Fluid Responsiveness

A fluid bolus is intended to raise preload and, with it, stroke volume and oxygen delivery - but only when the ventricle is preload-dependent. Beyond the ascending limb of the Frank-Starling curve, added volume raises filling pressure, not flow.

• Fluid is first-line in most shock states; the principal exception is cardiogenic shock with pulmonary oedema. ReviewVincent J-L, De Backer D. Circulatory shock. N Engl J Med, 2013.
• Blood pressure can be maintained by vasoconstriction with no rise in flow.

The endpoint worth committing to from the outset is flow, not the pressure reading.

Roughly half of unstable patients respond to a bolus; the rest gain nothing and accumulate the fluid as oedema. Because this distinction changes management and cannot be made clinically, fluid is more safely regarded as a question to be answered than an intervention to be assumed.

• About 50% of haemodynamically unstable patients are fluid responsive. ReviewMichard F, Teboul J-L. Predicting fluid responsiveness in ICU patients. Chest, 2002.
• Examination and static filling pressures, including CVP, do not discriminate responders. ReviewMarik PE, Cavallazzi R. Does CVP predict fluid responsiveness? Crit Care Med, 2013.
• Cumulative positive fluid balance is associated with congestion and increased mortality in sepsis and ARDS. GuidelineSurviving Sepsis Campaign, 2021.

Responsiveness asks whether a bolus will raise stroke volume; tolerance asks whether the patient can accept it without driving venous and pulmonary pressures into congestion. A responsive but intolerant patient gains output at the cost of oedema, so fluid is justified only when both answers are yes.

Preload is the myocardial stretch present at end-diastole; on echo, end-diastolic cavity size is its surrogate. Stroke volume rises steeply with preload along the ascending limb of the Frank-Starling curve, then plateaus. A responder is a patient on the steep limb, where a preload challenge raises stroke volume by more than about 15%; a non-responder sits on the plateau. A true response requires both ventricles to be on the steep limb. ReviewMichard F, Teboul J-L. Chest, 2002.

• Stroke volume - measured on echo as the LVOT velocity-time integral - is the reference variable, not blood pressure or heart rate.

On the flat limb, added volume produces little extra output but still raises filling pressures, so the patient takes on the harm of fluid without the benefit - interstitial and pulmonary oedema, and venous congestion that impairs perfusion of the kidneys, gut and liver. Cumulative positive balance tracks with worse outcomes in sepsis and ARDS. GuidelineSurviving Sepsis Campaign, 2021.

The curve moves with contractility and afterload, which is why preload-dependence is a moving target. Increased contractility shifts it up and to the left; reduced contractility (sepsis, ischaemia, beta-blockade) shifts it down and to the right; increased afterload flattens it. A patient can move on and off responsiveness over hours, so it must be reassessed, not assumed. ReviewPinsky MR. Functional haemodynamic monitoring, 2015.

A static measure records loading at a single moment; a dynamic measure deliberately changes loading and watches how stroke volume responds. Because responsiveness is a question of change, dynamic measures predict it far better; static measures earn their keep only at the extremes. ReviewMichard F, Teboul J-L. Chest, 2002.

Static measures estimate preload from a single snapshot and, in most patients, predict responsiveness poorly. Only the extremes carry useful information; the cut-offs and how to measure each are covered in the Static measures section.

A small, hyperdynamic LV or a very small IVC can also occur with severely reduced afterload, so the extremes are read in context.

Every dynamic test applies a challenge that transiently changes preload, then measures the change in stroke volume (on echo, the LVOT VTI). The larger the change, the more likely the heart is on the steep limb. The tests differ only in how the challenge is delivered.

Thresholds and preconditions are in the detailed sections. In brief, the ventilator (heart-lung) indices need a passive patient in sinus rhythm with an adequate tidal volume and an intact chest; otherwise the leg raise or a mini-fluid challenge are the reliable fallback.

A measurement made under a single loading condition (usually end-expiration) to estimate preload or filling pressure — for example LVEDA, IVC diameter, CVP or PAWP.

Because preload alone does not locate the patient on the Frank–Starling curve.

• The curve's shape varies between patients, so identical filling pressures may indicate either a responder or a non-responder (Michard & Reuter, 2003).
• The failing ventricle shows limited preload-dependence.
• Intrathoracic pressure (positive-pressure ventilation) and reduced ventricular compliance distort intravascular pressures.
• CVP does not predict fluid responsiveness (Marik & Cavallazzi, meta-analysis, 2013).

Caution — it reflects elevated LV diastolic pressure.

• A poorly compliant LV may be under-filled despite high filling pressures, so it can still respond to fluid.
• The optimal filling range is narrow, and such ventricles decompensate into pulmonary oedema readily (Michard & Reuter, 2003).

• Measured in the PSAX mid-papillary view (trans-gastric short axis on TOE); volumes by the biplane method of discs (Simpson's), which underestimates true volume.

A small, hyperdynamic ventricle.

• LVEDA <10 cm² (Tousignant et al., 2000), or <6 cm²/m² indexed (Feissel et al., 2004) — consistent with overt hypovolaemia.
• End-systolic papillary apposition (“kissing papillaries”). These signs are specific but not sensitive.

Poorly — it does not track PAWP reliably and is a weak predictor of fluid responsiveness in septic and cardiac-surgical patients (Tousignant et al., 2000; Michard & Reuter, 2003).

In a spontaneously breathing patient, IVC diameter and its collapse with a sniff estimate right atrial pressure — a static pressure used principally to complete the systolic PA pressure estimate.

• (Lang et al., ASE/EACVI chamber-quantification recommendations, 2015; Rudski et al., ASE, 2010; BSE Normal Reference Intervals)

During positive-pressure ventilation (the IVC is commonly dilated and non-collapsing), and in trained athletes, in whom it may be dilated at normal pressures (Lang et al., 2015).

Only at the extremes, and even then specifically rather than sensitively:

Respiratory variation of the IVC (collapsibility / distensibility) is a dynamic measure and is addressed in Heart–lung interactions.

The septum bows away from the chamber with the higher pressure.

• Persistent bowing toward the right atrium indicates LA pressure greater than RA pressure (e.g. volume loading or raised left-sided pressures).
• Mid-systolic reversal of the normal leftward bowing indicates raised right atrial pressure.
• It is a qualitative adjunct to the IVC and is not a validated stand-alone test of fluid responsiveness.

Source notes (OneNote)

What is a static parameter of fluid responsiveness?

• A 'static' parameter is measured under a single ventricular loading condition to indirectly estimate cardiac preload, usually at end expiration to reduce the effects of heart–lung interactions.

IVC diameter variation

• Cyclical changes in intrathoracic pressure induce changes in RAP, which alter venous return. In controlled ventilation, the IVC expands in inspiration and reduces in expiration. Assess in M-mode or (better) 2D.

RAP estimation (sniff, spontaneous breathing):

• IVC <2.1 cm, collapse >50% → RAP 0–5 (3) mmHg
• IVC >2.1 cm, collapse >50% → 5–10 mmHg
• IVC >2.1 cm, collapse <50% → 10–20 (15) mmHg
• 3–8–15 scheme: RAP 3 mmHg if IVC ≤21 mm and collapse ≥50% with sniff; 15 mmHg if IVC >21 mm and collapse <50%; otherwise 8 mmHg (intermediate). [ASE/EACVI chamber quantification]
• In patients on positive pressure ventilation the IVC is commonly dilated and may not collapse, so it should not be routinely used to estimate RAP. IVC measured on TEE at the cavoatrial junction has been used to derive CVP in anaesthetised ventilated patients.

What is a dynamic parameter of fluid responsiveness?

• A 'dynamic' parameter is measured under different cardiac loading conditions which may result from heart–lung interactions (driven by pressure variations during the respiratory cycle in mechanically ventilated patients) or from postural changes (e.g. PLR).

Dynamic parameters in mechanically ventilated patients — measured at end-expiration during insufflation. Display airway pressure to identify respiratory phases. Greater variation = higher probability of FR. Must be sinus rhythm, adapted to ventilator (no inspiratory efforts), low respiratory rate, non-reduced tidal volume.

ΔSVC Collapsibility — formula: (D_max − D_min) / D_max × 100%

• SVC is intrathoracic; mechanical ventilation causes cyclical reduction of SVC size during insufflation (decreased transmural pressure). Requires TOE (transverse view qualitatively; long axis 90° for inspiratory/expiratory diameters). Vieillard-Baron (66 septic shock): ΔSVC accurately predicted FR. Lower sensitivity with more ARDS/low TV. SVC partially collapses in mechanical inspiration; collapsibility index predictive with cutoff ~36% using 100×(Dmax−Dmin)/Dmin.

Question explanations (1)

• SBA 4701 — The maximum diameter is measured during expiration and minimum diameter is measured during inspiration The effects of positive pressure ventilation on SVC diameter are opposite to those on the IVC diameter. In mechanically ventilated patients, the SVC diameter decreases during inspiration and increases during expiration. The SVC collapsibility index is not reliable during spontaneous ventilation, low tidal volume and poor lung compliance but maintains its accuracy during cardiac arrhythmias [25].

Source notes (OneNote)

Are there any static parameters that can predict fluid responsiveness?

Whilst static parameters have poor predictability, some measurements at the extremes are predictive:

• Hyperdynamic LV with papillary apposition, OR LVEDA of less than 10 cm² (in PSAX)
• Small IVC <1 cm with more than 50% collapse

However these may also be seen in settings of severely reduced afterload.

