Tailored Volume Resuscitation in the Critically Ill is Achievable. Objectives. Clinical Case 2/16/2018

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Tailored Volume Resuscitation in the Critically Ill is Achievable Heath E Latham, MD Associate Professor Fellowship Program Director Pulmonary and Critical Care Objectives Describe the goal of resuscitation in shock. Recognize potential adverse outcomes of over resuscitation of the critically ill. Increase awareness of guided volume resuscitation strategies. Recognize applications and limitations of bioreactance derived hemodynamic monitoring.. Recognize applications and limitations of pulse contour analysis derived hemodynamic monitoring. Describe potential benefits of volume targeted resuscitation to limit volume overload. Clinical Case AR is a 72 yo 80 Kg female admitted from a SNF with a 1 day history of altered mental status and fevers. She is hypotensive on presentation with evidence of a UTI from an indwelling foley. She has a history of ischemic cardiomyopathy with an EF of 20% and chronic renal failure with crtof 2.4 She is given two 500mL boluses of fluid and abxin the ED and admitted to the ICU. First bolus resulted in 20% improvement in SV Second bolus resulted in 8% improvement in SV Post fluid vitals: T 39, BP 80/40, HR 95 (NSR), RR 28 1

Surviving Sepsis Campaign Guidelines 1. Severe Sepsis and Septic Shock are medical emergencies, and treatment and resuscitation should begin immediately. (BPS) 2. We recommend that, in the resuscitation from sepsis-induced hypoperfusion, at least 30 ml/kg of IV crystalloid fluid be given within the first 3 hours Strong recommendation, low quality of evidence SSC. Crit Care Med. 2017; 45:486-552. History of 30mL/Kg? Rivers EGDT. NEJM 2001;345:1368-77. Pre-randomization resuscitation 20-30mL/Kg ProCESS. NEJM 2014; 370:1683-93. Pre-randomization resuscitation 20 ml/kg 2010 amendment at least 1L ProMISe NEJM 2015; 372:1301-11 Pre-randomization resuscitation At least 1L ARISE NEJM 2014;371:1495-506. Pre-randomization resuscitation At least 1L 30 ml/kg seems to be standard practice Trial Time to randomization (hours) Fluids received prior to randomization (ml) Fluids Received prior to randomization (ml/kg) Between 0 and 6 h after randomization (ml) Rivers 0.8 NA NA 3499 ± 2438 ProCESS 3.0 2083 ± 1405 28 ± 21 2279 ± 1881 ARISE 2.7 2591 ± 1331 34.7 ± 20.1 1713 ± 1401 PROMISE 2.5 1790 (1000, 2500) 24* 2022 ± 1271 2

The IMPRESS-SSC Study An International Multi-Centre Prevalence Study of Sepsis 3 Hour Bundle Compliance % Measurement of Lactate 56 Obtain Blood Cultures Prior to Antibiotics Administer Broad Spectrum Antibiotics Administer 30 ml/kg crystalloid for hypotension or lactate 4mmol/L 49 64 57 Rhodes et al. Intensive Care Med. 2015 Sep;41(9):1620-8 NYS Sepsis Initiative Seymour et al. N Engl J Med 2017;376:2235-44 Leisman et al. CritCare Med. 2017: 45(10) 3

Leisman et al. CritCare Med. 2017: 45(10) Leisman et al. Crit Care Med. 2017: 45(10) Goal of Resuscitation Achieve Adequate Perfusion Pressure MAP > 65 mmhg Volume Replacement Vasopressors Inotropic Improve Microcirculatory Flow Rapidly treat underlying cause of shock Limit Tissue Edema 4

What s the Goal of Fluid Resuscitation? Improve Stroke Volume/Cardiac Output Fluid Responsiveness in Severe Sepsis/Septic Shock? Approx50% Marik, et al. Ann CritCare. 2011; 1:1 Marik, et al. Br J Anaesth. 2014; 112:620-22 Cavallaro et al. Inten Care Med. 2010; 36:1475-83 Latham et al. J CritCare. 2017; 42:42-46 What are the Consequences? Boyd, J. Crit Care Med. 2011; 39:259-65. What are the Consequences? 5

What is Too Much? Premiere Database Severe/Septic Shock 23,513 encounters Day 1 ICU Fluid Adjusted for Severity Marik, P et al. Int Care Med. 2017; 43:625-32. Other Volume Sensitive Outcomes? Retrospective Chart Review Medical ICU Severe Sepsis/Septic Shock April 2014-September 2014 Usual Care (91) vs SV Guided Resuscitation (100) Hypothesis: Guided Resuscitation < Fluid Latham HE, et al. Journal of Critical Care. 2017: 42;42-46. Other Volume Sensitive Outcomes? Latham HE, et al. Journal of Critical Care. 2017: 42;42-46. 6

