Post on 02-Apr-2020
Brain under pressure
Impact of vasopressors
Brain dysfunction in sepsis• Incidence:
- Varying nomenclature: sepsis-associated encephalopathy, delirium, brain dysfunction…
- Consistently recognized as frequent: prevalence up 70%Ebersoldt et al. Int Care Med 2007
Brain dysfunction in sepsis• Incidence:
- Varying nomenclature: sepsis-associated encephalopathy, delirium, brain dysfunction…
- Consistently recognized as frequent: prevalence up 70%
• Clinical manifestations- Acute: delirium, altered level of consciousness, seizures…
- Chronic: deficits in memory, executive functions…
Adjusted OR moderate-severe cognitive impairment 3.34 (95% CI, 1.53-7.25)
Ebersoldt et al. Int Care Med 2007
Pytel et al. Curr Op Neurol 2009
Iwashyna et al. JAMA 2010
Brain dysfunction in sepsis• Underlying mechanism
- Unclear
- Multifactorial
Ischemia Inflammation
Brain damage Cellular dysfunction
Encephalopathy
Siami et al. Crit Care Clin 2008
Brain dysfunction in sepsis
• Underlying mechanism- Ischemia
Reduced microcirculatory flow
Taccone et al. Crit Care Med 2014
Brain dysfunction in sepsis
• Underlying mechanism- Ischemia
Metabolic anomalies
Taccone et al. Crit Care Med 2014
Brain dysfunction in sepsis
• Underlying mechanism
‘…most metabolic disturbances occurred during the hypotensive phase, and the effect of MAP correction, for example, by administering vasopressors, on alterations of microvascular flow, oxygenation, and metabolism need to befurther evaluated.’
Taccone et al. Crit Care Med 2014
Objectives and design• Objectives: compare cerebral blood flow
- Septic patients receiving vasopressors vs. healthy volunteers
- Septic patients at MAP 65 mmHg vs. ≥ 75 mmHg
- Healthy volunteers under sedation vs. awake
• Design- Randomized crossover study
Arterial spin labeling• Radiofrequency pulses
• Excite magnetization from nuclear spin hydrogen atoms in water molecules
• Effectively ‘labeling’ water molecules on T1-weighted image
• Cerebral blood flow = difference between labeled and nonlabeled images
Ferré et al. Diag Int Imag 2013
ParticipantsInclusion – septic patients
• 18 years old
• Clinical diagnosis of septic shock
• Receiving vasopressors
• Mechanically ventilated
• Sedated with propofol infusion
• Assessed as stable by the intensivist
Inclusion – healthy volunteers• 18 years old
Exclusion – septic patients• Pregnant
• Contraindication to MRI
• Active cerebral pathology
• Not committed to life-sustaining Tx
Exclusion – healthy volunteers• Pregnant• Contraindication to MRI• Allergic to propofol• Potentially difficult intubation/ventilation
(as assessed by anesthesiologist)
ProtocolMonitoring
• Continuous monitoring: blood pressure, cardiac rhythm, O2 saturation, CO2
• Accompanied by: critical care nurse, respiratory therapist, anesthesiologist/intensivist
ProtocolSeptic patients
• Norepinephrine titrated for MAP 65 mmHg and ≥ 75 mmHg
Healthy volunteers
• Propofol administered for Richmond Agitation-Sedation Scale score of -2 to -3
April 2016 to January 2017
• 10 septic patients(n=4 with HTN)
1.5 (range 0-3) days
after ICU admission
• 12 healthy volunteers(n=6 with HTN)
Results - Participants
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Table1.Baselinecharacteristicsofhealthyvolunteersandsepticpatients
CharacteristicHealthyvolunteers
(N=12)Septicpatients
(N=10)
Meanage,years(range) 44(21-68) 61(39-75)Femalesex–no.(%) 2(17) 3(30)Chroniccomorbidities–no.(%) Hypertension 6(50) 4(40) Coronaryarterydisease 0(0) 2(20) CongestiveHeartfailure 0(0) 2(20) Diabetesmellitus 0(0) 4(40) Chronicobstructivepulmonarydisease 0(0) 2(20) Cancer 0(0) 1(10) Immunosuppression 0(0) 1(10)Sourceofinfection–no.(%) Respiratory N/A 9(90) Abdominal N/A 1(10) Other N/A 0(0)BaselineAPACHEII,mean(SD) N/A 28(6.6)MRIdoneonICUday#,mean(range) N/A 1.5(0-3)
Legend:APACHEII:AcutePhysiologicandChronicHealthEvaluation,MRI:MagneticResonanceImaging,ICU:Intensivecareunit
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Figure3.CerebralbloodflowinhealthyvolunteerswithandwithoutsedationandinsedatedsepticpatientsusingMAPtargetsof65and75mmHg
CBF:cerebralbloodflow.Graylinesrepresentindividualparticipants.Dashedlinesrepresentparticipantswithamedicalhistoryofchronichypertension;fulllinesarenormotensiveparticipants.Thethickerblacklinesrepresentgroupmeans.
At baselineMean (SD) MAP: 91 (15) mmHg
Similar MAP in hypertensive pts
During image acquisitionMean propofol dose: 156 (85) mg
MAP, pH and CO2 unchanged
Effects of sedation in healthy volunteers
No interaction with HTN
At baselineMean (SD) MAP: 69 (7) mmHg
No difference in hypertensive patients
Mean arterial pH: 7.36 (0.07)
Mean arterial CO2 40.0 (7.9) mmHg
During image acquisitionMean (SD) MAP:
66 (4) mmHg
84 (13) mmHg (p<0.001)
pH and CO2 unchanged
Effects of MAP targets in septic patients
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Figure3.CerebralbloodflowinhealthyvolunteerswithandwithoutsedationandinsedatedsepticpatientsusingMAPtargetsof65and75mmHg
CBF:cerebralbloodflow.Graylinesrepresentindividualparticipants.Dashedlinesrepresentparticipantswithamedicalhistoryofchronichypertension;fulllinesarenormotensiveparticipants.Thethickerblacklinesrepresentgroupmeans.
