FLUID RESUSCITATION AND MONITORING IN SEPSIS PROTOCOLIZED VS USUAL CARE DEEPA BANGALORE GOTUR MD, FCCP ASSISTANT PROFESSOR, WEILL CORNELL MEDICAL COLLEGE NOVEMBER 10 TH 2017 TEXAS SCCM SYMPOSIUM
Disclosures - None
Usual care is better Objectives 1.Updates in resuscitation protocol 2.Hemodynamic targets 3.Hemodynamic tools
DEFINITIONS Protocolized definition Usual care definition Premise for EGDT - usual care lacked aggressive, timely assessment and treatment Protocol for EGDT called for- 1. MAP targets, CVC for CVP and Scvo2 with set targets 2. Used to guide the use of intravenous fluids, vasopressors, packed red-cell transfusions, and dobutamine
EARLY GOAL-DIRECTED THERAPY IN THE TREATMENT OF SEVERE SEPSIS AND SEPTIC SHOCK Early Goal-Directed Therapy Collaborative Group
EGDT NNT 6
Argument Is it reproducible?
PROCESS TRIAL Timeline - From March 2008 through May 2013 P- Multicenter 31 EDs, USA; 1341 patients I- EGDT C- Protocol Standard No CVC, inotropes, blood products mandates Usual Care
PROCESS O- Primary end point 60 day mortality Secondary end points 1. rate of death at 90 day 2. 90-day mortality EGDT group N=439 3. Duration of cardiovascular respiratory and renal failure 4. LOS hospital and ICU 5. disposition Total n= 1341 Protocol based standard therapy N=446 Usual care N=456
N Engl J Med 2014; 370:1683-1693
N Engl J Med 2014; 370:1683-1693
SEEMINGLY River s study when compared to ProCESS Higher APACHE II score Lower mean ScVO2 Higher lactate
GOAL DIRECTED RESUSCITATION FOR PATIENTS WITH EARLY SEPTIC SHOCK : ARISE INVESTIGATORS Timeline - From October 5, 2008, to April 23, 2014 P- 51 centers; Australia, New Zealand; 1600 pts I- EGDT C- Usual Care O- Primary 90 day mortality
Secondary outcomes 1. Survival time till 90 days 2. ICU mortality mortality 3. 28 day mortality 4. In-hospital mortality at 60 days 5. Cause-specific mortality at 90 days 6. LOS in ED, ICU, hospital 7. Duration of mechanical ventilation, vasopressor support, or RRT 8. Destination at the time of discharge 9. Adverse events
N Engl J Med 2014; 371:1496-1506
PROMISE TRIAL Timeline From February 16, 2011, to July 24, 2014 P- 56 sites in UK 1260 patients enrolled I- EGDT C- Usual care O- Primary outcome- 90 day mortality
Secondary outcome 1. 6 hr, 72 hr SOFA 2. Free days from Cardiac, respiratory and renal support 3. LOS ED, ICU, Hospital 4. duration of survival 5. 28 day, hospital discharge and 1 year mortality 6. Health-related QOL 7. Costs at 90 days and 1 year 8. Adverse events
N Engl J Med 2015; 372:1301-1311
Argument Can procotolized care be generizable to specific population groups?
JAMA. 2017;318(13):1233-1240
Argument Are the targets for resuscitation valid?
Flaws in resuscitation targets - CVP placement of CVC for CVP and its associated complications Marik PE, Baram M, Vahid B. Does central venous pressure predict fluid responsiveness? A systematic review of the literature and the tale of seven mares. Chest. 2008 Jul;134(1):172-8
Alan E. Jones, MD; Nathan I. Shapiro, MD, MPH; Stephen Trzeciak, MD, MPH; et al JAMA. 2010;303(8):739-746. doi:10.1001/jama.2010.158
THE END OF THE LINE FOR EARLY GOAL DIRECTED THERAPY Voluntarily submitted data were analyzed on 15 022 patients with severe sepsis and septic shock Attainment of CVP of >8mmHg and ScvO2 of >70% did not influence survival in patients with septic shock The only early interventions found to be independently associated with survival benefit were timely antibiotics and blood cultures prior to administration (p<0.001) Emerg Med J. 2011 Jan;28(1):3-4
Argument Fluid is a drug, higher doses increases mortality
Semler M, Rice T. Sepsis resuscitation
FLUID ADMINISTRATION IN SEVERE SEPSIS AND SEPTIC SHOCK, PATTERNS AND OUTCOMES: AN ANALYSIS OF A LARGE NATIONAL DATABASE MARIK, P.E., LINDE-ZWIRBLE, W.T., BITTNER, E.A. ET AL. INTENSIVE CARE MED (2017) 43: 625. P - 2013 Premier Hospital Discharge database n=23,513 I - none C - Day 1 fluid was grouped into categories 1 L wide, starting with 1 1.99 L up to 9 L, to examine the effect of day 1 fluids on patient mortality O 1. low volume resuscitation (1 4.99 L) - reduction in mortality, of 0.7% per liter (95% CI 1.0%, 0.4%; p = 0.02). 2. high volume resuscitation (5 to 9 L), the mortality increased by 2.3% (95% CI 2.0, 2.5%; p = 0.0003) for each additional liter above 5 L. 3. Total hospital cost increased by $999 for each liter of fluid above 5 L (adjusted R 2 = 92.7%, p = 0.005).
