Mean Arterial Pressure Low could be good Prof. Jan Bakker MD, PhD Chair dept Intensive Care Adults jan.bakker@erasmusmc.nl www.intensivecare.me
Permissive hypotension 16yr old boy with St. aureus septic shock RRT and persistent hypotension with increasing lactate levels Goal of MAP: 70 mm Hg Dopamine, Norepinephrine, Epinephrine, Vasopressin current MAP: 45-50 mm Hg Lactate > 10 mmol/l Do you have an additional option to increase MAP?
Arterial blood pressure How much is enough? Dünser et al. Intensive Care med 2009;35:1225-1233 Dünser et al. Crit Care 2009;13:R181 Bourgoin et al. Crit Care Med 2005;33:780-786 Redfors et al. Intensive Care Med 2011;37:60-67 LeDoux et al. Crit Care Med 2000;28:2729-2732 Thooft et al. Crit Care 2011;15:R222 In critically ill patients the target MAP should probably be > 60 mmhg and < 75 mmhg for the majority of patients
Jean-François Georger Olfa Hamzaoui Anis Chaari Julien Maizel Christian Richard Jean-Louis Teboul Restoring arterial pressure with norepinephrine improves muscle tissue oxygenation assessed by near-infrared spectroscopy in severely hypotensive septic patients Intensive Care Med (2010) 36:1882 1889 Before norepinephrine (introduction/increase) After norepinephrine (introduction/increase) SAP (mmhg) 86 ± 19 126 ± 18* DAP (mmhg) 38 ± 7 52 ± 8* MAP (mmhg) 54 ± 8 77 ± 9* Heart rate (min -1 ) 98 ± 25 101 ± 28 Temperature ( C) 37.5 ± 1.4 37.5 ± 1.3 CI (L/min/m 2 ) 3.1 ± 1.0 3.6 ± 1.3* GEDVI (ml/m 2 ) 687 ± 117 730 ± 156* EVLWI (ml/kg) 13 ± 9 13 ± 7 SaO 2 (%) 94 ± 5 93 ± 4 PaO 2 (mmhg) 122 ± 73 115 ± 63 PaCO 2 (mmhg) 40 ± 16 40 ± 15 ph 7.34 ± 0.10 7.33 ± 0.10 ScvO 2 (%) 68 ± 9 72 ± 7* % 95 90 85 80 75 70 65 60 55 StO 2 before norepinephrine (introduction/increase) after norepinephrine (introduction/increase)
Effects of changes in arterial pressure on organ perfusion during septic shock Thooft et al. Crit Care 2011;15:R222 Key messages Increasing mean arterial pressure by norepinephrine during septic shock can increase cardiac output and improve microvascular flow and reactivity in stable resuscitated patients without modification of global oxygen consumption. There is considerable inter-individual variability in microvascular response, suggesting that the level of mean arterial pressure should be adapted to each patient.
Increasing arterial blood pressure with NE does not improve microcirculatory blood flow Dubin et al. Crit Care 2009;13:R92
Weil: However, the primary defect of shock is not so much a failure to maintain pressure as it is a failure to maintain flow of blood. California Medicine 1962 Huckabee on treatment of lactic acidosis: it seems likely that the circulatory defect is of the nature of a distributional change, since actual rates of blood flow are not low. It might prove very interesting if someone will try vasodilating drugs in such a patient. Am J Cardiol 1963
I~~~~~~~~~~ Endotoxin shock in the primate: Treatment with Phenoxybenzamine JA Vick. J Clin Invest 1964;43(2):279-284 i 5o I B4-PBZ KEY BLOOD PRESSURE 100 I -x-_x-= I, - ~ _ilk - mmhg 50 # Control w % - %/s survivors v at 24 hours RE SP. MIN. 0 X- 40 iox-l- -*-.lo DBZ - 20~zo ii- 10.0 0, 3/3 survivors *.--- at Z4 4 72 hours URINE OUTPUT < rb~~~~~~~~~ IJ CC/HOUR 5.0 XtX _ Y _ w~~~~ HCT 50 PERCENT 40 rl1 f2^ 7. 5 5 BLOOD 7.50. ph 7.45 f Endot1% fl%% 7.40 7.Smi9;/kg %X_~ 7. 3 5 L i I 2 3 4 5 6 7 8 9 ControlII Prz Endotoxin i HOURS POST ENDOTOXIN There is a growing interest in the treatment of endotoxin shock with vasodilating agents. I- L monkeys I I- 4r a I.X ll x L- &R fa... K--.X I Lethal injection of purified Escherichia coli endotoxin (7.5 mg per kg) Non-fluid resuscitated model
100 80 60 arteriolar vasodilation 40 20 arteriolar constriction arterial microcirculation venous
100 A 80 hypotension 60 40 arteriolar vasodilation venous constriction increased venous pressures 20 arterial microcirculation venous
