A Response to: Letter to the Editor Regarding “Neurophysiological Assessments During Continuous Sedation Until Death Put Validity of Observational Assessments Into Question: A Prospective Observational Study”
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Abstract
To the Editor,
We would like to thank Prod’homme and colleagues for their thoughtful comments on
our publication [1]. Their observations have prompted us to further clarify some aspects
of this work.
We agree with their first comment, indicating that the available data on ANI monitoring
in the palliative population are too limited to consider it as a new golden standard.
Indeed, more research is needed. The use of ANI monitoring in this population is still
a new development and the primary goal of our research was to assess whether or not
clinical observational assessments concur with neurophysiological monitoring. We included
both caregiver assessments, assessments by established observational tools and neurophysiological
indices of discomfort (ANI), and depth of sedation (WAVcns). Our results showed a
poor correlation, which led us to conclude that the validity of observational assessments
in this particular patient group needs to be further scrutinized. We would like to
reiterate that the medication used to induce continuous sedation until death (CSD)
also has an impact on motor responsiveness, while the traditionally used observation
scales, as well as clinical assessments, mainly reside on inferences from the patient’s
responsiveness and may therefore not be entirely reliable. Assessing awareness more
independently from (the assessment of) motor responsiveness may therefore contribute
to the quality of assessments of comfort during continuous sedation until death [2].
We further agree that neurophysiological correlates of depth of sedation and discomfort
always need interpretation by a skilled caregiver; a correlate is not the same as
the object it measures and additional research can help in clarifying different factors
involved. In our study, we did not recommend using WAVcns- and ANI-monitoring as standalone
measures, but as a top up besides clinical judgement and a tool to be included for
guiding treatment decisions so that the principle of proportionality regarding titration
of medication can be adhered to as good as currently possible [1, p. 386].
Our use of the term “objective” is meant to indicate that the numerical values of
a monitoring device do not depend on a subjective appraisal, as is the case with behavior-based
observation scales (and the problems associated with that, such as interrater disagreements,
lack of validated tools for use in CSD etc.) [3]. Of course, these monitor values
need to be interpreted as well, which is usually the case in medicine when correlates
are used. As we mentioned in the discussion section of our publication, our epistemological
stance is that for this particular problem (which is related to the hard problem of
consciousness) falsification of the hypothesis is not possible, and therefore we have
to make inferences based on our results, taking into account the results of other
studies where closely related research was carried out. These other studies suggest
that (1) neurophysiological monitoring of the level of consciousness by WAVcns, and
pain/discomfort by ANI, is more “objective” than behavior based observational tools
and (2) that these neurophysiological measures can more reliably detect insufficient
sedation and exclude the possibility of significant pain [4, 5].
Further, Prod’homme et al. mention that ANI measures not only pain but is also influenced
by stress and anxiety, and can be considered as a vagal tone index. Although studies
have shown that pain can be detected by ANI, we do agree that ANI is not restricted
to only pain detection. That’s why we, throughout our manuscript and on several occasions,
used the term ‘pain/discomfort’. In a context of continuous palliative sedation until
death, and within the concept of total pain, we believe it makes more sense to not
only exclude the possible presence of (nociceptive) pain, but also discomfort such
as stress and anxiety as well. The suggestion that when ANI is low, both pain-relief
and anxiolytic treatments should be adjusted seems to make sense in that regard.
It may be interesting to make the parallelism between the consciousness states potentially
encountered during anesthesia, and those seen during end-of-life deep sedation. General
anesthesia alters consciousness in a reversible way and, depending on the type of
medication, may produce different states of consciousness. These include (1) complete
absence of subjective experience (unconsciousness), (2) conscious experience without
perception of the environment (disconnected consciousness, like during dreaming),
and (3) episodes of oriented consciousness with awareness of the environment (connected
consciousness) [6]. During end-of-life deep sedation, recall cannot be assessed afterwards
(as with general anesthesia), but unpleasant disconnected consciousness episodes (e.g.,
nightmares) may potentially occur. This is difficult to assess in a non-communicative
dying patient but detecting them and adapt sedation to avoid them could be a goal
to further improve comfort in this situation [6]. We consider this as an important
argument for also measuring depth of sedation in this context by using a processed
EEG monitor (such as the NeuroSense in our study). In addition, as Prod’homme et al.
rightly point out, an ANI monitor cannot detect neuropathic pain, and therefore depth
of sedation should also be measured, as we did in this study, to allow a broader assessment
of pain and discomfort and to ensure that no undetected residual pain (whether nociceptive
or neuropathic) can be present or possibly consciously experienced.
