Number of disorders as comparison group in selected studies.
\r\n\tThe automotive sector is transforming its fleet of vehicles to adapt them to this requirement of society, which is also being translated into increasingly restrictive legislation.
\r\n\tOther alternative fuels are currently considered in the deployment of a new mobile fleet that will entail a change in the way we move - sharing resources, such as the vehicle - and the resources and way of refueling.
\r\n\tAnd this transformation takes us further and further away from the oil sector as the only fuel for mobility. It is already common to consider a fraction of biodiesel or bioethanol in current fossil fuels, but the policy is moving towards a greater penetration of renewable energy resources.
\r\n\tMost of the new renewable sources will be generated in a distributed scenario, so it is necessary to study the logistic to transport them in a cost-effective and sustainable way.
\r\n\tIn summary, the aim of the book encompases the whole cycle of the energy resources, both conventional and renewables, associated to mobility.
The earliest slow potentials (SPs) emerged from animal studies in the 1950s. Significant steps in man were only made, starting with Walter [1], when the switch to DC recording, or much longer time constants (TCs) were made, which was previously more common in animal work.
\nSince then, a flurry of studies has been published in an attempt to unravel the underlying processes concerned, variously characterized as arousal, activation, attention, priming, expectancy, motivation, etc. What all of the constructs had in common was an attempt to express the level of involvement existing between a subject and his test environment over a given period of (examination) time. From the 1980s onward, numerous studies on different patient populations were conducted in an effort to use the CNV as a diagnostic aid.
\nDespite all these efforts, a chasm seems to prevail between research findings and the experience of clinicians using the CNV as a clinical tool.
\nThis is partly due to the fact that SPs offer its own range of artifactual problems and special technical considerations, such as the use of long time constants (TCs) and the difficulty to elicit reliable responses [2].
\nAnother element that plays a role is addressed by the proposed four-step approach for developing diagnostic tests in psychiatry by Boutros et al. [3]. Most laboratory tests in psychiatry, such as the CNV, tend not to be developed into diagnostic tools. This can only lead to the above-mentioned disappointment and premature abandonment by early adopters or not even implementing a test by most practitioners.
\nFor the clinician, it is important to know what the current status is of a test that shows promising results and see if progress is being made to develop the test into a diagnostic tool. A survey of literature (meta-analysis) should apply the four-step approach not only for clinicians, but also for researchers. Researchers should take count of the need for (simple and low cost) diagnostic tools for psychiatry. They also need to have a clear idea what the current status is of their research tool before progressing further. Is more evidence needed or are the requirements met to proceed to the next level?
\nThe CNV was adopted in clinical practice in Belgium, thanks to the extensive work of Timsit-Berthier and some Belgium companies at the time that developed the equipment for clinical use. However, the clinical utility of the CNV is at present unknown and will be explored in this chapter.
\nFrom the above, it seems useful that there should be more interaction between the researcher and clinician, not only from the researcher to the clinician, but also the other way around. Clinicians have the advantage that in most cases they will adhere to a standardized procedure and will apply it for many more disorders than already explored in research. This could provide valuable feedback to researchers where they can best focus their attention first.
\nClinicians also have a closer relationship with the test and their patients. They also will do repeated test. This has the potential for interesting observations that can lead to new discoveries that can benefit further development. This potential will be illustrated in this chapter with two clinical examples.
\nEach subject is presented with a series of paired signals of which the first S1 (warning signal) is a sound of 1 kHz with a duration of 0.5 s. The second sound S2 (imperative signal) is a continuous sound of 750 Hz with a duration of 5 s, which is delivered 1.5 s after S1. Both sounds are delivered through a loudspeaker (open field). The subject is instructed to keep the eyes closed and press a button (motor response (MR)) to stop the S2 sound at the point that it is clear for the subject that this is the target.
\nThe signals are presented in series of three to five pairs and averaged in real time, four series in total. The duration of each trial is 8 s, with a prestimulus period of 1 s and post-S2 duration of 6 s. An intertrial randomized interval is used between 10 and 11.5 s (Figure 1).
\nCNV cycle.
Data from 20 EEG scalp electrodes placed according to the International 10–20 System of Electrode Placement with four artefact electrodes (one vertical and two horizontal eye movements, one EMG/ECG) are recorded with one ground electrode and two reference electrodes. Recording electrodes are referenced to linked ear electrodes and processed through analogue EEG amplifiers with a filter band-pass of 0.01–30 Hz with a total acquisition time of 8 s and digitalized with a sampling rate of 256 Hz.
\nA reject limit is set for each individual subject. This lets you automatically reject a transient high voltage pattern, such as eye-blink and eye-movement artifacts. The appropriate reject level is determined from monitoring the peak values of the first series of three to five pairs, which is discarded. The reject limit is usually set 10 μV higher than the maximum observed peak value. In most cases, this will be about 50 μV. On each trial, the reject limit is compared against the acquired signal amplitude in each channel. If 10 or more points in the input signal have an absolute amplitude value over the reject limit, the trial is rejected.
\nThe Contingent Negative Variation (CNV) slow waves were elicited using a modified version of the standard paradigm of Timsit-Berthier, more closely matching in some respects the author’s earlier work [4, 5] rather than the procedure described in her latest publication [6]. However, current method also deviates from Timsit-Berthier’s procedures.
\nCurrent procedure aims to study the development of the CNV with the focus on the late components of the CNV.
\nThe CNV reaches the maximum amplitude in normal adults in about 30 trials, although it can be fully developed in five to eight trials [7]. The assessment of the temporal evolution is done by applying the cumulative curve method presented by Timsit-Berthier at EPIC IV in 1976 [5] and was never picked up again in later publications. Here we deviate from the presented procedure taking into account the number of trials at which the maximum CNV amplitude is reached. This limits the number of trials to 30 instead of 76, and the number averaged segments from 6 to 4.
\nThe use of a constant-foreperiod reaction-time (S1-S2-MR) procedure is used to optimize the development of the CNV [7].
\nThe S1–S2 time interval of 1.5 s is based on the earlier work of Timsit-Berthier in order to separate the late from the early component of the CNV. With a time interval of 1 s, as used in later publications, the early and late CNV components overlap.
\nThree different parameters were measured on the CNV curve (Figure 2). First, the negative average amplitude of the late CNV was calculated between 1400 and 1600 ms (A3) after the start of S1 at Cz. Then, the positive average amplitude of the post-S2 amplitude was measured between 900 and 1100 ms (A5) after the start of S2 relative to average amplitude of the late CNV at Cz. Next, the difference between A5 and A3 was calculated. The difference is an expression of the post-imperative negative variation (PINV = A5 − A3).
\nCNV parameters.
These parameters are recorded for each of the four series of averaged trials.
\nTwo separate amplitude segments are mapped in a cumulative histogram, with negative values above the x-axis. On each of the four sequential averages, we note the amplitude of A3 and PINV. On the horizontal axis, the first segment contains four bins of A3 values, followed by the second segment with four bins of PINV values. Each bin of a segment gives the value of the amplitude plus the values of each previous bin.
