Low stroke volume. Fluid is best given as boluses, e.g. 200ml, to construct a Starling curv e for that patient. If there is less than a 5 \200\22310% increase in stroke volume with ea ch bolus it suggests that the plateau point has been reached. Low FTc. Most commonly repres ents hypovolaemia. Fluid challenge as above to achieve an FTc of 330 \200\223360ms. Other c auses, e.g. PE, will not improve with \202 uids. Low peak velocity. Consider positive ino tropes. Low peak velocity and low FTc. Consider moves to reduce afterload, e.g. peripheral warming, reduction of vaso- pressors, glyceryl trinitrate (GTN). \200 120 M CECCONI & G DELLA-ROCCA Pulse pressure algorithms this is not the case as the pressure wave is transmitted 20 times faster than the \202 o w wave. Moreover, even if it is true that in the proximal aorta the \202 ow is almost pul satile, blood \202 ows peripherally in both systole and diastole. A pulse pressure algori thm needs to take into considera- tion all these forces when transforming a pressure to a v olume in order to track stroke volume. Summarizing, an ideal algorithm should: \200 Cardiac output can be monitored continuously by different devices that analyze the arterial waveform to track changes in stroke volume and cardiac output. The analysis of the arteria l pressure wave to determine cardiac output is clas- si \201 ed as pulse contour analysis or pulse pressure analysis. Starting from a similar principle three main devices are now av ailable on the market, with different algorithms and features: \200 \200 \200 PiCCO system (Pulsion, Munich, Germany) LiDCO \204 plus system (LidCO, Cambridge, UK) Flotr ac technology and Vigileo Monitor (Edwards Lifesciences, Irvine, CA, USA) Work independently of the arterial site from where pressure is monitored despite changes in waveform shape and pressure through the arterial tree from the center to the periphery. Co rrect for non-linear compliance and take account of individual variations in aortic charact eristics, thus giving an absolute cardiac output. Not be affected by changes in vascular re sistance causing changes in re \202 ected wave augmentation of the arterial pressure. Not rely on identifying details of wave morphology. Be only minimally affected by the damping o ften seen in arterial lines. Physiological background Compliance Compliance describes the relationship between pressure and volume in the arterial vessels. Knowing the compli- ance is essential to estimate the c hanges in volume (stroke volume) from changes \200 C = ZV/ZP. Where C = compliance, ZV = changes in volume, ZP = changes in pressure. Without knowing the compliance of the arterial tree, more precisely the compliance of the proximal aorta, it i s not possible to understand the change in volume that corre- sponds to a change in pressur e. Compliance in the arterial tree is not a linear relationship, and so the same change in pressure does not always re \202 ect the same change in vol- ume. As a general rule, compl iance is higher for lower pres- sures and lower for higher pressures. Another peculiarity o f compliance is that it is not constant. The same arterial tree can behave differently in d ifferent situations and be characterized by different compliance. For example, vaso- constr iction during vasopressor therapy decreases compli- ance, vise versa vasodilation during va sodilator therapy or sepsis increases compliance. The aorta is the main arterial vessel of interest, as it is the part of the arterial tree that directly receives the stroke volume. There are three forces that contribute to how the proximal aorta is \201 lled with blood during every heart beat: \200 History The first algorithm used in clinical practice was the Wesseling algorithm in 1983. This algorithm is based on the hypothesis that the contour of the arterial pressure wavefor m is dependent on stroke volume, and that this can be estimated from the integral of the ch ange in pressure over time, considering the interval between the end of diastole to tyhe en d of systole (Asys). This is the \201 rst algorithm of pulse contour analysis used to det ermine car- diac output. From this point, new algorithms have been developed. Devices PiCCO system In clinical practice the \201 rst pulse contour method using a Wesse ling-based algorithm was the PiCCO system (Pulsion Munich, Germany). PiCCO is a cardiac mon itor that meas- ures cardiac output and several volumes (intrathoracic blood volume (ITBV), global end-diastolic volume (GEDV), extravascular lung water (EVLW)) via transpulmonary th ermodilution. This thermodilution is used to calibrate the pulse pressure algorithm. The pu lse pressure algorithm analyzes both the systolic and the diastolic part of the arte- rial pressure to study and determine the non-linear com- pliance, and the relationship \202 ow /pressure. This part of the process is called calibration and should be repeated every time there is a signi \201 cant haemodynamic change. In order to perform a thermodilutionm a c entral venous catheter needs to be in place. 