Technical field

[0001] The present disclosure relates to system for controlling medicament delivery and, in particular, systems that dictate a minimum period of time between administration of successive doses of a medicament. The present disclosure also relates to a computer process performed using such a system.

Background

[0002] More than 230 million major surgeries performed every year. Post-surgical pain is therefore common, leading to poor patient outcomes. Patients are thus often treated with postoperative pain medication. In particular, patients with moderate to severe postoperative pain are often treated with intravenous opioids. Opioids are chosen for their quick onset and can be titrated easy without a ceiling effect, so that pain relief can be achieved.

[0003] To remove the necessity for a medical professional to be present for administering each dose of pain medication, patient-controlled analgesia (PCA) using a medicament pump (e.g. an opioid pump) is often used. This provides a patient flexibility in titrating their analgesic needs. The patient presses on a button to self-administer pre-set doses of opioid pain relief, through an intravenous line operated by a computerized pump. A lockout time between each dose and a predetermined maximum hourly cumulative dose are usually set for safety purposes.

[0004] Despite the advantages of patient-controlled analgesia titration, PCA can be associated with side effects including nausea, vomiting, sedation and pruritus, respiratory depression and oxygen desaturation. There are numerous factors that potentially contribute to the onset of side effects, including prescribing errors and PCA pump programming errors. Even when a PCA pump is correctly programmed, therapeutic doses of opioids can suppress respiration. Comorbidities (such as advanced age, respiratory disease, obstructive sleep apnoea) will significant affect the safety and patient's response to delivery of opioids.

[0005] Failure to detect a patient's deteriorating oxygenation or respiratory status can lead to significant complications requiring critical care healthcare resources, with consequent increased length of stay, risk of hospital-acquired infections and increased costs. [0006] In addition, inadequate postoperative pain management can lead to physiological and psychological effects such as increased postoperative morbidity, delayed recovery to normal daily living, reduced patient satisfaction, and persistent postoperative pain.

[0007] It is desirable therefore to provide a system that addresses or ameliorates one or more of the abovementioned problems with medicament (i.e. pain medication) administration, or at least provides a useful alternative.

Summary

[0008] In accordance with the present disclosure there is provided a computer system for adaptive control of medicament availability, comprising:

at least one processor;

a counter;

a medicament controller;

at least one parameter sensor;

a threshold comparator; and

at least one memory, the memory storing instructions that, when executed by the processor(s), cause the system to:

make a first dose of a medicament available for administration to a subject using the medicament controller;

once the first dose is administered to the subject:

take measurements of one or more parameters of the subject using the parameter sensor(s), the one or more parameters being subject to change in response to administration of the medicament;

determine, using the threshold comparator, if at least one of the measurements breaches a relevant predetermined threshold;

if the measurements for a combination of the one or more parameters do not breach the relevant predetermined threshold, make a second dose of the medicament available for administration to the subject, using the medicament controller, only after expiry of a first predetermined time period from administration of the first dose, the first predetermined time period being set by the counter; and

if one or more of the measurements breaches the relevant predetermined threshold: taking successive further measurements of the one or more parameters using the parameter sensor(s); and once the further measurements no longer breach the relevant predetermined threshold, making the second dose of the medicament available for administration to the subject, using the medicament controller, only after expiry of a second predetermined time period from administration of the first dose, the second predetermined time period being set by the counter.

[0009] The step of taking successive further measurements of the one or more parameters using the parameter sensor(s) involves taking successive further measurements over a predetermined time period, a length of the predetermined time period being adjusted depending on whether the subject is receiving oxygen supplementation.

[0010] The second predetermined time period may be longer than the first predetermined time period. The second predetermined time period may be the same length as the first predetermined time period. The counter may reduce the first predetermined time period if none of the measurements have breached the relevant predetermined threshold during administration of a predetermined number of doses of the medicament.

[0011] The parameter sensor(s) may either continually measure the one or more parameters of the subject or measure the one or more parameters of the subject at regular intervals, and wherein the threshold comparator determines if at least one of the measurements breaches a relevant predetermined threshold by determining if any measurement taken since administration of the first dose has breached the relevant predetermined threshold.

[0012] The instructions, when executed by the processor(s), may further cause the counter to: measure one or more periods between administration of successive doses made available after expiry of the first predetermined time period; and

determine a length of time for the second predetermined time period based on an average of the one or more periods.

[0013] The instructions, when executed by the processor(s), may further cause the counter to: measure one or more periods between administration of successive doses made available after expiry of the first predetermined time period; and

determine a length of time for the second predetermined time period based on a longest period of the one or more periods. [0014] If one or more of the measurements breaches the relevant predetermined threshold, the medicament controller may lower a dosage level so that the second dose is smaller than the first dose. The medicament controller may increase a dosage level of the second dose, so that the second dose is larger than the first dose, if none of the measurements have breached the relevant predetermined threshold during administration of a predetermined number of doses of the medicament.

[0015] Also disclosed herein is a computer controlled process for adaptive control of medicament availability, comprising:

making a first dose of a medicament available for administration to a subject;

once the first dose is administered to the subject:

taking measurements of one or more parameters of the subject, the one or more parameters being subject to change in response to administration of the medicament;

determining if at least one of the measurements breaches a relevant predetermined threshold;

if the measurements for each parameter of a combination of the one or more parameters do not breach the relevant predetermined threshold, making a second dose of the medicament available for administration to the subject only after expiry of a first predetermined time period from administration of the first dose; and

if one or more of the measurements breaches the relevant predetermined threshold: taking successive further measurements of the one or more parameters; and once the further measurements no longer breach the relevant predetermined threshold, making the second dose of the medicament available for administration to the subject only after expiry of a second predetermined time period from administration of the first dose.

[0016] The step of taking successive further measurements of the one or more parameters may involve taking successive further measurements over a predetermined time period, a length of the predetermined time period being adjusted depending on whether the subject is receiving oxygen supplementation.

[0017] The combination of the one or more parameters may be a single parameter - e.g. oxygen saturation/desaturation, respiratory rate, heart rate - or may be a combination - e.g. oxygen saturation/desaturation and heart rate. So the system will make a second dose of medicament available if each parameter of the combination of parameters remains in a safe range. In this sense " breach" a predetermined threshold refers to crossing from a safe range to an unsafe range - e.g. heart rate dropping below a desired threshold or oxygen saturation dropping below a desired threshold.

[0018] The second predetermined time period may be longer than the first predetermined time period. The second predetermined time period may instead be the same length as the first predetermined time period.

[0019] The computer controlled process may further comprise reducing the first predetermined time period if none of the measurements have breached the relevant predetermined threshold during administration of a predetermined number of doses of the medicament.

[0020] The computer controlled process may involve taking measurements of one or more parameters of the subject by continually measuring the one or more parameters of the subject. The computer controlled process may instead involve taking measurements of one or more parameters of the subject by measuring the one or more parameters of the subject at regular intervals. Determining if at least one of the measurements breaches a relevant predetermined threshold may comprise determining if any measurement taken since administration of the first dose has breached the relevant predetermined threshold.

