Limitations of assessing fluid responsiveness in the perioperative period Simon Tilma Vistisen Associate Professor Department of Anesthesiology and Intensive Care, Aarhus University Hospitals, Denmark

Conflicts of interest None to declare

Agenda The (relevant) physiologic limitations to pulse pressure variation (PPV) and stroke volume variation (SVV) Briefly: What to do when encountering limitations? The mini-fluid challenge and its limitations What are the more “clinical” limitations? What can fluid responsiveness prediction not predict? Does fluid responsiveness prediction matter for patients?

Definition: Fluid responsiveness prediction Answering the question: Will flow (stroke volume and/or cardiac output) increase with volume expansion?

All the limitations Background PPV prediction Crit Care Med. 2009 Sep;37(9):2642-7

LIMITS

HR/RR ratio – the explanation Destructive interference between the “low RVSV” and the “purge effect” towards the LV

HR/RR ratio

HR/RR ratio Single study, small cohort – BUT convincing! Not confirmed – particularly not in GA

Increased abdominal pressure (laparoscopic procedures) Rationale for this limitation: Increased abdominal pressure impedes venous return (filling) Some experimental and clinical studies…

Increased abdominal pressure (laparoscopic procedures) PPV and SVV did not change with pneumoperitoneum

Increased abdominal pressure (laparoscopic procedures)

Increased abdominal pressure (laparoscopic procedures)

Increased abdominal pressure (laparoscopic procedures) For now, SVV appears useful to predict fluid responsiveness Perhaps at a slightly higher threshold (12-14%) We need more studies in this area to settle thresholds.

The tidal volume limitation Some issues… De backer et al. ICM 2005 n=15 Sens n=12 Spec 15 100 12 14 93.3 11 91.7 13 86.7 10 83.3

The tidal volume limitation

PPV proportional to tidal volume Liu et al. BMC Anesthesiology (2016) 16:75

Indexing PPV to tidal volume or driving pressure

On the other hand…

What is it with this tidal volume?!? Are we looking at the “right” data? Changes in pleural pressure changes could be the key?

Liu et al. CCM 2016, 342-351

What is your tidal volume during surgery? 6? 8? 10?

LIMITS REMEMBER: PPV is not perfect!

What to use when limitations are present? Manipulate ventilator settings Tidal volume challenge (6  8 ml/kg) (and maybe reduce RR at he same time) End-expiratory occlusion test Recruitment maneuver (Extrasystoles) Mini-fluid challenge – to be continued… Fluid challenge Vistisen et al. Curr Opin Cit Care, 2017, 318-325

The mini-fluid challenge…

What is the mini-fluid challenge? Consists of 100 ml infusion in 1 (few) minute(s) - Muller et al., Anesthesiology 2011 - Mallat et al, BJA 2015 - Guinot et al, EJA 2015 - Jacquet-Legrèze et al. AIC 2016 - Biais, Anesthesiology, 2017 - Smorenberg, j Clin Anest, 2018 Vistisen et al. Curr Opin Cit Care, 2017

How is it evaluated? MFC induced changes in hemodynamic variables Jacquet-Legrèze et al. AIC 2016 MFC induced changes in hemodynamic variables VTI (Muller et al.) PPV (Mallat et al.) SV (Guinot et al., Biais et al.) CO (Smorenberg et al.) EtCO2 (Jacquet-Legrèze et al.) Meant to predict fluid responsiveness: Hemodynamic response of the entire “normal” FC (250-500 ml)

Does it predict fluid responsiveness? MFC variable AUC Sens. Spec. Threshold Muller et al., 2011 VTI 0.92 95 78 10% Guinot et al., 2015 SV 0.93 89 7% Mallat et al., 2015 PPV 86 85 2% Jacquet-Legrèze et al, 2016 EtCO2 0.74 33 100 3% Biais et al., 2017 0.95 93 6% Smorenberg et al, 2018 CO 1 5%

Ready to endorse the mini-fluid challenge! Design issues… A self-fulfilling prophecy design? BL MFC BL2 FC Design MFC var FR var Muller BL-MFC-FC VTI Guinot BL1-MFC-BL2-FC SV Mallat PPV CO Jacquet-Legrèze EtCO2 Biais Smorenberg

A self-fulfilling prophecy design? ∆VTI500 ∆VTI400 ??? ∆VTI100 Discard the mini-fluid challenge! ∆VTI400 ~ 15% Sensitivity: 63% (95%) Specificity: 37% (78%) AUC: ???

Regression to the mean! Have I fooled you twice? ∆VTI500 ∆VTI100 ∆VTI400 VTI0 VTI100 VTI500 Measurement error and physiologic variation Regression to the mean! ∆VTI100 = VTI100 - VTI0 ∆VTI100 = VTI100 - VTI0 ∆VTI500 = VTI500 - VTI0 ∆VTI400 = VTI500 - VTI100 Sensitivity: 70% - 95% Specificity: 39% - 78%

To conclude on the mini-fluid challenge It’s an interesting approach! May limit fluid infusion There is one study with optimal design – two baselines Guinot et al., AUC: 0.93 There are two studies with suboptimal/questionable design Changes in PPV or EtCO2 (not the outcome variable) Mallat et al., AUC: 0.91 and 0.92 Jacquet-Lagrèze et al., AUC: 0.74 There are three studies that are inconclusive due to the study design (in my opinion!)

“Clinical” limitations … Fluid responsiveness prediction is answering the question: Will stroke volume increase with increased intravascular volume? It is NOT: Assessing the risk of fluid side effects Coagulation? Dilution? (Congestion?) (Edema formation?) Advising on choice of fluid type

Fluid responsiveness prediction – beneficial for patients? Hear-say evidence: “You’re drowning the patients with that monitor”

High risk surgery – GDT coupled with valid fluid responsiveness monitoring Perioperative goal-directed therapy with uncalibrated pulse contour methods: impact on fluid management and postoperative outcome, BJA,119 (1): 22–30 (2017) – with comments

High risk surgery – GDT coupled with valid fluid responsiveness monitoring Results: Post-operative morbidity Michard F et al, BJA, 2017, 22–30

High risk surgery – GDT coupled with valid fluid responsiveness monitoring Results: Colloid infusion Michard F et al, BJA, 2017, 22–30

High risk surgery – GDT coupled with valid fluid responsiveness monitoring Results: Crystalloid infusion Michard F et al, BJA, 2017, 22–30

High risk surgery – GDT coupled with valid fluid responsiveness monitoring Results: Total volume infusion Michard F et al, BJA, 2017, 22–30

Drowning patients? Perhaps some overload – if you SV MAXimize NO! If you use valid fluid responsiveness monitoring

OPTIMISE II trial – the fluid protocol https://optimiseii.org/documents, accessed 7/11-2018

Sepsis:% GA: OK Monnet and Teboul Ann. Intensive Care (2018) 8:54

Take home… PPV and SVV are good-excellent predictors of fluid responsiveness in most GA settings In laparoscopic surgery, PPV and SVV work well but perhaps not excellently and perhaps thresholds needs adjustment Tidal volume can be set at approx. 8 ml/kg (temporarily) Be aware of the HR/RR ratio limitation… A SV increase after a mini-fluid challenge of 100 ml may not merit additional 400-500 ml infusion PPV and SVV have a central role to play in the GDT framework  Prevents fluid overload! ICU and GA are not the same settings!