Mean Arterial Pressure - intensivecare.me · Christian Richard Jean-Louis Teboul ... J.-F. Georger...

Mean Arterial PressureLow could be good

Prof. Jan Bakker MD, PhD

Chair dept Intensive Care Adults

[email protected]

www.intensivecare.me

Thursday, March 22, 12

mailto:[email protected]

mailto:[email protected]

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 pressureHow much is enough?

Dünser et al. Intensive Care med 2009;35:1225-1233Dünser et al. Crit Care 2009;13:R181Bourgoin et al. Crit Care Med 2005;33:780-786Redfors et al. Intensive Care Med 2011;37:60-67LeDoux et al. Crit Care Med 2000;28:2729-2732Thooft 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-Francois GeorgerOlfa HamzaouiAnis ChaariJulien MaizelChristian RichardJean-Louis Teboul

Restoring arterial pressurewith norepinephrine improves muscle tissueoxygenation assessed by near-infraredspectroscopy in severely hypotensive septicpatients

Received: 18 January 2010Accepted: 19 July 2010Published online: 6 August 2010! Copyright jointly held by Springer andESICM 2010

Jean-Louis Teboul is a member of themedical advisory board of Pulsion.

Electronic supplementary materialThe online version of this article(doi:10.1007/s00134-010-2013-3) containssupplementary material, which is availableto authorized users.

J.-F. Georger ! O. Hamzaoui ! A. Chaari !J. Maizel ! C. Richard ! J.-L. Teboul ())Service de reanimation medicale,Centre Hospitalo-Universitaire de Bicetre,Assistance Publique-Hopitaux de Paris,EA 4046, Universite Paris Sud,78, rue du General Leclerc,94 270 Le Kremlin-Bicetre, Francee-mail: [email protected].: ?33-1-45213547Fax: ?33-1-45213551

Abstract Purpose: To examinethe consequences of administration ofnorepinephrine on muscle tissueoxygenation in severely hypotensiveseptic shock patients. Meth-ods: This was a prospectiveobservational study conducted in amedical intensive care unit of a uni-versity hospital. We included 28septic shock patients that receivedearly volume resuscitation. All wereeligible for receiving norepinephrinebecause of life-threatening hypoten-sion and low diastolic arterialpressure. Muscle tissue oxygen satu-ration (StO2) and its changes during avascular occlusion test were mea-sured at the level of the thenareminence using a near-infrared spec-troscopy (NIRS) device.Transpulmonary thermodilution car-diac index (CI) and NIRS-derivedvariables were obtained before andafter the mean arterial pressure(MAP) was increased by norepi-nephrine. The baseline StO2 and thevascular occlusion test-derived vari-ables of 17 healthy volunteers were

measured and served as controls.Results: In healthy volunteers, StO2

ranged between 75 and 90% and StO2

recovery slopes ranged between 1.5and 3.4%/s. Administration of nor-epinephrine, which was associatedwith an increase in MAP from 54 ± 8to 77 ± 9 mmHg (p\ 0.05), alsoinduced increases in CI from3.14 ± 1.03 to 3.61 ± 1.28 L/min/m2 (p\ 0.05), in StO2 from 75 ± 9to 78 ± 9% (p\ 0.05) and in StO2

recovery slope from 1.0 ± 0.6 to1.5 ± 0.7%/s (p\ 0.05). Conclu-sions: Norepinephrine administra-tion aimed at achieving a MAP higherthan 65 mmHg in septic shockpatients with life-threatening hypo-tension resulted in improvement ofNIRS variables measured at the levelof the thenar eminence.

Keywords Muscle tissue oxygensaturation ! Norepinephrine !Septic shock ! Microcirculation !Near-infrared spectroscopy

Introduction

Septic shock is characterised by disturbances of macro-and microcirculation [1–3]. The impairment of microcir-culation is characterised by a decrease in the capillarydensity [4, 5] and in the blood flow in the remainingmicrovessels [6]. Endothelial dysfunction is implicated inthe alteration of microcirculatory perfusion [7]. Bedside

performance of a vascular occlusion test (VOT) allowsevaluation of the response of the microvascular bloodflow to a local hypoxic stimulus created by a transientischaemia of the occluded vascular bed. As soon as theupstream artery occlusion is released microvascular bloodflow markedly increases to compensate for the transientoxygen deficit created by the ischaemic stimulus. Vaso-dilation of arterioles and recruitment of closed capillaries

Intensive Care Med (2010) 36:1882–1889DOI 10.1007/s00134-010-2013-3 ORIGINAL

Jean-Francois GeorgerOlfa HamzaouiAnis ChaariJulien MaizelChristian RichardJean-Louis Teboul

Restoring arterial pressurewith norepinephrine improves muscle tissueoxygenation assessed by near-infraredspectroscopy in severely hypotensive septicpatients

Received: 18 January 2010Accepted: 19 July 2010Published online: 6 August 2010! Copyright jointly held by Springer andESICM 2010

Jean-Louis Teboul is a member of themedical advisory board of Pulsion.

