To keep tissue and organs adequately perfused and oxygenated, enough blood flow should reach all human districts; one of the causes at the origin of too low cardiac output can be identified in an inadequate heart preload.

Cardiac preload is one of the four levers determining CO.

The preload is the maximum stretch of cardiac myocytes prior to contraction; as sarcomere length cannot be measured in an intact heart, often ventricle end diastolic volume has been considered as an indirect indicator of it (the more is the ventricle content, the more the cardiac myocytes will be stretched).  Left ventricle end diastolic volume/area can be esteemed by transesophageal echocardiography (TEE)[1]-[2] but till now, pulmonary artery wedge pressure (PAWP) and central venous pressure (CVP) have been the most widely used preload indicators[3]. 

Clinical examination, central venous pressure and pulmonary artery occlusion pressure have been shown to be poor indicators[4]-[5] to differentiate patients who respond to intravascular volume loading (responders) and patients who do not (non responders[6]-[7]-[8]). Fluid Responsiveness is considered to be present when an increase in Cardiac Index of at least 15% after a volume loading can be documented[9].

These measurements are moreover affected from some limits or side effects. The benefit/risk ratio of pulmonary artery catheter is subject of ongoing controversy[10]-[11]-[12], and echocardiography is an operator-dependent technique, which is not available in all ICUs and is not appropriate for monitoring of haemodynamically unstable patients. Moreover, the estimation of left ventricular end-diastolic area by echocardiography does not always accurately reflect left ventricular end-diastolic volume[13] and hence left ventricular preload.[14]

CVP, PAWP, TEE are anyway all static, preload indexes. Preload esteems, physiologically don’t linearly correlate with stroke volume; it is not always valid the assumption that increasing preload, stroke volume and cardiac output increase.

The relation between preload and stroke volume is regulated by Frank-Starling low; understanding where, on pressure-volume curve, can be ideally positioned the patient under observation, let the doctor understand if giving fluids will improve cardiac output and overall conditions. It is not the preload measurement itself, but how the patient reacts to fluid increase (preload dependent or not) [15] the useful information the operator needs.

Frank-Starling's law states that the greater the diastolic volume or fibre stretch at the end of diastole, the stronger the subsequent force of contraction during systole. This phenomenon will occur until a physiological limit has been reached. Once this threshold is achieved, the force of contraction will begin to decline, regardless of the increase in fibres stretch.  

An haemodynamic monitoring-guided resuscitation, when early performed, may surely improve outcome; on the other side, an inappropriate fluid administration may equally degenerate; the result of a fluid overload can likely result in pulmonary and interstitial edema.

In a normal, spontaneously breathing person, blood pressure falls with inspiration and rises with expiration (normal pulse). The range of normal peak decreases in systolic pressure are usually between 5 – 10 mmHg and an accompanying inspiratory fall in the venous pressure normally occurs.

Normal arterial pressure curve: 

The exaggeration of this phenomenon was first described by Adolf Kussmal[1]. He defined it “pulsus paradoxus” referring to the pulse disappearing during inspiration and returning during expiration despite the continued presence of the cardiac activity during both respiratory phases. “Pulsus paradoxus” is characterized by the inspiratory diminution in arterial pressure exceeding 10 mmHg and the inspiratory venous pressure remaining steady or increased. This fluctuation occurs during forced respiratory effort, like heart failure, pericardial tamponade, severe ashma, hypovolemia.

Pulsus paradoxus: 

A phenomenon that is the reverse of the conventional pulsus paradoxus has been reported during positive pressure ventilation (i.e. mechanical ventilation). The inspiratory increase in arterial blood pressure followed by a decrease on expiration has been called at different times reversed pulsus paradoxus[2], paradoxical pulsus paradoxus[3], respirator paradox[4], systolic pressure variation (SPV)[5], and pulse pressure variation[6]. In 1978, Rick and Burke[7] were the first to suggest a link between the volume status of critically ill patients and the SPV. From 1987, Perel’s group[8]-[9]-[10]conducted several animals studies clarifying the physiologic determinants of the Systolic Pressure Variations, and emphasizing the major role of volume status on its magnitude[11].

A number of peer-reviewed studies have, until now, demonstrated the usefulness of the respiratory variation in arterial pressure (or its surrogates) in answering a crucial clinical question: “Can we improve cardiac output and hence hemodynamics by giving fluid?”

A growing interest can be nowadays noticed in blood pressure variation measurement in mechanically ventilated patient. Positive pressure ventilation, when applied to a patient at rest and with no spontaneous respiratory effort, is associated with a cyclic increase in right atrial pressure during the inflation. It follows that, since right atrial pressure is the back-pressure to venous return, if upstream venous pressures do not simultaneously increase, right ventricular (RV) filling will also decrease in a cyclic fashion. In presence of RV and left ventricle (LV) preload responsiveness, this cyclic variation in RV filling will induce a cyclic variation in left ventricular (LV) filling. The latter phenomenon will induce a cyclic variation in LV SV and Pulse Pressure (systolic arterial pressure minus diastolic arterial pressure) in presence of preload responsiveness.

Therefore, Stroke Volume Variation (SVV), Pulse Pressure Variation (PPV), and Systolic Pressure Variation (SPV), are useful predictors of volume responsiveness when exceeded 10-15% if some conditions of cardiac rhythm and ventilator pattern are respected[12]-[13].

•          Clinically examine the patient, (mottling and oliguria), verify with biological tests (eg, renal failure and high lactate level), or/and other haemodynamic parameters (eg, low CO and low mixed venous oxygen saturation)

•           Exclude contraindications to fluid loading (severe pulmonary edema)

Only after verifying effective CO increase need, fluid responsiveness parameters can be considered to discriminate patient who can benefit from volume loading and these in whom inotropic support would be more indicated[1].

This applies only if:

•          Patient is mechanically ventilated  (>8ml/kg tidal volume)

•          He doesn’t have arrhythmias/atrial fibrillations/frequent extrasystoles[2]

•          Arterial pressure signal is good

SVV - PPV - SPV can be considered to decide the fluid therapy; if overcomes 10-15%, fluid responsiveness can be recognized.

Attention: only small variation can occur in spontaneous breathing, in MV with small tidal volume (<6ml/kg), in case of patient with increased chest compliance (i.e. open chest); do not exclude fluid responsiveness in case of low SVV/PPV.

SVV is calculated from percentage changes in calculated Stroke Volume during the ventilatory cycle.

SVV (%) = (SVmax - SVmin)/SVmean

Arterial pulse contour analysis, which has been clinically validated for continuous CO measurement, now enables the continuous quantification of the real-time left ventricular SVV, accounting for these undulations in arterial blood pressure.

•          SVV > 9,5% was found to predict a positive SV increase (+5%) in response to 100ml of plasma expander (79% sensitivity, 85% specificity in healthy patients undergone neurosurgery)[1]

•          Usefulness of SVV to guide volume therapy in cardiac surgery patients was shown[2]

•          SVV predicted fluid responsiveness in mechanically ventilated patients with reduced myocardial function[3]

PPV is calculated from percentage changes in measured differential pressures during the ventilatory cycle.

PPV (%) = [ (PPmax - PPmin)/ (PPmax - PPmin)/2] * 100

·         PPV > 12-13% was shown to predict fluid responsiveness in ARDS[1] patients

·         The parameter has been validated in septics[2], cardiac[3], general critically ill[4] patients

·         Michard et al.[5] demonstrated a slight but significant superiority of PPV over SPV in identifying responders and nonresponders to a volume load. Their findings have later been confirmed in postoperative cardiac surgery patients[6].

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