15ml of cold saline is injected through a sens or that detects the temperature and time of the injection. A specialized arterial catheter (usually a femoral artery) detects the changes in blood temperature, produc- ing a thermodi lution curve. The same arterial catheter is used to monitor blood pressure, and the arteria l waveform is analyzed by the pulse pressure algorithm. PiCCO continuous cardiac output had been studied and validated against the pulmonary artery catheter in several conditions and has proven to be a reliable device, requiring calibration more often only in cases of majo r haemody- namic changes. The force of injection of the blood by the pumping of the heart The opposing force dependen t on the pulsatile in \202 ow (impedance) The opposing force dependent on the change in vo lume that we described as compliance When blood leaves the aorta there is also another force that opposes the blood \202 owing peripherally. This is the peripheral resistance. Re \202 ected waves A further problem that has to be overcome is the accurate measurement of pressure in the periphery. The arterial pressure recorded is not only dependent on the a ortic arterial pressure, but is also the result of the re \202 ection of waves generated p eripherally and returning back up the arterial system. Non-pulsatile \202 ow Although the \202 ow wave and the pressure wave in the prox- imal aorta occur almost simultaneously, more peripherally 121 CHAPTER 7.10 Pulse pressure algorithms The algorithm also provides the user with the analysis of the variation in either stroke vo lume (SVV) or pulse pres- sure (PPV). SVV and PPV represent the variation of stroke volume and of the pulse pressure during the respiratory cycle. In sedated ventilated patients, the se indexes have proven to predict the response to a \202 uid challenge. A large variation (>10 \200\22312%) identifies responders and non- responders with good sensitivity and spec i \201 city. monitor. The most interesting characteristic of this device is that it does not need to be calibrated and it needs just an arterial line to work. Compliance and resistance are derive d from the analysis of the arterial waveform. The hypothesis is that in order to calculate the effects of com- pliance and peripheral resistance on \202 ow, all the necessary infor mation can be obtained by the analysis of the arterial pressure waveform. Age, weight and s ex of the patient are the only variables that the clinician needs to input into the Vigileo monitor. The transducer (Flotrac) can be connected to any functioning arterial access. The algorithm recalcu- lates the compliance continuously, thus bypassing the need for calibrat ion. The Vigileo algorithm also allows the analy- sis SVV and PPV to be performed. This alg orithm is now under validation. LiDCO The LiDCO \204 plus system is a cardiac output monitor that measures cardiac output v ia lithium transpulmonary ther- modilution. The LiDCO algorithm for continuous cardiac outp ut monitoring is based on the hypothesis that the change in power in the system (arterial t ree) during systole is proportional to the difference in the amount of blood entering the s ystem (stroke volume) minus the amount of blood \202 owing out peripherally. It is based on the principle of conservation of mass/power and an assumption that following correction for compliance and calibration there is a linear relationship between net power and net \202 ow. This algorithm de \201 nes which part of the \200\230change in power \200\231 is determined by the stroke volume. When this is identi- \201 ed, then cardiac output is de rived. The calibration is obtained via a lithium dilution technique. In order to per- form the calibration, a dose of 0.3mmol of lithium is injected using either central or periphera l venous access. A sensor connected to an arterial line (there is no need for a specialized catheter) which makes it possible to generate a concentration \200\223time curve, and the cardiac output is then calculated. This value is then used to calibrate the pulse pressure algorithm. Further calibrations should be per- formed in the case of major haemodynamic cha nges. Continuous cardiac output of LiDCO has already been validated in several studies. Thi s new algorithm has so far proven to be reliable in both surgical and intensive care patien ts. The LiDCO algorithm also allows the analysis of the SVV or PPV and of the systolic pres sure variation (SPV). As discussed for PiCCO, these indexes are useful predictors of \202 uid responsiveness. Clinical use of pulse pressure-based algorithms The most interesting feature of all these d evices is that they are able to track changes in cardiac output in real