288 ANAESTHESIOLOGY, INTENSIVE CARE Zdrav Vestn | May – June 2021 | Volume 90 | https://doi.org/10.6016/ZdravVestn.3055 Department of Anaesthesiology, Intensive Therapy and Pain Therapy, University Medical Centre Maribor, Maribor, Slovenia Correspondence/ Korespondenca: Andreja Möller Petrun, e: andreja.mollerpetrun@ ukc-mb.si Key words: pain measurement; confusion; fear; sleeplessness; intensive therapy Ključne besede: merjenje bolečine; zmedenost; strah; nespečnost; intenzivna terapija Received: 26. 3. 2020 Accepted: 10. 11. 2020 eng slo element en article-lang 10.6016/ZdravVestn.3055 doi 26.3.2020 date-received 10.11.2020 date-accepted Anaesthesiology, intensive care Anesteziologija, intenzivna nega discipline Professional article Strokovni članek article-type Assessment of analgesia, sedation, delirium and sleep disturbance in the intensive care therapy unit and description of non-pharma- cological interventions Ocenjevanje analgezije, sedacije, delirija in motenj spanja v enoti intenzivne terapije ter opis nefarmakoloških ukrepov article-title Wellbeing assessment of critical ill patient and non-pharmacological treatment Ocena počutja kritično bolnega ter nefarmakološ- ki ukrepi alt-title pain measurement, confusion, fear, sleepless- ness, intensive therapy merjenje bolečine, zmedenost, strah, nespečnost, intenzivna terapija kwd-group The authors declare that there are no conflicts of interest present. Avtorji so izjavili, da ne obstajajo nobeni konkurenčni interesi. conflict year volume first month last month first page last page 2021 90 5 6 288 306 name surname aff email Andreja Möller Petrun 1 andreja.mollerpetrun@ukc-mb.si name surname aff eng slo aff-id Department of Anaesthesiology, Intensive Therapy and Pain Therapy, University Medical Centre Maribor, Maribor, Slovenia Oddelek za anesteziologijo, intenzivno terapijo in terapijo bolečine, Univerzitetni klinični center Maribor, Maribor, Slovenija 1 Assessment of analgesia, sedation, delirium and sleep disturbance in the intensive therapy unit and description of non- pharmacological interventions Ocenjevanje analgezije, sedacije, delirija in motenj spanja v enoti intenzivne terapije ter opis nefarmakoloških ukrepov Andreja Möller Petrun Abstract Treatment in the intensive therapy unit is very stressful for most patients. It has an important im- pact on their quality of life and can have long-term consequences. Among others, there are serious complaints such as pain, fear, sleeplessness, thirst, helplessness, fatigue, confusion and agitation. These all can exert adverse impact on the therapy process and clinical outcome. Patients often develop delirium, which is not only a great burden for the patient but also for the personnel caring for the patient. Delirium also has a long-term negative impact on the patient’s cognitive functions. Medical staff has a great responsibility for detecting and dealing with these problems, especially in patients with limited cognitive functions or impaired communication ability. There are different tools for the assessment of pain, sedation, delirium and sleep quality. In this article, we describe the most frequently used validated scoring systems for the assessment of pain, sedation, delirium and sleep disturbance. Furthermore, the non-pharmacological approach is described. Izvleček Za bolnike je zdravljenje v enoti intenzivne terapije v veliki večini primerov zelo stresno obdobje, ki pomembno poseže v kakovost njihovega življenja in lahko pusti dolgotrajne posledice. Bo- lečine, strah, nespečnost, žeja, nemoč, utrujenost, zmedenost, vznemirjenost so resne težave, ki lahko pomembno vplivajo na potek in izid zdravljenja. Pogosto se pri takih bolnikih razvije še delirij, ki pomeni veliko obremenitev tako za bolnika kot za osebje, ki zanj skrbi. Delirij lahko dolgoročno negativno vpliva na bolnikove spoznavne funkcije. Medicinsko osebje nosi veliko od- govornost pri prepoznavanju in reševanju bolnikovih težav, še posebej pri bolnikih z omejenimi spoznavnimi funkcijami oziroma z omejeno sposobnostjo sporazumevanja. Poznamo različna orodja za ocenjevanje bolečine, sedacije, delirija in kakovosti spanja. V prispevku so natančneje opisani najpogosteje uporabljani validirani točkovniki za oceno bolečine, sedacije, delirija in mo- tenj spanja. Na koncu so opisane tudi možnosti nefarmakološkega ukrepanja. Cite as/Citirajte kot: Möller Petrun A. Assessment of analgesia, sedation, delirium and sleep disturbance in the intensive therapy unit and description of non-pharmacological interventions. Zdrav Vestn. 2021;90(5– 6):288–306. DOI: https://doi.org/10.6016/ZdravVestn.3055 Copyright (c) 2021 Slovenian Medical Journal. This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. Slovenian Medical Journal 289 PROFESSIONAL ARTICLE Wellbeing assessment of critical ill patient and non-pharmacological treatment 1 Introduction In addition to the underlying disease, critically ill patients in the intensive thera- py unit (ITU) also have problems that are more difficult to evaluate and therefore easier to overlook. During treatment in the ITU, patients suffer from insomnia, fa- tigue, thirst, pain, stress, fear, helplessness, noise, confusion (1). Three months after being treated in the ITU, 40% of patients report confusion and disorientation, as well as impaired cog- nitive functions. This condition persists in 24–34% of patients for longer than a year (2). 25–33% also have post-traumatic stress disorder (PTSD) after one year (3). According to data from the literature, the incidence of PTSD is higher in those who were sedated for a longer period of time (3,4). Risk factors for the development of PTSD include the use of benzodiazepines, fear, isolation for hygienic reasons, de- pendence on replacement therapy due to failure of one or more organs (e.g. haemo- dialysis, mechanical ventilation, and ex- tracorporeal membrane oxygenation) (5). To reduce or prevent all side effects in critically ill patients, it is extremely im- portant to identify and assess pain, se- dation, fear, delirium, stress and other phenomena. In 2015, extensive updated guidelines were published by the German Association for Anaesthesiology and Intensive Care (Deutsche Gesellschaft für Anästhesiologie und Intensivmedizin, DGAI) and the German Interdisciplinary Association for Intensive and Emergency Medicine (Deutsche Interdisziplinäre Vereinigung für Intensiv- und Notfallmedizin, DIVI), and in 2018, the Society of Critical Care Medicine (SCCM) published the updated American guidelines (6,7). According to the cited literature, the German guidelines are the most comprehensive of their kind, and are currently in the process of being updated. Both guidelines provide recommenda- tions for identifying, preventing and treat- ing pain, agitation/sedation, delirium, sleep disturbances, stress, and fear. This article describes the most com- mon tools for assessing pain, sedation, delirium and sleep disorders, and possible non-pharmacological measures. 