More particularly, the present invention relates to a method for the non-invasive determination of oxygen saturation in patients suffering from or at risk of shock, or organ failure e. g. such as patients undergoing surgery.

It is generally believed that oxygen saturation of certain body organs is a measure of shock as blood may be diverted from regional organs, such as the bladder, the gastrointestinal tract, the kidney, etc. , to critical organs.

International Patent Application No WO 95/29629 describes an apparatus and a method for the continuous monitoring of bladder epithelial oxygen (pbO2) which comprises the introduction of a catheter carrying an oxygen sensor into the bladder of a patient. The method described in the prior art is specifically aimed at the determination of shock in a patient.

International Patent Application No WO 00/09004 described an optical device which is adapted to measure blood oxygen saturation, SO2. The device is non-invasive and operates by passing light through biological tissue, such as the human finger, to monitor the transmitted or reflected output signal from a photodetector of this device continuously.

However, it has previously been considered that optical sensors, such as that described in WO 00/09004 would not be suitable for use in aqueous systems, for example, in conjunction with body organs which have, or are generally considered to be in, an aqueous environment, such as, the bladder.

However, we have now found that such an optical sensor, e. g. as that described in WO 00/09004, can be used in a non-invasive method for the determination of, inter alia, shock in a patient, by measuring oxygen saturation (SO2).

Thus, according to the invention we provide a method of measuring oxygen saturation in a body organ which comprises the use of an optical sensor device, e. g. such as described in WO 00/09004 which is incorporated herein by reference.

In the method of the invention, the body organ may preferentially be a regional, i. e. an accessible, body organ.

Thus, in the method of the invention such body organs may be selected from, organs such as the eye, the bladder, the gastrointestinal tract and the kidney. According to a preferred aspect of the invention the method comprises measurement of oxygen saturation in the bladder. Alternatively, the method of the invention may include foetal monitoring e. g. via the scalp.

In a further embodiment of the invention, the method is especially one in which the measurement is used to determine oxygen saturation in patients suffering from or at risk of shock, or organ failure e. g. such as patients undergoing surgery.

According to a further aspect of the invention we provide the use of a sensor as described in WO 00/09004 in a method as hereinbefore described.

The method of the invention uses a spectral wavelength of from 500 to 600 nm.

In a preferred embodiment of the invention the light beam will emit a plurality of wavelengths, the arrangement being such that the signal levels corresponding to the different wavelengths bear a predetermined relationship with each other. A particular advantage of the method of the invention is that the use of a range of different wavelengths allows for a pattern recognition technique to be employed.

Generally the technique of the present invention measures oxygen saturation (SO2) i. e. the value of the oxygen saturation in venous and arterial blood combined passing through tissue.

The method of the invention may use a light source which emits white light containing all wavelengths between 500nm and 600nm in the visible range of the spectrum Said light source may comprise a bulb such as a tungsten halogen light bulb or a preferred embodiment may comprise a white LED or a plurality of white LEDs.

White light is transmitted along an optical fibre to the organ where multiple scattering occurs as photons interact with cellular and subcellular particles. Light can be absorbed by the haemoglobin present in the blood flowing in the tissue below the sensor before being transmitted along receiving optical fibres.

The light source may be placed so that it shines directly onto biological tissue or as a preferred embodiment it may transmit white light into an optical fibre or a plurality of optical fibres and thereby along said fibre (s) to the biological tissue. This optical fibre makes up the optical sensor and is substantially as described in WO 00/09004.

The light source or optical sensor may be held or fixed to, or in proximity to, tissue.

The use of the optical sensor as in the preferred embodiment may also allow the tip to be introduced onto inaccessible places such as the internal wall of the bladder or gastrointestinal tract or other organ.

The optical sensor also incorporates an optical fibre or a plurality of optical fibres for capturing and transmitting light reflected (remitted) from the biological tissue back to the measuring instrument.

In the method of the invention the tip of the optical sensor may be placed in contact with the biological tissue in order to capture the remitted light. Alternatively, in the same method of the invention, the tip of the optical sensor may be placed so that is at some distance from the biological tissue when it captures the remitted light. This distance may be as much as several centimetres.

Either when in contact or when at a distance, the tip of the optical sensor may be positioned either perpendicular to, or at a variety of angles to the biological tissue.

In one embodiment of the invention, the measuring instrument contains a spectrometer, a device for measuring the intensity of the light at every different wavelength almost simultaneously.

In this embodiment, the remitted light from the biological tissue is transmitted into the spectrometer and produces a spectrum of light intensities over the desired range.

The spectrum is converted into an electronic signal and then manipulated in a software program in the measuring instrument.

Before taking a measurement, the optical sensor is exposed to a standard white reflective surface to give a white reference spectrum. A dark reference spectrum is also obtained by excluding all light from the optical sensor.

The white reference spectrum, the dark reference spectrum and the spectrum produced by the light remitted from the biological tissue being measured are all used in the following mathematical formula to obtain a spectrum of absorbance. <BR> <BR> <P>A =-logic -D<BR> t DS J

where A is the absorbance at wavelength X, S is the sample intensity at wavelength X, D is the dark reference intensity at wavelength/%, R is the white reference intensity at wavelength B.

Absorbance spectra are a measure of how much light is absorbed by a sample.

Absorbance can also be expressed as proportional to the concentration of the substance interacting with the light.

In the method of the invention, the absorbance spectrum obtained from the biological tissue is further manipulated by means of a software program in the measuring instrument.

A correction may be used in order to compensate for some of the scattering effects in biological tissue.