time. Intermittent techniques are not appropriate to meas- ure changes when these occur in a very short time ( sec- onds, minutes). This is particularly useful when evaluating the effect of a \202 uid challenge or inotrope administration on haemodynamics. When performing a \202 uid challe nge, rec- ognizing an increase in SV (>10%) identi \201 es patients that bene \201 t from \202 uids. All the devices discussed have features that make them suitable to monitor ch anges in cardiac output in real time when a therapeutic intervention is applied. Further reading Della Rocca G, Costa MG, Pompei L, et al. Continuous and inter- mittent car diac output measurement: pulmonary artery catheter versus aortic transpulmonary technique. Br J Anaesth 2002; 88: 350 \200\2236. Hamilton TT, Huber LM, Jessen ME. PulseCO: a less-invasive method to monitor cardiac output from arterial pressure after cardiac surgery. Ann Thorac Surg 2002; 74: S1408 \200\22312. Jansen JRC, Wesseling KH, Settels JJ. Continuous cardiac output monitoring by pulse contour during cardiac surgery. Eur Heart 1990; 11: 26 \200\22332. Michard F, Teboul JL. Using heart \200\223lung interactions to assess \202 uid responsive ness during mechanical ventilation. Crit Care 2000; 4: 282 \200\2239. FloTrac and Vigileo Flotrac (Edwards Lifescience, Irvine, CA, USA) is the name of the speci \201 c transducer incorporated into the Vigileo 122 M CECCONI & G DELLA-ROCCA Non-invasive methods Echocardiography also allow a more global overview of cardiac dimensions and function (see Chapter 7.7). The major criticism to the pulmonary artery catheter is that its level of invasiveness is n ot supported by an improve- ment in the patient \200\231s outcome. Monitoring cardiac outpu t is essential in haemodynamic patients, so new devices have been developed with the aim of monitoring the circulation, avoiding the invasiveness of pulmonary artery catheter- izatio n. Some of these methods, such as pulse pressure analysis, are less invasive but still requ ire the catheteriza- tion of blood vessels (arteries, veins or both). Methods that do not n eed the catheterization of blood vessels are called \200\230non-invasive methods \200\231. These include: \200 \200 \200 \200 Echiocardiography summary \200 \200 Requirements: a trained operator Complete vision of cardiovascular dynamics in expert hands Disadvantage: operator dependent; long learning curve. Electric impedance Electric impedance uses stimulation with a constant elec- tric current w ith the aim of identifying the electrical imped- ance variations induced by vascular blood \202 ow. The theory is that the cardiac output is responsible for the variation of the el ectric impedance. This variation is analyzed by an algorithm that estimates the changes in cardiac output. The electrodes can be placed either on the thorax (thoracic electric bioimp edance (TEB)) or on the limbs (whole body electrical bioimpedance (WBEB)). There are severa l devices using this principle to track changes in cardiac output, such as BioZ (Cardiodyna mics International, San Diego, CA, USA) or Cardioscreen (Messtechnik, Illmenau, Germany). V alidation studies so far have shown the accuracy and precision of this technique. The main advantage is that it is a totally non-invasive technique, while the main disadvan- tages ar e that severe \202 uid shifts (severe oedema, pleural effusions, etc.), arrhythmias, vent ilation, etc. affect the reli- ability of these techniques, making them dif \201 cult to t rust in critically ill patients. Oesophageal Doppler Echocardiography Electric impedance Partial carbon dioxide re-breathing Doppler ultrasound The Doppler effect describes why a moving object creates a shift in freq uency when referred to an observer. The shift in frequency (emitted or re \202 ected) is p roportional to the relative velocity between the object and observer and can be used to est imate the velocity. Several devices able to measure the \202 ow velocity in the aorta are available. Flow can be measured in the ascending part of the aorta (with a suprasternal no tch probe) or in the descending part of the aorta (with an intraoesopha- geal probe). This method is most widely used. The two most popular oesophageal Doppler devices are CardioQ (D eltex Medical Ltd, Chichester, UK) and Hemosonic 100 (Arrow, Reading, PA, USA). In order to know the \202 ow, it is necessary to understand the diameter of the descending aorta. Th e main difference between CardioQ and Hemosonic is that CardioQ uses a normogram to obtain information about the diameter of the aorta. This normogram incorporates age, height and we ight. Hemosonic, in order to obtain the information about the diameter of the aorta, uses a n M-mode determi- nation. Both CardioQ and Hemosonic cardiac output have been validated aga inst thermodilution. The accuracy and the precision of Doppler devices have shown