CARDIOVASCULAR ANALYTIC SYSTEM AND METHOD

Abstract

We describe a system for determining relative changes in at least one parameter of cardiovascular function. The system provides an output showing a relative change of the parameters associated with cardiovascular function over a period of time. This relative change is between a time averaged mean of cardiovascular parameters (for each pulse within a series of pulses from an arterial blood pressure waveform data) and a baseline cardiovascular parameter value based on first and second pulses within the blood pressure waveform data. The relative change of the parameters over time is used to project a trend in the parameters associated with cardiovascular function.

Claims

1-25. (canceled)

26. A system for determining relative changes in at least one parameter of cardiovascular function, the system comprising: an input for receiving arterial blood pressure waveform data; and signal processing apparatus, coupled to said input and configured to: detect a series of pulses from the arterial blood pressure waveform data; calculate at least one baseline cardiovascular parameter value for a first pulse using data from the first pulse and a second pulse within the detected series of pulses, wherein the first pulse is consecutive to the second pulse; calculate at least one cardiovascular parameter value for a plurality of pulses within a time period comprising a sequence of n pulses in the arterial blood pressure waveform data; determine a time averaged mean of each of the plurality of cardiovascular parameter values; for each of the time averaged mean cardiovascular parameter values, calculate the relative change of the respective time averaged mean cardiovascular parameter value based on the difference between the respective time averaged mean cardiovascular parameter value and the baseline cardiovascular parameter value.

27. A system according to claim 26, wherein there is a predetermined and constant time period between the first pulse of the detected series of pulses and the sequence of n pulses.

28. A system according to claim 26, wherein the at least one parameter of cardiovascular function comprises nominal cardiac output.

29. A system according to claim 28, wherein the at least one parameter of cardiovascular function comprises systemic vascular resistance, and wherein the signal processing apparatus is further configured to calculate the relative change in systemic vascular resistance using the relative change in nominal cardiac output.

30. A system according to claim 29, wherein the relative change in systemic vascular resistance is calculated by dividing a determined time average mean of mean arterial blood pressure by the relative change in nominal cardiac output.

31. A system according to claim 29, wherein the relative change in systemic vascular resistance is calculated by: calculating a baseline total systemic vascular resistance for a first pulse; calculating total systemic vascular resistance for a plurality of pulses within a time period comprising a sequence of n pulses in the arterial blood pressure waveform data: determining a time averaged mean of total systemic vascular resistance; for each of the time averaged mean total systemic vascular resistance values, calculating the relative change of the respective time averaged mean total systemic vascular resistance based on the difference between the respective time averaged mean total systemic vascular resistance value and the baseline total systemic vascular resistance value.

32. A system according to claim 31, wherein total systemic vascular resistance is calculated by dividing mean arterial blood pressure by nominal cardiac output.

33. A system according to claim 28, wherein the at least one parameter of cardiovascular function comprises venous return driving pressure, and wherein the signal processing apparatus is further configured to calculate the relative change in venous return driving pressure using nominal cardiac output and mean arterial blood pressure; and optionally wherein the relative change in venous return driving pressure is calculated from the relative change in cardiac output and a change in mean arterial pressure.

34. A system according to claim 26, wherein the system further comprises a memory configured to store input arterial blood pressure waveform data and parameter of cardiovascular function data.

35. A system according to claim 26, wherein the signal processing apparatus is further configured to determine if the at least one cardiovascular parameter is within a predetermined range; and optionally wherein the system is configured to alert a user if said at least one cardiovascular parameter is outside the predetermined range.

36. A system according to claim 35, wherein the signal processing apparatus is further configured to assign a signal abnormality index value to a pulse in the sequence of n pulses dependent upon the outcome of said determination, wherein the pulse corresponds to a pulse for which the at least one cardiovascular parameter is outside the predetermined range; and/or wherein the signal processing apparatus is further configured to determine a length of time the at least one cardiovascular parameter is outside the predetermined range.

37. A system according to claim 26, wherein the signal processing apparatus is further configured to extrapolate the at least one cardiovascular parameter to a future time; and optionally wherein the signal processing apparatus is configured to determine if a statistical trend is present in the at least one cardiovascular parameter, and wherein the signal processing apparatus is configured to output the extrapolated cardiovascular parameter at a future time dependent upon said outcome of determination of statistical trend.

38. A system according to claim 37, wherein the signal processing apparatus is configured to extrapolate the at least one cardiovascular parameter at a future time using a linear regression technique.

39. A system according to claim 38, wherein the signal processing apparatus is configured to determine if a statistical trend is present in the at least one cardiovascular parameter by calculating the number of standard deviations of the cardiovascular blood pressure parameter about a regression line and determining if the number of standard deviations is greater than a predetermined threshold.

40. A system according to claim 37, wherein the signal processing apparatus is configured to extrapolate the at least one cardiovascular parameter at a future time if a treatment is administered.

41. A system according to claim 37, wherein the system is configured to alert a user if said extrapolated at least one cardiovascular parameter at a future time is outside the predetermined range.

42. A system according to claim 26, further comprising a user interface configured to display the relative change in at least one parameter of cardiovascular function; and/or wherein the signal processing apparatus is configured to remove artefacts from the arterial blood pressure waveform data.

43. A system according to claim 26, wherein the system is configured to selectively output the calculated relative change of the time averaged mean cardiovascular parameter value dependent upon the signal quality of the arterial blood pressure waveform data received from the input, and wherein the system outputs the calculated relative change of the time averaged mean cardiovascular parameter value only when the signal quality of the arterial blood pressure waveform data is above a threshold value.

44. A method of determining relative changes in at least one parameter of cardiovascular function, the method comprising: receiving arterial blood pressure waveform data; detecting a series of pulses from the arterial blood pressure waveform data; calculating at least one baseline cardiovascular parameter value for a first pulse using data from the first pulse and a second pulse within the detected series of pulses, wherein the first pulse is consecutive to the second pulse; calculating at least one cardiovascular parameter value for a plurality of pulses within a time period comprising a sequence of n pulses in the arterial blood pressure waveform data; determining a time averaged mean of each of the plurality of cardiovascular parameter values; and for each of the time averaged mean cardiovascular parameter values, calculating the relative change of the respective time averaged mean cardiovascular parameter value based on the difference between the respective time averaged mean cardiovascular parameter value and the baseline cardiovascular parameter value.

