www.ainv.it Un nuovo approccio strumentale integrato per l analisi dei riflessi cardiovascolari

Un nuovo approccio strumentale integrato per l analisi dei riflessi cardiovascolari Ivan Corazza Dipartimento Cardiovascolare, Università di Bologna

Diagnosi Frequenza cardiaca Pressione

Una misura è caratterizzata da: ACCURATEZZA E PRECISIONE. Le misure standard (pressione e frequenza cardiaca) su cui si basa la diagnosi in un laboratorio SNV, sono accurate e e precise?

La misura della pressione al dito è una buona misura per la valutazione della pressione arteriosa? Compressore Fotodiodo Fototransistor Per settare il sistema vengono applicati valori crescenti e noti di pressione e si rileva la pulsatilità del vaso col sistema ottico: il massimo di pulsatilità si ha col valore di pressione esterna applicata corrispondente al valore medio della pressione endovasale. Nella fase operativa di misura, il sistema ottico controlla la valvola in uscita al compressore in modo da mantenere in ogni istante la pressione nella fascia al valore della pressione interna del vaso ed avere la parete vasale scarica (vascular unloading technique). In pratica, se la trasparenza del dito aumenta, indicando una costrizione, la pressione esterna viene ridotta, se la trasparenza diminuisce, la pressione esterna viene aumentata. La pressione applicata in ogni istante alla fascia segue quindi con continuità la pressione endovasale e viene registrata per il monitoraggio continuo pressorio non invasivo.

La pressione al dito è uguale alle pressione brachiale? 1) P idrostatica (dovuta al dislivello ditocuore) 2) Caduta di pressione dovuta alla distanza dal cuore e riflessioni P g h Onda incidente Onda riflessa

Z f f P F Z C i i i i i i i 0 i i i i 0 F P Z ) sen( F F F(t) ) sen( P P P(t) Carico arterioso: impedenza vascolare 0 0 0 F P R Resistenza vascolare periferica Zc: impedenza caratteristica (media dei valori dopo il primo minimo, in genere dalla 3a alla 10a armonica) 2 ) ( ) ( ) ( 2 ) ( ) ( ) ( t F Z t P t P t F Z t P t P c b c f

Pressione totale ottenuta modificando (anticipando e posticipando) il delay dell onda riflessa (+/-100ms, +/-200ms).

Finger arterial versus intrabrachial pressure and continuous cardiac output during head-up tilt testing in healthy subjects W.T. Jellema, B.P.M. Imholz, J. Van Goudoever, K.H. Wesseling, J.J. Van Lieshout Clinical Science 1996; 91:193-200 8 soggetti normotesi Età: 25 anni (range 19-32). Altezza: 186 cm (range 181-197) Peso: 76 kg (range 72-90). (Nessun episodio sincopale, nessuno pratica sport) Original tracings during the three stages of tilt of all subjects: after 1 min head-up tilt (TILTinitial), halfway head-up tilt (TILTmid) and 1 min before tilt back (TILTend). Thin lines: finger waveforms (FINAPRES) bold lines: brachial waveforms.

Differenze fra le pressioni sistoliche (SBP), diastoliche (DBP) e medie misurate (MBP) con il finapress (FINAP) e quelle intrabrachiali (IAP). Ogni valore rappresenta la media su 10s per ogni minuto di esame. I simboli diversi indicano soggetti diversi. Le linee orizzontali indicano il valore medio ± 1.96 SD. Finger arterial versus intrabrachial pressure and continuous cardiac output during head-up tilt testing in healthy subjects W.T. Jellema, B.P.M. Imholz, J. Van Goudoever, K.H. Wesseling, J.J. Van Lieshout Clinical Science 1996; 91:193-200