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Figure3.CerebralbloodflowinhealthyvolunteerswithandwithoutsedationandinsedatedsepticpatientsusingMAPtargetsof65and75mmHg
CBF:cerebralbloodflow.Graylinesrepresentindividualparticipants.Dashedlinesrepresentparticipantswithamedicalhistoryofchronichypertension;fulllinesarenormotensiveparticipants.Thethickerblacklinesrepresentgroupmeans.
No interaction with HTN
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Figure3.CerebralbloodflowinhealthyvolunteerswithandwithoutsedationandinsedatedsepticpatientsusingMAPtargetsof65and75mmHg
CBF:cerebralbloodflow.Graylinesrepresentindividualparticipants.Dashedlinesrepresentparticipantswithamedicalhistoryofchronichypertension;fulllinesarenormotensiveparticipants.Thethickerblacklinesrepresentgroupmeans.
Cerebral blood flow of septic patients (sedated and MAP target of 65 mmHg)62% higher than healthy volunteers (sedated)
40.4 (10.9) versus 24.9 (5.9) mL/100 g/min; p=0.001
Healthy volunteers vs. septic patients
Cerebral blood flow by regions of interest
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Table2.Cerebralbloodflowbyregionofinterestinhealthyvolunteerswithoutandwithsedation;andinsepticpatientsatameanarterialpressuretargetof65mmHgand75mmHg
RegionofinterestHealthyvolunteers
(N=11)Septicpatients
(N=9)
Meancerebralbloodflow–mL/100g/min(SD)Withoutsedation
Withsedation Pvalue
MAP65mmHg
MAP75mmHg Pvalue
Cerebrum CingulateCortex 38.0(7.3) 38.5(7.9) 0.81 44.8(12.4) 43.6(10.1) 0.65 FrontalLobe 34.1(6.0) 33.6(7.7) 0.79 49.1(13.0) 50.9(12.5) 0.57 OccipitalLobe 27.4(4.8) 27.0(6.1) 0.75 47.3(16.5) 48.8(15.3) 0.56 ParietalLobe 31.2(5.2) 31.7(6.5) 0.70 46.7(11.0) 46.9(10.1) 0.93 TemporalLobe 26.7(6.6) 26.9(8.5) 0.94 44.2(10.8) 44.9(10.5) 0.73 Amygdala 16.2(5.7) 15.5(4.5) 0.72 30.6(10.8) 30.2(10.3) 0.76 BasalGanglia 25.7(3.6) 28.2(6.0) 0.20 36.2(7.5) 35.7(6.2) 0.77 Hippocampus 22.1(4.9) 22.4(3.4) 0.82 28.4(7.0) 29.1(6.2) 0.71 Thalamus 25.3(4.5) 26.0(4.6) 0.72 41.8(13.7) 43.5(10.5) 0.69 CerebralWhiteMatter 24.6(3.8) 24.1(4.4) 0.74 38.7(10.7) 40.0(9.3) 0.65Cerebellum CerebellarCortex 6.8(5.1) 6.8(5.2) 0.99 24.3(13.1) 25.6(12.1) 0.51 CerebellarWhiteMatter 5.4(4.9) 4.9(4.6) 0.86 22.0(17.9) 24.0(15.9) 0.27GlobalCerebralBloodFlow 24.8(4.2) 24.9(5.9) 0.93 40.4(10.9) 41.3(9.8) 0.65
Cerebral blood flow in all regions of interest was consistent with global cerebral blood flow
Interpretation
• Septic patients who have been resuscitated and stabilized…
exhibit a greater cerebral blood flow than healthy volunteers
• The impact of this hyperperfusion, beneficial or harmful, remains unclear
• Raises questions regarding the utility/safety of continuing vasopressor therapyfor a mean arterial pressure of 65 mmHg once patients are stabilized
Limitations
• The number of participants was small, reducing the precision of our estimatesWe may have missed smaller effects on CBF induced by sedation in healthy volunteers and different MAP levels in septic patients
• Observations regarding the effects of septic shock, sedation or variations in MAP targets for vasopressors do not extend to earlier phases of resuscitation
• We did not assess associations between CBF measures and clinical manifestations
• CBF values in this study were lower than previously reportedPotential explanation: acquisition field in this study truncated the superior cerebral cortex, an area of the brain that is highly perfused
Thank youfrancois.lamontagne@usherbrooke.ca
MH MasseF D’AragonM MayetteW FraserS PalanchukL Lanthier
MA RichardC St-ArnaudN AdhikariA CarpentierD GauthierM Touchette
A LamontagneS MehtaÉ CroteauJ ChénardY SansoucyM Lepage
Cerebral autoregulatory threshold
Strandgaard et al. BMJ 1973
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Figure4.ArterialspinlabelingsuperimposedonaT1-weightedimagein(a)asepticpatienttreatedwithvasopressors,(b)anawakehealthyvolunteer,and(c)apatientwithanacutehemisphericischemicstroke.a)
b)
c)
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Figure4.ArterialspinlabelingsuperimposedonaT1-weightedimagein(a)asepticpatienttreatedwithvasopressors,(b)anawakehealthyvolunteer,and(c)apatientwithanacutehemisphericischemicstroke.a)
b)
c)
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Panela–Awakehealthyvolunteer;panelb–Septicpatienttreatedwithvasopressors;panelc-Patientwithanacutehemisphericischemicstroke