good, but not excellent, agreement. Despite this, there are several studies proving that oesophageal Doppler can accurately track changes in cardiac output and guide \202 uid therapy. Indee d protocols that have used Oesophageal Doppler in the perioperative period to guide \202 uid therapy have produced an improved outcome. Electric impedance summary \200 \200 Requirements: none. Disadvantage: affected by many clinical situations. Partial carbon dioxide re-breathing This method is usually classi \201 ed as non-invasive because it does not require any invasive access, though it can be done only in mechanically ventilated patients. This method is based on a modi \201 cation of Fick \200\231s princip le. Fick \200\231s principle says that if oxygen uptake happens in the lungs, the cardiac o utput can be estimated as the ratio between oxygen con- sumption and the oxygen difference between arteries and veins is known. There is one device that uses this principle (applied to CO2): the NICO System (Novametrix Medical System, Wallingford, CT, USA). The main advant age of this system is that it can be connected to any mechanical venti- lator. The NICO Sys tem creates a partial CO2 re-breathing circuit and analyzes the CO2 concentrations from the end- tidal CO2 sensor. The shunt percentage is estimated from the analysis of the O2 utili zation (O2 saturation is obtained via a pulse oximeter connected to the machine). The main disadvantages are that shunts are often present in critically ill patients and NICO compens ation is not accurate enough. Indeed not all the studies have proved that NICO is a reliabl e CO2 monitor when compared with pulmonary artery catheterization. If implemented, ideally it could be used for every patient on a ventilator. Doppler utrasound summary \200 Requirements: an intraoesophageal probe (suprasternal notch probe available) Easy to use, g ood level of accuracy and precision Disadvantage: difficult to manage in non-intubated pati ents. \200 Echocardiography Cardiac output can be measured with echocardiography with the use of Doppl er, looking at \202 ow across the aortic or pulmonary out \202 ow tract. This technique is reliable and accurate although it is user dependent. Studies exam- ining cardiac output by transoesophageal echocardi- ography have shown acceptable precision and accuracy when co mpared with pulmonary artery catheterization. Partial carbon dioxide concentration summary \200 \200 Requirements: a mechanically ventilated patient Disadvantages: the shunt fraction is dif \201 cult to measure; a low level of precision when high levels of shunt are present. 123 CHAPTER 7.11 Non-invasive methods Further reading Gan TJ, Soppitt A, Maroof M, et al. Goal-directed intraoperative \202 uid administration reduces length of hospital stay after major surgery. Anesthesiology 2002; 9 7: 820 \200\2236. Rocco M, Spadetta G, Morelli A, Dell \200\231Utri et al. Intensive Care Med 2004; 30: 82 \200\2237. Vignon P. Hemodynamic assessment of critically ill patients using echocardiography Doppler. Curr Opin Crit Care 2005; 11: 227 \200\22334. Moshkovitz Y, Kalushi E, Milo O, et al. Recent developments in car- diac output determinati on by bioimpedance: comparison with invasive cardiac output and potential cardiovascular ap plications. Curr Opin Cardiol 2004; 19: 229 \200\22337. 124 M CECCONI & G DELLA-ROCCA Measurement of preload status Preload is the initial stretching of the myocyte before con- traction. Unfortunately this s tretching cannot be measured in vivo and therefore other methods have been developed to est imate preload in clinical practice. Preload can be con- sidered to be the volume of blood a t the end of diastole (after atrial contraction) in the ventricles. Knowledge of the preloa d is important when treating haemodynamically unstable patients to identify which patients will require vol- ume expansion and how much they will need. measuring the CVP or the PAoP at the end of the expiratory cycle and without PEEP. This is not always easy nor possible to carry out at the bedside. A further problem with this relat ionship is that the compli- ance of the heart is not linearly related to pressure. If com- pliance was linear then for every increase or decrease in venous pressure there would be a constant increase or decrease in stroke volume. Unfortunately, this is not the case and eve n in the preload-dependent part of the Frank \200\223 Starling curve changes in volume cann ot be accurately pre- dicted by changes in pressure. Preload indexes A preload index is an indirect measure of preload that gives us an estimati on of the preload itself. A good preload index should correlate with stroke volume in the p reload as shown in the Frank \200\223Starling curve (Fig. 7.12.1). The most studied preload indexes are the following: 1 Filling Pressures (CVP, PAoP) 2 Left ventricular end-diastoli c area 3 Volumetric