Confronto fra le pressioni misurate con FINAP e IABP nell ultimo minuto di tilt in 4 soggetti nei quali la pressione sistolica è calata di > 20mmHg e il tilt è stato interrotto. Linee sottili: FINAP Neretto: IABP Non ci sono differenze significative fra gli andamenti. ESISTONO DIFFERENZE SIGNIFICATIVE FRA I VALORI ASSOLUTI DI SISTOLICA E DIASTOLICA. Finger arterial versus intrabrachial pressure and continuous cardiac output during head-up tilt testing in healthy subjects W.T. Jellema, B.P.M. Imholz, J. Van Goudoever, K.H. Wesseling, J.J. Van Lieshout Clinical Science 1996; 91:193-200

Gli strumenti nati dopo il Finapress, hanno quindi implementato degli algoritmi per correggere le onde pressori misurate al dito e rendere affidabili non solo gli andamenti ma anche i valori assoluti. Come? Misura Onda di Pressione Brachiale Misura Onda di Pressione Aortica Onda di Pressione al dito Onda di Pressione al dito In contemporanea Funzioni di trasferimento (nel domino delle frequenze) Quindi il processo inverso: Funzione di trasferimento Funzione di trasferimento Misura Onda di Pressione al dito Onda di Pressione Brachiale Onda di Pressione Aortica

TF tra Pressione aortica e brachiale durante vasodilatazione in soggetto normale. TF tra Pressione aortica e brachiale in funzione dell età (in soggetti normali)

Portapres (la pressione è corretta dal sw beatscope) FINOMETER BRACHIAL ARTERY PRESSURE RECONSTRUCTIONS There is a delay of several dozen milliseconds between finger blood pressure pulsations and intra-brachial pulsations since the former travel further. In addition, their levels are generally lower and the waveforms appear more distorted, mainly due to reflections and pressure gradients. To correct the distortion in finger pressure relative to brachial artery pressure, a frequency dependent filter can be used to restore the waveform at the brachial level. This brachial artery pressure reconstruction technique allows clinicians and researchers to obtain the brachial arterial pressure if they wish to perform a more precise measurement at the heart level. Waveform filtering is done in real time. The transfer function from brachial to finger resonates at about 8Hz (thin top trace). This causes oscillatory distortions of the finger wave. Distortions can be removed by a digital filter that has an anti-resonance at 8Hz (bottom trace). The two transfer functions compensate each other almost perfectly to produce a desirably flat overall transfer function (thick trace). Correzione pressione idrostatica e nel FinometerPRO calibrazione con pressione brachiale (metodo Return-toFlow)

NEXFIN (BMEYE) The arterial BP wave changes shape as it travels along the arteries, with systolic pressure increasing while diastolic and mean pressure decrease. These effects are compensated by applying a physiological model, yielding brachial BP finger arterial BP

Le funzioni di trasferimento usate dagli strumenti in commercio sono ricavate come media di funzioni di trasferimento di soggetti normali e sani (si trovano in letteratura) in condizioni stazionarie e stabili. Sono fisse e memorizzate nel software residente sull apparecchio.!!!! La morfologia dell onda di pressione si modifica: In funzione dell età (cambia l elastanza vascolare); In presenza di patologie vascolari e cardiache congenite; In presenza di situazioni fisiologiche anomale (ipotensione ortostatica, sincope, etc). Le pressioni fornite da questi strumenti vanno sempre considerate criticamente!! Possiamo considerare affidabili gli andamenti ma non i valori assoluti!! Alcuni strumenti usano la pressione brachiale misurata con metodo oscillometrico per calibrare il segnale di pressione ricostruito. In tal modo otteniamo dei valori di sistolica e diastolica più affidabili (sicuramente in condizioni stazionarie) anche se le forme d onda rimangono alterate.

