CA1331886C - Method and apparatus for precision monitoring of infants on assisted ventilation - Google Patents

Abstract

ABSTRACT
METHOD AND APPARATUS FOR PRECISION
MONITORING OF INFANTS ON ASSISTED VENTILATION
An apparatus and method are disclosed for monitor-ing physiological parameters associated with the ventilation of infants during assisted ventilation. The infant is placed in a plethysmograph and various sensor means are used to measure flow of gas into and out of the plethysmograph and infant respiration. The outputs of the sensor means are supplied to a microcomputer system for processing. A unique calibration system is provided which constantly corrects for changing system parameters such as plethysmographic chamber air leaks, compliance and the like. Additionally, a heating system which exhibits radiant as well as convective heating properties is provided to maintain the infant in a constant temperature environment with a minimal amount of temperature fluctuation. From this data, ventilator breaths are discriminated from infant breaths.

Description

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METHOD AND APPARATUS ~OR PRECISION
MONIT0R~ OF INPANTS ON ASSISTED VEN~ILATION

3ACKG~OUND OP T~E INVENTION

A portion of the disclosure of this patent document contains material to which a claim of copyright protection is made The copyright owner has no objection to the electro-photographic reproduction by anyone of the patent document or the patent disclosure, as it appear~ in the Patent & Trade-mark Office patent file or records, but reserves all other copyright rights whatsoever Mechanical ventilatory assistance is now widely accepted as an effective form of therapy and means for 15 monitoring respiratory failure in the neonate Mechanical ventilators are a conspicuous and fundamental part of neo-natal care When on assisted ventilation, the newborn infant becomes part of a co~plex interactive system which is expected to provid- adequate ventllation and gas exchange The overall p-rformance of the assi~ted ventilatory systeQ ia deterQin-d by both physiological and mechanical factors Th- physiological det-r~inants, over which the physician ha- relatively littl- control, change with time and 25 are difficult to define Thes- include th- nature of any pulmonary di~-as-, th- ventilatory efforts of the infant, and many oth-r anatomical and physiological variables Mechani-cal input to th- systeQ, on th- oth-r hand, i9 to a large ext-nt controll-d and can be rea~onably w-ll characterized by 30 examining the parameters of a ventilator pressure pulse Optimal ventilatory assi tance requires a balance between physiological and mechanical v-ntilation ~his balance should in~ure that the infant is neither overstrossed nor oversupported Insùfficient ventilatory ~upport would place unn-cessary demands on the infant's comproQised respiratory ~. ........ .... . . . .. . .
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system. Excessive ventilation places the infant at risk ~or pulmonary barotrauma and other complications o~ mechanical ventilation.

Intelligent management of ventilatory assistance in the neonate requires that information about the performance of the overall system be available to the clinician. Instru-ments for continuous monitoring of infants on assisted venti-lation, as weil as certain component variables of ventila-1a tion, are known and are discussed in ~Instruments for theContinuous Heasurement of Gas Exchange and Ventilation of Infants During Assisted Ventilation", K. Schulze, M.
Stefanski, J. Masterson, L. S. James, Critical Care Medicine, Vol 11, No. 11, pp. 892-896 (1983).
However, at the present time, physicians rely largely on intermittent measurement of arterial blood gases to monitor the overall effects of the system on qas exchange.
These measurements, while important in clinical care, have several limitations. Data acquired by such measurements 20 provides little information about the separate contributions of the infant and the mechanical ventilator to overall venti-lation and gas exchange of the infant. It has also bèen recognized that mechanical ventilation, although potentially a very promising technique, may indeed be harmful to the 25 lungs and brain of the infant in the event that the mechani-cal ventilator is not properly synchroni2ed with the infant's breathing. For example, see A. Greenough, C. Morley, J. A.
Davl~, ~Interaction of Spontaneou~ Respiration with Art~ficlal Ventilation in Pre Term Babies~, Journal of 30 Pediatrics 103:769 (1983). Furthermore, difficulty has been encountered in calibrating known systems to provide accurate and preci~e measurements of flow rates and the like.

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Absent information concerning the respective contributions of ventilation, the effects of changes in ventilator support are not as readily observable For example, it is ~requently desirable to monitor how an infant S responds to respiratory therapy such as positive end expira-tory pressure ("PEEP") therapy To administer this therapy, the ventilator decreases resistance to expiratory gases, thus decreasing the burden on an infant's lungs In addition, arterial blood qas measurements are available only intermittently in known systems Unfortu-nately, this makes both trends and abrupt changes in clinical condition of the patient difficult to recognize Continuous value~ are appreciably more helpful in describing the time course of changes in the patient's clinical condition than instantaneous or intermittent values When acquiring measurement~ of infant ventilation for research purposes, it is customary to place the infant in a container known as a plethysmograph A plethysmograph is a standard device for measuring change in volume of any mass contained within it 8ecaus- change~ in volume of animals or hum ns are due entirely to th- flow of ga~ into and out of the lungn this device afford~ an elegant approach for the 25 measurement of pulmonary function Normally, a plethysmograph i~ configured as an airtiqht box enclo~ing a subject who breathe~ externally supplied gas directly through an endotracheal tube inserted into the subject's nose, through his throat and into his windpipe Thu~, any ga~ breathed by the subject must be suppled from and exit via appropriate portion~ of the endo-tracheal tube and related piping Thi~ gas breathed by the subject is supplied from a gas source and does not communi-cate with air contained within the plethysmograph A~ the ~ ` `" - '`

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-4- 1 3~ 36 subject inspire~, the volume of the chest increases and causes either the pressure to rise inside the plethysmograph chamber if it is closed or, if the plethysmograph chamber has an opening, air to flow out, or a combination thereof These 5 changes in pressure or flow can be measured using any of a variety of sensors With the exception of openings used for respiratory support of the infant, and quantitative measure-ment of the infant's respiration, the interior of the plethysmograph must be isolated from the external environ-10 ment Also, for these quantitative measurements to be usefulin patient care, it is desirable to configure the plethysmo-graph such that the sensors are in a relatively stable environment At the same time, however, it i~ essential that the infant remain warm and undl~turbed and also be accessible 15 in a very short period in the event that an emergency arises Unfortunately, accuracy of measurements made by known plethy~mograph~ is severely compromised by the inherent compliance of air contained within the plethysmograph, as 20 well a~ compliance of elements such a~ tubes within the plethysmograph and the resistance of openings through the plethysmograph As will be appreciated, volumetric displace-ment of gas caused by an infant's breathing i9 not mea~ured directly, rather,'the air expelled from the interior of the 25 plethysmograph through a resistive opening(~) through a wall of the plethysmograph is quantitatively mea~ured Although an infant's inspiration of gas will result in the expiration of air through th- re~istive opening in the plethysmograph (caus~d by a change in the volume of the infant~, such 30 in~piration will also tend to increase the pre~sure of air within the plethysmograph due to the resi~tivity of the open-ing, typically a fine mesh type structure, to gas flow Similarly, expiration of gas from the infant's lungs will caus- inspiration of air through the re~istive op-ning 35 accompanied by a decrease in the pre~sure within the ~. .: - ^ -, `^ -:, :- - ' . ~

, 133~85 plethysmograph. As a result, the quantity of gas expired/inspired by the infant's lungs and the quantity of air inspired/expired by the plethysmograph are not equal, thereby introducing another source of error which limits the S accuracy and precision which may be achieved by known plethysmographs.

Additionally, leakage through various portions of the plethysmograph contribute to the introduction of error in 10 caleulations for determining flow rates and volumetric dis-placement. For example, leakage through the large seals which separate two halves of the plethysmographic chamber has been found to be a common source of error.
An additional deficiency of known plethysmographs is their inability to maintain a constant temperature environment for the infant. This disadvantaqe i5 also shared by other devices sueh as an ineubator whose very purpose is to maintain a eonstant temperature environment for the 20 infant. A eonstant temperature environment is critical to the survival of infants and, in particular, of premature infants.

Known ineubators and/or plethysmographs generally 25 attempt to maintain a eonstant temperature environment by either one of two methods, namely, by radiant heating or by eonveetive heating. A typieal radiant heater eomprises a heat soure- sueh as a light souree of appropriate wavelength radiat~ng heat energy towards an expo~ed infant. A typieal 30 eonveetive heater eomprises a heating eoil and, optionally, means for transporting air heated by such coil to the infant.
Unfortunately, neither of these two methods has been found entirely satisfaetory in maintaining a eonstant temperature environment for the infant.

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-6- ~ S3 1 ~36 SUMMARY OF THE INVENTIO~

In accordance with the present invention, a method and apparatus are describet herein for providlng continuous 5 measurement of infant ventiiation during assistet ventila-tion, which is particularly adapted for proviting a precise determination of flow rates and volumetric displacement occa~ioned by an infant's breathing. In addition, means are provided for maintaining a highly constant temperature 10 environment for the infant. Information is also available regarding the respective contributions to ventilation by the infant and the ventilation mechanism.

