Patent Publication Number: US-2009240192-A1

Title: Insufflation of body cavities

Description:
CROSS-REFERENCES TO RELATED APPLICATIONS 
     The present application is a continuation-in-part of U.S. patent application Ser. No. 12/058,255 filed Mar. 28, 2008 which claims the benefit of U.S. Provisional Application No. 60/907,311 filed Mar. 28, 2007. The present application also claims the benefit of U.S. Provisional Application No. 61/100,510 filed Sep. 26, 2008. The complete contents of all of these are incorporated herein by reference. 
    
    
     BACKGROUND OF THE INVENTION 
     Laparoscopic surgery, also called minimally or less invasive surgery (MIS or LIS) or keyhole surgery is a modern surgical technique in which operations in the body are performed through small incisions as compared to the larger incisions needed in traditional surgical procedures. Gas such as carbon dioxide is delivered, via an insufflator, into a body cavity such as the abdomen leading to the formation of a pneumoperitoneum, thereby providing sufficient space for the surgeon to operate. The insufflator maintains the pneumoperitoneum and acts to renew the gas when leaks occur. 
     Gas such as carbon dioxide that is used for insufflation is both cold and dry and it is not surprising therefore those patients undergoing laparoscopic procedures often suffer a significant drop in core body temperature, which can result in considerable post-surgical pain and significant complications, such as cardiac stress, immunological and clotting problems, for the patient. By using standard thermo physical principles it has been shown that the major cause of patient heat loss is due to evaporation from the body acting to humidify the large volumes of dry insufflated gas at ATPD (Ambient Temperature Pressure Dry) passing into the body which is at BTPS (Body Temperature Pressure Saturated). If such heat loss could be minimised, post-operative pain and the significant side effects suffered by the patient could be considerably alleviated. 
     Various attempts have been made to condition insufflation gas by heating, humidifying and or filtering the gas. However in general, known insufflation gas conditioning systems suffer from one or more disadvantages including complexity of construction involving expensive monitoring devices, inaccurate control and/or difficulties in using them in a controlled working environment. 
     Some systems employ heat moisture exchangers (HME). These operate directly in the flow path of the insufflation gas and are therefore inherently susceptible to affecting pressure or flow, dependent upon their level of saturation and condition. Other systems require manual intervention to respond to patients needs by the adding of moisture. Other prior art devices require the cumbersome procedure of passing gas over and through non-heated or heated liquid containers. Such devices present the major drawback of impeding pressure measurement in the insufflation cavity. 
     Systems using conventional jet nebulisers or nebulisation catheters exhibit one or more of the following disadvantages: impaction of larger particles, fogging in the body cavity thus reducing the surgeon&#39;s visibility, interference with insufflator settings increasing flow/pressure in the system. 
     This invention is directed towards providing a method and an apparatus that will address at least some of these problems. 
     STATEMENTS OF INVENTION 
     According to the invention there is provided an apparatus for use in laparoscopic surgery comprising:
         an insufflator for generating an insufflation gas;   an aerosol generator for aerosolising a fluid and entraining the aerosol with the insufflation gas wherein the aerosol generator comprises a vibratable member having a plurality of apertures extending between a first surface and a second surface; and   a controller to control the operation of the aerosol generator.       

     The controller may be configured to control the flow rate of the fluid to be aerosolised. 
     In one embodiment the controller is configured to deliver different flow rates of aerosol at different stages of a surgical procedure. The controller may be configured to deliver full flow at the start and/or end of a procedure. The controller may be configured to deliver reduced flow during a procedure. 
     In one embodiment the controller is set to deliver a pre-set amount of aerosol into insufflation gas. The apparatus may comprise means for varying the pre-set amount of aerosol. The means for varying the pre-set amount of aerosol may comprise a user interface such as a key pad or switch. 
     In one embodiment the controller is configured to control operation of the aerosol generator responsive to the insufflation gas. 
     The controller may be configured to control operation of the aerosol generator responsive to the flow rate of the insufflation gas. 
     In one case the apparatus comprises a device to determine the fluid flow rate of the insufflation gas. The determining device may comprise a flow sensor such as a flowmeter. Alternatively a differential pressure sensor may be used. 
     In one case a humidity meter is included in the circuit, preferably close to the patient to measure the level of humidification of the gas entering the body. In this case a feedback loop to the controller may be provided to control output from the nebulizer so as to ensure sufficient humidity is present in the insufflation gas. Such a system can be used to provide real time measurement to adjust the output from the nebulizer. 