FinometerPRO calibrazione con pressione brachiale (metodo Return-toFlow). Return to flow: si gonfia il bracciale e si misura la pressione sistolica in corrispondenza del ritorno del flusso al dito. Il bracciale va allo stesso braccio in cui si misura la pressione al dito e la calibrazione viene eseguita all inizio della procedura soltanto usando il valore di sistolica. Bos W J W et al. Circulation 1996;94:1870-1875

TASK FORCE MONITOR Continuous non-invasive AP (CNAP) is obtained by applying pressure via the finger cuffs such that the blood volume flowing through the finger arteries is held constant (i.e. volume-clamping). The finger arterial pressure was scaled to central AP every 15 min by a scaling function with NIAP values as arguments. After applying this scaling operation, CNAP values correspond to the values measured at the brachial artery. Il bracciale va all arto controlaterale rispetto a quello in cui si misura la pressione al dito e la calibrazione viene eseguita durante tutta la procedura usando due valori pressori misurati con il metodo oscillometrico.

Misura della frequenza cardiaca Devo misurare l intervallo temporale fra un battito e il successivo Posso ottenere la stessa informazione utilizzando le curve di pressione arteriosa? Alcuni apparecchi che vengono proposti stand-alone per la valutazione dei riflessi cardiovascolari non prevedono l acquisizione dell ecg

Caso 1 E impossibile misurare la frequenza cardiaca dalle onde di pressione (sia che si valuti il piede di salita sia che si valuti il picco )

Caso 2 In caso di asistolia è importante poter monitorare il tracciato ECG!!! L ECG è fondamentale per la corretta valutazione della frequenza cardiaca e per il monitoraggio del paziente.

Altri parametri di interesse clinico CARDIAC OUTPUT e STROKE VOLUME: indici della performance cardiaca e necessari per la valutazione delle resistenze vascolari. EEG: informazioni sulla attività cerebrale e verifica in tempo reale delle modificazioni dello stato neurologico. RESPIRO: corretta valutazione dell aritmia sinusale, valutazione di iperventilazione o apnee sui parametri cardiovascolari; monitoraggio della corretta esecuzione della fase di respiro profondo. FLUSSO CUTANEO: vasodilatazione e vasocostrizione come conseguenza della attività simpatica. FLUSSO TRANSCRANICO: parametri emodinamici cerebrali in funzione dell attività simpatica e vagale (es. durante Tilt Test)

CARDIAC OUTPUT Metodi standard: Fick; flussimetro elettroagnetico, termodiluizione (continua o a bolo); Diluizione di indicatori (continua o a bolo), flussimetria doppler. Sono evidentemente non applicabili in valutazioni ambulatoriali del SNV Possibili alternative: Pressure Contour Method (Finometer, portapres con Beatscope, Nexfin) Impedenziometria transtoracica (es. TFM)

Pressure Contour Method (AORTIC PRESSURE WAVE) Sagawa K, Lie RK, Schaefer J. Translation of Otto Frank s paper Die Grundform des Arteriellen Pulses Zeitschrift fur Biologie 1899;37:483-526. J Mol Cell Cardiol. 1990;22(3):253-77.

Ann Card Anaesth. 2008 Jan-Jun; 11(1):56-68. Cardiac output monitoring. Mathews L, Singh RK. Diastolic pulse contour analysis (Compliance considerata costante e introdotta a mano nel modello) Systolic pulse contour analysis (Z A introdotto come una costante calcolata su soggetti sani) PiCCO system (Pulsion Medical Systems, Munich, Germany) (Z A è parametrizzata in funzione dell età del soggetto con una formula ricavata sempre su soggetti sani) Modelflow pulse contour analysis (La compliance aortica e Z A sono funzioni non lineare di genere ed età e sono ricavate sempre da precedenti studi su soggetti sani) Usato da Finometer e Nexfin Pulse power analysis (scompone l onda di pressione in incidente e riflessa e consente di misurare cambiamenti nello SV e non valori assoluti, a meno di una calibrazione) Long time interval analysis of peripheral arterial blood pressure waveform (l analisi viene effettuata non beat to beat ma su scale di tempi più lunghe) Pulse contour cardiac output estimation without external calibration (Z A è funzione di sesso, età, altezza, peso, body surface area) Pressure recording analytical method (PRAM) (non necessita calibrazione ma è una metodica ancora poso usata

