Christian RICHARDChristian RICHARD

Bicêtre HospitalBicêtre Hospital

AP- HPAP- HP

PARIS XI UniversityPARIS XI University

FRANCEFRANCE

Which shocked patients should be monitored with a pulmonary artery catheter

and does it impact their outcomes?

« « Pulmonary artery catheter is not just Pulmonary artery catheter is not just important for the speciality of critical care, important for the speciality of critical care, it is responsible for the speciality of critical it is responsible for the speciality of critical carecare » »

Marino PL. the ICU Book, 2Marino PL. the ICU Book, 2ndnd edition, Williams and Wilkins 1997 edition, Williams and Wilkins 1997

The Arc of the Pulmonary Artery The Arc of the Pulmonary Artery Catheter Catheter Robert A. Fowler, MD; Deborah J. Cook, MD ,Robert A. Fowler, MD; Deborah J. Cook, MD ,JAMA. 2003;290:2732-2734JAMA. 2003;290:2732-2734. .

Assessment of a monitoring technologyAssessment of a monitoring technology

• Safety (effectiveness): Safety (effectiveness): safe and accurate safe and accurate monitoring , without explicit monitoring , without explicit recommendations and guidance to the recommendations and guidance to the clinician.clinician.

• Efficacy (impact on the outcome):Efficacy (impact on the outcome): explicit treatment protocols; goal explicit treatment protocols; goal oriented therapy (GOT) protocols.oriented therapy (GOT) protocols.

SAFETYSAFETY

EFFECTIVENESSEFFECTIVENESS(Technology used as a monitor and without explicit guidance to the physician)(Technology used as a monitor and without explicit guidance to the physician)

PAC without GOT versus no PACPAC without GOT versus no PAC

JAMA 1996; 270:899-897

Prospective cohort of 5735 ICU patients with 9 disease categoriesProspective cohort of 5735 ICU patients with 9 disease categories

PAC inserted in 38 %PAC inserted in 38 %

Patients with a PAC were matched with patients without a PAC Patients with a PAC were matched with patients without a PAC who had comparable diagnosis and severity based on a 18-item propensity scorewho had comparable diagnosis and severity based on a 18-item propensity score

No RHCNo RHC

Pro

port

ion

surv

ivin

gP

ropo

rtio

n su

rviv

ing

Follow-up time Follow-up time (days)(days)

JAMA 1996; 270:899-897JAMA 1996; 270:899-897

RHCRHC

p = 0.02p = 0.02

• Significantly higher mean cost of Significantly higher mean cost of hospital stayhospital stay: 49300 versus 35700 : 49300 versus 35700 US Dollars.US Dollars.

• Significantly longer length of stay Significantly longer length of stay in ICUin ICU :14.8 versus 13.0 days :14.8 versus 13.0 days

• Higher baseline probability of Higher baseline probability of surviving at two months, highest surviving at two months, highest relative risk of death with PAC userelative risk of death with PAC use

Non randomized clinical Non randomized clinical trialstrials

- Mackirdy et al: Clin Intensive Care 1997;8:9-13(Scottish ICU)

Similar results than Connors AF et al

- Polanczyk CA et al: Jama 2001; 286: 309- 314(non cardiac surgery)

Significant increase in post operative major cardiac and non cardiac events in patients undergoing

PAC

MORTALITY:MORTALITY:1087/4181 (26%), 1087/4181 (26%), 12.6%12.6% in patients in patients without PAC without PAC 42.9%42.9% in those with a in those with a PAC (P<0.0001). PAC (P<0.0001).