Electronic supplementary materialThe online version of this article(doi:10.1007/s00134-010-2013-3) containssupplementary material, which is availableto authorized users.

J.-F. Georger ! O. Hamzaoui ! A. Chaari !J. Maizel ! C. Richard ! J.-L. Teboul ())Service de reanimation medicale,Centre Hospitalo-Universitaire de Bicetre,Assistance Publique-Hopitaux de Paris,EA 4046, Universite Paris Sud,78, rue du General Leclerc,94 270 Le Kremlin-Bicetre, Francee-mail: [email protected].: ?33-1-45213547Fax: ?33-1-45213551

Abstract Purpose: To examinethe consequences of administration ofnorepinephrine on muscle tissueoxygenation in severely hypotensiveseptic shock patients. Meth-ods: This was a prospectiveobservational study conducted in amedical intensive care unit of a uni-versity hospital. We included 28septic shock patients that receivedearly volume resuscitation. All wereeligible for receiving norepinephrinebecause of life-threatening hypoten-sion and low diastolic arterialpressure. Muscle tissue oxygen satu-ration (StO2) and its changes during avascular occlusion test were mea-sured at the level of the thenareminence using a near-infrared spec-troscopy (NIRS) device.Transpulmonary thermodilution car-diac index (CI) and NIRS-derivedvariables were obtained before andafter the mean arterial pressure(MAP) was increased by norepi-nephrine. The baseline StO2 and thevascular occlusion test-derived vari-ables of 17 healthy volunteers were

measured and served as controls.Results: In healthy volunteers, StO2

ranged between 75 and 90% and StO2

recovery slopes ranged between 1.5and 3.4%/s. Administration of nor-epinephrine, which was associatedwith an increase in MAP from 54 ± 8to 77 ± 9 mmHg (p\ 0.05), alsoinduced increases in CI from3.14 ± 1.03 to 3.61 ± 1.28 L/min/m2 (p\ 0.05), in StO2 from 75 ± 9to 78 ± 9% (p\ 0.05) and in StO2

recovery slope from 1.0 ± 0.6 to1.5 ± 0.7%/s (p\ 0.05). Conclu-sions: Norepinephrine administra-tion aimed at achieving a MAP higherthan 65 mmHg in septic shockpatients with life-threatening hypo-tension resulted in improvement ofNIRS variables measured at the levelof the thenar eminence.

Keywords Muscle tissue oxygensaturation ! Norepinephrine !Septic shock ! Microcirculation !Near-infrared spectroscopy

Introduction

Septic shock is characterised by disturbances of macro-and microcirculation [1–3]. The impairment of microcir-culation is characterised by a decrease in the capillarydensity [4, 5] and in the blood flow in the remainingmicrovessels [6]. Endothelial dysfunction is implicated inthe alteration of microcirculatory perfusion [7]. Bedside

performance of a vascular occlusion test (VOT) allowsevaluation of the response of the microvascular bloodflow to a local hypoxic stimulus created by a transientischaemia of the occluded vascular bed. As soon as theupstream artery occlusion is released microvascular bloodflow markedly increases to compensate for the transientoxygen deficit created by the ischaemic stimulus. Vaso-dilation of arterioles and recruitment of closed capillaries

Intensive Care Med (2010) 36:1882–1889DOI 10.1007/s00134-010-2013-3 ORIGINAL

No difference in terms of baseline values of MAP,lactate plasma concentration, ScvO2, CI and SOFA scorewas found between the subgroup of 14 patients in whomthe StO2 recovery slope increased by more than 38% and

the subgroup of 14 patients in whom the StO2 increasedby less than 38%.

Discussion

The main finding of our study was that administration ofnorepinephrine aimed at achieving a MAP of at least65 mmHg during septic shock with life-threatening

Table 2 Macrocirculatory variables (mean ± SD) in septic shockpatients

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 ± 28Temperature (!C) 37.5 ± 1.4 37.5 ± 1.3CI (L/min/m2) 3.1 ± 1.0 3.6 ± 1.3*GEDVI (mL/m2) 687 ± 117 730 ± 156*EVLWI (mL/kg) 13 ± 9 13 ± 7SaO2 (%) 94 ± 5 93 ± 4PaO2 (mmHg) 122 ± 73 115 ± 63PaCO2 (mmHg) 40 ± 16 40 ± 15pH 7.34 ± 0.10 7.33 ± 0.10ScvO2 (%) 68 ± 9 72 ± 7*

SAP systolic arterial pressure, DAP diastolic arterial pressure, MAPmean arterial pressure, CI cardiac index, GEDVI global end-dia-stolic volume index, EVLWI extravascular lung water index, SaO2arterial oxygen saturation, PaO2 partial pressure of oxygen inarterial blood, PaCO2 partial pressure of carbon dioxide in arterialblood, ScvO2 central venous oxygen saturation* p\ 0.05 versus before either introduction or increase ofnorepinephrine