Carico arterioso: impedenza vascolare P(t) F(t) Z R i 0 P F Pi F i P F 0 0 0 0 i i P F i i sen( sen( Resistenza vascolare periferica i i i i ) ) P F Z Z C Zc: impedenza caratteristica (media dei valori dopo il primo minimo, in genere dalla 3a alla 10a armonica) f f

Carico arterioso: P max P Aorta R 1 P(t) k P F 0 0 2 P 1 RC 0 e kt 3 Resistenza Idraulica Pmin C V P Compliance V

Change in heart rate aortic characteristic impedance (Zc) at rest and during handgrip in normotensive and hypertensive patients Linea continua: pz ipertesi Linea tratteggiata: soggetti normotesi Chirinos J A et al. Am J Physiol Heart Circ Physiol 2010;298:H320-H330 2010 by American Physiological Society

Osservazioni: Questi metodi necessitano della pressione aortica (che nel nostro caso è ricavata da quella al dito, con tutti i problemi legati alla ricostruzione della forma d onda corretta). Alcune assunzioni fatte per applicare alcuni metodi sono sbagliate (es. Compliance costante). I metodi più complessi si basano sui risultati di altri studi pubblicati e tutti riferiti a soggetti sani con pressioni prelevate in condizioni stazionarie. Tutti i sistemi a parte gli ultimi due necessitano di calibrazione con metodi validati e affidabili (invasivi). Calcolare le resistenze vascolari come rapporto fra pressione media e flusso medio quando il flusso è ricavato direttamente dalla pressione pone sicuramente un dubbio sul valore scientifico del risultato.

December 2009, vol. 67, no 11 Relative changes in cardiac output can be accurately monitored noninvasively with data obtained from the finger arterial pressure waveforms. However, an invasively derived calibration of cardiac output is needed to obtain more reliable absolute data on cardiac output Although accuracy and reproducibility have been investigated in some small trials, these should be further assessed thoroughly in various patient groups in different clinical conditions before this technique can be widely used. Moreover, further development to obtain absolute values of cardiac output without invasive calibration might give a substantial added value to the method

An evaluation of cardiac output by five arterial pulse contour techniques during cardiac surgery 1.R. B. P. De Wilde 1, J. J. Schreuder 2, P. C. M. Van Den Berg 1, J. R. C. Jansen 1 Volume 62, Issue 8, pages 760 768, August 2007 Conclusion All pulse contour techniques need a reliable invasive calibration. After calibration, most methods may replace the thermodilution method with a precision of 10% (i.e. the averaged result of three randomly performed measurements). The Modelflow and Hemac techniques could replace the thermodilution estimates based on the averaged result of four measurements done equally, spread over the ventilatory cycle. The slightly lower precision of the continuous pulse contour cardiac output techniques may, in clinical settings, be outweighed by the advantages of being automatic and continuous. Under research conditions the use of the conventional thermodilution method with four measurements equally spread over the ventilatory cycle remains the method of choice.

SERVE UN METODO PER LA MISURA DEI PARAMETRI EMODINAMICI CHE SIA INDIPENDENTE DA QUELLO PER IL PRELIEVO DELLA PRESSIONE.

Impedenziometria transtoracica SV ( dz 3 L dt) TLVE 1.4 Z (Sramek) 0 MAX LVET dz ( ) dt MAX Z(t)

Ann Card Anaesth. 2008 Jan-Jun;11(1):56-68. Cardiac output monitoring. Mathews L, Singh RK. Recent technological advances have allowed the development of completely non-invasive CO monitoring using impedance cardiography. This technique is ideal for continuous online and intermittent CO monitoring. However, large amount of thoracic fluid may interfere with the impedance signal making the haemodynamic data less reliable L utilizzo della impedenza transtoracica, pur non essendo privo di errori, garantisce affidabilità e indipendenza dal metodo di misura della pressione, consentendo la valutazione delle resistenze vascolari che sono effettivamente un risultato indipendente del metodo!!!