[0021] The computer controlled process may further comprise determining a length of time for the second predetermined time period based on the first time period.

[0022] The computer controlled process may further comprise:

measuring one or more periods between administration of successive doses made available after expiry of the first predetermined time period; and

determining a length of time for the second predetermined time period based on an average of the one or more periods.

[0023] The computer controlled process may further comprise:

measuring one or more periods between administration of successive doses made available after expiry of the first predetermined time period; and

determining a length of time for the second predetermined time period based on a longest period of the one or more periods. [0024] The computer controlled process may further comprise lowering a dosage level so that the second dose is smaller than the first dose, if one or more of the measurements breaches the relevant predetermined threshold.

[0025] The computer controlled process may further comprise increasing a dosage level of the second dose, so that the second dose is larger than the first dose, if none of the measurements have breached the relevant predetermined threshold during administration of a predetermined number of doses of the medicament.

[0026] Embodiments of the present invention seek to avoid complications arising from pain management, which exist with PCA methodologies even if intermittent manual vital signs (i.e. parameters or the patient or subject) monitoring is performed. In addition, some embodiments provide intelligent responses that reduce or prevent alarm fatigue - in other words, responses by medical professionals are often only required when the patient's vital signs are not recovering.

Brief description of the drawings

[0027] Some embodiments of the present invention will now be described, by way of non-limiting example only, with reference to the accompanying drawings in which:

Figures 1, 4 and 5 illustrate computer controlled processes for adaptive control of medicament availability;

Figure 2 is an example of a graph of vitals signs or parameters, over time, with predetermined, fixed thresholds;

Figure 3 is a schematic illustration of a computer system for implementing the methods of Figures 1 and 4 to 7;

Figure 6 illustrates a method for adapting dose size for use in a dosage regime implementing according to any one of Figures 1, 4 and 7;

Figure 7 is an overview of a process for using a lockout timer in the computer controlled processes of Figures 1, 4 and 5;

Figure 8 illustrates a process for lockout period adjustment;

Figure 9 illustrates a relationship between measurements taken during administration of a dosage regime, human (e.g. medical professional) inputs and vital signs or parameter thresholds; and

Figure 10 illustrates a medicament (e.g. morphine) dosage regimen and adjustment process. Detailed description

[0028] The following detailed description of embodiments of the invention illustrate systems for adaptive control of medicament availability, and related computer processes. The systems and processes each enable a patient to administer doses of a pain medicament with prescribed or predetermined lockout periods between doses. In addition, one or more parameters of a subject, which may be interchangeably by referred to as vital signs of a patient and similar, are monitored. Based on measurements of those vital signs or parameters, the systems and processes may do one or more of: allow the current dosing regime to continue unchanged - e.g. not vary the predetermined period of time between doses - the lockout period - and/or not change the dosage;

increase the predetermined period of time between doses if one or more of the patient's vital signs suggest the dosage is too high;

decrease the predetermined period of time between doses if the patient is successfully dosing without complication for a predetermined number of doses or predetermined period of dosing; increase the dosage if the patient is successfully dosing without complication for a predetermined number of doses or predetermined period of dosing; and

decrease the dosage if one or more of the patient's vital signs suggest the dosage is too high.

[0029] A computer process or method 100 for adaptive control of medicament availability is illustrated in Figure 1. The process 100 can enable the time period between doses and the size or volume of each dose to be adjusted without intervention of a medical professional. In addition, the process 100 can prevent dosing while a patient or subject appears to have unstable vital signs.

[0030] The process 100 broadly comprises:

Step 102: making a "first" dose available;

Step 104: measuring parameter(s) of the subject or patient;

Step 106: determine if measurements breach relevant predetermined threshold(s);

Step 108: making a "second" dose available;

Step 110: measuring parameter(s) of the subject or patient;

Step 112: determining when measurements no longer breach relevant predetermined threshold(s);

Step 114: setting predetermined time period;

Step 116: making a "second" dose available; and

Step 118: generating alarm. [0031] Step 102 involves making a first dose of a medicament available for administration to a subject or patient. In this context, a medicament is a pain, or pain relief, medication such as an opioid and administering that medicament refers to administering one or more doses of the medicament.

[0032] The dosage, or size or volume of the dose, will be set by a medical professional as will a first predetermined time period (i.e. a lockout period), being the minimum period of time between successive doses. A system implementing process 100 thus prevents a dose from becoming available to the patient for at least the first predetermined time period after administration of the most recently administered dose.

[0033] The medical professional will set the dosage regime (i.e. size of the dose) in advance of the process 100 taking place. The medical professional may also set the first predetermined time period as part of the dosage regime. For example, the medical professional may program a medicament administration system with the dosage regime in advance of the present process 100 being performed. These steps will be understood by the skilled person in view of the present teachings and common general knowledge.

[0034] The process 100 is taken to commence at any time during the dosage regime. Thus the term "first" dose is not used to assert the dose must be the initial dose of medicament administered in accordance with the dosage regime. Instead, the term "first" provides an illustrative frame of reference with regard to the "second" dose, in a successive series of doses, made available in accordance with step 108 or 116.

[0035] Once the first dose is made available in accordance with step 102 it can be administered by the patient - e.g. the patient may press a button for activating dosing using a PCA system. Once administered, measurements of one or more parameters of the subject are taken - step 104.

[0036] The one or more parameters, each of which may be a vital sign of the patient, are selected due to their being subject to change in response to administration of the medicament. Such vital signs or parameters include oxygen saturation, pulse rate, respiratory rate, C0 ₂ - e.g. end tidal C0 ₂ - and peripheral capillary oxygen saturation - SP0 ₂ . This ensures the parameters respond to adverse conditions that may arise in the subject resulting from administration of the medicament. [0037] These parameters may be measured directly (e.g. pulse rate) or inferred from measurements taken in accordance with step 104 (e.g . if measurements indicate a downward trend in SP0 ₂ then this may not meet a threshold for that parameter). The measurements may be taken once, shortly before expiry of the first predetermined time period (i.e. first lockout period) discussed with reference to step 108, or any other lockout period, to determine whether or not to make a second or further dose of the medicament available for administration by the subject. However, it is preferred that measurements are taken continuously or at regular intervals (e.g. every 10 seconds, 20 seconds or 30 seconds). This ensures the process 100 can capture an acute or rapid deterioration of the subject's vital signs.

[0038] This also allows a system (e.g. system 300 of Figure 3) to check if vital signs data has, or has lost, continuity - e.g. if there is a sudden drop, and thus lost continuity. This can be achieved by sampling at a sufficiently high rate or frequency, where the meaning of "sufficiently high" depends on the rapidity of response of the patient's body in respect of the particular vital sign being monitored, or on the rapidity of the need for a clinician to respond once that vital sign deteriorates or drops.