Table 3 Microcirculatory variables in healthy volunteers (n = 17)

Variables Values (mean ± SD)

StO2 (%) 82 ± 4Occlusion time (s) 207 ± 40StO2 desaturation slope (%/min) 13.2 ± 3.0StO2 recovery slope (%/s) 2.3 ± 0.5StO2 max (%) 93 ± 3DStO2 (%) 11 ± 4

StO2 thenar eminence tissue oxygen saturation

Table 4 Microcirculatory variables (mean ± SD) in septic shockpatients



StO2 (%) 75 ± 9 78 ± 9*Occlusion time (s) 263 ± 104 274 ± 170StO2 desaturationslope (%/min)

9.5 ± 4.4 10.1 ± 4.6

StO2 recoveryslope (%/s)

1.0 ± 0.6 1.5 ± 0.7*

StO2 max (%) 81 ± 10 86 ± 8*DStO2 (%) 8 ± 4 10 ± 5*

StO2 thenar eminence tissue oxygen saturation* p\ 0.05 versus before introduction/increase of norepinephrine

StO2

beforenorepinephrine

(introduction/increase)

afternorepinephrine


95

90

85

80

75

70

65

60

55

%

p<0.05

introduction ofnorepinephrine

increase in the dose of norepinephrine

Fig. 1 Individual values of the muscle tissue oxygen saturation(StO2) before and during administration of norepinephrine in septicpatients. The eight patients who had already received norepineph-rine are represented by dotted lines. The grey cross-hatched zonerepresents the range of values of the StO2 measured in our group ofhealthy volunteers

StO2 recovery slope3.5

3.0

2.5

2.0

1.5

1.0

0.5

0.0

%/s

ec

p<0.05





afternorepinephrine


Fig. 2 Individual values of the StO2 recovery slope before andduring administration of norepinephrine in septic patients. Theeight patients who had already received norepinephrine arerepresented by dotted lines. The grey cross-hatched zone representsthe range of values of the StO2 recovery slope measured in ourgroup of healthy volunteers

1885

No difference in terms of baseline values of MAP,lactate plasma concentration, ScvO2, CI and SOFA scorewas found between the subgroup of 14 patients in whomthe StO2 recovery slope increased by more than 38% and

the subgroup of 14 patients in whom the StO2 increasedby less than 38%.

Discussion

The main finding of our study was that administration ofnorepinephrine aimed at achieving a MAP of at least65 mmHg during septic shock with life-threatening

Table 2 Macrocirculatory variables (mean ± SD) in septic shockpatients



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 ± 28Temperature (!C) 37.5 ± 1.4 37.5 ± 1.3CI (L/min/m2) 3.1 ± 1.0 3.6 ± 1.3*GEDVI (mL/m2) 687 ± 117 730 ± 156*EVLWI (mL/kg) 13 ± 9 13 ± 7SaO2 (%) 94 ± 5 93 ± 4PaO2 (mmHg) 122 ± 73 115 ± 63PaCO2 (mmHg) 40 ± 16 40 ± 15pH 7.34 ± 0.10 7.33 ± 0.10ScvO2 (%) 68 ± 9 72 ± 7*

SAP systolic arterial pressure, DAP diastolic arterial pressure, MAPmean arterial pressure, CI cardiac index, GEDVI global end-dia-stolic volume index, EVLWI extravascular lung water index, SaO2arterial oxygen saturation, PaO2 partial pressure of oxygen inarterial blood, PaCO2 partial pressure of carbon dioxide in arterialblood, ScvO2 central venous oxygen saturation* p\ 0.05 versus before either introduction or increase ofnorepinephrine

Table 3 Microcirculatory variables in healthy volunteers (n = 17)

Variables Values (mean ± SD)

StO2 (%) 82 ± 4Occlusion time (s) 207 ± 40StO2 desaturation slope (%/min) 13.2 ± 3.0StO2 recovery slope (%/s) 2.3 ± 0.5StO2 max (%) 93 ± 3DStO2 (%) 11 ± 4

StO2 thenar eminence tissue oxygen saturation

Table 4 Microcirculatory variables (mean ± SD) in septic shockpatients



StO2 (%) 75 ± 9 78 ± 9*Occlusion time (s) 263 ± 104 274 ± 170StO2 desaturationslope (%/min)

9.5 ± 4.4 10.1 ± 4.6

StO2 recoveryslope (%/s)

1.0 ± 0.6 1.5 ± 0.7*

StO2 max (%) 81 ± 10 86 ± 8*DStO2 (%) 8 ± 4 10 ± 5*

StO2 thenar eminence tissue oxygen saturation* p\ 0.05 versus before introduction/increase of norepinephrine