45. A method of preventing or treating hypotension, comprising: determining the relative changes in at least one parameter of cardiovascular function according to claim 44; and administering a treatment in response to said relative changes in at least one parameter of cardiovascular function.

Description

LIST OF FIGURES

[0084] The present invention will now be described, by way of example only, and with reference to the accompanying figures, in which:

[0085] FIG. 1 shows a plot of the Mean Arterial Pressure over a 2 hour time period during a major gastro-intestinal surgical procedure;

[0086] FIG. 2 shows a simplified systems diagram;

[0087] FIG. 3 shows an example implementation of the software architecture;

[0088] FIG. 4 shows an example beat detection, feature extraction and signal quality checking algorithm;

[0089] FIG. 5 shows the beat detection algorithm in more detail; and

[0090] FIG. 6 shows an example User Interface for the system.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0091] The technology and innovations described here are intended to enable the creation of clinical decision support systems and semi- and fully-automated care systems for reducing the incidence of low blood pressure (hypotension) and improving cardiovascular stability during surgical procedures and in other critical care environments such as intensive care, emergency departments and casualty care.

[0092] In brief, the present invention provides a system for determining relative changes in at least one parameter of cardiovascular function. Ultimately, the present invention provides an output showing a relative change of the parameters associated with cardiovascular function over a period of time. This relative change is between a time averaged mean of cardiovascular parameters (for each pulse within a series of pulses from an arterial blood pressure waveform data) and a baseline cardiovascular parameter value based on first and second pulses within the blood pressure waveform data.

[0093] FIG. 2 shows a very simplified functional diagram of the system.

[0094] In its most fundamental form, the system 10 comprises an input 30 for receiving arterial blood pressure waveform data, a signal processor 20 that may receive the arterial blood pressure waveform data and that is configured to process the data. A display 40 may be coupled to this system in order to display the resulting output that assists in the determination of which action to take.

[0095] The input 30 may be a patient monitor; which can include a catheter, such as an indwelling catheter or arterial line connected to a pressure transducer.

[0096] The signal processor may perform a number for functions or calculations. The signal processor may be a single unit performing a plurality of functions or calculations, or a plurality of units communicating with each other to perform the plurality of functions or calculations.

[0097] The arterial blood pressure waveform data comprises a sequence of data for a patient's blood pressure over a period of time. Preferably the waveform data is a continuous stream of blood pressure waveform data, or it may be a block of data.

[0098] The signal processor is configured to detect a series of pulses from the arterial blood pressure waveform data (this will be described in more detail below).

[0099] The signal processor then calculates a baseline cardiovascular parameter value for a first pulse using data from the first pulse and a second pulse within the detected series of pulses. The first pulse and second pulses are consecutive pulses. The baseline data provides a baseline value against which other values are compared. The cardiovascular parameter value may, for example, be nominal cardiac output and/or systemic vascular resistance.

[0100] The signal processor calculates at least one cardiovascular parameter value for a plurality of pulses within a time period comprising a sequence of n pulses in the arterial blood pressure waveform data. This cardiovascular parameter values for the plurality of pulses is then used to determine a time averaged mean of each of the plurality of cardiovascular parameter values.

[0101] The signal processor then calculates, for each of the time averaged mean cardiovascular parameter values, a relative change of the respective time averaged mean cardiovascular parameter value based on the difference between the respective time averaged mean cardiovascular parameter value and the baseline cardiovascular parameter value.

[0102] This value of relative change over time for each of the points can then be used to determine what action to take and when to take it, since the relative change over time will show a likely trend for example in the blood pressure that would indicate that, if no action were taken, the patient may experience hypotension in the immediate future.

[0103] When the cardiovascular parameter value is systemic vascular resistance, the signal processing apparatus is configured to calculate the relative change in systemic vascular resistance using the relative change in nominal cardiac output.

[0104] When the cardiovascular parameter value is venous return driving pressure, the signal processing apparatus is further configured to calculate the relative change in venous return driving pressure using nominal cardiac output and mean arterial blood pressure.

[0105] Based on these trends from the relative change over time compared to a baseline, methods of treatment for the possible onset of hypotension may be administered in good time to prevent those conditions from occurring. This may be done through notification to a suitably qualified clinician operating the system. It is within the scope of the present invention that automatic or semiautomatic systems for the administering of medicaments in response to the output of the system.

[0106] The technology is intended to provide an assistive decision support system that helps clinicians prevent hypotension by reacting earlier with the right treatment.

[0107] Some of the advantages of this system are presented below: [0108] Better situation awareness [0109] A focus on arterial blood pressure, especially mean arterial pressure (MAP) [0110] Setting of patient-specific targets [0111] Projection of how MAP is likely to evolve over the next period, in relation to the patient specific targets [0112] A panel of recent changes in associated cardiovascular parameters that informs the clinician about the underlying causes and thus appropriate treatment [0113] Labelling of physiological data with treatment interventions to enable the clinician to better assess the patient response to different treatments [0114] Computation of cumulative time patient is in different MAP ranges, associated with different levels of post-operative complication risk

[0115] Below is a summary of components and functions that may be advantageous in the formation of the system: [0116] A medical touch-screen computer connected to the multi-parameter monitor (MPM) [0117] Software performing the following functions: [0118] Communication with the MPM to acquire arterial blood pressure waveform data continuously [0119] Beat detection, feature extraction and signal quality checking [0120] Censoring beats and periods of signal where there are signs of signal abnormalities [0121] Remove noise by filtering the signal after abnormality censoring [0122] Compute derived parameters based on the filtered values [0123] A user interface to allow user input and to display numeric and graphical values [0124] Use of the Liljestrand and Zander algorithm (LZA, (Liljestrand and Zander, 1928)) to estimate cardiac output (CO) and in turn use this to estimate systemic vascular resistance (SVR) [0125] Restrict the display of CO and SVR information to relative changes over a recent period of time (eg 5 minutes) rather than using absolute values [0126] The advantages of this approach are that LZA has been shown to be the most reliable of pulse contour CO algorithms, it is most precise for changes in CO than absolute values (Broch et al., 2016a) and that CO and SVR relative changes are more meaningful to clinicians in assessing the patient and deciding treatment than absolute values [0127] Compute an estimate of the driving pressure for venous return (Pvr) and its changes over time. This provides the anaesthetist with an assessment of the changes in the volume state and cardiac function of the patient [0128] Statistical methods to detect MAP trends over the recent past (usually 2 minutes). If there are consistent trends to project them forward, compared to targets, for the next period (usually 2 minutes) [0129] Computation of cumulative times in different MAP ranges that correspond to different risks of hypotensive post-operative complications [0130] An innovative user interface design method: [0131] Gives prominence to MAP as the primary parameter [0132] Highlights MAP compared to a clinician-set target range [0133] Includes multiple simultaneous timescales to aid the clinician in assessing the patient and deciding treatment: [0134] 20 minutes default MAP history adjustable to the whole procedure duration [0135] 5 minutes of recent trends in the casual cardiovascular parameters including CO, SVR and heart rate (HR) [0136] 2 minutes forward projection of MAP trend compared to targets [0137] Display of cumulative time in MAP risk ranges [0138] Ability to add treatment markers to the physiological trends in order to show the effects of different treatments

