WO2007147505A2 - A system for controlling administration of anaesthesia - Google Patents
A system for controlling administration of anaesthesia Download PDFInfo
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- WO2007147505A2 WO2007147505A2 PCT/EP2007/005165 EP2007005165W WO2007147505A2 WO 2007147505 A2 WO2007147505 A2 WO 2007147505A2 EP 2007005165 W EP2007005165 W EP 2007005165W WO 2007147505 A2 WO2007147505 A2 WO 2007147505A2
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M19/00—Local anaesthesia; Hypothermia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
- A61B5/14542—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring blood gases
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
- A61B5/1468—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using chemical or electrochemical methods, e.g. by polarographic means
- A61B5/1477—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using chemical or electrochemical methods, e.g. by polarographic means non-invasive
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/41—Detecting, measuring or recording for evaluating the immune or lymphatic systems
- A61B5/414—Evaluating particular organs or parts of the immune or lymphatic systems
- A61B5/417—Evaluating particular organs or parts of the immune or lymphatic systems the bone marrow
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/48—Other medical applications
- A61B5/4821—Determining level or depth of anaesthesia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/05—Phenols
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
- A61M5/168—Means for controlling media flow to the body or for metering media to the body, e.g. drip meters, counters ; Monitoring media flow to the body
- A61M5/172—Means for controlling media flow to the body or for metering media to the body, e.g. drip meters, counters ; Monitoring media flow to the body electrical or electronic
- A61M5/1723—Means for controlling media flow to the body or for metering media to the body, e.g. drip meters, counters ; Monitoring media flow to the body electrical or electronic using feedback of body parameters, e.g. blood-sugar, pressure
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2202/00—Special media to be introduced, removed or treated
- A61M2202/04—Liquids
- A61M2202/0468—Liquids non-physiological
- A61M2202/048—Anaesthetics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2230/00—Measuring parameters of the user
- A61M2230/20—Blood composition characteristics
- A61M2230/202—Blood composition characteristics partial carbon oxide pressure, e.g. partial dioxide pressure (P-CO2)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2230/00—Measuring parameters of the user
- A61M2230/20—Blood composition characteristics
- A61M2230/208—Blood composition characteristics pH-value
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2230/00—Measuring parameters of the user
- A61M2230/40—Respiratory characteristics
- A61M2230/43—Composition of exhalation
- A61M2230/432—Composition of exhalation partial CO2 pressure (P-CO2)
Definitions
- the invention relates generally to a system and associated procedures to administer one or more respiratory depressant drugs to a spontaneously breathing patient. More particularly, the invention relates to an arrangement for providing patient sedation and alleviating pain, discomfort and/or anxiety during a medical or surgical treatment. Said arrangement determines and delivers the optimal administration profile based on the monitored and/or inferred respiratory drive, expressed as body contents of respiratory gases and/or breathing activity. The invention enables the delivery of efficacious patient sedation while minimizing drug-induced adverse effects under both open- and closed-loop operation .
- Anaesthesia refers to a condition of reduced sensibility in the body. It is a reversible pharmacologic state induced by the administration of anaesthetic drugs. Delivery of adequate anaesthesia during medical treatments ensures patient unconsciousness, analgesia and/or muscle relaxation.
- IASP International Association for the Study of Pain
- regular re-evaluation of drug dosing during medical and surgical treatments is required.
- Tailoring the administration profile to a patient is based on a continuing process of effect appraisal and dose titration.
- the objective is to optimize the desired effects (e.g. analgesia, anxiolysis and sedation) while minimizing the undesired effects (IASP Task Force, 2005) .
- the present invention relates to a care system and method to effectively address these issues.
- Sedation techniques are currently available to provide patient analgesia and anxiolysis during medical and surgical procedures.
- "Conscious sedation” and “monitored anaesthesia care” (MAC) are defined as medically controlled states of depressed consciousness that allow protective reflexes to be maintained.
- the sedated patient retains the ability to breathe autonomously and to protect the airways.
- the patient can respond to verbal commands and tactile stimulation with different degrees of purposefulness (Novak, 1998) .
- a physician supervises or personally administers sedative and/or analgesic drugs that allay patient anxiety and ensure analgesia throughout a diagnostic or therapeutic procedure.
- MAC allows for the safe administration of a maximal depth of sedation in excess of that provided during conscious sedation (ASA Relative Value Guide, 2006) .
- conscious sedation and MAC are widespread for, but not limited to, the following treatments: endoscopy (such as gastro- scopy, colonoscopy, endoscopic retrograde cholangiopancreatography (ERCP) ) ; bronchoscopy or fiber optic intubation; cystoscopy; extracorporeal Shockwave lithotripsy (ESWL) ; evacuation of chronic epidural haematoma (combined with local anaesthesia) ; debridement of wounds/burns, abscess drainage; virtual probe plastic surgery; interventional radiology; oocyte harvest for artificial fertilization; dental surgical interventions
- Opioids such as re- mifentanil, alfentanil, fentanyl, sufentanil and meperidine
- benzodiazepines as midazolam, diazepam and lorazepam
- propofol and ketamine are examples.
- sedatives and analgesics are delivered orally, rectally, intravenously or intramuscularly.