\nA normal cumulative curve shows an increasing negativity of A3 and an increasing activity (positivity) of the PINV. Both reach the same absolute value at the end.
\nFrom the normal cumulative curve, four major distinguishing types (A–D) can be constructed (Figure 3).
\nNormal and four abnormal types (A-D) of cumulative curve.
Type A: the absolute maximum value of A3 is clearly lower than the absolute maximum value of the PINV. The maximum value of the PINV is positive.
Type B: the absolute maximum value of the PINV is clearly lower than the absolute maximum value of A3. The maximum value of A3 is negative.
Type C: the absolute maximum value of A3 is clearly lower than the absolute maximum value of the PINV. The maximum value of the PINV is negative.
Type D: the absolute maximum value of the PINV is clearly lower than the absolute maximum value of A3. The maximum value of the A3 is positive.
As mentioned before, as clinicians, we like to see research findings developed into clinical (diagnostic) tools. With this in mind, it seems useful to not only contrast current clinical findings of the CNV cumulative curve with research findings, but also assess the current status of CNV research in regard to its potential as a clinical tool. This was done with a survey of literature and by applying the four-step approach for developing diagnostic tests in psychiatry [3].
\nRelevant articles were selected on PubMed, from the National Center of Biotechnology Information (
This resulted in a total of 674 references which were scored following the proposed four-step model for developing diagnostic tests in psychiatry [3]:
\nStep 1 demonstrates the presence of a deviant variable in a target group compared to a healthy group and the test-retest reliability. This provides evidence of a consistent abnormality in the target group.
Step 2 demonstrates a significant differential prevalence of a deviant variable between disorders and a healthy group. This demonstrates the potential for clinical utility.
Step 3 demonstrates how promising the findings are for development as a diagnostic test by comparing the target group to proper control groups. It defines the test-performance characteristics and the clinical utility.
Step 4 extends the comparison of the target group versus control groups by using larger groups or by multicenter trials. This step demonstrates the clinical application and sets up standards for clinical use.
This procedure gives us a solid methodology to evaluate literature in prospect of the data analysis of the selected major disorder classes and clinical observations.
\nA large part of the 674 references were dropped because they were about the Bereitschaftspotential (194) or did not provide sufficient information (97) for classification.
\nAbout the same amount of studies were excluded, due to the lack of Healthy Control (71) or Target Group (219). The remaining 93 studies were then classified according to the four-step approach. Next, the number of studied disorders was counted.
\nSchizophrenia is the most studied population (19), followed closely by migraine/headache (16). To a lesser extent, Parkinson’s disease (7), depression (6) and dementia (5) were researched. The remaining disorders were mostly studied only once and are not considered here (Table 1).
\nDisorder | \nNumber | \n
---|---|
Schizophrenia | \n19 | \n
Migraine/headache | \n16 | \n
Parkinson\'s disease | \n7 | \n
Depression | \n6 | \n
Dementia | \n5 | \n
Others | \n52 | \n
Total | \n105 | \n
Number of disorders as comparison group in selected studies.
The classification on the four-step approach method resulted in 84 studies classified at step 1 and 9 at step 2. In the studies reaching step 2, schizophrenia is the most prevalent disorder used as comparison group, seven out of the nine studies.
\nStudies show that there is a clear presence of a PINV in the schizophrenic patient. Half of the studies found a reduced amplitude of the CNV with an indication of a more frontal distribution.
\nThe migraine patient is characterized with increased amplitude, especially of the early CNV. Several studies also show a perturbed habituation.
\nPatients with headache rather show a PINV.
\nIn the Parkinson patient, both the early CNV and the late CNV are reduced in amplitude.
\nTwo of the seven studies seem to indicate that there is a correlation between the amplitude and mental functioning.
\nIt was not possible to come to any meaningful conclusion due to the use of a wide variety of paradigms, which made a comparison rather senseless.
\nFrom literature survey, it seems promising to use the CNV, at least for schizophrenia, since the studies demonstrate the potential for clinical utility (step 2). To a lesser extent, only two studies, depression also holds promise for clinical utility. However, due to a lack of consistent methodology across studies, further studies are needed to support this.
\nAt present, the comparison of these studies suggests that it seems premature to link a deviant parameter to a single disorder: for example, low CNV amplitude can be found in a schizophrenic as well as a Parkinson patient.
\nSince there are more parameters (see Section 4.3) that can be measured on the CNV, it seems reasonable to use them in combination in an attempt to differentiate between disorders that show the same change on one parameter.
\nA total of 3757 clinical patients (mean ± SD age = 44.5 ± 15.9) were selected on the following criteria: hospitalized on the psychiatric ward, classified on the DSM-IV-TR and underwent a CNV.
\nAfter classifying the patients into the major DSM-IV categories, the groups that had a minimum of 100 individuals were retained.
\nThis resulted in a total of 4196 clinical subjects assigned to six major disorder classes: (1) Substance-Related Disorders, (2) Mental Disorders Due to a General Medical Condition Not Elsewhere Classified, (3) Dissociative Disorders, (4) Schizophrenia and Other Psychotic Disorders, (5) Mood Disorders and (6) Impulse-Control Disorders Not Elsewhere Classified.
\nDue to the fact that a patient can have multiple DSM-IV numbers assigned, the total number of classified subjects is larger than the population total.
\nIn all major categories, a minimum of 91% (mean ± SD = 92.2 ± 0.9) of the patients show a normal amplitude of the late CNV. There are also no major differences between the groups for increased or decreased amplitude (Table 2).
\nDSM-IV-TR class | \n\n | A3 | \nA5 | \nA5-A3 | \n||||||
---|---|---|---|---|---|---|---|---|---|---|
\n | N | \n≤−2SD | \n≥2SD | \nNS | \n≤−2SD | \n≥2SD | \nNS | \n≤−2SD | \n≥2SD | \nNS | \n
SRD | \n1525 | \n0.6 | \n8.2 | \n91.2 | \n1.2 | \n1.7 | \n97.0 | \n8.9 | \n0.4 | \n90.8 | \n
MDG | \n766 | \n0.4 | \n6.7 | \n93.0 | \n0.9 | \n2.3 | \n96.7 | \n11.5 | \n0.4 | \n88.1 | \n
DD | \n155 | \n0.0 | \n9.0 | \n91.0 | \n0.6 | \n1.9 | \n97.4 | \n11.6 | \n0.0 | \n88.4 | \n
SPD | \n111 | \n0.0 | \n8.1 | \n91.9 | \n0.0 | \n0.9 | \n99.1 | \n9.0 | \n0.0 | \n91.0 | \n
MD | \n1497 | \n0.4 | \n6.7 | \n92.9 | \n1.2 | \n1.9 | \n96.9 | \n10.4 | \n0.3 | \n89.4 | \n
ICD | \n142 | \n0.7 | \n6.3 | \n93.0 | \n1.4 | \n0.7 | \n97.9 | \n11.3 | \n0.0 | \n88.7 | \n
Average | \n\n | 0.4 | \n7.5 | \n92.2 | \n0.9 | \n1.6 | \n97.5 | \n10.5 | \n0.2 | \n89.4 | \n
SD | \n\n | 0.3 | \n1.1 | \n0.9 | \n0.5 | \n0.6 | \n0.9 | \n1.2 | \n0.2 | \n1.2 | \n
Percentage of subjects in each major diagnostic class that shows a significant decreased (≤−2SD), increased (≥2SD) or normal (NS) amplitude for each parameter.