ΔIVC Collapsibility (spontaneous breathing) — IVC variability/collapsibility validated as measure of FR in spontaneously breathing patients; one study IVC variability >42% suggested FR. Lanspa et al (Shock 2013).

Question explanations (5)

• SBA 4682 — Fluid responsiveness cannot be established, need additional information. IVC diameter in a spontaneously breathing patient is a good tool to non-invasively estimate right atrial pressure (RAP). However, RAP is a static parameter of cardiac preload and does not accurately predict response to fluid administration [8, 9]. IVC variability or collapsibility has been validated in multiple studies as measure of fluid responsiveness in spontaneously breathing patients. In one study, IVC variability of >42% was found to suggest fluid responsiveness, which was also not the case here [10].
• SBA 4698 — Estimated RAP is 3 mmHg Right atrial pressure is typically estimated based on IVC diameter and response to a sniff test. The maximum IVC diameter is measured from M-mode or 2D in the subcostal view, 1–2 cm from IVC–RA junction. Estimated RAP (mmHg) IVC diameter (cm) Collapsibility (%) IVC <2.1 >50 3 IVC diameter (cm) Collapsibility (%) Estimated RAP (mmHg) IVC >2.1 >50 8 IVC <2.1 ≤50 IVC >2.1 <50 15
• SBA 4704 — Right atrial pressure is >10 mmHg Echocardiographic measurements of the IVC are commonly used to estimate right atrial pressure. Current guidelines recommend size and variability during an inspiratory sniff to estimate RAP—Table. Brennan assessed echocardiographic measures of the IVC to estimate right atrial pressure both during quite breathing and an inspiratory sniff. In quite breathing, a cut-off of 20% in the IVC collapsibility index was able to accurately predict a right atrial pressure over 10 mmHg—answer C is correct. Collapse during sniff (%) >50 IVC diameter Estimated RAP (mmHg) <2.1 0–5 >2.1 cm >50 5–10 >2.1 cm <50 10–20 _[…1 non-FR sentence(s) trimmed]_
• SBA 4876 — In a normal bladder with a Foley catheter there is no anechoic space seen around the catheter as the bladder is drained and empty. If the Foley catheter or bulb is visualized surrounded by anechoic space (fluid) then the likely cause is an obstructed Foley catheter; this should be flushed or replaced. If the bladder is visualized collapsed around the Foley catheter and patient is anuric; this would be indicative of a more proximal problem or absence of urine production (intrinsic renal or pre-renal etiology) [1, 3]. _[…12 non-FR sentence(s) trimmed]_
• SBA 4959 — No DVT. The image of this patient demonstrates and pre and post compression view of the femoral vein demonstrating complete collapsibility. Normal veins are thin walled, anechoic and collapsible as demonstrated by complete obliteration of the vessel and apposition of the vessel walls with compression. Presuming collapsibility throughout the deep venous system, an acute DVT can be confidently excluded. An acute thrombus will often appear as echogenic material within the vessel that prevents collapsibility. While the patent portion of the vessel lumen in an acute or chronic thrombus may collapse, there will be no apposition of the vessel walls [11]. _[…1 non-FR sentence(s) trimmed]_

Source notes (OneNote)

Pitfalls of great vein variations — with respiration the IVC can move out of the US beam plane, faking diameter change; keep both walls in view. Spontaneous breathing and TV <8 mL/kg may invalidate. Arrhythmia less confounding for IVC than for LV outflow variation.

Question explanations (1)

• SBA 4639 — The patient is unlikely to be volume responsive, as there is no respiratory variation. IVC distensibility(dIVC) index more than 18% predicts volume responsiveness. The use of IVC for volume responsiveness has been validated for patients who are on mechanical ventilation (caveat is that the patients in this study were on an average of 8.5 cc/kg tidal volume of ideal body weight). The M-Mode image of this patient does not demonstrate any respiratory variation. The Distensibility Index of the IVC(dIVC) should be used if there is variability noted (Dmax-Dmin/Dmin). [7, 8].

Question explanations (1)

• SBA 4700 — Position 2; 36% The ultrasound examination of the SVC collapsibility and fluid responsiveness by TEE is performed by measuring SVC diameter variations in a longitudinal view focused on the mid-esophageal bicaval view. The collapsibility index (CI) = (SVC max − SVC min) × 100/SVC max, of greater than 36% was predictive of preload responsiveness with a sensitivity of 90% and specificity of 100% [27].

Question explanations (1)

• SBA 4689 — LVOT VTI is accurately estimated by using high sweep speed and reduced gain. Stroke volume measurement by echocardiography is an essential variable in the assessment of unstable critically ill patients. It is determined by measuring the LV outflow tract diameter and LVOT velocity time integral using the following formula: the following formula: SV = LVOTVTI × πr^2. The LVOT diameter is measured at the aortic valve cusps in zoomed parasternal long axis view in mid-systole. The PW Doppler is set at high speed, low filters and reduced gain for accurate assessment of LVOT-VTI. In patients with atrial fibrillation, five to seven LVOTVTI measurements should be averaged, preferably at the same time of respiratory cycle.

Source notes (OneNote)

If the right ventricle is preload-dependent, the decrease in its preload during mechanical insufflation should result in a decreased right ventricular stroke volume at the same time and thus in a decreased left ventricular preload during expiration due to the pulmonary transit time. This can in turn induce a decrease in left ventricular stroke volume if the left ventricle is preload-dependent. Therefore, the more the left ventricular stroke volume and the pulse pressure change during the mechanical ventilation cycle, the more likely the patient's heart is preload-dependent and hence, the patient is fluid responsive. If one of the two ventricles is preload-independent, mechanical ventilation-induced changes in right ventricular preload do not result in significant changes in left ventricular stroke volume so that PPV is low. Many clinical studies confirmed the validity of these hypotheses in different clinical settings, although several limitations exist in critically ill patients, the most frequent ones being low tidal volume ventilation, persistent spontaneous breathing activity, and cardiac arrhythmia.

Because LV stroke volume is a major determinant of systolic arterial pressure, analysis of respiratory changes in systolic pressure has been proposed to assess respiratory changes in LV stroke volume during mechanical ventilation. In 1983, Coyle et al proposed that the respiratory changes in systolic pressure could be analyzed by calculating the difference between the maximal and the minimal value of systolic pressure over a single respiratory cycle ('systolic pressure variation', SPV) divided into two components (Δup and Δdown), calculated using a reference systolic pressure measured during an end-expiratory pause.

ΔLVOT VTI & ΔLVOT Vpeak

• ΔVpeak formula: (V_max − V_min) / V_mean × 100%
• ΔVTI formula: (VTI_max − VTI_min) / VTI_mean × 100%
• In absence of aortic valvulopathy, LVOT VTI reflects stroke volume → cardiac output. Cyclical variations of LVOT Doppler VTI (or peak velocities) under PPV identify fluid responders (Feissel et al, 19 septic shock patients: ΔVpeak accurate to predict FR; blood volume expansion increased cardiac index correlated with ΔVpeak). Validated in ventilated children. Slama et al (experimental): ΔVTI during stepwise blood withdrawal/restitution a reliable indicator of volume depletion. Biais et al: ΔVTI accurately predicted FR in ventilated patients without respiratory activity.

Utility of SVV limited in: small tidal volumes (must be ≥8 mL/kg); spontaneous breathing (must be 100% controlled at fixed rate); ARDS / low lung compliance (false negatives); PEEP (may increase SVV); arrhythmia (R-R must be regular); low HR/RR ratio; open chest; RV systolic dysfunction; norepinephrine (may decrease SVV); vasodilators (may increase SVV); beta-blockers.

PPV mechanism — transmission of airway pressure to pleural and pericardial spaces induces changes in venous return and cardiac preload. Conditions where transmission is limited (low TV, low compliance as in ARDS, stiff chest wall) lead to false-negative PPV.

Question explanations (5)

• SBA 4686 — PPV cannot be used in patients with low lung compliance Pulsed pressure variation is caused by the transmission of airway pressure to the pleural and pericardial spaces, which induces changes in venous return and cardiac preload. Conditions where transmission of airway pressures is limited could lead to false negative PPV. This could be due to use of low tidal volumes or in lungs that have low compliance like in ARDS. Transmission of intrapulmoary pressure to the mediastinum and thus the heart is decreased in conditions with increased lung stiffness (ARDS, pulmnary fibrosis) and further accentuated by increased chest wall stiffness. Therefore, during low tidal volume ventilation in ARDS, even though the driving pressure is high, the transmission of these pressure through the stiff lung is lower which in turn leads to less PPV [18–20].
• SBA 4692 — A hyperdynamic left ventricle. Static parameters have poor predictability for fluid responsiveness. A hyperdynamic LV with papillary apposition on PSAX view, a LVEDA of less than 10 cm² and small IVC <1 cm with more than 50% collapse are strong echocardiographic markers of reduced filling pressure, but may also occur in setting of reduced afterload. VTI change in spontaneously breathing patients may be a reflection of respiratory efforts rather than fluid responsiveness and thus is not reliable. E-point septal separation (EPSS) has classically been used for estimation of LVEF and cardiac function and is not validated for fluid responsiveness. IVC collapsibility index ≥15% and stroke volume variation ≥17% and greater suggest fluid responsiveness in spontaneously breathing patient.
• SBA 4694 — The sensitivity and specificity of SVV in mechanically ventilated patients are more than 80% with area under ROC >0.9 The aortic flow velocity variation parameters have good specificity and sensitivity of more than 80% with area under ROC curve >0.9. A flow variation across the LVOT of >12% is predictive of fluid responsiveness. They are, however, not accurate in the setting of arrhythmias and low tidal volume. Significant variation in VTI may be related to the arrhythmia and low tidal volume ventilation <8 mL/kg IBW may cause small changes in VTI and responsible for false negative results.
• SBA 4696 — Respiratory variations of the maximal Doppler velocity in left ventricular outflow tract had the better overall sensitivity. In a multicenter prospective study conducted in France, various echocardiographic parameters used to predict fluid responsiveness were compared. Respiratory variations of the maximal Doppler velocity in left ventricular outflow tract (ΔVmax Ao >10%) had the best sensitivity and respiratory variations of superior vena cava diameter (ΔSVC >21%) had the best specificity. Both the aforementioned indices fared better than in inferior vena cava diameter changes and pulse pressure variation [25]. _[…1 non-FR sentence(s) trimmed]_
• SBA 4705 — Right atrial pressure is undetermined. Using IVC collapsibility to assess central venous pressure assumes a drop in intra-thoracic pressure with inspiration. In a patient on PPV, it is not possible to estimate the changes in pleural pressure induced by patient effort due to presence of positive pressure throughout the respiratory cycle. Size and variability should not be used to assess right atrial pressure in patients on positive pressure ventilation [32, 34]. _[…1 non-FR sentence(s) trimmed]_