- Opioids are administered intravenously.
- Hypnotics are delivered either intravenously or by inhalation in case of volatile agents.
- respiratory acidosis (equivalent terms are hypercapnic acidosis and carbon dioxide acidosis) .
- Acute respiratory acidosis can be life-threatening when a sharp increase in PaC02 is associated with severe hypoxemia and acidemia.
- ASA American Society of Anesthesiologists
- U.S. Pat. No. 5,806,513 discloses a control system, which enables closed-circuit anaesthesia delivery systems to maintain user-defined oxygen and anaesthetic concentrations via flow minimization routines.
- U.S. Pat. No. 7,034,692 discloses a system to monitor the ventilatory conditions of a patient and prevent false, an- noying or oversensitive alarms during the performance of a medical procedure. Monitoring data are processed by a high- sensitivity alarm algorithm and a high-specificity alarm algorithm, which generate silent, semi-overt, or overt alarm conditions and/or activate a hyper-vigilant state in the system. Said system provides automated responses to the high-sensitivity, high-specificity alarm algorithms and reduces false positive/false negative alarms in a user-transparent way.
- P. C. T. Pat. No. WO 2005/082369 discloses an opioid formulation for pulmonary administration in the treatment of pain.
- the formulation is dispensed by a pulmonary drug delivery device, which can require a deliberate patient effort to be actuated.
- Said formulation comprises at least one rapid-onset opioid and at least one sustained-effect opioid (for example, an opioid encapsulated in a biocompatible carrier that delays release of the drug at the lung surface, such as a liposome- encapsulated opioid) .
- the formulation employs the side effects of the rapid-onset and liposomally encapsulated opioids to permit patients to self-limit drug intake.
- anaesthetic practice A wide variety of drugs is used in modern anaesthetic practice. Some of the most common general anaesthetics are barbiturates, benzodiazepines, ketamine and propofol. Opioids, on the other hand, represent the most relevant class of analgesics. In the clinical setting anaesthetics and analgesics are delivered intravenously, intramuscularly, rectally or by inhalation, in the case of volatile agents. The pharmacologic effects achieved by the administered drug(s) depend on dosage, administration profile and patient sensitivity, amongst other factors.
- TCI target controlled infusion
- PCS patient controlled sedation
- the former cannot be evaluated and corrected intraopera- tively.
- the latter can be compensated for by adjusting the targeted concentration to desired and/or undesired effects observed in the patient. That is to say, the appropriate targeted concentration can only be established after transient under- and/or overdosing.
- PCS devices can only be used in cooperative and adequately instructed patients. Their design leads to fluctuating levels of sedation and analgesia. PCS is regarded as a safe dosing strategy since an unresponsive patient is not able to operate the device. Drug administration ceases as a result. However, the time lag between dose delivery and maximal drug effect can lead to unintentional patient self- overdosing .
- U.S. Pat. No. 6,745,764 discloses a drug delivery system with an integrated patient interface.
- the patient can operate the interface device to send dosage change requests to the drug delivery apparatus.
- the system is capable of determining patient responsiveness by evaluating the voluntary response of the patient to a stimulus (e.g., an auditory or vibratory command) .
- Said system manages drug delivery in accord with patient interface requests and patient responsiveness data.
- European Pat. No. 1,547,631 discloses a computer-aided system, which increases the safety of intravenous drug delivery and enables the transfer of expert knowledge to less experienced caregivers.
- U.S. Pat. No. 6,807,965 discloses a system to conservatively manage drug delivery in accord with a safety data set, which is stored in a memory device. Said data set reflects both safe and undesirable physiological parameters and predefines normal ranges. The system monitors the physiological conditions of the patient, including the depth of patient unconsciousness. It compares the signals provided by patient monitors with the stored safety data set and responds by conservatively controlling (id est curtailing, limiting or ceasing) drug delivery.
- P. C. T. Pat. No. WO 2001/083007 provides a system and method to run the administration of a drug based on a response profile of the patient.
- the patient's individual response profile is identified by means of a least-square algorithm. Following this approach, the differences between a sensed attribute of the patient and the estimated curve are minimized as to obtain the best fitting pharmacodynamic Hill curve.
- said system employs the patient's electroencephalograph ⁇ (EEG) signal or the Bispectral Index (BISTM) to evaluate the depth-of-sedation response profile of the patient.
- EEG electroencephalograph ⁇
- BISTM Bispectral Index
- P. C. T. Pat. No. WO 2005/072792 discloses a care system, which manages the delivery of a medication in accord with a patient-specific response profile.
- the system determines the patient's response profile via the Bispectral Index and other processed EEG measures, such as the median frequency, the spectral edge and entropy metrics.
- Said system applies techniques from Bayesian statistics to adapt response profile parameters to changes occurring in the patient's response to the drug.
- the problem of sedation is compounded by the lack of an artifact resistant respiration monitor for use during MAC and conscious sedation.
- Possible ways of monitoring patient respiration in the clinical setting include: visual inspection of the thorax; detection of thoracic electrical impedance changes; strain gauge measurement of thoracic circumference; ECG-derived detection of respiratory rate (e.g. respiratory sinus arrhythmia (RSA) detection, autoregressive spectral analysis of heart period, variations of electrical main axis of the heart and others) ; nasal thermistors; plethysmography; spirometry or airway pressure monitoring; capnographic appraisal of end-tidal CO2 partial pressure (PetCO2) .
