Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/02—Detecting, measuring or recording for evaluating the cardiovascular system, e.g. pulse, heart rate, blood pressure or blood flow
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/40—Detecting, measuring or recording for evaluating the nervous system
  • A61B5/4058—Detecting, measuring or recording for evaluating the nervous system for evaluating the central nervous system
  • A61B5/4064—Evaluating the brain
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/02—Detecting, measuring or recording for evaluating the cardiovascular system, e.g. pulse, heart rate, blood pressure or blood flow
  • A61B5/02028—Determining haemodynamic parameters not otherwise provided for, e.g. cardiac contractility or left ventricular ejection fraction
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/02—Detecting, measuring or recording for evaluating the cardiovascular system, e.g. pulse, heart rate, blood pressure or blood flow
  • A61B5/021—Measuring pressure in heart or blood vessels
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/02—Detecting, measuring or recording for evaluating the cardiovascular system, e.g. pulse, heart rate, blood pressure or blood flow
  • A61B5/026—Measuring blood flow
  • A61B5/0261—Measuring blood flow using optical means, e.g. infrared light
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/14—Devices for taking samples of blood ; Measuring characteristics of blood in vivo, e.g. gas concentration within the blood, pH-value of blood
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue
  • A61B5/1455—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue using optical sensors, e.g. spectral photometrical oximeters
  • A61B5/14551—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue using optical sensors, e.g. spectral photometrical oximeters for measuring blood gases
  • A61B5/14553—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue using optical sensors, e.g. spectral photometrical oximeters for measuring blood gases specially adapted for cerebral tissue
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/02—Detecting, measuring or recording for evaluating the cardiovascular system, e.g. pulse, heart rate, blood pressure or blood flow
  • A61B5/021—Measuring pressure in heart or blood vessels
  • A61B5/022—Measuring pressure in heart or blood vessels by applying pressure to close blood vessels, e.g. against the skin; Ophthalmodynamometers
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/03—Measuring fluid pressure within the body other than blood pressure, e.g. cerebral pressure ; Measuring pressure in body tissues or organs
  • A61B5/031—Intracranial pressure
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue
  • A61B5/1455—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue using optical sensors, e.g. spectral photometrical oximeters
  • A61B5/1459—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue using optical sensors, e.g. spectral photometrical oximeters invasive, e.g. introduced into the body by a catheter

Definitions

• This application relates to cerebral blood pressure autoregulation and more particularly to devices and methods to diagnose and/or treat cerebrovascular autoregulation in a patient.
• Cerebral pressure autoregulation is defined as the maintenance of a constant cerebral blood flow (CBF) in the face of changing cerebral perfusion pressure (CPP). In health, this process protects the brain during transient changes in the arterial blood pressure (ABP) from diminished or excessive blood flow. Traumatic brain injury (TBI)( Muizelaar JP, Marmarou A, DeSalles AA, et al. Cerebral blood flow and metabolism in severely head-injured children, part 1 : Relationship with GCS score, outcome, ICP, and PVI. J Neurosurg.
• Changes in ABP can be induced via drugs, tilt- table, or thigh cuff (Aaslid R, Lindegaard KF, Sorteberg W, Nornes H. Cerebral autoregulation dynamics in humans. Stroke. 1989; 20(l):45-52), or they can occur spontaneously.
• Using spontaneous changes in ABP is preferable to inducing ABP changes in an unstable patient with an acute intracranial process.
• spontaneous and often subtle ABP fluctuations for this measurement results in an inferior signal-to-noise ratio.