[0139] FIG. 3 shows an example implementation of the software architecture. It preferably consists of the following items: [0140] User Interface: Display patient data and derived data trends and forecasts. Frontend displays data and receives user input but does not perform any physiological calculations. [0141] Device Drivers: Implement communications with multiparameter monitors. This item provides a stream of real-time data in a common data format. [0142] Signal Processing and Signal Quality Checking: Perform any processing on data from the device drivers and signal quality assurance. [0143] Physiological Data Processing: Computation of derived physiological parameters from quality-checked physiological signals. [0144] Patient Data and User Input Logging: User interactions, all displayed data in the User Interface, and raw input signals to be logged to the disk.

[0145] We will now go into more detail of the processing of the arterial blood pressure waveform data in order to provide the required trending data upon which a determination of the patient's condition may be made.

[0146] Beat Detection, Feature Extraction and Signal Quality Checking

[0147] The beat detection, feature extraction and signal quality checking algorithm follows that of Sun et al (Sun, Reisner and Mark, 2006) and consists of several components as shown in FIG. 4. (This algorithm has been shown to have a sensitivity of 1 and specificity of 0.91 compared to an expert annotator.)

[0148] ABP is the sampled arterial blood pressure waveform, and SAI is the signal abnormality index. The ABP is a signal sampled at a rate between 100 Hz and 250 Hz, and obtained from the MPM. The beat detection algorithm follows that of (Zong et al., 2003). (In comparison with 39,848 beats in a reference database, the difference between manually edit and algorithm determined ABP pulse onset was less than or equal to 20 ms).

[0149] The beat detection algorithm consists of three components: a low-pass filter, a windowed and weighted slope sum function, and a decision rule.

[0150] FIG. 5 shows the beat detection algorithm in more detail.

[0151] x.sub.n is the input of the low-pass filter and y.sub.n is the filtered ABP. The slope sum function converts y.sub.n to a slope sum signal z.sub.n. A decision rule is applied to z.sub.n to determine the ABP pulse onsets denoted by t.sub.onset(0), t.sub.onset(1), . . . , t.sub.onset(k), . . . .

[0152] Low-pass filter. The purpose of the low-pass filter is to suppress high frequency noise that might affect the ABP onset detection. The following second order recursive filter may be used:

y.sub.n=2y.sub.n-1−y.sub.n-2+(x.sub.n−2x.sub.n-5+x.sub.n-10)/25

[0153] At a sampling rate of 250 Hz, this has a 3 dB cut-off of about 16 Hz, at 125 Hz the 3 dB cut-off is about 8 Hz and at 100 Hz the 3 dB cut-off of about 7 Hz. The gain is 1× at 0 Hz. The phase shift is 20 ms at a sampling rate of 250 Hz (equivalent to 5 samples). The phase shift is 32 ms at a sampling rate of 125 Hz (equivalent to 4 samples). The phase shift is 40 ms at a sampling rate of 100 Hz. A phase adjustment should be made of 4 samples at 125 Hz and 4 samples at 100 Hz.

[0154] The time precision of heart period estimates from discrete time sampled data is 4 ms for 250 Hz, 8 ms for 125 Hz and 10 ms for 100 Hz sampling respectively.

[0155] Slope-sum function. The purpose of the slope-sum function (SSF) is to enhance the upslope of the ABP pulse and to suppress the remainder of the waveform. The windowed and weighted SSF at time i, z.sub.1 is defined as:

[00001]$z_i=\underset{k=i-w}{\overset{i}{.Math.}}\Delta u_k,\mathrm{where}\Delta u_k=\{\begin{array}{c}\Delta y_k:\Delta y_k>0\\ 0:\Delta y_k\le 0\end{array}$

[0156] Where w is the length of the analyzing window. Zong et al (2003) use w=128 ms or 32 samples for a sampling frequency 250 Hz. For a sampling frequency of 125 Hz, 16 samples is used. For a sampling frequency of 100 Hz, 13 samples is used.

[0157] The onset of the SSF pulse generally coincides with the onset of the ABP pulse as the SSF signal can only rise when the ABP signal rises.

[0158] Decision rule. The SSF is compared with a threshold to identify a potential ABP pulse onset. The threshold is defined as 60% of a threshold base value. The initial value of the threshold base value is three times the mean SSF signal averaged over the first 10 seconds of signal.