[0039] The measuring step 104 may further involve averaging, filtering and/or removing noise or signal interference from the measurements in accordance with known processes. This helps ensure no external or artificial artefacts remain in the measurements that might otherwise result in one or more of the parameters appearing, incorrectly, to breach the relevant threshold for the respective parameter as discussed with reference to step 106.

[0040] The measuring step 104 may also weight the parameters and or combine them in any desirable manner to make a more confident assessment of whether or not to make a further dose of medicament available.

[0041] Once the parameter(s), directly measured or inferred, have been measured in accordance with step 104, the parameter(s) are compared to relevant predetermined thresholds - step 106. In this context, the word "relevant" refers to the fact that different parameters have different thresholds. For example, a parameter that is indicative of pulse rate will be expected to have a considerably higher threshold than a parameter that is indicative of respiratory rate.

[0042] "Predetermined" in the term "predetermined threshold" refers to a threshold value that is pre set or predetermined by a medical professional. The value is a threshold insofar as that value being breached (hereinafter interchangeably termed "exceeded" and similar) by a measurement, the measurement being indicative of a vital sign of the subject, indicates that the vital sign has fallen or moved outside an acceptable range. For example, a threshold for pulse rate may be 160 such that if the subject's pulse rate moves higher than 160 it exceeds a relevant predetermined threshold. Similarly, a threshold for pulse rate may be 45 such that if the subject's pulse rate drops below 45 it exceeds the relevant predetermined threshold. Thus, the there may be more than one threshold for any parameter - the pulse rate example provides a high threshold and a low threshold - and "exceeding" that threshold may mean dropping by too great an amount such that the threshold is exceeded in a negative sense - e.g. a measurement corresponding to a heart rate that has dropped below a low threshold is a measurement that exceeds that low threshold.

[0043] More than one parameter may be measured, and a measurement of any one parameter exceeding its predetermined threshold(s) may indicate a need to change the dosage regime. Thus step 104 involves determining if at least one of the measurements exceeds a relevant predetermined threshold.

[0044] In the event that none of the measurements exceed the relevant predetermined threshold(s), the process 100 waits until expiry of a first predetermined time period from administration of the first dose, and then makes a second dose of the medicament available for administration to the subject - step 108. Thus, the process 100 only makes a second (or subsequent) dose available exclusively after - i.e. not before, but immediately after - expiry of the first predetermined time period. That second dose can then be selectively administered by the subject - in other words, the subject may choose when to have the second dose administered.

[0045] If one or more of the measurements exceeds the relevant predetermined threshold, then the process 100 assumes the patient is responding poorly to the medicament. The process 100 responds by immediately (and automatically) pausing treatment - this may be a default 5 minute pause, or may be any other desired period of time between, for example, 1 to 10 minutes. Then successive further measurements of the one or more parameters are taken -step 110. In general, for measurements taken continuously, steps 104 and 110 will form part of the same measuring or monitoring process. The same may also be the case for measurements taken at regular intervals. However, in some embodiments, if one or more of the measurements exceeds the relevant predetermined threshold then the process 100 may respond by reducing the intervals between measurements, thereby providing higher resolution measurements. [0046] The process 100 does not make any further doses available for administration by the patient until it is determined, from further measurements of the one or more parameters taken in accordance with step 110, that the further measurements no longer exceed the relevant predetermined threshold - step 112. The vital signs of the subject, the vital signs being associated with the parameter(s) measured in accordance with steps 104 and 110, may thus respond in three ways: the vital signs may remain the same, may deteriorate further or may improve.

[0047] To illustrate, Figure 2 provides an example graph 200 of changes in measurements of parameters corresponding to vital signs of a subject, during administration of administration of boli (i.e. doses) of medicament. The graph 200 provides two fixed, predetermined thresholds. These are line A, being a 95% SP0 ₂ threshold, and line B, being a respiratory rate of 6 breaths per minute. The graph 200 maps the change in SP0 ₂ and respiratory rate over time. Line C represents the SP0 ₂ and lines D and E represent the respiratory rate. Line D provides the respiratory rate using non-overlapping, 1 minute windows, with a new window beginning on each minute marked on the time axis X. Line E provides the respiratory rate using overlapping, 1 minute windows with a new window beginning every 15 seconds.

[0048] Despite a bolus of medicament being self-administered by the patient at time 0, until time 1 (line 206) all measurements defining lines C to E have remained at or above the relevant thresholds. Thus the process 100 proceeds as per normal, using the first predetermined time period as the lockout period for administering boluses.

[0049] In one embodiment, step 104 and step 110 determine if any measurement has dropped below the relevant predetermined threshold for each parameter, at any time. The measurements would therefore exceed the predetermined threshold at point 206 for SPO ₂ and point 204 for respiratory rate. Step 106 thus involves determining if any measurement taken since administration of the first dose (i.e. the most recently administered dose) has exceeded the relevant predetermined threshold.

[0050] Notably, using higher resolution (i.e. smaller or overlapping) windows to measure the respiratory rate means that the exceeded threshold can be detected earlier, namely at point 208 on line E as compared with point 204 on line D. Thus the process 100 can respond earlier to deterioration in vital signs. Similarly, when vital signs improve, the process 100 can respond sooner. In addition, using overlapping windows for measurements of the various parameters allows the measurements to be aligned in time - for example, measurements taken over 15 second, non-overlapping windows for SP0 ₂ can be aligned with measurements taken over 60 second, overlapping windows for respiratory rate. [0051] In some embodiments, a predetermined threshold may be determined based on a combination of a fixed threshold and a period of time. For example, a measurement may fail step 106 if it results in there being an accumulation of 300 SP0 ₂ desaturation seconds in the last 60 second interval, or since the previous dose of medicament. In one case, it may be that the SP0 ₂ level has remained at 90% (i.e. 5% below the 95% fixed threshold of Figure 2) for 60 seconds - 5 x 60 = 300. In another case, the SP0 ₂ may have remained at 85% for 30 seconds - (95-85) x 30 = 300. A similar threshold may be predetermined for each of respiratory rate, end tidal C0 ₂ and pulse rate.

[0052] In some instances, noise on sensors used for vital signs or parameter measurement may cause results to exceed a relevant predetermined threshold, where an actual measurement of the relevant vital sign or parameter would show they do not exceed that threshold, and conversely not to exceed the threshold, a result may not exceed a relevant predetermined threshold, where an actual measurement of the relevant vital sign or parameter would show they do in fact exceed that threshold. To reduce the effect of noise, steps 104 and 110 may involve averaging over an interval. For example, SP0 ₂ measurements may be averaged over a 1 minute window such that, at point 206, the measurements would not fail step 106 (i.e. would not be found to exceed the threshold). This avoids some of the alarm fatigue - i.e. where an alarm continues to be generated due to the vital signs of a subject falling for very brief periods below the relevant predetermined threshold.