• CBF cerebrospinal fluid
• flow velocity measured by transcranial Doppler (Czosnyka M, Smielewski P, Kirkpatrick P, Menon DK, Pickard JD. Monitoring of cerebral autoregulation in head-injured patients. Stroke. 1996; 27(10): 1829-1834); red blood cell flux, measured by laser-Doppler (Lam JM, Hsiang JN, Poon WS. Monitoring of autoregulation using laser doppler flowmetry in patients with head injury. J Neurosurg. 1997; 86(3):438-445); parenchymal oxygen tension, measured using a Licox monitor (Lang EW, Czosnyka M, Mehdorn HM. Tissue oxygen reactivity and cerebral autoregulation after severe traumatic brain injury. Crit Care Med. 2003;
• a method of diagnosing cerebrovascular autoregulation in a patient includes measuring blood pressure of the patient, measuring, non-invasively, venous oxygen content of the patient's brain substantially simultaneously with the measuring blood pressure, correlating the blood pressure and the venous oxygen content measurements, and determining a cerebrovascular autoregulation state of the patient based on the correlating the blood pressure and the venous oxygen content measurements.
• a system for diagnosing cerebrovascular autoregulation in a patient has a cerebral oximeter arranged proximate an external position of the patient's head, a blood pressure monitoring device attached to the patient, and a signal processing unit in communication with the cerebral oximeter and the blood pressure monitoring device.
• the cerebral oximeter obtains oxygen content measurements of blood within the patient's brain taken at a plurality of times and outputs an oxygen content signal to the signal processing unit
• the blood pressure monitoring device obtains arterial blood pressure measurements of the patient at a plurality of times substantially synchronously with the oxygen content measurements and outputs an arterial blood pressure signal to the signal processing unit
• the signal processing unit calculates a linear correlation coefficient based on the oxygen content signal and the arterial blood pressure signal in the time domain for a plurality of times.
• a method of treating a patient includes measuring blood pressure of the patient, measuring, non- invasively, venous oxygen content of the patient's brain substantially simultaneously with the measuring blood pressure, correlating the blood pressure and the venous oxygen content measurements in a time domain, determining a cerebrovascular autoregulation state of the patient based on the correlating the blood pressure and the venous oxygen content measurements, and causing a change of blood pressure of the patient based on the cerebrovascular state of the patient determined based on the correlating.
• a data processing unit for use with a system for diagnosing cerebrovascular autoregulation in a patient has at least one signal input port adapted to receive a blood pressure signal from measured blood pressure data from the patient and to receive a venous oxygen content signal from externally measured venous oxygen content data of the patient's brain, a signal correlation component adapted to receive and correlate the blood pressure signal with the venous oxygen content signal to provide a correlation coefficient indicative of a cerebrovascular autoregulation state of the patient, and a signal output port to output the correlation coefficient to indicate the cerebrovascular autoregulation state of the patient based on the correlation coefficient.
• a computer readable medium programmed to process data for a system for diagnosing cerebrovascular autoregulation in a patient includes at least one signal receiving component adapted to receive a blood pressure signal from measured blood pressure data from the patient and to receive a venous oxygen content signal from externally measured venous oxygen content data of the patient's brain, a signal correlation component adapted to receive and correlate the blood pressure signal with the venous oxygen content signal to provide a correlation coefficient indicative of a cerebrovascular autoregulation state of the patient, and a signal output component adapted to output the correlation coefficient to indicate the cerebrovascular autoregulation state of the patient based on the correlation coefficient.
• Figure 1 is a schematic illustration of a system for diagnosing cerebrovascular autoregulation according to an embodiment of the current invention
• Figure 2 is a schematic diagram to help explain a method of diagnosing and/or treating cerebrovascular autoregulation in a patient according to an embodiment of the current invention
• Figure 3 shows time trends of recordings from a single piglet. ICP, ABP, and CPP are shown in mmHg; laser-Doppler red blood cell flux is in arbitrary units; and cerebral oximetry (NIRS) is expressed as a percent saturation of hemoglobin. Time on the x-axis covers a spread of 4 hours and 10 minutes. Slow "B" waves of ICP are seen in the top tracing at low ABP prior to failure of autoregulation (solid arrow). The oximeter readout showed a more gradual decline relative to the laser-Doppler flux, which had a pattern more indicative of autoregulation (dashed arrows). A similar trend was observed in all 6 piglets;
• Figure 4A shows a steady-state autoregulatory graph of laser-Doppler flux versus CPP in a single piglet. The breakpoint was defined as the division that resulted in regression lines with the lowest combined residual squared error (34 mmHg in this piglet).