- respiratory rate e.g. respiratory sinus arrhythmia (RSA) detection, autoregressive spectral analysis of heart period, variations of electrical main axis of the heart and others
- nasal thermistors e.g. respiratory sinus arrhythmia (RSA) detection, autoregressive spectral analysis
- Capnography the gold standard in respiration monitoring, suffers instead from false low readings, especially when upper airway obstruction occurs.
- the capnographic apparatus employs a nasal cannula for exhaled breath sampling.
- the cannula 3 to 5 cm in length, does not impair spontaneous respiration; however it yields incorrect measurements if the patient breathes through the mouth.
- Another sampling setup makes use of a facial mask.
- the deadspace of the tubes and of the mask itself reduces the reliability of the PetCO2 measurements, therefore only the respiratory rate data are usually considered. Both setups are sensitive to shallow breathing and airway obstruction.
- the adequacy of patient respiration can be indirectly determined by measuring transcutaneous C02 tension (PtcCO2) and oxygen saturation (SpO2) (Akio et al . , 2004).
- PtcCO2 transcutaneous C02 tension
- SpO2 oxygen saturation
- innovative devices combining pulse oximetry with transcutaneous CO2 sensing have recently entered the market.
- monitors are commercially available: V-SignTM Sensor of SenTec AG (Therwil, Switzerland); TCM4, TCM40, TOSCA500 and MicroGas 7650 of Radiometer A/S (Copenhagen, Denmark) .
- These devices employ a sensor positioned at the ear lobe for continuous measurement of patient heart rate, SpO2 and PtcCO2. Steady state bias and response time are satisfactory, therefore the sensors provide a fast and reliable respiratory indicator, which is suitable for use during MAC and conscious sedation.
- P. C. T. Pat. No. WO 2002/041770 provides a sensor for measuring blood physiological parameters such as oxygen and carbon dioxide. Said sensor comprises of a measuring device and a digital sensor signal processor and provides a digital output signal.
- P. C. T. Pat. No. WO 2005/110221 discloses a process to measure transcutaneous C02 partial pressure at an ear lobe by means of a sensing device. The process employs a transcutaneous C02 partial pressure measuring device and a heating system, which heats the sensor's contact surface.
- the PtcCO2 signal can serve as a surrogate endpoint for drug dosing.
- the underlying concept is derived from administration protocols used in cancer treatment. Drug dosing in oncology is frequently limited by the emergence of side effects rather than the achievement of the optimal therapeutic effect .
- This dosing paradigm is termed the "maximum tolerated systemic exposure" (MTSE) .
- MTSE maximum tolerated systemic exposure
- the application of the MTSE paradigm to MAC and conscious sedation implies the provision of analgesia and anxiolysis (the desired effects) by control of drug delivery based on respiratory inhibition (the adverse effect) .
- To provide optimal analgesic or sedative treatment it is mostly not necessary to induce maximum tolerable respiratory depression (i.e. the systemic exposure), but rather the individualized optimal amount of respiratory depression will guide the treatment. Further on we will refer to this concept as IOSE (Individualized Optimal Systemic Exposure) .
- IOSE has a clear clinical value when the following conditions are met : a) a simple and robust measure of the desired effect is not available; b) the concentration-to-effect curves of the desired and unde- sired effects are related to each other.
- Ad a Ad a
- the desired effects of MAC and conscious sedation can be easily measured in the awake and in the drowsy.
- Spontaneous complaints, movements, the VAS scale, and the OASS scale provide clear information whether the desired effects have been achieved. Nevertheless, these measures can be detected following a stimulus only.
- Undesired patient responses often lead to "overcorrections" by the anaesthetist, which in turn cause the occurrence of side effects. It has also been suggested that EEG-based indicators could provide a continuous measurement of the desired effects.
- the Bispectral Index (BISTM) by Aspect Medical Systems is an EEG- derived parameter that evaluates the hypnotic component of anaesthesia independently of patient stimulation.
- the EEG shows wide fluctuations in moderately sedated patients and it is insensitive to opioids within the therapeutic range.
- Ad b For mu-agonistic opioids and GABAergic drugs (such as benzodiazepines and propofol) the intensity of respiratory inhibition parallels that of analgesia and sedation. The interaction between drugs and nervous receptors explains this behaviour. Mu receptors in the brainstem and the thalamus mediate both the analgesic and the respiratory depressant effect of highly potent opioids. Benzodiazepines and propofol exert their sedative/hypnotic effect at GABA receptors, which have also been shown to cause respiratory inhibition. Therefore the drugs induce a respiratory depressant effect, which always correlates to analgosedation, and vice versa.
- GABAergic drugs such as benzodiazepines and propofol
- IOSE intensive care unit
- conscious sedation is mainly delivered to provide tolerance of the endotracheal tube as well as postoperative/postinjury analgesia.
- All established methods to control ICU sedation are suboptimal. For example, measuring electrical CNS activity via BISTM monitoring is not reliable at light sedation levels, and sedation scores cannot be obtained continuously.