[0053] Considering the example where the vital signs are improving. In this case, it is determined that the further measurements taken in accordance with step 110 no longer exceed the predetermined threshold - step 112. With reference to Figure 2, line F shows a downward trend of measurements corresponding to deteriorating vital signs - this trend, or its gradient, may alone be used to determine that the measurements exceed the relevant predetermined threshold(s). In contrast, line G illustrates an improvement in condition of the subject, since the measurements suggests an improvement in parameters and thus vital signs of the patient. The process 100 can thus be configured to respond in a variety of ways. In some embodiments the parameters are weighted so that they have unequal influence over how the process 100 responds to movements of parameters above and below their respective relevant predetermined thresholds. On the one hand, if parameters are not weighted or given equal weight, at point 210 the measurements will fail step 112. On the other hand, if the trend parameter illustrated by lines F and G is weight more heavily than the actual SP0 ₂ parameter, then the measurements at point 210 may pass step 112 on the basis that SP0 ₂ is now higher than the relevant predetermined threshold of 95% (line A) and is trending upwardly despite the average SP0 ₂ for the last 1 minute not exceeding 95%.

[0054] Similarly, at point 212 SP0 ₂ line C has reached the threshold and is falling (see trend line F). The measurements may thus fail step 112.

[0055] The lockout period is then set to be a second predetermined time period - step 114 -so that no further dose can be administered before expiry of the second predetermined time period from administration of the first dose. After expiry of that second predetermined time period, another dose of the medicament is made available for administration to the subject -step 116. A second predetermined threshold is used to enable the process 100 to dynamically adapt to the patient or subject.

[0056] In some embodiments, the second predetermined time period will be the same as the first predetermined time period such that the dosage regime remains unchanged once the subject's vital signs, and thus the measurements thereof taken in accordance with step 110, have recovered. In such cases - i.e. if one or more of the measurements exceeds the relevant predetermined threshold - the process 100 may optionally provide another step, step 120, involving lowering the dosage level. Thus the second dose (and subsequent doses), that is made available after step 112, is smaller than the first dose. This reduces a likelihood of recurrence of measurements that fail step 106, in the circumstance where the lockout period remains fixed - i.e. the first and second predetermined time periods are the same.

[0057] In other embodiments, the second predetermined time period is longer than the first predetermined time period. This is because a dosage regime using the first predetermined time period as the lockout period, has shown to involve potentially too high or too regular a dose for the subject. Thus using a second predetermined time period that is longer than the first predetermined time period can reduce the volume of medicament administered to the subject over time. In one example, process 100 commences using a first predetermined time period of 5 minutes as the lockout period. When at least one measurement of the one or more parameters exceeds the relevant predetermined threshold, the lockout period is set to be a second predetermined time period of 6 minutes. Subsequent iterations of the process 100 may thus increase the lockout period by successive 1 minute increments, or some other increment (e.g. 2 minutes) as desired. Thus, the length of the second predetermined time period is determined based on the first predetermined time period. [0058] Importantly, though a dose is made available upon expiry of the lockout period, that dose is only administered upon the patient or subject requesting it -e.g. by pressing a button. Therefore, the lockout period may not be indicative of the length of time between doses. Thus the subject may administer a dose every 8 minutes even though a lockout period of 5 minutes is provided. Thus increasing the lockout period to 6 minutes will not result in improvement of the vital signs of the subject if they continue to administer medicament every 8 minutes. Therefore, in some embodiments, a counter (see, e.g., counter 318 in Figure 3) may measure one or more periods between administration of successive doses of the medicament (actual dosage intervals) that are made using the first predetermined time period as the lockout period. The length of the second predetermined time period may then be determined based on an average of the actual dosage intervals. For example, for an actual dosage interval of 8 minutes, the second predetermined time period may be set to be 9 minutes. Thus the lockout period may incrementally increase depending on the average of the actual dosage intervals.

[0059] Similarly, after measuring the actual dosage intervals, the lockout period may be set to be incrementally higher than the longest measured dosage interval. Thus, the length of the second predetermined time period is based on the longest of the measured dosage intervals.

[0060] Considering now the cases where the subject's vital signs remain the same (i.e. a measurement of at least one parameter exceeds the relevant predetermined threshold(s)) or deteriorate further. The subject is therefore either remaining unstable or is becoming increasingly less stable, despite no further medicament being administered. In these cases, the process may generate an alarm - step 118 - to alert medical staff that the subject is in a critical condition. The nature of alarms associated with patient monitoring equipment, such as audible and visible alarms, is well understood in the art.

[0061] In addition, rather than monitoring for improvement or further deterioration, if one or more of the measurements exceeds the threshold by a large amount, the process may immediately generate an alarm - step 118 - to alert medical staff that the subject is in a critical condition. An alarm may thus be sounded for rapid or acute deterioration of the subject's vital signs even where the direct or actual measurement of the relevant vital sign is not yet problematic. For example, an alarm may sound where a measurement indicates a rapid downward trend in SP0 ₂ even though the actual oxygen concentration may be in the low end of the acceptable range or just below that range.

[0062] The above circumstances describe responses of the process 100 to circumstances in which the measurements of one or more parameters show that vital signs of the subject are deteriorating. The above circumstances also illustrate the case where the dosage regime does not change if the measurements do not fail step 106.

[0063] In some cases a subject has been prescribed an insufficient dose of the medicament. This may be that the individual doses are too small, or that those doses are made available too infrequently, the process may thus count or determine - step 120 - when:

a specified period of time (e.g. 1 hour) has elapsed since the patient either started the dosage regime or since the patient registered a measurement that exceeded the relevant predetermined threshold; and/or

a specified number of doses have been administered since the patient either started the dosage regime or since the patient registered a measurement that exceeded the relevant predetermined threshold.

[0064] Either of the conditions under step 120 being met may indicate that the subject is being under medicated. In response, the process 100 may increase the dosage regime - step 122. This can involve: reducing the first predetermined time period if none of the measurements have exceeded the relevant predetermined threshold during administration of a predetermined number of doses of the medicament; and/or

increasing a dosage level of the second dose, so that the second dose is larger than the first dose, if none of the measurements have exceeded the relevant predetermined threshold during administration of a predetermined number of doses of the medicament.

[0065] As with determining the length of the second predetermined time period, the first predetermined time period may be incrementally reduced (e.g. the second predetermined time period may be shorter than the first predetermined time period) in response to step 120 being satisfied. Similarly, the dosage level may be increased, so that the second dose is larger than the first dose, in response to step 120 being satisfied.

[0066] Lastly, the process 100 may involve step 124 of administering the first, second and/or any subsequent dose of medicament in response to receiving a medicament dosing request from the subject - e.g. in response to registering a button press by the subject.

[0067] The above computer controlled process 100 may be implemented by a computer system. A schematic illustration of an embodiment of a computer system 300 for implementing process 100 is shown in Figure 3. The computer system 300 broadly comprises the following components in electronic communication via a bus 302:

(a) a display 304;

(b) non-volatile (non-transitory) memory 306;

(c) random access memory ("RAM") 308;

(d) N processing components or processor(s) 310;

(e) a transmitter (presently embodied by transceiver component 312 that includes N transceivers);

(f) user controls 314;

(g) an audible alarm speaker 316;

(h) a counter 318;

(i) a medicament controller 320;

(j) at least one parameter sensor 322; and

(k) a threshold comparator 326.