• Figure 4B shows near-infrared spectroscopy (NIRS)-derived cerebral oximetry versus CPP. This relationship did not have the obvious plateau seen with laser-Doppler flux.
• NIRS near-infrared spectroscopy
• the laser-Doppler index (LDx, ⁇ SE, Figure 4C) and the cerebral oximetry index (COx, Figure 4D) were concordant, showing low values above a CPP of 35 mmHg and high values below a CPP of 35 mmHg (arrows);
• Figures 5A-5C show static autoregulation curves derived from 6 piglets ( ⁇ SE).
• Figure 5A is Laser-Doppler flux as a percent of baseline flux at 60 mmHg.
• Figure 5B is Cerebrovascular resistance (CVR), calculated as CPP/CBF from the same data set and expressed as a percentage of CVR at CPP of 60 mmHg.
• Figure 5C is Cerebral oximetry, measured by NIRS, shown as a percentage of baseline tissue oxyhemoglobin saturation. P O.0001 by ANOVA for both laser-Doppler flux and oximetry curves.
• Figure 6A shows average LDx and
• Figure 6B shows COx for the six piglets ( ⁇ SE) stratified by the CPP at which they were measured.
• the horizontal dashed line shows the 90% sensitivity cutoff for detecting autoregulatory failure.
• the receiver-operator characteristics are compared between the LDx (Figure 6C) and COx (Figure 6D) calculations of 6 piglets, averaged for each 5 mmHg increment of CPP.
• AUC is area under the curve. Confidence intervals for sensitivity and specificity and likelihood ratios are tabulated for different sensitivity levels for each index; and
• Figures 7A-7D show linear regression (7A, 7B) and Bland Altman plots (7C,7D) comparing LDx and COx for all data points (7A,7D) and averaged data points taken at the same CPP for each piglet (7B,7D). Agreement improves substantially by averaging, which implies a low signal-to-noise ratio for individual index measurements. Dashed lines are 95% confidence intervals (regression) and 95% limits of agreement (Bland- Altman).
• Transcranial monitors of cerebral oxygenation using NIRS have attractive features.
• COx cerebral oximeter index
• Continuous assessment of autoregulation is a promising monitoring method for actively optimizing cerebral perfusion pressure (CPP) in critically ill patients.
• this correlation is performed continuously on overlapping epochs of 300 seconds, updated every 60 seconds, and does not require induced changes in ABP to detect autoregulatory failure.
• a system for diagnosing cerebrovascular autoregulation of a patient 100 according to an embodiment of the current invention is illustrated schematically in
• the system for diagnosing cerebrovascular autoregulation 100 includes a cerebral oximeter 102 that is arranged proximate an external position of the patient's head 104.
• a blood pressure monitoring device 106 is attached to the patient.
• a signal processing unit 108 is in communication with the cerebral oximeter 102 and with the blood pressure monitoring device 106.
• the cerebral oximeter obtains oxygen content measurements of blood within the patient's brain. Signals from the cerebral oximeter 102 may be processed internally within the cerebral oximeter 102 and/or processed by the signal processing unit 108.
• the oxygen content measurements of blood within the patient's brain is taken a plurality of times by the cerebral oximeter 102 to input an oxygen content signal to the signal processing unit 108.
• a blood pressure monitoring device 106 obtains arterial blood pressure measurements of the patient at a plurality of times substantially synchronously with the oxygen content measurements and outputs an arterial blood pressure signal to the signal processing unit 108.