« PAC was, associated « PAC was, associated with mortalitywith mortality when no when no adjustment had been adjustment had been made for severity of made for severity of illness. »illness. »

Pulmonary artery catheterization and mortality in critically ill patients Pulmonary artery catheterization and mortality in critically ill patients

S. D. Murdoch, A. T. Cohen and M. C. BellamyS. D. Murdoch, A. T. Cohen and M. C. Bellamy Br J AnaesthBr J Anaesth 2000; 2000; 8585: 611–5: 611–5

« The data we have « The data we have examined show no examined show no increase in mortality increase in mortality in those patients in those patients receiving a receiving a pulmonary artery pulmonary artery catheter, nor do we catheter, nor do we demonstrate a demonstrate a beneficial effect of its beneficial effect of its use. These results use. These results were observed after were observed after correction for correction for treatment bias using treatment bias using a propensity score »a propensity score »

Sakr et al , Sakr et al , Chest 2005, 128: 2722- 2731Chest 2005, 128: 2722- 2731

Mortality (PAC):Mortality (PAC):

-ICU, ICU, 28 VS 17%28 VS 17%-In Hospital, In Hospital, 33 VS 23%33 VS 23%

Propensity score to Propensity score to match patientsmatch patients

SAFETY/ EFFECTIVENESSSAFETY/ EFFECTIVENESSRandomized clinical studiesRandomized clinical studies

• Rhodes ARhodes A, Intensive Care Med 2002; 28: , Intensive Care Med 2002; 28: 256- 264256- 264

• Richard CRichard C, JAMA 2003; 290: 2713- 2720, JAMA 2003; 290: 2713- 2720

• Harvey SHarvey S, Lancet 2005; 366: 472- 477, Lancet 2005; 366: 472- 477

201 patients, 95 PAC + and 106 PAC -201 patients, 95 PAC + and 106 PAC -

mortality:mortality:

PAC + PAC + PAC -PAC - 46/95, 47.9%46/95, 47.9% 50/106, 47.6 % 50/106, 47.6 %

More fluids (day 1) , renal failure and More fluids (day 1) , renal failure and thrombocytopeniathrombocytopenia

in the PAC + (day 3)in the PAC + (day 3)Underpowered Underpowered

studystudy

JAMA 2003; 290:2717-2720JAMA 2003; 290:2717-2720

ShockShock

64 %64 %

ARDSARDS

30 %30 %

Shock + ARDSShock + ARDS

6 %6 %

676 patients676 patients

JAMA 2003, 290:2717-20

Admission characteristics of the patientsAdmission characteristics of the patientsType of admissions Type of admissions

0

10

20

30

40

50

60

70

80

90

medicalmedical scheduled scheduled surgerysurgery

unscheduled unscheduled surgerysurgery

PAC +PAC +PAC -PAC -

%%

Diagnostic categories at inclusionDiagnostic categories at inclusion

0

10

20

30

40

50

60

70

PAC +PAC +PAC -PAC -

shockshock shock / ARDSshock / ARDSARDSARDS

%%

Mortality at day 28Mortality at day 28

Days after randomizationDays after randomization

00 22 44 66 88 1010 1212 1414 1616 1818 2020 2222 2424 2626 2828

.1.1

.2.2

.3.3

.4.4

.5.5

.6.6

.7.7

.8.8

.9.9

11

00

PAC - (n=341)PAC - (n=341)

PAC + (n=335)PAC + (n=335)

p (log-Rank test) = 0.82p (log-Rank test) = 0.82

Ove

rall

Su

rviv

al %

Ove

rall

Su

rviv

al %

Richard C et al JAMA 2003; 290: 2713- 2720

Richard C et al JAMA 2003; 290: 2713- 2720

Complications related to PACComplications related to PACRichard C et al Jama, 2003, 290, 2713Richard C et al Jama, 2003, 290, 2713

Arterial puncture (n= 17)Arterial puncture (n= 17) Hemothorax (n=1)Hemothorax (n=1) Arrhythmias,conduction disturbance Arrhythmias,conduction disturbance

(n=60)(n=60) Knots (n=6)Knots (n=6) No death attributable to the PACNo death attributable to the PAC No pulmonary embolismNo pulmonary embolism Primary positive blood cultures in 2 of 10 Primary positive blood cultures in 2 of 10

patients with positive PAC culture after patients with positive PAC culture after insertioninsertion

PAC left PAC left indwellingindwelling

for a mean for a mean 2.3 days2.3 days

(range, 1- 10)(range, 1- 10)

JAMA 2003; 290:2717-2720JAMA 2003; 290:2717-2720

Clinical management involving the early use Clinical management involving the early use

of PAC in patients with shock, ARDS or both of PAC in patients with shock, ARDS or both

did not significantly affect did not significantly affect

morbidity and mortality.morbidity and mortality.