In the presently preferred embodiment, the appara-15 tus comprises a plethysmographic chamber in which an infantis placed, a pneumotachometer and a differential pressure transducer for detecting infant respiration, a pressure transducer for measuring pressure in a respirator tubing portion of an endotracheal tube inserted into an infant's 20 airway in order to discriminate the infant's breaths from ventilator breaths, an environment temperature control system for maintaining a constant t-mperature environment within the plethysmograph, means for preci~ely and constantly correcting for error introduced by the compliance of th- system and 25 leakage through the plethysmograph, means for determining the gain of the plethysmoqraph, and a preprogrammed microcomputer syste~ for proces-ing and storing data acquired by the afore-mentioned components. In another embodiment, the invention compris-s a second pneumotachometer and a second differential 30 pressure transducer for determining when ventilator breaths occur.

Details of the performance of a known plethysmo-graph are described in Karl Schulze, et al., ~Computer 35 Analyses of Ventilatory Parameters ~or Neonates On Assisted ., -7- 1 ~ 3 1 ~ .

Ventilation," IEEE Enqineeri~c-In Medicine And Bioloqy Maqazine Vol. 3, No. 3, pp. 31-33 (Sept. 1984) and u.s.
Patent No. 4,6~1,297 to Schulze.

In an alternate embodiment, data from the differen-tial pressure transducer and from the airway pressure tran-sducer or second differential pressure transducer are processed off-line.
In accordance with the invention, accurate measure-ment of flow rates is possible through the use of a calibra-tion system which constantly corrects for leaks in components of the plethysmograph as well as its compliance. The flow 15 rate corrected due to errors introduced by the compliance is calculated by adding a first correction factor onto the measured flow rate. This first correction factor is oro~Qr-tional to the time constant of the plethysmographic chamber, namely, the resistance of an airflow ope~ing in the chamber 20 multiplied by the compliance of the ai`r inside the box.
Since the compliance of such air is affected by the volume of the infant, calculation of the compliance is advantageously performed in real time, while the infant is in the chamber.
Furthermore, by constantly updatinq the time constant, 25 extremely accurate and precise measurements can be made.

Additionally, calculation of pneumotograph gain provides an additional correction factor which can be used to increa~e the accuracy and precision of calculated flow rates.
30 Applicat~on o a pressure pulse of known volume to the plethysmographic chamber results in detection of a measured volume of air expelled out of the chamber. The ratio of the known volume of the pressure pulse to the measured volume of air expelled is a measure of the gain of the chamber.
35 ~hrough appropriate signal processing, the most current gain . . .. ~ ~ - , .~.. - - , - ~
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An additional feature of the present invention i9 that the plethysmograph, which i9 ordinarily utilized as a research tool, is adapted for clinical patient care. The 10 plethysmographic chamber i9 provided with means or maintain-ing a very constant temperature environment and advanta-geously functions not only as a plethysmograph but addition-ally as an incubator. Furthermore, the data obtained through real-time monitoring of physiological parameters and 15 responses to stimuli is of great clinical value. Addition-ally, due to the mobility of the present invention, it is suitable for use in an operating room, x-ray suite and other such areas of a hospital where intensive care is not cur-rently available.

3RIEF DESCRIPTION OF ~HE FIGURES

These and other objects, features and advantages of 25 the invention will be more readily apparent from the follow-ing d-tailed de~cription of the preferred embodiment in which:

Fig. l is a block diagram showing an overview of 30 the presently preferred embodimcnt of the apparatus as employed in a system for ventilating an infant:

Fig. 2 is a real-time tracing of an infant's tidal air flow, airway pressure and arterial blood pressure:
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Fig. 3 i9 a tracing depicting an infant's total pulmonary ventilation, partitioned between the amount pro-vided by the ventilator and the amount derived from the infant's own breathing efforts;

Fig. 4 is a tracing depicting the relationship between ventilator pressure and lung inflation for each ventilator pulse;
Pig. 5 is a tracing depicting the beat by beat instantaneous heart rate, systolic, diastolic, and mean blood pressure plotted over a user-selectable range, illustra-tively, 200 heart beats;
Fig. 6 is a tracing depicting trends oS heart rate, blood pressure, minute volume, and respiratory rate over a ùser-selectable period of time, illustratively 60 minutes;

Fig. 7 is a tracing depicting the relationship 20 between ventilator pressure and lung inflation fo~ each ventilator pulse in which the infant is interacting unfavor-ably with the mechanical ventilator;

Fig. ~ depicts a tracing of an actual step response 25 of a pressure pulse superimposed on a traeing of a step respon~e derived from the actual step response;

Fig. 9 is a flow chart depicting the main program loop control;

Fig. 10 is a flow chart depicting interrupt rou-tines employed by the main program loop control of Fig. 9;

Fig. 11 is a flow chart depicting service events 35 employed by the main program loop control of Fig. 9;

, ~ ' ~f ' '' 1 ~3 1 ~6 Fig. 12 is a flow chart depicting the pattern recognition for the air ~low signal:

Fig. 13 is a ~low chart depicting the airway pres-5 sure (AP) waveform;

Fig. 1g is a flow chart depicting the blood pressure ~BP) waveform; and Fig. 15 i9 a flow chart depicting the ventilator controller algorithm.

DETAILED DESC~IPTION OF THE PRE~ERRED EM30DIMENT

As depicted in Fig. 1, the presently preferred embodiment of the apparatus compri~es a plethysmograph 10 in which is place~ an infant to be monitored, a ventilator such as a respirator pump 20 for ventilating the infant, a pneumo-20 tachometer 30 and a differential pres~ure transducer 40 formeasuring gas flow into and out of plethysmograph 10, a pres-sure transducer 50 for detecting pressure in the infant's airway, means 60 for ~aintaining a constant temperature environment and a pres-ure pulse source 120. A gas i~ource 70 25 feeds ventilator 20 via pipe 80 with gas for ventilation of the infant. This gas, typically an oxygen-nitrogen mixture, is provided to the infant in the plethysmograph 10 through pipe 75 and an endotracheal tube 90. Illustratively, pipeis 75, 80 are coupled together at port 77. Pipe 85 carries 30 expiratory ga~e~ back to ventilator 20. When ventilator 20, illustratively a Healthdyne model 100 ventilator, fires to respirate the infant, t~e ventilator occludes pipe as 5O that - gas provided to the infant by pipes 75, 80 will be forced through endotracheal tube 90 and into the infant's airway.

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:: ~. - - ~ .. ` , ' -11- 1 33 1 ~,6 Analog data provided by differential pressure transducer 40 is provided to a microcomputer system 130 by line 100. Pressure transducer 50 also provides microcomputer system 130 with analog data by a line ~not shown). Computer 5 130 digitizes this analog data from transducers 40 and 50 and processes it to obtain total tidal volume, volume due to infant respiratory efforts and volume due to the effects of mechanical ventilation. These values are then displayed by the microcomputer on a suitable video display terminal (VDT) 10 150. Illustratively, this display unit provides both digital and analog displays and a printer 160 provides a nursing report or a hard copy of the VD$ display. Advantageously, all of the equipmcnt depicted in Fig. l i9 mounted on a movable cart so that the infant can readily be moved, for 15 example, for emergency treatment, without adversely affecting either the infant's respiratory support or the monitoring thereof.

In the presently preferred embodiment, plethysmo-graph lO comprises a plexiglas~ plethysmographic chamber or box, capable of containing an infant. The interior atmos-phere of the plethysmograph i~ isolated from the exterior environment, except for one or more ports necessary for 25 respiration of the infant, i.e., port~) for pipe~ 80, 85.

Plethysmograph lO preferably comprises a plexiglass box whlch ha~ b-en ~plit in half. The top is hinged along on- ~id- and soft rubber gasketing material i~ applied along 30 the edges of the top and bottom such that when the top closes a very tight seal i~ formed. Although this seal is nearly air-tight, access to the infant is quite easy since the plethy~mograph top need only be swung to the open po~ition.
$he hinge means is constructed using a "tongue-in-pocket"
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1 33 1 ~6 entire top of the plethysmograph lifts off allowing access from both sides of the infant The hinge means preferably provides for a certain degree of vertical movement in the area where it is attached to the two halves so that the 5 gasket material there is not pinched or otherwise misaligned Alternatively, only the bottom half of the plethysmograph is provided with a suitable gasketing material and the top half of the preferably plexiglass box is provided with a tapered edge to mate and seal with the gasketing material of the 10 lower half of the box Even though very little air escapes at the junction between the top and bottom halves of the box, a method for performing repeated calibrations of the box, while the infant is in it, will correct for any leaks This method provides a means of makinq frequent measurement~ o 15 key parameters which, in turn, makc measurements of gas flow into and out of the infant's chest extremely accurate Advantageously, the plethysmograph accommodates monitoring leads, intravenous tubes and the like through 20 sterile adaptors that fit into the wall of the plethysmograph.