• the signal processing unit 108 calculates a linear correlation coefficient based on the oxygen content signal and the arterial blood pressure signal in a time domain for a plurality of times. This linear correlation coefficient may be referred to as the cerebral oximeter index (COx) according to some embodiments of the current invention.
• the oxygen content signals transmitted from the cerebral oximeter 102 to the signal processor 108 are low pass filtered by any one of the cerebral oximeter itself, the signal processing unit 108 or by an intermediate low pass filter in the signal line between the cerebral oximeter 102 and the signal processing unit 108.
• the blood pressure monitoring device 106, the signal processing unit 108 or an intermediate device in the signal line between blood pressure monitoring device 106 and signal processor 108 provide low pass filtering of the measured blood pressure signal.
• the blood pressure monitoring device 106 may include an intracranial pressure monitoring device (not shown).
• An intracranial pressure monitoring device may include a catheter-based device which is surgically inserted into the patient to directly measure intracranial pressure within the patient's brain.
• the blood pressure monitoring device 106 may include an arterial blood pressure monitoring device that can be selected from available arterial blood pressure monitoring devices.
• the cerebral oximeter 102 can be a near-infrared spectrometer.
• the system for diagnosing cerebrovascular autoregulation 100 may also include a display unit 1 10 that is in communication with the signal processing unit 108 to display the linear correlation coefficient values calculated by the signal processing unit with respect to other biophysical data of the patient.
• the display unit may display the linear correlation coefficients calculated as a function of arterial blood pressure.
• the signal processing unit 108 may determine the cerebral perfusion pressure based on the difference between the arterial blood pressure and the intracranial pressure and provide signals to the display unit 1 10 to display the calculated linear correlation coefficients as a function of the cerebral perfusion pressure.
• the cerebral oximeter 102, the blood pressure monitoring device 106, the display unit 1 10 and the signal processing unit 108 may be connected by physical wires or other suitable means such as optical or wireless data communications.
• the signal processing unit 108 can be a stand alone physical component, or may be added as a component to other systems such as to a rack system.
• the signal processing unit 108 is not necessarily limited to processing only signal data. It may include generally data processing capabilities.
• the signal processing operations of the signal processing unit 108 may be hard-wired or may be implemented by programming the signal processing unit.
• Figure 2 is a schematic illustration that facilitates the description of a method of diagnosing cerebrovascular autoregulation in a patient 200 according to an embodiment of the current invention.
• the method of diagnosing cerebrovascular autoregulation 200 includes measuring blood pressure of a patient 202, measuring, non-invasively, venous oxygen content of the patient's brain 204 substantially simultaneously with the measuring arterial blood pressure 202, and correlating the blood pressure and the venous oxygen content measurements in a time domain 205.
• a cerebrovascular autoregulation state of the patient is determined 206 based on the correlating of the blood pressure 202 and venous oxygen content 204 measurements.
• the blood pressure signals 202 are low pass filtered 208 according to an embodiment of the current invention.
• the low pass filtering 208 allows slow variations of blood pressure signals to pass through the filter while filtering out the more rapid variations in blood pressure signals.
• the low pass filtering 208 may be implemented with either hardware or software according to various embodiments of the current invention.
• the low pass filtering can be analog low pass filtering or digital low pass filtering, depending on whether an analog or digital signal is being processed.
• the blood pressure signal may be sampled to provide a digital signal and the low pass filtering can be accomplished by selecting a desired sampling frequency.
• the venous oxygen content measurements may be low pass filtered 210 prior to being correlated 205 with the blood pressure signals.
• the venous oxygen content data may be obtained by sampling substantially synchronously with sampling of a blood pressure data to provide a digital signal.
• the low pass filtering 210 may be achieved by selecting the sampling frequency at a desired sampling frequency.
• the blood pressure measurement data 202 may correspond to arterial blood pressure or may correspond to cerebral perfusion pressure determined by also measuring intracranial pressure.