StO2



afternorepinephrine


95

90

85

80

75

70

65

60

55

%

p<0.05



Fig. 1 Individual values of the muscle tissue oxygen saturation(StO2) before and during administration of norepinephrine in septicpatients. The eight patients who had already received norepineph-rine are represented by dotted lines. The grey cross-hatched zonerepresents the range of values of the StO2 measured in our group ofhealthy volunteers

StO2 recovery slope3.5

3.0

2.5

2.0

1.5

1.0

0.5

0.0

%/s

ec

p<0.05





afternorepinephrine


Fig. 2 Individual values of the StO2 recovery slope before andduring administration of norepinephrine in septic patients. Theeight patients who had already received norepinephrine arerepresented by dotted lines. The grey cross-hatched zone representsthe range of values of the StO2 recovery slope measured in ourgroup of healthy volunteers

1885


Effects of changes in arterial pressure on organ perfusion during septic shockThooft 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 flowDubin et al. Crit Care 2009;13:R92

Critical Care Vol 13 No 3 Dubin et al.

Page 6 of 8(page number not for citation purposes)

vascular flow and tissue partial pressure of oxygen (PO2) with-out significant changes in sublingual microcirculation [18].They also showed, however, that when MAP was augmentedfrom 70 to 90 mmHg, the MFI, proportion of perfused vessels,and perfused vessel density fell by about 10%. The remarkablesimilarity between the study by Jhanji and colleagues [18] andthe current study emphasizes the reproducibility of the tech-niques and results.

In addition, our results expand previous knowledge byaddressing the variation of interindividual responses. In partic-ular, the change in the perfused capillary density was stronglydependent on the basal state of microcirculation. In this way,perfused capillary density improved in patients with an alteredsublingual perfusion at baseline, and decreased in patients

with preserved basal microvascular perfusion. Sakr and col-leagues described a similar microvascular response to redblood cell transfusion [30]. Other studies have also shown thatvasopressors could decrease sublingual microcirculation[31,32], suggesting that excessive vasoconstriction might bedeleterious to microcirculation.

Our study has several limitations. First, this observational studylacks a control group. Each patient, therefore, served as his/her own control. Second, the number of patients included inthis study was small. Despite the sample size, significant

Figure 3

Individual behavior of sublingual percentage of perfused capillariesIndividual behavior of sublingual percentage of perfused capillaries. Results are shown as the mean arterial pressure was increased from 65 mmHg to 85 mmHg with norepinephrine.

Figure 4

Individual behavior of sublingual perfused capillary densityIndividual behavior of sublingual perfused capillary density. Results are shown as the mean arterial pressure was increased from 65 mmHg to 85 mmHg with norepinephrine.

Figure 5

Individual behaviour of sublingual capillary heterogeneity flow indexIndividual behaviour of sublingual capillary heterogeneity flow index. Results are shown as the mean arterial pressure was increased from 65 mmHg to 85 mmHg with norepinephrine.

Figure 6

Relationship between the changes of perfused capillary density, when mean arterial pressure (MAP) was increased from the baseline to a MAP of 85 mmHg, with the basal perfused capillary density at a MAP of 65 mmHgRelationship between the changes of perfused capillary density, when mean arterial pressure (MAP) was increased from the baseline to a MAP of 85 mmHg, with the basal perfused capillary density at a MAP of 65 mmHg.

Critical Care Vol 13 No 3 Dubin et al.

Page 6 of 8(page number not for citation purposes)

vascular flow and tissue partial pressure of oxygen (PO2) with-out significant changes in sublingual microcirculation [18].They also showed, however, that when MAP was augmentedfrom 70 to 90 mmHg, the MFI, proportion of perfused vessels,and perfused vessel density fell by about 10%. The remarkablesimilarity between the study by Jhanji and colleagues [18] andthe current study emphasizes the reproducibility of the tech-niques and results.

In addition, our results expand previous knowledge byaddressing the variation of interindividual responses. In partic-ular, the change in the perfused capillary density was stronglydependent on the basal state of microcirculation. In this way,perfused capillary density improved in patients with an alteredsublingual perfusion at baseline, and decreased in patients

with preserved basal microvascular perfusion. Sakr and col-leagues described a similar microvascular response to redblood cell transfusion [30]. Other studies have also shown thatvasopressors could decrease sublingual microcirculation[31,32], suggesting that excessive vasoconstriction might bedeleterious to microcirculation.

Our study has several limitations. First, this observational studylacks a control group. Each patient, therefore, served as his/her own control. Second, the number of patients included inthis study was small. Despite the sample size, significant

Figure 3

Individual behavior of sublingual percentage of perfused capillariesIndividual behavior of sublingual percentage of perfused capillaries. Results are shown as the mean arterial pressure was increased from 65 mmHg to 85 mmHg with norepinephrine.

Figure 4

Individual behavior of sublingual perfused capillary densityIndividual behavior of sublingual perfused capillary density. Results are shown as the mean arterial pressure was increased from 65 mmHg to 85 mmHg with norepinephrine.