[0068] Measurements of parameters or vital signs and physical movements may be uploaded to remote storage, such as a hospital server, or may be stored in the cloud 324.

[0069] Although the components depicted in Figure 3 represent physical components. Figure 3 is not intended to be a hardware diagram. Thus, many of the components depicted in Figure 3 may be realized by common constructs or distributed among additional physical components. Moreover, it is certainly contemplated that other existing and yet-to-be developed physical components and architectures may be utilized to implement the functional components described with reference to the processes of Figures 1 and 2.

[0070] The display 304 generally operates to provide a presentation of content to a user, and may be realized by any of a variety of displays (e.g., CRT, LCD, micro-projector and OLED displays). This may display individual measurements of the one or more parameters as taken by the parameter sensor(s) 322, or may display time-based graphs such as that shown in Figure 2. In this regard, the parameter sensor(s) will be selected to sense the desired parameters in a known way - e.g. a pulse oximeter may be used as the sensor for determining SP0 ₂ , or a C0 ₂ sensor for measuring C0 ₂ levels in blood - e.g. a capnometer for measuring end tidal C0 ₂ . In addition, the processor(s) 310 may check operation of the sensor(s) 322 to ensure proper connection between the sensor(s) 322 and processor(s) 310. Through this connection, the processor(s) 310 can also ensure the sensor(s) 322 are sending valid data. This could be achieved by the processor(s) 310 polling the sensor(s) 322 to determine if vital signs data is delivered from the sensor(s) 322 regularly (i.e. without undue delay) and that the data, when sent from the sensor(s) 322, is within valid ranges - i.e. the data is tested against upper and lower bounds, such as 20mmHg (low threshold - lower bound) for C0 ₂ in blood and 50mmHg (high threshold - upper bound) for C0 ₂ level in blood.

[0071] Moreover, the parameter sensor(s) 322 may continually measure the one or more parameters of the subject or may measure the one or more parameters at regular intervals. As discussed below, the threshold comparator 326 can then determine if any measurement taken since administration of the first dose, an average of those measurements or any other combination of parameters, has exceeded the relevant predetermined threshold.

[0072] In general, the non-volatile data storage 306 (also referred to as non-volatile memory) functions to store (e.g., persistently store) data and executable code. Though illustrated as a single block, memory 306 may be distributed across multiple components such as audible alarm speaker 318 (which issues audible alarms in a known manner), medicament controller 320 and parameter sensor(s) 322.

[0073] In some embodiments for example, the non-volatile memory 306 includes bootloader code, modem software, operating system code, file system code, and code to facilitate the implementation of components, well known to those of ordinary skill in the art, which are not depicted nor described for simplicity.

[0074] In many implementations, the non-volatile memory 306 is realized by flash memory (e.g., NAND or NOR memory), but it is certainly contemplated that other memory types may be utilized as well. Although it may be possible to execute the code from the non-volatile memory 306, the executable code in the non-volatile memory 306 is typically loaded into RAM 308 and executed by one or more of the N processing components 310.

[0075] The N processing components 310 in connection with RAM 308 generally operate to execute the instructions stored in non-volatile memory 306. As one of ordinarily skill in the art will appreciate, the N processing components 310 may include a video processor, modem processor, DSP, graphics processing unit (GPU), and other processing components. The N processing components 310 may comprise a single component or may include multiple components, such as one or more components provided in the threshold comparator 324 to facilitate analysis of input from the parameter sensor(s) 322 (e.g. blood pressure, SP0 ₂ and pulse measurements).

[0076] The transceiver component 312 includes N transceiver chains, which may be used for communicating with external devices via wireless networks. Each of the N transceiver chains may represent a transceiver associated with a particular communication scheme. For example, each transceiver may correspond to protocols that are specific to local area networks, hospital networks and infrastructure, cellular networks (e.g., a CDMA network, a GPRS network, a UMTS networks), and other types of communication networks.

[0077] The transceiver component 312 may operate in a standard manner, to send and receive information over network 324. Component 312 may also serve to receive firmware updates and the like.

[0078] The computer system 300 is used for adaptive control of medicament availability. With reference to the processes shown in Figure 1, the memory 306, 308 stores the dose (i.e. the volume), the length of the first predetermined period, and relevant predetermined threshold(s) for the measurements of the one or more parameters of a subject. The memory 306, 308 further stores instructions that, when executed by the processor(s) 310, cause the medicament controller 320 to make the first dose of a medicament available for administration to a subject. In some cases, the instructions will also cause the medicament controller 320 to administer the dose of medicament to the subject. This may be by direct infusion through a needle inserted into the subject (i.e. the medicament controller 326 comprises an infusion system), or may be by connection of the medicament controller 320 with an infusion system (not shown, but known in the art) connected to the subject that is controlled by instruction from the medicament controller 320 to dispense a dose of the medicament.

[0079] The instructions further cause the parameter sensor(s) 322 to take measurements of one or more parameters of the subject once the first dose has been administered to the subject - as mentioned above, the one or more parameters are subject to change in response to administration of the medicament - and the threshold comparator 326 to determine if at least one of the measurements obtained by the parameter sensor(s) 322 exceeds a relevant predetermined threshold. If the threshold comparator 326 determines that none of the measurements exceed the relevant predetermined threshold, the processor(s) 310 make available a second dose of the medicament available for administration to the subject, using the medicament controller 320, only after expiry of a first predetermined time period from administration of the first dose. If a predetermined number of doses has been administered without any measurement exceeding its relevant predetermined threshold(s), then the medicament controller 320 may increase a dosage level of the second dose so that the second dose is larger than the first dose (e.g. the second dose may contain lOOmg of pain medication, whereas the first dose may contain 80mg of that medication).

[0080] The counter 318 sets the first predetermined time period - i.e. sets the length of that period - and counts down to expiry of that period, after which it alerts the processor(s) 310 of that expiry. To this end, the counter 318 may comprise:

one or more countdown timers for counting down the first and second predetermined threshold periods;

a timer for recording a length of time between consecutive or successive doses, those lengths of time being stored in memory 306, 308;

a dosage counter for counting a number of doses and/or recording dosage volume (e.g. mg or mL administered over a 60 minute period); and

a comparator for identifying the longest and/or shortest length of time between consecutive or successive doses for the purposes of determining an appropriate length of time for the second predetermined time period in accordance with step 114.

[0081] The dosage counter of the counter 318 may count the number of doses of the medicament over which none of the measurements of the one or more parameters have exceeded the relevant predetermined threshold(s). If the dosage counter reaches a predetermined number of doses before a measurement exceeds the relevant threshold(s), the counter 318 may reduce the first predetermined time period. As discussed above, the reduction may be incremental and thus based on the first predetermined time period (e.g. the first predetermined time period may be 5 minutes, and the reduction may be a 1 minute reduction, thus making the new first predetermined time period a 4 minute lockout period).