• the venous oxygen content data may be obtained, for example, by measuring differential absorption of near-infrared radiation directed into the patient's brain from a source of near-infrared radiation disposed proximate an external position of the patient's head.
• Another embodiment of the current invention is directed to a method of treating a patient that includes measuring blood pressure of the patient, measuring, non-invasively, oxygen content of the patient's brain substantially simultaneously with measuring blood pressure, and correlating the blood pressure measurements and oxygen content measurements in a time domain.
• the blood pressure measurement data may correspond to arterial blood pressure or may correspond to cerebral perfusion pressure determined by also measuring intracranial pressure.
• a cerebrovascular autoregulation state of the patient is determined based on the correlating of the blood pressure and venous oxygen content measurements and a change of blood pressure or cerebral perfusion pressure is effected based on the determined cerebrovascular autoregulation state of the patient.
• the data processing unit 108 includes at least one signal input port 1 12 that is adapted to receive blood pressure signals from measured blood pressure data from the patient and to receive venous oxygen content signals from externally measured venous oxygen content data of the patient's brain.
• the data processing unit 108 also has a signal correlation component adapted to receive and correlate the blood pressure signal and venous oxygen content signal to provide a linear correlation coefficient indicative of a cerebrovascular autoregulation state of the patient.
• the data processing unit 108 also includes a signal output port 1 14 to output the linear correlation coefficient to be further processed, stored and/or displayed.
• the data processing unit 108 may include a low-pass filter to filter the blood pressure data and may include a low-pass filter to filter the venous oxygen content data in an embodiment of the current invention.
• the blood pressure data and/or the venous oxygen content data may have already been filtered prior to being received by the data processing unit.
• the blood pressure data may include arterial blood pressure in some embodiments of the current invention.
• the data processing unit 108 may also be adapted to receive intracranial pressure signals from measured intracranial pressure of the patient. This may be received through the same input port 1 12, or through an additional data input port.
• the arterial blood pressure signal may be transmitted to the data processing unit 108 through the same signal input port 1 12 as the venous oxygen content signals or may be provided through a separate port.
• the broad concepts of the invention are not limited to any particular number of data input and output ports or whether data is multiplexed for input and/or output over any of the data ports.
• the signal input/output ports may be electrical, optical, or wireless data input/output ports.
• a computer readable medium is programmed to process data from a system for diagnosing cerebrovascular autoregulation in a patient.
• the computer readable medium is programmed to receive and process at least one signal from blood pressure measurements and a signal from venous oxygen content measurements and to calculate a linear correlation coefficient based on the correlation between the arterial blood pressure data and the venous oxygen content data in a time domain.
• the computer readable medium is programmed to output the linear correlation coefficient to provide information upon which cerebrovascular autoregulation of the patient can be determined.
• the COx according to an embodiment of the current invention would be sensitive for autoregulatory failure due to hypotension in a piglet model of the infant brain and measured the COx continuously in piglets, while slowly lowering their ABP below the breakpoint of autoregulation, as determined by laser- Doppler flowmetry.
• LDx laser-Doppler index
• vecuronium 5-mg bolus and 2-mg/hr infusion
• fentanyl 25- ⁇ g bolus and 25- ⁇ g/hr infusion
• the anesthetic for the recording period was primarily narcotic based, with a sub-anesthetic supplementation of inhalational agent. This combination was chosen to ensure the comfort of the animal and reduce the effect of inhaled anesthetic on cerebrovascular responsiveness. Piglets were kept on a warming pad to maintain brain and rectal temperature at 38.5- 39.5 0 C. Ventilation was adjusted to keep pH at 7.35-7.45 and P 3 O 2 at 200-300 mmHg.
• the femoral veins were cannulated bilaterally for placement of a central venous line for drug infusion and pressure monitoring and a 5 Fr esophageal balloon catheter (Cooper Surgical, Trundall, CT), which was used for interruption of venous return to the heart to produce hypotension.