2 Assessment of sedation, analgesia, stress, sleep disorders and delirium Therapeutic concepts in intensive care medicine must be patient-oriented and must include goals that are tailored to each individual (6). Achieving the goals first requires an appropriate assessment of the patient’s problems (e.g. pain) and then an assessment of the effects of the treat- ment. Nurses and physicians carry a great responsibility of properly assessing the pa- tient’s condition, comfort, well-being, and the appropriate action. One and the other are a dynamic process, as action needs to be constantly adapted to the results of the assessment. Regular assessment of deliri- um, pain, fear and other problems should be as self-evident as, for example, the long-established control of haemodynam- ics. Assessment of sedation, analgesia and occurrence of delirium with the help of validated scoring systems should provide guidance for the adjustment of therapy to the individual patient, and assessments should be regularly recorded in medical records (6,7). The goal is to optimize the patient’s health condition and well-be- ing, while avoiding too low or too high a dose of medication as well as reducing the accompanying side effects of these medi- cations. A multidisciplinary approach to 290 ANAESTHESIOLOGY, INTENSIVE CARE Zdrav Vestn | May – June 2021 | Volume 90 | https://doi.org/10.6016/ZdravVestn.3055 analgesia and sedation has been shown to reduce the duration of mechanical venti- lation, nosocomial infections, ITU treat- ment, mortality and treatment costs (8,9). There are various validated scoring systems for monitoring and assessing the depth or adequacy of sedation and anal- gesia and the assessment of delirium. The German guidelines recommend assessing and recording the adequacy of analgesia, sedation and signs of delirium at least once per shift (every 8 hours). The draft- ers of these guidelines are of the opinion, however, that it is not so important which validated scoring system is used. It is more important that the evaluation is carried out on a regular basis (6). In a 1995 study, 75% of patients reported inadequate anal- gesia during treatment at the ITU, while 80% of their physicians were mistaken in believing that their patients had satisfac- tory analgesia (10). 3 Assessment of pain and adequacy of analgesia Pain is the symptom that patients and their relatives fear the most. Pain is a very individual symptom. Patients may have acute and/or chronic pain, but chronic pain may worsen. Depending on the origin, the pain can be visceral, somatic, neuropathic, or a mixture of all of the above. Individual patients experience and tolerate pain very differently. By definition, it is an unpleas- ant sensory and emotional experience that may be associated with existing or poten- tial tissue damage, and the presence of the latter is not necessary for the sensation of pain (11). Critically ill patients suffer from pain both while resting and during proce- dures (1,7). The experience of pain while resting is negatively affected by psycho- logical factors (e.g. fear and depression) and demographic factors such as youth, associated illnesses, previous surgeries, and chronic use of analgesics, especially opioids. Pain during the procedure de- pends on the type of procedure, previous pain, recent surgery, or injury. Severe pain is usually experienced by younger people, women and non-white people (6,7,12). According to patients, the most painful procedures performed during treatment in the ITU include: insertion of an arterial cannula, removal of a chest drain, removal of a wound drain, turning and placement in bed, and suction of secretions (aspiration) from the trachea (7). Severe pain during the procedure can also cause serious side effects: a marked decrease or increase in heart rate and/or blood pressure, and a dangerous decrease in arterial blood ox- ygen saturation (13). Due to the great in- fluence of the subjective experience of pain and its multidimensionality, there is no universal scale for assessing pain. The first rule is that the patient must be trusted! In the literature, the most recommended scale to assess pain and adequacy of analgesia in patients who are able to express themselves independently is the visually enlarged lam- inated Numeric  Rating  Scale  (NRS-V). With the help of the NRS-V, the patient rates the pain from 0–10 (14). The NRS-V has the highest negative predictive value of all pain self-assessment scales; it is a one-dimensional scale (14). Twinning et al. have embarked on a multidimensional approach to pain assessment that is slowly penetrating clinical practice abroad. It is a Clinically Aligned Pain Assessment tool (CAPA tool), the components of which are shown in Table 1 (15). This tool should facilitate communication between the patient experiencing pain and his or her caregivers. Using the pain assessment from different angles should thus reduce dis- satisfaction on both sides: the patient can manage pain better and the staff are more satisfied with the efficiency and quality of their work (16). 291 PROFESSIONAL ARTICLE Wellbeing assessment of critical ill patient and non-pharmacological treatment It is significantly more difficult to as- sess the pain and adequacy of analgesia in sedentary patients and in patients with limited cognitive functions or limited ability to communicate. In such patients, a third-party assessment is required. The staff must be properly trained to assess pain, because the reliability of pain assess- ment is essential (17). On the one hand, pain is often underestimated, and on the other hand, analgesics have clinically im- portant side effects (nausea, vomiting, constipation). All this needs to be recog- nized, recorded and acted upon. It is even better to prevent side effects if at all possi- ble (18). The most commonly used assess- ments in these cases are: The Behavioural Pain Scale (BPS) with the version for in- tubated and non-intubated patients, the Area Responses Comfort intolerable tolerable with great discomfort relative comfort that can be improved negligible pain Change in Pain the pain gets worse the pain does not change the pain decreases Pain Relief insufficient in part enough Functioning can’t do anything because of pain pain keeps me from doing most of what I need to do can do most things, but pain gets in the way of some can do everything I need to do Sleep awake with pain most of the night awake with occasional pain normal sleep Table 1: Clinically Aligned Pain Assessment tool, CAPA tool. Adapted from Twinning et al., 2019 (15). components of which are shown in Table 2, and the Critical Care Pain Observational Tool (CPOT) shown in Table 3 (6,7,19,20). Both scales are expected to be equivalent in terms of predictive value (21-23). At this point, I would like to specifically mention the problem of patients with head injuries, as research on pain assessment using these scales has been done in a small number of such patients. And what is more, often no grimacing and muscle rigidity are ob- served in such patients (7). However, the American guidelines nonetheless recom- mend the use of BPS or CPOT even in se- vere head injury (7,24). Changes in physiological variables (e.g. heart rate, blood pressure…) should not be the sole criterion for assessing pain because they coincide very poorly with the degree and experience of pain. However, they are an important warning sign for staff that something is going on with the patient; it can also be a consequence of pain (7). It is practically impossible, however, to reli- ably assess pain in deeply sedated patients. Despite some promising results, currently reliable objective measurement methods for assessing analgesia (e.g. measurement of skin resistance, pupillometry, heart rate variability…) are not yet available due to a number of interfering factors. Further re- search is needed to clarify their reliability (7,25). The American guidelines also men- tion the possibility of assessing a relative’s pain. However, there is currently no good evidence in the literature for the reliability of pain assessment using this method (7). 