[0082] The counter 318 may similarly adapt the second predetermined time period. For example, the counter 318 may measure one or more periods between administration of successive doses made available after expiry of the first predetermined time period. The counter 318 may then determine a length of time for the second predetermined time period based on an average of the one or more periods. The timer 318 thus sets the second predetermined time period based on the actual time between administration of doses, rather than the minimum possible time, being the first predetermined time period. The counter 318 may instead determine a length of time for the second predetermined time period based on a longest period of the one or more periods. The second predetermined time period, which may also be referred to as a second time period, is therefore at least as long, or longer, than the longest interval between self-administered doses of the medicament.

[0083] The instructions can further cause the processor(s) 310 to take successive further measurements of the one or more parameters using the parameter sensor(s) 322 in the event that one or more of the measurements exceeds the relevant predetermined threshold, as determined by the threshold comparator 326. The threshold comparator 326 receives the successive further measurements and determines when those further measurements no longer exceed the relevant predetermined threshold. At this time, the medicament controller 326 makes the second dose of the medicament available for administration to the subject. To reduce the risk of over-medicating the subject, the medicament controller may lower the dosage level so that the second dose is smaller than the first dose. In either case, the second dose is administered only after expiry of a second predetermined time period from administration of the first dose. As with the first time period, the second predetermined time period is set by the counter.

[0084] It should be recognized that Figure 3 is merely exemplary and in one or more exemplary embodiments, the functions described herein may be implemented in hardware, software, firmware, or any combination thereof. If implemented in software, the functions may be transmitted or stored as one or more instructions or code encoded on a non-transitory computer-readable medium 306. Non- transitory computer-readable medium 306 includes both computer storage medium and communication medium including any medium that facilitates transfer of a computer program from one place to another. A storage medium may be any available medium that can be accessed by a computer.

[0085] Figure 4 provides a further, broad overview of a computer controlled process 400 for adaptive medicament availability and administration. The process 400 automates vital signs monitoring and adapts to changing vital signs data (which, in the present embodiment, equate to one or more parameters as measured by the parameter sensor(s) 322). The process 400 involves human configured treatment (e.g. patient controlled administration of a medicament using a PCA pump) starting with continuous vital sings data acquisition - step 402.

[0086] Monitoring of vital signs may begin before pain medication is administered for the first time, or may begin after administration of the first dose of medicament - step 404. [0087] After acquisition of vital signs data, a determination is made as to whether the vital signs data meets the criteria - in other words, whether the vital signs data either exceeds or satisfies (i.e. does not exceed) the relevant predetermined threshold(s) - step 406. If the vital signs data meets the relevant predetermined threshold(s), then the process 400 continually cycles back to step 402 (i.e. continually monitors the vital signs) and continues with the treatment - step 408.

[0088] If the vital signs exceed the relevant predetermined threshold(s), the process 400 pauses treatment for a period of time - step 410. During the pause, further vital signs measurements are taken and compared to recovery criteria - step 412. The recovery criteria are the same as the relevant predetermined thresholds against which a determination is made under step 406.

[0089] Thus at step 410, and similarly for step 110, the process 100, 400 and the processor(s) 310 of the system 300 implementing that process 100, 400, may pause for a predetermined pause time (5 minutes in the present example, as counted by counter 318). While vital signs may continue to be monitored, step 116 and step 414 can only take place after expiry of the pause time. In the present embodiment, once the pause time has elapsed, the process 400 determines if the vital signs data has met the criteria - step 412 - this step being performed by the threshold comparator 326.

[0090] The period of the pause implemented at step 410 may be by default period, e.g. 5 mins, but may be configured during initial set up to be anywhere between, for example, 1 to 10 mins in whole-minute increments of 1 min. This may be 5 minutes from administration of a dose of medicament per step 404, 5 minutes in addition to the first predetermined time period, or 5 minutes from the time the measurement was taken at step 402.

[0091] After the pause time, if the new, or further, vital signs data meets the recovery criteria, the process 400 resumes treatment to a lower state - step 414 - when compared with the state of treatment at step 402. The "lower state" involves either one or both of:

the dose being lowered such that the second dose is smaller than the first dose; or the lockout period being extended such that the second predetermined time period is greater than the first predetermined time period.

[0092] At step 414 the system automatically resumes treatment to a lower state and continues to acquire vital signs data. The lower state of treatment is relative to the initial treatment starting point. In other words, the "lower state" of treatment will implement a use a lower dose of medicament or a longer lockout period between doses, than the initial state of treatment. This will ensure that the amount of pain relief drug being administered by the infusion system or device (i.e. medicament controller 320 with, or attached to, the infusion system) is lower upon resumption of treatment per step 414. The key assumption upon which the change in dosage regime is based is that the previous state of treatment responsible, at least in part, for the slight temporary deterioration of vital signs.

[0093] It an alternative scenario, the process 400 resumes treatment to the original state with none of the changes described above, if the deterioration in vital signs was only very slight.

[0094] The process 400 may further suspend treatment altogether if the new, or further, vital signs data does not meet the recovery criteria - step 416, or if the deterioration of vital signs is too great (i.e. there may be a hard, unsafe limit that the vital signs have crossed). This stops any possibility of automatic resumption of treatment - step 414. Treatment will thus only resume with human intervention, e.g. by a medical professional, to dismiss or unsuspend the treatment after assessment of the patient or subject. When instruction is received from a human operator to unsuspend treatment, treatment may be resumed in the lower state as described above, or may resumed in its original or initial state as it was at the time of performance of step 402.

[0095] Steps 414 and 416 enable the process 400, and thus system 300 implementing the process 400, to avoid further deterioration of vital signs of the subject (as a complication of pain management) yet allow for treatment to be resumed if vital signs recover. This avoids manual intervention (additional labor) that would otherwise be required to restart the system 300 where only treatment suspension is required. Moreover, the process 400 lowers the state or dosage regime of the process 400, thus resuming treatment in a safe manner.

[0096] During step 402 and step 410, vital signs data is preferably continuously acquired. This may involve multiple monitors (e.g. parameter sensor(s) 322) connected in a wired or wireless fashion, that measure all relevant vital signs data directly or by inference - e.g. oxygen saturation, pulse rate, respiratory rate, end tidal C02.

[0097] Figure 5 illustrates the different states of treatment for patient controlled pain management - 500. A state of treatment and associated parameters is defined - step 502 - providing the treatment starting point. In the present embodiment, the lock out timer (first predetermined time period) is set to 7 minutes - step 504 - and thus the system 300 counts down from 7 mins before a second dose is made available to the patient for administration. When treatment is automatically resumed or unsuspended, the lockout timer is increased by one unit- e.g. 1 minute - step 506. This unit may be configured by user and could be in the range of 0.5 - 5 minutes. By default, it would be 1 minute and so when treatment is resumed from safety pause, the countdown timer is increased from 7 mins to 8 mins.