     In one embodiment the first surface of the vibratable member is adapted to receive the fluid to be aerosolised. 
     The aerosol generator is configured to generate an aerosol at the second surface of the vibratable member. 
     In one embodiment the vibratable member is dome-shaped in geometry. Alternatively it may be of stretched flat shape. 
     In one case the vibratable member comprises a piezoelectric element. 
     The apertures in the vibratable member are sized to aerosolise the first fluid by ejecting droplets of the first fluid such that the majority of the droplets by mass have a size of less than 5 micrometers. The apertures in the vibratable member may be sized to aerosolise the first fluid by ejecting droplets of the first fluid such that the majority of the droplets by mass have a size of less than 3 micrometers. 
     The apertures in the vibratable member may be sized to aerosolise the first fluid by ejecting droplets of the first fluid such that the majority of the droplets by mass have a size in a particular predetermined range of less than 10 micrometers. In one case the range may be in a band of 1 to 3 microns and also a different range band of for example 7-9 microns. 
     In one case the controller is configured to control the pulse rate at a set frequency of vibration of the vibratable member. 
     The controller may be impedance matched to the aerosol generator. 
     In one embodiment the apparatus comprises means to determine whether the fluid is in contact with the aerosol generator. 
     The determining means may be configured to determine at least one electrical characteristic of the aerosol generator. The determining means may be configured to determine at least one electrical characteristic of the aerosol generator over a range of vibration frequencies. 
     In one case the determining means is configured to compare the at least one electrical characteristic against a pre-defined set of data. 
     The invention also provides a method for carrying out a procedure involving insufflation comprising the steps of:—
         generating an insufflation gas;   aerosolising a fluid using an aerosol generator wherein the aerosol generator comprises a vibratable member having a plurality of apertures extending between a first surface and a second surface; and   entraining the aerosol with the insufflation gas.       

     The method may comprise the step of controlling the aerosolisation of the fluid. 
     The method may comprise controlling the flow rate of the fluid. 
     In one embodiment the method comprises delivering different flow rates of aerosol at different stages of a surgical procedure. The method may comprise delivering full flow at the start and/or end of a procedure. The method may comprise delivering reduced flow during a procedure. 
     In one embodiment the method comprises delivering a pre-set amount of aerosol into insufflation gas. The method may comprise the step of varying the pre-set amount. An interface may be operated to vary the pre-set amount. 
     In one case the method comprises controlling aerosolisation of the fluid responsive to the insufflation gas so as to ensure adequate humidification of the insufflation gas. The amount of water a gas can hold is known. Consequently, nebulizer output when linked to insufflator flow can be used to provide sufficient aerosol to humidify the gas. 
     In one case a humidity meter is included in the circuit, preferably close to the patient to measure the level of humidification of the gas entering the body. In this case a feedback loop to the controller may be provided to control output from the nebulizer so as to ensure sufficient humidity is present in the insufflation gas. Such a system can be used to provide real time measurement to adjust the output from the nebulizer. 
     In one case the method comprises controlling aerosolisation of the fluid responsive to the flow rate of the insufflation gas. 
     In one embodiment the method comprises the step of determining the flow rate of the insufflation gas. 
     In another embodiment the method comprises the step of determining if the fluid is in contact with an aerosol generator. This may involve determining at least one electrical characteristic of the aerosol generator. Electrical characteristics of the aerosol generator may be determined over a range of vibration frequencies. 
     In one case the method comprises the step of comparing the at least one electrical characteristic against a pre-defined set of data. 
     In one embodiment the method comprises the step of delivering the entrained fluid and insufflation gas into a body to insufflate at least part of the body. 
     In one case the fluid is an aqueous solution. 
     The aqueous solution may be saline having a salt concentration &gt;1 μM 
     In one embodiment the fluid contains a therapeutic and/or prophylactic agent. The agent may be one or more selected from the group comprising an analgesic, an anti-inflammatory, an anti-infective, an anaesthetic, an anti-cancer chemotherapy agent, and/or anti-adhesion agent. 