[0159] When the SSF crosses the threshold at a crossing point: [0160] Search back −150 ms for the minimum value of SSF, z.sub.min(k) and search forward +150 ms for the maximum value of SSF, z.sub.max(k) at t.sub.max(k); [0161] If z.sub.max(k)−z.sub.min(k)>threshold then accept the pulse detection for pulse k, else reject the pulse detection; [0162] If pulse detection is accepted, then: [0163] Search backwards to the point where SSF exceeds 2.5% of the maximum value—this is the onset point, t.sub.onset(k); [0164] Search forward +150 ms for the maximum value of raw ABP, x(k) at systolic t.sub.sys(k); [0165] Adjust calculated ABP onset time, t.sub.onset(k), by the phase lag (20 ms or 5 samples at 250 Hz sampling rate, 32 ms or 4 samples at 125 Hz sampling rate, 40 ms or 4 samples at 100 Hz sampling rate) to give diastolic t.sub.dia(k) and systolic t.sub.sys(k) times; [0166] Feature Extraction. Compute the features of the previous pulse k−1 for which the onset time marks the close: [0167] Look up from the raw ABP wave x.sub.n, diastolic pressure P.sub.dia(k−1) at diastolic time t.sub.dia(k−1) and systolic pressure P.sub.sys(k−1) at systolic time t.sub.sys(k−1); [0168] Compute heart period for this beat as

T.sub.H(k−1)=t.sub.dia(k)−t.sub.dia(k−1) sec; [0169] Compute pulse rate as

HR(k−1)=f(k−1)=60/T.sub.H(k−1) bpm; [0170] Compute pulse pressure

P.sub.pulse(k−1)=P.sub.sys(k−1)−P.sub.dia(k−1); [0171] Compute the noise of the pulse k−1, n(k−1), as the average of the negative slopes over the full pulse, using units of mmHg/100 ms. [0172] Apply a 300 ms “eye-closing” window to avoid double crossing. The eye closing window will start from the pulse onset time;

[0173] Abnormality indexing. With blood pressure features available, they are compared with the following table. If any one criteria is met, the signal abnormality index SAI is set to 1 for this beat.

TABLE-US-00001 Feature Abnormality Criterion Type P.sub.sys    P.sub.sys > 300 mmHg Physiological range P.sub.dia   P.sub.dia < 20 mmHg Physiological range P.sub.pulse  P.sub.pulse < 20 mmHg Physiological range MAP MAP < 30 or      Physiological range    MAP > 200 mmHg ƒ ƒ < 20 or Physiological range   ƒ > 200 bpm η        η < −40 mmHg/100 ms High frequency noise present ΔP.sub.sys = P.sub.sys[k] − P.sub.sys[k − 1]  |ΔP.sub.sys| > 20 mmHg Maximum change between 2 pulses ΔP.sub.dia = P.sub.dia[k] − P.sub.dia[k − 1]  |ΔP.sub.dia| > 20 mmHg Maximum change between 2 pulses ΔT = T.sub.H[k] − T.sub.H[k − 1] |ΔT| > 2/3 sec  Maximum change between 2 pulses

[0174] Update Threshold. If the beat is not abnormal, then update the threshold to current SSF maximum value threshold(k+1)=0.9*threshold(k)+0.1*0.6*z.sub.max(k).

[0175] Filtering

[0176] Physiological signals to be used in further processing or for display are filtered with a time-moving mean filter with a time window of T.sub.filt seconds (30 sec). A bar (.sup.−) is used as an accent over a variable X to denote the mean value. The subscript Now denotes the most current time. The mean filter is

[00002]$\stackrel{\_}{X_{\mathrm{Now}}}=\mathrm{mean}(\left(X\left(t_k\right).Math.t_k\in \left[t_{\mathrm{Now}}-T_{\mathrm{filt}},t_{\mathrm{Now}}\right]\wedge X\left(t_k\right)\neg \mathrm{abnormal}\right)$

[0177] (In words, “the mean

[00003]$\stackrel{\_}{X_{\mathrm{Now}}}$

is the mean of all X(t.sub.k) where t.sub.k is in the range from T.sub.filt seconds ago until the current time t.sub.Now excluding all X(t.sub.k) which have been labelled abnormal in the signal quality checking”.)

[0178] If there are less than N.sub.Med.sub.Min non-abnormal values in the filter, the filter returns NaN (“not a number”). This indicates that there is insufficient quality data to estimate a filtered value. N.sub.Med.sub.Min will take the value of 6.

[0179] The mean filter is applied to mean arterial pressure, systolic pressure, diastolic pressure and heart rate as follows:

[00004]$\stackrel{\_}{\mathrm{MAP}}=\mathrm{mean}\left(\mathrm{MAP}\right)\stackrel{\_}{P_{\mathrm{sys}}}=\mathrm{mean}\left(P_{\mathrm{sys}}\right)\stackrel{\_}{P_{\mathrm{dia}}}=\mathrm{mean}\left(P_{\mathrm{dia}}\right)\stackrel{\_}{\mathrm{HR}}=\mathrm{mean}\left(f\right)\stackrel{\_}{T_H}=\mathrm{mean}\left(T_H\right)\stackrel{\_}{P_{\mathrm{pulse}}}=\mathrm{mean}\left(P_{\mathrm{pulse}}\right)$

[0180] For simplicity the subscript Now has been omitted in the above, and it is understood that the current t.sub.Now value is used in subsequent processing.

[0181] Pulse pressure variation (PPV) is computed over the last T.sub.PPV seconds (30 seconds), as follows:

PP.sub.Max=Max((P.sub.Pulse(t.sub.k)|t.sub.k∈[t.sub.Now−T.sub.PPV,t.sub.Now]ΛP.sub.Pulse(t.sub.k)¬abnormal)

[0182] (In words, “the maximum pulse pressure PP.sub.Max is the maximum of all pulse pressures P.sub.Pulse(t.sub.k) where t.sub.k is in the range from T.sub.PPV, seconds ago until the current time t.sub.Now excluding all P.sub.pulse(t.sub.k) which have been labelled abnormal in the signal quality checking”.)

[00005]${\mathrm{PP}}_{\mathrm{Min}}=\mathrm{Min}(\left(P_{\mathrm{Pulse}}\left(t_k\right).Math.t_k\in \left[t_{\mathrm{Now}}-T_{\mathrm{PPV}},t_{Now}\right]\wedge P_{Pulse}\left(t_k\right)\neg \mathrm{abnormal}\right)$${\mathrm{PPV}}_{\mathrm{Now}}=\frac{{\mathrm{PP}}_{\mathrm{Max}-}{\mathrm{PP}}_{\mathrm{Min}}}{\left({\mathrm{PP}}_{\mathrm{Max}}+{\mathrm{PP}}_{\mathrm{Min}}\right)/2}$

[0183] T.sub.PPV usually takes the value 30 seconds. If there are less than N.sub.PPV.sub.Min non-abnormal values in the Max and Min functions, PPV.sub.Now is set to NaN (“not a number”). This indicates that there is insufficient quality data to estimate a filtered value. N.sub.PPV.sub.Min will take the value of 6.