SRD: Substance-Related Disorders, MDG: Mental Disorders Due to a General Medical Condition Not Elsewhere Classified, DD: Dissociative Disorders, SPD: Schizophrenia and Other Psychotic Disorders, MD: Mood Disorders and ICD: Impulse-Control Disorders Not Elsewhere Classified.
At least 96% (mean ± SD = 97.5 ± 0.9) of the patients in each major group show a normal amplitude of the post-S2 amplitude. No significant differences were found between the groups for decreased or increased amplitude (Table 2).
\nA normal PINV amplitude was found for a minimum of 88% (mean ± SD = 89.4 ± 1.2) of the patients in each group. Up to 11.6% (mean ± SD = 10.5 ± 1.2) showed an increased amplitude of the PINV, but no significant differences were found between groups (Table 2).
\nThe type B is the most prevalent with an average of 61.7% (±SD = ±3.0), with no significant differences between groups. Following is the type A with an average of 23.1% (±SD = ±2.9) and type C with an average of 12.2% (±SD = ±2.2). The smallest group is type D with an average of 3% (±SD = ±1.5). Once again, no significant differences between groups were found (Table 3).
\nDSM-IV-TR class | \n\n | Cumulative curve | \n|||
---|---|---|---|---|---|
\n | N | \nType A | \nType B | \nType C | \nType D | \n
SRD | \n1404 | \n21.0 | \n63.6 | \n13.1 | \n2.3 | \n
MDG | \n713 | \n24.5 | \n59.6 | \n14.8 | \n1.1 | \n
DD | \n140 | \n26.4 | \n58.6 | \n9.3 | \n5.7 | \n
SPD | \n105 | \n19.0 | \n66.7 | \n11.4 | \n2.9 | \n
MD | \n1394 | \n22.2 | \n60.6 | \n14.3 | \n2.9 | \n
ICD | \n133 | \n25.6 | \n60.9 | \n10.5 | \n3.0 | \n
Average | \n\n | 23.1 | \n61.7 | \n12.2 | \n3.0 | \n
SD | \n\n | 2.9 | \n3.0 | \n2.2 | \n1.5 | \n
Percentage distribution of the different types of cumulative curves in each major diagnostic class.
SRD: Substance-Related Disorders, MDG: Mental Disorders Due to a General Medical Condition Not Elsewhere Classified, DD: Dissociative Disorders, SPD: Schizophrenia and Other Psychotic Disorders, MD: Mood Disorders and ICD: Impulse-Control Disorders Not Elsewhere Classified.
Data analysis of clinical subjects show that for the six major class disorders studied, the amplitude of the late CNV and the presence or absence of a PINV is unable to differentiate between these classes. The cumulative curve can also not be used to differentiate between the studied major class disorders.
\nThese negative results does not necessary mean that we need to abandon the CNV and the cumulative curve. First of all, there are more parameters than the two that have been used in this analysis:
\nM1 (early CNV): average value between 500 and 700 ms after S1
M2 (late CNV): average value of the 200 ms pre-S2 epoch
M3 (post-sensory positivity): average value between 300 and 500 ms after S2
M4 (post-motor positivity): average value between 300 and 500 ms after motor response
M5 (post-sensory positivity): average value between 500 and 700 ms after S2
M6 (post-motor positivity): average value between 500 and 700 ms after motor response
SM1 (total surface between M1 and M2): sum of values of all points between 500 ms after S1 and start of S2 relative to the average baseline
SM2 (total surface between 300 and 800 ms after S2): sum of values of all points between 300 and 800 ms after S2 relative to the average baseline
Apart from using a single parameter, any combination of parameters could be used to improve the differential diagnosis of disorders. This can be extended with a cumulative curve, comparing any pre-S2 averages with one of the post-S2 averages.
\nSecondly, the author’s clinical experience has demonstrated that there is another potential for the CNV and the cumulative curve that has not been considered. Two clinical examples not only help to illustrate this, but also to give some indication why the data analysis was unable to differentiate between disorders.
\nThis patient was examined five times on average every 139.25 days (±SD 40.66 days). The subject was initially examined with an indication of depression. Only on the second hospitalization the patient was sent for examination with the indication for bipolar affective disorder.
\nTwo alternating types of cumulative curves were seen across the five subsequent visits: type A and type B (Figure 4). The type A corresponds to the depressive episode and type B matches the manic episode.
\nCumulative curves of a bipolar affective disorder case for each visit.
When the respective averages were made of the CNV curves for the depressive and manic episodes, classified as such using the cumulative curve (Figure 5), differences in amplitude of the late CNV (A3) and PINV (A5-A3) became apparent. Both episodes show decreased amplitude of the late CNV (A3) and also early CNV and is more pronounced in the depressive episode. The manic episode has a value of −9.572 μV for A3 and −0.207 μV for PINV and the depressive episode −3.961 μV for A3 and 8.254 μV for PINV (Figure 6).
\nCumulative curves of the averaged CNV curves of the depressive and manic episodes of a bipolar affective disorder case.
Average curves of the manic and depressive episode of a bipolar affective disorder case.
This patient was examined 15 times on average every 228.21 days (±SD 75.20 days).
\nThe subject is known with a recurrent major depressive disorder, which was stable as reflected in the cumulative curve of the CNV during eight subsequent visits, on average every 266.00 days (±SD 78.46 days), lasting six years. The stable period was interrupted with one episode of decline following a subsequent number of negative personal dramatic incidences. This was reflected in the CNV by an overall decline of the amplitude and a type C cumulative curve.
\nThe patient recovered and corresponds to the average CNV of six subsequent visits, on average every 198.60 days (±SD 66.65 days). The overall amplitude returned to the previous stable period (Figure 7) and a type B cumulative curve was seen again (Figure 8).
\nAverage curves of the stable and recuperation period of a depressive case together with the curve of the single episode of decline.
However, the comparison of the cumulative curves of the recuperation and the stable period shows that the maximum amplitude of the PINV is higher in the last curve. From this, one could either conclude that the patient has not yet fully recovered or will continue to show a lasting impact of this decline (Figure 8).
\nCumulative curves of a depressive case: stable period, episode of decline and period of recuperation.
From literature survey, it seems that the CNV could only be applied for schizophrenics with certainty. Yet, one must remark that this is due to the lack of sufficient studies and the use of a standard paradigm within other patient populations.
\nFrom the data analysis of clinical patients, it is clear that the research findings for schizophrenics, the decreased amplitude and the presence of PINV are also found in other disorders. The data analysis also suggests that the CNV cannot be used for differential diagnosis.
\nDoes this really mean that we need to discard the CNV from clinical practice?