     In one case the procedure is a laparoscopic procedure. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The invention will be more clearly understood from the following description of some embodiments thereof, given by way of example only, with reference to the accompanying drawings, in which:— 
         FIG. 1  is a perspective view of an apparatus according to the invention for use in a procedure involving insufflation of a body cavity, such as laparoscopic surgery; 
         FIG. 2  is a schematic illustration of a part of an apparatus according to the invention; 
         FIG. 3  is a schematic illustration of a part of the apparatus of  FIG. 1 ; 
         FIG. 4  is an exploded isometric view of an aerosol generator used in the invention; 
         FIG. 5  is a cross-sectional view of the assembled aerosol generator of  FIG. 4 ; 
         FIG. 6  is a perspective view of a controller housing used in the apparatus of the invention; 
         FIGS. 7(   a ) and  7 ( b ) are graphs of DC voltage versus time and AC voltage versus time respectively to achieve a 100% aerosol output; 
         FIGS. 8(   a ) and  8 ( b ) are graphs of DC voltage versus time and AC voltage versus time respectively to achieve a 50% aerosol output— FIG. 8(   a ) illustrates the waveform output from a microprocessor to a drive circuit and  FIG. 8(   b ) illustrates the waveform output from a drive circuit to a nebuliser; 
         FIGS. 9(   a ) and  9 ( b ) are graphs of DC voltage versus time and AC voltage versus time respectively to achieve a 25% aerosol output — FIG. 9(   a ) illustrates the waveform output from a microprocessor to a drive circuit and  FIG. 9(   b ) illustrates the waveform output from a drive circuit to a nebuliser; 
         FIG. 10  is a graph of AC voltage versus time; and illustrates an output waveform from a drive circuit to a nebuliser; 
         FIG. 11  is a graph of frequency versus current for another apparatus according to the invention; 
         FIG. 12  is a view similar to  FIG. 1  of another apparatus of the invention; 
         FIG. 13  is a view similar to  FIG. 1  of a further apparatus of the invention; 
         FIG. 14  is a view similar to  FIG. 1  of a still further apparatus of the invention; 
         FIG. 15  is a view similar to  FIG. 1  of another apparatus of the invention; 
         FIG. 16  is a view similar to  FIG. 1  of a further apparatus of the invention; 
         FIG. 17  is a partially cross sectional view of a detail of the apparatus of  FIG. 16 ; 
         FIG. 18  is a view similar to  FIG. 1  of another apparatus of the invention; and 
         FIG. 19  is an enlarged view of a detail of the apparatus of  FIG. 18 . 
     
    
    
     DETAILED DESCRIPTION 
     Referring to  FIG. 1  there is illustrated an apparatus according to the invention for use in insufflation of a body cavity. One such application is laparoscopic surgery. The device is also suitable for use in any situation involving insufflation of a body cavity such as in arthroscopies, pleural cavity insufflation (for example during thoracoscopy), retroperitoneal insufflations (for example retroperitoneoscopy), during hernia repair, during mediastinoscopy and any other such procedure involving insufflation. 
     The apparatus comprises a reservoir  1  for storing an aqueous solution, an aerosol generator  2  for aerosolising the solution, and a controller  3  for controlling operation of the aerosol generator  2 . The aqueous solution is fed from a reservoir  9  to the aerosol generator  2  along a delivery tube  13 . In the invention aerosolised aqueous solution is entrained with insufflation gas. The gas is any suitable insufflation gas such as carbon dioxide. Other examples of suitable insufflation gases are nitrogen, helium and xenon. 
     The insufflation gas is delivered into an insufflation gas tubing  15  by an insufflator  12 . The insufflator  12  may be of any suitable type such as those available from Karl Storz, Olympus and Stryker. The insufflator  12  has an outlet  20  through which insufflation gas is delivered. A bacterial filter  21  may be provided within the insufflator or, as illustrated, downstream of the insufflator outlet  20 . 
     In this case a flow rate sensor/meter  11  is located in the flow path of the insufflation gas from an insufflator  12  to the aerosol generator  2 . The flow rate sensor/meter  11  is connected by a control wire  70  to the controller  3 , and the aerosol generator  2  is connected to the controller  3  by a control wire  16 . The flow rate sensor/meter  11  may be a hot wire anemometer, or in the case where the flow is laminar or can be laminarised, a differential pressure transducer. 
     Sterile water may be used. In the case of an aqueous solution any suitable solution may be used. Solutions with a salt concentration in the range 1 μM (micro molar) to 154 mM (milli molar) (0.9% saline) are optimum as they cover the majority of medical applications. In addition, such saline concentrations can be readily nebulised using the aerosolisation technology used in the invention. 
     Liquid, saline or water for humidifying purposes only and/or medicament, can be delivered into the nebulizer reservoir through the opening in the top of the nebulizer that is appropriately sized to receive standard nebules or alternatively may be applied by syringe or other delivery means. In another embodiment it would be possible to supply the nebulizer pre-loaded with medicament avoiding the requirement to separately add medicament to the system. 