4 Assessment of sedation In order to reduce the feeling of fear, anxiety, stress, discomfort during mechan- ical ventilation, agitation or even aggres- sion in patients, various drugs with sed- ative effects (sedatives) are often used in the ITU. Sedatives have a number of side 292 ANAESTHESIOLOGY, INTENSIVE CARE Zdrav Vestn | May – June 2021 | Volume 90 | https://doi.org/10.6016/ZdravVestn.3055 effects associated with many complications and increased morbidity and thus patient mortality (7,28). In addition to complica- tions in the cardiovascular system, pro- longed need for mechanical ventilation, and undesirable drug interactions, patients often have short-term and long-term con- sequences in terms of mental problems, reduced cognitive functions and poorer locomotor rehabilitation (7,29). The deci- sion to sedate should always be based on appropriate indications. The target depth of sedation and its duration must be clear- ly defined. It is necessary to check the need for sedation at least once a day and Indicator Description Score Facial expression Relaxed 1 Partially tightened (e.g. brow lowering) 2 Fully tightened (e.g. eyelid closing) 3 Grimacing 4 Upper limbs No movement 1 Partially bent 2 Fully bent with finger flexion 3 Permanently retracted 4 Compliance with the ventilator (intubated) or Tolerating movement 1 Coughing while moving 2 Cannot bear (“fights”) the ventilator 3 Ventilation is impossible 4 Vocalization (extubated) Does not vocalize due to pain 1 Moaning ≤ 3 times/min and ≤ 3s 2 Moaning > 3 times/min and > 3s 3 Crying or verbally expressing him-/herself, including “ow” or holds breath > 3s. 4 Table 2: Behavioural Pain Scale (BPS) for patients with or without intubation (non-intubated). Adapted from Aissaoui et al., 2005 (27). Note: The goal of satisfactory analgesia is for the patient to score less than 6 points. In patients with a ventilator (intubated), compliance with the ventilator is assessed, and in those without it (extubated) vocalization is assessed. determine the target depth of sedation for an individual patient at a specific time. It is recommended to check the depth of se- dation and achieve the target sedation at least once in each shift, which should also be recorded in the patient’s documentation (6). The American and German guide- lines recommend mild sedation in criti- cally ill patients who require mechanical ventilation (6,7). In practice, we are faced with the problem of the concept of mild, moderate and deep sedation not being clearly defined (7). Mild sedation is gen- erally considered when a patient scores –2 to +1 points on the most commonly used Richmond Agitation-Sedation Scale (RASS) (Table 4) (7). There is also no clear connection between the type of sedative, the depth of sedation and the physiological or genetic characteristics of the individual patient. It is not clear what the relationship is between the depth of sedation and the ability to assess pain, delirium and sleep quality (7). Data from recent meta-analy- ses do not confirm the advantage of a daily sedation cessation protocol (reduction of sedative dosing during the day to achieve the RASS score of -1 to +1 in a patient) over protocol-based sedation depth adjust- ment (sedatives are dosed to reach a pre- agreed target sedation depth, according to the RASS, for example) (7,30). The authors of the American guidelines believe that both of the above-mentioned options for achieving mild sedation are comparatively safe. At the same time, they note that most studies comparing the two options have been conducted with benzodiazepines, which are no longer recommended as the first choice among sedatives. They also note that the protocol of daily cessation of sedation is associated with a greater work- load of staff, and at the same time, such a protocol should not be an excuse for the sedation being too deep in the afternoon and at night (7,31). 293 PROFESSIONAL ARTICLE Wellbeing assessment of critical ill patient and non-pharmacological treatment There are various scoring systems for controlling the depth of sedation. The most reliable and validated is the Richmond Agitation-Sedation Scale (RASS), which is recommended by both the German and the American guidelines (6,7,32). Other scales may also be used, e.g. the RAMSAY Sedation Scale (RSS) and others, like the Sedation-Agitation Scale (SAS) and Motor Activity Assessment Scale (MAAS) (6). To control deep sedation, there are ob- jective measurement methods that have Indicator Score Description Facial expression Relaxed, neutral 0 No muscle tension observed Tense 1 Frowning, brow lowering, orbit tightening, facial tension, opening eyes or tearing during painful procedures Grimacing 2 All signs above plus eyelid tightly closed (mouth may be open or biting the tube) Body movement Absence of movements, normal position 0 Does not move at all (does NOT necessarily mean absence of pain) or normal position (movements not aimed toward the pain site, not made for the purpose of protection) Protective posture – careful movements 1 Slow, cautious movements, touching, rubbing the pain site, seeking attention through movements Restlessness, agitation 2 Pulling tube, attempting to sit up, trying to climb out of bed, moving limbs, not following commands, striking at staff Compliance with the ventilator (intubated) or Tolerating ventilator and movement 0 Alarms not activated, easy ventilation Coughing, but tolerating ventilation and movement 1 Coughing, alarms may be activated but stop spontaneously Fighting the ventilator 2 Asynchrony: blocking ventilation, alarms frequently activated Vocalization (extubated) Talking in normal tone 0 Talking in normal tone or no sound Sighing, moaning 1 Sighing, moaning Screaming, crying, sobbing 2 Screaming, crying, sobbing Muscle tension Relaxed 0 No resistance to passive movements Tense, rigid 1 Resistance to passive movements Very tense or rigid 2 Strong resistance to passive movements or incapacity to complete them Total: __________ / 8 Table 3: Critical-Care Pain Observational Tool (CPOT) in ITU. Adapted from Gellinas C et al., 2006 (26). Note: The goal of satisfactory analgesia is for the patient to collect ≤ 2 points. In patients with a breathing tube (intubated), compliance with the ventilator is assessed, and in those without it (extubated) vocalization is assessed. certain shortcomings. Deep sedation is rarely required in clinical practice (in- creased intracranial pressure, tetanus) (6). Different monitors are available that capture the EEG and convert it to differ- ent indexes (e.g. a BIS monitor) (6). The American guidelines express the opinion that, according to data from the litera- ture, a BIS monitor is probably currently the best option for monitoring deep se- dation. In addition to the limitations of the BIS monitor itself, the problem is the 294 ANAESTHESIOLOGY, INTENSIVE CARE Zdrav Vestn | May – June 2021 | Volume 90 | https://doi.org/10.6016/ZdravVestn.3055 non-standardized methodology of various studies comparing the BIS monitor with rating scales. The problem of EEG signal processing is in many factors that interfere with the capturing of the relevant signal and are difficult to avoid in the ITU (e.g. patient care, other devices that interfere with the EEG signal, noise) (34). It is al- so possible to measure the raw EEG. The problem is reading the EEG, as only a few can master it. The raw EEG measurement is recommended in cases where the cause of impaired consciousness is unknown (6). In particular, it can be used to confirm or rule out non-convulsive status epilep- ticus, which, according to data from the literature, occurs in approximately 20% of cases of impaired consciousness of criti- cally ill patients (35). It makes sense to use the sedation depth control in the ITU as a complementary method of subjective as- sessment to avoid the sedation being too deep. When using monitors to measure the depth of sedation, we must always keep in mind the possible influence of ex- ternal interfering factors (6,7). 