Question explanations (2)

• SBA 4702 — The respiratory variations of flow are normal respiratory variation The values show normal respirophasic variation in flow. Under normal circumstances, peak velocity of tricuspid inflow varies by up to 25%, mitral inflow varies by up to 15%. Peak velocity and time velocity integral of aortic and pulmonary flow profiles vary by up to 10% with normal respiration [28–30].
• SBA 4703 — In spontaneous breathing, the diameter of the extra thoracic IVC decreases during inspiration. Respiro-phasic variation of the diameter of the vena cava are related to the changes of transmural pressure (intravascular pressure − extravascular pressure) throughout the respiratory cycle. Since the SVC is located within the thoracic cavity, a decrease in pleural pressure during active inspiration in spontaneous breathing will increase transmural pressure and increase SVC diameter. During PPV, pleural pressure rises during inspiration leading to decreased transmural pressure and a decrease in SVC diameter. The transmural pressure of the extrathoracic IVC is determined by the central venous pressure (intravascular pressure) and the abdominal pressure (extravascular pressure). In spontaneous breathing, the pleural pressure and thereby central venous pressures drops during inspiration, while abdominal pressure increases. This leads to a decrease in transmural pressure and a decrease in IVC diameter during inspiration. In PPV, pleural pressure rises during inspiration leading to an increased intravascular pressure. Abdominal pressure may also increase albeit to a lesser extent, leading to a net increase in transmural pressure and an increase in IVC diameter. It is important to note that the degree of respirophasic variations of vena cava diameter is highly variable depending on fluid status, central venous pressure, respiratory effort, lung compliance and abdominal pressure. In hypovolemia the effect is exaggerated whereas respiratory variations may be blunted or absent in hypervolemia. _[…1 non-FR sentence(s) trimmed]_

Source notes (OneNote)

Pitfalls of LVEDV / LVEDA to predict FR:

• Lack of sensitivity (surrogate for filling pressure; filling pressures don't accurately predict FR due to individual Frank-Starling differences).
• LV cavity size may be intrinsically altered by: ventricular remodelling (hypertrophic, infiltrative, dilated cardiomyopathy); restriction by stiff pericardium, acute cor pulmonale, or tamponade.
• LVEDA measured in short-axis. Reproducible, good correlation with LV end-diastolic volume. Mean reference LVEDA 23 ± 4 cm² (range 15–34 cm²); indexed 13 ± 2 cm²/m². In ICU septic patients and during cardiac surgery, LVEDA is a poor predictor for FR. Overt hypovolaemia: LVEDA <10 cm² or <6 cm²/m². Cut-offs specific but lack sensitivity. End-systolic obliteration not consistently associated with reduced preload (also influenced by contractility and afterload).

False positives (PPV):

• RV dysfunction: inspiration increases RV afterload → decreased RV ejection during mechanical ventilation → high PPV due to afterload variation (false-positive PPV).
• LIMITS acronym (PPV/SVV limitations): Low heart rate/respiratory rate ratio (false negatives), Irregular heartbeats (false positives), Mechanical ventilation with low tidal volume (false negatives), Increased abdominal pressure (false positives), Thorax open (false negatives), Spontaneous breathing (false positives).
• Other false-positive settings: tamponade, constrictive pericarditis, LV dysfunction, massive PE, bronchospasm.

Question explanations (5)

• SBA 4680 — Decrease the PEEP, inhaled pulmonary vasodilators The video shows significant bubbles appearing on the left side of heart, confirming an intra-cardiac shunt (Video 12.2). PEEP applied during mechanical ventilation increases RAP. Higher levels of PEEP increases lung volume from functional residual capacity (FRC) to total lung capacity. This increase in FRC leads to an increase in intra thoracic pressure and increased pericardial, myocardial, and pulmonary vascular transmural pressures. The RV afterload is increased due to increased pulmonary vascular resistance. This combination leads to increased RV pressure and RAP, causing the shunting of blood across the PFO [4, 5]. Decreasing PEEP and inhaled pulmonary vasodilators will decrease the RV afterload decreasing the right sided pressures, thereby reducing the right to left shunt across the PFO. _[…2 non-FR sentence(s) trimmed]_
• SBA 4802 — This patient with ARDS is being ventilated with low tidal volume, high FiO₂ and high PEEP pressures. The presence of significant B lines suggests inadequate lung recruitment on lung ultrasound images. In patients such as these, the effects of high airway pressures on RV preload and afterload can contribute to hemodynamic instability and RV failure. In this patient, the echocardiography image shows an increased RVEDA: LVEDA >1 and depressed RV FAC < 35%, consistent with acute cor-pulmonale. RVFAC is defined as RV end diastolic area (RV EDA) minus RV endsystolic area (RV ESA), all divided by RV EDA (FAC = (RVEDA-RVESA)/RVEDA). Increasing PEEP (choice B) would likely worsen the RV afterload by raising the mean airway pressure. A fluid bolus (choice C) is unlikely to improve hypotension in this patient since the most likely cause of hypotension is RV dysfunction in the setting of acute cor pulmonale. In this patient, VV ECMO is indicated to provide adequate ventilation while allowing for lower airway pressures and improved RV afterload (Fig. _[…5 non-FR sentence(s) trimmed]_
• SBA 4807 — This patient has ARDS pathology and initially demonstrates ultrasound findings consistent with insufficient lung recruitment. The physiologic impact of over distended lungs is increased RV afterload. This occurs from compression of intra-parenchymal pulmonary vessels when lung is over distended and can cause hemodynamic instability as well as echocardiographic findings consistent with RV dysfunction and acute cor-pulmonale. Neither fluid bolus (Choice C) nor neuromuscular blockade (choice D) have shown any benefit in improving acute cor pulmonale in patients with ARDS. _[…8 non-FR sentence(s) trimmed]_
• SBA 5096 — Obstructive shock Acute Cor pulmonale or acute right heart failure can result from increased resistance in the pulmonary circulation or direct injury to myocardium. Parasternal short axis view shows dilated right ventricle with septal flattening, suggesting RV pressure overload. _[…3 non-FR sentence(s) trimmed]_
• SBA 5105 — TAPSE. The cause of hemodynamic instability is probably caused by RV failure as evidenced by a dilated RV, and septal flattening which are echocardiographic signs of RV dysfunction. _[…6 non-FR sentence(s) trimmed]_

Source notes (OneNote)

In ARDS with high PEEP, a high PPV might relate to RV failure / afterload dependence rather than FR. Suggested check: assess PPV during PLR — if no change, high PPV indicates RV afterload dependence; if PPV decreases, suggests FR.

How should a PLR be performed?

• Raise lower extremities to 45° from a semi-recumbent position of 45°. Measure cardiac output (or surrogate) before and 1 min after. Mobilises ~300 mL from lower extremities to heart, simulating fluid administration without IV fluid. Change in CO measured via change in LVOT-VTI. ≥10% increase in LVOT-VTI = positive (≈10% increase in CO). Validated, widely accepted. Particularly helpful when respiratory variation of SV is unreliable: spontaneous breathing, arrhythmias, low tidal volume, low lung compliance.

How does PLR work?

• Reversible transfer of venous blood from lower body to central circulation (~300 mL fluid bolus equivalent). PLR-induced increase in CO or derivatives more accurate than changes in arterial pulse pressure. Augments preload within a minute. LVOT surface unchanged during PLR so induced VTI increase reflects LV stroke volume change.
• Pain, discomfort, cough, awakening cause sympathetic stimulation → tachycardia → mistaken CO change. Precautions: inform patient; adjust bed (don't manually raise legs); careful tracheal suctioning before; monitor heart rate.
• Remained valid in ventilated patients with breathing activity or non-sinus rhythm. A 90° rotation from semi-recumbent (trunk 45°) gives greater preload increase.