\nTo start answering this question, let’s return to the two clinical examples.
\nFrom the bipolar case, we not only learn that the CNV can at least be used as an aid to diagnose bipolar affective disorder but also might explain why there is a lack of clinical useful findings in CNV research. Within the same patient group, each individual is not in the same state when examined in clinical practice or taking part in a scientific study. This averages out many or all differences one might find if we would take into account the current state of each subject. In mixing both episodes of the bipolar patient, we fail to see the difference in amplitude of the late CNV between the depressive and manic episodes. This mix might also explain the absence of significant differences between patient groups. This clinical case also demonstrates that the CNV cumulative curve could be used to classify subjects on current state of mental disorder.
\nThe depression case demonstrates the strongest that we can follow the progression of a patient through time. When a patient is worse off, it is reflected in the CNV. Also, any change or no change at all in the state of the patient becomes apparent when comparing previous results. This suggests that the CNV could be used as a follow-up for any possible therapy that is initiated. Ideally, this might be used to increase the effectiveness of a therapy, either tailored to a specific disorder or even the individual patient.
\nBoth cases illustrate that the cumulative curve is the easiest analysis method of the CNV to express the current state and follow the progression of a subject. In general, if the state of a patient continues to worsen, the cumulative curve will change from a type B, through type C and finally to type D in the most unfavorable situation (Figure 9). When the patient improves, the cumulative curve will change in the opposite direction. In contrast, the bipolar patient will swing back and forth between the types A and B, bipolar cycle (Figure 9), as long as there is no improvement in the patient’s condition.
\nEvolution cycles of the cumulative curve.
To return to the question, clinical observations seem to support the position that there is no need to abandon the use of the CNV in clinical practice. The CNV cumulative curve shows potential as a diagnostic aid, although limited at this time to bipolar affective disorder. However, the greatest potential might lie in the therapeutic decision process. When a therapy is initiated, its progress can be followed with the cumulative curve. From the proposed model, one can expect that the success of a therapy will be reflected in the cumulative curve. If successful, the natural progression would deviate from its natural course and develop toward a normal cumulative curve. If this can be substantiated, the CNV would have a role as an aid to increase therapeutic effectiveness and reducing treatment cost.
\nIt must be clear that more research is needed to confirm these clinical observations. Apart from this, recommendations for further research have been highlighted in this chapter.
\nFirst, research should be aware that there is a need for clinical (diagnostic) tools in psychiatry. The four-step approach can be used to assess at what level a test is and ascertain if more research is needed at the current level or the requirements are met to move forward into the next level.
\nMore and better interaction is needed between researchers and clinicians to guide the development process. This close collaboration could result in a full development of a test, from discovery of a consistent abnormality to a standardized clinical (diagnostic) tool. It can also assure that a test will closely meet the needs of the clinician.
\nWe should also not forget previous research. Technology has further developed and offers many more possibilities. This should not blind us from the more ‘simple’ analysis that has been done in the past. Instead of moving these aside, we should use them to look at them from a new perspective. With current technology, we are no longer restricted to select one or a few parameters, but can also do multiple combinations with a simple push of a button.
\nThe patient requiring extracorporeal membrane oxygenation (ECMO) for any etiology is almost always managed in the intensive care unit (ICU) and requires care around the clock, which is delivered by a collaboration of physicians, nurses (RNs), respiratory therapists, perfusionists, and many others. Close collaboration between care providers is crucial, particularly between the RN managing hemodynamic medication infusions and the ECMO specialist managing the pump. RNs provide extensive, holistic care for ICU patients and their families, much of it geared toward traditional, clinical care with the additional implications of ECMO therapy, which requires additional specialized training. Acuity, unpredictability, and heavy resource requirements of the ECMO patient, especially when initiating therapy, can necessitate unusual and innovative staffing models, which rely on flexibility and often extra hours and shifts to accommodate individual patient and unit needs.
\nRNs are essential to the delivery of optimal healthcare and play an integral role in the care of patients admitted to the ICU, so it is important that, when staffed well, RNs reduce the risk of inhospital mortality anywhere from 14 to 36% [10, 29]. A recent expert consensus suggests RN-to-ECMO patient ratios should be at least 1:1 or 1:2 to deliver safe and quality patient care [33]. A recent survey found that RNs were allocated 1:1 in nearly 60% of ECMO centers internationally when also monitoring and intervening on the ECMO circuit [9]. This chapter will further discuss the nursing implications involved in the care of the ECMO patient, the RN’s role in prevention of associated complications, and the importance of the holistic approach required at the bedside.
\nNursing care should include monitoring of the ECMO circuit as nurses and associated staff, such as respiratory therapists and perfusionists, are at the bedside with the patient continually. ECMO cannulae require the same, if not more, attention that any peripheral or central venous catheter would, including assessment for erythema, purulence, adequacy of securement, and dressing integrity. It is significantly important to monitor for fixation of the ECMO cannulae. Initial placement of ECMO cannulae is usually confirmed by echocardiography and the position reaffirmed by radiographs [19]. Thus, ensuring the securement and stability of the cannulae by routine and repeated physical assessment is integral, as misplaced cannulae, loose sutures, or distant lashing straps can lead to specific complications such as inadequate flows or cannula dislodgment [28]. Ideal placement of lashing straps and appropriate securement of cannulae can be seen in Figure 1.
\nAppropriate lashing strap distance demonstrating safe securement and appropriate tension on the ECMO cannulae.
It is particularly important for the nurse and other bedside clinicians to be mindful of the integrity of the pump, as mispositioning of cannulae or hypovolemia can result in end-organ injury [11]. Suction events involve disruption of flow secondary to venous collapse onto the drainage cannula and can result in thrombus formation [11]. The occurrence of thrombi in the pump or oxygenator can be recognized by a visible thrombus, an increasing pressure decrease across the oxygenator, or a low post-oxygenator pCO2 [11].
\nThere are additional considerations that the nurse caring for the ECMO patient will need to exercise specific to the therapy. Disruption of innate circulatory flow secondary to ECMO can result in limb ischemia. Thus, it is important to monitor limbs, especially those distal from cannulation sites. Clinical judgment, pulse palpation, and Doppler sonography of limb vessels are effective tools for this purpose [28]. Another modern tool for monitoring tissue oxygenation in lower extremities in ECMO patients is near-infrared spectroscopy [28]. The nurse may also note that clinicians will often place distal perfusion catheters to help prevent or treat distal limb ischemia, as demonstrated in Figure 2 [28]. Harlequin syndrome can present in patients with venoarterial (VA) cannulation, where the heart has recovered but the lungs are still poorly functioning. The hallmark assessment finding for this is upper extremity cyanosis [28].
\nLeft femoral artery perfusion catheter in place providing flow from the arterial ECMO cannula to the left lower extremity.
