FLUID RESUSCITATION-WHERE ARE WE? SWINGING HIGH AND SWINGING LOW AND SWINGING JUST RIGHT DEBATE CONTINUES ON AND ON

MIHAE YU, MD FACS

PROFESSOR OF SURGERY, UNIVERSITY OF HAWAII DEPARTMENT OF SURGERY

MEDICAL DIRECTOR OF SURGICAL INTENSIVE CARE UNIT AT QUEEN’S MEDICAL CENTER

FLUID DEBATE CONTINUES ON AND ON AND ON…

• Debate with no end… politics or religion • Everyone has an opinion • Very few institutions measure intravascular blood volume as the

endpoint of fluid resuscitation

HISTORIC PERSPECTIVE

• 3:1 crystalloid to red cell replacement to compensate for interstitial losses (Shires et al, Sug Clinic N America 1973;53:1341). Vietnam war 1960’s

• Types of fluids: hypertonic saline, + colloids – no outcome difference

• Lactated Ringers (N America): increase expression of neutrophil adhesion molecules, apoptosis in various organs, (D-isomer of lactate related)

• Large amounts of crystalloids: abdominal compartment syndrome, acute lung injury… Really. Fluids vs Reperfusion injury

INTEREST IN LESS VOLUME…

• MAP of 40-60 in animal studies of hemorrhagic shock, but not prolonged (>8 hours) – improve mortality. Lu et al (J Trauma 2007, 63:798) (Skarda et al ,Acad Emerg Med 2008;15:845

• Delayed fluid resuscitation. Prehospital setting, Young (mean 31 years), penetrating torso, short transport time. Bickell et al NEJM 1994;331:1105

• Extrapolation to all victims: blunt, old, long transport time: problems

DEBATE OF THE CENTURY IN RESUSCITATION…

• What is the patients intravascular volume? • Heated discussions at bedside, diuresis vs fluids • Endpoint of fluid resuscitation? • Endpoint of red cell transfusion

ALL ROADS LEAD TO “EUVOLEMIA”: EVERY GUIDELINE

• ACC/AHA guidelines in chronic CHF patients. • Septic shock, trauma, critically ill: adequate preload. • First basic principle in treatment of all patients: EUVOLEMIA • BUT HOW?

EARLY GOALS: EMERGENCY ROOM

• BEFORE HEMORRHAGE CONTROL: • Keep BP lower than patients anticipated normal dependent on

Age, other non-tolerant organ injury (brain).

LAST CENTURY: SURROGATE MARKERS TO GUIDE FLUID MANAGEMENT, CREATURES OF HABIT

• Blood pressure

• Heart rate

• Urine output

• Base deficit

• Lactic acid

• CXR

• Central cardiac pressures: CVP, PAOP,

• Dynamic cardiac volume measurements: SVV, PPV

• Venous oxygenation saturation: ScVo2, SvO2

• BNP

BP IS A LATE SIGN – DON’T WAIT FOR THE FALL

• BP late sign due to hormonal response and compensation: 60%low, 30% normal, 10% high ( Little RA et al J of Accident and Emergency Medicine 1995:12:1.

• Be careful in extremes of age

BP GOALS BASED ON AGE, LINKED TO MORTALITY

• Once bleeding is under control, then aim for a BP more normal for that patient (AGE and Co-MORBIDITIES)

• Age ≥65 years: SBP >110 mm Hg, HR<90 (Heffernan et al, J Trauma 2010;69:813)

• “Adequate BP” may be higher than 90 mm Hg (Eastridge BJ et al J Trauma 2007;63:291) • Age 18-35, SBP 85 mm Hg. • Age 36-64 years, SBP of 96 mm Hg.

• Age ≥65 years, SBP of 117 mm Hg (Oyetunji et al, Arch Surg 2011;146:865)

HEART RATE

• HR Heart rate (HR) is not a reliable guide to detect hypotension ( Victorino GP et al J Am Col Surg 2003;196:679)

• Beta-blockers • Patients baseline heart rate • Street drugs

URINE OUTPUT, KIDNEY FUNCTION..

• 0.5 mL/kg/hours? ? • Adequate UO” adequate depends on the concentrating ability of

the kidneys and nitrogenous waste. Oliguria is a late sign of Renal failure (Brown R et al Crit Care Med 1980; 8:68)

• I+O, weights (third spacing fluid),

• BUN/creatinine elevated: hypovolemia, hypervolemia and heart failure

METABOLIC ACIDOSIS

• Elevated lactic acid is predictor of mortality, but NORMAL lactic acid does not mean all tissue beds are perfused.

• Lactate clearance at 6 hours: >60%, 30-59%, <30%, odds ratio for death of 1.0, 3.5, 4.3 respectively (Odom et al, J Trauma 2013;74:999

• Base Deficit greater than -6

• GUIDE TO FLUID AND BLOOD MANAGEMENT, BUT NOT BY HOW MUCH

HOW MUCH IS ENOUGH? WHEN DO WE DECREASE FLUIDS?