Laser Doppler Se un onda investe un oggetto in movimento, l onda riflessa o diffusa ha una frequenza diversa dall onda incidente. La variazione di frequenza è direttamente proporzionale alla velocità dell oggetto rispetto alla sorgente dell onda. f D f f 0 2f 0 (1 v v )cos Il segnale doppler rilevato è una media dei segnali diffusi da capillari, arteriole e venule (in genere entro 1mm di profondità) I valori di flusso non sono calibrati ma espressi in unità arbitrarie. 0

Doppler pulsato f D f f 0 2f 0 (1 v v 0 )cos A/D t F.F.T t A(f) f 0 f-f 0

Cosa troviamo oggi sul mercato per lo studio dei riflessi cardiovascolari: Soluzioni all-in-one

Parameter Portapres (FMS, The Nederlands) Finometer (FMS, The Nederlands) Blood Pressure SYS, DIA and MEAN Heart rate Inter beat interval Cardiac output Stroke volume Pulse rate variability Baroreflex sensitivity Total peripheral resistance Total arterial compliance Max. steepness of current upstroke Ascending aortic impedance at DIA Left ventricular ejection time Rate pressure product Nexfin HD (BMEYE) Parameter (Portapres con BeatScope software) Blood Pressure SYS, DIA and MEAN Heart rate Inter beat interval Cardiac output Stroke volume Total peripheral resistance

Criticità: 1) L acquisizione dell ECG viene fatta con moduli opzionali esterni. 2) I parametri emodinamici sono derivati dall onda di pressione: - Questa è alterata dagli algoritmi di correzione (correzione per misurazione al dito e non al braccio); -In caso di eventi patologici, l onda di pressione si modifica (in condizioni particolari scompare) e i parametri derivati non sono più affidabili (MEGLIO UN METODO INDIPENDENTE PER LA MISURA DI CO E SV!!!) 3) Non esiste la possibilità di personalizzare le analisi che rimangono generiche e non dedicate allo studio delle manovre. 4) Non c è acquisizione di EEG, respiro, doppler transcranico e flussi cutanei.

Task Force Monitor, CNSystem, Austria Parameteri acquisiti: ECG; Pressione oscillometrica; Pressione beat-to-beat con metodica finapres; Impedenza transtoracica. Parametri derivati: gittata sistolica e cardiaca; resistenza periferica vascolare; inotropia del cuore; tono simpatico e vagale (variabilità della pressione e della frequenza cardiaca); sensibilità del riflesso barorecettore. Vantaggi: 1) Misura dei parametri emodinamici indipendente dalla misura della pressione (CO e SV tramite impedenziometria transtoracica). Criticità: 1) Non esiste la possibilità di personalizzare le analisi che rimangono generiche e non dedicate allo studio delle manovre. 2) Gli algoritmi di analisi sono chiusi e non verificabili dall operatore. 3) Non c è acquisizione di EEG, respiro, doppler transcranico e flussi cutanei.

Nel 18% dei casi il TFM ha fornito un risultato errato. Perché? Possiamo solo fare delle ipotesi: (assenza di stazionarietà del tacogramma, ordine del modello sbagliato ) Confronto fra HRV automatica eseguita dal TFM e analisi autoregressiva controllata dall operatore I. Corazza, M.C. Tozzi, G. Barletta, L. Soliera, P. Cortelli, R. Zannoli. (2007). Monitoraggio clinico del Tilt Test: Task Force monitor e analisi HRV (Heart rate Variability). GIORNALE ITALIANO DI ARITMOLOGIA E CARDIOSTIMOLAZIONE. 3 Congresso Multidisciplinare sulla Sincope. Firenze. 18-2 Novembre 2007. vol. 10(3), pp. 44.