Vessel perforation may take place on insertion; but, symptoms may not present immediately [28]. The most serious complication is a large retroperitoneal hematoma; but, considerable local bleeding at the insertion site is also possible, and site assessment, as well as assessment of the abdomen, flanks, and inguinal areas for ecchymosis, hypotension, and acutely worsening anemia, is necessary [28]. Additional assessment findings may include bulging or swelling at the insertion site, most consistent with pseudoaneurysm. Mild insertional hematomas may be mitigated and controlled by application of manual pressure, with subsequent monitoring of flows and distal pulses, both of which are imperative for clinical safety.
\nInfection is an associated risk of ECMO therapy as well and linked to greater likelihood of mortality. In one study, patients on ECMO experienced an overall mortality of 68.3:75.6% in patients with infections and 67.1% in patients without infections [30]. The use of steroids in acute respiratory distress syndrome (ARDS) or adrenal insufficiency, body temperature control, and multiple blood transfusions after cardiac operations for coagulopathy during ECMO can interfere with the presentation of infection in patients undergoing ECMO [30]. Thus, routine inspection and care of all invasive lines, including ECMO catheters, become integral. Implementing standard decolonization practices set forth by the nurse’s institution is appropriate for ECMO catheters, such as antimicrobial scrubs and occlusive dressings.
\nHospital-acquired pressure ulcers (HAPUs) are seen often in the intensive care setting and continue to be a significant financial burden within the healthcare system. The costs range anywhere from $500 to $70,000 per pressure ulcer and can cause length of stay (LOS) to increase by as much as 11 days [26]. While incidence of pressure ulcer development ranges per hospital and patient population, in a database of 710,626 patients, an estimated 3.6% of all patients within the adult critical care and step-down units developed a HAPU [31]. In the acute care setting, a range from 0.4 to 12% has been found [31]. Within the cardiac surgery patients which comprise a portion of patients on ECMO, pressure ulcer incidence as high as 29.5% occurs [26]. The consequences of these pressure ulcers often include infection leading to sepsis, increased pain, further disability, and sometimes death [26]. Although general risk factors such as age, immobility, poor nutritional status, altered sensory perception, moisture, diabetes mellitus, vascular disease, and other comorbidities have been identified, patients receiving ECMO support are also at an increased risk for pressure ulcer development due to multiple factors unique to this population [7, 26]. If patients do undergo cardiothoracic surgery, factors that increase the likelihood of a HAPU include cardiopulmonary bypass time, vasopressor therapy, and body temperature while in the operating room [26]. While on ECMO support, hemodynamic instability related to turning can inhibit appropriate prevention measures, leading to higher incidence of skin breakdown. Nurses can experience apprehension related to routine turning due to the potential of accidental decannulation or risk of worsening hemodynamic instability. High doses of multiple vasopressors that are utilized in patients newly placed on ECMO can lead to decreased peripheral perfusion and have also been shown to increase risk of HAPU. These risk factors make it essential to establish a dedicated skin care regimen for patients receiving ECMO support to prevent HAPU.
\nSkin care goals for patients receiving ECMO support should largely be similar to any patient that is in the intensive care setting. “At-risk” patients are identified by using a standardized risk screening tool such as the Braden Scale score and treated with stratified skin care interventions implemented based on severity of risk. Patients with a Braden Scale score of 14 or less (moderate to high risk) receive maximum interventions [31]. Patients need to be turned and repositioned every 2 h as tolerated. Turns should be scheduled and require a multidisciplinary team to ensure patient safety (perfusionist or respiratory therapist to hold ECMO cannulas, nurse for lines, etc.). For patients who do not tolerate a full turn, such as those who are hemodynamically unstable on ECMO, specialty beds have been shown to be very effective in reducing HAPU [20]. These rotation and pressure redistribution beds can be set to rotate every 30 min to different ranges as patients tolerate. Even subtle and small frequent position changes have been shown to reduce HAPUs [7]. Many facilities also use fluidized repositioning devices to offload pressure [31]. Silicone gel adhesive dressings should be utilized when possible and can be applied on the sacrum, elbows, and heels. Specialized heel-protective boots can also be used if available. Nutritional status also has a significant impact on the body’s ability to repair wounds. This makes dietitians an essential part of the treatment team to ensure these patients receive adequate nutrition in order to prevent skin breakdown and promote healing.
\nThere are multiple factors all contributing to this patient population’s increased risk of HAPU. Staff education, awareness, and motivation are essential in delivering the proper skin care measures in ECMO patients. When possible, a multidisciplinary skin care team can address each of the challenges present in this population to ensure that adequate prevention measures are being implemented.
\nEarly physical rehabilitation and mobility implemented in patients receiving ECMO support have been shown to significantly improve patient outcomes, including decreased LOS in the ICU and hospital, decreased rate of delirium, shorter durations of mechanical ventilation, decreased time to ambulation, increased function, and increased likelihood of returning home to family versus a rehabilitation facility [1, 36]. In spite of the obvious importance of early mobility in ECMO patients, there are limitations to this, particularly hemodynamic instability. The first 24–48 h after the initiation of ECMO are typically the most critical and often do not allow for aggressive physical therapy regardless of the type of ECMO. Most patients during this time are requiring the maximum amount of ventilatory and circulatory support. Eligibility for physical therapy is based upon hemodynamic stability and degree of mechanical and pharmacological support and is specific to each patient case.
\nHistorically, a dual-lumen ECMO catheter would occupy one vessel, usually the internal jugular vein, and provide veno-venous (VV)-ECMO through one cannulation site, allowing bridge-to-transplant patients to participate in early mobility more easily. This was optimal for ambulation because both lower extremities were free and the patients were seen as less high risk for accidental decannulation. However, recently there has been a significant push to mobilize all types of ECMO patients whether they are bridge-to-transplant patients or bridge-to-recovery patients, despite the location and type of cannulation. Whatever the level of physical therapy the patient can tolerate, whether this is passive range of motion or ambulation in the hallway has been shown to improve patient outcomes [1]. Typically, VV-ECMO patients are more stable than VA-ECMO patients, and thus bedside nurses are more comfortable with early mobility in these patients. Patients on VA-ECMO with bi-femoral cannulation are some of the most difficult to ambulate. Fear of accidental decannulation, risk of hemodynamic instability, and lack of training in the physical rehabilitation of these patients have all been barriers to early mobilization. However, the study at the University of Maryland demonstrates that physical mobility is safely possible regardless of the type of ECMO or cannulation site [36].
\nMany institutions who have an established ECMO program have developed a dedicated multidisciplinary team highly trained in the initiation of physical therapy for ECMO patients [36]. These teams typically include a physical therapist, one to two critical care nurses, a perfusionist or respiratory therapist, and a critical care attending physician. When assessing for eligibility, it is helpful to have a standardized screening tool [36]. The University of Maryland developed a protocol for the initiation of ECMO physical therapy [36]. The initial screening was composed of two parts: a medical screening and a physical therapy assessment [36]. The medical screening criteria included hemodynamic stability specific for each patient, coagulopathy: no bleeding at the cannulation site, stable ECMO flows with RN activities, a RASS goal of −1 to 0 with a range (−2 to +2), and stability of cannulation position [36]. The physical therapy assessment included vital signs, assessment of mental status, ECMO flow remaining stable (hip flexion with femoral cannulated lower extremities), and documented ECMO cannulation position [36]. If both of these screens were passed, then the patient met the criteria for further rehabilitation as tolerated [36]. The common physical therapy progression included bed activities/bed mobility such as passive range of motion and resistive training [36]. If that was well tolerated, then patients progressed to the edge of bed activities including balance training and pre-transfer activities [36]. Following this were sit-to-stand transfers, standing and pre-gait activities, and lastly ambulation [36]. Stabilization devices to secure the ECMO cannulas are recommended before physical therapy is initiated [1]. Adjustments on the sweep gas flow rates and increased oxygenation settings can be used during physical therapy based on clinician assessment [1].