Question explanations (8)

• SBA 4683 — Fluid challenge with lactated ringer’s and assess the response. The passive leg raise test consists of raising the lower extremities to 45° from a semi-recumbent position of 45°. Cardiac output or surrogates of cardiac output are measured before the maneuver and 1 min after the maneuver. This maneuver mobilizes around 300 mL of blood from the lower extremities to the heart, simulating fluid administration without the need of IV fluid administration. Change in cardiac output can be reliably measured by assessing the change in LVOT-VTI. An increase in LVOT-VTI of 10% with positive leg raise is consistent with increase in cardiac output of 10% and is considered as a positive. Positive response of LVOT- VTI to the passive leg raise maneuver has been validated and is a widely accepted method to assess fluid responsiveness [11, 12]. The PLR is particularly helpful in conditions where respiratory variation of stroke volume is unreliable, such as spontaneous breathing, cardiac arrhythmias, low tidal volume ventilation and low lung compliance [13].
• SBA 4430 — Increase in E/e′ with a fluid bolus or passive leg raising can help identify patients who may be non-responders to volume loading. This is a patient with known history of diastolic dysfunction who remains hypotensive despite receiving intravenous fluid resuscitation. Although the presence of diastolic dysfunction does not preclude the use of intravenous fluids, clinicians should be cognizant of the dangers of volume loading in this patient population. With passive leg raising, diastolic dysfunction has worsened and the E/e′ has increased accordingly. These findings are helpful in identifying non-responders who are no longer volume responsive. Therefore, further fluid loading may be detrimental in this patient (Option A is incorrect). Norepinephrine would be the first line vasopressor of choice in this patient with septic shock who is no longer volume responsive (Option C is correct). _[…2 non-FR sentence(s) trimmed]_
• SBA 4445 — Ar (~70 ms), or the duration of the Atrial wave in the pulmonary vein pulse Doppler images indicates the duration of retrograde flow during atrial systole. ‘A’ duration (~30 ms, is the length of time the atria contraction results in Doppler. Diastolic dysfunction is highly prevalent in the intensive care unit, risk factors include age, hypertension, ischemic heart disease, valvular heart disease and diabetes mellitus. Diastolic dysfunction is almost invariably present in those patients with systolic dysfunction. However, in patients with preserved ejection fraction, diastolic dysfunction is often overlooked as a cause of decompensation. Due to the deviation in the left ventricular pressure-volume curve, patients with diastolic dysfunction are sensitive to small changes in afterload/preload leading to exaggerated responses in left ventricular pressure. Acute pulmonary edema can be precipitated by volume overload, tachycardia, dysrhythmias, and hypertensive crisis. Mitral inflow velocities show characteristic early (E) and late diastolic filling waves (A). With increasing severity of diastolic dysfunction there is a predictable progression through the various stages of diastolic dysfunction from Grade 1 (impaired relaxation) to Grade 2 (pseudonormal pattern) to Grade 3 (restrictive filling pattern). Mitral annular tissue Doppler velocities (e′), mitral inflow velocities (E, A, deceleration time, E/A ratio), left atrial volume index, and tricuspid regurgitant velocity are all important diastolic parameters that help in grading the severity of diastolic dysfunction and estimating left atrial pressures. Elevated E/e′ ratios >14 have a high specificity for increased LV filling pressures and has been validated against mean PCWP 7. Diastolic parameters may change between different grades along the diastolic continuum in response to changes in afterload and preload. This can be demonstrated after therapeutic interventions such as volume loading, volume removal, and afterload reduction. The Valsalva is a simple maneuver that can impede venous return, decrease preload and cardiac filling that helps distinguish normal diastolic function from pseudonormal pattern. Diastolic assessment in atrial fibrillation is challenging and characterized by lack of A-waves, however, high E wave velocities, short deceleration times, presence of a mitral L-wave, Low e′, high E/e′ ratio, and lack of variability of E wave despite irregular R-R intervals are all signs consistent with increased left atrial pressures. Increase in E/e′ ratio in response to a fluid bolus or passive leg raise may identify non-responders. Similarly, high E/e′ in response to a spontaneous breathing trial may identify patients likely to fail a weaning trial or used to diagnose weaning induced cardiogenic pulmonary edema. Diastolic dysfunction plays an important role in prognostication, evidence of severe dysfunction is associated with worse outcomes in the intensive care unit population. _[…14 non-FR sentence(s) trimmed]_
• SBA 4630 — The PW doppler angle is markedly different in the two images. The Pre-PLR image has a PW angle of interrogation that is >20° as compared to the post- PLR image, which is close to 0°. It is essential to keep the angle and site of interrogation consistent for pre and post-intervention VTI measurements as this error can lead to erroneous conclusions. Volume responsiveness can be assessed by volume administration or passive leg raise with a pre and post VTI measurement. Volume responsiveness is defined by a 10–15% increase in VTI or cardiac output in response to a passive leg raise and fluid bolus respectively. The use of PLR with LVOT VTI has been validated in spontaneously breathing patients [2, 11] (Figs. _[…1 non-FR sentence(s) trimmed]_
• SBA 4631 — This patient is high risk for extubation failure due to cardiac dysfunction. Based upon the lack of VTI change with PLR, the patient is likely on the flat portion of the Frank-Starling Curve and at risk for elevated pulmonary hydrostatic pressures if Left Ventricle (LV) preload or afterload increases. Removal of positive pressure increases venous return and increases LV afterload, which can contribute to worsened respiratory mechanics upon extubation and predisposing to reintubation. The high E/e′ is persuasive evidence for elevated LAP and has been shown to predict extubation failure. There would have been an increase in VTI with PLR if the patient was on the steep portion of the Frank-Starling Curve [12–14] (Figs. _[…2 non-FR sentence(s) trimmed]_
• SBA 4643 — Distributive Shock. This patient had a PLR performed with LVOT VTI as the surrogate for stroke volume, and there was minimal change. Given the lack of VTI response with the PLR, the patient is not likely to be volume responsive; therefore, they may not benefit from additional fluids. In hypovolemic shock patient’s VTI should significantly respond to PLR. Cardiogenic shock is unlikely as the VTI would likely be low. [1, 31].
• SBA 4652 — A patient is deemed to be “volume responsive ” if the administration of intravenous fluids improves cardiac output by optimizing myocardial function consistent with the Frank-Starling law. Stroke volume will increase with increased venous return until the ventricle is stretched to a specific limit, and further fluids will not improve stroke volume, cardiac output, and oxygen delivery. Mean arterial pressure (MAP) is often used to determine volume responsiveness but is proportional to flow only for a given systemic vascular resistance (SVR). Preload measures such as central venous pressure (CVP), pulmonary capillary wedge pressure (PCWP), and ventricle volumes influence myocardial contractility depending on the patient’s physiologic position on the Frank-Starling curve. However, these static parameters do not reliably predict volume responsiveness (Answer A is incorrect). Stroke volume (SV) can be measured via the left ventricular outflow tract velocity time integral (VTI) multiplied by the cross-sectional area of the left ventricular outflow tract (LVOT). SV LVOTVTI CSA = ()× () = CSA pr The cross-sectional area of the LVOT does not vary significantly through the respiratory cycle or with changes in preload. Therefore, a single measurement should suffice when calculating changes in stroke volume (Answer B is incorrect). Stroke volume increase greater than 12–15% with 250–500 cc crystalloid or with passive leg raise is associated with volume responsiveness (Answer D is correct) [36, 37]. _[…1 non-FR sentence(s) trimmed]_
• SBA 5125 — Aortic peak velocity and VTI variation >12– 14% correlates with volume responsiveness. Passive leg raise (PLR) is a none invasive maneuver that can be done at bedside to assess responsiveness to IV fluid bolus. LVOT VTI is expected to increase with PLR. The other echocardiographic finding which correlates with volume responsiveness is aortic peak velocity variation. Aortic peak velocity of pulse wave (PW) doppler with respiration variation of >12–14% in a passive state like our patient who’s paralyzed with neuromuscular blockade correlates with volume responsiveness. On another note, volume responsiveness does not always mean necessity of IV fluid administration. Other clinical findings should be considered once initial volume expansion is achieved. _[…1 non-FR sentence(s) trimmed]_

Source notes (OneNote)

PLR thresholds (table):

• ΔVTI LVOT with 30° PLR: 12% — sens 69%, spec 89%
• ΔVTI LVOT with 45° PLR: 12.5% — sens 81%, spec 93%
• ΔVTI LVOT with 90° PLR: 10–13% — sens 77–100%, spec 80–100%
• Keep PW Doppler angle and site consistent pre/post (angle of interrogation should be near 0°; >20° error invalidates). Volume responsiveness defined by 10–15% increase in VTI or CO. PLR with LVOT VTI validated in spontaneously breathing patients.

Question explanations (2)

• SBA 4690 — Cardiac arrhythmias are not a major limitation of the use of passive leg raising The passive leg raising (PLR) test has been shown to reliably detect preload responsiveness in both spontaneously breathing and mechanically ventilated patients. Stroke volume is measured 1-min post PLR. The cutoff value the most frequently found to predict fluid responsiveness with good sensitivity and specificity was 10%. _[…3 non-FR sentence(s) trimmed]_
• SBA 4699 — In a meta-analysis, the pooled sensitivity and specificity of respiratory variation of the IVC in predicting preload responsiveness are 76% and 86% respectively. The IVC diameter variation induced by the cyclical changes in intra-thoracic pressure during mechanical ventilation is used to predict preload responsiveness. During controlled mechanical ventilation (no spontaneous breathing), the IVC dilates during inspiration and collapses in expiration. The IVC diameter is measured with transthoracic echocardiography just distal to the hepatic vein, preferably in 2D or in M-mode with the vessel perpendicular to the US beam. The IVC can also be visualized with TEE in bicaval view. In a metanalysis of 8 studies assessing the accuracy of respiratory variation of IVC diameter (ΔIVC) in predicting preload responsiveness, the pooled sensitivity was 0.76 and pooled specificity was 0.86. The ΔIVC performed better in mechanically ventilated than spontaneously breathing patients. The ΔIVC has the same limitation than PPV and SVV, however, it can be used in patients with arrhythmias [26].