- ICU practice offers the possibility of using minute ventilation and/or respiratory gas measures (such as PCO2) as surrogate parameters for adequate sedation.
- PCO2 minute ventilation and/or respiratory gas measures
- oversedation results in decreasing minute ventilation and increasing PCO2; for undersedation the opposite applies. Therefore IOSE can be considered as a suitable dosing paradigm for intensive care analgosedation .
- anaesthetists can apply the IOSE concept by titrating drug delivery to the observed undesired effect since the measured endpoint is correlated to the therapeutic effect.
- the care provider can manage drug administration by targeting a PCO2 of 50, 55 or 60 mmHg.
- the difference between the target PCO2 and the non-sedated value of about 40 mmHg accounts for the desired extent of pharmacologic effect.
- the IOSE paradigm can be embodied into an automated dosing device, as the present invention discloses.
- the system herein disclosed provides an arrangement to control the administration of analgesics, sedative and/or hypnotics with respiratory depressant side effects.
- Drug delivery occurs to a spontaneously breathing patient who can be subject to drug- induced depression of consciousness.
- the drug delivery control apparatus takes into account monitored physiological conditions to determine the administration profile, which ensures adequate and safe sedation with minimal side effects. Respiratory impairment, blood deoxygenation and hypercapnic acidosis are the most significant adverse effects induced by the drug.
- the control apparatus manages drug delivery in accord with the feedback information provided by one or more patient monitoring devices.
- the feedback data reflect the respiratory state of the patient, including respiratory acidosis and the content of respiratory gases .
- Feedback loop control systems usually comprise: a sensor of the variable to be controlled; a reference input or setpoint that specifies the value the controlled variable should have; a comparator that compares the actual sensed value, or feedback signal, with the setpoint or reference input. The output of the comparator is usually called an error signal, whose polarity determines which way a correction needs to be made; a control mechanism or controller, which is activated by the error signal and manipulates the input of the system by means of an actuator to obtain the desired effect on the output of the system.
- a simple type of controller is a proportional controller. With this type of control, the controller output (that is, the control action) is proportional to the error signal. Proportional control is characterized by a very low degree of complexity but it has drawbacks, the most important being that for most systems it does not entirely remove the error, or deviance of the measured value from the desired value (setpoint) .
- Alternatives to proportional control include proportional-integral (PI) control and proportional-integral-derivative (PID) control. These controllers can adjust process outputs based on the history (integral action) and the rate of change (derivative action) of the error signal, which increases the accuracy and stability of control.
- MPC Model Predictive Control
- An MPC controller relies on an empirical model of the dynamical system to predict the future behaviour of the dependent variables based on known values of the independent variables. MPC improves on simpler types of control by predict- ing how a system reacts to the inputs, that is, the effects produced by the inputs are known ahead of time. Feedback information is used to correct for model inaccuracies, since mathematical models often cannot completely describe system behaviour.
- Another advanced type of control is fuzzy logic control. In fuzzy logic the truth of any statement is a matter of degree. Fuzzy logic relies on mapping an input space to an output space by means of a set of rules, for example a list of "if-then" statements.
- a fuzzy logic controller is a controller that interprets the values of the inputs and, based on some set of rules, assigns values to the outputs.
- the error signal provides information on the magnitude and the direction of the adjustments made by the control mechanism on the input to the system.
- a feedback loop control mechanism manipulates the input as to produce a decrease in the output if this exceeds the setpoint, and vice versa.
- the overall result is to stabilize the system and maintain the equilibrium around the desired setpoint even in the occurrence of disturbances.
- Drug delivery is curtailed if the pharmacologic effect is too strong; it is increased if the effect is too weak. This can be understood as titrating drug delivery to effect.
- the scope of a feedback controller goes well beyond that of an alarm or safety system which detects a dangerous condition for the patient and reduces or stops drug administration as a result.
- an open-loop controller is a type of controller, which computes its input into the sys- tern using only the current state and/or its model of the system.
- An open-loop controller (also called a non-feedback controller) does not use feedback to determine whether its input has achieved the setpoint . This means that the system does not observe the output of the process it is controlling. Consequently, a true open-loop system cannot compensate for disturbances in the system.
- Open-loop control principles have found a few applications in anaesthesia care, for example in TCI (Target Controlled Infusion) technology.
- TCI Target Controlled Infusion
- Such influence is exerted via the following physiological mechanisms: pain intensifies carbon dioxide metabolism, that is, following a painful stimulation the rate of C02 production in the body is increased. In fact, pain causes the release of catecholamines, which in turn intensify the cardiac and respiratory activity. Augmented physiological work determines an increase in both 02 consumption and C02 production; pain causes the physiological PCO2 setpoint in arterial blood to decline (Glynn et al., 1981).
- the effect of pain is a chemoreceptor-independent tonic drive that increases minute ventilation, that is, the respiratory response to pain is not mediated by the central chemorecep- tors in the medulla and the peripheral chemoreceptors of the carotid bodies, but rather centrally through the respiratory neurons within the brainstem (Sarton et al., 1997) painful stimulation does not affect the slope of the CO2 response curve (representing minute ventilation versus PCO2 at different PO2 values) .