Regarding the comment about the complementarity of clinical hetero-assessment by family
and caregivers and ANI assessment, claiming that neither is superior to the other,
we feel more research is still needed to clarify this. It is still unclear how some
of these assessment methods relate to each other; for example, previous research has
shown that family members tend to overestimate pain in a loved one, while caregivers
tend to underestimate pain [7]. Other factors such as cultural values and norms regarding
pain and dying, and intergenerational differences could play a role as well [8, 9].
The time has indeed come to introduce various monitoring techniques as standard care
to support medical decision-making and hetero-evaluation during continuous sedation
until death. The final goal regarding comfort assessment during continuous sedation
until death should be objective monitoring of both absence of pain and optimal sedation,
thereby strengthening hetero-evaluation, which will ultimately lead to better care
for the terminally ill patient. This article is based on previously conducted studies
and does not contain any new studies with human participants or animals performed
by any of the authors.
General anesthesia reversibly alters consciousness, without shutting down the brain globally. Depending on the anesthetic agent and dose, it may produce different consciousness states including a complete absence of subjective experience (unconsciousness), a conscious experience without perception of the environment (disconnected consciousness, like during dreaming), or episodes of oriented consciousness with awareness of the environment (connected consciousness). Each consciousness state may potentially be followed by explicit or implicit memories after the procedure. In this respect, anesthesia can be considered as a proxy to explore consciousness. During the recent years, progress in the exploration of brain function has allowed a better understanding of the neural correlates of consciousness, and of their alterations during anesthesia. Several changes in functional and effective between-region brain connectivity, consciousness network topology, and spatio-temporal dynamics of between-region interactions have been evidenced during anesthesia. Despite a set of effects that are common to many anesthetic agents, it is still uneasy to draw a comprehensive picture of the precise cascades during general anesthesia. Several questions remain unsolved, including the exact identification of the neural substrate of consciousness and its components, the detection of specific consciousness states in unresponsive patients and their associated memory processes, the processing of sensory information during anesthesia, the pharmacodynamic interactions between anesthetic agents, the direction-dependent hysteresis phenomenon during the transitions between consciousness states, the mechanisms of cognitive alterations that follow an anesthetic procedure, the identification of an eventual unitary mechanism of anesthesia-induced alteration of consciousness, the relationship between network effects and the biochemical or sleep-wake cycle targets of anesthetic agents, as well as the vast between-studies variations in dose and administration mode, leading to difficulties in between-studies comparisons. In this narrative review, we draw the picture of the current state of knowledge in anesthesia-induced unconsciousness, from insights gathered on propofol, halogenated vapors, ketamine, dexmedetomidine, benzodiazepines and xenon. We also describe how anesthesia can help understanding consciousness, we develop the above-mentioned unresolved questions, and propose tracks for future research.
Behavioural pain tools are used in Intensive Care Unit (ICU) patients unable to self-report their pain-intensity but need sustained efforts to educate and train the ICU team because of the subjective nature of these clinical tools. This study measured the validity and performance of an electrophysiological monitoring tool based on the spectral analysis of heart rate variability, the Analgesia Nociception Index (ANI) which varies from 0 (minimal parasympathetic tone, maximal stress-response and pain) to 100 (maximal parasympathetic tone, minimal stress-response and pain).
[1
]GRID grid.8767.e, ISNI 0000 0001 2290 8069, Mental Health and Wellbeing Research Group, , Vrije Universiteit Brussel, ; Laarbeeklaan 103, 1090 Jette, Belgium
[2
]GRID grid.8767.e, ISNI 0000 0001 2290 8069, Department of Anesthesiology and Perioperative Medicine, , Vrije Universiteit Brussel, ; Laarbeeklaan 103, 1090 Jette, Belgium
[3
]GRID grid.411374.4, ISNI 0000 0000 8607 6858, Coma Science Group, Cyclotron Research Centre and Neurology Department, , University and University Hospital of Liège, ; Avenue de l’hôpital 11, 4000 Liège, Belgium
[4
]GRID grid.8767.e, ISNI 0000 0001 2290 8069, Department of Experimental and Applied Psychology, , Vrije Universiteit Brussel, ; Pleinlaan 2, 1000 Brussels, Belgium
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