Pneumotachometer 30 illu~tratively comprises a pliable and semi-permeable ~creen, oppo~ite sides of which, 25 at time~, are exposed to dlfferent pressure level~ Pneumo- -tachom-ter 30 communicates with and receive~ air flow through an opening in a wall of the plethysmographic chamber Although many appropriately selected commercial pneumotacho-meter~ will be suitable for use in the practice of the inven-30 tion, a preferred pneumotachometer comprise~ a screen struc- -`
ture such as a ~00 mesh pneumotachometer This device pro-vides a known resistance to air flow and is exposed on one side to the interior of the plethysmograph and on the opposite side to the exterior Alternatively, a desc~iption 35 of another suitable pneumotachometer may be found in ., .~

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t -13- 1331~6 ~Pneumotechograph For Use With Patients During Spontaneous or A~sisted Ventilation," G Gregory, J Kitherman, Journal o~
ADDlied Physics, Vol 31, p 76~ ~Nov 1971) Air flow into and out of the plethysmograph is computed by monitoring the pressure difference across a known resistance provided by pneumotachometer 30 Pressure varia-tions occurring on the interior of the plethysmograph, such as those resulting from expansion and contraction of an infant's chest, are reflected by a pressure drop across the pneumotachometer Pneumotachometer 30 serves to provide a pressure differential between the interior of the plethysmo-graph and the exterior environment by creating a resistance to air flow ~hi~ pressure differential is measured by 15 differential pressure transducer 40 which has a first port communicating with thc interior of plethysmograph 10 and a second port communicating with the external environment The ventilatory flow ~ignal is computed from the pressure difÇer-ential These two ports of differential pressure transducer 20 40 are separated by pneumotachometer 30 Alternatively, a separate opening through the wall of the chamber for pneumo-tachometer is not nec-ssary if there is sufficient leakage el~ewh-r- in the plethy~mograph For exampl-, if the seals between the two halve- of th- chamber leak, a suitable Z5 pressure diff-r-nc- between the int-rior and the exterior oÇ
the chamb~r may d-v-lop and be mea~ured by transducer 40 in this situation, a separate pneumotachometer is not necessary as th l-aking seals or the like may suffice Alternatively, pneumotachometer 30 and difÇerential pressure transducer 40 may be located inside the plethysmo-graph, with a port of the pneumotachometer open to the plethysmograph interior Placement of pneumoeachometer 30 and transducer 40 insidc the plethysmograph may reduce the 35 potential for inaccuracies in the data acquired due to a;~ :- -- . : -~, ,: , . - . . ~ . - :

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1331~6 temperature differences between said elements and the plethy~mograph, although placement of pneumotachometer 30 through a wall of the chamber generally provides a better signal to noise ratio Differential pressure transducer 40 S sense~ the pressure on the two sides of pneumotachometer 30 and outputs an analog signal to line 100 showing the amount and direction of gas flow into and out of plethysmograph 10 Illustratively, the pre~sure transducer i~ a variable reluc-tance type that is driven at 5 KHz by a carrier-demodulator 10 preamplifie~ 105 A suitable differential pre~ure trans-ducer and preamplifier comprises pressure transducer model number MP-45-871 available from Validyne Engineering, Inc and prcamplifier model number CD-15-871 also available from Validyne The analog signal output by pneumotach preampli-15 fier 105 is intcrfaced with comput-r 130 and is preferably digitized at 50 ~amples per second by an A/D converter 110 In the presently preferred embodim nt, the amount and direction of gas flow are reflected by th- magnitude and 20 polarity, re~pectively, of the output sign~l from transducer Thu~, inJpiration and xpiration re~ult in dlfferent polarity outputs from th- transducer - ::
; Pip tS is coupl-d to endotracheal tube 90, which ~ -~;~ 25 is in turn ins-rted into the airw y of the infant Pressure transducer 50 is located in the endotracheal tu~e and sen~es pressur- in the infant's airway Transducer 50 output~ an analog sign-l indicating such pre~sure and provides ~uch output to computer 130 by way of A/D converter 110, which 30 illustratively samples at 50 samples per second Pressure transducer 50 is preferably a Novametrix Pneumogard Model 1200 pressure transducer ln an alternat- embodiment the function of pre~sure tran~ducer 50 is in~tead accomplished by a second pneumotachometer and pressure tran~ducer 56 These 35 components detect pressure changes ln pipe 58 ..;.- ~ :.. .- . - .
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~.... . . ~ ,,.. - .. .... , . - ,, 1331~6 Airflow into and out of the plethysmograph is computed from the pressure differences measured across the resistance to airflow provided by pneumotachometer 30 This pressure drop i9 directly proportional to the airflow 5 Subsequent integration of the flow measurements provides a direct measure of the volume of air that flows through the pneumotachometer Since airflow in and out of the box is cauced by chest wall expansion and contraction these volume measurements provide a highly accurate measure of inspired 10 and expired air volume with each breath, regardless of whether these breaths were generated by the infant or the ventilator More specifically, the zero flow point for the 15 pneumotachometer i~ con~tantly calculated and provided to the computer Zero crossing in the positive direction coupled with a positive slope thre~hold detection are used to deter-mine when a positive airflow that ls due to inspiration exi~ts In a similar fashion zero cro~sing in the negative 20 direction coupled with a negative slope threshold detection is used to determine when expiration occurs In addition, once a breath has been identified, it must fall within pre-d-fined limits for volume and duration before it is included for analysis A real time moving average filter and differ-25 entiator is employ-d nd provid-s for accurate and precise measurements M-ans 60 for maintaining a con~tant temperature environ~ent permit~ utilization of plethysmographic chamber 30 lO as an incubator A desired temperature level i~ accu-rately and preci~ely maintained by combining radiant heating with convective heating, yielding a heating system with a minimal amount of temperature fluctuation Preferably, means 60 comprise~ a radiant heater mounted external to the 35 plethysmograph and radiating heat towards the plethysmograph _, .
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-16- 1 331 ~a6 Such radiated heat travels through the translucent plethysmo-graph and is absorbed by the skin of the infant. Simultane-ously, the interior of the plethysmograph i~ convectively warmed by the contact of interior air with the heated portion 5 of the plethysmograph exposed to the radiant heat of the heater. Thus, the interior of the plethysmograph will generally be at a higher temperature than the external environment due to this double-staqe heating employing radiant as well as convective heating aspects. This combined effect of warming by both radiant and convective mechanisms allows temperature to be maintained at a given level with less fluctuation than is normally associated with conven-tional radiant warmer~. Studies have been performed on a large number of low birth weight infants and indicate that the metabolic rates of infants in this system are not different from those cared for in either pure convective or pure radiant heating systems.

Alternatively, heating means 60 may comprise, 20 either alone or in combination with radiant heating and/or convective heating, heating elements directly incorporated into the wall(s) of the plethysmograph, slmi1ar in form to defrosting systems typically employed in rear windows of automobiles. Advantageously, such heating element~ require a 25 relatively s~all amount of current to properly heat a plethysmograph. In such an alternative embodiment, the heat flow will be regulated by a servo-mechanism coupled to temper~ture probes within the plethysmograph and on the infant's skin.
Microcomputer 130 and associated hardware performs on-line computations of ventilatory parameters, collects and integrates information available from phy~iologic monitors such as pulse oximeter 170, blood pres~ure transducer 175, 35 temperature module and sensor 180 and ECG monitor 185. The ;,``-- ' ~ :
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1 S ~ f) computer derives relationships among variables and parameters from these monitors, displays graphic outputs of the analyses, records the data into disk files for later retrie-val, and produces written hard copy reports. A preerable 5 computer is the AST Premium Computer which is designed around the Intel 80286 microprocessor and 80287 math co-processor.
It is configured with 640 kilobytes of random access memory, a 40 megabyte hard disk drive, a 1.2 megabyte floppy disk drive, and a Yamaha PCDC II graphic controller.
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~ emperature module and sensor 180 are used to monitor the chamber wall and air temperature. More particu-larly, temperature is continuously recorded at a number of sites. These sites include th- patient's skin, ambient air, 15 and two surfaces of the incubator. These data are plotted on the temperature display for retrospective review of the thermostability of the patient and the environment. A
suitable temperature monitor is model 208 available from Cryotronics, Inc. ~his monitor is coupled to computer 130 by 20 way of an RS232 interface which has been modified for proper transmission of date (pins 4 and 5 are connectcd to each other, pins 6, 8 and 20 are connectcd to each other, pins 2 and 3 are reversed).