\nIn the aforementioned study, 167 of the 254 patients supported on ECMO received physical therapy [36]. One hundred and thirty-four of those patients had at least one femoral cannula, while 66 patients had two, 44 of which were on VA-ECMO and 39 of whom were on VA-ECMO with bi-femoral cannulas. Only five patients had a dual-lumen catheter. Only three minor events were recorded during physical therapy: one episode of hypotension and two episodes of arrhythmias. Of the patients who received physical therapy, 109 patients survived hospital discharge, and 26 of those patients were discharged home. The patients who received physical therapy while on ECMO scored higher on their ICU mobility scale (IMS) than the ones who only received physical therapy after decannulation [36]. It is important to note that this was only possible due to a dedicated team of individuals specifically trained for the initiation and completion of physical therapy and mobility in ECMO patients and that the resources necessary to develop this type of team may not exist at all institutions who utilize ECMO support [36].
\nThe Society of Critical Care Medicine developed the ABCDEF (Assess, prevent, and manage pain; Both spontaneous awakening and breathing trials; Choice of analgesia and Sedation; Delirium assess, prevent, and manage; Early mobility and exercise; Family engagement/empowerment) bundle as an ICU Liberation Collaborative [25]. A recent study measured the success of this bundle on over 15,000 patients spread across 68 academic, community and federal intensive care units. Patients who received more of the ABCDEF bundle each day showed lower delirium rates, less use of physical restraints, decreased length of mechanical ventilation, avoidance of ICU readmission, increased instances of being discharged to home, and ultimately decreased mortality rates [25]. The significance of this bundle is that it can be applied to every ICU patient regardless of their diagnosis, including the ECMO patient population. Implementing the ABCDEF bundle on ECMO patients potentially increases the likelihood of returning to their baseline function sooner.
\nThe use of ECMO is accompanied by a myriad of potential complications across multiple body systems that are considered calculated risks upon initiation of therapy; however, without it, mortality may increase in conditions like severe acute heart failure [32]. A recent, international, randomized controlled trial (RCT) also suggests a potential mortality benefit with the use of ECMO in severe acute respiratory distress syndrome (ARDS); however, it was found to not be statistically significant [8]. There is abundant literature surrounding the complications of ECMO; but, despite these risks, survival to hospital discharge is greater than 50% [4, 12]. In one recent meta-analysis, the most frequently reported complications associated with ECMO include acute kidney injury (AKI), bleeding, and infection [6]. Specialized RNs have knowledge and understanding of potential complications related to ECMO therapy and can assist with early detection through critical thinking, performing frequent assessments, and reporting them through an open dialog with the team of providers involved.
\nThe incidence of acute kidney injury (AKI) has been reported as high as 80% of ECMO patients and is associated with a quadrupled mortality risk [13, 34]. Severe fluid overload is one of the major reasons that renal replacement therapy (RRT) is initiated in this population and is often performed through the ECMO circuit but can also be performed after the pump, which could lower the risk of air embolism not trapped by the oxygenator [34]. Fluid overload is independently associated with increased mortality, prolonged LOS, prolonged ventilator time, and prolonged ECMO time [13, 34].
\nThis consideration can lead providers to assume earlier RRT for therapeutic fluid removal would reduce these comorbidities; however, there is little data to suggest the efficacy of this. In fact, studies suggest increased mortality in ECMO patients who require RRT during their time on pump [16, 37]. Of ECMO patients who suffer AKI, an estimated 46% of survivors require RRT after ECMO is completed [6]. The bedside RN can assist in early identification of AKI by monitoring urine output; measuring strict fluid intake and output; assessing serial serum chemistry values, particularly serum creatinine and trends of electrolyte dyscrasias; and identifying physical exam findings consistent with fluid overload.
\nAbdominal compartment syndrome (ACS) is a known complication of ECMO [3]. This can be caused by massive fluid overload, which can be necessary to keep ECMO flows appropriate (read aforementioned suction events) [3]. This significantly positive fluid balance is associated with generalized edema, pleural effusions, and ascites, all of which are known to be causes of ACS. ACS can also compress femoral cannulas, thus diminishing the effectiveness of the ECMO therapy [28]. Clinical assessments significant for the monitoring of abdominal compartment syndrome include physical monitoring of abdomen for tension, distention (diameter), discoloration, and, if the technology is readily available, measurement of intraabdominal pressure.
\nBleeding is the most frequent complication associated with ECMO and affects approximately 30% of the patients receiving the therapy [2]. Bleeding may occur secondary to primary injury such as trauma and surgery or as a result of ECMO itself. Disruption of the red blood cell membrane leads to hemolysis, which is a common complication of patients on ECMO [11]. SIRS and contact between the patient’s blood and the ECMO circuit lead to activation of the coagulation cascade, affecting fibrinolysis, thrombin formation, and platelet function [2].
\nLarge amounts of bleeding will cause losses and consumption of coagulation factors and platelets, leading providers to believe that a heparin overdose may be occurring, thus decreasing the heparin, leading to acute thrombosis of the ECMO circuit or in other places where blood flow may be stagnant [22]. Thrombosis is mainly associated with VA-ECMO and can occur in the atria, ventricles, upper and lower extremity deep vein thrombosis (DVT), pulmonary vasculature, brain, or the ECMO circuit [22]. Unfractionated heparin (UFH) is well known, easily monitored, and easily reversible, allowing its frequent use managing hypercoagulability in the ECMO patient. Institutional guidelines vary; but, systemic anticoagulation with UFH infusion to target aPTT between 50 and 70, with some variations [2]. Despite ease of use, UFH can be associated with complications such as heparin-induced thrombocytopenia (HIT), further contributing to bleeding [22]. Alternatives such as warfarin, lepirudin, or argatroban may also be used in lieu of UFH for anticoagulation in the event of HIT [2]. The ECMO patient provides a unique challenge for providers, who must balance hypercoagulability with coagulopathy with careful but aggressive, administration of blood product transfusions and anticoagulants.
\nIt is clear that there is a litany of reasons the patient on ECMO may experience bleeding and bleeding often results in the need for transfusion. Adult patients on ECMO may require 2–3 units of packed red blood cells (PRBCs) and up to 14 units of plasma or cryoprecipitate daily [11]. Additionally, platelet counts of 45,000–60,000 count/μL are associated with mild to moderate bleeding [11]. Demands on bedside clinicians can be burdensome, as transfusion requirements have been reported to average 45 units of packed red blood cells transfused per adult ECMO patient [11].