Figure 5

Individual behaviour of sublingual capillary heterogeneity flow indexIndividual behaviour of sublingual capillary heterogeneity flow index. Results are shown as the mean arterial pressure was increased from 65 mmHg to 85 mmHg with norepinephrine.

Figure 6

Relationship between the changes of perfused capillary density, when mean arterial pressure (MAP) was increased from the baseline to a MAP of 85 mmHg, with the basal perfused capillary density at a MAP of 65 mmHgRelationship between the changes of perfused capillary density, when mean arterial pressure (MAP) was increased from the baseline to a MAP of 85 mmHg, with the basal perfused capillary density at a MAP of 65 mmHg.


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


Endotoxin shock in the primate: Treatment with PhenoxybenzamineJA Vick. J Clin Invest 1964;43(2):279-284

monkeys

There is a growing interest in the treatment of endotoxin shock with vasodilating agents.

•Lethal injection of purified Escherichia coli endotoxin (7.5 mg per kg)

•Non-fluid resuscitated model

ENDOTOXIN SHOCK IN THE PRIMATE: TREATMENT WITH PHENOXYBENZAMINE

BLOOD PRESSUREmmHg

i 5o10050v

RE SP.MIN.

40- 20~zo

10.0URINE OUTPUTCC/HOUR

HCTPERCENT

BLOODpH

5.0

5040f2^

7. 5 57.507.457.407. 3 5

|I B4-PBZI -x-_x-=I, - ~- _ilk _ _

# w - %

ll

4r

Endot7.Smi

ControlIIPrz Endotoxin i

KEY

Control%/s survivorsat 24 hours

DBZ3/3 survivorsat Z4 4 72 hours

0, *.---IJ< rb~~~~~~~~~

XtX _ Y _ w~~~~

&R fa.I~~~~~~~~~~ . . .

fl%%;/kg %X_~

I 2 3 4 5 6 7 8 9HOURS POST ENDOTOXIN

FIG. 1. ENDOTOXIN SHOCK IN THE MONKEY. A comparison of mean changes in arterialblood pressure, respiratory rate, urine output, hematocrit, and arterial blood pH observed inthree control and three phenoxybenzamine (DBZ)-treated monkeys after a lethal injection ofendotoxin.

TABLE IIIControl endotoxin group*

Time BP RPF GFR UO EPAIT

hr mm Hg m/kg/min ml/kg/min mil/min

Control1 115 (105-120) 16.9 (11.5 -17.8) 3.35 (2.41-4.62) 0.25 (0.19 -0.29) 0.84 (0.69-0.91)2 120 (110-125) 18.2 (13.6 -20.0) 3.20 (2.22-4.28) 0.19 (0.10 -0.21) 0.76 (0.68-0.84)3 115 (100-125) 17.1 (12.8 -21.2) 3.25 (2.62-4.91) 0.21 (0.15 -0.26) 0.79 (0.62-0.85)4 112 (105-125) 17.0 (11.6 -20.8) 3.22 (2.12-5.01) 0.22 (0.11 -0.25) 0.80 (0.70-0.91)

After endotoxin, 7.5 mg/g1 90 ( 60-100) 5.9 (1.8- 7.5) 1.85 (0.62-2.10) 0.08 (0.01 -0.12) 0.56 (0.28-0.68)2 60 ( 40- 85) 3.9 ( 0.8 - 6.6) 1.15 (0.50-2.05) 0.09 (0.04 -0.11) 0.52 (0.26-0.64)3 65 ( 45- 80) 4.8 ( 0.6 - 6.1) 1.10 (0.40-2.20) 0.18 (0.04 -0.22) 0.16 (0.08-0.51)4 75 ( 40- 85) 0.3 ( 0.1 - 2.5) 0.08 (0.02-0.95) 0.10 (0.08 -0.14) 0.16 (0.06-0.48)5 50 ( 30- 65) 0.25 ( 0.1 - 1.8) 0.09 (0.01-0.65) 0.03 (0.01 -0.08) 0.14 (0.09-0.46)6 45 ( 20- 60) 0.20 ( 0.05- 1.1) 0.01 (0.00-0.85) 0.01 (0.005-0.04) 0.12 (0.05-0.34)

Average survival time, 10.8 hrs

* Six animals. Mean values and ranges (in parentheses) given. BP = blood pressure, RPF = renal plasma flow,GFR = glomerular filtration rate, UO = urine output, EPAH = extraction ratio of para-aminohippurate.

I-

L

I-

I

L

iI-

L1r

L-

x

f1%9i

I.X

281

K--.X0 X-iox-l- -*-.lo

I

a


100

80

60

40

20

arterial microcirculation venous

arteriolar constriction

arteriolar vasodilation


100

80

60

40

20


venous constrictionincreased venous pressures


A

hypotension


100

80

60

40

20


decreased venous pressures


B

venous constrictionincreased venous pressuresA


normal


The effects of intravenous nitroglycerine and norepinephrine on gastric microvascular perfusion in an experimental model of gastric tube reconstructionvan Bommel et al. Surgery 2010;148:71-77

parameters on gastric tube perfusion. The impor-tance of venous congestion has been proposedpreviously5-7; now we have clearly demonstratedthat this mechanism is independent from cardiacoutput and arterial blood pressure.

