Brain under pressure Impact of vasopressors

Transcription

1 Brain under pressure Impact of vasopressors

2 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

3 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 Ebersoldt et al. Int Care Med 2007 Pytel et al. Curr Op Neurol Chronic: deficits in memory, executive functions Adjusted OR moderate-severe cognitive impairment 3.34 (95% CI, ) Iwashyna et al. JAMA 2010

4 Brain dysfunction in sepsis Underlying mechanism - Unclear - Multifactorial Ischemia Inflammation Brain damage Cellular dysfunction Encephalopathy Siami et al. Crit Care Clin 2008

5 Brain dysfunction in sepsis Underlying mechanism - Ischemia Reduced microcirculatory flow Taccone et al. Crit Care Med 2014

6 Brain dysfunction in sepsis Underlying mechanism - Ischemia Metabolic anomalies Taccone et al. Crit Care Med 2014

7 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 be further evaluated. Taccone et al. Crit Care Med 2014

8 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

9 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

10 Participants Inclusion septic patients 18 years old Clinical diagnosis of septic shock Receiving vasopressors Mechanically ventilated Sedated with propofol infusion Assessed as stable by the intensivist Exclusion septic patients Pregnant Contraindication to MRI Active cerebral pathology Not committed to life-sustaining Tx Inclusion healthy volunteers 18 years old Exclusion healthy volunteers Pregnant Contraindication to MRI Allergic to propofol Potentially difficult intubation/ventilation (as assessed by anesthesiologist)

11 Protocol Monitoring Continuous monitoring: blood pressure, cardiac rhythm, O 2 saturation, CO 2 Accompanied by: critical care nurse, respiratory therapist, anesthesiologist/intensivist

12 Protocol Septic patients Norepinephrine titrated for MAP 65 mmhg and 75 mmhg Healthy volunteers Propofol administered for Richmond Agitation-Sedation Scale score of -2 to -3

13 Results - Participants April 2016 to January septic patients (n=4 with HTN) 1.5 (range 0-3) days after ICU admission 12 healthy volunteers (n=6 with HTN) Table 1. Baseline characteristics of healthy volunteers and septic patients Characteristic Healthy volunteers (N = 12) Septic patients (N = 10) Mean age, years (range) 44 (21-68) 61 (39-75) Female sex no. (%) 2 (17) 3 (30) Chronic comorbidities no. (%) Hypertension 6 (50) 4 (40) Coronary artery disease 0 (0) 2 (20) Congestive Heart failure 0 (0) 2 (20) Diabetes mellitus 0 (0) 4 (40) Chronic obstructive pulmonary disease 0 (0) 2 (20) Cancer 0 (0) 1 (10) Immunosuppression 0 (0) 1 (10) Source of infection no. (%) Respiratory N/A 9 (90) Abdominal N/A 1 (10) Other N/A 0 (0) Baseline APACHE II, mean (SD) N/A 28 (6.6) MRI done on ICU day #, mean (range) N/A 1.5 (0-3)

14 Effects of sedation in healthy volunteers At baseline Mean (SD) MAP: 91 (15) mmhg Similar MAP in hypertensive pts Figure 3. Cerebral blood flow in healthy volunteers wit sedated septic patients using MAP targets of 65 and 75 During image acquisition Mean propofol dose: 156 (85) mg MAP, ph and CO 2 unchanged No interaction with HTN

15 Figure 3. Cerebral blood flow in healthy volunteers Figure 3. Cerebral with and blood without flow sedation in healthy and volunteers in wi sedated septic patients using MAP targets of 65 and 7 Effects of sedated MAP septic targets patients using MAP in targets septic of 65 and patients 75 mmhg At baseline Mean (SD) MAP: 69 (7) mmhg No difference in hypertensive patients Mean arterial ph: 7.36 (0.07) Mean arterial CO (7.9) mmhg During image acquisition Mean (SD) MAP: 66 (4) mmhg 84 (13) mmhg (p<0.001) ph and CO 2 unchanged No interaction with HTN

16 Healthy volunteers vs. septic patients Cerebral blood flow of septic patients (sedated and MAP target of 65 mmhg) Figure 3. Cerebral blood flow in healthy volunteers with and without sedation and in sedated septic patients using MAP targets of 65 and 75 mmhg 62% higher than healthy volunteers (sedated) 40.4 (10.9) versus 24.9 (5.9) ml/100 g/min; p=0.001

17 Cerebral blood flow by regions of interest Table 2. Cerebral blood flow by region of interest in healthy volunteers without and with sedation; and in septic patients at a mea arterial pressure target of 65 mmhg and 75 mmhg Region of interest Healthy volunteers (N = 11) Septic patients (N = 9) Mean cerebral blood flow ml/100 g/min (SD) Without sedation With sedation P value MAP 65 mmhg MAP 75 mmhg P value Cerebrum Cerebral blood flow in all regions of Cingulate Cortex 38.0 (7.3) 38.5 (7.9) (12.4) 43.6 (10.1) 0.65 Frontal Lobe 34.1 interest (6.0) 33.6 was (7.7) consistent (13.0) with 50.9 global (12.5) 0.57 Occipital Lobe 27.4 (4.8) 27.0 (6.1) (16.5) 48.8 (15.3) 0.56 Parietal Lobe 31.2 (5.2) 31.7 (6.5) (11.0) 46.9 (10.1) 0.93 cerebral blood flow Temporal Lobe 26.7 (6.6) 26.9 (8.5) (10.8) 44.9 (10.5) 0.73 Amygdala 16.2 (5.7) 15.5 (4.5) (10.8) 30.2 (10.3) 0.76 Basal Ganglia 25.7 (3.6) 28.2 (6.0) (7.5) 35.7 (6.2) 0.77 Hippocampus 22.1 (4.9) 22.4 (3.4) (7.0) 29.1 (6.2) 0.71 Thalamus 25.3 (4.5) 26.0 (4.6) (13.7) 43.5 (10.5) 0.69 Cerebral White Matter 24.6 (3.8) 24.1 (4.4) (10.7) 40.0 (9.3) 0.65 Cerebellum Cerebellar Cortex 6.8 (5.1) 6.8 (5.2) (13.1) 25.6 (12.1) 0.51 Cerebellar White Matter 5.4 (4.9) 4.9 (4.6) (17.9) 24.0 (15.9) 0.27 Global Cerebral Blood Flow 24.8 (4.2) 24.9 (5.9) (10.9) 41.3 (9.8) 0.65

18 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 therapy for a mean arterial pressure of 65 mmhg once patients are stabilized

19 Limitations The number of participants was small, reducing the precision of our estimates We 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 reported Potential explanation: acquisition field in this study truncated the superior cerebral cortex, an area of the brain that is highly perfused

20 MH Masse F D Aragon M Mayette W Fraser S Palanchuk L Lanthier MA Richard C St-Arnaud N Adhikari A Carpentier D Gauthier M Touchette A Lamontagne S Mehta É Croteau J Chénard Y Sansoucy M Lepage Thank you francois.lamontagne@usherbrooke.ca

21 Cerebral autoregulatory threshold Strandgaard et al. BMJ 1973

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23 Figure 4. Arterial spin labeling superimposed on a T1-weighted image in (a) a septic patient treated with vasopressors, (b) an awake healthy volunteer, and (c) a patient with an acute hemispheric ischemic stroke. a) b) b) c) 14 Panel a Awake healthy volunteer; panel b Septic pa