     Aqueous solution may be stored in the reservoir  1  container of the nebuliser or the aqueous solution may be delivered to the reservoir  1  of the aerosol generator  2  in this case from the supply reservoir  9  along the delivery line  13 . The flow of aqueous solution may be by gravity and/or may be assisted by an in-line flow controlling device  17  such as a pump and/or a valve which may be positioned in the delivery line  13 . The operation of the flow controlling device  17  may be controlled by the controller  3  along a control wire  18  to ensure that the aerosol generator  2  has a supply of aqueous solution during operation. The device  17  may be of any suitable type. 
     The apparatus comprises a connector  30 , in this case a T-piece connector  30  having an insufflation gas conduit inlet  31  and an outlet  32 . The connector  30  also comprises an aerosol supply conduit  34  for delivering the aerosol from the aerosol generator  2  into the insufflation gas conduit  15  to entrain the aerosol with the insufflation gas, passing through the gas insufflation conduit  15 . The entrained aerosol/insufflation gas mixture passes out of the connector  30  through the outlet  32  and is delivered to the body cavity along a line  60 . 
     The aerosol supply conduit  34  and the insufflation gas conduit meet at a junction. Referring particularly to  FIGS. 4 and 5 , in the assembled apparatus the aerosol supply conduit of the connector  30  may be releasably mounted to a neck  36  of the aerosol generator housing by means of a push-fit arrangement. This enables the connector  30  to be easily dismounted from the aerosol generator housing  36 , for example for cleaning. The neck  36  at least partially lines the interior of the aerosol supply conduit  34 . 
     The nebuliser (or aerosol generator), has a vibratable member which is vibrated at ultrasonic frequencies to produce liquid droplets. Some specific, non-limiting examples of technologies for producing fine liquid droplets is by supplying liquid to an aperture plate having a plurality of tapered apertures extending between a first surface and a second surface thereof and vibrating the aperture plate to eject liquid droplets through the apertures. Such technologies are described generally in U.S. Pat. Nos. 5,164,740; 5,938,117; 5,586,550; 5,758,637; 6,014,970, 6,085,740, and US2005/021766A, the complete disclosures of which are incorporated herein by reference. However, it should be appreciated that the present invention is not limited for use only with such devices. 
     Various methods of controlling the operation of such nebulisers or aerosol generators are described in U.S. Pat. No. 6,540,154, U.S. Pat. No. 6,845,770, U.S. Pat. No. 5,938,117 and U.S. Pat. No. 6,546,927, the complete disclosures of which are incorporated herein by reference. 
     In use, the liquid to be aerosolised is received at the first surface, and the aerosol generator  2  generates the aerosolised first fluid at the second surface by ejecting droplets of the first fluid upon vibration of the vibratable member. The apertures in the vibratable member are sized to aerosolise the liquid by ejecting droplets of the liquid such that the majority of the droplets by mass have a size of less than 5 micrometers. The vibratable member  40  could be non-planar, and may be dome-shaped in geometry. 
     Referring particularly to  FIGS. 4 and 5 , in one case the aerosol generator  2  comprises a vibratable member  40 , a piezoelectric element  41  and a washer  42 , which are sealed within a silicone overmould  43  and secured in place within the housing  36  using a retaining ring  44 . The vibratable member  40  has a plurality of tapered apertures extending between a first surface and a second surface thereof. 
     The first surface of the vibratable member  40 , which in use faces upwardly, receives the liquid medicament from the reservoir  1  and the aerosolised medicament, is generated at the second surface of the vibratable member  40  by ejecting droplets of medicament upon vibration of the member  40 . In use the second surface faces downwardly. In one case, the apertures in the vibratable member  40  may be sized to produce an aerosol in which the majority of the droplets by weight have a size of less than 5 micrometers. 
     The complete nebuliser may be supplied in sterile form, which is a significant advantage for a surgical device. 
     Referring particularly to  FIG. 3 , the controller  3  controls operation of and provides a power supply to the aerosol generator  2 . The aerosol generator has a housing which defines the reservoir  1 . The housing has a signal interface port  38  fixed to the lower portion of the reservoir  1  to receive a control signal from the controller  3 . The controller  3  may be connected to the signal interface port  38  by means of a control lead  39  which has a docking member  50  for mating with the port  38 . A control signal and power may be passed from the controller  3  through the lead  39  and the port  38  to the aerosol generator  2  to control the operation of the aerosol generator  2  and to supply power to the aerosol generator  2  respectively. 