\nLarge transfusion volumes are independently associated with increased mortality [11]; despite this, anticoagulation remains the standard practice in patients undergoing ECMO due to thrombotic complications [2]. With the significant risk for bleeding and the subsequent need for anticoagulation, nursing can expect regular and repeated blood draws, transfusions, and anticoagulant titration to be a part of their daily practice in the care of the ECMO patient.
\nA prospective, 1-day study identified approximately 50% of adult patients in over 1200 ICUs internationally whom were thought to have some form of infection, increasing ICU, and hospital mortality rates by over double that of patients without infection [35]. The literature suggests that from anywhere 13–26% of reported nosocomial infection rate in adults receiving ECMO (particularly VA-ECMO) is significantly associated with infection before initiation of ECMO, prolonged LOS, ECMO duration (particularly >10 days), and prolonged ventilator days [5, 14, 15, 30]. In the ICU patient, respiratory infections are most common; however, with the addition of ECMO, blood stream infections become most prominent [17, 35]. Other reported nosocomial events in ECMO patients include respiratory, urinary, and surgical site infections [17].
\nCare provided by the specialized RN remains inherently important in the prevention of infection, particularly when caring for lines and their cannulation sites with thorough hand, cannulation site, and patient hygiene and the application of impermeable site dressings. Protocols preventing ventilator-acquired pneumonia (VAP) are common practice and include interventions like hand hygiene, meticulous oral care with chlorhexidine gluconate solution, endotracheal tube cuff pressure control, and control of sedation [27]. Further management of routine line and cannulation site management are further discussed earlier in this chapter under Section 2.
\nCardiopulmonary complications are often resultant of high left ventricular (LV) afterload, especially on prolonged ECMO (particularly VA-ECMO), which can lead to pulmonary edema [21]. Other cardiac sequelae include aortic valve regurgitation, biventricular failure, and LV thrombus which have been treated with a variety of modalities including intra-aortic balloon pump (IABP) and other percutaneous and surgical procedures to shunt elevated LV pressures [24]. Additional lung complications significantly associated with ECMO include pulmonary hemorrhage, hemorrhagic pulmonary infarct, pulmonary calcifications, and fibrinous pleuritis [18]. The bedside RN can assist with early detection of these complications by close assessment of vasopressor and inotrope requirements, endotracheal secretions, monitoring the ventilator for peak and plateau pressures, and ensuring daily chest radiographs and frequent echocardiograms which are ordered to monitor progression of cardiopulmonary disease.
\nA study reviewing nearly 24,000 patients on ECMO revealed 10.9% of incidence of nearly equal prevalence of seizure, stroke, or intracranial hemorrhage (ICH) [23]. These patients who suffered ICH while on ECMO had increased mortality, while strokes and ICH alike both demonstrated increased LOS and increased likelihood of requiring placement in a skilled nursing facility (SNF) or long-term acute care hospital (LTACH) upon discharge [23]. Other sources suggest up to 50% of patients on ECMO demonstrate severe neurological sequelae [19]. Intracranial hemorrhage has been identified in as high as 40% of non-survivors of ECMO, and thrombotic events have been identified in approximately 15% of ECMO courses [2].
\nThe clinical suspicion for stroke may be obscured in ECMO patients given the multitude of other systemic or metabolic derangements usually encountered in ICU patients [19]. The bedside RN becomes integral to monitoring subtle neurologic indicators such as pupilometer and bi-spectral index, which can read zero in the event of catastrophic neurologic injury.
\nWith the advent of advancing ECMO technology comes an expanded library for indications of use. VA and VV support are commonly being utilized for bridge-to-transplant and respiratory or cardiac failure. Additionally, ECMO therapy is being utilized as bridge to support the body through a medical emergency in the form of extracorporeal cardiopulmonary resuscitation (ECPR). With the introduction of high-tech innovation, critical care nursing frequently encounters stressors due to resource scarcity, increased workloads, and moral distress related to carrying out aggressive life-sustaining treatments that may conflict with the patient’s best interests or maybe even personal preferences.
\nECMO is a costly, resource-intensive therapy requiring commitment from the patient, family, and multiple disciplines. The impact of caring for an ECMO patient puts a mental and physical strain, not only on the patient and family but the entire medical team involved in the patient’s care. Providing the intense, complex nursing care impacts not only the nursing staff or ECMO provider but the entire nursing unit caring for the patient. Institutions employing the use of ECMO in treating complex, critically ill patients as one of their only means of survival must have a process that addresses the moral and ethical dilemmas that arise from caring for the critically ill. Common questions are “Who receives ECMO treatment?”, “When should support cease?”, and “What is the goal of therapy, quantity or quality of life?”
\nAllocation of nursing resources has become undoubtedly one of the most challenging aspects in caring for patients and families. Nursing staff ratios, complexity of patients, and the mental and physical impact on the bedside nurse become compounded when one critically ill patient draws a majority of a unit’s resources. ECMO patients can begin their treatment with significantly unstable hemodynamic parameters requiring multiple blood transfusions, circulatory support with several vasoactive medications, and frequent lab draws pulling a majority of the nursing unit’s resources for the care of one patient. This places an enormous burden on the nursing staff to be creative and flexible with patient care assignments. RN:patient ratios may be less than desirable, ultimately impacting the care provided to other patients on the unit as well. Everyone, from the unit manger to housekeeping, plays a hands-on role in supporting the entire unit as well as the ECMO care team.
\nHow do we reduce some of the ethical or moral dilemmas nurses experience caring for complex, critically ill patients? Communication is the key in healthcare. An integral part of communication is developing and maintaining a team not isolated to healthcare workers but also including the patient and family. Early involvement of the palliative care team and social work is crucial to providing consistent support to the patient and family. Interdisciplinary daily rounds including the bedside nurse, family members, palliative care team, and social work are integral to find commonalities for all regarding goals of care. If conflict arises about treatment benefits or burden and the patient’s best interest is no longer being served, support from the ethics committee can be beneficial to the family and healthcare team. These are just the foundation. In critical care nursing, it is important that the nursing staff’s voice be heard. It is vital to recognize the nursing assessment of not just the patient but the situation and to be included in the decision-making that nurses are ultimately responsible for performing.
\nUnfortunately, despite a team’s best efforts, an ECMO patient may continue to decline, with multiple organ systems failing or a devastating systemic event. In such cases, withdrawing care may be imminent, and the question must be asked of the patient and family should be “is the patient’s preference quantity or quality of life?” Can the patient make their wishes known? In the case of bridge-to-transplant, patients may be able to make their wishes known to their families and healthcare team. For the critically ill patient who is dependent on their family or the healthcare team for their medical decisions, is this truly representative of what the patient’s wishes would be? Does conflict arise between the healthcare team and family regarding withdrawal of care? These questions are applicable in any situation involving ECMO; however, they cannot be answered algorithmically or methodically, as they need to be answered uniquely to each situation.