[0184] Derived Variables

[0185] Derived variables are computed using the current values of the mean filtered values as specified above.

[0186] Nominal Cardiac Output (nCO)

[0187] Nominal cardiac output (nCO) is estimated using the Liljestrand and Zander (LZA) method (Liljestrand and Zander, 1928; Broch et al., 2016b).

[00006]$nCO=\frac{k_{\mathrm{LZ}}\stackrel{\_}{\mathrm{HR}}\left(\stackrel{\_}{P_{\mathrm{sys}}}-\stackrel{\_}{P_{\mathrm{dia}}}\right)}{\left(\stackrel{\_}{P_{\mathrm{sys}}}+\stackrel{\_}{P_{\mathrm{dia}}}\right)}$

[0188] k.sub.LZ is a calibration coefficient for the LZ method. A value of 0.42 is used. This is based on a blood pressure of 120/80 mmHg with a heart rate of 60 bpm and a cardiac output of 5 L/min.

[0189] It is important to note that only relative % changes in nominal cardiac output (nCO) are displayed and not absolute values.

[0190] If one or more of the input values are NaN, nCO is set to NaN.

[0191] The values of nCO over a given time period (for example, five minutes) are compared with a baseline value at the start of the latest time period (five minute period) (ΔCO) and expressed as a percentage change which is plotted on the display. The calculated baseline value is therefore dynamic and changing as the latest time period changes. In this example, the value of the latest time period is a 5 minute interval, and the percentage change is shown as a percentage relative to the baseline across the whole 5 minutes. In this manner, ΔCO can be not only shown as a single number change, but a series of ΔCO across the latest 5 minutes time period. This allows a user to view and identify changes within this latest 5 minutes time period.

[0192] The latest time period may be 5 minutes, however it could be less or more—for example, the latest time period could be up to 1 hour.

[0193] The percentage difference between the current and baseline values is also displayed numerically. This percentage difference is approximately the same percentage difference that would be calculated if a calibrated CO value had been used, as the calibration coefficient approximately cancels out in the percentage difference formula between baseline and current values. If there are periods where the arterial pressure signal quality is too low to compute ΔCO, the ΔCO trend chart will include gaps.

[0194] The accuracy of the Liljestrand and Zander formula in estimating cardiac output and its trend changes has been evaluated by Sun et al., (2009), Monge Garcia et al., (2013), Zhang et al., (2015) and Caillard et al., (2015).

[0195] Systemic Vascular Resistance (SVR)

[0196] The system uses a measure of total systemic vascular resistance (TSVR) to compute the recent changes in systemic vascular resistance (SVR). TSVR is defined as:

[00007]$TSVR=80*\frac{\mathrm{MAP}}{\mathrm{CO}}$

[0197] The conventional definition is:

[00008]$SVR=80*\frac{\mathrm{MAP}-\mathrm{CVP}}{\mathrm{CO}}$

[0198] Atlas et al., (2010) showed mathematically that changes in TSVR are approximately equal to changes in SVR (ΔTSVR≈ΔSVR).

[0199] The systemic vascular resistance (SVR) is computed using nominal cardiac output (nCO) as follows:

[00009]$SVR=\frac{\stackrel{\_}{\mathrm{MAP}}}{nCO}$

[0200] BP Assist will only use changes in systemic vascular resistance (SVR) and not absolute values.

[0201] The values of SVR over the last five minutes are compared with a baseline value at the start of the latest five minute period (ΔSVR) and expressed as a percentage change which is plotted on the display.

[0202] If one or more of the input values are NaN, SVR is set to NaN.

[0203] Venous Return Driving Pressure (Pvr)

[0204] The primary purpose of this technology is to highlight key trends in blood pressure, compared to target or threshold levels, and to project these forward. If blood pressure is about to drop too low, this is a call to action to the clinician to intervene. Low blood pressure itself may be an indication for giving a pressor bolus or increasing the pressor infusion rate. Similar arguments apply if the blood pressure is trending too high.

[0205] In deciding treatment, the clinician should consider all the key aspects related to blood pressure including the induction and depth of anaesthesia, the stage of surgery, blood loss, etc.

[0206] From a haemodynamic point of view, the causes of a falling blood pressure are reduced vasomotor tone (vasodilation, eg caused by anaesthesia), reduced volume state (eg through bleeding) or reduced heart function.

[0207] Most clinicians can make this assessment and decide treatment by analysing the patterns of changes in blood pressure (MAP), cardiac output (CO) and systemic vascular resistance (SVR). However changes in each of these variables can be caused by changes in any of the underlying states: volume, tone or heart. It would be helpful, therefore, to provide further information to help clinicians make this decision.

[0208] Guyton coined the term “mean systemic filling pressure” (P.sub.ms) for the pressure of an average element in the circulation that drives blood back to the heart. This is not simply the average of arterial and venous pressures. Actually, it is the pressure that the circulation would equilibrate to if the heart was stopped. P.sub.ms is a result of the contained volume of blood stressing an elastic set of tubes in the circulation, and hence a measure of “how well filled the circulation is”—or volume state.

[0209] A measure of P.sub.ms would be very useful clinically. Clearly, stopping the heart is not a desirable nor practical method. Parkin (Parkin et al., 1994) had the insight that a simple mathematical model could be fitted to the current patient parameters, and the heart stopped in the model, rather than the patient. His analysis yielded the following formula for estimating P.sub.ms,

P.sub.msa=aRAP+bMAP+cCO

[0210] Where P.sub.msa is referred to as the “mean systemic filling pressure analogue”. RAP is right atrial pressure, MAP is mean arterial pressure and CO is cardiac output. a and b are fixed constants, with values a=0.96 and b=0.04. The coefficient c is a function of age, height and weight, ranging from 0.6 (young and large adult) to 1.3 (old, frail, small adult). Note that central venous pressure (CVP) may be used to replace RAP in this formula.

[0211] The Parkin P.sub.msa formula has been independently validated (Maas et al., 2012; Cecconi, Aya, et al., 2013; Lee et al., 2013) and was used as the basis of the Navigator clinical decision support system (Parkin and Leaning, 2008; Pellegrino et al., 2011; Sondergaard et al., 2012).