     The power source for the controller  3  may be an on-board power source, such as a rechargeable battery, or a remote power source, such as a mains power source, or an insufflator power source. When the remote power source is an AC mains power source, an AC-DC converter may be connected between the AC power source and the controller  3 . A power connection lead may be provided to connect a power socket of the controller  3  with the remote power source. 
     Referring particularly to  FIG. 6  the controller  3  has a housing and a user interface to selectively control operation of the aerosol generator  2 . Preferably the user interface is provided on the housing which, in use, is located remote from the aerosol generator housing. The user interface may be in the form of, for example, an on-off button. In one embodiment a button can be used to select pre-set values for simplicity of use. In another embodiment a dial mechanism can be used to select from a range of values from 0-100%. 
     Status indication means are also provided on the housing to indicate the operational state of the aerosol generator  2 . For example, the status indication means may be in the form of two visible LED&#39;s, with one LED being used to indicate power and the other LED being used to indicate aerosol delivery. Alternatively one LED may be used to indicate an operational state of the aerosol generator  2 , and the other LED may be used to indicate a rest state of the aerosol generator  2 . 
     A fault indicator may also be provided in the form of an LED on the housing. A battery charge indicator in the form of an LED may be provided at the side of the housing. 
     Referring particularly to  FIG. 1 , the aqueous solution in the reservoir  9  flows by gravitational action towards the aerosol generator  2  at the lower medicament outlet. The controller  3  may then be activated to supply power and a control signal to the aerosol generator  2 , which causes the piezoelectric element  41  to vibrate the non-planar member  40 . This vibration of the non-planar member  40 , causes the aqueous solution at the top surface of the member  40  to pass through the apertures to the lower surface where the aqueous solution is aerosolised by the ejection of small droplets of solution. 
     Referring particularly to  FIGS. 4 and 5 , the aerosol passes from the aerosol generator  2  into the neck  36  of the aerosol generator housing, which is mounted within the aerosol supply conduit of the connector  30  and into the gas conduit of the connector  30  (flow A). The aerosol is entrained in the insufflation gas conduit with gas, which passes into the gas conduit through the inlet  31  (flow B). The entrained mixture of the aerosol and the insufflation gas then passes out of the gas conduit through the outlet  32  (flow C) and on via an insufflator line  60  to a patient, for example into the abdomen of the patient. 
     In use during laparoscopic surgery the flow of the insufflation gas into the abdomen of a patient is commenced to insufflate the abdomen. The flow rate sensor/meter  11  determines the flow rate of the insufflation gas. In response to the fluid flow rate of the insufflation gas, the controller  3  commences operation of the aerosol generator  2  to aerosolise the aqueous solution. The aerosolised aqueous solution is entrained with the insufflation gas, and delivered into the abdomen of the patient to insufflate at least part of the abdomen. 
     In the event of alteration of the fluid flow rate of the insufflation gas, the flow rate sensor/meter  11  determines the alteration, and the controller  3  alters the pulse rate of the vibratable member of the nebuliser accordingly. 
     The controller  3  is in communication with the flow rate sensor/meter  11 . The controller  3  is configured to control operation of the aerosol generator  2 , responsive to the fluid flow rate of the insufflation gas and also independent of the fluid flow rate of the insufflation gas as required. 
     In one case, the controller  3  is configured to control operation of the aerosol generator  2  by controlling the pulse rate at a set frequency of vibration of the vibratable member, and thus controlling the fluid flow rate of the aqueous solutions. 
     The controller  3  may comprise a microprocessor  4 , a boost circuit  5 , and a drive circuit  6 .  FIG. 2  illustrates the microprocessor  4 , the boost circuit  5 , the drive circuit  6  comprising impedance matching components (inductor), the nebuliser  2 , and the aerosol. The inductor impedance is matched to the impedance of the piezoelectric element of the aerosol generator  2 . The microprocessor  4  generates a square waveform of 128 KHz which is sent to the drive circuit  6 . The boost circuit  5  generates a 12V DC voltage required by the drive circuit  6  from an input of either a 4.5V battery or a 9V AC/DC adapter. The circuit is matched to the impedance of the piezo ceramic element to ensure enhanced energy transfer. A drive frequency of 128 KHz is generated to drive the nebuliser at close to its resonant frequency so that enough amplitude is generated to break off droplets and produce the aerosol. If this frequency is chopped at a lower frequency such that aerosol is generated for a short time and then stopped for a short time this gives good control of the nebuliser&#39;s flow rate. This lower frequency is called the pulse rate. 
     The drive frequency may be started and stopped as required using the microprocessor  4 . This allows for control of flow rate by driving the nebuliser  2  for any required pulse rate. The microprocessor  4  may control the on and off times to an accuracy of milliseconds. 