• the femoral artery was cannulated for placement of a pressure and blood gas monitoring line.
• a craniotomy was performed 4 mm lateral and rostral to the bregma at midline for placement of an external ventricular drain catheter, which was transduced for ICP monitoring.
• An additional craniotomy was performed 4 mm lateral and rostral to the first craniotomy for placement of a laser-
• Doppler probe (Moor Instruments, Devon, U.K.), which was advanced across the incised dura mater to contact the surface of the frontoparietal cortex. The probe was positioned to avoid high baseline flux values associated with placement over large vessels and was secured in place by a rubber washer cemented to the skull. A third craniotomy in the occipital skull lateral to the midline was used to place a brain temperature probe. Skin was reapplied to the skull, and the wound was sutured closed for heat retention and to create conditions for which the cerebral oximeter had been calibrated.
• the INVOS (in vivo optical spectroscopy) pediatric cerebral oximeter probe (Somanetics, Troy, MI) was placed above the eye, across the frontal and parietal cortex, opposite the side of craniotomies, with the emitting diode situated 1 cm lateral to midline to avoid the sagittal sinus.
• the cerebral specificity of the probe was then tested with a CO 2 challenge: ventilation was increased to reduce end-tidal CO 2 by at least 10 mmHg.
• Cerebral oximetry was compared with oximetry obtained from a probe that was placed over the kidney. Cerebral oximetry values decreased (1.2 ⁇ 0.1 %/mmHg; ⁇ SD), whereas the renal oximetry values were static (0.0 ⁇ 0.1%/mmHg).
• Waveforms from the pressure transducers (ABP, ICP), the laser-Doppler probe, and the INVOS cerebral oximeter were sampled from an analog-to-digital converter by ICM+ software (Cambridge University, Cambridge, UK) at 60 Hz.
• the time resolution of INVOS oximetry is 4 seconds.
• These signals were then time-integrated as non-overlapping 10-second mean values, which is equivalent to applying a moving average filter with a 10-second time window and resampling at 0.1 Hz. This operation eliminates high-frequency noise from the respiratory and pulse frequencies of the animals but, according to the Nyquist theorem, allows detection of oscillations and transients that occur below 0.05 Hz.
• CPP was calculated as the difference between the 10-second mean values of ABP and ICP.
• the present results show that time-domain correlation of ABP and cerebral oximetry can quantify spontaneous autoregulatory vasoreactivity, and the resultant index is sensitive for loss of autoregulation caused by hypotension in a piglet model.
• This method has several features that are attractive for clinical application.
• the COx output is continuous and updated every 60 seconds, as configured in the animals presented.
• the COx can be displayed at the bedside as a function of clinical parameters, such as CPP, showing the effect of changes in management on the autoregulatory process.
• the COx requires no intracranial surgery for calculation and can use spontaneous changes in ABP, obviating the need to induce rapid changes in ABP in an unstable patient.
• Associative relationships between ABP and CBF surrogates can be dynamically assessed by methods that fall into two broad categories: analysis in the frequency domain and analysis in the time domain.
• Frequency-domain analysis (based on coherence, transfer function, or phase shifts) is well suited for regular, periodic waves or induced changes in ABP in an otherwise static system. This analysis has assumptions of linearity and stationarity that are not always strictly present in a biologic system (Giller CA, Mueller M. Linearity and non-linearity in cerebral hemodynamics. Med Eng Phys. 2003; 25(8):633-646).
• Time-domain analysis can be performed as a linear correlation between low-pass filtered ABP and CBF waves, as presented here with the COx and LDx, but this filtering limits the spectral range of the test.
• the clinically relevant wavelength periods that encompass CPP and oximetry correlations caused by autoregulatory failure must be known.
• Brain Temperature CC 38.7 + 0.8 38.6 + 0.8 38.6 + 0.7

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