ControlControl

PACPACSu

rviv

al p

rob

abil

ity

(%)

Time from randomisation (days)

1041 pts1041 pts

Complications related to PACHarvey S et al, Lancet 2005; 366, 472. PACman

study) 46 of 486 (10%)

Hematomata at the insertion site (n=17, 4%)

Arterial punctures (n= 16, 3%)

Arryhthmias needing treatment within 1h of insertion (n=16, 3%)

Pneumothoraces (n=2)

Haemothorax (n=1)

Retrieval of lost insertion guidewires (n=2)

PAC PAC leftleftindwellingindwellingfor a for a mean mean

3 3 daysdays(range,2(range,2-- 4)4)

Is there a proven benefit of Is there a proven benefit of pulmonary artery catheter pulmonary artery catheter

use in the overall use in the overall management of patients?management of patients?

EFFICACYEFFICACY(The technology linked to explicit treatment protocols (The technology linked to explicit treatment protocols

dictated by the study)dictated by the study)

PAC with GOT versus no PACPAC with GOT versus no PAC

High risk surgical patientsHigh risk surgical patients

Congestive heart failure patientsCongestive heart failure patients

High risk surgical patientsHigh risk surgical patients• Twelve post operative hours: Twelve post operative hours:

higher mean valueshigher mean values of of CI (4.5 L/min/m2), CI (4.5 L/min/m2), DO2 (600 mL/min/m2) and VO2 DO2 (600 mL/min/m2) and VO2 (170 mL/min/m2) (170 mL/min/m2)

in survivors than in non survivorsin survivors than in non survivors

• Physiologic compensation for the increased metabolic Physiologic compensation for the increased metabolic demanddemand

• Supraphysiologic hemodynamic values could Supraphysiologic hemodynamic values could represent target goals to achieve to improve represent target goals to achieve to improve prognosis.prognosis.

Shoemaker et al. Chest 1988; 94: 1176- 1186Shoemaker et al. Chest 1988; 94: 1176- 1186

N Engl J Med 2003, 348:5-14N Engl J Med 2003, 348:5-14

> 60 yrs, ASA class III or IV risk, scheduled for urgent or > 60 yrs, ASA class III or IV risk, scheduled for urgent or elective major surgery, followed by a stay in ICU. elective major surgery, followed by a stay in ICU.

997 pts received PAC 997 pts received PAC with a goal-oriented with a goal-oriented

protocolprotocol

997 patients 997 patients did not receive PAC did not receive PAC with standard carewith standard care

randomizationrandomization

Goal oriented therapy Goal oriented therapy objectivesobjectives

DO2 >550 mL/min/m2DO2 >550 mL/min/m2CI> 3.5 L/min/ m2CI> 3.5 L/min/ m2MAP> 70 mmHgMAP> 70 mmHgPAPO= 18 mmHgPAPO= 18 mmHgHR< 120 bpmHR< 120 bpmHt> 27 %Ht> 27 %

Pro

por

tion

su

rviv

ing

Pro

por

tion

su

rviv

ing

monthsmonths

Standard careStandard care

PACPAC

nsns

Sandham et al N Engl J Med 2003; 348:5-14 Sandham et al N Engl J Med 2003; 348:5-14

One or more One or more adverse effects:adverse effects:1.5 % with PAC1.5 % with PAC

0.7 % with 0.7 % with standard carestandard care

433 patients:433 patients:

« sufficiently ill with advanced heart failure « sufficiently ill with advanced heart failure to make use of the PAC reasonable, but also sufficiently to make use of the PAC reasonable, but also sufficiently stable to make cross- over to PAC for urgent management stable to make cross- over to PAC for urgent management unlikely »unlikely »

DiscussionDiscussion(RCTs PAC versus no PAC)(RCTs PAC versus no PAC)

• No needNo need for the routine use of a cardiovascular for the routine use of a cardiovascular monitoring tool. The clinical evaluation of the monitoring tool. The clinical evaluation of the patients is widely sufficientpatients is widely sufficient.