\nNurses are in a unique position in healthcare. They are at the bedside for 8- or 12-hour shifts as most consistent patient advocate. They support and inform family members and build personal and emotional bonds with them. Although valuable, this rapport can be morally taxing to the bedside RN. As nurses witness a patient and families suffering during clinical decline, they begin to question the continued aggressiveness of care that likely will not benefit from treatment, thus causing moral distress to the nursing staff. Sadness, frustration, and anxiety felt by the nursing staff for prolonged periods of time can lead to staff burnout, job dissatisfaction, and decreased staff retention.
\nThe ECMO patient is often the most critically ill within the hospital at any given moment, prompting highly trained bedside RNs as well as other healthcare providers, familiar with the therapy, to be readily available to provide the multifaceted care this population requires. In addition to routine ICU care, the ECMO patient necessitates additional monitoring due to associated risk factors assumed when being placed on pump. Medical, ethical, and emotional considerations exist and must be addressed regularly in order to provide the best care of this unique patient population. Despite high mortality associated with ECMO, the survivability continues to increase as time progresses and the bedside RN will continue to be responsible for vital functions in continuing that trend.
\nEdited by Jan Oxholm Gordeladze, ISBN 978-953-51-3020-8, Print ISBN 978-953-51-3019-2, 336 pages,
\nPublisher: IntechOpen
\nChapters published March 22, 2017 under CC BY 3.0 license
\nDOI: 10.5772/61430
\nEdited Volume
This book serves as a comprehensive survey of the impact of vitamin K2 on cellular functions and organ systems, indicating that vitamin K2 plays an important role in the differentiation/preservation of various cell phenotypes and as a stimulator and/or mediator of interorgan cross talk. Vitamin K2 binds to the transcription factor SXR/PXR, thus acting like a hormone (very much in the same manner as vitamin A and vitamin D). Therefore, vitamin K2 affects a multitude of organ systems, and it is reckoned to be one positive factor in bringing about "longevity" to the human body, e.g., supporting the functions/health of different organ systems, as well as correcting the functioning or even "curing" ailments striking several organs in our body.
\\n\\nChapter 1 Introductory Chapter: Vitamin K2 by Jan Oxholm Gordeladze
\\n\\nChapter 2 Vitamin K, SXR, and GGCX by Kotaro Azuma and Satoshi Inoue
\\n\\nChapter 3 Vitamin K2 Rich Food Products by Muhammad Yasin, Masood Sadiq Butt and Aurang Zeb
\\n\\nChapter 4 Menaquinones, Bacteria, and Foods: Vitamin K2 in the Diet by Barbara Walther and Magali Chollet
\\n\\nChapter 5 The Impact of Vitamin K2 on Energy Metabolism by Mona Møller, Serena Tonstad, Tone Bathen and Jan Oxholm Gordeladze
\\n\\nChapter 6 Vitamin K2 and Bone Health by Niels Erik Frandsen and Jan Oxholm Gordeladze
\\n\\nChapter 7 Vitamin K2 and its Impact on Tooth Epigenetics by Jan Oxholm Gordeladze, Maria A. Landin, Gaute Floer Johnsen, Håvard Jostein Haugen and Harald Osmundsen
\\n\\nChapter 8 Anti-Inflammatory Actions of Vitamin K by Stephen J. Hodges, Andrew A. Pitsillides, Lars M. Ytrebø and Robin Soper
\\n\\nChapter 9 Vitamin K2: Implications for Cardiovascular Health in the Context of Plant-Based Diets, with Applications for Prostate Health by Michael S. Donaldson
\\n\\nChapter 11 Vitamin K2 Facilitating Inter-Organ Cross-Talk by Jan O. Gordeladze, Håvard J. Haugen, Gaute Floer Johnsen and Mona Møller
\\n\\nChapter 13 Medicinal Chemistry of Vitamin K Derivatives and Metabolites by Shinya Fujii and Hiroyuki Kagechika
\\n"}]'},components:[{type:"htmlEditorComponent",content:'This book serves as a comprehensive survey of the impact of vitamin K2 on cellular functions and organ systems, indicating that vitamin K2 plays an important role in the differentiation/preservation of various cell phenotypes and as a stimulator and/or mediator of interorgan cross talk. Vitamin K2 binds to the transcription factor SXR/PXR, thus acting like a hormone (very much in the same manner as vitamin A and vitamin D). Therefore, vitamin K2 affects a multitude of organ systems, and it is reckoned to be one positive factor in bringing about "longevity" to the human body, e.g., supporting the functions/health of different organ systems, as well as correcting the functioning or even "curing" ailments striking several organs in our body.
\n\nChapter 1 Introductory Chapter: Vitamin K2 by Jan Oxholm Gordeladze
\n\nChapter 2 Vitamin K, SXR, and GGCX by Kotaro Azuma and Satoshi Inoue
\n\nChapter 3 Vitamin K2 Rich Food Products by Muhammad Yasin, Masood Sadiq Butt and Aurang Zeb
\n\nChapter 4 Menaquinones, Bacteria, and Foods: Vitamin K2 in the Diet by Barbara Walther and Magali Chollet
\n\nChapter 5 The Impact of Vitamin K2 on Energy Metabolism by Mona Møller, Serena Tonstad, Tone Bathen and Jan Oxholm Gordeladze
\n\nChapter 6 Vitamin K2 and Bone Health by Niels Erik Frandsen and Jan Oxholm Gordeladze
\n\nChapter 7 Vitamin K2 and its Impact on Tooth Epigenetics by Jan Oxholm Gordeladze, Maria A. Landin, Gaute Floer Johnsen, Håvard Jostein Haugen and Harald Osmundsen
\n\nChapter 8 Anti-Inflammatory Actions of Vitamin K by Stephen J. Hodges, Andrew A. Pitsillides, Lars M. Ytrebø and Robin Soper
\n\nChapter 9 Vitamin K2: Implications for Cardiovascular Health in the Context of Plant-Based Diets, with Applications for Prostate Health by Michael S. Donaldson
\n\nChapter 11 Vitamin K2 Facilitating Inter-Organ Cross-Talk by Jan O. Gordeladze, Håvard J. Haugen, Gaute Floer Johnsen and Mona Møller
\n\nChapter 13 Medicinal Chemistry of Vitamin K Derivatives and Metabolites by Shinya Fujii and Hiroyuki Kagechika
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I am also a member of the team in charge for the supervision of Ph.D. students in the fields of development of silicon based planar waveguide sensor devices, study of inelastic electron tunnelling in planar tunnelling nanostructures for sensing applications and development of organotellurium(IV) compounds for semiconductor applications. I am a specialist in data analysis techniques and nanosurface structure. 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Today his focus is on defining the growth and development strategy for the company.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"19816",title:"Prof.",name:"Alexander",middleName:null,surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/19816/images/1607_n.jpg",biography:"Alexander I. Kokorin: born: 1947, Moscow; DSc., PhD; Principal Research Fellow (Research Professor) of Department of Kinetics and Catalysis, N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow.\nArea of research interests: physical chemistry of complex-organized molecular and nanosized systems, including polymer-metal complexes; the surface of doped oxide semiconductors. 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