Argument How good is adherence rate to complex protocols?
THE SURVIVING SEPSIS CAMPAIGN BUNDLES AND OUTCOME: RESULTS FROM THE INTERNATIONAL MULTICENTRE PREVALENCE STUDY ON SEPSIS (THE IMPRESS STUDY)
THE SURVIVING SEPSIS CAMPAIGN BUNDLES AND OUTCOME: RESULTS FROM THE INTERNATIONAL MULTICENTRE PREVALENCE STUDY ON SEPSIS (THE IMPRESS STUDY) September 13, 2013, the SSC, ESICM and SCCM will be conducting an international point prevalence study of severe sepsis and septic shock Overall compliance with all the 3-h bundle metrics was 19 %. This was associated with lower hospital mortality than non-compliance (20 vs. 31 %, p < 0.001). Overall compliance with all the 6-h bundle metrics was 36 %. This was associated with lower hospital mortality than non-compliance (22 vs. 32 %, p < 0.001).
Argument How cost-effective is protocolized care?
Argument No monitoring device can improve patient centered outcomes unless it is coupled to a treatment that improves outcome.
HOW SHOULD WE DEAL WITH THE INACCURACIES AND LIMITATIONS OF OUR MONITORED PARAMETERS? Maximize the information that can be provided by real-time continuous measurement Beware of protocols, especially those with pre-defined physiological end-points
IMPORTANT QUESTIONS THAT NEED TO BE ANSWERED Is the patient fluid responsive?- volume / preload status- PLR, CVP, LVEDA, SVC/IVC collapsibility Is the forward flow adequate?- cardiac output/ cardiac index, SVO2 Is there obstructive pathology limiting stroke volume?- pulsus paradoxus, equalization of pressures, diastolic chamber collapse Is there elevated filling pressure in the LV?- PAOP Is there adequate perfusion to the end organs?- MAP, SVR, urine output Is the tissue oxygenation adequate?- oxygen delivery, lactic acid level
HEMODYNAMIC MONITORING Straight leg raise Stroke volume variance (SVV) Bio reactance Ultrasound
SLR sensitivity of 72.7% and specificity of 80%
PULSE CONTOUR ANALYSIS Currently, three devices (the FloTrac system, PiCCO monitor, and LiDCO system) are available for measurement of ArterialWaveformAnalysis-based CO. Dynamic preload parameters such as stroke volume variation (SVV) and pulse pressure variation (PPV) are determined, which may be useful to predict fluid responsiveness in mechanically ventilated patients.
PICCO
SHOCK PROTOCOL USING SVV & SV
Minimally-invasive cardiac output monitoring added to usual care does not facilitate early hemodynamic stabilization in the ICU, nor does it alter the hemodynamic support or outcome.
BIOREACTANCE Squara, P., Denjean, D., Estagnasie, P. et al. Intensive Care Med (2007) 33: 1191
ECHOCARDIOGRAPHY TTE and TEE is being more routinely used in the OR and in the ICUs for managing the hemodynamics. Again the most important parameters of interest 1. Preload 2. Stroke volume /cardiac output 3. Filling pressures to give insight into diastolic function 4. Any ongoing pericardial process 5. Any valvular abnormalities
PRELOAD IVC Preload SVC collapsibility (>36% indicates hypovolemia), Change in the IVC diameter during respiration(>12%), LVEDA are some of the common measurement in assessing the preload state of the patient.
CARDIAC OUTPUT Systolic function can me assessed by various measurements like- 1. Ejection fraction 2. Shortening fraction 3. Fractional area change 4. Measuring stroke volume with doppler technique When striving to achieve a pre-defined level of CO, one has to use an accurate device!
ECHOCARDIOGRAPHY
FILLING PRESSURES Diastolic function can be evaluated by studying the transmitral inflow velocities using pulsed wave echo doppler technique.
Argument Do all centers across the world have master physiologist to monitor and titrate fluids to changing physiology?
Rebuttal
MORE PATIENTS ARE BEING RECOGNIZED AS BEING IN SEPSIS
EARLY RECOGNITION AND ANTIBIOTIC ADMINISTRATION IMPROVES MORTALITY, PROTOCOL DRIVEN APPROACH IS NOT NEEDED Kumar A, et al. Crit Care Med 2006; 34:1589-1596
SOFA AND QSOFA HAVE VALIDITY FOR PROGNOSTICATION AND PREDICTION OF MORTALITY BUT NOT FOR SCREENING Crit Care Med. 2009 May ; 37(5): 1649 1654
HEMODYNAMIC MONITORING FOCUSES ON MACRO- CIRCULATORY FAILURE, WHILE SEPSIS PATHOLOGIES ARE MORE PRONOUNCED IN MICROCIRCULATION Rev. colomb. anestesiol. vol.44 no.2 Bogotá Apr./June 2016
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