- the physiological mechanisms described above produce an overall increase in minute ventilation following painful stimulation.
- the effect on respiration reaches steady state in about 3 minutes and can be quantified as an approx. 20% increase in minute ventilation, producing in turn a decrease in carbon dioxide level .
- PK/PD pharmacokinetics/pharmacodynamics
- caregivers must learn the behaviour of the physiological system in the non-steady state and deal with inter-individual variability.
- automated devices can be supplemented with safety overrides.
- a minimal value of arterial oxygen saturation can be predefined to limit drug administration within a safe range.
- Other possible safety parameters are: the predicted drug concentration in the effect compartment or in blood; the total dose supplied to the patient; the administration rate.
- Safety overrides can either produce immediate cessation of drug delivery or maintain the existing drug concentration/administration rate.
- a system for controlling administration of a respiratory depressant drug or mixture of drugs to a spontaneously breathing patient comprises a drug delivery unit, being adapted for indexed or continuous and automatic titration of a respiratory depressant drug or mixture of such drugs to said patient, and a control apparatus, receiving measurement signals relative to the respiratory state of said patient and issuing control signals to said drug delivery unit, wherein the control apparatus is adapted to keep said measurement signals relative to the respiratory state to a predetermined condition and thereby providing adequate sedation and/or analgesia to said patient .
- the invention provides an apparatus and related methods for delivering one or more anaesthetic and/or analgesic drugs to a spontaneously breathing patient.
- the invention is directed towards alleviating the pain, discomfort and/or anxiety associated with medical or surgical treatments through the delivery of adequate and safe sedation.
- the invention is further directed towards optimizing drug administration, preventing patient under- and/or overdosing and minimizing the risks associated with respiratory depressant anaesthetics.
- the system is apt for use during medical or surgical treatments where relief of patient pain, discomfort and/or anxiety through patient sedation is desirable or required.
- a care system in accordance with the invention comprises: one or more patient monitoring devices to monitor at least one physiologic condition reflecting the respiratory state in said patient; a drug delivery system to supply one or more drugs; a control apparatus to drive the delivery system.
- the patient monitoring device provides one or more signals for the detection, measurement or inference of at least one physiologic condition reflecting said respiratory state in said patient.
- the drug delivery system supplies one or more drugs or mixtures of drugs to said patient.
- the control apparatus drives said drug delivery system and, in one form of the invention, interconnects said patient monitoring device and said drug delivery system.
- the arrangement has the objective of controlling the administration of analgesics, sedative and/or hypnotics with respiratory depressant side effects to a spontaneously breathing patient who can be subject to some degree of drug-induced depression of consciousness.
- the drug delivery control apparatus takes into account monitored and/or inferred patient physiological conditions which reflect the respiratory state, including patient body contents of respiratory gases, to determine the optimal administration profile and ensure drug delivery within effective and safe ranges .
- the procedure for managing patient pain and/or anxiety herein described includes the aspect of controlling the delivery of an anaesthetic agent based on predicted drug concentrations in the body.
- drug administration can be based on the predicted drug concentration in the effect compartment or in blood.
- the prediction of anaesthetic concentrations is achieved via pharmacokinetic modeling and can take into account demographic covariates of the patient (such as age, sex, weight, height, and others) .
- the method takes into account the predicted pharmacologic side effects in order to determine the administration profile. Side effects are evaluated from the behaviour of a respiratory model built into the control system. For respiratory depressants such as opioids and propo- fol, respiratory impairment is the most visible undesired effect.
- the method controls drug delivery based on respiratory indicators such as the respiratory rate (e.g. in non-intubated patients), minute ventilation (e.g. in intubated patients), tidal volumes.
- An extension of the method makes use of predicted body content of respiratory gases as an indirect appraisal of respiratory inhibition. Parameters reflecting the oxygen and carbon dioxide contents in the body, such as 02 saturation and C02 partial pressure (or tension) , are employed to determine the administration profile.
- the control apparatus makes use of predicted transcutaneous PCO2 values .
- the administration profile is determined on the basis of a feedback signal provided by the patient monitoring device.
- the feedback signal reflects one or more physiological conditions, which allow the monitoring of the respiratory state and undergo modifications in presence of the anaesthetic.
- the monitoring device provides information on patient respiration and/or respiratory acidosis and/or on body content of respiratory gases following the administration of respiratory depressants.
- the drug delivery control apparatus receives data from a combined pulse oximetry/transcutaneous PCO2 sensor.
- the method uses the information inherent in the feedback signal to improve the safety of drug delivery.
- the control apparatus continuously redetermines the administration profile based on measured respiratory indicators with the combined objective of achieving the required therapeutic effect and preventing drug overdosing. If the impairment of the respiratory drive becomes pronounced, the system limits or ceases drug delivery to minimize patient endangerment .
- the feedback signal provided by the monitoring device is used to tune the behaviour of the underlying respiratory model to the responsiveness of the patient.
- the control system can switch from closed- loop to open-loop operation and continue providing effective pain and/or anxiety management through adequate drug delivery.