However, systemic hemodynamic parameterswere not completely similar in both groups. First,central venous and PCWPs were lower in the NTGgroup. In a previous study we found that the use of afixed NTG dosage (1 mcg/kg/min) does not haveany effect on gastric tube MBF.16 Therefore we con-cluded that it would be preferable to titrate the infu-sion of NTG on a determinant of venous outflow.Because we needed a parameter that is often andeasily used in clinical practice as well, we chose cen-tral venous pressure. According to our hypothesis, alower systemic venous pressure should facilitate ve-nous drainage of the gastric tube, thereby increas-ing gastric tissue blood flow. Second, the higherSvO2values at baseline indicated that the ratio be-tween systemic oxygen delivery and uptake was in-creased in the NTG group. Because arterialoxygen content was similar in both groups and car-diac output showed a trend towards higher values,we conclude that administration of NTG caused amore dynamic circulation. Apparently, this was

accompanied by an increased tissue bloodflow; it re-mains speculative whether this was caused by the in-crease in cardiac output or vice versa.

Although the effect of NTG is immediatelyvisible in the higher MBF baseline values, thesurgical procedure decreased MBF in the corpusand fundus to comparable low levels. Subse-quently, recovery occurred in the NTG groupover time; throughout the experimental protocolfundus and corpus MBF values were significantlyhigher than in the control group (Figs 1 and 3).This is supported by the mHbcon data: increasedin both groups following operation but signifi-cantly lower corpus and fundus values in theNTG group during the actual experiment (Figs 2and 4). In retrospect, we could have shown this ef-fect even better with a longer stabilization intervalbefore the postoperative measurements and addi-tion of a second baseline measurement beforethe start of the experimental protocol.

Nitroglycerine is a nitric oxide (NO)-donatingcompound; in the vascular endothelium NO func-tions as a regulator of vascular tone, and thereby ofmicrovascular perfusion. NO plays an importantrole in the autoregulation of gastric mucosal bloodflow, and it is likely thatNOplays a role in protecting

Fig 2. Microvascular hemoglobin concentration (mHbcon) measurements on gastric pylorus, corpus and fundus atbaseline (BL) and immediately following operation (S). Data represent mean ± SEM; bP < .05 vs BL.

Fig 3. Microvascular blood flow (MBF) measurements on gastric pylorus, corpus and fundus at increasing MAP levels.Data represent mean ± SEM. #P < .05 vs CTRL, bP < .05 vs baseline, ^P < .05 vs MAP 50, $P < .05 vs MAP 60.

ARTICLE IN PRESSSurgeryVolume j, Number j

Van Bommel et al 5

0

2

4

6

8

10

12

BL S 50 60 70 80 90 100 110

CV

P m

m H

g

CTRLNTG

* * * * * * * * *


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

METHODSAnimal Preparation

Nine female pigs (Yorkshire, Landrace of Durok) witha mean weight of 30.6 ! 0.6 kg (mean ! sd) wereincluded in this study. The study was approved bythe institutional animal investigation committee, and thecare and handling of the animals were in accordancewith the European Community guidelines. All ani-mals received premedication with azaperone (2.5mg/kg IM). Anesthesia was induced with ketaminehydrochloride (30 mg/kg IM) and midazolam (1mg/kg IM). All animals were intubated through acervical midline tracheostomy and ventilated in avolume-controlled mode (Servo 300, Siemens-Elema,Solna, Sweden). Neuromuscular blockade was in-duced with pancuronium bromide (0.13 mg/kg, IV),and anesthesia was maintained with a continuousinfusion of fentanyl (20 !g ! kg"1 ! h"1), midazolam(0.3 mg ! kg"1 ! h"1), and pancuronium bromide (0.3mg ! kg"1 ! h"1). As maintenance fluid, crystalloid so-lution was administered at a rate of 10 mL ! kg"1 ! h"1.After surgery, hypovolemia was excluded with a fluidchallenge consisting of 150 mL of crystalloid solution.When cardiac output (CO) increased by 15%, theanimal was considered hypovolemic, and fluid chal-lenges were repeated until CO did not increasefurther. The left carotid artery was cannulated forcontinuous arterial blood pressure monitoring and toobtain blood gas analyses. A pulmonary artery cath-eter (Edwards, Irvine, CA) was inserted through theright jugular vein for measurements of central venous,pulmonary artery, and pulmonary artery occlusionpressures. In addition, the CO was calculated using aVigilance CO computer (Edwards). At the end of theexperiment, the animals were killed with a bolus ofpotassium chloride.