• CXR discrimination for cardiac filling pressures is poor (Ely EW et al, Crit

Care Med 2001;29:1502)

• CVP ≠ circulating BV • Ryan GM et al Anesth Analg 45:7541966 • Friedman E et al Lancet sept 17, 1966; p. 609 • Shippy CR et al Crit Care Med 1984;12:107 • jones JG 2000; Br J Anesth 84:226 • oohashi S et al J Anesth 2005;19:21 • Alrawi SJ et al Saudi Med J 2002;23;1367 • kuntscher MV et al Resuscitation 2006;70:37 • Nouira S et al Crit Care Med 2005;33:2339 (vs ppv, svv) • yamauchi H et al 2008; Hawaii Medical J;67:7

CVP, PAOP ≠ BLOOD VOLUME

• The PAOP seems to have better correlation to cardiac response

than CVP (Wagner 1998, michard 2002, Androne 2004 )

• Poor relationship between BV and PAOP (jones)

• BV correlate best with CO (Alrawi)

• Wagner J et al, Chest 1998; 113:1048 • Michard F et al Am J Resp Crit Care Med 2000;162:134 • Shippy C et al, CCM 1984: 12:107 • Alrawi SJ et al. Saudi Med J 2002;23:1367 • Oohashi (see slide above) • Androne 2004 is on severe chf patients. • Jones et al, Br J Anaesth 2000;84;226

SCVO2, SVO2, SIMILAR CONNOTATIONS AS LACTIC ACID

• Global balance between Oxygen delivery and Oxygen consumption. Does not tell you of individual tissue beds

• Bad if low values • Not meaningful if normal or high values

BRAIN NATRIURETIC PEPTIDE: MYOCARDIAL STRETCH VS INTRAVASCULAR VOLUME

• In CHF, no correlation between BNP and BV (Androne 2004)

• Change in BV correlate better with hemodynamics than changes in BNP (James KB 2005)

• For BNP >500 pg/mL, 11% associated with hypovolemia (Takahashi et al, J Trauma Acute Care Surg 2013: 75:813

• Androne et al Am J Cardiol 2004;93:1254

• James KB et al, Am Heart J 2005;150:984

• Katz SD. Am J Med Sci 2007;334:47

SVV AND BV PEI K ET AL CRIT CARE MED 2007:35:A86

• SVV and BV in 18 ventilated patients with no spontaneous respiration, 74 data points

• r= .11, R2 = .012 • 8/54 (15%) instances hypovolemia SVV <9.5%

PPV AND BLOOD VOLUME DOMINGO S ET AL, CRIT CARE MED 2008;36:A55

• 1 resp cycle. PP = SBP – DBP

• 100 x (PPmax – PPmin)/{(PPmax + PPmin)/2}. Normal is 30-50 mm hg

• Simultaneous BV and PPV

• 29 patients, 84 data points

• 14/69 (20%) hypovolemic when PPV was <13% (imply adequate preload) • 13/15 (86%) hypervolemic when PPV ≥13% (imply inadequate preload) • 57/84 (68%) = congruent information

WHY NOT MEASURE INTRAVASCULAR VOLUME?

• First blood volume 1915, radioisotope- cumbersome

• Tag albumin (I-125, I-131 present only in plasma, PV)

• Tag RBC-chromium 51 (red cell volume)

• Cumbersome

• 1970’s: Shoemaker and colleagues

• Single dye system, (Tag albumin only).

• Resurrection of BV

C1 x V1 = C2 x V2 Add known amount of dye: 1 ml of 10,000 black balls; unknown volume and mix thoroughly and sample 1 ml again and count the new concentration of black balls. MIX THOROUGHLY For ECF: radioactive Na, Cl, Bromide, radioiothalamate, thiosulfate, thiocyanite, inulin, sucrose For plasma: Radioactive iodine

PRINCIPLES OF MEASUREMENT

• Albumin not treated as foreign material but does transudate at a rate which is a semilogarithmic function of its concentration in plasma

• Inject tagged I-131 over 1 minute push, wait 12 minutes (full mixing) 5 Samples every six minutes

• Multipoint analysis and extrapolate to time zero to compensate for transudation of albumin from plasma. Slope gives information on how quickly albumin is leaking, “capillary leak”.

Measure PV (I-131), Measure Hct, Calculate RBCV Normal RBCV + Normal PV Euvolemic Anemia: Low RBCV + High PV = Hct 30% Hypovolemic Anemia: Low RBCV + High PV = Hct 30%

Pilot study 2004 (Takanishi et al, AM J Surg 09)

First observational phase: sample analyzed in New York Identify patients who need the information (all have edema): BP, UO, HR, unexplained acidosis,↑BUN or Creatinine, I+O, PaO2, BNP, PAC, CXR Treat patients with traditional information. 13 of 29 instances (1/3): changed treatment. 6 less fluid, 3 less blood, 2 more blood, 2 more fluid. SEE THE DELAY IN CLINICAL MANIFESTATIONS by 1-2 days

TREAT & OBSERVE TAKANISHI ET AL 09 • 40 subsequent SICU patients, change in treatment

occurred in 36% of instances, desirable response in 39%, and no negative response (n=86)

• BP, HR, urine output, low PaO2, increasing renal dysfunction, pressor requirements, inability to wean.