5 Assessing the presence of delirium It often happens that an ITU patient develops delirium (36). This is an acute disorder of attention with a disorder of consciousness, perception and thinking as a consequence of disease activity in any organ system (37). It can be accompanied by a number of other nonspecific symp- toms (38). The diagnosis is made on the basis of the clinical picture. It is basical- ly a reversible state of brain dysfunction. Delirium is the result of the concomitant action of various factors that may have been present even before admission to the ITU. Factors are divided into basic factors related to various interventions within the treatment, and psychological, social and environmental factors (38,39). The basic factors include previous illnesses, previous cognitive deficits, dementia, increasing age, alcoholism and dependence on other psychoactive substances, pre-existing de- pression, severity of acute illness, chron- ic pain, current limitations in mobility or immobility (38,40,41). Factors associated with various interventions include blood transfusion, recent emergency surgical and other invasive procedures, recent injuries, depth and duration of sedation, use of an- ticholinergics, benzodiazepines, antipsy- chotics, and anticonvulsants (7,28,42,43). When delirium occurs, it is important to look for and treat possible causes such as infection, hypoxia, hypoperfusion, post-withdrawal condition, metabolic and endocrine disorders (43,44). According to recent literature, gender, the use of opioid Score Term Description + 4 Combative Presents immediate danger to him-/herself and staff + 4 Very agitated Pulls or removes the breathing tube or catheter, is aggressive towards staff + 2 Agitated Frequent non-purposeful movement or non-synchronized mechanical ventilation (“fights ventilator”) or non-synchronized breathing during mechanical ventilation + 1 Restless Anxious, but movements not aggressive or vigorous 0 Alert and calm – 1 Sleepy, drowsy Not fully alert, but has sustained awakening (>10 s), eye contact to voice – 2 Light sedation Briefly awakens (<10 s), eye contact to voice – 3 Moderate sedation Movement without eye contact to voice – 4 Deep sedation No response to voice, movement to physical stimulation – 5 Unarousable No response to voice or physical stimulation Table 4: Richmond-Agitation-Sedation-Scale (RASS). Adapted from Sessler et al., 2001 (33). 295 PROFESSIONAL ARTICLE Wellbeing assessment of critical ill patient and non-pharmacological treatment analgesics, and mechanical ventilation have not been associated with an increased risk of delirium (7). In the literature, there is a large range in the occurrence of delirium (30–80%), which differs according to the examined groups of patients (45,46). The occurrence of delirium negatively affects the outcome of treatment (38,47). It prolongs the need for mechanical ventilation, treatment time in the ITU and hospital, and has a long- term negative effect on the patient’s cog- nitive functions (2,48-52). Risk factors for delirium can also be divided into pre- disposing and precipitating factors (53). Predisposing factors are the basic factors listed earlier, which in most cases cannot be changed, while the precipitating factors are factors the patient is exposed to during treatment. The precipitating factors in- clude all invasive procedures (operations, procedures for replacing organ function, establishing vascular access...), use of anti- cholinergics, benzodiazepines, depth and duration of sedation, mechanical ventila- tion, presence of a breathing tube, large fluctuations in blood pressure, hypox- ia, severe anaemia, large fluctuations in blood sugar, and septic shock (43,55-58). Precipitating factors also include the envi- ronment (noise, light ...) and psychologi- cal and social factors (e.g. isolation due to microbiological reasons). It is important to know the possible precipitating factors, minimize them or even prevent them. Monitoring and recording the occur- rence of signs of delirium in each nursing shift is recommended to detect delirium as well. The American guidelines consider the recommendation to be a recommen- dation of good clinical practice because of the weak evidence of a better outcome in patients due to the diagnosis and treat- ment of delirium (7). Without targeted checking, as much as 2/3 of the signs of delirium are overlooked (6,7). The most commonly used scoring systems are: The Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) shown in Figure 1 and the Intensive Care Delirium Screening Checklist (ICDSC), shown in Table 5. To use them, staff must be prop- erly trained (6,7,59,60). With the CAM- ICU, the presence of delirium can be confirmed or ruled out, but the degree of delirium cannot be determined. There is a simpler scoring system called the Nursing Delirium Screening Scale (Nu-DESC). If signs of delirium (1 point or more) are de- tected with the Nu-DESC, a more accurate assessment with a CAM-ICU or ICDSD is required (6,61). Contrary to popular belief, delirium rarely occurs exclusively as agitation, with 2/3 of patients having hypoactive delirium and approximately 1/3 patients having a mixed form (6). This raises the question of what effect the level of awakeness/alert- ness has on the assessment of delirium with the aforementioned scoring systems. So far, there is little data in the literature on the influence of awakeness/alertness on the reliability of delirium assessment; it is only clear that in deeply sedated patients (RASS –4 or –5) assessment is not possible (6,7). 6 Assessment of stress, fear and sleep disorders There are not many proven tools for measuring stress, fear and sleep quality that are suitable for everyday use. Stress is one of the most common symptoms in critically ill patients. Not only does it have psychological consequences, but it also affects cognitive functions, the neuroen- docrine system and the mechanisms of inflammation (62). Mental and cognitive consequences, in particular, may persist long after treatment at the ITU and re- quire long-term treatment. 296 ANAESTHESIOLOGY, INTENSIVE CARE Zdrav Vestn | May – June 2021 | Volume 90 | https://doi.org/10.6016/ZdravVestn.3055 Fi gu re 1 : C on fu si on A ss es sm en t M et ho d fo r t he In te ns iv e Ca re U ni t ( CA M -IC U) . I n th e ca se o f d ee p se da tio n (-4 o r - 5 ac co rd in g to th e RA SS ), th e pr es en ce o f de lir iu m ca nn ot b e as se ss ed . I t i s a lw ay s n ec es sa ry to lo ok fo r t he ca us e of a nx ie ty , s ed at io n an d/ or so m no le nc e. A da pt ed fr om E ly e t a l., 2 00 1 (5 9) . C o n fu si o n A ss e ss m e n t M e th o d f o r th e I n te n si v e C a re U n it ( C A M -I C U ) S T O P N O d e li ri u m 1 P sy ch o lo g ic a l C h a n g e s? A s u d d e n o n se t? C o m p a re d t o t h e d a y b e fo re ( p ri o r to h o sp it a li za ti o n ) D o e s th e b e h a vi o u r ch a n g e d u ri n g t h e d a y? • • R A S S ? 2 I n a tt e n ti o n ? S p e ll : P I N E A P P L E o r C A S A B L A N C A L e t th e p a ti e n t sq u e e ze y o u r h a n d o n ly o n l e tt e r “ A ” . E rr o r: t h e p a ti e n t d o e s n o t sq u e zz e y o u r h a n d w it h “ A ”, o r sq u e e ze s it o n le tt e r o th e r th a n “ A ”. • • 3 A lt e re d L e v e l o f C o n sc io u sn e ss ( “ cu rr e n t R A S S ” ) O n ly w h e n R A S S i s 0 , m o v e t o t h e n e x t le v e l. • D E L IR IU M S T O P : D e e p s e d a ti o n /c o m a ? P o ss ib le r e d u ct io n i n s e d a ti o n ? T h e re w il l b e a r e -e v a lu a ti o n s o o n ! F in d a m e d ic a l e xp la n a ti o n f o r a g it a ti o n , s e d a ti o n , o r so m n o le n ce : F e a r? W it h d ra w a l? A n in fe ct io n ? C o n st ip a ti o n ? D is co m fo rt , p a in ? S T O P N O d e li ri u m S T O P N O d e li ri u m A sk t h e p a ti e n t: 1 . W il l a s to n e f lo a t o n w a te r? 2 . A re t h e re f is h i n t h e s e a ? 3 . D o e s 1 k g w e ig h m o re t h a n 2 k g ? 4 . C a n y o u u se a h a m m e r to p o u n d a n a il ? 5 . A sk t h e p a ti e n t: “ H o ld u p 2 f in g e rs ( fo r e x a m p le ). N o w d o t h e s a m e t h in g w it h t h e O T H E R h a n d .” If t h e p a ti e n t ca n c o o p e ra te w it h o n ly o n e h a n d , le t h im /h e r a d d o n e f in g e r in t h e s e co n d a tt e m p t. A lt e rn a ti ve q u e st io n s: 1 . C a n d u ck s sw im ? 2 . A re t h e re e le p h a n ts i n t h e s e a ? 