indexes (RVEDV, ITBV, GEDV) Central venous pressure (CVP) Many studies have failed to prove that CVP is a good preload index. Not even the changes in CVP can predict precisely the changes in stroke volume. Desp ite this, there is some evidence and good sense that in some situations maintaining a CVP a bove a minimal level is necessary to avoid hypovolaemia. For example, in a ventilated patie nt a CVP <10 correlates with a bigger decrease in cardiac out- put when PEEP is applied. De spite a lack of proof that CVP is a reliable preload index, CVP is still used as a surrogat e of preload in many study protocols. For example, a CVP of 8 \200\22312mm Hg is often used to de \201 ne \200\230normovolaemia \200\231 arbitrarily. This is probably guided by com mon sense and also some evidence that very low and very high values of CVP may be detriment al to the patient. Increased contractility Normal contractility SV Pulmonary artery occlusion pressure (PAoP) No study has ever proven that the PAoP is a reli able preload index. The PAoP cannot reliably guide \202 uid resus- citation. Despite the fact that the absolute values of PAoP show a poor or no correlation with stroke volume, the re is some evidence that a very low or very high PAoP would have some clinical impact. Valu es <8mm Hg are generally accepted to identify patients who may bene \201 t from volume exp ansion, while values >18mm Hg may iden- tify patients who probably will not respond to volu me expansion and may instead be at risk of developing pulmo- nary oedema. Decreased contractility Preload Fig. 7.12.1 Frank \200\223Starling curve. Filling pressures key points \200 Poor preload indexes \200 A wedge pressure >18mm Hg i s associated with a higher incidence of hydrostatic pulmonary oedema. A wedge pressure <8mm Hg in a mechanically ventilated patient identi \201 es a patient who is more likely to re spond to a \202 uid challenge. Filling pressures Physiological background Historically pressures such as CVP and PAoP have been used to estimate preload. CVP is a pressure proportional to the volume of blood in th e right side of the heart; PAoP is proportional to the volume of blood in the left side of the heart. The assumption behind their use as preload indexes revolves around the belief th at myocyte stretching is proportional to the filling pressure of the heart. Unfortunately b oth CVP and PAoP are intravascular pres- sures while the pressure that is proportional to t he cardiac chamber dilatation is a transmural pressure. A transmural pressure is the result of the difference between an intra- vascular pressure (that we can measure) and an extrava s- cular pressure, i.e. the intrathoracic pressure. The intrathoracic pressure can be affec ted by various factors such as mechanical ventilation and PEEP. If changes in intrathoracic pressure were fully transmitted to the intra- vascular pressure, then the transmural press ure would be the same. This is unfortunately unpredictable. One way of minimizing this prob lem during mechanical ventilation is by Left ventricular end-diastolic area (LVEDA) Echocardiography is a valuable tool, but requir es training to use it and even then it is an operator-dependent tool. In expert hands echoc ardiography probably represents the most complete tool to assess the cardiovascular system. A \200\230quick view \200\231 in expert hands can be useful if hypovolaemia is suspected. The area measured in bidimensional mode at the end of diastole is a well accepted measurem ent of preload and it is considered by many intensivists to be the gold standard. Its role in guiding \202 uid therapy in the operat- ing theater is well recognized. In the critica lly ill patient, LVEDA is more reliable than either CVP or PAoP as a preload index. 125 CHAPTER 7.12 Measurement of preload status Volumetric indexes With the development of new technologies, new preload indexes have been studied. The most studied volumetric indexes are: \200 Single indicator ITBVI and GEDVI The ITBVI and GEDVI are some of the volumes that the PiCCO system can measure using the transpulmonary thermodilution technique. Analysis of the ther modilution slope allows the PiCCO system to estimate different ther- mal volumes (such as p ulmonary blood volume (PBV), EVLW and the ITBVI and GEDVI). The ITBVI and GEDVI are strictl y correlated in their calculation. GEDVI is meas- ured directly and ITVBI is extrapolated u sing the following formula: Right ventricular end-diastolic volume (RVEDV) by a modi \201 ed pulmonary artery catheter . Intrathoracic blood volume index (ITBVI) and global end-diastolic volume index (GEDVI) by the PiCCO sys- tem (Pulsion, Munich, Germany) Right ventricular end-diastolic volume index (RV EDVI) RVEDVI is a parameter available in s ome rapid response sensor pulmonary artery catheters. The RVEDV represents the volume of bl ood in the right ventricle at