Source notes (OneNote)

SV variation: conditions to be satisfied

1. Sinus Rhythm 2. Tidal volumes >8 ml/kg 3. Normal intra-abdominal pressure 4. Intact thorax

Which preconditions must be met to use variations as a predictor of FR?

• Patient must be mechanically ventilated
• Patient must have no spontaneous respiratory effort (no negative intrathoracic pressure should interrupt mandatory PPV)
• Patient must be in sinus rhythm
• Tidal volumes should be >7 ml/kg (lower TV may give false negatives)
• Intra-abdominal pressure has to be normal
• Thorax cavity has to be intact

During a one-day prevalence study, only 6 of 316 ventilated patients (2%) fulfilled prerequisites to use ΔPP. When preconditions are met, these tests have a very high positive predictive value.

Limitations of dynamic indices:

• Multiple pre-conditions restrict usefulness in much of the ICU population.
• Confounders: high respiratory rates decrease ΔPP and ΔVTI (poorly predictive when HR/RR ratio ≤3.6 — De Backer). Low lung compliance (Crs <30 cmH₂O) reduces airway pressure transmission and decreases cyclic effects (Monnet, ARDS). Failing RV is sensitive to afterload, less to preload: tricuspid annulus systolic velocity <15 cm/s identifies false-positive ΔPP; acute cor pulmonale increases ΔPP (ACP in 22% of moderate-to-severe ARDS). PLR limitations: cannot be used when position change impossible (limb/pelvic fractures, surgery), or with elevated ICP; increased intra-abdominal pressure (≥16 mmHg) is a good predictor of false-negative PLR.

Pitfalls of using LV outflow variation — valid only with: sinus rhythm; no spontaneous respiratory effort; tidal volumes ~8 mL/kg (lower causes false negatives); normal intra-abdominal pressure; intact thorax.

ΔIVC distensibility — formulae:

• (D_max − D_min) / D_mean × 100% → threshold >12%
• (D_max − D_min) / D_min × 100% → threshold >18%
• IVC is intra-abdominal; during insufflation transmural pressure tends to increase so IVC size increases (opposite to spontaneous breathing). TTE subcostal, strict longitudinal view, 1–2 cm upstream of RA junction. Barbier/Feissel: ΔIVC 18% and 12% predicted FR with accuracy >90%; ΔIVC correlated with cardiac output increase. ΔSVC better than ΔIVC in ventilated septic shock.

Question explanations (8)

• SBA 4685 — Increase norepinephrine Pulse pressure variation is a method of determining fluid responsiveness in intubated patients. It works on the premise of changing stroke volume with insufflation of the lungs. The increase in intrathoracic pressure during inspiration leads to decrease in venous return to the right atrium, thereby leading to reduced right ventricular (RV) preload. Insufflation during inspiration also increases RV afterload because of the increase in transpulmonary pressure during inspiration. As a result, RV stroke volume decreases during inspiration and is minimal at the end-inspiration. The inspiratory decrease in RV stroke volume leads to a decrease in left ventricular (LV) filling after a phase lag of two to four heartbeats due to the blood pulmonary transit time. This generally occurs during expiration. This cyclical change in LV stroke volume because of reduction in RV stroke volume leads to PPV in patients whose right ventricle is pre-load dependent and whose LV is fluid responsive. However, a failing RV is more sensitive to afterload changes than to preload changes. Increased afterload leads to decrease in RV stroke volume which in turn leads to decrease in LV stroke volume. In addition, in cases of severe RV pressure overload, increased RV afterload during mechanical inspiration leads to a leftward shift of the intraventricular septum, further decreasing LV diastolic filling and thus stroke volume. This leads to a significant respirophasic variation of LV stroke volume and PPV. This, however, is “false positive PPV”. Other conditions that can lead to false positive PPV are cardiac arrhythmias, intraabdominal hypertension and vigorous spontaneous breathing especially in patients with obstructive lung disease [17].
• SBA 4691 — Patient with severe necrotizing pancreatitis and IAP >20 mmHg The great advantage of the PLR test compared to other dynamic parameters, i.e., PPV, SVV, is that it maintains its accuracy in patients with cardiac arrhythmias, low lung compliance and during spontaneous breathing and ventilation with low tidal volume. The most important limitations are inability to measure the cardiac output in “real time” and increased intra-abdominal hypertension.
• SBA 4695 — Very high respiratory rate could be responsible for false negative results SVV is a well-established echocardiographic parameter for assessing fluid responsiveness in the right settings. _[…1 non-FR sentence(s) trimmed]_
• SBA 4627 — IVC size and variation has been studied extensively in spontaneously breathing patients with conflicting data. In the extremes of ultrasound findings, a fully collapsible or a dilated IVC, there may be a role for the use of the IVC in clinical determination of volume responsiveness, but not as an isolated data point. The determinants of IVC size and variation include cardiac function, intraabdominal pressure, intrathoracic pressure, and venous return. Therefore, to determine intravascular volume purely from the IVC is overly simplistic. IVC distensibility index is validated for use in patients who are on mechanical ventilation though it was studied with tidal volumes 8–10 cc/kg/ IBW. Clinical context should be taken into account when using IVC ultrasound for volume assessment and responsiveness [5–7].
• SBA 4628 — The use of IVC for volume responsiveness has been validated in patients who are on passive on mechanical ventilation on 8–10 cc/kg tidal volume and in normal heart rhythm. The M-Mode image of this patient does not demonstrate any respiratory variation (IVC with no respiratory variation). The Distensibility index of the IVC(dIVC) is calculated as (Dmax − Dmin/Dmin). dIVC below 18% predicts a lack of volume responsiveness. IVC measurements have not been conclusively shown to predict volume responsiveness in spontaneously breathing patients. Intrabdominal hypertension may affect IVC size and variability affecting the validity of measurements [7–9].
• SBA 4638 — The LVOT VTI variation in this patient on passive mechanical ventilation with appropriate tidal volume is >14%. However, these results should be interpreted with caution as RV failure is associated with false positive LVOT VTI variation. LVOT VTI variation is calculated as (VTImax–VTImin)/ [(VTImax–VTImin)/2] 100%. Prerequisites to use Heart lung interaction method for volume responsiveness assessment are below: 1. Tidal volumes of 8–10 mL/kg. _[…11 non-FR sentence(s) trimmed]_
• SBA 4653 — The inferior vena cava (IVC) is a compliant vessel whose size varies with changes in CVP and intravascular volume. When the IVC is continuous with the right atrium, CVP is considered equivalent to right atrial pressure (RAP). External factors such as body position, negative intrathoracic pressures, and increased intra-abdominal pressures can influence the size and respiratory variation of the IVC (Answers A and C are incorrect). In young athletes, the IVC often has larger diameters than non-trained counterparts, thus limiting the reliability as a measurement of CVP (Answer B is incorrect). In the absence of these external factors, IVC diameter and respiratory variation or sniff testing can be used to estimate CVP (Answer D is incorrect) [38, 39].
• SBA 4776 — A dilated IVC is common in patients with pulmonary hypertension due to chronically elevated right atrial pressures. In patients with pulmonary hypertension, a dilated and non-collapsible IVC does not help to clarify decisions regarding volume manageof the inferior vena cava ment (choice A). IVC collapsibility is a reasonable predictor of right atrial pressure, but overreliance on this interpretation can lead to errors in determining whether or not a patient would benefit from IV fluids or diuresis. There are numerous other factors in spontaneously breathing patients than can confound interpretation of IVC measurements, including heavy breathing, variable patient effort on a ventilator, intraabdominal hypertension, and cirrhosis. Therefore, IVC measurement in isolation should not be used to guide fluid administration (choice B) or the need for diuresis (choice C), but rather should be integrated as part of the clinical picture. Adjunctive methods of volume responsiveness assessment should be employed to help guide decision-making. The IVC can be mistaken for the abdominal aorta, leading to measurement error (choice D). Confirmation that the image is indeed the IVC can be done by observing the hepatic vein draining into it, and by observing subsequent entry into the right atrium. IVC may appear pulsatile in patient with severe tricuspid regurgitation, a common finding in advance pulmonary hypertension, making this an unhelpful distinction.

Source notes (OneNote)

Which echo techniques can be used to assess fluid responsiveness?

• Static Measures:
  • End-diastolic ventricular volumes, area and diameters
  • IVC diameter/collapsibility
• Dynamic Measures — Based upon variations due to heart-lung interactions:
  • Stroke volume variation* (*mechanically ventilated patients only)
  • LVOT maximum velocity variation*
  • LVOT VTI variation*
  • Collapsibility index of IVC
  • Distensibility index of IVC / SVC*
• Dynamic — Based upon changes following passive leg raise (PLR):
  • Increase in stroke volume
  • Increase in LVOT maximum velocity
  • Increase in LVOT VTI
• Dynamic — Based upon changes following End Expiratory Occlusion Test (EEOT)

Refs: Monnet (ICM 2015), Zhang (UMB), Vignon (AJRCCM).

• ΔSVC ≥21% by TOE: specificity 84% in predicting FR (large trial).
• LVOT-VTI increase of 9% on a 12 s end-expiratory occlusion test: sensitivity 89%, specificity 95%.
• PLR threshold 9%: positive and negative predictive value 91% and 89%.

