | 25 | Prospective observational | Manuscript | 58.2 years (range, unknown) | Severe TBI |
Primary: To determine the association between CMD markers and PRx within the first 7 days of injury
Secondary: Determine association between CMD markers and patient outcome |
Imaging-based positive association studies | ||||||
Bouzat et al. [11] | 27 | Prospective observational | Manuscript | 39 years (range, 24–54) | Severe TBI |
Primary: To determine the relationship between CMD, PbtO2 and ICP measures to CBF as measured via CTP
Secondary: None mentioned |
Hutchinson et al. [39] | 13 | Prospective observational | Manuscript | 34 years (range, 16–66) | Severe TBI |
Primary: To determine relationship between CMD measures and H2
15O PET
Secondary: None mentioned |
Hutchinson et al. [40] | 17 | Prospective observational | Manuscript | 43.4 years (range, 17–66) | Severe TBI |
Primary: To determine the relationship between CMD measures and FDG PET
Secondary: None mentioned |
Reinert et al. [74] | 85 | Prospective observational | Manuscript | Unknown | Severe TBI |
Primary: Determine the relationship between CMD potassium and ICP/CBF/other CMD substrates and patient outcome
Secondary: None mentioned |
Sala et al. [78] | 24 | Prospective observational | Manuscript | 36 years (range, unknown) | Severe TBI |
Primary: To determine the relationship between CMD measures and CBF post-TBI
Secondary: None mentioned |
Vespa et al. [97] | 19 | Prospective observational | Manuscript | 32.3 years (range, 16–57) | Severe TBI |
Primary: To evaluation the presence of CMD measures during changes in CMRO2 and CMRglu
Secondary: None mentioned |
Vespa et al. [99] | 30 | Prospective observational | Manuscript | 34.4 years (range, unknown) | Severe TBI |
Primary: To describe the trend of CMD glucose after TBI
Secondary: Evaluate the lactate response to low CMD glucose; also assess FDG-PET and Xe CT CBF response |
Zauner et al. [109] | 25 | Unknown | Meeting abstract | Unknown | Severe TBI |
Primary: To evaluate the relationship between CMD glutamate and CBF as measured by Xe CT
Secondary: None mentioned |
Negative association studies | ||||||
Alessandri et al. [3] | 34 | Unknown | Meeting abstract | Unknown | Severe TBI |
Primary: To determine the association between CMD sodium and glutamate to outcome and ICP
Secondary: None mentioned |
Chamoun et al. [13] | 135 | Prospective observational | Manuscript | 36.6 years (range, 16–91) | Severe TBI |
Primary: Determine the association between CMD glutamate and prognosis
Secondary: Correlation between glutamate and MABP/ICP/PbtO2/SjvO2
|
Johnston et al. [44] | 11 | Prospective single arm | Manuscript | 32 years (range, unknown | Severe TBI |
Primary: To evaluate the relationship between 15O PET, PbtO2 and CMD to CPP augmentation in TBI
Secondary: Determine association to outcome |
Nelson et al. [60] | 26 | Retrospective case series | Manuscript | 52.2 years (range, 15–77) | Severe TBI |
Primary: To determine patterns between CMD measures and ICP/CPP
Secondary: Determine association between CMD markers and outcome |
Peerdeman et al. [70] | 15 | Prospective observational | Manuscript | 39.5 years (range, 18–69) | Severe TBI |
Primary: Determine the association between secondary events (elevated ICP, low CPP, elevated temp) to CMD and outcome
Secondary: None mentioned |
Petzold et al. [71] | 10 | Prospective observational | Manuscript | 39 years (range, 20–68) | Severe TBI |
Primary: To correlate CMD measured neurofilament protein to injury pattern, physiologic measures, and outcome
Secondary: Assess other CMD measures relation to outcome |
Sanchez-Porras et al. [81] | 29 | Retrospective case series | Manuscript | 37.2 years (range, unknown) | Severe TBI |
Primary: To evaluate long PRx and its relationship to patient outcome
Secondary: To correlated PRx to other monitoring (i.e., CMD) |
Vespa et al. [100] | 21 | Retrospective case series | Manuscript | 31.4 years (range, 18–58) | Severe TBI |
Primary: To determine the relationship between CPP and LPR
Secondary: None mentioned |
Tissue outcome studies
Reference | Number of patients | Study type | Article location | Mean age (years) | Patient characteristics | Primary and secondary goal of study |