[0212] As noted earlier, CVP (and RAP) are not routinely monitored in surgical procedures. Further, it is becoming a less popular measurement in intensive care, where it requires careful quality control, including levelling of the transducer when the patient moves. This makes the Parkin P.sub.msa formula limited in its application.

[0213] Nonetheless the Parkin formula can be used to shed light on whether there are changes in volume state or heart function.

[0214] The difference between mean systemic pressure P.sub.ms and right atrial pressure RAP is the driving pressure for venous return, P.sub.vr:

P.sub.vr=P.sub.ms−RAP

[0215] Note that if the volume state decreases, it follows from this formula that P.sub.vr will also drop. Hence decreases in P.sub.vr may be an indicator for reduced volume state.

[0216] When heart function decreases for a given volume state, it also follows that P.sub.vr will drop as RAP will rise. Hence decreases in P.sub.vr may be an indicator for decreased heart function.

[0217] The change ΔP.sub.vr may thus be a useful clinical parameter in addition to MAP, CO, SVR and HR.

[0218] We note that in the P.sub.msa formula, the coefficient a has the value 0.96, hence the RAP term approximately cancels so that:

ΔP.sub.vr=bΔMAP+cΔCO

[0219] This parameter does not depend on the absolute value of CO, only its change.

[0220] Recent Changes

[0221] Recent changes in nCO, , SV and P.sub.vr nay be computed over a period of T.sub.delta before the current time t.sub.Now.

[0222] Their values at t.sub.Now−T.sub.delta is used as baseline values.

[0223] Intermediate values between t.sub.Now−T.sub.delta and t.sub.Now is computed and expressed as a percentage of their baseline values. There is a sufficient number of intermediate points as required graphically.

[0224] T.sub.delta is typically 300 seconds (5 minutes).

[0225] Cumulative Time Under Thresholds

[0226] Total time in minutes under the different thresholds in the patient mean arterial pressure (MAP) target range and the warning threshold is computed from the start of the receipt of data from the patient monitor.

[0227] MAP Projection

[0228] The method computes and project (extrapolate) a trend and uncertainty band based on the last few minutes of mean arterial blood pressure.

[0229] The concept is that if there is a confirmed statistical trend in the signal it will be projected.

[0230] If there is no confirmed statistical trend, the projection will not be made.

[0231] Any statistical trend method that is able to yield a measure of effective fit and uncertainty bands of projection may be used, as long as the method is adequately determined by the data.

[0232] Below we use a linear regression technique to evaluate whether the filtered MAP signal is following a consistent linear trend. We have found this to provide a high accuracy projection technique (>90%) on real surgical datasets, as shown below.

[0233] The performance during periods of increasing or decreasing MAP was evaluated to cover the 60-110 mmHg range of MAP.

[0234] The performance of the projection feature was evaluated by: [0235] 1. Bench testing by creating such situations using a calibrated source of analog arterial blood pressure waveform signals. The Rigel UNI-SIM was programmed with a sequence of systolic (SBP) and diastolic (DBP) blood pressure changes to shape the output waveform and change MAP. The sequences corresponded to 3 situations during which the projection line should be visible (a relatively stable MAP, MAP increasing rapidly (>4 mmHg/min), MAP decreasing rapidly (<−4 mmHg/min)) and 2 situations in which the projection line is not expected to be displayed continuously (highly variable MAP and MAP undergoing a direction change). [0236] 2. Re-analyzing the processed log file data sets from the system verification. The accuracy of the projection was analyzed in terms of how fast the MAP is changing, confirmation that the projection was not displayed during periods of high MAP variance or direction change and evaluation of the uncertainty cone that appears with the projection line.

[0237] Bench Testing

[0238] Tests were done using a Rigel UNI-SIM (30L-0268) vital signs simulator that provides an electrical simulation of a pressure transducer and is used as a reference signal, a Philips Healthcare MX 550 monitor, GE Healthcare CARESCAPE Monitor 450, and Serial cables to connect to the vital signs monitor's digital data export outputs.

[0239] The test data for the bench testing verification of the projection function was the calibrated source of analog arterial blood pressure waveform signals produced by the Rigel UNi-SIM (30L-0268) vital signs simulator. The test data for the re-analysis of the system verification were the log files that were produced when the data sets were processed in the original system verification. Three datasets were used.

[0240] The vital signs simulator was configured to produce arterial pressure traces that vary over time as specified in 5 scenarios of:

[0241] 1. MAP relatively stable

[0242] 2. MAP very fast increase (>4 mmHg/min)

[0243] 3. MAP very fast decrease (<−4 mmHg/min)

[0244] 4. MAP fast noisy increase (projection should not display)

[0245] 5. MAP turning point (projection should not display during the turning point)

[0246] The determined projection values were compared to values that are independently calculated, and are shown below in Tables 1 and 2.

TABLE-US-00002 TABLE 1 The results for this test (scenarios 1-3) for the GE Monitor Visual Comparison HDA Log File Test Projection Trend Projected Calculated Acceptance Time from On Aligns Value Values Difference Criteria Start (Secs) (Yes/No) (Yes/No) (mmHg) (mmHg) (mmHg) (+/−4 mmHg) Scenario 1 Relatively Stable 90 Yes Yes 101.7 100.5 1.2 Pass 120 Yes Yes 101.6 101.5 0.1 Pass 150 Yes Yes 100.2 100.2 0 Pass 180 Yes Yes 101.5 101.5 0 Pass Scenario 2 Fast Increase (>4 mmHg/min) 90 Yes Yes 87.1 87.2 0.1 Pass 120 Yes Yes 90.6 90.7 0.1 Pass 150 Yes Yes 93.7 93.8 0.1 Pass 180 Yes Yes 98.1 98.3 0.2 Pass Scenario 3 Fast Decrease (>4 mmHg/min) 90 Yes Yes 72.8 72.1 −0.7 Pass 120 Yes Yes 70.6 70.5 −0.1 Pass 150 Yes Yes 66.9 66.8 −0.1 Pass 180 Yes Yes 68.6 68.6 0 Pass