     The nebuliser  2  may be calibrated at a certain pulse rate by measuring how long it takes to deliver a know quantity of solution. There is a linear relationship between the pulse rate and the nebuliser flow rate. This allows for accurate control over the delivery rate of the aqueous solution. 
     The nebuliser drive circuit consists of the electronic components designed to generate output sine waveform of approximately 100V AC which is fed to nebuliser  2  causing aerosol to be generated. The nebuliser drive circuit  6  uses inputs from microprocessor  4  and boost circuit  5  to achieve its output. The circuit is matched to the impedance of the piezo ceramic element to ensure good energy transfer. 
     The aerosol generator  2  may be configured to operate in a variety of different modes, such as continuous, and/or phasic, and/or optimised. 
     For example, referring to  FIG. 7(   a ) illustrates a 5V DC square waveform output from the microprocessor  4  to the drive circuit  6 .  FIG. 7(   b ) shows a low power, ˜100V AC sine waveform output from drive circuit  6  to nebuliser  2 . Both waveforms have a period p of 7.8 μS giving them a frequency of 1/7.8 μs which is approximately 128 KHz. Both waveforms are continuous without any pulsing. The aerosol generator may be operated in this mode to achieve 100% aerosol output. 
     Referring to  FIG. 8(   a ) in another example, there is illustrated a 5V DC square waveform output from the microprocessor  4  to the drive circuit  6 .  FIG. 8(   b ) shows a low power, ˜100V AC sine waveform output from the drive circuit  6  to the nebuliser  2 . Both waveforms have a period p of 7.8 μS giving them a frequency of 1/7.8 μs which is approximately 128 KHz. In both cases the waveforms are chopped (stopped/OFF) for a period of time x. In this case the off time x is equal to the on time x. The aerosol generator may be operated in this mode to achieve 50% aerosol output. 
     In another case, referring to  FIG. 9(   a ) there is illustrated a 5V DC square waveform output from microprocessor  4  to drive circuit  6 .  FIG. 9(   b ) shows a low power, ˜100V AC sine waveform output from the drive circuit  6  to the nebuliser  2 . Both waveforms have a period p of 7.8 μS giving them a frequency of 1/7.8 μs which is approximately 128 KHz. In both cases the waveforms are chopped (stopped/OFF) for a period of time x. In this case the off time is 3× while the on time is x. The aerosol generator may be operated in this mode to achieve 25% aerosol output. 
     Referring to  FIG. 10 , in one application pulsing is achieved by specifying an on-time and off-time for the vibration of the aperture plate. If the on-time is set to 200 vibrations and off-time is set to 200 vibrations, the pulse rate is 50% (½ on ½ off). This means that the flow rate is half of that of a fully driven aperture plate. Any number of vibrations can be specified but to achieve a linear relationship between flow rate and pulse rate a minimum number of on-time vibrations is specified since it takes a finite amount of time for the aperture plate to reach its maximum amplitude of vibrations. 
     The drive frequency can be started and stopped as required by the microprocessor; this allows control of flow rate by driving the nebuliser for any required pulse rate. The microprocessor can control the on and off times with an accuracy of microseconds. 
     A nebuliser can be calibrated at a certain pulse rate by measuring how long it takes to deliver a known quantity of solution. There is a linear relationship between the pulse rate and that nebuliser&#39;s flow rate. This allows accurate control of the rate of delivery of the aerosolised aqueous solution. The ability to calibrate each nebulizer ensures that any inherent variation in output rate between each nebulizer can be eliminated. The output from each nebulizer when in-line in the insufflator circuit will be equivalent to a second nebulizer although the inherent flow rates of the two nebulizers are different. For example, to achieve a standard output of 0.044 ml/min at 1 Lmin from two nebulizers, one with an inherent output of 0.088 ml/min and a second with an inherent output of 0.176 ml/min the first nebulizer is controlled with a 50:50 on:off pulse rate, with the second set to a 25:75 on-off pulse rate so that both nebulizers give a 0.044 ml/min output. This feature ensures that the nebulizers when located in the insufflation circuit have the potential to provide exactly the same rate of aerosol output as each other. This is possible because the amount of humidity a gas can hold is a known constant dependent on controllable factors. 
     The pulse rate may be lowered so that the velocity of the emerging aerosol is much reduced so that impaction rain-out is reduced. 