ECG monitor 185 may b- any of a number of commer-cially available electrocardiog:am monitors. Electrocardio-gra~ preprocessor 186 i~ used to determine the beat to beat int-rval of each heartbeat. This interval i9 timed to the neare~t tenth of a millisecond.
' More particularly, the preprocessor is an elec-tronic "front-end" ECG preproce~sor available from K ~ M Inte~face, Inc. of New York which detects the times when R-waves reach their peak and computes the interval 35 between successive R-waves with a resolution of + 0.1 msec.

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` 1 33 1 ~6 The computer receives RR intervals from the preprocessor over a parallel port and uses these to compute instantaneous heart rate The beat-to-beat rates are plotted sequentially on a cardiorespiratory display along with blood pressure and tidal 5 volume In addition, the mean heart rate is computed each minute and logged in the date base and these means are used for display in the trend screen and archival storage on disk.

Advantageously, circular buffers are used for the 10 storage of heart rate information In this way, continuous scrolling of the graphic data, from right to left, can be achievcd without the necessity of moving large amounts of data in memory Advantageously, the pres-nt invention permits on-line assessment of heart rate variability E~timates of ~long-term~ and ~short-term~ heart rate variability, defined a~ the coefficient of the change in RR interval~, (standard deviation of M interval/mean of RR interval) and the coeffi-20 cient of variation of the M interval~ (standard deviation of difference in adjacent M invervals/mean of difference in adjacent RR interval~), respectively, are computed each minute and are stor-d in the data base In addition, a fast Fourier transform ~FFT) power spectrum analysis of each 25 ~ucce~-lv- s-t of 128 M-interval~ is performed From these analy~e~ the contribution to overall heart rate variability that are a~sociated with speci~ied frequencies are then ~ummed One frequency band over which power is summed are the fr quencies that encompa~ ~ 1 standard deviation of the 30 respiratory rate that wa~ computed during the relevant 128 beat interval This portion of h-art rate variability, which i~ coupled to breathing activity, is referred to in the art a~ respiratory sinus arrhythmia This mea~ure ls believed to arise solely from variations in vagal nerve activity which 35 regulate~ cardiac timlng T~ls indirect measure of autonomic .Q

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-19- ~ s3 1 ~,6 nervou~ system influence on the heart of~ers an innovative tool for examining the integrity of brain mechanisms that influence cardiorespiratory function S In the presently preferred embodiment, precision and accuracy are maintained by constantly correcting ~or errors introduced by compliance and leakage of the system In particular, compliance of the air within the plethysmo-graph and of other compliant elements ~uch as tubing within the plethysmograph as well as the resistance of the pneumo-tachometer to air flow contribute to inaccurate measurements unless they are properly compensated for Factors such as the size of an infant will affect the total compliance of the system and the rate of air flow and must be compensated for 15 on a case by-case ba~is As will be appreciated, an accurate determination of the frequency re~ponse of the plethysmograph will aid in the calculation of flow rates which are corrected due to the compliance of the system Theoretically, the frequency characteristics of the plethysmographic system may be modelled as a fir~t order low pass filter In thi~ case the respon~e to an abrupt change in pressure provides information about the time constant of the plethysmograph In particular, the time constant (TC) of 25 the plethysmograph is the inverse of the re~istance to flow multiplied by the compliance ~l/RC) The time constant can be de~ived from the decay rate of flow following application of a stepped change in pressure This is done by modelling th- d-cay as an exponential of the form Y(t) = A ~ exp(-k ~ t) ~1) where Y~t) is the flow measured at time t after the step change in pressure, A is the initial flow, i e , peak flow, 35 and k is the inverse of the time constant 8y sampling the ,, ~ -~:.. . : , . : :

,3 1 ~86 decay curve at frequent intervals, equations can be created that allow for a simultaneous solution for the two unknowns, namely A and k.

Yl = A * exp(-k * tl) (2) Y2 = A * exp(-k * t2) (3) rearranging each equation, A = Yl / (exp(-k * tl)) (4) A - Y2./ (exp(-k * t2)) (S) thus, Yl / (exp(-k * tl)) ~ Y2 / (exp(-k * t2)) (6) :-taking the log of both sides, LN(yl) - LN(exp(-k * tl)) ~ LN(y2) - LN(exp(-k * t2)) ~7) LN(yl) ( k * tl) ~ LN(y2) - (-k * t2~ (B) LN~yl) LN(y2) ~ (-k * tl) - (-k * t2) (9) LN(yl) - LN(y2) ~ k (t2 tl) (10) thus, (LN(yl~ LN(y2)) / (t2 - t1) ~ 1 / $C (11) -:
Substitution of k into either equation (4) or (5) will yield a value for A. Once a value for TC is known, flow can be corrected by multiplying the time constant times the first derivative of flow and adding thi3 to the flow signal.
35 That is, ~'~.. -- ' '` ' ... .

',.;
, -~` 1 33 1 ~86 . -frequency corrected flow =
measured flow ~ ~C ~ d(measured flow)/dt (12) Equation ~12) is a formula known in the pertinent 5 art and useful herein for calculating a frequency corrected actual f low rate from a measured flow rate and knowledge of the proper time constant In this way, the frequency response of the 10 plethysmograph (which is normally down 3 db at 2 Hz) can be extended well beyond S Hz providing unprecedented accuracy in real-time measurements of flow through a plethysmographic system Although actual respiration rate~ rarely exceed 2 ~z, such an increase in frequency response provides a sub-15 stantial increase in accuracy since respiration is not purelysinusoidal but, rather, contains many higher order frequencies As will be appreciated, the time constant (TC or 20 R~C) comprises two terms, the resistance of the airflow opening (R) and the compliance of the air inside the box (C) Change in the measured time constant reveal information about the change in the leakage and/or compliance of the box Since the box compliance is depend-nt upon the volume of air 25 in the plethy~mograph, and hence on the volume of air dis-placed by the infant within th- plethysmograph, the measured tim constant will change with different si2e infant~ which displace different volume~ from within the plethysmograph Ther-fore, it i critical to be able to measure the time 30 constant of a whole body plethysmograph in order to obtain accurate result Moreover, since the time con~tant is dependent on the ~ize of the infant within the plethysmo-graph, the time constant must be measured while the infant is in~ide the plethy~mograph -22- 1 33 1 ~86 In the preferred embodiment of the invention, determination of the time constant of a whole body, i.e., including infant and plethysmograph, in order to ultimately calculate the corrected flow rate from the measured ~low 5 rate, comprises three steps, namely, 1. Extraction Of A Decay Response To A Step Change In Volume.
2. Determination Of The Maximum Value Of The Transient Wareform.

3. Calculation Of The Time Constant.

Step 1: Extraction Of A Decay R-spons-To A Step Change In Volume Referring again to Pig. 1, pressure pulse source 120 is the means by which a step change in volume is pro-duced. More specifically, pulse source 120 preferably 20 comprises a linear displacement actuator in the form of a modified polypropylene audio speaker which is optimized for suitably high rates of acceleration. The displacement actuator is housed within a plexiglass box (not shown) or the like so that a minimum volum- of air is contained between the 25 actuator surface and the inside of the plethysmographic chamber. Th- connection between the displacement actuator and the plethysmographic chamber is through a hole in the wall of the plethysmographic chamber. In alternate embodi-ments, the connection is made through a high resistance, 30 i.e., ~mall, hole in order to decouple the compliance of the two systems when the pulse source i9 not in use. The dis-placement actuator is stepped in and out by a high accuracy power amplifier module (not shown) available from K~M
~nterface, Inc. of New York. When the displacement actuator 35 is s~epped in the positive direction, injecting air lnto the ., ~. .
. . ... ~.

, ~ ~"
.. ~
;'` -:
,L^' ;~ :' ~-, - :.