Surgical ProcedureAfter induction of anesthesia, the gastric tube was

reconstructed as described by Schroder et al.9 In brief,after median laparotomy, the stomach was mobilizedalong the smaller and greater curvature. This included

ligation of the 1 or 2 short gastric arteries, the gastricarteries, and the left gastroepiploic artery. The rightgastroepiploic artery along the greater curvature wascarefully preserved. After opening of the hiatus, theesophagus was dissected and transected at the gastro-esophageal junction. Finally, a 3-cm-wide gastric tubewas formed by dissection of the lesser curvature andthe gastroesophageal junction with a linear stapler(Proximate 55 mm TLC linear cutter, Ethicon, Johnson& Johnson, The Netherlands). In this way, the perfu-sion of the gastric tube was completely dependent onthe right gastroepiploic artery, comparable with theclinical setting.

An important difference with human anatomy isthe left dominancy of the gastroepiploic artery.9 Liga-tion of the left gastroepiploic artery and short gastricarteries results in profound ischemia of the gastricfundus, limiting the length of the gastric tube. For thisreason, it is impossible to perform a transthoracicgastric pull-up to restore continuity in the neck, andmeasurements were performed with the gastric tubein the abdomen. The gastric tube was carefully posi-tioned on top of the abdominal content and covered toprevent evaporation and cooling.

Experimental ProceduresAfter construction of the gastric tube, baseline

values of blood flow (LSI) and temperature (video-thermography) were obtained from 4 positions on theserosal side of the gastric tube: the top (Fig. 1; locationA), the virtual anastomotic site (Fig. 1; location B), themedial part (Fig. 1; location C), and the base of thegastric tube (Fig. 1; location D). A small suture wasplaced centrally in each region of interest to assure thateach measurement was taken from exactly the sameplace. These landmarks correspond with the letters inFigures 1 and 3. Depending on baseline arterial bloodpressure, the norepinephrine dose was adjusted to attaina mean arterial blood pressure (MAP) of 50 mm Hg.When baseline MAP was higher than the desired values,additional propofol was titrated to decrease MAP. Sub-sequently, norepinephrine was administered to attain a

Figure 1. Laser speckle images and video images of the distal part of the gastric tube (upper panel) and base (lower panel)for different values of mean arterial blood pressure (MAP) in a representative pig (#4). Laser speckle images are shown in acolor-coded fashion. The colors are related to flow values (in arbitrary units) according to the color bar at the right. A # top;B # anastomosis; C # medial; D # base.

542 Effect of Perfusion Pressure on Gastric Tube Blood Flow ANESTHESIA & ANALGESIA

MAP of 60, 70, 80, 90, 100, and 110 mm Hg. After eachstep of increase in MAP, a 15-min stabilization periodwas included before both LSI and thermography mea-surements were performed. The total duration of a singleexperiment was 6–7 h.

Laser Speckle and Thermographic Imaging and AnalysisLSI was performed with a full-field laser perfusion

imager (Moor Instruments, Axminster, UK), whichwas mounted perpendicular to the gastric tube, at adistance of 30 cm. Scans were captured with a samplingfrequency of 25 Hz. The device uses a Class 1 near-infrared laser source with a wavelength of 785 ! 10 nm.The charge-coupled device camera incorporates abandpass filter, which attenuates other wavelengths.The raw speckle images are used to compute thespeckle-contrast image. The software calculates thespeckle contrast k for any given square of 5 " 5 pixelsand assigns this value to the central pixel of thesquare. This process is then repeated across the imageof 576 " 768 pixels to obtain the contrast map. Foreach pixel in the speckle contrast map, the relativevelocity of blood flow is obtained.

The temperature of the gastric tube tissue wasregistered with a computer-assisted infrared thermo-graph (ThermaCAM SC2000, Flir Systems, Danderyd,Sweden). The thermal sensitivity is 0.05°C at 30°C, thespectral range 7.5–13 mm, and the built-in digitalvideo 320 " 240 pixels (total 76,800 pixels). Data wereobtained through a high-speed (50-Hz) analysis andrecording system coupled with a desktop personalcomputer (ThermaCAM Researcher 2001 HS). Ther-mograms were stored on a hard disk (14-bit resolu-tion) awaiting further analysis. With an interval of#40°C until 120°C, this results in a resolution of 9.8 "10#3°C per bit, which fits well in the range of the thermalsensitivity. The thermograph camera produces a matrixof temperature values. These temperature values eachrepresent a pixel in the image measured. The distancebetween the objective and the gastric tube being mea-sured was adjusted to 68 cm. Thereby, the resolution onthe gastric tube was 0.8 " 0.8 mm2.