Two isobestic points are chosen on the compensated spectrum. An isobestic point is a wavelength at which oxyhaemoglobin and deoxyhaemoglobin have the same optical absorbance. The wavelengths used may typically be 526nm and 586nm.

There are other isobestic points which may be used in a different embodiment of the invention.

A straight line gradient is then drawn between the isobestic points at 526nm and 586nm. This represents the contribution to the absorbance spectrum of Melanin in the tissue.

By subtracting the value of the gradient at each wavelength from the value of the spectrum at the same wavelength, the spectrum is adjusted so that the start and end points, at 526nm and 586nm are both zero and each wavelength between is adjusted relative to these points.

The integral of the values between 526nm and 586nm is then calculated and subtracted from each point on the spectrum. This has the effect of scaling the spectrum so that it can be compared with other spectra of a similar shape.

A series of absorption spectra relating to 0% oxygenation and 100% have been previously obtained by in vitro experimentation. In practice it is difficult to achieve these extremes and therefore a process of extrapolation may be used.

Said reference spectra have previously been mixed together mathematically to produce a table of reference spectra relating to the whole range of oxygenation between 0% and 100%, in increments of 1%. The correction for scattering has also been applied to the reference spectra.

Another embodiment of the invention may, instead of incorporating a spectrometer in the measuring instrument, use a plurality of photodetectors. Optical fibres may transmit the remitted light from the biological tissue, through separate narrow band optical filters to separate photodiode detectors. By this method, a series of discrete wavelengths, typically 6, may be sampled, almost simultaneously.

By this method of the invention, the values at the isobestic points can be connected by straight line gradients and the SO2 value calculated accordingly.

Although the method of the invention may use a sensor adapted to operate with either transmitted light or reflected light, it is preferred that it operates on reflectance (remittance). Thus in contrast to, e. g. a pulse oximeter the transmitters and the sensors are situated on the same side of the tissue when in use.

Before use, the sensor is normalised against darkness and a standard white reference, and the signal from each photodiode is measured to obtain the overall dark and "white reference"figures. Signal processing includes averaging for a period between 10 milliseconds to 10 seconds, subtracting the white balance signal, and taking a logarithm to produce an absorbance at each wavelength.

The use of six or more wavelengths in this embodiment gives the technique stability against spurious disturbances at a particular wavelength, enables flexibility in the algorithm to cope with factors such as skin colour.

Although the method of the invention may have a variety of applications, it is especially suited for the measurement and/or monitoring of oxygen saturation in the bladder, e. g. bladder SO2. To facilitate the measurement and/or monitoring of the bladder S02, the method may comprise the incorporation of a sensor as hereinbefore described in a catheter. Such a catheter is novel per se.

Thus, according to a further aspect of the invention we provide a catheter comprising a sensor as hereinbefore described.

We particularly provide a catheter comprising a sensor device adapted to measure oxygen in blood which comprises a white LED light source means for emitting a light beam, photodetector means for receiving the light beam after passing through or being reflected within living tissue and arranged to provide signals corresponding to the intensities of the respective wavelengths of light received by the photodetector.

We further provide a catheter comprising a sensor device adapted to measure blood oxygen saturation which comprises light source means for emitting a light beam, photodetector means for receiving the light beam after passing through or being reflected within living tissue and arranged to provide signals corresponding to the intensities of the respective wavelength of light received by the photodetector wherein the sensor uses spectral wavelengths in the range from 500 to 600 nm.

The catheter of the invention may comprise any conventionally known catheter means, e. g. a urinary catheter. However, for use in the measurement of bladder SO2 the catheter is preferably a drainage catheter, such as a Foley catheter. A Foley

catheter is a type of indwelling urinary catheter, which is usually in a soft plastic, silicone or rubber tube.

In an especially preferred embodiment of the invention the sensor may comprise one or more, e. g. three, optical fibres which are situated adjacent or in the wall of the catheter. In such a catheter the optical fibres may run substantially the whole length of the catheter. The tip of the optical fibres can be either directly exposed at the end of the catheter or be contained within the catheter wall. In a further alternative, the optical system may include one or more prisms, lenses, etc which might facilitate the transmission or detection of light.

The catheter of the invention fulfils the drainage function of a conventional Foley catheter, but also is adapted to be able to shine light onto the bladder wall and obtain a remitted spectrum from which S02 can be derived.

The catheter of the invention may be adapted to be in intimate contact with the bladder wall, although it will be appreciated that it is not essential that the sensor actually makes contact with the bladder wall in order to measure SO2.

According to a further aspect of the invention we provide a catheter which is adapted to measure the S02 of the blood in the bladder wall whilst in the presence of urine, or whilst the bladder is empty, i. e. in the absence of urine.

According to a further feature of the invention we provide a method which measures SO2 as hereinbefore described wherein the sensor is coupled to e. g. a pulse oximeter, which is conventionally known per se.

The method of the invention is advantageous in that, inter alia, it can be used to determine shock or organ failure in a patient by a non-invasive technique.

The method is further advantageous in that measurements may be made. adjacent the surface of the body organ or remotely.

The invention will now be described by way of example only and with reference to the accompanying drawings, in which Figure 1 is an illustration of optical fibres passed along a Foley catheter.

Figure 2 is a recording which illustrates the change in SO2 of the blood in the bladder wall of a pig put through different physiological manoeuvres.

Example 1 A Foley type catheter was constructed and optical fibres (contained in a plastic tube) were passed through the catheter to measure the SO2 of the blood in the wall of the bladder of a pig.

A catheter with optical fibres contained in a tube which is passed along the catheter is illustrated in Figure 1.

Figure 2 is a recording which illustrates how the SO2 of the blood in the bladder wall changed with time as the pig was put through different physiological manoeuvres.