- An advantage of the method herein described is that it can tailor drug administration to the specific needs of the patient, depending on the stimulation level, the desired analgesic and anxiolytic effect, the individual sensitivity to the drug. Regardless of the clinical setting, drug and endpoint, the method ensures patient safety and comfort, minimizes the risk of drug under- and overdosing, and reduces clinical costs.
- Figure 1 Basic conceptual schematic drawing of a system according to one embodiment of the invention
- Figure 2 Diagram of effect and side effect vs. drug concentration for the opioid remifentanil
- Figure 4 Diagram of effect and side effect vs. drug concentration for propofol. Description of preferred embodiments
- Figure 1 shows the preferred basic structure of a device according to an embodiment of this invention, providing analgesics, sedatives and/or hypnotics with respiratory depressant side effects to a spontaneously breathing patient 1 undergoing a medical or surgical procedure.
- the block 1 although mentioned as and designating the patient, comprises at least one sensor 7, providing an output signal 24, being a sensory signal relative to the respiratory state of the patient.
- an output signal 24 being a sensory signal relative to the respiratory state of the patient.
- the patient 1 has no input signal as such.
- Figure 1 shows that the device comprises a drug delivery unit 3 having as output an indexed or continuous output of analgesics, sedatives and/or hypnotics, to be applied to the patient via a drug delivery means 22 (e.g. an infusion line) .
- a drug delivery means 22 e.g. an infusion line
- an electronic representation of the actual output of analgesics, sedatives and/or hypnotics from the drug delivery unit 3 is submitted via 23 as an entry signal to a processor unit 2 (inside control apparatus 6) , representing a database and computer software product within a processor unit for a Patient Model.
- a Patient Monitor Device 4 is measuring the respiratory state of the patient 1 through the input signals provided by one or more of the sensors 7.
- a Model Prediction Calculator 5 (inside control apparatus 6) is inferring respiratory state from the Patient Model 2 received via an electronic representation 25 and a control unit 8 (inside control apparatus 6) issuing electronic dosing communication 27 to the device delivery unit 3 for indexed or continuous titration.
- Said drug delivery is according to the respiratory state based on direct patient measurements 20 (closed-loop mode, one of the preferred embodiments) or on model predictions 26 (open- loop mode, one of the preferred embodiments, especially in case of loss of sensor signal and target controlled infusion mode) .
- the said titration by the control unit 8 comprising a control mechanism running on a processor unit with a decision-making principle such as PID (proportional-integral-derivative) implemented in software is guided by the error signal calculated by comparing setpoint and patient measurement 20 or model prediction 26.
- the decision-making principle of the control mechanism of this embodiment is not restricted to PID but can be based on other suitable principles.
- the Patient Model 2 is adapted and updated in a continuous or indexed form via 21 based on actual patient measurements 20.
- control unit 8 contains a Display 9 and one or more Input-Output Systems 12 for user interaction.
- a preferred embodiment furthermore comprises a Drug Database 10 containing pharmacokinetic and pharmacodynamic properties of drugs or mixtures of drugs to be administered to the patient, especially enabling presetting of the control unit 8 and the patient model 2 inside the control apparatus 6.
- the pharmacodynamic data includes not only properties for the therapeutic effect but also data about the side effects, particularly with regard to the impact on dynamics of breathing and cardiovascular regulation. In this preferred embodiment such data from the said Drug Database 10 is loaded into the control apparatus 6 for subsequent use .
- Control Apparatus 6 is supplemented with additional safety overrides consisting of a) a mini- mal tolerable arterial oxygen saturation as a "hard” safety override with immediate cessation of drug administration in case of violation, b) a user presetable maximum and minimum predicted drug concentration in the effect compartment as a "soft" safety override at which the concentration will be maintained when reached, resulting in an open loop mode of operation and notification of the user and c) limits on infusion rates (in case of i.v. drugs), total drug dose and lock-out times for drug administration.
- all safety information and constraints are stored in a safety database 11 which is attached to the control apparatus 6.
- the respiratory state of the patient is evaluated by appraisal of the respiratory acidosis.
- the respiratory acidosis is preferably measured by quantifying carbon dioxide content in blood, or in another preferred embodiment by quantifying the pH in blood. This can be done in various ways and the information is obtained as such to deliver an indication relative to the respiratory state of the patient.
- the carbon dioxide content in the blood of the patient is measured by a fast transcutaneous carbon dioxide partial pressure measurement.
- the carbon dioxide content in the blood of the patient is measured by end-tidal measurement of carbon dioxide. All such measurement systems are preferably complemented with an independent sensor for respiratory rate for the detection of a single fault condition in the sensory system.
- opioids specifically alfentanil, fentanyl, remifentanil and sufentanil.
- a mixture of respiratory depressant drugs with non respiratory depressant analgesic or sedative drugs is preferred in patient cases where atypical respiratory depressant drug and/or carbon dioxide sensitivity is observed.
- the non respiratory depressant drug is ketamine.
- Figure 2 shows a diagram of effect and side effect vs. drug concentration for the preferred use of the opioid remifentanil for analgesia.
- Remifentanil is used since the mid 1990' s, predominantly for intraoperative analgesia and conscious sedation.