     Detection of when the aperture plate is dry can be achieved by using the fact that a dry aperture plate has a well defined resonant frequency. If the drive frequency is swept from 120 kHz to 145 kHz and the current is measured then if a minimum current is detected less than a set value, the aperture plate must have gone dry. A wet aperture plate has no resonant frequency. The apparatus of the invention may be configured to determine whether there is any of the first fluid in contact with the aerosol generator  2 . By determining an electrical characteristic of the aerosol generator  2 , for example the current flowing through the aerosol generator  2 , over a range of vibration frequencies, and comparing this electrical characteristic against a pre-defined set of data, it is possible to determine whether the aerosol generator  2  has any solution in contact with the aerosol generator  2 .  FIG. 11  illustrates a curve  80  of frequency versus current when there is some of the solution in contact with the aerosol generator  2 , and illustrates a curve  90  of frequency versus current when there is none of the solution in contact with the aerosol generator  2 .  FIG. 11  illustrates the wet aperture plate curve  80  and the dry aperture plate curve  90 . 
     If an application requires a constant feed from a drip bag then a pump can be added in line to give fine control of the liquid delivery rate which can be nebulised drip by drip. The rate would be set so that liquid would not build up in the nebuliser. This system is particularly suitable for constant low dose delivery. Referring now to  FIG. 12  there is illustrated another insufflation apparatus which is similar to the apparatus of  FIG. 1  and like parts are arranged the same reference numerals. In this case the controller  3  is integrated into the insufflator  12 . The insufflator  12  would have information on the rate of flow that it is producing and using an integrated circuit board may directly communicate with the nebuliser  2 . This would eliminate the need for the separate flowmeter  11  and the stand-alone controller  3  to be present. 
     In another case there may be a common information bus between the insufflator  12  and the controller  3 . The insufflator  12  would have information on the rate of flow that it is producing and would communicate this to the controller  3  and on to the nebuliser  2 , thereby eliminating the need for the flowmeter  11 . This would allow the invention to be backward compatible with a variety of types of insufflator. 
     Referring to  FIG. 13  there is illustrated another insufflation apparatus which is similar to the apparatus of  FIG. 1  and like parts are again identified by the same reference numerals. In this case the insufflation gas flow signal is provided directly from the insufflator along a lead  71 . One advantage of this arrangement is that no separate meter/sensor required. 
     Referring to  FIG. 14  there is illustrated another apparatus according to the invention which is similar to that illustrated in  FIG. 1  and like parts are assigned the same reference numerals. In this case the nebuliser reservoir  1  has a top opening  100  which is closable by removable plug  101 . Liquid, saline or water for humidifying purposes and/or medicament is delivered into the nebuliser reservoir through the opening  100 . The opening  100  is appropriately sized to receive standard nebules containing liquid to be nebulised. The liquid may be applied by syringe or other suitable delivery means. 
     It is also possible to provide the nebuliser  1  pre-loaded with medicament to avoid the requirement to separately add medicament to the system. 
     The apparatus of  FIG. 14  is operated in a similar way to the modes of operation described above with reference to  FIGS. 2 to 11 . 
     Referring to  FIG. 15  there is illustrated another apparatus of the invention which is similar to that described above with reference to  FIG. 12  and like parts are assigned the same reference numerals. In this case the nebuliser reservoir  1  has a top opening  100  and a removable plug/lid  101  as described with reference to  FIG. 14  and the apparatus is operated as described above with the liquid being introduced through the opening  100 . Again the nebuliser may be pre-loaded with medicament. 
     Referring to  FIG. 16  there is illustrated another apparatus of the invention which is similar to that described above with reference to  FIG. 13  and like parts are assigned the same reference numerals. In this case the nebuliser reservoir  1  again has a top opening  100  and a removable lid  101  as described with reference to  FIG. 14  and the apparatus is operated as described above with the liquid being introduced through the opening  100 . The nebuliser may be pre-loaded with medicament. The apparatus is operated as described above.  FIG. 17  shows the connection of the controller lead  71  to the control circuit  105  of the insufflator  12 . 
     Referring to  FIGS. 18 and 19  there is illustrated a further apparatus according to the invention which is similar to those described above and like parts are assigned the same reference numerals. In this case the nebuliser reservoir  1  is closed by a lid  110  and the nebuliser is pre-loaded with medicament/liquid which avoids the requirement to separately add medicament to the system. 
     Humidity may be generated via the aerosolisation of any aqueous solution. Relative humidity in the 50-100% range would be optimum. The control module can generate a nebuliser output of any defined relative humidity percentage based on the insufflator flow. These solutions include any aqueous drug solution. Solutions with salt concentrations in the range 1 μM-154 mM would be optimum. 