Latham HE, et al. Journal of Critical Care. 2017: 42;42-46. Other Volume Sensitive Outcomes? Secondary Outcomes Mortality: 21% vs 20% ICU LOS: 6 vs 9 Days (p = 0.03) Mechanical Ventilation 29% vs 57% (p = 0.001) MV Days: 6.3 vs 6.7 (p = 0.76) Secondary Outcomes Vasopressors 48% vs 57% (p = 0.25) Duration: 32 vs 65 hrs(p = 0.001) Hemodialysis 6% vs 19% (p = 0.01) Latham HE, et al. Journal of Critical Care. 2017; 42:42-46. SV Guided Resuscitation Latham HE, et al. Journal of Critical Care. 2017: 42;42-46. 7

Tailored Resuscitation Technology Bioreactance NICOM Starling Doppler Derived Bedside US USCOM Pulse Contour Analysis Flotrack/EV1000 LiDCO PiCCO Challenge Technique Volume Expansion 500mL w/in 30 min Passive Leg Raise (PLR) Volume Responsiveness Passive Leg Raise Reversible Volume Expansion 250-350 ml 3-5 Minutes in supine position Caution Labile Hemodynamics Severe Ventilatory Insufficiency At Risk Airway Passive Leg Raise Meta-Analysis 9 Articles 366 Pooled Interventions ICU/Shock Mixed CI/SVI assessment Doppler derived Pulse contour analysis Mixed spontaneous ventilation Mixed Rhythms Results PLR Accurately Predicts Volume Responsiveness ΔSVI/CI > ΔPP Unaffected Technology used Spontaneous Respiration Arrhythmia Cavallaro, F. Inten Care Med. 2010; 36:1475-83. 8

Cavallaro, F. Inten Care Med. 2010; 36:1475-83. Passive Leg Raise Boluses % Resp AUC 15 22 45 0.95 71 52 0.96 24 54 0.96 24 54 34 50 0.89 34 50 0.89 102 46 0.89 34 68 0.94 30 67 0.96 30 67 0.92 34 41 0.94 Overall 366 52.9 0.95 Bioreactance Completely Non-Invasive 4 Electrodes on Chest Assess change in current Spontaneous Breathing Mobile Patient Updates every minute Keren H, et al. 2007. Am J Physiol Heart Circ Physiol; 293:H583-H589. How it Works Ventricular outflow drives changes in Phase (Phase Shift) of radiofrequency waves as they cross the chest Measuring the Frequency (Phase Shift) enables exact calculation of flow Keren H, et al. 2007. Am J Physiol Heart Circ Physiol; 293:H583-H589. 9

Bioreactance Tested in Various Settings ER ICU Pregnancy Pulmonary HTN Not Effected by External Electronics Applicable in Non-Physician Algorithms Limitations Electrode Durability Inaccurate Severe AI Thoracic Aneurysms Balloon Pump LVAD? Dense Infiltrates Cautery Pulse Contour Analysis Estimation of SV Area under the curve Systolic portion Presumed constants Vascular compliance Aortic impedance PVR Pulse Regularity Improves accuracy Huber, et al. BMC Anesthesiology. 2015; 15:45. Pulse Contour Analysis Advantages Simple to use Real time data Utilize arterial line already in place Continuous CO Non-physician resuscitation protocols Disadvantages Requires excellent waveforms Re-calibration SVV Limited to Optimal Parameters Sinus Rhythm Vt >8 ml/kg HR/RR > 3.6 No Spontaneous Resp 10

Doppler Derived Stroke Volume Bedside US with Doppler Echocardiography Peripheral artery Doppler Esophageal Doppler USCOM Device Bedside Ultrasound Advantage of US in Shock Assess Cause of Shock Cardiac Pulmonary Septic Assess Volume Responsiveness Assess Therapeutic Result Bedside Ultrasound Disadvantage of US in Shock Competence of User Training* in bedside ultrasound Training* in doppler-based measurements Inter/Intra-observer Variability How Many Devices Are Needed No Form of Continuous Measurement Nursing can t monitor change in hemodynamics 11

Is Fluid Limited Care Realistic? Single Center Targeted Fluid Management (TFM) 82 Randomized Septic Shock Patients Usual Care vs Targeted Fluid Therapy Followed by Conservative Fluid Net Fluid Balance Day 3: 3.1L vs 1.9 L Day 5: 3.6L vs 2.6L No Difference: Mortality RRT Ventilator Days Vasopressors Chen C, Kollef M. CHEST. 2017; 148:1462-69. Is Fluid Limited Care Realistic? FACTT Trial 2006 Multicenter ARDSnet Trial Fluid Conservative vs Liberal Sepsis Major Cause of ARDS ARDSnet. NEJM. 2006; 354:2564-75. Conclusion Guidelines Serve to Limit Care Variation 30mL/Kg = Low Level of Evidence Mounting Evidence of Potential Harm From Excess Volume Mortality Secondary Outcomes Technology is Available for SV Guided Resuscitation Prospective RCT Are Needed to Further Assess the 30mL/Kg 12