1 33 1 ~86 plethysmographic chamber, there is a transient pressure increase that rapidly decays This docay rate i9 measured and taken as the time constant of the system S As will be appreciated, ~ince the system must measure the time constant in the presence of an infant, the step response to the displacement actuator must be separated from the breathing movements of the infant For thl~, a signal averaginq algorithm i~ preerably employed The dis-10 placement actuator is repeatedly stepped in and out, provid-ing transient pressure increases and decreases The decreases are preferably inverted rendering these waveforms identical to those which follow the transient increases This allows the transient decreases to be averaged along with the ~5 transient increase~ providing twice as many events for signal averaging Illustratively, for an infant re~piration rate of 60-80 breaths per minut- and a volumetric dl~placement of Scc per kilogram of infant weight, a step pulse of 60 cycles per minute and a volumetric di~placement of 80-100cc ha~ been 20 found suitable St-p 2 Deter~ination Of The Maxi~um Value Of The Tran~ien5_~aveform The maximum value of th- transient waveform i~ the ~ start of the exponential decay, i e , the variable A in -~ e~uation~ ~3) and (4) This value i~ determined using ampli-~ tud~ an~ly~is by locating th- local maximum of the step ; 30 re~pon~e Once the start of the decay period is determined, a following portion oS the decay (until the step response is rever~ed) i9 included in the analysi~ according to the previ-ou~ly enumerated equations A portion of approximately 80 of the decay ha~ been found suitable ;~

::
A
. ~

1 33 1 ~6 S~ep 3: Calculation Of The Time Constant Repeating equation (ll), it is seen that:

k = (LN(yl) - ~N(y2)) / (t2 tl) / (ll) However, if only two points are sampled (Yl and Y2), the measurement is subject to substantial error from noise. ThereEore, a plurality of such points are preferably 10 utilized to accurately calculate the value k as follows.
~irst, the decay curve is log-linearized and then least squares linear regression is performed on a plurality of data points to estimate the slope of the linearized decay, namely, the yalue k. Any suitable number of such points may be 15 utilized with fifty such points having been found suitable.

Thus, determination of the time constant in the above manner enables calculation of the frequency corrected flow rate in accordance with equation (12). As will be 20 discussed in conjunction with Fig. 8, this method provides for very accurate and precise determination of the time constant .

;~ As will be appreciated by one skilled in the art, 25 calculation of actual, a~ opposed to relative, volumetric displacement~ and flow rates i~ only possible by knowing the gain of the system, i.e., the pneumotachograph gain. ~he known volume of air injected by the pressure pulse source ~- provide~ the means for calculating this gain.
` 30 More specifically, the gain of the pneumotachograph can be determined when the average response to the displace- ~}
ment actuator i9 known. ~his is because a constant and known volume is injected into and withdrawn from the plethysmo-35 graphic chamber on each cycle of the actuator. ~he volume .. .

, , . , ` ~
~ . .

)J l ~3~)G
injected in measured by integrating the flow signal at the pneumotachometer during the step response. This measured volume is compared to the known volume displaced by the pulse source. The gain of the system is then determined by the 5 ratio of measured to actual volume ~Vact/Vmea~).
Thus, the ~'gain-corrected~' flow i~ given by:

gain-corrected flow = measured flow ~ (Vact/Vmea~) (13) ~ herefore, the actual flow is given by either of the following formula~:

actual flow ~ gain-corrected flow +
TC * d(gain-corrected flow) / dt (14) or actual flow ~ frequency-corrected flow * (Vact/Vmeas) (15) In the pre~ently preferred embodiment, the output ~iqnal of diffcrential pre~sure transducer 40 is po~itive during inspiratory flow and negative during expiratory flow.
Ideally, the integration of positive value inspiratory flow 25 data should equal the integration of negative expiratory flow data, since, over time, the volume of gas into and the volume -~of ga~ out of the infant's lungs are ordinarily the same. To obtain a calibration factor to compensate for the difference betw--n measured inspiration volume and measured expiration 30 volume, a predetermined amount of flow data obtained during a ~-recent sample injection and withdrawal of ga~ i~ integrated.
A bias value is derived during the calibration proce~ which is obtained by calculating the mean flow of the positive and ~5 - J--, ` ! :`- ::. .' - :

1 33 1 ~,6 -negative step responses. Advantageously, the bias value is constantly updated and represents a moving average, thereby providing a highly current and accurate dynamic bias value.

Next, the positive inspiratory data, only, are integrated, with the bias value being subtracted from each sample of flow data as it is included in the integration computation. The volume of gas which was injected in this calibration procedure, in cubic centimeters, is then divided 10 by the adjusted integration to determine the calibration factor. The data obtained during monitoring i~ then processed.

Advantageously, this cal~bration factor, like the 15 bia~ value, is constantly updated and represents a moving average, thereby providing a highly current and accurate calibration factor. Since such calibration is performed utilizing data gatbered over a period of time, irregularities occurring within one or two breath~ are not mistaken for a 20 general inaccuracy in measurement. In this-embodiment, the predetermined volume of gas injected into and withdrawn from ~ plethysmograph lO is sufficiently large such that ventilatcr`~ and infant breaths will compci~e a relatively small percent- age of total flow. A predetermined amount of flow data 25 obtained from tran~ducer 50 during injection and withdrawal i9 inteqrated and a real-time bia~ value is then obtained by ~ dividinq this integration by the product o the number of ;.
;~ flow data sample~ obtained and the sampling rat-. This real-time biaJ value i~ an index of the degree to which 30 in~piration and expiration diffec, and is useful to physi-cians as an estimate of ~uch factor~ as endotracheal tube leakage and thermal transients. Optionally, the real-time bia~ value also ~erve~ a~ an alarm indicator when the , _ ~ ,~
' .

., i~ . ~ .. ~ :
.
,~: ~
': `

3 1 ~6 endotracheal tube is leaking or is slipping from the infant's airway. The bias value also gives the physic$an an indica-tion of the stability of the monitoring system.

It is anticipated, however, that some flow data which appears to represent breathq will actually be the result of factors other than respiratory activity. Movement by the infant, for example, may generate such flow data. In order to obtain an accurate measurement of breath tidal 10 volume, actual breath must be discriminated from noise.
Illustratively, the flow data acguired during the relevant period is tested to determine whether it meets the followin~
criteria: the data contain~ only two polarity changes, a negative-to-positive polarity change followed by a positive-15 to-neqative polarity chan~e: the flow data must indicate that the breath was of at least a minimum duration and a minimum tidal volume; and the highe~t value data point of the flow data must be of at least a minimum value.

In the presently preferred embodiment, the criteria -~
for a valid breath, either v-ntilator induced or infant, are that it must be at lea~t 0.1 seconds in duration and must ; result in a tidal volume of at least 0.5 cubic centimeters.

Tidal volume of valid breaths is computed by integratin~ the inspiratory ~low data obtained during those breath~ and multiplying the result by the calibration factor.
Illu~tratively, for each minute of monitorin~, the tidal volum-, duration and maximum amplitude of each inspiratory 30 volume or breath and the total tidal volum and frequency of breaths are stored in a memory file for minute total data. --~

In accordance with the present invention, the minute total data is indexed to and processed in conjunction 35 with pres~ure data from pressure tran~ducer 50 to determine . ~ -` ' ' ' ' ' ' :' j ' .F~` . - .-.. - - ; . ~: .

-28- 1 s3 1 886 whether each breath is the result of inant respiratory ef~orts or is due to mechanical ventilation. Por each minute of monitoring, tital volume of each breath i5 referenced to airway pressure data obtained from pressure transducer 50 5 during the same period. More particularly, unter control of the computer program set forth in Appendix I, microcomputer system 130 compares each inspiratory volume, within a given minute, with the airway pressure data obtained from pressure transducer 40, or alternatively with the data output by 10 second tran~ducer 56, during the period that the inspiratory volume was collected.

The data associated with a given breath is input to microcomputer syatem 130 to dctermine whether the inspiratory 15 volume associated with that data was due to an infant breath or re~ulted from mechanical ventilation. An inspiratory volume which occurs simultaneously with a change in airway pressure which exceeds a predetermined magnitude is considered to relate to a mechanical ventilator breath. In 20 the presently preferred embodiment, the predetermined change in airway pressure is approximately 20mm. of Hg., but this va~ue is subject to change dep-nding upon the ventilator output pre~sur-. Conv-rs~ly, a bceath occurring without any such change in airway pressure is conJidered to relate to an 25 infant breath. In the event that pressure data from pneumo-tachom~ter and pre~sure tran~ducer 56 is used instead of data fro~ tran~ducer 50, compari~on is made between the breath volum and the data oueput by transducer 50 during the period of th~ breath. ln this case the program detects a drop in 30 pres-ure in tube 58 caused by ventilator 20 occluding tube 85.

A disk file is created and updated in real time with minute averages for a number of variable~ for use in the 35 processing of data and calculation of flow rates, reports, A
~ -~, F~
C~' :
i.,``' :
, ~
~`' ' '' : ` ' ' . ' ,~ : - , ~, ' , ~ 33 1 ~86 etc. Illustrative of such variables are the time of day, tidal volume of the baby and its standard deviation, tidal volume of the ventilator, RR interval and its standard deviation, heart rate standard deviation, respiratory cycle 5 time and its standard deviation, inspiratory time and its standard deviation, respiratory frequency and its standard deviation, respirator minimum pressure, respirator maximum pressure, airway mean pressure, short term variability (SDD) and its standard deviation, respiratory sinus arrhythmia (RSA), calibration qain factor, calibration time constant, zero flow, average of average blood pressure and its standard deviation, stystolic blood pressure and its standart devia-tion, diastolic blood pressure and its standard deviation and temperature of the infant, the air in the plethysmographic 15 chamber, the inside wall of the plethysmographic chamber and the outside wall of the plethysmographic chamber.