     The use of the nebulizer to humidify the insufflation gas prior to entering the body will eliminate the need for the body to humidify the gas once it is inside the body, thereby minimizing body heat loss by internal evaporation. 
     The control in nebulizer output allows proportional delivery of the required amount of humidity according to the amount of insufflation gas entering the body. In addition this control of aerosolization rate will prevent overloading of the insufflation gas with aerosol which would obscure the surgeons view. 
     The invention provides a system that can deliver different flow rates at different stages of the surgical procedure. Examples of such different flow rates include:
         (i) delivering at 100% at the start of the procedure (Bolus);   (ii) delivering at a much lower rate say 5% during the procedure itself (Lower flow rate avoid fogging);   (iii) delivering at 100% at the end of the procedure (Bolus);   (iv) any combination of the above sequencing with variable % values.       

     In one case the controller which controls the operation of the aerosol generator is pre-set to deliver a set amount of aerosol into the insufflation gas. For example, the controller may be set to deliver an amount of 5% into a flow of 1 litre per minute of insufflation gas to avoid fogging. The controller may be pre-set in the factory to operate in this manner. Alternatively there may be a user interface such as a switch, or keypad which may be used to change the setting. In these arrangements control responsive to an insufflation gas flow sensor is not essential. 
     In addition to acting as a humidifying agent the nebulizer can also act to deliver any agent presented in an aqueous drug solution. The system facilitates delivery of, for example, pain-relief medications, anti-infectives, anti-inflammatory and/or chemotherapy agents in aerosol form to the body cavity. These therapeutic agents could also act as humidifying substances in their own right. 
     The nebulised liquid entrained in the insufflation gas may contain any desired therapeutic and/or prophylactic agent. Such an agent may for example be one or more of an analgesic, an anti-inflammatory, an anaesthetic, an anti-infective such as an antibiotic, an anti-cancer chemotherapy agent, and/or any agent which interferes with processes that result in the adhesion function. 
     Typical local anaesthetics are, for example, Ropivacaine, Bupivacaine and Lidocaine. 
     Typical anti-infectives include antibiotics such as an aminoglycoside, a tetracycline, a fluoroquinolone; anti-microbials such as a cephalosporin; and anti-fungals. 
     Anti-inflammatories may be of the steroidal or non-steroidal type. 
     Anti-cancer chemotherapy agents may be alkylating agents, antimetabolites anthracyclines, plant alkaloids, topoisomerase inhibitors, nitrosoureas, mitotic inhibitors, monoclonal antibodies, tyrosine kinase inhibitors, hormone therapies including corticosteroids, cancer vaccines, anti-estrogens, aromatase inhibitors, anti-androgens, anti-angiogenic agents and other antitumour agents. 
     The agent which interferes with the adhesion function may be any of those outlined in WO2005/092264A, the entire contents of which are herein incorporated by reference. In particular, the agent may be a crystalloid, hyaluronic acid, polyethyleneglycol, Tranilast (N-(3 1 ,4 1 -dimethoxycinnamoyl) anthranilic acid) or a Neurokinin 1 receptor (NK-1R) agonist, such as Aprepitant. 
     Typical analgesics include aspirin, acetaminophen, ibuprofen, naproxen, a Cox-2 inhibitor such as celecoxib, morphine, oxycodone and hydrocodone. 
     The system of the invention can be used for precise controlled delivery of drug and/or humidity during insufflation. No heating is required. Consequently there is no risk of damage to drugs due to heating The system may be used to provide precise control over aerosol output can be exercised by utilising pulse rate control. 
     The system may be used for targeted delivery of a range of drugs, thereby reducing systemic side effects. In addition the system provides alleviation of post-surgical pain experienced by the patient. 
     The system need not be located in the direct flow path of insufflation gas. In addition, minimal caregiver intervention during laparoscopic procedure is required. The system is small and compact and allows for integration with an insufflator. 
     The device of the invention can be used throughout the procedure carried out by a surgeon. The device ensures that humidity is actively controlled during the procedure and thus ensures that a surgeon&#39;s view is clear as fogging is avoided. 
     In the system of the invention the nebuliser output is controlled by pulsing to provide delivery of humidity and/or medicament into the insufflation gas during surgery without causing fogging. 
     The control may be provided either by providing a maximum output limit on the nebuliser or by linking directly to the insufflator flow. 
     All parts of the device (except the controller and associated leads) are autoclavable which provides a significant advantage for a device used in surgery. 
     The invention is not limited to the embodiments hereinbefore described which may be varied in construction and detail.