---|---|---|---|---|---|---|
Positive association studies | ||||||
Filippou et al. [23] | 6 | Prospective observational | Meeting abstract | Unknown | Severe TBI |
Primary: CMD measures and MRS/ADC imaging
Secondary: None stated |
Marcoux et al. [53] | 15 | Retrospective case series | Manuscript | 30.1 years (range, 18–58) | Severe TBI |
Primary: Determine association between CMD-based metabolic dysfunction and long-term tissue atrophy
Secondary: Determine association with long-term outcome |
Nil association studies | ||||||
Filippou et al. [22] | 10 | Prospective observational | Meeting abstract | Unknown | Severe TBI |
Primary: Determine CMD measure correlation to MRS/ADC
Secondary: None mentioned |
Stein et al. [89] | 21 | Prospective observational | Meeting abstract | Unknown | Severe TBI |
Primary: To determine if CMD defined metabolic crisis (LPR > 25; glucose <0.8 mmol/l) correlates with MRI-based ADC changes |
CMD measurement technique
Measures of outcome
Patient functional outcome - positive association studies
Glucose
Glutamate
Glycerol
Lactate/LPR
Potassium
Neuro-physiologic measures – positive association studies
CMD association with ICP/CPP
CMD association with SjvO2
CMD association with PbtO2
CMD association to autoregulation
CMD associations with cerebral blood flow and metabolism
Tissue outcome – positive association studies
Nil association studies
Complications of CMD monitoring
Functional outcome studies
Neuro-physiologic measure studies
Tissue outcome studies
Assessment of bias
Level of evidence
Functional outcome
CMD measure | Association with patient functional outcome | GRADE level of evidence |
---|---|---|
Glucose | Low mean glucose is associated with poor outcome/mortality at 3–6 months post-injury | C (Low) – Large number of studies with significant limitations |
Glutamate | High mean glutamate is associated with poor outcome/mortality at 3–6 months post-injury | C (Low) – Large number of studies with significant limitations |
Glycerol | High mean glycerol is associated with poor outcome/mortality at 3–6 months post-injury | C (Low) – Large number of studies with significant limitations |
LPR | Elevated mean LPR (>25 to 40) is associated with poor outcome/mortality at 3–6 months post-injury | C (Low) – Large number of studies with significant limitations |
Lactate | Elevated mean lactate is associated with poor outcome/mortality at 3–6 months post-injury | C (Low) – Large number of studies with significant limitations |
Pyruvate | Persistently low mean pyruvate levels, in the presence of elevated LPR, is associated with üoor outcome | D (Very Low) – limited number of studies evaluating pyruvate in isolation; significant limitations identified within these studies |
Potassium | Mean potassium levels less than 1.8 mmol/l is associated with a good GOS at 3 months post-injury | D (Very Low) – one study with limitations |
Sodium | There is no association between mean CMD sodium levels and outcome | D (Very Low) – one study with limitations |
Neuro-physiologic measures
Physiologic measure | GRADE level of evidence | CMD measure(s) | Rationale |
---|---|---|---|
ICP/CPP | C (low) | LPR, glutamate, glycerol | Several studies with large patient numbers and statistically significant relations but major study limitations in all |
D (very low) | Lactate (alone), pyruvate (alone), glucose, potassium | Small number of studies with severe limitations | |
SjvO2
| D (very low) | Lactate (alone), glutamate, glycerol | Very limited number of studies with significant bias/limitation |
PbtO2
| C (low) | LPR | Several studies with severe limitations |
D (very low) | Glycerol, glutamate, lactate, potassium glucose | Very limited number of studies. All significantly flawed. Publication bias high in this area. | |
Autoregulation (PRx and ICP waveform analysis) | D (very low) | LPR, glutamate, glycerol | Very limited number of studies. Bias high. Publication bias very high. |
Imaging | No GRADE applied | N/A | This area of the literature was extremely scarce, heterogeneous, suffering from publication bias, design bias. Thus, we felt it inappropriate to assign any GRADE level to this area at this time |