OTHER STUDIES…

• (BP, HR, UO, Urine sodium, Hemoglobin (Hb)) may lead to different fluid management in 30-50% of the time in ICU patients if BV results were used (Stephan F et al Br J ANesth 2001;86:754

• Unexpected BV results depends on the type of patients studied. found

unsuspected hypovolemia in 50% of ICU patients. Shoemaker Arch Surg 1973;106:630

PROSPECTIVE RANDOMIZED TRIAL, BLOOD VOLUME VS PAC MEASUREMENTS. YU ET AL, SHOCK 2011;35:220

CONTROL Blood Volume

(n=50) (n=50)

Age 63 ±16 60 ± 17 Female:Male 18:32 23:27 APACH II 24 ± 3 25 ± 4 Septic shock 28 30 Severe sepsis 6 5 ARDS 14 21 CV failure 9 6

CVP, PAOP, SvO, DO2, CI, Hct,BV, RBCV

GOALS OF TREATMENT WITHIN 24 HRS: (TRADITIONAL + TISSUE PERFUSION GOALS) • BP >100 mm Hg or within 40 mm Hg from known baseline. • Heart rate <100 beats/minute

• Urine output >0.5 ml/kg/hour • Lactate to normal values within 24 hours of resuscitation • DO2 adequate to achieve SvO2 ≥70% and (PtcO2) Oxygen Challenge test ≥25 mm Hg.

• Fluid management: Control group using PAOP, and hemoglobin/Hct

• Blood volume group: red cell volume and blood volume • BV: day 1, 2, 3, 5-7 (Control group blinded)

Control BV (n=50) (n=50) Age 63 ±16 60 ± 17 Female:Male 18:32 23:27 APACH II 24 ± 3 25 ± 4 Septic shock 28 30 Severe sepsis 6 5 ARDS 14 21 CV failure 9 6 Lactic acid (meq/L) 4.1 ±3.1 4.0 ±2.8 Creatinine clearance 48 ± 25 52± 30

CONTROL GROUP BLOOD VOLUME GROUP # of BVA 198 254 # BVA w/ Rx change 121/198 (61%) 112/254 (44%) .004 More fluid 21/198 (11%) 34/ 254 (13%) .39 Less fluid/diuresis 62/198 (31%) 56/254 (22%) .03 More red cell 53/198 (27%) 32/254 (13%) .0002 Less or no red cell 21/198 (11%) 16/254 (6%) .12 Units of red cells given 133 158 Units of red cell/patient 2.66 3.16 Favorable response 87/198 (44%) 150/254 (59%) .002 Unfavorable response 49/198 (25%) 46/254 (18%) .10 Neutral response 62/198 (31%) 58/254 (23%) <.05 Response: change of: 10 mm Hg in BP, 10 beats per minute in HR, 15% in CI or SVI (michard), 25% on vasoactive agents, 20 points in PaO2/FiO2, (jochberger), 25% in BUN or Creat)

Control BV (n=50) (n=50) PAC days 9.3 ± 5.2 8.3 ± 5.1 .57 Ventilator days 29.2 ± 33.5 23.8 ± 23.9 .38 ICU days 28.0 ± 24.6 28.7 ± 27.0 .90 Hospital days 54.7 ± 41.0 43.7 ± 31.3 .14 Mortality 13/50 (26%) 4/50 (8%) .02 Mortality 12/50 (24%) 4/50 (8%) .03 from MSOF

A TALE OF 2 VOLUMES

•CARDIAC VOLUME: SVV, PPV, RVEDV • INTRAVASCULAR VOLUME

A DEBATE WITH NO CONCLUSION UNLESS WE KNOW THE ANSWER: GUESS THE VOLUME BY MEASURING VOLUME

• RADIO-ISOTOPE STUDIES ARE EXPENSIVE, INTERMITTENT.

• IF YOU HAVE RESOURCES, CURRENT TECHNOLOGY ALLOWS THE MEASUREMENT AND GUIDES FLUID AND RED CELL MANAGEMENT

• WE NEED TO LOOK FOR BETTER WAYS OF MEASURING INTRAVASCULAR VOLUME, NOT JUST CARDIAC VOLUMES

• ICG GREEN (Japan), ultrasound techniques (CO status)……

• We have not progressed in 40 years: BP, HR, UO, lactic acid, BE…..

THE DEBATE CONTINUES

•Keep patients euvolemic…