TABLE-US-00003 TABLE 2 The results for this test (scenarios 1-3) for the Philips Monitor Visual Comparison HDA Log File Test Projection Trend Projected Calculated Acceptance Time from On Aligns Value Values Difference Criteria Start (Secs) (Yes/No) (Yes/No) (mmHg) (mmHg) (mmHg) (+/−4 mmHg) Scenario 1 Relatively Stable 90 Yes Yes 106.2 106.2 0 Pass 120 Yes Yes 101.1 101.2 0.1 Pass 150 Yes Yes 102.9 102.9 0 Pass 180 Yes Yes 100.0 100.0 0 Pass Scenario 2 Fast Increase (>4 mmHg/min) 90 Yes Yes N/A N/A N/A N/A 120 Yes Yes 87.5 87.5 0.0 Pass 150 Yes Yes 88.5 88.6 0.1 Pass 180 Yes Yes 93.4 93.4 0.0 Pass Scenario 3 Fast Decrease (>4 mmHg/min) 90 Yes Yes 85.7 85.5 0.2 Pass 120 Yes Yes 75.5 75.4 0.1 Pass 150 Yes Yes 71.6 71.6 0.0 Pass 180 Yes Yes 68.1 68.0 0 Pass

[0247] Log File Data Re-Analysis

[0248] The results for this test are shown below, where MAPE is mean absolute percentage error.

TABLE-US-00004 TABLE 3 Relationship between Rate of Change of MAP and Projection Accuracy Acceptance Criteria MAPE value Criteria MAPE Values must Change Condition Data Set 1 Data Set 2 Data Set 3 be 0-20% Comparison Across Range 3.3% 6.6% 4.4% Pass Highly (60-110 mmHg) Accurate MAP Increasing Very fast N/A 18.2%  9.3% Pass Good Fast N/A 7.0% 6.3% Pass Highly (2-4 mmHg) Accurate Moderate N/A 6.40% 4.5% Pass Highly (1-2 mmHq/min) Accurate Flat/slow N/A 4.2% 2.8% Pass Highly (0-1 mmHq/min) Accurate MAP Decreasing Flat/slow 3.1% 3.9% 2.2% Pass Highly (−1 to 0 mmHq/min) Accurate Moderate 3.5% 5.1% 4.9% Pass Highly (−2 to −1 mmHq/min) Accurate Fast 2.2% 8.2% 9.2% Pass Highly (−4 to −2 mmHq/min) Accurate Very fast 7.8% 15.6%  15.7%  Pass Good (<−4 mmHq/min)

[0249] The projection is for up to T.sub.proj (typically 2) minutes into the future.

[0250] The projection will show the implications of continuing the current trend. This will enable the user to make decisions about patient state and need for treatment.

[0251] The dataset for fitting will consist of the last 2 minutes of filtered data points preceding the current time, (t.sub.Now).

[0252] Use a linear fit to the data

y=A+Bx

[0253] Where x=time, y=MAP. Subscript k denotes the values at time t.sub.k. There are n.sub.k data points in the fitting period.

[0254] The sample estimates are a (of A) and b of (B).

[0255] The means are

[00010]$\stackrel{\_}{x}=\frac{.Math.x_k}{n_k}\mathrm{and}\overline{y}=\frac{.Math.y_k}{n_k},$

and the standard deviations are

[00011]$S_x=\sqrt{\frac{{.Math.}_{i=1}^{n_k}{\left(x_i-\stackrel{\_}{x}\right)}^2}{\left(n_k-1\right)}}\mathrm{and}{S}_y=\sqrt{\frac{{.Math.}_{i=1}^{n_k}{\left(y_i-\stackrel{\_}{y}\right)}^2}{\left(n_k-1\right)}}$

[0256] Slope and Intercept

[0257] The slope estimate is

[00012]$b=\frac{{.Math.}_{i=1}^{n_k}{x}_i{y}_i-n_k\stackrel{\_}{x}\stackrel{\_}{y}}{{.Math.}_{i=1}^{n_k}{x}_i^2-n_k{\overline{x}}^2}$

and the intercept estimate is a=y−x.

[0258] The residual standard deviation of y about the regression line is

[00013]$S_{\mathrm{res}}=\sqrt{\frac{\left(n_k-1\right)\left(S_y^2-b^2{S}_x^2\right)}{\left(n_k-2\right)}}$

[0259] High values of s.sub.res may suggest that there is a poor fit to the data, and lack of a consistent trend. In the preferred embodiment we use a threshold of 1.5, although may of course be different in other implementations. If S.sub.res exceeds the threshold, the visual display of the projection may be suppressed.

[0260] Other methods such as the Kruskal Wallis test may be used.

[0261] Confidence Interval of the Regression Line (Altman and Gardner, 1988)

[0262] The confidence interval (CI) of the regression line is estimated to contain 95% of all lines through the current sample.

[0263] The estimated mean value of y for any x, say x.sub.0, is

y.sub.fit=a+bx.sub.0

[0264] The standard error of y.sub.fit is

[00014]$SE\left(y_{\mathrm{fit}}\right)=S_{\mathrm{res}}\sqrt{\frac{1}{n_k}+\frac{{\left(x_0-\stackrel{\_}{x}\right)}^2}{\left(n_k-1\right)S_x^2}}$

[0265] The 100(1−α)% confidence interval for the population mean value of ŷ at x=x.sub.0 is

[00015]$\hat{y}=y_{\mathrm{fit}}\pm t_{1-\frac{\alpha }{2},n_{k-2}}SE\left(y_{\mathrm{fit}}\right)$

[0266] Where

[00016]$t_{1-\frac{\alpha }{2},n_k-2}$

is the t-value for a level of

[00017]$1-\frac{a}{2}\left(\mathrm{eg}1-0.05/2=97.5/100\right)$

and n.sub.k-2 is the degrees of freedom.

[0267] Prediction Interval

[0268] The uncertainty of y.sub.fit as a prediction for y—the “prediction interval”—is wider than the associated confidence interval.

[0269] Estimated standard deviation of individual values:

[00018]$S_{\mathrm{pred}}=S_{\mathrm{res}}\sqrt{1+\frac{1}{n_k}+\frac{{\left(x_0-\overline{x}\right)}^2}{\left(n_k-1\right)S_x^2}}$

[0270] The 100(1−α)% prediction interval is

[00019]$\hat{y}=y_{\mathrm{fit}}\pm t_{1-\frac{\alpha }{2},n_{k-2}}{S}_{\mathrm{pred}}$

[0271] The value of

[00020]$t_{1-\frac{\alpha }{2},n_{k-2}}$

when α=0.001 and n.sub.k-2.fwdarw.∞ is 2.326.