the end of diastole. It has shown to be a better preload inde x than \201 lling pressures. Knowledge of the RV EF is important to evaluate the RVEDVI a nd to identify RV dysfunction. Knowledge of the RV EF allows the Frank \200\223Starling cur ve to be drawn for the individual patient. The lower the RV EF, the higher will be the valu e of the RVEDVI. Due to the fact that it requires the placement of a pulmonary artery cath- eter and because it is not possible to estimate the LVEDV accurately from the RVEDV, the v ariable has not gained widespread acceptability. ITBVI = GEDVI x 1.25 These measurements have been validated against the dou- ble indicator technique (COLD syste m, Pulsion). Due to the linear relationship between the GEDVI and ITBVI, it is acceptable t o extrapolate results from the GEDVI to the ITBVI and vise versa. Investigators have studie d both the ITBVI and GEDVI, dem- onstrating that they are better indicators of preload than \201 lling pressures (CVP and PAoP). These clinical settings involve both the operating theater and the ICU. The accu- racy of these indicators in terms of measuring preload has b een studied even during \202 uid loading. Volume loading is re \202 ected in increased v alues of the GEDVI. Whereas the changes in CVP do not re \202 ect changes in stroke volume , changes in GEDVI re \202 ect the changes well. RVEDVI key points \200 \200 Better preload Index than \201 lling pressures EDV target 80 \200\223120ml/m2 (may be ada pted according to the RV EF) Disadvantage: requires placement of a pulmonary artery cathete r. Clinical use of the ITBVI and GEDVI In the majority of studies, the ITBVI and GEDVI were ta r- geted to values of 800 \200\2231000ml/m2 and 650 \200\2231000ml/m2, respectively. In cri tically ill patients, optimizing the preload is challenging. Capillary leak is often presen t, with the risk of overloading patients and increasing oedema. A way of solving this probl em is to guide \202 uid therapy not by the ITBVI and GEDVI alone, but integrated into pro tocols that assess all other haemodynamic data such as cardiac output and venous saturation . Intrathoracic blood volume index (ITBVI) and global end-diastolic index (GEDVI) History: th e double indicator technique The original transpulmonary indicator technique used two indic ators to determine cardiac output and volumes. The principle was simple: one indicator woul d stay only within the vascular system (indocyanin green dye) and a second indicator would spread extravascularly (thermal indicator). From the analysis of the dilution curves of the two indica- tors, the system (COLD System, Pulsion Medical System, Munich, Germany) was ab le to measure cardiac output and intravascular and extravascular volumes. The ITBVI repre- sents the volume of blood in the chest; The GEDVI repre- sents the volume of blood in all t he heart chambers at the end of diastole. Because of these physiological properties, they h ave been proposed and validated as preload indexes. These indexes have been studied and val idated in many clinical scenarios, proving to be better preload indexes than \201 lling p ressures. The COLD system is no longer avail- able; however, a simpli \201 ed technology h as been developed to obtain the same volumetric information with just a sin- gle indicator: the PiCCO system. Key points of ITBVI and GEDVI \200 \200 \200 Good preload index ITBVI target 800 \200\2231000ml/m2 GEDVI 650 \200\2231000ml/m2. Further reading Della Rocca G, Costa MG, Pietropaoli P. How to measure and inter- pret volu metric measures of preload. Curr Opin Crit Care 2007; 13: 297 \200\223302. Ganter CG, Jacob SM, Takala J. Min Anestesiol 2006; 72: 21 \200\22336. Magder S. Central ve nous pressure: a useful but not so simple measurement. Crit Care Med 2006; 34: 2224 \200\2237. Wiesenack C, Fiegl C, Keyser A, et al. Continuously assessed right ventricular end-diastoli c volume as a marker of cardiac preload and \202 uid responsiveness in mechanically venti lated cardiac surgi- cal patients. Crit Care 2005; 9: R226 \200\22333. 126 JL TEBOUL & O HAMAZAOUI Detection of \202 uid responsiveness How to de \201 ne \202 uid responsiveness? Fluid responsiveness is de \201 ned as the a bility of the heart to increase its stroke volume signi \201 cantly in response to vol- um e expansion because of the presence of biventricular preload reserve. However, except for their lowest and highest ranges, static markers of ventricular preload such as \201 lling pressures (CVPs and PAoP) or cardiac chamber dimensions (LVEDA) fail t o predict volume responsiveness reliably. Indeed, there is not one single curve but several relating stroke volume to cardiac preload, depending on the ventricular contrac- tile func tion. Thus a given value of cardiac preload can be associated with the presence of preload reserve in the case of normal cardiac function or with the absence of preload reserve in th e case of decreased contractility. Why and when to predict \202 uid responsiveness Three different scenarios must be disting uished. 