Brain under pressure Impact of vasopressors · 2019-09-27 · the effect of MAP correction, for...

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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

• Underlying mechanism- Ischemia

Metabolic anomalies

• 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.’

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

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

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

No interaction with HTN

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

Table2.Cerebralbloodflowbyregionofinterestinhealthyvolunteerswithoutandwithsedation;andinsepticpatientsatameanarterialpressuretargetof65mmHgand75mmHg

RegionofinterestHealthyvolunteers

(N=11)Septicpatients

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

Figure4.ArterialspinlabelingsuperimposedonaT1-weightedimagein(a)asepticpatienttreatedwithvasopressors,(b)anawakehealthyvolunteer,and(c)apatientwithanacutehemisphericischemicstroke.a)

Panela–Awakehealthyvolunteer;panelb–Septicpatienttreatedwithvasopressors;panelc-Patientwithanacutehemisphericischemicstroke

Brain under pressure Impact of vasopressors · 2019-09-27 · the effect of MAP correction, for...

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