3 . S D o 2 k g w e ig h m o re t h a n 1 k g ? 4 . C a n w e s a w w o o d w it h a h a m m e r? O n ly o n e e rr o r is a ll o w e d f o r a ll q u e st io n s. 4 D is o rg a n iz e d T h in k in g -4 o r -5 Y e s ≥ 3 e r r o r s R A S S = 0 N o -2 o r -3 R A S S ≠ 0 1 - 2 e r r o r s ≤ 1 e r r o r ≥ 2 e r r o r s 297 PROFESSIONAL ARTICLE Wellbeing assessment of critical ill patient and non-pharmacological treatment Description 1. Altered Level of Consciousness. Choose one of the answers from A to E: A. exaggerated response to normal stimulation (RASS +1 do +4) 1 point B. normal wakefulness (RASS 0) 0 points C. responds to mild or moderate stimulation (obeys commands) (RASS -1 do -3) 1 point D. oresponds only to intense repeated stimulation (e.g. strong voice, pain) (RASS -4) stop assessment* E. no response (RASS -5) stop assessment* 2. Inattention (1 point for each positive answer): A. difficulty following commands or B. the patient is easily distracted by external stimuli or C. difficulty transferring focus Does the patient follow you with their eyes? 3. Disorientation (1 point for each deviation): A. disorientated to time or place or does not recognize people Does the patient recognize ITU caregivers who have cared for him/her and not recognize those who have not? Does he/she recognize the place they’re in? (let them list the caregivers, place ...) 4. Hallucinations or delusions (1 point for each positive answer): A. equivocal evidence of hallucinations or behaviour due to hallucinations (hallucination is a perception of something that is not there with no stimulus) or B. delusions or gross impairment of the perception of reality (delusion is a false belief that is fixed/ unchanging) Does the patient currently have or have they had any hallucinations over the past 24 hours? Are they afraid of people or things around them? (fear that is inappropriate to the clinical situation) 5. Psychomotor agitation or retardation (1 point for each positive answer): A. hyperactivity requiring the use of additional sedative drugs or restraints in order to control potential danger (e.g. pulling catheters out, hindering the staff ...) or B. inactivity or clinically noticeable psychomotor slowing or retardation Based on observation and documentation of the caregiver who cares for the patient over a shift. 6. Inappropriate speech or mood (1 point for each positive answer): A. inappropriate, disorganized, or incoherent speech or B. inappropriate mood related to events or situation Is the patient apathetic to current clinical situation? (e.g. lack of emotion) Any gross abnormalities in speech or mood? Is the patient inappropriately demanding? Table 5: Intensive Care Delirium Screening Checklist (ICDSC). Adapted from Bergeron et al., 2001 (58). 298 ANAESTHESIOLOGY, INTENSIVE CARE Zdrav Vestn | May – June 2021 | Volume 90 | https://doi.org/10.6016/ZdravVestn.3055 Notes: If the patient scores 4 points or more, it is delirium (99% sensitivity). RASS (Richmond Agitation- Sedation Scale, RASS). * In patients who are stuporous or comatose, assessment of delirium is not possible. Description 7. Sleep/wake cycle disturbance? (1 point for each abnormality): A. sleeping less than 4 hours at night or B. waking frequently at night (no disturbances by the staff or noise) or C. sleeping more than 4 hours during day Based on the caregiver assessment. 8. Symptom fluctuation (1 point for each item that changes): Fluctuation of any of the above items (under points 1–7) over 24 hours Based on the caregiver assessment. We do not currently have validated scoring systems or useful commercial monitors for stress detection. It is indi- rectly determined by monitoring vegeta- tive functions and vital parameters, which are not a reliable measure of stress level. It is also possible to measure the concen- tration of cortisol and interleukins in the blood, which is less useful for everyday clinical practice (63). For measuring the level of fear there are two validated scoring systems avail- able: The State-Trait Anxiety Inventory (STAI) and the anxiety subscale of the Brief Symptom Inventory (BSI) (64). Both scoring systems go beyond the nature of this article. At this point, let me empha- size that deeper sedation, despite popular belief, is not associated with a reduced in- cidence of fear (65). Lack of sleep and poor sleep quality is a very common problem in critically ill patients and is one of the main stressors. To date, the duration and effectiveness of sleep have been found to be normal in critically ill patients in most cases (7). However, a severe sleep disorder often occurs due to sleep fragmentation (fre- quent awakenings), disrupted day-night (circadian) rhythm (more sleep during the day, less at night), as well as a greater presence of shallow sleep phases (N1 and N2) and a lower proportion of deep sleep phases (N3, N4 and REM) (66). Normally, the phases of REM (rapid eye movement) and non-REM alternate at approximately 90-minute intervals, while in critically ill patients the phase of REM, especially, is missing (67). The frequent occurrence of atypical sleep patterns in the electroen- cephalogram has also been described in the literature; patients are often pathologi- cally awake (7). Patients who had had trouble sleep- ing before the onset of the critical illness and those who had been using sleeping pills are particularly prone to poor sleep quality during ITU treatment (7). In addi- tion, pain, disturbing environmental fac- tors such as noise, light, bed quality, staff intervention (care, recording vital signs, therapeutic interventions), psychological factors (e.g. fear, disorientation, foreign environment), breathing problems (dys- pnoea, coughing) and certain medicines contribute to the poor quality of sleep of critically ill patients (7,68). Lack of sleep and poor sleep quality 299 PROFESSIONAL ARTICLE Wellbeing assessment of critical ill patient and non-pharmacological treatment have a number of undesired effects. Quality sleep accelerates cellular immunity and wound healing, there is less chance of delirium and neurological-cognitive dys- function, and there is less chance of a pro- longed need for mechanical ventilation (7). Poor sleep quality increases the chance of developing delirium. The onset of delir- ium, however, concludes a vicious circle because it negatively affects the quality of sleep. Patients with delirium have a lower proportion of the REM sleep phase. Their day-night rhythm is also disrupted as they sleep more during the day. The exact effect of delirium on individual stages of sleep is not yet known (7,69). According to the limited data from the literature, inade- quate mechanical ventilation is also likely to negatively affect sleep quality, day-night rhythm, and sleep architecture. On the other hand, properly adjusted mechanical ventilation in certain patients with respi- ratory insufficiency is expected to improve sleep quality. The actual impact of poor quality and lack of sleep on the patient’s treatment outcome is currently unknown (7). The only well-validated objective method for measuring sleep quality (90-minute REM and non-REM sleep cy- cles) is polysomnography, which is too de- manding for everyday use in the ITU (6). In the literature, single-channel EEG, BIS monitor, and continuous measurement of skin potential are mentioned as possi- ble methods for measuring sleep. Due to the lack of reliable data, the guidelines do not recommend any of these methods (6). The American guidelines recommend that patients who are able to respond and are oriented be asked how they slept, or that their sleep be assessed using the Richards- Campbell Sleep Questionnaire shown in Table 6 (7,70). Contrary to popular belief, the use of sedatives further disrupts the already poor sleep structure of the critically ill patient (7). The effect of sleep quality during treat- ment at the ITU on the patient’s treatment outcome is unknown (7). 