1 Patients admitted with evidence of acute body \202 uid losses: the diagnosis of hypovolaemia is almost certain and the pres- ence of clinical signs of haemodynamic instab ility (hypoten- sion, tachycardia, oliguria, mottled skin, altered mental status, etc.) str ongly suggests that a positive haemodynamic response to volume resuscitation will occur. Dynamic markers of preload responsiveness Heart \200\223lung interaction indexes Mechanical insuf \202 ation may decrease RV \201 lling through a decrease in venous return. This r esults in decreased RV stroke volume when the right ventricle has some preload reserve. Bec ause of the long pulmonary transit time, the \201 lling of the left ventricle senses the decrease in RV stroke volume two or three heart beats later and thus generally during expir ation. This results in decreased LV stroke vol- ume during expiration if the left ventricle also has some preload reserve. Thus, cyclical changes in LV stroke volume occur in cases o f biventricular preload reserve. Since vol- ume responsiveness occurs only in cases of bive ntricular preload reserve, it has been postulated that the magnitude of the cyclical change s in stroke volume or of its surrogates such as arterial pulse pressure should correlate wi th the degree of \202 uid responsiveness. Thus numerous dynamic indices using heart \200 \223lung interactions are proposed to assess volume responsiveness in patients receiving co ntrol- led mechanical ventilation. \200 2 Patients admitted with early severe sepsis or septic shock: large volume resuscitation is necessary, and there is no need for sophisticated parameters to predict volume responsiven ess since a positive haemodynamic response is always expected at this early stage. 3 Patients who have been in the ICU for several hours or days and who experience haemodynam ic instability that requires urgent therapy: only half of these patients still have some pr eload reserve since they have frequently already been resuscitated. Further \202 uid infu sion has the potential to promote pulmonary oedema in cases of increased pul- monary permea bility. Therefore, predictors of volume responsiveness are needed in order to distinguish b etween patients who can bene \201 t from \202 uid resuscita- tion and those in whom \202 uid loading can be useless and even deleterious. Respiratory variation of arterial pulse pressure (ZPP) Since the arterial pulse pressure (s ystolic minus diastolic pressure) is directly proportional to LV stroke volume, the magnitu de of \210\206PP has been proposed as a predictor of \202 uid responsiveness in patients equipped with an arterial catheter. The \210\206PP is calculated as the difference betwee n the maximal (PPmax) and the minimal (PPmin) value of pulse pressure over a single respira tory cycle divided by the average of the two values, and expressed as a percentage: ZPP (%) = (PPmax \200\223 PPmin)/((PPmax + PPmin)/2) x 100. In numerous categories of mechanicall y ventilated patients (septic shock, acute respiratory distress syndrome, cardiac surgery, liver transplantation, etc.), \210\206PP was demonstrated to be an accurate marker of \202 uid responsiveness. Threshold values of \210\206PP ranging from 10 to 17% have been r eported. Moreover, the \202 uid-induced decrease in \210\206PP correlates well with the percentage changes in cardiac output induced by 500ml \202 uid infusion. Thus, the \210 \206PP can be used not only to predict \202 uid responsiveness but also to assess the act ual haemodynamic response to volume infusion. Finally, \210\206PP better predicts \202 u id responsiveness than the systolic pres- sure variation or its \210\206down component. \200 How to detect \202 uid responsiveness? Because clinical evaluation is of poor value for d etecting \202 uid responsiveness, sophisticated parameters have been proposed to help the clinician in the therapeutic decision- making process. Static markers of cardiac preload Considering the Frank \200\223Starling relationship (stro ke vol- ume vs ventricular preload; Fig. 7.13.1), the response to volume infusion is more l ikely to occur when the ventricu- lar preload is low than when it is high. Stroke Volume no preload reserve Pulse contour-derived stroke volume variation Pulse contour cardiac output monitoring devices can con- tinuously measure and display stro ke volume variation (SVV) which represents the variation of pulse contour stroke volume ove r a \202 oating period of a few seconds. In patients fully adapted to their ventilator, S VV accurately predicts \202 uid responsiveness. Threshold values of SVV range between 9.5 and 12.5%. preload reserve Ventricular preload Fig. 7.13.1 Ventricular function curve demonstrating relationship between stroke volume and ventricular preload. 