• Need Need for a safe cardiovascular monitoring to for a safe cardiovascular monitoring to understand what we do and to try to improve understand what we do and to try to improve prognosis.prognosis.

PAC with GOT versus PAC without GOTPAC with GOT versus PAC without GOT

PAC with GOT versus PAC without GOTPAC with GOT versus PAC without GOT

- High risk surgical patientsHigh risk surgical patients

- Critically ill patients- Critically ill patients

Postoperative daysPostoperative days

Pat

ien

ts s

urv

ivin

g %

Pat

ien

ts s

urv

ivin

g % Protocol Protocol (n=53)(n=53)

Control Control (n =54)(n =54)

p = 0.015p = 0.015

JAMA 1993; 270:2699- 2707JAMA 1993; 270:2699- 2707

PAC with orPAC with orwithout without

oriented oriented therapytherapy

Effects of maximizing oxygen delivery on morbidity Effects of maximizing oxygen delivery on morbidity and mortality in high risk surgical patients.n=37and mortality in high risk surgical patients.n=37Lobo et al.Lobo et al. Crit Care Med 2000; 28: 3396-3404

0 10 20 30 40 50 60

Time, daysTime, days

100

90

80

60

50

40

30

Protocol groupProtocol group

ControlControl groupgroup

10

0

70

20

p = 0.01

Su

rviv

al, %

Su

rviv

al, %

PAC with orPAC with orwithout without

oriented oriented therapytherapy

« A significant improved A significant improved outcome was observed outcome was observed when PAC with GOT was when PAC with GOT was used early or used early or prophylactically in prophylactically in patients who were patients who were optimized optimized preoperatively and preoperatively and maintained in the maintained in the intraoperative and intraoperative and immediate post immediate post operative period »operative period »

Critically ill patients

• PAC with GOT versus PAC without PAC with GOT versus PAC without GOTGOT

Gattinoni et alGattinoni et al

Alia et alAlia et al

Hayes et alHayes et al

Alia et al. Alia et al. Chest 1999; 115:453-61Chest 1999; 115:453-61

Length of stay in the intensive care unit after enrollment (days)

Su

rviv

al p

rob

abil

ty

Gattinoni et al. Gattinoni et al. N Engl J Med 1995; 33: 1025-32N Engl J Med 1995; 33: 1025-32

Days after randomization

Pro

bab

ilit

y of

su

rviv

al

0.00.0

0.20.2

0.40.4

0.60.6

0.80.8

1.01.0

0 45 90 135 1850 45 90 135 185

Control group

Cardiac-index group

Oxygen-saturation group

no differenceno difference

Hayes et al. Hayes et al. N. Engl. J. Med. 1994 ; 330 : 1717-1722N. Engl. J. Med. 1994 ; 330 : 1717-1722

Days

% o

f p

atie

nts

su

rviv

ing

p= 0.04

N=762N=762N=63N=63

N= 100N= 100

Could it possible to ameliorate the results of Could it possible to ameliorate the results of these PAC (or any other cardiovascular these PAC (or any other cardiovascular

monitoring device) with GOT versus PAC monitoring device) with GOT versus PAC without GOT studies?without GOT studies?

Limitations of these studiesLimitations of these studies

Heterogeneity of the populationHeterogeneity of the population

Very late inclusion of the patients when MOF is Very late inclusion of the patients when MOF is

definitively installeddefinitively installed

Well known difficulties to achieve Well known difficulties to achieve

pharmacological goalspharmacological goals

PROPRO

• PatientsPatients• Hemodynamic targetsHemodynamic targets• Primary end pointsPrimary end points

RCT in Homogeneous PopulationRCT in Homogeneous Population

Early goal directed therapy in Early goal directed therapy in the treatment of severe sepsis the treatment of severe sepsis and septic shock and septic shock (Rivers et al New Engl J Med 2001; 345: 1368- 1377)(Rivers et al New Engl J Med 2001; 345: 1368- 1377)