Soluzione integrata Sistema di acquisizione Analogico/Digitale a cui interfacciare i sensori di interesse: - Elettrocardiografo - Sistema per il prelievo della pressione arteriosa - CO e SV tramite impedenza transtoracica - Flusso cutaneo - EEG - Respiro nasale e addominale - Doppler transcranico -. Software di analisi per l estrazione dei parametri di interesse

Finapres Possibili sensori di pressione Portapres Nexfin HD (BMEYE) Finometer

ECG (Cardioline) EEG (EBNeuro) Flussi cutanei (Perimed) Impedenza transtoracica (Biopac) Quad AC Amplifier System for EEG and breath (Grass) Doppler transcranico

Grazie.

Misura delle portata cardiaca mediante analisi dell onda di pressione aortica (Ann Card Anaesth. 2008 Jan-Jun; 11(1):56-68. Cardiac output monitoring. Mathews L, Singh RK.)

Diastolic pulse contour analysis Diastolic pulse contour analysis is based on the basic windkessel model, in which it is assumed that the arterial compliance is constant over the physiological pressure range and peripheral vascular resistance does not vary with in the diastolic interval. Based on these assumptions the arterial blood pressure should decay exponentially during diastolic time intervals with a time constant (τ). The time constant, τ, is given as τ = C A R The standard equation for the diastolic pressure (voltage) for the circuit shown in figure is P(t) = A 1 exp[-(t-t 0 )/τ+ + A 2 where, t, is the time, (A 1 + A 2 ) represent end-diastolic pressure, A 2 is mean circulatory pressure. The time constant, τ, is obtained by fitting the above analytical expression into the diastolic portion of the waveform. By measuring the pulse wave velocity over the aorta (carotid to femoral) C A could be estimated. Knowing τ and C A, peripheral resistance R is calculated. From the mean arterial pressure (MAP) and R, using ohm's law flow (SV) is calculated. In this model since the arterial compliance is assumed to be constant, which is not in reality, the derived SV values does not reflect the true SV. For accurate values calibration against a standard method is carried out. Indietro

Systolic pulse contour analysis In the windkessel model, the pulsatile systolic area (PSA) under the pressure curve above a horizontal line drawn from the diastolic point and bounded by a vertical line through the lowest point of incisura (area under the pressure curve from the start of the upstroke to the incisura as shown in figure and SV are related by means of characteristic impedance of the aorta (Z A ). Wesseling and coworkers developed a pulse contour analysis technique based on a transmission line model of the arterial tree. In this model the SV is related to PSA and Z A by the equation, SV = PSA/Z A PSA = ejection {P AO (t) - P ED }dt where P AO (t) is aortic pressure at time t and P ED is end-diastolic pressure. Although PSA can be found from the area under the curve there are no simple direct methods to establish the appropriate value of Z A. Taking into account the combined effects of varying heart rate and MAP Wesseling and coworkers formulated an equation for SV as, SV = K (163 + HR - 0.48 MAP) ejection {P AO (t) - P ED }dt Where K is an individual calibration constant, HR heart rate. Since Z A is influenced by aortic cross section and compliance, both of which are pressure and age dependant and also a computer model of the circulation indicated that Z A is dependant on HR and aortic properties change with age the above equation is modified as SV = [PSA/(Z A ) ini ] [1,320 + HR 10 - age (0.28MAP-16)]/2000 Where the initial value for Z A, (Z A ) ini, is (90+age)/1,000. In the Wesseling model a linear combination of HR, MAP and age multiplied by an individual calibration factor is used to estimate Z A. Antonutto and coworkers used a multiple linear regression including pulse pressure (PP), HR and MAP to estimate Z A. Both the methods have been validated. Since Z A is not accurately known only uncalibrated SV is derived. For accurate SV values calibration against a standard method is carried out. Indietro