127 CHAPTER 7.13 Detection of \202 uid responsiveness from the lower limbs toward the intrathoracic compart- ment and thus increases cardiac prel oad. An increase in cardiac output or stroke volume in response to PLR is sug- gestive of t he presence of cardiac preload reserve and hence predictive of \202 uid responsiveness. B ecause of the short duration of this test ( 1min), a real-time cardiac out- put or stroke v olume measurement method is mandatory. In patients with spontaneous breathing activity and/ or cardiac arrhythmias, a PLR-induced increase (>10%) in descending aorta blood \202 ow ( oesophageal Doppler) or a PLR-induced increase (>12.5%) in pulsed Doppler stroke volume (ec hocardiography) can accurately predict \202 uid responsiveness. Respiratory variation of the peak Doppler aortic blood velocity (ZVpeak) Doppler echocardiography allows aortic blood velocity to be measured at the level of aortic annulus (left ventricle out \202 ow track). A value of \210\206Vpeak >12% is predictive of \202 uid responsiveness. \200 Respiratory variation of descending aorta blood velocity (ZABV) or blood \202 ow (ZABF) Oesophageal Doppler monitoring devices allow for the measurement of descending aorta blood velocity or blood \202 ow on a beat to beat basis. A value of \210\206ABF >18% is pre- d ictive of \202 uid responsiveness. Since the aortic diameter also varies over the ventila tory cycle, \210\206ABF is a better pre- dictor of \202 uid responsiveness than \210 \206ABV. \200 Conclusion Minimally invasive ( \210\206PP, SVV) as well as non-invasive dynamic parameters ( \210\206Vpeak, \210\206ABV, \210\206ABF, \210\206DIVC, \210\206Ppleth) testing the s ensitivity of the heart to changes in intratho- racic pressure during a mechanical breath c an accurately discriminate between responders and non-responders to \202 uid infusion. In the cases where these indexes are not interpretable (inspiratory efforts, cardiac arrhythm ias, low tidal volume), the response of stroke volume (or its surrogates) to PLR is helpful to predict \202 uid responsiveness. Respiratory changes in inferior vena cava diameter ( \210\206DIVC) The IVC diameter can be measured using echocardiogra- phy from short axis or long axis subc ostal views. A value of \210\206DIVC ((maximal diameter \200\223 minimal diameter))/mean of the two values) >12% is predictive of \202 uid responsiveness. \200 Superior vena cava (SVC) collapsibility The diameter of the SVC can be measured using tran- soesophageal echocardiography. A value of SVC collapsibil- ity (difference between maximal and minimal diameter divided by maximal diameter) >36% allowed excellent pre- diction of \202 uid responsiveness. \200 Further reading Feissel M, Michard F, Mangin I, et al. Respiratory changes in aortic blood velocity as an indicator of \202 uid responsiveness in ventilated patients with septic sh ock. Chest 2001; 119: 867 \200\22373. Respiratory changes in pulse oxymetry plethysmo- graphic waveform amplitude ( \210\206Pplet h) Feissel M, Michard F, Faller JP, et al. The respiratory variation in inferior vena cava dia meter as a guide to \202 uid therapy. Intensive Care Med 2004; 30: 1834 \200\2237. A value of \210\206Ppleth >14 \200\22315% is predictive of \202 uid respon- siveness in mechanically ventilated patients. Feissel M, Teboul JL, Merlani P, et al. Plethysmographic dynamic indices predict \202 uid responsiveness in septic ventilated patients. Intensive Care Med 2007; 33: 993 \200\2239. Limitations of using heart \200\223lung interaction indexes \200 Michard F, Teboul JL. Predicting \202 uid responsiveness in ICU patients: a critical analysis of the evidence. Chest 2002; 121: 2000 \200\2238. Volume responsiveness is a physiological phenomenon related to a normal preload reserve. Th us, detecting volume responsiveness must not systematically lead to the decision of infusin g \202 uid, in particular in the absence of clinical or biological signs of tissue hypope rfusion. The respiratory variation of surrogates of stroke volume cannot be used to assess \202 uid responsiveness in patients receiving a tidal volume <7ml/kg, in patients with sp onta- neous breathing activity and in patients with arrhythmias (except for respiratory var iation of vena cava diameter). Monnet X, Rienzo M, Osman D, et al. Esophageal Doppler monitor- ing predicts \202 uid res ponsiveness in critically ill ventilated patients. Intensive Care Med 2005; 11: 1195 \200 \223201. Monnet X, Rienzo M, Osman D, et al. Passive leg raising predicts \202 uid responsiveness in the critically ill. Crit Care Med 2006; 34: 1402 \200\2237. Natalini G, Rosano A, Taranto M, et al. Arterial versus plethysmo- graphic dynamic indices to test responsiveness for testing \202 uid administration in hypotensive patients: a cli nical trial. Anesth Analg 2006; 103: 478 \200\22384.