[0098] Step 506 places an upper bound on the lockout period. Any upper bound may be used. If a further measurements is taken that is determined to have exceeded the relevant predetermined threshold(s) - step 510 -and the lockout period is already at the upper bound, then the system 300 may suspend treatment- step 512 - and generate an alarm using audible alarm speaker 316. This will alert a medical professional to the potential of the dose of medicament being too high for the patient to sustain.

[0099] Step 508 places a lower bound on the lockout period. Any lower bound may be used. If the patient or subject continues to administer doses without any measurement being determined to have exceeded the relevant predetermined threshold(s) - step 514 - then the lockout period is lowered per step 508. For the lower bound to be reached there would appear to be little danger of the subject being overmedicated. Nevertheless, to avoid a circumstance in which the lockout period becomes too short and enables the subject to rapidly overdose on the medicament before the system 300 can detect a change in vital signs, a lower bound is set - presently 3 minutes, but may instead be the lockout period specified during set up (e.g. the first predetermined time period).

[0100] The lockout timer (i.e. counter 318) affects the amount of pain relief drug infused by the infusion system 300 over time. The interaction between the button operated by the patient, and the system 300, is illustrated by process 700 of Figure 7. In process 700, a dosage request is received from patient by the receiver - step 702. This results from the patient depressing or activating a button that facilitates self- medication.

[0101] The dosage request is transmitted to the controller (e.g. processor(s) 310) that checks if the system is locked out - step 704. If the system is not locked out, the controller will initiate a patient initiated dose command to the medicament controller 318 (comprising or attached to an infusion device) that delivers the pain relief drug intravenously - step 706.

[0102] Once the patient dose is initiated, the system 300 enters a lockout state and starts the current lockout timer - step 708 - as described in with reference to counter 318 and step 504 of Figure 5. Only after the lockout period, e.g. 7 minutes, will the system 300 exit the lockout state - step 710 - and thus makes a further dose of the medicament available for administration. While in the lockout state, any dosage from patient during lockout will be ignored insofar as it will be disregarded for medicament dosage administration purposes. However, if a patient repeatedly presses the button to make a dosage request during the lockout period, the system 300 may raise an alarm (e.g. using alarm 316) to bring to a medical professional's attention that the pain medication does not appear to be working. This may also assist medical professionals in identifying faulty buttons for making dosage requests. Moreover, where the processor(s) 310 detect improper connection or operation of one or more sensor(s) 322, the audible alarm may sound to ensure the clinician properly connects the sensor(s) 322 to the processor(s) 310 and/or replaces faulty sensor(s) 322.

[0103] Together with the pause time described with reference to step 110 of Figure 1 and 410 of Figure 4, the lock out operates in such a manner as to reduce the opportunity for a dosage request from patient to result in a patient initiated dosage. The aim is to titrate less drug so as to prevent complications associated with pain management. However, increasing lockout without a counterbalance to decrease lockout may result in under treatment and inadequate pain relief which in turn will result in a failed pain management session. Thus increases and decreases in the lockout period are provided for in Figure 5.

[0104] Figure 8 illustrates a process 800 for changing the lockout period. To decrease the lockout period, process 800 observes a pattern or trend of successful patient initiated delivery - this is performed using the dosage counter or timer of counter 318 - step 802. Successful patient initiated delivery is delivery of a dose of medicament without any measurement exceeding the relevant predetermined threshold. In the present embodiment, the counter 318 logs or counts three successive successful patient initiated doses and then decreases the lockout time from 5 mins to 4 mins - step 804.

[0105] The trend or pattern of successive patient doses could vary from three successful doses in 1 hour or 2 hours or in any time frame. The trend or pattern may also require only two successive doses so that lockout is reduced faster, or up to four successive doses depending on user preference and the size of default or initial dose (e.g. the "first" dose).

[0106] Conversely, if the system 300 has suspended treatment in line with step 106 of Figure l and step 410 of Figure 4, upon resumption - step 806 - the lockout period may be increased - step 808. [0107] Instead of, or in addition to, modulating the lockout time the system 300 may modulate the size of the dose using a process 600 illustrated in Figure 6. Given an original bolus size - e.g. 1ml (602) - and a case in which treatment has resumed after vital signs deterioration and recovery- step 112 of Figure 1 - will decrease the next dose by a predetermined amount - presently a 0.25mL reduction to 0.75 ml (606) - so that next patient initiated dose is smaller than the previous patient initiated dose. Conversely, a trend of successful patient initiated doses will result in the increase of dose size by a predetermined amount - e.g. 0.25mL to 1.25mL (604) - per step 806 of Figure 8.

[0108] Again, an upper bound and a lower bound may be set for the size of the dose, presently, the upper bound is 2mL and the lower bound is 0.5m L. So the dose cannot be larger than 2mLand cannot be smaller than 0.5mL.

[0109] As discussed above, in some cases variation of only one of the lockout period (first predetermined time period and/or second predetermined time period) and dose size may be appropriate. In other cases, a combination of lockout and dose size modulation may be desirable. For example, an original dose size of lmL with a lockout time of 7mins may be increased to 1.25mL with a lockout time of 6 mins, when the counter 318 and threshold comparator 326 log a trend of successful patient initiated doses. Thus each of the embodiments of processes and systems described above can be combined in various ways to achieve the needed functionality.

[0110] A situation may also arise in which the initial thresholds assessed at Step 106 of Figure 1 and step 406 of Figure 4 are inadequate - the thresholds may be too low or too high. There may also be other interventions that cause signal interference on the parameter sensor(s) 322 or cause a reduction in sensitivity of the parameter sensor(s) 322 towards changes in vital signs - i.e. changes in patient or subject condition thus the predetermined thresholds may be adjusted by a medical professional if it is found that the original predetermined thresholds are inappropriate.

[0111] Referring to Figure 9, the system 300, particularly the counter 318 and threshold comparator 326, is able to record trends of:

902: safety pauses (per step 410 of Figure 1 and 406 of Figure 4);

904: treatment suspension (per step 416 of Figure 4);

906: vital signs data (per steps 104 and 110 of Figure 1 and steps 406 and 412 of Figure 4); and 908: human operator intervention. [0112] These quantities can be used to make decisions or prompt for vital signs criteria adjustment - i.e. adjustment of the predetermined thresholds used in assessments at steps 106 and 112 of Figure 1 and steps 406 and 412 of Figure 4. For example, if there has been a pattern of treatment suspension that was dismissed after operator review - step 904 - the system 300 will be able to suggest a lowering of vital signs criteria - step 910 - that could be a few percentage points of the medium or mean of vital signs as recorded per step 104 of Figure 1 and step 406 of Figure 4, or of the relevant predetermined thresholds for measurements associated with those vital signs.

[0113] Conversely, if human operator is able to input that more support such as oxygen is provided to the patient, the vital signs criteria may now be increased to ensure the system remain responsive -908. For example, where oxygen is administered to the subject, SP0 ₂ would be expected to increase and be higher, even when the subject is becoming unstable, than it would have been prior to oxygen administration. The adjustment of thresholds may be performed automatically, using the threshold comparator 326 and/or processor(s) 310 to examine the distance between measurements of the one or more parameters and the relevant predetermined thresholds, in real time.