StatisticsValues are reported as median and interquartile

ranges. Each variable was analyzed using analysis ofrepeated measurements. When appropriate, post hocanalyses were performed using the Dunn multiplecomparison test. Comparison of LSI blood flow valuesand thermographic temperature values was done bylinear regression analysis and Pearson correlation anal-ysis. P $ 0.05 was considered statistically significant. Allanalyses were performed using GraphPad Prism (ver-sion 5.0, GraphPad Software, San Diego, CA).

RESULTSDuring the stepwise increase of MAP, all other

global hemodynamic values remained constantthroughout the experiment. Systemic hemodynamicdata and norepinephrine dosages after surgery and foreach step of MAP are shown in Table 1. The volume offluids administered was 2170 mL (1830–2177 mL)

Figure 2. Blood flow for different locations on the gastric tubefor different values of mean arterial blood pressure measuredwith laser speckle imaging. Boxes show median [interquartilerange] and bars 5%–95%. †P $ 0.01 compared with top; *P $0.001 compared with top. NS % nonsignificant.

Table 1. Hemodynamic Data

BL 50 mm Hg 60 mm Hg 70 mm Hg 80 mm Hg 90 mm Hg 100 mm Hg 110 mm Hg

MAP(mm Hg)

80 (69–91) 51 (49–52) 61 (59–63) 71 (70–72) 81 (79–82) 90 (88–90) 100 (100–101) 110 (109–111)

HR (bpm) 120 (99–151) 125 (86–163) 117 (84–156) 126 (98–156) 117 (109–139) 100 (82–117) 106 (77–129) 114 (86–137)CVP

(mm Hg)9 (7–10) 8 (7–9) 10 (9–11) 9 (8–10) 9 (8–10) 10 (9–11) 10 (9–11) 10 (9–10)

PCWP(mm Hg)

10 (9–10) 9 (8–10) 10 (9–11) 10 (10–11) 10 (10–11) 11 (9–12) 10 (10–12) 10 (10–11)

CO (L/min) 4.1 (3.7–4.6) 3.8 (3.2–4.8) 3.8 (3.1–4.6) 3.3 (3.3–4.8) 3.9 (3.4–4.4) 4.0 (3.4–4.8) 3.8 (3.1–5.1) 3.9 (3.2–4.9)SvO2 (%) 78 (70–91) 78 (63–89) 72 (61–92) 77 (66–91) 77 (67–92) 75 (64–87) 73 (65–91) 78 (59–93)NE (!g ! kg#1 !

min#1)— — — — 0.1 (0–0.1) 0.2 (0.1–0.2) 0.4 (0.4–0.5) 0.5 (0.5–0.6)

Values are represented as median and interquartile ranges.BL % baseline after surgery; MAP % mean arterial blood pressure; HR % heart rate; CVP % central venous pressure; PCWP % pulmonary capillary wedge pressure; CO % cardiac output;SvO2 % venous oxygen saturation; NE % norepinephrine.

Vol. 110, No. 2, February 2010 © 2010 International Anesthesia Research Society 543


Admission Evolution during first 24h ICU mortality

StO2 n=221

StO2 n=221

StO2 n=221

StO2 n=221

Normal(>75%) n=166

Normaln=160

15%Normal(>75%) n=166 Abnormal

n=2157%

Abnormal(<75%) n=39

Normaln=15 13%Abnormal

(<75%) n=39 Abnormaln=25

56%

Dynamics of StO2mortality

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)

• march-september 2011 § 221 consecutive patients enrolled expected LOS: 2 days

• complete initial resuscitation and stabilization § follow up to Day 28


Abnormal peripheral perfusioneffect 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 ToC >2 (or PFI<1,4),



cold extremities/delayed CRT (>5s) § forearm – finger ToC >2 § PFI<1.4



Tbaseline TMax Tend

Heart rate, bpm95

[90-103]

97

[91-100]

98

[89-106]

Mean arterial pressure, mmHg71

[70-80]

62*

[57-69]

71

[70-76]

Values are expressed as median [25th-75th] § * P<0.05 vs. TBL1 and TBL2

Global hemodynamic variables during execution of the study protocol (n = 13). Time points are defined as before

nitroglycerine infusion (Tbaseline), at the maximum dose of nitroglycerine (TMax) and 30 min after cessation of

nitroglycerine (TBend)


Effect of NTG on StO2

50#

55#

60#

65#

70#

75#

80#

85#

90#

95#

100#

40# 45# 50# 55# 60# 65# 70# 75# 80# 85# 90#

MAP (mm Hg)

StO

2 (%

)

y"="$0,6667x"+"119,06"R²"="0,71029"

50"

55"

60"

65"

70"

75"

80"

85"

90"

95"

100"

40" 45" 50" 55" 60" 65" 70" 75" 80" 85" 90"

4 patients



Values are expressed as median [25th-75th] § * P<0.05 vs. TBL1 and TBL2

Tbaseline Tmax Tend

Capillary refill time, sec9

[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, 0C3

[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]



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


Mean Arterial Pressure - intensivecare.me · Christian Richard Jean-Louis Teboul ... J.-F. Georger...

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