End-Expiratory Occlusion Test

• Performing an expiratory hold decreases intrathoracic pressure → net increase in blood return to RA and increase in CO if fluid responsive (ascending Frank-Starling). An increase ≥5% on LVOT-VTI with an expiratory hold predicts FR.

Source notes (OneNote)

Which parameters can be used to assess FR in mechanically ventilated patients? (table from OneNote)

• Based on respiratory variations:
  • Spontaneous/Negative pressure: ΔIVC Diameter >40% (% of max diameter) — sens 70, spec 84% (Muller; Zhang)
  • Passive mechanical ventilation (TV 8–10 ml/kg):
    • ΔVpeak LVOT >12% — sens 100%, spec 89%
    • ΔVTI LVOT >9% — sens 100%, spec 88%
    • ΔSVC Diameter >29–36% (% of max diameter) (31%) — sens 89–90%, spec 90–100% (Vignon)
    • ΔIVC Diameter >12% (% of mean diameter)
    • ΔIVC Diameter >18% (% of min diameter) — sens 42–90%, spec 39–90%
• Following PLR (spontaneous or mechanical): ΔVTI LVOT >10; ΔVpeak LVOT (Monnet)
• Following EEO test (mechanical): ΔVpeak LVOT 5
• Following "mini-fluid challenge" (spontaneous or mechanical): ΔVpeak LVOT
• Following "fluid challenge" (spontaneous or mechanical)
• Tidal volume challenge

Passive Leg Raise and Mini-Fluid Challenge

Mini Fluid Challenge

• A 10% change of CO/LVOT-VTI by PLR is reliable; not in unstable fractures; PLR in intra-abdominal hypertension (>16 mmHg) may give false negatives. Mini fluid challenge: LVOT-VTI change >10% after rapid injection of 100 mL crystalloid → FR, sensitivity 95%, specificity 78%. ΔSVV and ΔPPV in response to mini-challenge predicted FR with AUC 0.91 and 0.92.

Question explanations (5)