- Available data describe its analgesic and respiratory depressant potency (target concentrations aimed for by the individual using patient controlled analgesia (Schraag et al . , 1998; Cortinez et al . , 2005) and entire concentration effect curves based on multiple observations within individuals for respiratory depression, with measured PaCO2 for respiratory depression capture (Bouillon et al . , 2003) .
- the diagram shown in Figure 2 has a) on the left ordinate percentage of specific maximum effect as described below, b) on the right ordinate partial CO2 pressure in [mm Hg] and c) on the abscissa concentration of remifentanil in [ng/ml].
- the legend to the data traces of the diagram in Figure 2 is as follows: 1) On left ordinate: analgesia measured as percentage of patients experiencing adequate pain relief (visual analogue scale ⁇ 3 with 0 denoting no pain, 10 worst imaginable pain) . A C50 (concentration required to achieve half of the effect) of 2.8 ng/ml was reported, slope extrapolated.
- Figure 3 shows a diagram of effect and side effect vs. drug concentration for the preferred use of the opioid alfentanil for analgesia.
- Alfentanil is used since the late 1980s for both intra- and postoperative analgesia. Available data describe its analgesic and respiratory depressant potency.
- Target concentrations aimed for by the individual using patient controlled analgesia van den Nieuwenhuyzen et al . , 1997; Schraag et al . , 1999
- entire concentration effect curves based on multiple observations within individuals for respiratory depression with PaCO2 to capture respiratory depression (Bouillon et al., 1999) are available.
- the diagram shown in Figure 3 has a) on the left or- dinate percentage of specific maximum effect as described below, b) on the right ordinate partial C02 pressure in [mm Hg] and c) on the abscissa concentration of alfentanil in [ng/ml] .
- the legend to the data traces of the diagram in Figure 3 is as follows: 1) On left ordinate: analgesia measured as percentage of patients experiencing adequate pain relief (visual analogue scale ⁇ 3 with 0 denoting no pain, 10 worst imaginable pain) . A C50 of 52 ng/ml was reported, slope extrapolated, based on cases in general surgery, gynaecological and orthopedic procedures.
- Figure 4 shows a diagram of effect and side effect vs. drug concentration for the preferred use of propofol for sedation.
- Pro- pofol is used since the late 1980' s, both for conscious sedation and provision of anaesthesia.
- Available data describe its sedative (e.g. suppression of the Bispectral Index, an EEG derived parameter (Bouillon et al . , 2004, “Pharmacodynamic interaction --)) and respiratory depressant potency (Bouillon et al . , 2004, “Mixed-effects modeling --) .
- sedative e.g. suppression of the Bispectral Index, an EEG derived parameter (Bouillon et al . , 2004, “Pharmacodynamic interaction --)
- respiratory depressant potency e.g. suppression of the Bispectral Index
- respiratory depressant potency e.g. suppression of the Bispectral Index
- respiratory depressant potency e.g. suppression of the Bispectral Index, an
- the diagram shown in Figure 4 has a) on the left ordinate percentage of specific maximum effect as described below, b) on the right ordinate partial CO2 pressure in [mm Hg] and c) on the abscissa concentration of propofol in [ ⁇ g/ml] .
- the legend to the data traces of the diagram in Figure 4 is as follows: 1) On left ordinate: hypnosis measured as decrease of the Bispectral index (BISTM) , an EEG derived surrogate endpoint for hypnosis/sedation. A value of 50 corresponds to surgical anaesthesia, 60-75 is adequate for conscious sedation.
- BISTM Bispectral index
- the setpoint for carbon dioxide level for therapeutic effect in a preferred embodiment ranges from 35 to 80 mmHg, preferably in a range of 45 to 65 mmHg and ideally in a range of 48 to 55 mmHg partial pressure of carbon dioxide. These ranges of values are especially useful for transcutaneous acquisition of the carbon dioxide level. However, it is also possible to measure CO2 directly as a gas near the lungs of the patient, even within an intubation of the patient. The values to be chosen can be adjusted by the care provider.
- the preferred drug is a mixture of propofol and remifentanil .
- the dosing ratio between remifentanil and propofol is preferably chosen such as to maintain a fixed concentration range in plasma or effect site in the range of 0.0015:1 and 0.0035:1.
- the preferred ratio between remifentanil and pro- pofol is in the range of 0.0002:1 and 0.0008:1.
- the control apparatus is adapted to keep said measurement signals relative to the respiratory state to a predetermined condition and thereby providing adequate sedation and/or analgesia to said patient.
- a preset setpoint as mentioned above, e.g. the carbon dioxide level .
- This condition can be a given point on a control curve, which is controlled with usual closed-loop control systems, where a feedback control monitors the system.
- closed-loop control systems known from control theory can also use intervals with lower and upper levels, e.g. of the carbon dioxide level.
- Such conditions are meant to be achieved with the control apparatus 6 in connection with the further elements as e.g. shown in Figure 1.
- the said continuous system mode is implemented as discrete time based system or indexed system using time constants that are in relation to but preferably lower than the underlying physiological system time constants.
- a preferred range of system time constant is 1 to 60 seconds. Consequently a system update rate (e.g system internal states update, drug delivery unit update, patient monitor read-out) is preferably chosen in the same range of 1 to 60 seconds, e.g. with 5 seconds intervals, 10 seconds intervals or 20 seconds intervals.