7 Non-pharmacological measures for preventing pain, fear, stress, insomnia, discomfort and delirium Nonpharmacological measures are too often an underestimated part of pre- venting pain, fear, stress, insomnia, dis- comfort, and delirium. These are mostly inexpensive measures and do not require additional equipment, but require prop- erly educated and motivated staff. Simpler nonpharmacological measures logically follow the assessment of pain, delirium, and sedation. According to the recommendations, nonpharmacological measures are the basis for preventing the occurrence of delirium (9,71,72). More than the imple- mentation of a single measure, it is recom- mended to implement a combination of different measures, which mostly have a beneficial effect on several of the patient’s problems at the same time (e.g. better sleep, less pain, less delirium) (7). One im- portant measure is to maintain a day-night (circadian) rhythm (73). This is helped by reducing noise (establishing a quiet en- vironment) and light at night. A patient who does not have delirium should be offered the option of using sleeping mask and earplugs at night. In doing so, we take into account his or her wishes (75). The American guidelines recommend that the assist-control mode of mechanical venti- lation be used in patients who require in- vasive mechanical ventilation overnight. This should improve the quality of sleep. Due to a lack of data, there are current- ly no recommendations for the use of 300 ANAESTHESIOLOGY, INTENSIVE CARE Zdrav Vestn | May – June 2021 | Volume 90 | https://doi.org/10.6016/ZdravVestn.3055 adaptive breathing methods. It is also rec- ommended to use non-invasive forms of mechanical ventilation (NIV – non-inva- sive ventilation) overnight in patients who are suitable for NIV (7). During the day, the patient should be adequately stimulated and activated (74). Cognitive stimulation and diversion of attention are important. The assistance of staff and relatives in orienting the patient in time and space is recommended (53). The patient should start using his or her glasses, hearing aid, denture and other aids as soon as possible (72). It also makes sense to use different media, e.g. radio, television, computer, or newspaper, tak- ing into account the patient’s wishes and needs (76). The presence of relatives who, according to some experts, could be in- cluded in the patient’s treatment process (e.g. conversation with the patient, care as- sistance) also has a beneficial effect (6,7). The latter requires a significant mental and organizational shift in each ITU. During the day, it is important that the patient is exposed to daylight, which con- sists of more blue light of shorter wave- lengths. The light from the blue spectrum affects the melatonin system, which helps to maintain a state of wakefulness (76). Indicator Response Sleep depth My sleep was: Very light (0) ... very deep (100) Sleep latency Last night I fell asleep: I just never could fall asleep (0)... I fell asleep immediately (100) Awakenings Last night: I was awake all night (0) ... I rarely woke up (100) Return to sleep Last night, when I woke up or was awakened: I couldn’t get back to sleep (0) ... I got back to sleep immediately (100) Sleep quality I would describe my sleep last night as: bad (0) ... good (100) Table 6: Richards Campbell Sleep Questionnaire. Adapted from Rivosecchi et al., 2016 (70). Note: The closer a patient gets to 100, the better he or she slept. When planning the construction of an intensive care unit or its renovation, it is essential to provide an adequate number of windows that allow a sufficient amount of daylight (77). If possible, it is recommended that all invasive and non-invasive procedures be performed on the patient in the morning shift (6). This allows them more time for quiet and uninterrupted rest in the after- noon and at night. A peaceful environ- ment is easier to ensure in large enough single rooms, which is also a recommen- dation of the ITU spatial planning guide- lines (77). There is growing evidence in the litera- ture of the beneficial effect of early mobili- zation on the reduced incidence of deliri- um and a better overall treatment outcome in the ITU (78). Early mobilization (in bed and out of bed) and rehabilitation are also recommended by the American guidelines (7). Despite the accumulation of data on the positive effects of early rehabilitation in the literature, some questions remain open. Given the contraindications, early rehabilitation has no serious side effects (78). Removal of drains, venous cannulas and enteral feeding tubes has been shown 301 PROFESSIONAL ARTICLE Wellbeing assessment of critical ill patient and non-pharmacological treatment to reduce the risk of delirium, discomfort and often pain (72,79). It is recommended to assess the need for these devices on a daily basis and to remove them as soon as the patient no longer needs them. As soon as possible, a switch to enteral or oral feeding is also recommended (6). A comfortable position of the patient in bed is important, especially in patients who cannot position themselves (sedated, plegic, immobilized). Positions that re- duce pain are also important. The literature mentions the beneficial effects of massage, aromatherapy, acupres- sure and various relaxation techniques on the patient’s general comfort. All of these techniques should be performed throughout the day, taking into account the patient’s wishes. These techniques are mentioned with a low level of recom- mendation in both the American and the German guidelines (6,7). Massage and re- laxation techniques can also be used as an additional measure to prevent pain during procedures. These two approaches have virtually no serious side effects. The main problem is that the current research in the literature is very poorly comparable due to the use of different techniques in individu- al studies. There is also a problem in prac- tice that there is often a shortage of staff in the ITU, but this technique must also be properly taught. Unlike massage and relaxation tech- niques, the American guidelines do not recommend virtual reality and hypnosis therapy due to a lack of evidence (7). The beneficial effect of music therapy is described. When choosing music, the pa- tient’s wishes are taken into account when- ever possible, otherwise it is recommend- ed to choose calmer, slow music without lyrics, which should not be too loud. The American guidelines recommended music therapy primarily as an additional mea- sure for reducing pain, especially during procedures, although the level of evidence for its effectiveness in the literature is low. The main problem in performing music therapy is the need for appropriate devices (headphones, music source), which must also meet hygienic or microbiological standards (possibility of disinfection). To prevent pain during procedures, the American guidelines recommend the use of cooling (low level of evidence). It is therefore recommended to cool the drain area for 10 minutes before removing the drains. The method, while taking precau- tions to prevent frostbite (cooling through a cloth), has no serious side effects, is inex- pensive, and can be quickly taught to staff (7). The view of the use of physical restraint on a patient is highly controversial in the literature. According to the American guidelines, physical restraints are not used at all in some European countries, and in North America they are used in up to 75% of all ITUs (7). Physical restraint involves various measures, e.g. tying the patient’s limbs to the bed, wrapping the patient’s fingers in a “boxing glove”, fastening the patient to the bed with a band tied over the chest. The reasons for the use of phys- ical restraint are different: one of the most important in everyday practice is a lack of staff (7). The latter is the main reason