PiCCO system (Pulsion Medical Systems, Munich, Germany) The PiCCO system is a continuous CO monitor whose working principle is based on the Wesseling's model and the software used have the original Wesseling algorithm. However, it deviates from Wesseling's modified method in that no age related corrections for pressure dependant non-linear changes in aortic cross sectional area are incorporated. In the second generation PiCCO equipment a more sophisticated algorithm that analyzes the actual shape of the waveform in addition to the PSA is used. From the shape of the arterial pressure curve after the dicrotic notch the exponential decay time constant (τ = C A R) is calculated and R = MAP/CO. CO is obtained from the reference method. Since τ and R are known C A can be computed. SV is computed using the formula, SV = K * ejection {P AO (t) - P ED }(t) + C A dp/dt] dt Where K is the calibration factor and it is done by transpulmonary thermodilution. Several clinical studies and an experimental study showed good agreement between PiCCO and thermodilution. Two different groups demonstrated that SV variation measured with PiCCO in patients before, during and after coronary artery bypass grafting (CABG) could predict fluid responsiveness. The technique may also be used in children. Peters and coworkers reported the haemodynamic response to terlipressin in an 11 year-old patient with septic shock. Indietro

Modelflow pulse contour analysis The Modelflow method computes an aortic flow waveform from the arterial pressure waveform using the three element model. The model is developed by Wessling and coworkers. The aortic impedance is a function of aortic cross sectional area, the instantaneous flow and compliance. Both compliance and impedance are nonlinear and depend on the elastic properties of the aorta. Unlike the previous models in Modelflow, the impedance and compliance nonlinearity are taken into account for SV calculations. The elastic properties of the human thoracic and abdominal arteries and changes in aortic cross sectional area with changing pressure were studied by Langewouters and coworkers. The aortic cross sectional area is described by them as a function of pressure by an arctangent relation with three parameters. Aortic impedance and arterial compliance are then presented in terms of the aortic pressure area relation and its derivative. In the Modelflow method, the two elements the aortic impedance and arterial compliance are computed making use of a built in data base of arctangent area-pressure relationships. Subject's gender and age were the input. Instantaneous impedance and compliance values so obtained are used in a model simulation to compute an aortic flow waveform. The peripheral vascular resistance is calculated for each beat and updated. Thus in short, the method computes arterial flow waveform from arterial pressure waveform with continuous nonlinear corrections for variations in aortic diameter, impedance and compliance during the arterial pulsation. Integration of flow waveform per beat gives SV. The model assumes a normal human aorta and proper functioning of aortic valve. The maximal aortic diameter during ejection is the parameter included in the model that does not regress with age and its variability is considerable, hence derived SV does not reflect the true value. For accurate values calibration against a standard method is needed. The commercially available system based on the above algorithm is Modelflow R (Netherland's Organization for Applied Scientific Research, Biomedical Instrumentation, BMI-TNO) and is calibrated by the mean of 3 or 4 conventional thermodilution measurements equally spread over the ventilatory cycle. Several clinical studies carried out in different clinical settings demonstrated good correlation with thermodilution. The results of Jellema and coworkers showed that once calibrated by thermodilution, Modelflow CO correlated well with thermodilution CO even after 48 hours of monitoring in ICU patients. Indietro

Pulse power analysis The pulse pressure measured from the arterial trace is a combination of an incident pressure wave (ejected from heart) and reflected wave (from the periphery). In order to calculate SV the two waves need to be separated. This is further complicated by the fact that the reflected wave changes in size depending upon the proximity of the sampling site to the heart and also the patient's age. The algorithm used in pulse power analysis technique takes care of this aspect. The algorithm used is based on the assumption that the net power change in a heart beat is SV minus blood lost to the periphery during the beat and there exists a relation between net power and net flow. Since the whole beat is taken for analysis the method is independent of the position of the sampling site. In this method the pressure wave is transformed to a volume wave and using the mathematical technique of autocorrelation of the volume waveform the net power and beat period are derived. Net power is proportional to net flow (SV). It is only possible to calculate changes in SV rather than absolute values using this method. For accurate values, calibration against a standard method (Lithium dilution technique) is carried out. The commercial equipment based on the pulse power analysis is the LiDCO plus (LiDCO Ltd, Cambridge, UK). Several studies have compared thermodilution and LiDCO plus and found agreement. Despite a negligible bias, the limits of agreement were close to (±1.5L/min). Indietro