Although the invention has been described as an apparatus and method wherein data is accumulated, processed 20 and displayed on-line it will be apparent to those skilled in the art that an off-line data accumulation, processing and -~
display system in which data is accumulated on a continuous basi~ for a predetermined period and is then loaded into a -~
microcomputer system for processing, i~ equally contemplated 25 by the invention. In this mbodim-nt lines rom the various transduc-rs and monitors are coupled to an digital tape recorder whlch al90 receives a tim- ~tamp signal from a time marking device. This analog tape recorder subseguently inputs uch data to a microcomputer system. -Referring now to Fig. 2 there is depicted a real-time tracing of an infant's tidal air flow, airway pressure and arterial blood pres~ure. Appropriate blood pres~ure processinq elements of the master progra~ receive input in :. :

, -.: ---, --. .. -- .. . ,.,, . -~ -. , .- . . ,, ,.. .;.. ,.,, ,, .:,, - . . ::........ . . ...

- 1 J31 ~86 the form of digitized values of blood pressure. Such digi-tized values are obtained from known analog to digital conversion of the outputs available on typical commercial heart rate monitors. The digitized corrected and calibrated values are avallable as real-time tracings as shown in the lower tracing of Figure 2. This figure also shows real-time tracings of airflow and airway pressure.

The program computes beat-to-beat systolic, diastolic and mean arterial pres~ures from the raw heart rate signal. These beat-to-beat values are then plotted seguen-tially in a cardiorespiratory screen along with heart rate and tidal volume as depicted in Fig. 5. This display is very useful in summarizing the changes in vital signs during apnea or other acute events. The blood pressure values are also averaged each minute and displayed on the trend screen. This screen summarizes the changes in blood pressure during user selected intervals over time periods up to 24 hours in length. The user may choose to review a defined interval length, e.g. the preceding 30 minutes, 6 hours etc., or a specific period of clock-time, e.g. from 12:00 to 13:30.
These data, and all other important patient data, are written to a disk file which accumulate~ a detailed history of the infant's clinical progress.
A patt-rn recognition algorithm i~ provided for detection of systolic and diastolic pressures in the blood pres-ure waveform. This process consists of two steps.
Initially, the first derivative of the blood pressure wave-form i9 examined for a positive then negative threshold.Then the maximum amplitude of the blood pressure waveform between these two points is located and taken to be the systolic pressure. Secondly the blood pressure waveform is ~. .......... ~ .

. . . .
, : . .
.., ~
. :: . . .

-~. ~

-- 1 33 1 ~6 examined between the currently located systolic pressure and the previous systolic pressure foc a local minimum. This is taken to be the diastolic pressure.

Fig. 3 is a tracing depicting an infant's total pulmonary ventiiation, partitioned between the amount provided by the ventilator and the amount derived from the infant's own breathing efforts.
The pressure applied by the ventilator to the airway of the infant can be recorded by any of a variety of commercially available airway pressure monitors. The system uses the measurement of airway pre~sure for two reasons.
First, it is important to quantify several parameters of the 5 pressure pulse being applied to the airway of the patient, namely, peak pressure, trough pres~ure, mean pressure, respiratory cycle time, and the general shape of the pressure wave. The second use of the airway pressure measurement is to track the firing of the mechanical ventilator. When the ~ -20 airway pressure i~ observed to rise acutely, as it does when the ventilator delivers a pulse of air to the airway, the accompanying tidal volume is identified by the program and is recorded in the data file a~ a Hventilator" or "mechanical"
breath. When breath~, i.e. patterned change~ in airflow, are 25 detected by the software, and these are not coincident with a ventilator pul~e, the program file~ these a~ "infant"
breatha.

By grouping tidal volumes into mechanical and 30 infant ~ubfiles the program is able to partition the total ventilation of the infant between that attributable to the infant's effort and that which i~ provided by the ventilator.
~n fact, the program computes the percent of the total volume ~., .

-32- ~ ~3 1 ~86 provided by the mechanical ventilator on a continuous bas1s and displays this value on the ventilatory assistance screen as illustrated in Fig. 3.

S An algorithm is also providet for detecting the presence of a pressure pulse in the airway pressure waveform.
This process consists of several steps and will be discussed in detail in conjunction with Fig. 13. The first step is to locate the occurrence of a pressure pulse by examining the first derivative of the waveform for a positive threshold value followed by a negative threshold value. This indicates that an airway pressure pulse has occurred. The second step is to locate the end of the pressure pulse by examining the second derivative of the waveform for a local minimum between the positive and negative threshold values. This point corresponding to such local minimum i~ taken as the end of the pressure pulse from the ventilator. The start of the pressure pulse i5 determined by locating the local maximum in the second derivative of the pressure pulse waveform between 20 the time of the positive threshold in the first derivative and a previous predetermined time interval, illustratively 0.5 seconds.
.~
Fig. 4 is a tracing depicting the relation~hip 25 between ventilator pressure and lung inflation for each ventilator pulse. As will be appreciated, changes in airway pressure are al~o related to the concomitant tidal flows and may be plotted, in real-time, as a continuou~ series of "pressure/volume inflation curvesn. The relationship between 30 changes in airway pre~sure and changes in lung volume is an important indicator of pulmonary function. If substantial lung inflation occurs at low levels of airway pressure the lung i5 said to be compliant and, in general, healthy. If - large pre~sures are re~uired to inflate the lung it is non-35 compliant, and this i5 not healthy. The pres ure-volume . . .--.- . ' - ~ . , ; ' .',' ' . ' "

' ' ..... ..

_33_ 1 33 1 ~J

, plots, which are displayed after each firing of the ventila-tor, are invaluable indices of the compliance of the lung, as depicted in Pi~ 4 The effective compliance of the lung is calculated from the slope of thiQ inflation curve and logged into the patient's data base Thus, changes in the effective compliance of the lung can be eaQily related to other events and variables associated with the infant's care record Additional important information about the inter-action between the infant the mechanical ventilator is available from inspection of the "pressure-volume loops"
When the infant is interacting favorably with the ventilator these loops take on a sigmoid, or S shaped appearance and the -~
volume delivered by th- machin- is consistent from breath to breath This type of favorable interaction is shown in Figure 4 In contrast, these inflation curves can take on other much less de~irable forms Examples of these devia-tions can be seen in Figure 7 These forms occur as a result of a mismatch between the infant's own breathing efforts and that provided by the ventilator Large tidal volumes, and steep slopes are seen when infants breath in at the same time - -the ventilator fire~ Thus, the volume is additive between -the two and th- lung is ov-r-inflated On the other hand, small tidal volume~ are ob~erved when the ventilator fires while th- infant i~ exhaling Occ-~ionally the ventilator fire~ wh-n th- infant is exhaling forcefully and, in these instance~, tidal volume is negative This situation, known as ~fighting~ the ventilator, i~ extremely unde irable becau~a pressure i~ built up as th- ventilator forces air in to the lung while the infant i~ forcefully exhaling This places the infant at risk for lung rupture or cerebral hemorrhage Inspection of the form of the lung inflation curves allows the clinician to continuously monitor the synchrony between the infant and the ventilator When this interaction appears unfavorable, appropriate changes in s ~