that physical restraint is still present in Slovenian ITUs. The historical purpose of physical restraint is to “calm down” rest- less and aggressive patients (they are often delirious) and to prevent potential harm to the patient and staff. However, we know from everyday clinical practice that pa- tients are often even more restless when physically restrained. There is also some information in the literature that physi- cal restraint results in even more adverse events, such as e.g., accidental removal of the airway, catheters, drains and oth- er devices, occurrence of pressure ulcers, 302 ANAESTHESIOLOGY, INTENSIVE CARE Zdrav Vestn | May – June 2021 | Volume 90 | https://doi.org/10.6016/ZdravVestn.3055 prolonged ITU treatment, increased agi- tation, increased use of benzodiazepines, opioids and antipsychotics, and increased risk of developing delirium (7,80). All of the above contradicts the results that staff expect from the use of physical restraint. Last but not least, the question of the eth- ics of physical restraint also arises. The personal opinion of the author of this ar- ticle is that it is necessary to take all pos- sible measures to minimize the need to use physical restraint or make sure there is no need for it at all. At the same time, the abandonment of physical restraint should not result in excessive use of sedatives, opioids and antipsychotics. 8 Conclusion In addition to the underlying disease, patients usually have a number of other problems during treatment at the ITU. These can arise from the underlying dis- ease (e.g. pain, delirium), from the envi- ronment (noise, insomnia, bed rest), as a result of various invasive procedures or as a result of previous illnesses and addiction to certain active ingredients (e.g. alcohol). Pain, insomnia, fear, delirium, fatigue and thirst are important stressors that neg- atively affect the patient’s treatment. As these stressors can potentially be mitigat- ed or completely prevented, it is extreme- ly important to identify them promptly and take appropriate action. It is crucial to communicate with the patient, if he or she is able to do so, and to take his or her needs into account. However, in uncon- scious or unfocused patients, it is essential to know the appropriate validated assess- ment tools. In addition to all the above, we must not forget that in addition to satisfying ba- sic physiological needs (e.g. feeding, bowel movements and urination), patients often want to talk about their distress, pain, and fear. They also want staff nearby who, in addition to their professional skills, are also empathetic and attentive to their problems. References 1. Puntillo KA, Arai S, Cohen NH, Gropper MA, Neuhaus J, Paul SM, et al. Symptoms experienced by intensive care unit patients at high risk of dying. Crit Care Med. 2010;38(11):2155-60. DOI: 10.1097/ CCM.0b013e3181f267ee PMID: 20711069 2. Pandharipande PP, Girard TD, Jackson JC, Morandi A, Thompson JL, Pun BT, et al.; BRAIN-ICU Study Investigators. Long-term cognitive impairment after critical illness. N Engl J Med. 2013;369(14):1306-16. DOI: 10.1056/NEJMoa1301372 PMID: 24088092 3. Sricharoenchai T, Parker AM, Zanni JM, Nelliot A, Dinglas VD, Needham DM. Safety of physical therapy interventions in critically ill patients: a single-center prospective evaluation of 1110 intensive care unit admissions. J Crit Care. 2014;29(3):395-400. DOI: 10.1016/j.jcrc.2013.12.012 PMID: 24508202 4. Nelson BJ, Weinert CR, Bury CL, Marinelli WA, Gross CR. Intensive care unit drug use and subsequent quality of life in acute lung injury patients. Crit Care Med. 2000;28(11):3626-30. DOI: 10.1097/00003246- 200011000-00013 PMID: 11098964 5. Wade D, Hardy R, Howell D, Mythen M. Identifying clinical and acute psychological risk factors for PTSD after critical care: a systematic review. Minerva Anestesiol. 2013;79(8):944-63. PMID: 23558761 6. Bürkle H, Eggers V, Horter J, Kessler P, Kleinschmidt S, Meiser A, et al. Analgesie, Sedierung und Delirmanagement in der Intensivmedizin (DAS-Leitlinie 2015). Nürnberg: Deutsche Gesellschaft für Anästhesiologie und Intensivmedizin; 2015 [cited 2020 Mar 20]. Available from: https://www.awmf.org/ uploads/tx_szleitlinien/001-012p_S3_Analgesie_Sedierung_Delirmanagement_Intensivmedizin_2015-08- abgelaufen.pdf. 303 PROFESSIONAL ARTICLE Wellbeing assessment of critical ill patient and non-pharmacological treatment 7. Devlin JW, Skrobik Y, Gélinas C, Needham DM, Slooter AJ, Pandharipande PP, et al. Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU. Crit Care Med. 2018;46(9):e825-73. DOI: 10.1097/ CCM.0000000000003299 PMID: 30113379 8. Jakob SM, Lubszky S, Friolet R, Rothen HU, Kolarova A, Takala J. Sedation and weaning from mechanical ventilation: effects of process optimization outside a clinical trial. J Crit Care. 2007;22(3):219-28. DOI: 10.1016/j.jcrc.2007.01.001 PMID: 17869972 9. Girard TD, Kress JP, Fuchs BD, Thomason JW, Schweickert WD, Pun BT, et al. Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (Awakening and Breathing Controlled trial): a randomised controlled trial. Lancet. 2008;371(9607):126-34. DOI: 10.1016/S0140-6736(08)60105-1 PMID: 18191684 10. Whipple JK, Lewis KS, Quebbeman EJ, Wolff M, Gottlieb MS, Medicus-Bringa M, et al. Analysis of pain management in critically ill patients. Pharmacotherapy. 1995;15(5):592-9. DOI: 10.1002/j.1875-9114.1995. tb02868.x PMID: 8570431 11. Loeser JD, Treede RD. The Kyoto protocol of IASP basic pain terminology. Pain. 2008;137(3):473-7. DOI: 10.1016/j.pain.2008.04.025 PMID: 18583048 12. Al Sutari MM, Abdalrahim MS, Hamdan-Mansour AM, Ayasrah SM. Pain among mechanically ventilated patients in critical care units. J Res Med Sci. 2014;19(8):726-32. PMID: 25422657 13. de Jong A, Molinari N, de Lattre S, Gniadek C, Carr J, Conseil M, et al. Decreasing severe pain and serious adverse events while moving intensive care unit patients: a prospective interventional study (the NURSE- DO project). Crit Care. 2013;17(2):R74. DOI: 10.1186/cc12683 PMID: 23597243 14. Chanques G, Viel E, Constantin JM, Jung B, de Lattre S, Carr J, et al. The measurement of pain in intensive care unit: comparison of 5 self-report intensity scales. Pain. 2010;151(3):711-21. DOI: 10.1016/j. pain.2010.08.039 PMID: 20843604 15. Twining J, Padula C. The measurement of pain in intensive care unit: comparison of 5 self-report intensity scales. Pain Manag Nurs. 2019;20(5):462-7. DOI: 10.1016/j.pmn.2019.02.005 PMID: 31103512 16. Gordon DB. Acute pain assessment tools: let us move beyond simple pain ratings. Curr Opin Anaesthesiol. 2015;28(5):565-9. DOI: 10.1097/ACO.0000000000000225 PMID: 26237235 17. McGuire DB, Kaiser KS, Haisfield-Wolfe ME, Iyamu F. Pain assessment in non-communicative adult palliative care patients. Nurs Clin North Am. 2016;51(3):397-431. DOI: 10.1016/j.cnur.2016.05.009 PMID: 27497016 18. Osterbrink J. Pain management in nursing care—experts standard. MMW Fortschr Med. 2005;147(15):34. PMID: 15884501 19. Payen JF, Bru O, Bosson JL, Lagrasta A, Novel E, Deschaux I, et al. Assessing pain in critically ill sedated patients by using a behavioral pain scale. Crit Care Med. 2001;29(12):2258-63. DOI: 10.1097/00003246- 200112000-00004 PMID: 11801819 20. Gélinas C, Klein K, Naidech AM, Skrobik Y. Pain, sedation, and delirium management in the neurocritically ill: lessons learned from recent research. Semin Respir Crit Care Med. 2013;34(2):236-43. DOI: 10.1055/s- 0033-1342986 PMID: 23716314 21. Rijkenberg S, Stilma W, Endeman H, Bosman RJ, Oudemans-van Straaten HM. Pain measurement in mechanically ventilated critically ill patients: Behavioral Pain Scale versus Critical-Care Pain Observation Tool. J Crit Care. 2015;30(1):167-72. DOI: 10.1016/j.jcrc.2014.09.007 PMID: 25446372 22. Rahu MA, Grap MJ, Ferguson P, Joseph P, Sherman S, Elswick RK. Validity and sensitivity of 6 pain scales in critically ill, intubated adults. Am J Crit Care. 2015;24(6):514-23. DOI: 