[0272] The prediction ŷ is taken as the projection of MAP. It consists of 3 values—low, fit and high. These values is computed at the current time t.sub.Now, one minute ahead and T.sub.proj minutes ahead.

[0273] User Interface (UI)

[0274] The features of the user interface are preferably: [0275] Gives prominence to MAP as the primary parameter [0276] Highlights MAP compared to a clinician-set target range [0277] Includes multiple simultaneous timescales to aid the clinician in assessing the patient and deciding treatment: [0278] 20 minutes default MAP history adjustable to the whole procedure duration [0279] 5 minutes of recent trends in the casual cardiovascular parameters including CO, SVR and heart rate (HR) [0280] 2 minutes forward projection of MAP trend compared to targets [0281] Display of cumulative time in MAP risk ranges [0282] Ability to add treatment markers to the physiological trends in order to show the effects of different treatments

[0283] FIG. 6 shows an example implementation of the UI, in this case showing data after 30 minutes of the patient's session.

[0284] In practice, the system is connected to the digital output ports of multiparameter patient vital signs monitors (for example from manufacturers such as Philips and GE) that are routinely used in the operating room. The vital signs monitor will also provide continuous arterial blood pressure waveform data and cardiovascular-related numeric parameters.

[0285] The medical user, an anaesthetist, has the option to set up a patient in the system by entering patient-specific information (height, weight, age) and define a target range for mean arterial blood pressure (MAP). The user will confirm that system is correctly communicating with the vital signs monitor that is connected to the patient.

[0286] In a routine operation, the system will track the vital signs of the patient. It may check that data are being acquired correctly and that the signals are of adequate quality and consistent, alerting the user with an appropriate action if not. The system will compute additional derived variables to help with its function and algorithms. For example, changes in cardiac output will be derived from the blood pressure waveform.

[0287] The system continually processes and displays, in graphical charts and numeric format, the data and derived variables in comparison with the user defined targets. It will detect and indicate to the user when blood pressure shown as MAP is below or is likely to fall below the target range. The system will allow the user to add labels to the graphic display chart to show the administration of vasopressors, as bolus or infused, and volume challenges.

[0288] Similarly, the system will indicate when MAP is above or likely to trend above the target range.

[0289] The intent of system is that with this information, the anaesthetist, or other medical professional, will make faster and more accurate assessment and treatment decisions regarding cardiovascular management. The anaesthetist may then implement these decisions manually with syringe boluses or vasopressors, or by changing the infusion rate of vasopressors, by volume challenges, or other means.

[0290] With reference to FIG. 6, which is an example implementation of the system UI, the “Running Mode” screen displays MAP in the upper panel. Trend data (previous five minutes) for the selected parameter (CO/HR/SVR) are displayed in the lower panel. The percentage change over the last 5 minutes of the selected parameter is displayed immediately adjacent to the right of the trend display panel.

[0291] The default parameter displayed in the trend window is CO. The information in the other windows in this screen are described in subsequent sections of this user manual.

[0292] Target ranges for blood pressure may be set in the system. Upper and lower target levels for blood pressure can be set.

[0293] The upper pressure range limit can be varied between 70 mmHg and 190 mmHg. The lower pressure range limit can be varied between 40 mmHg and 100 mmHg.

[0294] The system's default setting for severe hypotension is <55 mmHg.

[0295] The “Cumulative BP Thresholds” panel located in the upper right of the main “Running Mode” screen contains three icons that show the current target range and thresholds for moderate and severe hypotension. These are highlighted on the main MAP trace by colour.

[0296] Projection Line

[0297] When there is a consistent statistical trend (for example, when S.sub.res is below the threshold) in the mean arterial pressure (MAP), be it fast or slow, up or down, or flat, the trend and an uncertainty cone is projected forward from the current MAP value for the next 2 minutes. This is intended to help the medical professional decide whether the change is something they need to act on, and the user may use the MAP and recent changes parameters to decide what treatment they may take.

[0298] Marker labels can be entered on the screen display and data record to record/annotate specific events such as the bolus delivery of a drug.

[0299] Activation buttons for “Bolus Marker”, “Infusion Marker” (up or down) and “Volume Marker” are located at the bottom left of the main display screen when in “Running Mode”.

[0300] Adding a bolus marker to the display reveals a pop-up screen that includes a list of routinely used vasopressors (which may be pre-configured differently for different sites). The list specifies the formal name of the vasopressor, the standard colour of vials containing the drug and the abbreviated name that will be displayed on the drug label added to the timeline when the bolus marker is activated. The vasopressor administered can be selected from the menu displayed. Adding the bolus marker adds a triangular symbol with the 3-letter drug abbreviation, to the display screen as well as recording the event and time in the data record.

[0301] Adding an infusion marker to the display reveals a pop-up screen. Markers can be added to the screen display and data record for both increases and decreases in the infusion rate of drugs delivered to the patient during the blood pressure monitoring session.

[0302] As with the bolus marker, a list of routinely used vasopressors is presented on the screen. The list specifies the formal name of the vasopressor, the standard colour of vials containing the drug and the abbreviated name that will be displayed on the drug label added to the timeline when the marker is activated. Touching the “OK” button adds a marker to the display screen and records the event and time in the data record.

[0303] To add a marker signifying a volume challenge has been initiated, the user may press an icon that reveals a pop-up screen. Touching the “OK” adds a marker to the display screen and records the event and time in the data record.

[0304] Alerts Displayed on Screen During Use of HDA.

[0305] If there has been a period of time (for example more than 30 seconds) with no signal being received, when a new blood pressure signal is detected by the system, the user will be alerted on the UI. Various status alerts may be displayed, for example: “Disconnected”, “Connecting” and “Connected”.

[0306] An alert may be displayed on the main screen if the quality of the blood pressure signal being received from the multiparameter vital signs monitor is such that system cannot compute accurate parameter values. If there are periods where the arterial pressure signal quality is too low to compute parameters (such as ACO), the trend chart will include gaps.

[0307] No doubt many other effective alternatives will occur to the skilled person. It will be understood that the invention is not limited to the described embodiments and encompasses modifications apparent to those skilled in the art lying within the scope of the claims appended hereto.

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