- the said model predictions are used for target controlled infusion (TCI, an infusion method to reach a preset concentration as fast as possi- ble without overshoot) .
- TCI target controlled infusion
- the Patient Monitor Device 4 and therefore measurements 20 are a) not used or they are not provided within one form of this embodiment or b) they are used as an input value in another form of this embodiment.
- the level of predicted respiratory depression expressed as fractional respiration of baseline respiration is used to limit the infusion rate that is calculated to reach a preset plasma or effect site concentration.
- the actual measurements (20) relative to the respiratory state of the patient are used to calculate the fractional respiration by means of the respiratory model.
- the maximal accepted reduction of fractional respiration represents an infusion rate limiting factor in the TCI method and is selectable by the care provider.
- the said fractional respiration is in a range of 0.4 to 0.95 and ideally in the range of 0.6 to 0.8 of baseline respiration.
- patient monitor device model prediction calculator control apparatus (dotted box) sensor unit control unit display drug database safety database Input-Output Systems patient measurements patient model update drug delivery to patient (e.g. infusion line) electronic representation of drug delivery sensory signals electronic model representation electronic representation of model predictions electronic dosing communication
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Abstract
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Priority Applications (3)
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EP07725978A EP2029197A2 (en) | 2006-06-21 | 2007-06-12 | A system for controlling administration of anaesthesia |
JP2009515741A JP2009540890A (en) | 2006-06-21 | 2007-06-12 | System for controlling anesthetic administration |
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PCT/EP2007/005165 WO2007147505A2 (en) | 2006-06-21 | 2007-06-12 | A system for controlling administration of anaesthesia |
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JP (1) | JP2009540890A (en) |
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Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2002041770A1 (en) * | 2000-11-23 | 2002-05-30 | Sentec Ag | Sensor and method for measuring physiological parameters |
WO2004000400A2 (en) * | 2002-06-24 | 2003-12-31 | University Of Florida | Method and apparatus for monitoring respiratory gases during anesthesia |
FR2858237A1 (en) * | 2003-08-01 | 2005-02-04 | Draegerwerk Ag | SYSTEM FOR MEASURING PROPOFOL CONCENTRATION IN A BREATHING GAS CURRENT |
US20050054942A1 (en) * | 2002-01-22 | 2005-03-10 | Melker Richard J. | System and method for therapeutic drug monitoring |
US20050092322A1 (en) * | 2003-11-05 | 2005-05-05 | Collins William L.Jr. | Cannula assembly and medical system employing a known carbon dioxide gas concentration |
WO2005082369A1 (en) * | 2003-02-28 | 2005-09-09 | Delex Therapeutics Inc. | Opioid delivery system |
WO2005110221A1 (en) * | 2004-05-18 | 2005-11-24 | Linde Medical Sensors Ag | Process for measuring partial transcutaneous co2 pressure at an ear lobe |
WO2006133825A1 (en) * | 2005-06-17 | 2006-12-21 | Bayer Technology Services Gmbh | Device for the time-controlled intravenous administering of the anesthetic propofol |
-
2007
- 2007-06-12 CN CNA2007800233349A patent/CN101472631A/en active Pending
- 2007-06-12 EP EP07725978A patent/EP2029197A2/en not_active Withdrawn
- 2007-06-12 WO PCT/EP2007/005165 patent/WO2007147505A2/en active Application Filing
- 2007-06-12 JP JP2009515741A patent/JP2009540890A/en not_active Withdrawn
Patent Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2002041770A1 (en) * | 2000-11-23 | 2002-05-30 | Sentec Ag | Sensor and method for measuring physiological parameters |
US20050054942A1 (en) * | 2002-01-22 | 2005-03-10 | Melker Richard J. | System and method for therapeutic drug monitoring |
WO2004000400A2 (en) * | 2002-06-24 | 2003-12-31 | University Of Florida | Method and apparatus for monitoring respiratory gases during anesthesia |
WO2005082369A1 (en) * | 2003-02-28 | 2005-09-09 | Delex Therapeutics Inc. | Opioid delivery system |
FR2858237A1 (en) * | 2003-08-01 | 2005-02-04 | Draegerwerk Ag | SYSTEM FOR MEASURING PROPOFOL CONCENTRATION IN A BREATHING GAS CURRENT |
US20050092322A1 (en) * | 2003-11-05 | 2005-05-05 | Collins William L.Jr. | Cannula assembly and medical system employing a known carbon dioxide gas concentration |
WO2005110221A1 (en) * | 2004-05-18 | 2005-11-24 | Linde Medical Sensors Ag | Process for measuring partial transcutaneous co2 pressure at an ear lobe |
WO2006133825A1 (en) * | 2005-06-17 | 2006-12-21 | Bayer Technology Services Gmbh | Device for the time-controlled intravenous administering of the anesthetic propofol |
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Also Published As
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WO2007147505A3 (en) | 2008-04-17 |
CN101472631A (en) | 2009-07-01 |
JP2009540890A (en) | 2009-11-26 |
EP2029197A2 (en) | 2009-03-04 |
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