-34- 1 J~ 6 ventilator firing rate can be made, and using the continuous feedback provided by the present invention, the effectiveness of these changes can be readily evaluated In alternative embodiments the present invention uses thi3 ability to S monitor infant/ventilator synchrony to develop a servo-mechanism for optimizing ventilator firing patterns Fig 6 is a tracinq depicting trends of heart rate, blood pressure, minute volume, and respiratory rate over a 10 user-selectable period of time Such a period of time may be any suitable range, for example, the previous 60 minutes Microcomputer System 130 advantageously outputs a wide variety of charts, displays, reports and the like Illu~tratively, a display chart may indicate calibration lS measurement specificQ, an infant's date of birth, age, weight and telephone number of parents Any additional desired information may be provided on this display chart Minute by minute av-rages of the respiratory 20 freguency, heart rate, blood pre~sure, etc are preferably averaged over each hour These hourly averages of patient history are used to compile a nursing ~hift report A single summary sheet serves as a formal record of the major trends ~of the patient over each eight hour shift This greatly ;; 25 reduces the amount of record keeping reguired of the nurses and free~ them to att-nd to the patient rather than ~paper-work~
.
Data recorded by the aystem is preferably related 30 to the time of day and age of th- infant When a patient is placed in the plethysmograph, the clinician enters the following pertinent information; the infant's name, tim- and date of birth, telephone number of parents, and the patient's birth weight As physiologic data i5 accumulated it is 35 written, once each minute, into th- data bas- in the proper . 8 6 time slot Discontinuous signals such as daily weight, arterial blood gases, serum chemistries, etc are manually entered at the keyboard and are entered into the data base at time specified The data base, which is stored on a disk file, can be examined and edited by the user at any time off-line In addition, with the aid of special purpose -software, any of the variables can be plotted and analyzed further in an off-line mode The data file is made available in a standard ASCII format which allows the raw data to be easily read by any of a variety of commercially available data base and statistical analysis software packages Pig 3 depicts an exponentially decreasing first waveform which r-pre~ents an actu-l measured respons- of the sy~tem to a single pres~ure pulse from actuator 120, i e , a response to an ideal step Pig 8 also depicts a second waveform, initially increasing, and then decreasing in an exponential manner The second waveform is derived from the -time constant o~ the sy~tem in accordance with the three steps previously disclosed As will be app~eciated, the two waveforms are very similar after an initial transitory period Fig 9 is a flow chart depicting the main progeam loop control Initially, system variables are initialized and a Log file is created Once A/D sample~ are received patt-rn recognition software is run and detects patterns relating to air flow (Fij 12), airway pres~ure (Piq 13) and blood pressure (Fig 14) Data indicative of these pattern-~
and other useful data are provided to the computer system bydifferential pressure tran~ducer 40, pressure transducer 50 and blood pressure, temperature and ECG monitoring devices as well as a pulse oximeter Once an cvent is ready to be serviced, i e , data collected and ~uitably processed or stored, an algorithm corresponding to the flow chart depicted ~,~
~'~

-36- ~ 33 1 ~6 in Fig. 11 is run. Such events illustratively include the RR ~;
interval, i.e., the distance between R-waves ~spikes) on an ECG output waveform, inspiration cycle, pressure pulse, and systole measurement. For example, a breath cycle may be serviced by calculating inspiration (TI) and expiration (TE) times, total respiration cycle time (TTOT-TI + TE1 and tidal volume (VT); a pressure pulse may be serviced by calculating the ventilator pressure pulse tidal volume (VT), its peak value and its mean pressure; a heart R wave may be serviced by calculating the respiratory ~inus arrhythmia (RSA); and a blood pressure waveform may be sierviced by calculating the systolic, diastolic and mean blood pressures. Once the events are serviced and an entire minute has not passed, the process is repeated until a minute has passed in which case the Log file is updated and an average calculation performed for illustrating trends on the system. A user request such asi a mode or display change request may also be performed and provide a means for exiting th- data gathering and processing process, if desired.
; Fig. 12 d-pict~ the air flow signal pattern recog-nition algorithm. In particular, once a breath has begun, a neqative flow siignal having a negative slope indicates that a breath i9 ending while a positive flow having a positive slope indicate~ that a breath has started.

Fig. 13 depicts the airway pressure (AP) waveform pattern recognition algorithm. ~n particular, once a thres-hold po~itive AP slope is encountered and stored, additional data is read until a threshold negative slope i~ encountered and stored. The minimum of the second derivative of this waveform between the points corresponding to the threshold positive encountered AP slope and the threshold negative encountered AP slope i9 determined and stored as the end of the pulse. Similarly, the maximum of the second derivative .. ~ ... . . . . ., - ~ .. . -r.~. :.: - ~ , .
:. .; ' ` ' ' ` - ` . ' : .
~: , - `- - , :, - .: .

1331~36 of the waveform before the threshold positive slope is deter-mined and stored as the start of the pulse. If the range between the start and end of ~he pulse is greater than a predetermined threshold, the AP value i9 con4idered valid and --stored, otherwise it is declared invalid. This process is repeated and a plurality of valid AP values are determined.

Fig. 14 depicts the blood pressure (BP) waveform pattern recognition algorithm. In particular, once a posi-t0 tive BP slope is encountered, the minimum value between thecurrent and last positive slopes are calculated and stored as the diastolic. Once the 8P slope becomes negative, the maximum value between the positive and negative slopes is determined and stored as the systolic. If the systolic minus the diastolic is not greater than a predetermined threshold, then the systolic and diastolic BP values are considered invalid and the procedure repeated. If the difference is greater, then the interval between blood pressure waves is examined. If such interval is not greater than a threshold, the systolic and diastolic aP values are considered invalid and the procedure repeated. If such interval is greater than a threshold, the systolic and dia-tolic values are considered valid and stored. This process is rep-ated and a plurality of valid BP systolic and diaJtolic values determined.
Pig. 10 is a flowchact depicting the interrupt software for use with the master program of Fig. 9, while Fig. 15 is a flowchart of the algorlthm for automatically controlling the rate of the ventilator, if desired. In particular, the number of breaths are counted until either the time for such counting equals or exceeds the desired ventilator interval or the number of breaths equals the average number of breaths N between ventilator pulses. If the number of breaths equals the average number of breaths between ventilator pulses or lf the time is equal to or ~; . - . . . .
, -38- 1~31~6 greater than N and an inspiratory flow is in process, a determination i~ made whether an expiratory flow has started.
Once it has, and once the slope of the flow is greater than a threshold value, a determination ig made whether the flow signal is greater than a threshold value. If the flow signal is greater than the threshold value or if it is not but a time greater than T has passed, the respirator is triggered.
If it had been determined that an inspiratory flow was not in progress, the respirator would have been immediately triggered. Advantageously, this algorithm will produce lung inflation tracings more in accordance with Fig. 4 than Fig.
8. ~n other words, use of this algorithm will reduce the "fightinq" between the infant's ventilation and the ventilator.

While the invention has been described in conjunc-tion with specific embodiments, it is evident in light of the foregoing de~cription that numerous alternatives, modifica-tion~, and variations will be apparent to those skilled in the art.

.

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Claims (44)

We Claim:

1. An apparatus for obtaining continuous measurements of infant ventilation during assisted ventilation by an assisted ventilation gas source comprising:
a plethysmograph having at least an input port, means for coupling an assisted ventilation gas source to said input port of said plethysmograph, a pressure pulse source coupled to said plethysmograph for applying a pressure pulse of known volume into said plethysmograph, an endotracheal tube having a first end which is coupled to said input port and a second end which is insertable into an airway of an infant placed in said plethysmograph such that said airway is isolated from the interior of said plethysmograph, a pneumotachometer attached to said plethysmograph and having a resistance to air flow and being adapted for providing a pressure differential on opposite sides of said pneumotachometer, a differential pressure transducer coupled to said pneumotachometer for outputting a differential pressure signal reflecting said pressure differential, said differential pressure signal being proportional to a flow signal indicating a flow rate through said pneumotachometer, means for detecting pressure changes in said endotracheal tube caused by said assisted ventilation gas source and breathing efforts of said infant and for outputting an airway pressure signal in accordance with such pressure changes, means for converting said differential pressure signal into digital data, a preprogrammed computer system having:
means for calculating digitized flow data from said digitized differential pressure data, means for frequency correcting said digitized flow data, means for determining from said frequency corrected digitized data at last whether pressure changes in the interior of said plethysmograph are due to assisted ventilation or to the infant's breathing efforts and for determining a resultant volumetric displacement from said frequency corrected digitized flow data.

2. The apparatus of claim 1 further comprising means for gain correcting said digitized flow data.

3. The apparatus of claim 2 wherein said gain correcting means comprises means for integrating said digitized flow data and comparing said integrated flow data with a known volume displaced by activation of said pressure pulse source.

4. The apparatus of claim 3 wherein said pressure pulse source comprises a linear displacement actuator.

5. The apparatus of claim 1 further comprising a radiant heater located external to said plethysmograph and which radiates heat energy towards said plethysmograph and said infant and which produces convective heating within said plethysmograph.

6. The apparatus of claim 1 wherein said frequency correcting means comprises means for calculating a time constant of said plethysmograph and multiplying said time constant by a first derivative of said flow data with respect to time and adding the result to said flow data to provide frequency corrected flow data.

7. The apparatus of claim 6 wherein said time constant is the resistance of air flow openings in said plethysmograph multiplied by the compliance of air inside the plethysmograph.

8. The apparatus of claim 1 wherein said means for detecting pressure changes caused by said ventilation source comprises a pressure transducer adapted for sensing pressure in said endotracheal tube.

9. The apparatus of claim 8 wherein said pneumotachometer is positioned in an opening through a wall of said plethysmograph.

10. The apparatus of claim 1 wherein said means for detecting pressure changes caused by said ventilation source comprises:
a second pneumotachometer coupled to an exhaust port of said ventilator, and a pressure transducer coupled to said second pneumotachometer.