• SBA 4684 — Start vasopressors There has been an increasing body of evidence pointing to harmful effects of over-resuscitation, giving rise to the concept of “fluid tolerance”. Stroke volume/ CO assessment combined with a leg-raise maneuver or a mini fluid bolus can reliably assess volume responsiveness. However, the expected clinical benefit of a small and likely transient increase in cardiac output in a patient deemed to be fluid-responsive needs to be weighed against potential harms of over-resuscitation. Capillary leakage of fluid into the interstitial is greatly increased in septic patients [14]. The patient may still be volume responsive, but may be at risk to develop pulmonary edema (as evidenced by the appearance of B-lines on chest ultrasound) and abdominal compartment syndrome [15]. A common practice is to limit fluid administration by appearance of B lines [16].
• SBA 4688 — Give a 100 mL of LR bolus and assess LVOT VTI change A change of 10% of cardiac output/LVOT- VTI by PLR is a reliable way of assessing fluid responsiveness. One study suggested PLR in patients with intraabdominal hypertension (abdominal pressures >16 mmHg) may leed to false negative results [22]. In patients in whom PLR cannot be reliably performed, a “mini fluid challenge” bolus is another reliable alternative. LVOT-VTI change of >10% after raid injection of 100 mL of crystalloid fluid was associated with fluid responsiveness with a sensitivity and specificity of 95% and 78%, respectively [23]. Another study evaluated change in stroke volume variation (ΔSVV) and change in pulse pressure variability (ΔPPV) in response to a “mini fluid challenge” in patients with circulatory failure and ventilated with low tidal volumes. The ΔSVV and ΔPPV predicted fluid responsiveness with AUCs of 0.91 and 0.92, respectively [24]. _[…1 non-FR sentence(s) trimmed]_
• SBA 4697 — LVOT VTI increase by more than 10% after “Mini”-fluid challenge (100 mL). A change in LVOT VTI by more than 10% following a 100 mL infusion of a colloid over 1 min, predicted fluid responsiveness with a sensitivity and specificity of 95% and 78% respectively. The VTI was measured with transthoracic echocardiography. _[…1 non-FR sentence(s) trimmed]_
• SBA 4706 — Increase of LVOT VTI during inspiration. Effect of PPV on the right ventricle: – Increased intrathoracic pressure decreases the pressure – gradient between mean systemic filling pressure and right atrial pressure, resulting in decreased TR inflow and decreased RV stroke volume. – Transpulmonary pressure (TPP) is maximal at end inspi- – ration. As TPP rises it can exceed pulmonary venous pressure and pulmonary artery pressure, leading to partial or complete collapse of pulmonary capillaries resulting in an increase in pulmonary vascular resistance and RV afterload—which may lead to decreased stroke volume. Effect of PPV on the left ventricle – Rise of TPP during inspiration compresses the pulmonary – capillaries and veins, increasing pulmonary venous flow to the left atrium and increasing LV preload at end inspiration. – As long as the LV is functioning on the ascending limb of – the Frank-Starling curve, this transient increase in LV preload leads to increase in LV stroke volume, which is at its maximum at end-inspiration [35]. Which of the following can most likely be detected using echocardiography? Decrease of LVOT-VTI from baseline B. Increase of LVOT-VTI from baseline C. Increase IVC diameter D. Decrease IVC diameter You perform a 15 s inspiratory hold in a healthy patient, who is sedated and passive in mechanical ventilation. Which of the following can most likely be detected using echocardiography? Decrease of LVOT-VTI from baseline B. Increase of LVOT-VTI from baseline C. Increase IVC diameter D. Decrease IVC diameter Answers 29—B Increase of LVOT-VTI from baseline; 30—A Decrease of LVOT-VTI from baseline. Compared to the normal respiratory cycle, performing an expiratory hold effectively decreases intrathoracic pressure. This results in a net increase in blood return to the RA and increase in cardiac output, if the patient is “fluid responsive” i.e., on the ascending portion of the Frank Starling curve. An increase in 5% or greater on LVOT-VTI with an expiratory hold has been shown to predict fluid responsiveness. In contrast, an inspiratory hold, increases intrathoracic pressure, decreasing pre-load and in turn decreasing cardiac output in a pre-load sensitive patient [36]. Subcostal long axis view of the IVC is shown in below image. Which of the following statements best describes the most likely hemodynamic effects of initiation of positive pressure ventilation (PPV) in the patient above? PPV will reduce LV afterload, increase LV preload and increase cardiac output and blood pressure. PPV will cause a sudden increase of transpulmonary pressure, decreased RV afterload and therefore increase in cardiac output and blood pressure. Initiation of PPV will have minimal hemodynamic effects. PPV will cause a sudden increase of intrathoracic pressure, thereby causing decreased RV preload and a drop in cardiac output and blood pressure. IV volume resuscitation before intubation C. Proceed with intubation without additional intervention Answer 31—D PPV will cause a sudden increase of intrathoracic pressure, thereby causing decreased RV preload and a drop in cardiac output and blood pressure and 32—B IV volume resuscitation before intubation. Based on history and the echocardiographic images provided, the patient in question is hypovolemic. In hypovolemia, a low stressed volume of blood in the venous capacitance vessels leads to a relatively low mean systemic filling pressure (MSFP) and a low pressuregradient for venous blood return to the right atrium. Even small changes in right atrial pressure will therefore significantly decrease the pressure gradient between MSFP and the right atrium, and thereby dramatically reduce RV preload, leading to a drop in cardiac output. This effect can be minimized volume resuscitation. In the absence of heart or lung disease there is no indication that initiation of PPV would result in significantly elevated TPP or reduce large negative swings in pleural pressure. Therefore, the effect of PPV in RV and LV afterload in this situation would be negligible [29, 37]. IV volume resuscitation before intubation C. PPV will reduce LV afterload, increase LV preload and increase cardiac output. PPV will cause an increase in transpulmonary pressure, increased RV afterload and a decrease in cardiac output. Initiation of PPV will have minimal hemodynamic effects. PPV will cause a sudden increase of intrathoracic pressure, a decrease RV preload and a drop in cardiac output. The IVC is dilated without respiratory variation suggesting high central venous pressure with a dilated RV with septal flattening suggesting both pressure and volume overload. Initiation of PPV will increase alveolar pressure, with minimal increase in pleural pressure, thus increasing transpulmonary pressure (TPP) and therefore dramatically increasing RV afterload. The increase in TPP will increase RV afterload and decrease cardiac output. To minimize adverse effects of PPV in this patient, the best next step is to stabilize blood pressure with a vasopressor—Norepinephrine, and attempt to reduce PVR with a pulmonary vasodilator. Question 35 A 74-year-old woman with depression, diabetes, hypertension, hyperlipidemia, COPD and chronic atrial fibrillation is admitted to your unit after being found unresponsive at home. Only subcostal long axis view can be obtained, which shows and IVC of 2.4 cm without respiratory variation. IV fluid bolus C. Check ET-tube position and auto-PEEP A plethoric IVC without respiratory variability suggest high pressure in the central venous system. Therefore the plethoric IVC may be due to high intrathoracic pressure from auto-PEEP in the setting of obstructive lung disease ventilated with high tidal volume and respiratory rate or right main stem intubation [38, 39]. The IVC variability index is 43% B. The IVC collapsibility index in 43% C. The IVC dispensability index is 43% D. The IVC variability index is 43% Answer B. The IVC collapsibility index in 43% Passive Mechanically Ventilated patient. Variability index (IVCmax − IVCmin)/ IVCmean = (IVCmax − IVCmin)/(IVCmax + IVCmin)/2 Distensibility index (IVCmax − IVCmin)/IVCmin Spontaneously Breathing patient. Collapsibility index (IVCmax − IVCmin)/IVCmax Cyclical changes in intrathoracic pressure induce changes in RAP, which alters venous return. In spontaneously breathing patients, intrathoracic pressure decreases during inspiration, leading to IVC collapse. During controlled ventilation, the IVC expands in inspiration because of increased intrathoracic pressure, and thus right atrial pressure. Echocardiographic assessment of IVC variability through the respiratory cycle can be used to predict response to fluid resuscitation. IVC variability can be expressed as variability index or dispensability index in passive mechanically ventilated patient and collapsibility index in spontaneously breathing patient. As the patient is breathing spontaneously on RA, the measurement is collapsibility index. Fluid challenge D. High tidal volumes lead to high driving and plateaus pressures. This in turn causes high transpulmonary pressures and overdistention of the alveoli during inspiration. Repeat Echocardiogram shows unchanged RV/LV size and function, mild mitral regurgitation with an average E/e′ of 15.5. Stop SBT, optimize afterload, diurese and evaluate for ischemia B. Stop SBT, optimize afterload, diurese and evaluate for ischemia Which of the following is true regarding weaning failure in the patient above? A positive passive leg raise (increase in LVOT-VI >10%) prior to SBT predicts failure to wean. Increased work of breathing during the SBT can unmask previously undetected diastolic dysfunction E. COPD, obesity and preexisting structural heart disease and diastolic dysfunction have been shown to be risk factors. Weaning from positive pressure ventilation increases left ventricular preload and afterload, it increases work of breathing and increases myocardial oxygen consumption. Elevated LVEDP as assessed by bedside echocardiography before or during weaning has been shown to correlate with failure to wean or post extubation respiratory failure with high sensitivity and specificity. A negative passive leg raise (failure to increase CO by >10%) prior to SBT can predicted weaning failure due to cardiovascular dysfunction with a sensitivity of 97% and specificity of 81% [42–47]. Lung ultrasound shows B-line pattern. LVOT diameter 2.1 cm, LVOT VTI 18.5 cm, MV peak E velocity 74 cm/s, MV peak A velocity 51 cm/s, medial mitral annulus e′ velocity 16.1 cm/s, lateral mitral annulus e′ velocity 16.7 cm/s, IVC maximal diameter is 1.5 cm during expiration and a minimal diameter of 0.9 cm during inspiration. Profoundly negative swings in intrathoracic pressure (ITP) commonly occur during forced spontaneous inspiratory efforts in patients with airway obstruction, such as biting on a small ET tube, bronchospasm, laryngospasm etc. The fact that the IVC collapses during inspiration suggests that despite positive pressure ventilation, the patient generates enough inspiratory effort, that the pleural pressure becomes negative. Highly negative ITP swings also selectively increase LV afterload, which has been shown to contribute to pulmonary edema, even in the absence of underlying heart disease [29]. Which of the following is most accurately predicts increase in cardiac output by >10% following a fluid bolus? Respiratory variation of stroke volume assessed by LVOT-VTI of 11% B. IVC distensibility index of 11% C. Increase of LVOT-VTI by 11% after passive leg raise Answer D. Increase of LVOT-VTI by 11% after passive leg raise Static parameters such as CVP or PACWP measure preload but cannot predict a patient’s response to increase in preload without knowing the shape of the Frank- Starling curve for this specific patient. Dynamic parameters of fluid responsiveness (stroke volume variation, end-expiratory occlusion test, response to PLR) are all more specific then static parameters. There are few contraindications to performing a PLR and it can be used where other methods fail (arrhythmias, ARDS, low tidal volume ventilation, spontaneously breathing). Pooled analysis of 50 trials with over 2000 patients showed that augmentation of cardiac output following a passive leg raise is highly predictive of fluid responsiveness, with a positive LR of 11 and a pooled specificity of >92% [12, 25, 48, 49]. Method Threshold (%) Limitations PPV/SVV 12 Cannot be used in spontaneous breathing, cardiac arrhythmias, low VT, low lung compliance IVC variation 12 Not in spontaneous breathing, low VT SVC variation 36 Requires TEE, not in spontaneous breathing PLR 10 Direct measurement of cardiac output within 1 min Fluid challenge 500 cc 15 May contribute to fluid overload End-expiratory occlusion test (EEOT) 5 Requires intubated patient, able to tolerate 15 s inspiratory hold Combined end-inspiratory/end-expiratory occlusion test 13 Requires intubated patient, able to tolerate inspiratory and expiratory hold Question 42 An end-expiratory occlusion test is performed in the above patient. Cardiac output assessment based on LVOT-VTI increased from 3.5 to 3.74 L/min. The patient is fluid responsive, give fluids B. The patient is not fluid responsive, place a central line and start norepinephrine C. Perform both end-expiratory and end-inspiratory occlusion test D. Echocardiography lacks sensitivity to assess changes in cardiac output in response to end-inspiratory and end-expiratory occlusion tests and alternative measures to assess fluid responsiveness should be used Answer C. Perform both end-expiratory and end-inspiratory occlusion test The reported threshold to detect fluid responsiveness with the end-expiratory occlusion test is 5%. This is below the precision threshold reported for cardiac output measurement using TTE. They concluded 10% to be the least significant change, i.e. the minimum change that can be considered significant and not due to imprecision of the measurement of LVOT- VTI. The change in CO in the question stem is above 5%— which suggests the patient is fluid responsive, but below the 10% leastsignificantchange threshold of TTE. The same group of authors demonstrated that by combining the sum of absolute values of changes in velocity-time integral during both endinspiratory and end-expiratory occlusions, fluid responsiveness could be assessed using a threshold of 13%. This threshold is within the precision of transthoracic echocardiography and allowed assessment of fluid responsiveness with both sensitivity and specificity above 90% [36, 50]. She has been started on empiric antibiotics and has received 30 mL/kg of crystalloids and an arterial line is inserted for close monitoring. IVC diameter end expiration 1.8 cm, IVC diameter inspiration 1.4 cm. Pulse pressure variation on the arterial line wave form is 14%. Based on pulse pressure variation, this patient should be given a fluid bolus B. Based on IVC variability of >20% this patient should receive a fluid bolus D. Continue antibiotic therapy and monitor clinically Answer D. Continue antibiotic therapy and monitor clinically The goal for fluid resuscitation in septic shock is to improve organ perfusion and oxygen utilization by increasing cardiac output and oxygen delivery. However, excess fluid is associated with excess risk of death in patients with sepsis. After initial resuscitation, additional fluid resuscitation is only indicated if the patient has both evidence of tissue hypoperfusion and will likely increase cardiac output in response to additional fluid—i.e. is “fluid responsive”. Clinically, the patient appears to have restored organ perfusion (normal mentation, decreased lactate, normal capillary refill and improved urine output). Additional administration of IV fluid in this case is unlikely to improve organ function, indeed may lead to iatrogenic fluid overload which is associated with poor outcomes. Pulse pressure variation, a surrogate of stroke volume variation, accurately predicts response to fluid in patients who are passive on mechanical ventilation. Should not be used to predict response to fluid loading in spontaneously breathing patients. Similarly, IVC size and collapsibility has been extensively studied to assess fluid responsiveness in spontaneously breathing patients. Recent meta-analysis of various studies of IV variability have shown IVC size and variability to be relatively poor predictors of response to fluid loading. Only very high variability (cIVC >39–42%) and standardized inspiratory effort have been shown to be accurate in predicting a positive response in cardiac output [51–55]. Empiric antibiotics and 30 mL/kg of crystalloids have been given. LVOT diameter 1.8 cm, LVOT VTI 26.5 cm, MV peak E velocity 98 cm/s, MV peak A velocity 69 cm/s, medial mitral annulus e′ velocity 15.5 cm/s, lateral e′ velocity 17.3 cm/s, IVC end expiration 2.9 cm, IVC early inspiration 2.7 cm. Assess respiratory variation of LVOT VTI C. Fluid challenge and repeat LVOT VTI D. Fluid challenge and re-assess E/e′ Answer A. Start Norepinephrine The patient in this case has normal right and left ventricular function with a high VTI/cardiac output. While IVC variability has overall poor predictive value for fluid responsiveness in spontaneous breathing, an IVC of 2.8 cm and above has a high negative predictive value for fluid responsiveness. Given the already high cardiac output and dilated IVC it is unlikely that additional fluid loading would further increase cardiac output in this patient. Respiratory variation of stroke volume and peak aortic velocity should not be used to assess fluid responsiveness in spontaneously breathing patients. Left atrial pressure alone—either measure by PA catheter or estimated using E/e′—is also a poor predictor of response to fluid therapy [53, 56]. On arrival to your department he is intubated, given empiric antibiotics and 2 L of crystalloids for hypotension. Respirophasic variation of VTI: max VTI 19.4, min VTI 18.9. Which of the following is the most appropriate statement regarding fluid responsiveness based on respiratory variation of VTI in this patient? The patient is fluid responsive B. Decrease RR to determine fluid responsiveness C. The patient is not fluid responsive D. Fluid responsiveness cannot be determined without an accurate measurement of LVOT diameter. Decrease RR to determine fluid responsiveness Respiratory variation of stroke volume depends on the combined effect of PPV on RV and LV preload. During PPV inspiration, there is a simultaneously increase in LV preload from increased pulmonary vein drainage and decrease in RV preload from decreased venous return. This leads to an initial increase in LV stroke volume during inspiration, followed within a few beats to a decrease LV stroke volume. At high respiratory rates, the effect of increased pulmonary venous drainage and decreased RV stroke volume during inspiration may merge, abolishing respiratory variation of stroke volume. De Backer demonstrated that stroke volume variation becomes negligible if the HR to RR ratio decreases below 3.6 [57]. He is passively ventilated with a tidal volume of VT 6 mL/ kg and is in normal sinus rhythm. CVP is 6 mmHg and ICP is 14 mmHg with a MAP of 63 mmHg with a pulse pressure variation (PPV) of 11%. Which of the following is the most accurate statement regarding expected cardiac output response to an IV fluid bolus in this patient? Based on pulse pressure variation the patient is not fluid responsive, no fluid should be given B. Increase of PPV to 18% after a tidal volume challenge suggests fluid responsiveness C. The patient is fluid responsive, give 500 mL of crystalloid bolus and reassess PPV D. Fluid responsiveness should be assessed by LVOT–VTI before and after a passive leg raise Answer B. Increase of PPV to 18% after a tidal volume challenge suggests fluid responsiveness PPV has been extensively studied and can predict fluid responsiveness with high accuracy. Although, there are many limitations that will render PPV invalid, such as low VT ventilation, poor lung compliance as in ARDS, active respiratory effort, and atrial fibrillation. This patient is passive, in sinus rhythm, and has no indication of poor lung compliance or intra-abdominal HTN, so PPV can be used to predict fluid responsiveness. He has a PPV of 11%, which is within a “a grey zone” of indeterminate significance. The predictive value of the PPV can be increased using a “tidal volume challenge”. An increase of PPV by >3.5% or an increase in SVV of >2.5% during a brief period of passive ventilation at a higher tidal volume of 8–12 mL/kg has been shown to accurately predict fluid responsiveness. Passive leg raise has repeatedly been shown to accurately predict fluid responsiveness under conditions that render PPV and SVV inaccurate (arrhythmias, low tidal volume ventilation, ARDS, spontaneous breathing). Elevated ICP and lower extremity pathology, such as unstable fractures in this case, however are contraindications to PLR [48, 58, 59]. Bedside echo shows small, hyperdynamic LV with “kissing ventricles” LVOT VTI is 19.8, IVCmax 1.3 cm without respiratory variation. Give 500 cc bolus of crystalloids B. Perform a passive leg raise D. Check bladder pressure Intrabdominal hypertension is common in critically ill patients and may render assessment of fluid responsiveness using IVC and passive leg raise yield false negative results. Beurton recently demonstrated that in the presence of intraabdominal hypertension (defined as end-expiratory bladder pressure >12 mmHg), the passive leg raise had a sensitivity and specificity of only 43% and 89% respectively. The authors concluded elevated intraabdominal pressure may lead to decreased venous flow to the RA due to compression of the IVC and reduced capacitance of the splanchnic venous system. In the setting of known or suspected abdominal hypertension, alternatives to the PLR—such as a fluid challenge—may be more suitable to determine fluid responsiveness [21, 22, 60, 61]. She is on mechanical ventilation FiO₂ 50%, Volume control, VT 400 mL, PEEP 10 cmH₂O. After initial fluid resuscitation of 3 L crystalloids, she is requiring moderate doses of norepinephrine to maintain MAP >65 mmHg. IVC 2.4 cm without respiratory variability. Continue current therapy C. Give fluids Answer C. Place a pulmonary artery catheter to assess for tamponade physiology Classic echocardiographic findings of tamponade physiology are distorted by mechanical ventilation. Pulmonary artery catheter showing equalization of the diastolic pressures across all chambers without respiratory variation is highly diagnostic of tamponade physiology. After initial fluid resuscitation and initiation of empiric antibiotics he remains on norepinephrine and mechanical ventilation (PEEP 12 cmH₂O, VT of 6 mL/kg IBW, FiO₂ of 50%). Due to hypotension, renal replacement therapy has not yet been initiated. A passive leg raise is performed. LVOT VTI before PLR 18.1 cm, LVOT VTI 1 min after passive leg raise changes to 19.2 cm. Give 100 mL fluid challenge and re-assess VTI B. Volume resuscitation with 1000 mL of crystalloids C. Initiate renal replacement therapy D. Initiate renal replacement therapy Cumulative fluid balance is an independent predictor of mortality in sepsis and ARDS. A conservative fluid strategy has been shown to reduce time on mechanical ventilation. Fluid removal has been shown to reduce extrapulmonary lung volume and other volume indices. Concerns over hemodynamic instability may lead to delayed initiation of RRT and fluid removal. Decrease in cardiac output as an adverse effect of excessive fluid removal should occur in the case of preload dependence, i.e. when changes in cardiac preload physiologically result in changes in cardiac output. Changes in cardiac Index induced by passive leg raise have been shown to predict intradialytic hypotension with good sensitivity and specificity. Using a threshold of 9%, PLR has a positive and negative predictive value of 91% and 89% respectively [63, 64]. Immediately after intubation the LV preload will decrease, and LV afterload will decrease B. After intubation the intrathoracic pressure will abruptly rise causing the LV afterload to increase C. After intubation the intraventricular septum will abruptly shift causing a drop in CO D. Immediately after intubation the LV preload will decrease, and LV afterload will decrease Positive pressure ventilation leads to increased intratoracic pressure (ITP), which is transmitted to the right atrium, and RV preload decreases. This drop in RV preload eventually leads to decrease in LV preload too. An increase in ITP decreases LV afterload by decreasing the LV transmural pressure gradient. The impact of these changes on cardiac output is determined by the load dependency of the heart. In preload dependent heart, PPV will cause drop in stroke volume and cardiac output. In an afterload dependent heart, reduction in afterload will improve cardiac output. Question 51 You are about to perform a PLR in a patient who is intubated but awake, to assess for fluid responsiveness. Perform a 2 person PLR with you lifting one leg and another person lifting the second leg B. Perform a 2 person PLR with you lifting one leg and another person lifting the second leg Pain, discomfort, cough and awakening during the maneuver can cause sympathetic stimulation leading to tachycardia which can lead to mistaken cardiac output changes. Patients should be informed prior to start of the test, PLR must be performed by adjusting the bed and not by manually raising the patient’s legs, careful tracheal suctioning prior to the test to avoid coughing and monitoring heart rate before and during the maneuver [49]. Question 52 Which of the following is a reliable marker for assessing fluid responsiveness in mechanically ventilated-patients? Assessing LVOT-VTI change on PLR B. Assessing LVOT-VTI change on end-expiratory occlusion test C. Respiratory variations of superior vena cava diameter D. These cyclical changes cause changes in stroke volume and hence the cardiac output in the preload-dependent heart. This test has been widely accepted and validated as a method to assess fluid responsiveness [11]. In a large trial, Respiro phasic superior vena cava (∆SVC) diameter changes of greater or equal to 21%, as assessed by trans-esophageal echocardiogram had a specificity of 84% in predicting fluid responsiveness [25]. LVOT-VTI increase of 9% on a 12 s end-expiratory occlusion test had a sensitivity and specificity of 89% and 95% respectively [65]. _[…178 non-FR sentence(s) trimmed]_
• SBA 5115 — After initial volume resuscitation with 2 L of crystalloids, ~ 8 hrs later, lactic acid was noted to be 7.3 mmol/L, AST 1817 IU/L, ALT 1209 IU/L, INR 2.3. _[…4 non-FR sentence(s) trimmed]_