Long time interval analysis of peripheral arterial blood pressure waveform The varieties of pulse contour techniques described above are conceptually similar; the waveform analysis is performed only over time scales with in a cardiac cycle. However at such short time scales pressure waveforms are dominated by complex waves propagating back and forth the distributed arterial tree. According to the transmission line theory the confounding effects of the wave phenomena will diminish over large time scales. Based on the theory, Lu et al, developed a novel algorithm in which a long time interval mathematical analysis of the waveform is carried out. From the analysis of the waveform over time scales larger than cardiac cycles, the arterial blood pressure response to a single solitary cardiac contraction is estimated. Then the time constant, τ, is estimated by fitting a mono-exponential function P(t) = A exp[-t/τ+ + w(t) to the tail end of this response curve once the faster wave reflections are vanished. The parameters A and τ are estimated through least square minimization of the measured residual error [w(t)]. The validity of the technique was ascertained with respect to intra-arterial pressure waveforms obtained from open chest swines instrumented with aortic flow probes over a wide physiological state. This technique was also evaluated on humans based on previously published invasive and non-invasive arterial pressure data sets. Calibration against a standard method is necessary for measuring absolute SV. Indietro

Pulse contour cardiac output estimation without external calibration Flo Trac/Vigileo (Edwards Life Sciences, Munich, Germany). The pulse contour and pulse power based technologies described above require another standard technique to provide calibration constant compensating for the algorithms' inability to independently assess the ever changing effects of vascular tone on SV. Flo Trac/Vigileo system calculates CO, by using arterial pressure waveform characteristics in conjunction with patient demographic data, without external calibration. Preparation for monitoring consists only of entering the age, height, weight and gender into the unit and zeroing the transducer. The algorithm works on the principle that the pulse pressure (difference between the systolic and diastolic pressures) is proportional to SV and inversely proportional to aortic compliance. Aortic pressure is sampled at 100 Hz and analyzed and updated every 20 seconds. The standard deviation of the 2000 data points (SdAP) is proportional to pulse pressure, which is proportional to SV SV = K(SdAP) Where K is a constant quantifying vascular tone (arterial compliance and resistance) and is derived from patient characteristics (sex, age, height, weight, body surface area) according to the method described by Langewouters and coworkers. A recent study indicated that the algorithm works satisfactory when compared with intermittent and continuous thermodilution techniques in post operative cardiac surgical patients. Chakravarty and coworkers compared CO values obtained with PAC-CCO, PiCCO and Flowtrac techniques, in 15 patients undergoing offpump coronary artery bypass grafting. They found that the CO values obtained from all the techniques were interchangeable. The bias and precision were (in L/min), PAC (0.03, 0.06), PiCCO (0.13, 0.1) and Flowtrac (0.15, 0.04). Indietro

Pressure recording analytical method (PRAM) PRAM is a technique based on the mathematical analysis of pulse profile changes based on the theory of perturbations, by which any physical system under the effect of a perturbation tend to react to achieve its own state of minimum energy. The basic principle of PRAM is that, in any given vessel, the volume changes occur mainly because of radial expansion of the artery in response to variations in pressure. PRAM measure absolute SV without external calibration by determining the parameters able to characterize the elastic properties of the arteries from the objective analysis of the pressure wave profile. SV is calculated using the formula SV = PSA/(P/t) K Where P/t is pressure wave profile expressed as the variation of pressure over t during the entire cardiac cycle (dp/dt). K is a factor inversely proportional to instantaneous acceleration of the vessels cross sectional area. The value of K is obtained from the expected (theoretical) MAP, which is constant and measured MAP. Only three studies have been carried out so far to prove its efficacy to determine absolute CO values. The recent study is CO determination in animals under various haemodynamic conditions and has found to give CO values comparable to that obtained by electromagnetic flowmetry and conventional thermodilution. Indietro