Septic patients included very early Septic patients included very early after the diagnosisafter the diagnosis

Crit Care Med 2004; 32:911-915Crit Care Med 2004; 32:911-915

To examine the association between PAC and mortality rate To examine the association between PAC and mortality rate

in critically ill patients with a higher vs a lower severity of in critically ill patients with a higher vs a lower severity of

illnessillness

Aim :Aim :

Design :Design : Observational cohort study including 7310 pts (28 % with PAC)Observational cohort study including 7310 pts (28 % with PAC)

80

70

60

50

40

30

20

10

00

APACHE II APACHE II

< 18< 18

APACHE II APACHE II

18-2418-24

APACHE II APACHE II

25-3125-31

APACHE II APACHE II

>31>31

% Mortality

Chittock et al. Crit Care Med 2004

****

NSNS

##

PACPAC no PACno PAC

Crit Care Med 2005; 33:1119-22

Mixed venous oxygen saturationMixed venous oxygen saturationNormal hemodynamic targetsNormal hemodynamic targets

Hemodynamic targetsHemodynamic targets

http://gateway.ut.ovid.com/gw1/ovidweb.cgi?View+Image=00003246-200505000-00033%7CFF1&S=IDNJHKOAFFJEHM00D&WebLinkReturn=Full+Text%3DL%7CS.sh.15.16%7C0%7C00003246-200505000-00033

Primary end pointsPrimary end points

ConclusionConclusion• PAC is a classical tool for hemodynamic assessment PAC is a classical tool for hemodynamic assessment

since it enables continuous monitoring of numerous since it enables continuous monitoring of numerous hemodynamic parameters such as tissue hemodynamic parameters such as tissue oxygenation oxygenation variablesvariables and estimates of and estimates of cardiac filling pressurescardiac filling pressures that that are not provided by other monitoring devices.are not provided by other monitoring devices.

• A large recently published metaanalysis of RCT A large recently published metaanalysis of RCT demonstrated that its use does not cause harm to demonstrated that its use does not cause harm to critically ill patients. critically ill patients.

((Shah et al JAMA. 2005;294: 1664-1670)Shah et al JAMA. 2005;294: 1664-1670) • The heterogeneous results of the GOT should be The heterogeneous results of the GOT should be

interpreted in light of the specific interventions tested, interpreted in light of the specific interventions tested, the delay for inclusion and the case mixed of the the delay for inclusion and the case mixed of the patients, and not of the choice of PAC patients, and not of the choice of PAC per seper se as a as a monitoring tool.monitoring tool.

CONCLUSIONCONCLUSION

Whether Whether goal- oriented therapeutic protocolsgoal- oriented therapeutic protocols based on an individualized analysis of PAC data based on an individualized analysis of PAC data are able to improve the outcome of the critically are able to improve the outcome of the critically ill remains to be investigated. ill remains to be investigated.

It appears of paramount importance to develop It appears of paramount importance to develop educational programseducational programs to improve the quality of to improve the quality of recording and the acuity of the interpretation of recording and the acuity of the interpretation of the data afforded by PAC as well as by all other the data afforded by PAC as well as by all other cardio- vascular monitoring devicescardio- vascular monitoring devices

CONCLUSIONCONCLUSION

« PAC ( and all cardiovascular monitoring tool) « PAC ( and all cardiovascular monitoring tool) should not be used for the routine treatment should not be used for the routine treatment of of patients in the ICU until or unless effective patients in the ICU until or unless effective therapy can be found that improve outcomes therapy can be found that improve outcomes when coupled with the diagnostic tool. »when coupled with the diagnostic tool. »

((Shah et al JAMA. 2005;294: 1664-1670)Shah et al JAMA. 2005;294: 1664-1670)

The exact role of a cardiovascular monitoring tool The exact role of a cardiovascular monitoring tool in ICU patients remains to be determinedin ICU patients remains to be determined