Question explanations (4)

• SBA 4679 — Echocardiogram with agitated saline contrast Point-of-care echocardiography is often useful in the assessment of the patient with dyspnea, hypoxemia, or respiratory failure [2]. _[…8 non-FR sentence(s) trimmed]_
• SBA 4681 — Prone positioning ventilation Based on the Echocardiogram, the patient is likely in acute cor-pulmonale (ACP). Application of high PEEP may increase the right ventricle afterload leading to reduced function. Hypercapnia, which ensues because of increased dead space and decreased tidal volume leads to pulmonary vasoconstriction further leading to decreased RV function. Thus, routine echocardiography in ARDS patients should be used to identify ACP. 56-year-old male with a history of colorectal cancer on chemotherapy presented to the emergency department with fever and dizziness. _[…13 non-FR sentence(s) trimmed]_
• SBA 4878 — None available
• SBA 5117 — The patient has septic shock from a complicated UTI caused by obstructing nephrolithiasis resulting in hydronephrosis and is no longer fluid responsive. Renal ultrasonography can detect and grade obstructive uropathy and hydronephrosis. The patient in this case has already received a considerable amount of IV crystalloids and her IVC indicates that she is volume replete, therefore administering more IV fluids may be detrimental. _[…3 non-FR sentence(s) trimmed]_

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Fluid responsiveness is not the same as fluid tolerance — see the dedicated page: Venous Congestion.

Source notes (OneNote)

Fluid resuscitation is generally considered a fundamental aspect in managing critically ill patients because it is intended to help optimize cardiac output and enhance tissue perfusion. However, determining the appropriate volume of fluids to administer can be challenging, as both under- and over-resuscitation can result in significant morbidity and mortality. Fluid responsiveness, defined as the ability of a patient's cardiac output to increase in response to a fluid bolus, has become an important concept in guiding fluid therapy, both in spontaneously breathing and mechanically ventilated patients. New concepts have emerged assessing venous congestion. [ScienceDirect S2210844023001818]

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