11. The apparatus of claim 1 wherein said plethysmograph comprises a first section having a tapered edge and a second section hinged to said first section and sealable with said first section by way of a gasketing material placed on an edge of said second section for sealing contact with said tapered edge.

12. The apparatus of claim 11 further comprising means for moving said first section directly away from said second section to provide uniform sealing pressure between said tapered edge and said gasketing material.

13. The apparatus of claim 1 further comprising means for calculating systolic blood pressure and diastolic blood pressure of the infant.

14. The apparatus of claim 13 wherein said calculating means calculates a systolic pressure value by determining a maximum amplitude of a blood pressure waveform between a positive threshold value of a first derivative of said blood pressure waveform and a negative threshold value of said first derivative of said blood pressure waveform, said maximum amplitude being the diastolic pressure.

15. The apparatus of claim 14 wherein said calculating means calculates diastolic pressure by determining a local minimum of the blood pressure waveform between said systolic pressure value and a previous systolic pressure value, said local minimum being the diastolic pressure.

16. The apparatus of claim 1 further comprising means for synchronizing said infant's breath with said assisted ventilation.

17. A method for precisely calculating a flow rate of air into and out of a plethysmograph occasioned by breathing efforts of an infant and ventilatory assistance comprising:
measuring a difference in pressure across a pneumotachometer due to a flow rate into and out of said plethysmograph by a differential pressure transducer, frequency correcting a signal output by said differential pressure transducer, said signal being proportional to said flow rate and said difference in pressure, gain correcting the signal output by said differential pressure transducer, wherein said frequency correcting and said gain correcting of said signal provides a gain and frequency corrected signal which precisely and accurately represents the flow of gas into and out of said infant's lungs.

18. The method of claim 17 wherein said frequency correcting comprises calculating a time constant of said plethysmograph and multiplying said time constant by a first derivative of said signal with respect to time and adding the result to said signal to provide a frequency corrected signal.

19. The method of claim 18 wherein said time constant is the resistance of air flow openings in said plethysmograph multiplied by the compliance of air inside the plethysmograph.

20. The method of claim 17 wherein said gain correcting comprises integrating said signal output by said differential pressure transducer and comparing said integrated signal with a known volume displaced by activation of a pressure pulse source coupled to said plethysmograph.

21. An improved plethysmograph of the type having a substantially enclosed plethysmographic chamber for receiving an infant, an assisted ventilation gas source coupled to said chamber, and endotracheal tube insertable into an airway of said infant, and means attached to said plethysmographic chamber for measuring airflow into and out of said plethysmographic chamber, wherein the improvement comprises a radiant heater external to said plethysmographic chamber which radiates heat towards said plethysmographic chamber thereby raising the temperature of said infant's skin and which also convectively heats said infant by hearing air contained within said plethysmographic chamber, thereby accurately and precisely maintaining a desired temperature of said infant's skin.

22. An improved plethysmograph of the type having a substantially enclosed plethysmographic chamber for receiving an infant, an assisted ventilation gas source coupled to said chamber, an endotracheal tube insertable into an airway of said infant, and means attached to said plethysmographic chamber for measuring airflow into and out of said plethysmographic chamber, wherein the improvement comprises a linear displacement actuator coupled to said plethysmographic chamber for applying a pressure pulse of known volume into said plethysmograph.

23. An improved method of operating a plethysmograph of the type having a substantially enclosed plethysmographic chamber for receiving an infant, an assisted ventilation gas source coupled to said chamber, an endotracheal tube insertable into an airway of said infant, a pneumotachometer and a differential pressure transducer attached to said plethysmographic chamber, said transducer outputting a flow signal indicating a flow rate through said pneumotachometer, wherein the improvement comprises frequency correcting and gain correcting the flow signal output by said differential pressure transducer.

24. The improved method of claim 23 wherein said frequency correcting comprises calculating a time constant of said plethysmograph and multiplying said time constant by a first derivative of said flow signal with respect to time and adding the result to said flow signal to provide a frequency corrected flow signal.

25. The improved method of claim 24 wherein said time constant is the resistance of air flow openings in said plethysmograph multiplied by the compliance of air inside the plethysmograph.

26. The improved method of claim 25 wherein said gain correcting comprises integrating said flow signal output by said differential pressure transducer and comparing said integrated flow signal with a known volume displaced by activation of a pressure pulse source.

27. The improved method of claim 26 wherein said pressure pulse source displaces a known volume into and out of said plethysmograph.

28. An apparatus for obtaining continuous measurements of infant ventilation during assisted ventilation by an assisted ventilation gas source comprising:
a plethysmograph having at least an input port, means for coupling an assisted ventilation gas source to said input port of said plethysmograph, a pressure pulse source coupled to said plethysmograph for applying a pressure pulse of known volume into said plethysmograph, an endotracheal tube having a first end which is coupled to said input port and a second end which is insertable into an airway of an infant placed in said plethysmograph such that said airway is isolated from the interior of said plethysmograph.
means for outputting a flow signal indicating a flow rate into and out of said plethysmograph, means for detecting pressure changes in said endotracheal tube caused by said assisted ventilation gas source and breathing efforts of said infant and for outputting an airway pressure signal in accordance with such pressure changes, means for converting said flow signal into a digital flow signal, a preprogrammed computer system having:
means for calculating digitized flow data from said digitized flow signal, means for frequency correcting said digitized flow data, means for determining from said frequency corrected digitized data at least whether pressure changes in the interior of said plethysmograph are due to assisted ventilation or to the infant's breathing efforts and for determining a resultant volumetric displacement from said frequency corrected digitized flow data.

29. The apparatus of claim 28 wherein said means for outputting said flow signal comprises means adapted for creating a pressure differential between the interior of said plethysmograph and the exterior of said plethysmograph, and transducer means for outputting said flow signal which indicates a magnitude of said pressure differential.

30. The apparatus of claim 28 wherein said means for outputting said flow signal comprises:
a pneumotachometer attached to said plethysmograph and having a resistance to air flow and being adapted for providing a pressure differential on opposite sides of said pneumotachometer, and a differential pressure transducer coupled to said pneumotachometer for outputting a differential pressure signal reflecting said pressure differential, said differential pressure signal being proportional to a flow signal indicating a flow rate through said pneumotachometer.

31. The apparatus of claim 28 further comprising means for gain correcting said digitized flow data.

32. The apparatus of claim 31 wherein said gain correcting means comprises means for integrating said digitized flow data and comparing said integrated flow data with a known volume displaced by activation of said pressure pulse source.

33. The apparatus of claim 28 further comprising a radiant heater located external to said plethysmograph and which radiates heat energy towards said plethysmograph and said infant and which produces convective heating within said plethysmograph.

34. The apparatus of claim 28 wherein said frequency correcting means comprises means for calculating a time constant of said plethysmograph and multiplying said time constant by a first derivative of said flow data to provide frequency corrected flow data.

35. The apparatus of claim 34 wherein said time constant is the resistance of air flow openings in said plethysmograph multiplied by the compliance of air inside the plethysmograph.

36. The apparatus of claim 28 further comprising means for calculating systolic blood pressure and diastolic blood pressure of the infant.

37. The apparatus of claim 36 wherein said calculating means calculates a systolic pressure value by determining a maximum amplitude of a blood pressure waveform between a positive threshold value of a first derivative of said blood pressure waveform and a negative threshold value of said first derivative of said blood pressure waveform, said maximum amplitude being the diastolic pressure.

38. The apparatus of claim 37 wherein said calculating means calculates diastolic pressure by determining a local minimum of the blood pressure waveform between said systolic pressure value and a previous systolic pressure value, said local minimum being the diastolic pressure.

39. The apparatus of claim 28 further comprising means for synchronizing said infant's breath with said assisted ventilation.

40. An improved method of operating a plethysmograph of the type having a substantially enclosed plethysmographic chamber for receiving an infant, an assisted ventilation gas source coupled to said chamber, an endotracheal tube insertable into an airway of said infant, and means for producing a flow signal which indicates air flow into and out of said chamber, wherein the improvement comprises the steps of frequency correcting and gain correcting said flow signal output by said flow signal producing means.

41. The improved method of claim 40 wherein said frequency correcting step comprises calculating a time constant of said plethysmograph and multiplying said time constant by a first derivative of said flow signal with respect to time and adding the result to said flow signal to provide a frequency corrected flow signal.

42. The improved method of claim 41 wherein said time constant is the resistance of air flow openings in said plethysmograph multiplied by the compliance of air inside the plethysmograph.

43. The improved method of claim 42 wherein said gain correcting step comprises integrating said flow signal and comparing said integrated flow signal with a known volume displaced by activation of a pressure pulse source.

44. The improved method of claim 43 wherein said pressure pulse source displaces a known volume into and out of said plethysmograph.