normal arteriolar vasodilation 100 80 60 arteriolar vasodilation 40 A venous constriction increased venous pressures 20 Bdecreased venous pressures arterial microcirculation venous
The effects of intravenous nitroglycerine and norepinephrine on gastric microvascular perfusion in an experimental model of gastric tube reconstruction van Bommel et al. Surgery 2010;148:71-77 12 10 CTRL NTG * * * * * * * * * CVP mm Hg 8 6 4 2 0 BL S 50 60 70 80 90 100 110
The effect of perfusion pressure on gastric tissue blood flow in an experimental gastric tube model Klijn et al. Anesth Analg 2010;110:541-546 r speckle images and video images of the distal part of the gastric tube (upper panel) and base Figure 2. Blood flow for different locations on the gastric tube
Dynamics of StO2 mortality march-september 2011 221 consecutive patients enrolled expected LOS: 2 days complete initial resuscitation and stabilization follow up to Day 28 StO2 n=221 Admission Evolution during first 24h Normal n=160 Normal (>75%) n=166 Abnormal n=21 Abnormal (<75%) n=39 Abnormal n=25 ICU mortality 15% 57% Normal n=15 13% 56% Odds for mortality: persistent low StO2 during first 24h 7.9 (CI: 3-21, P<0.001) Odds for mortality: when StO2 decreased to <75% during first 24h 7.1 (CI: 2-21, P<0.001) Odds for mortality: persistent low StO2 and low peripheral perfusion 9.9 (CI: 3-41ß, P<0.001)
Abnormal peripheral perfusion effect of a stepwise increasing dose of NTG q Evaluation of the effects of nitroglycerine in the peripheral circulation q Study population : critically ill patients who had undergone initial resuscitation and stabilization within 24h of ICU admission with abnormalities in peripheral perfusion, defined as: - cold extremities/delayed CRT (>5s), - forearm finger T o C >2 (or PFI<1,4),
Abnormal peripheral perfusion effect of a stepwise increasing dose of NTG cold extremities/delayed CRT (>5s) forearm finger T o C >2 PFI<1.4
Abnormal peripheral perfusion effect of a stepwise increasing dose of NTG Global hemodynamic variables during execution of the study protocol (n = 13). Time points are defined as before nitroglycerine infusion (T baseline ), at the maximum dose of nitroglycerine (T Max ) and 30 min after cessation of nitroglycerine (T Bend ) T baseline T Max T end Heart rate, bpm 95 [90-103] 97 [91-100] 98 [89-106] Mean arterial pressure, mmhg 71 [70-80] 62* [57-69] 71 [70-76] Values are expressed as median [25th-75th] * P<0.05 vs. TBL1 and TBL2
Effect of NTG on StO2 StO2 (%) 100" 95" 90" 85" 80" 75" 70" 65" 60" 55" 50" y"="$0,6667x"+"119,06" R²"="0,71029" 40" 45" 50" 55" 60" 65" 70" 75" 80" 85" 90" 100# 95# 90# 85# 80# 75# 70# 65# 60# 55# 50# 40# 45# 50# 55# 60# 65# 70# 75# 80# 85# 90# MAP (mm Hg) 4 patients
Abnormal peripheral perfusion effect of a stepwise increasing dose of NTG T baseline T max T end Capillary refill time, sec 9 [8-12] 4 * [4-6] 7* [4-10] Perfusion index, % 0.7 [0.4-1.8] 2.7 * [2.1-3.0] 1.6 * [1.1-2.0] Tskin-difference, 0 C 3 [2.1-3.4] 0.8 * [-1.1-1.4] 1.4 * [0.8-2.0] StO2 (%) 77 [64-82] 85 * [74-92] 83 [73-88] Values are expressed as median [25th-75th] * P<0.05 vs. TBL1 and TBL2
Abnormal peripheral perfusion effect of a stepwise increasing dose of NTG Percent changes of StO2 during NTG infusion plotted against StO2 values at baseline before NTG infusion. The magnitude of changes in StO2 is more accentuated for lower StO2 values.
Conclusions The target blood pressure for the majority of patients should probably be higher than 60 mmhg and lower than 75 mmhg Improving tissue perfusion is the ultimate goal of manipulating perfusion pressure large inter-individual differences the worst microcirculations seem to benefit most increasing MAP may improve tissue perfusion decreasing MAP may improve tissue perfusion Setting the ultimate optimal MAP should be individualized by means of tissue perfusion and the target probably changes over time