[0114] Further to the above discussion, currently, patients are provided with a patient controlled infusion pump to deliver the medicament. The infusion pump is filled with morphine which is programmed to respond to patient demands with fixed doses and fixed lockout as previously discussed.

[0115] Once patients are on connected to this infusion pump, they are also regularly monitored for the negative side effects of the medicament - e.g. opioids. These postoperative patients on PCA opioids are intermittently monitored for oxygen saturation, heart rate, blood pressure and respiratory rate. Every hour, oxygen saturation and heart rate are measured with a pulse oximeter. Blood pressure is usually measured with a manual or electronic sphygmomanometer. The nurse measures respiratory rate through visual measurements of respiratory efforts manually. Clearly, the state of the art is a highly labour intensive process. Furthermore, these measures together with intermittent checks by nurses that occur on a periodic basis are insufficient for reliably recognizing clinically significant opioid- or medicament-induced respiratory depression in the postoperative period. Such monitoring fallaciously assumes that the vital signs taken intermittently could monitor and more importantly prevent acute clinical deterioration of the patients.

[0116] Safety Closed Loop systems operate on the basis of thresholds to pause and/or assess the clinical safety concern. Subsequently, the system should be able to make a clinically safe decision to stop therapy. In the alternative, the system should be able to make a clinically safe decision to resum therapy if an alarm is found to be a false positive - this will alarm fatigue and healthcare staff workload.

[0117] Due to the potential impact on the health of patients, there is a need to use the correct methods to assess the clinical safety concern. Previous methods of merely comparing vital signs parameters involved comparison against discrete thresholds. This oversimplifies the problem, creating false positive or negatives. Such an oversimplified method does not, for example, take into account the relationship between various vital signs during respiratory depression. There can be a reduction of respiratory rate prior to oxygen desaturation when patients breathe room air.

[0118] Similarly, such oversimplified methods do not accommodate changing clinical requirements in a postoperative ward. In such cases, measurements may be affected or potentially interfered with as a result of oxygen supplementation. In some cases, oxygen supplementation may mask the clinical monitoring of oxygen saturation. While the patient may appear to be experiencing oxygen saturation and thus be safe, the patient may rapidly decline if oxygen supplementation is removed. Oxygen desaturation in such cases will be a late event compared to the respiratory rate, which will reduce earlier. The respiratory rate should therefore be given attention, or successive further measurements of oxygen desaturation should be taken over a shorter period of time when compared with patients who are not on oxygen supplementation.

[0119] The method 100 may therefore take into account the presence or otherwise of oxygen supplementation and thus prioritise various vital signs monitoring using an adaptive vital signs monitoring process to improve patient safety individualize to clinical needs. The method 100, and system 300 for implementing it, may thus provide analysis and a recommendation based on continuous vital signs parameters or continuous monitoring, patient demands and clinical demands for oxygen support. This maximizes patient pain relief, mitigates opioid respiratory depression, and allows for effective pain control.

[0120] The present method 100 can be adapted to provide context specific threshold and vitals signs parameter classification. For example, the step 110 of taking successive further measurements of the one or more parameters using the parameter sensor(s) can be adapted to take those measurements of a predetermined time period. The length of that predetermined time period can be adjusted depending on whether the subject is receiving oxygen supplementation. This ensures particular vitals signs measurements, or combination of measurements for different vital signs, are prioritised over others. [0121] In some embodiments, the system 300 may generate an alarm (step 118) if the oxygen saturation level measured from the patient or subject is below the relevant threshold for a longer predetermined time period when the patient or subject is not on oxygen supplementation, when compared with when the patient or subject is on oxygen supplementation. For example, the system 300 may trigger a safety pause (during which medicament delivery is prevented) after a period of 5 minutes over which the oxygen saturation is below the threshold when the subject or patient is not on oxygen supplementation, whereas that period may be 2.5 minutes when the patient or subject is on oxygen supplementation. Thus the system has a faster response when the patient is on oxygen supplementation, since oxygen desaturation is then considered a late sign of deterioration of the subject.

[0122] In some embodiments, the predetermined thresholds for particular vital signs may be dynamically changed. For example, the threshold heart rate may be reduced if oxygen saturation and respiratory rate are within an acceptable range - i.e. do not exceed (including exceeding by dropping below/crossing over) the respective thresholds. The inventors have found that a patient's heart rate can lower (return to patient's baseline) several hours post operation. The reason is that during surgery anaesthesiologist may infuse inotropic agents to artificially elevate the heart rate to prevent hypotension. When these inotropic agents are metabolised, the patient can return to their normal heart rate which may be lower than the original threshold. For example, the method 100 and system 300 may lower the heart rate from 60bpm to 50bpm (beats per minute) if the oxygen saturation and respiratory rate are within the acceptable range. User input may then be used to manually drop the heart rate further - e.g. to 40bpm. Such further lowering may also be automatically performed by the method 100 and system 300.

[0123] In some clinical, a patient receives too much analgesia. In such cases, sedation can occur which may result in Bradycardia (lower heart rate). So a threshold is maintained, though it can be adjusted as set out above depending on the state of the patient and their treatment.

[0124] Step 106 and/or step 112 may also permit a further dose of medicament to be delivered if each parameter of a combination of parameters satisfies its respective threshold. For example, regardless of whether or not the respiratory rate (measured, e.g. using UCG, acoustic or plethysmograph techniques) breaches its predetermined threshold, a further dose of medicament may be made available if both the oxygen saturation and heart rate do not breach their respective thresholds. [0125] The method 100 may also involve recommending oxygen supplementation. For example, the method 100 may involve recommending oxygen supplementation is oxygen saturation, or another desired parameter, is below a predetermined threshold for at least a predetermined time period.

[0126] With reference to FIG. 10, sensor(s) 1000 take measurements that are interpreted by an adaptive vital signs controller 1002. A safety pause 1004 is implemented if a particular vital sign is below its predetermined threshold - e.g. for a predetermined period of time. The lockout time (i.e. second predetermined time period) may also be increased - e.g. by one minute (1006) - if the safety pause is implemented. An alarm 1008 is then raised if, at the end of the safety pause, one parameter, or each parameter of a combination of parameters, fails (i.e. breaches) its threshold.

[0127] Conversely, on repeated successful deliveries of a bolus of medication - e.g. three successful deliveries in one hour- the lockout time may be decreased 1010. The maximum lockout period may be 10 minutes and the minimum - to prevent against repeated deliveries with insufficient time for the subject's body to respond to the medicament before the next bolus is delivered - may be 3 minutes.

[0128] Throughout this specification, unless the context requires otherwise, the word "comprise", and variations such as "comprises" and "comprising", will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps.

[0129] The reference to any prior art in this specification is not, and should not be taken as, an acknowledgment or any form of suggestion that the prior art forms part of the common general knowledge.