10.4037/ajcc2015832 PMID: 26523009 23. Severgnini P, Pelosi P, Contino E, Serafinelli E, Novario R, Chiaranda M. Accuracy of Critical Care Pain Observation Tool and Behavioral Pain Scale to assess pain in critically ill conscious and unconscious patients: prospective, observational study. J Intensive Care. 2016;4(1):68. DOI: 10.1186/s40560-016-0192-x PMID: 27833752 24. Dehghani H, Tavangar H, Ghandehari A. Validity and reliability of behavioral pain scale in patients with low level of consciousness due to head trauma hospitalized in intensive care unit. Arch Trauma Res. 2014;3(1):e18608. DOI: 10.5812/atr.18608 PMID: 25032173 25. Paulus J, Roquilly A, Beloeil H, Théraud J, Asehnoune K, Lejus C. Pupillary reflex measurement predicts insufficient analgesia before endotracheal suctioning in critically ill patients. Crit Care. 2013;17(4):R161. DOI: 10.1186/cc12840 PMID: 23883683 26. Gélinas C, Fillion L, Puntillo KA, Viens C, Fortier M. Validation of the critical-care pain observation tool in adult patients. Am J Crit Care. 2006;15(4):420-7. DOI: 10.4037/ajcc2006.15.4.420 PMID: 16823021 27. Aïssaoui Y, Zeggwagh AA, Zekraoui A, Abidi K, Abouqal R. Validation of a behavioral pain scale in critically ill, sedated, and mechanically ventilated patients. Anesth Analg. 2005;101(5):1470-6. DOI: 10.1213/01. ANE.0000182331.68722.FF PMID: 16244013 304 ANAESTHESIOLOGY, INTENSIVE CARE Zdrav Vestn | May – June 2021 | Volume 90 | https://doi.org/10.6016/ZdravVestn.3055 28. Pandharipande P, Shintani A, Peterson J, Pun BT, Wilkinson GR, Dittus RS, et al. Lorazepam is an independent risk factor for transitioning to delirium in intensive care unit patients. Anesthesiology. 2006;104(1):21-6. DOI: 10.1097/00000542-200601000-00005 PMID: 16394685 29. Shehabi Y, Bellomo R, Kadiman S, Ti LK, Howe B, Reade MC, et al.; Sedation Practice in Intensive Care Evaluation (SPICE) Study Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Sedation intensity in the first 48 hours of mechanical ventilation and 180-day mortality: A multinational prospective longitudinal cohort study. Crit Care Med. 2018;46(6):850-9. DOI: 10.1097/ CCM.0000000000003071 PMID: 29498938 30. Burry L, Rose L, McCullagh IJ, Fergusson DA, Ferguson ND, Mehta S. Daily sedation interruption versus no daily sedation interruption for critically ill adult patients requiring invasive mechanical ventilation. Cochrane Database Syst Rev. 2014;7(7):CD009176. DOI: 10.1002/14651858.CD009176.pub2 PMID: 25005604 31. Mehta S, Burry L, Cook D, et al. SLEAP Investigators; Canadian Critical Care Trials Group: Daily sedation interruption in mechanically ventilated critically ill patients cared for with a sedation protocol: A randomized controlled trial. JAMA. 2012;308:1985-92. DOI: 10.1001/jama.2012.13872 PMID: 23180503 32. Ely EW, Truman B, Shintani A, Thomason JW, Wheeler AP, Gordon S, et al. Monitoring sedation status over time in ICU patients: reliability and validity of the Richmond Agitation-Sedation Scale (RASS). JAMA. 2003;289(22):2983-91. DOI: 10.1001/jama.289.22.2983 PMID: 12799407 33. Sessler CN, Grap MJ, Brophy GM. Multidisciplinary management of sedation and analgesia in critical care. Semin Respir Crit Care Med. 2001;22(2):211-26. DOI: 10.1055/s-2001-13834 PMID: 16088675 34. Vivien B, Di Maria S, Ouattara A, Langeron O, Coriat P, Riou B. Overestimation of Bispectral Index in sedated intensive care unit patients revealed by administration of muscle relaxant. Anesthesiology. 2003;99(1):9-17. DOI: 10.1097/00000542-200307000-00006 PMID: 12826836 35. Claassen J, Mayer SA, Kowalski RG, Emerson RG, Hirsch LJ. Detection of electrographic seizures with continuous EEG monitoring in critically ill patients. Neurology. 2004;62(10):1743-8. DOI: 10.1212/01. WNL.0000125184.88797.62 PMID: 15159471 36. American Psychiatric AssociationDiagnostic and Statistical Manual of Mental Disorders. 5th ed. Washington, D.C.: APA; c2013. 37. Lipowski ZJ. Update on delirium. Psychiatr Clin North Am. 1992;15(2):335-46. DOI: 10.1016/S0193- 953X(18)30240-5 PMID: 1603727 38. Korošec Jagodič H, Jagodič K, Pregelj P. Obravnava bolnika z delirijem. Zdrav Vestn. 2009;78:473-80. 39. Ahmed S, Leurent B, Sampson EL. Risk factors for incident delirium among older people in acute hospital medical units: a systematic review and meta-analysis. Age Ageing. 2014;43(3):326-33. DOI: 10.1093/ageing/ afu022 PMID: 24610863 40. Pisani MA, Murphy TE, Van Ness PH, Araujo KL, Inouye SK. Characteristics associated with delirium in older patients in a medical intensive care unit. Arch Intern Med. 2007;167(15):1629-34. DOI: 10.1001/ archinte.167.15.1629 PMID: 17698685 41. Van Rompaey B, Elseviers MM, Schuurmans MJ, Shortridge-Baggett LM, Truijen S, Bossaert L. Risk factors for delirium in intensive care patients: a prospective cohort study. Crit Care. 2009;13(3):R77. DOI: 10.1186/ cc7892 PMID: 19457226 42. Hirsch J, DePalma G, Tsai TT, Sands LP, Leung JM. Impact of intraoperative hypotension and blood pressure fluctuations on early postoperative delirium after non-cardiac surgery. Br J Anaesth. 2015;115(3):418-26. DOI: 10.1093/bja/aeu458 PMID: 25616677 43. van den Boogaard M, Schoonhoven L, Maseda E, Plowright C, Jones C, Luetz A, et al. Recalibration of the delirium prediction model for ICU patients (PRE-DELIRIC): a multinational observational study. Intensive Care Med. 2014;40(3):361-9. DOI: 10.1007/s00134-013-3202-7 PMID: 24441670 44. Pandharipande P, Cotton BA, Shintani A, Thompson J, Pun BT, Morris JA, et al. Prevalence and risk factors for development of delirium in surgical and trauma intensive care unit patients. J Trauma. 2008;65(1):34- 41. DOI: 10.1097/TA.0b013e31814b2c4d PMID: 18580517 45. Zhang WY, Wu WL, Gu JJ, Sun Y, Ye XF, Qiu WJ, et al. Risk factors for postoperative delirium in patients after coronary artery bypass grafting: A prospective cohort study. J Crit Care. 2015;30(3):606-12. DOI: 10.1016/j. jcrc.2015.02.003 PMID: 25708120 46. Slooter AJ, Van De Leur RR, Zaal IJ. Delirium in critically ill patients. Handb Clin Neurol. 2017;141:449-66. DOI: 10.1016/B978-0-444-63599-0.00025-9 PMID: 28190430 47. Ely EW, Girard TD, Shintani AK, Jackson JC, Gordon SM, Thomason JW, et al. Apolipoprotein E4 polymorphism as a genetic predisposition to delirium in critically ill patients. Crit Care Med. 2007;35(1):112-7. DOI: 10.1097/01.CCM.0000251925.18961.CA PMID: 17133176 48. Skrobik Y, Ahern S, Leblanc M, Marquis F, Awissi DK, Kavanagh BP. Protocolized intensive care unit management of analgesia, sedation, and delirium improves analgesia and subsyndromal delirium rates. Anesth Analg. 2010;111(2):451-63. DOI: 10.1213/ANE.0b013e3181d7e1b8 PMID: 20375300 305 PROFESSIONAL ARTICLE Wellbeing assessment of critical ill patient and non-pharmacological treatment 49. Ely EW, Shintani A, Truman B, Speroff T, Gordon SM, Harrell FE, et al. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA. 2004;291(14):1753-62. DOI: 10.1001/ jama.291.14.1753 PMID: 15082703 50. Girard TD, Jackson JC, Pandharipande PP, Pun BT, Thompson JL, Shintani AK, et al. Delirium as a predictor of long-term cognitive impairment in survivors of critical illness. Crit Care Med. 2010;38(7):1513-20. DOI: 10.1097/CCM.0b013e3181e47be1 PMID: 20473145 51. Shehabi Y, Riker RR, Bokesch PM, Wisemandle W, Shintani A, Ely EW; SEDCOM (Safety and Efficacy of Dexmedetomidine Compared With Midazolam) Study Group. Delirium duration and mortality in lightly sedated, mechanically ventilated intensive care patients. Crit Care Med. 2010;38(12):2311-8. DOI: 10.1097/ CCM.0b013e3181f85759 PMID: 20838332 52. Inouye SK, Bogardus ST, Charpentier PA, Leo-Summers L, Acampora D, Holford TR, et al. A multicomponent intervention to prevent delirium in hospitalized older patients. N Engl J Med. 1999;340(9):669-76. DOI: 10.1056/NEJM199903043400901 PMID: 10053175 53. Schiemann A, Hadzidiakos D, Spies C. Managing ICU delirium. Curr Opin Crit Care. 2011;17(2):131-40. DOI: 10.1097/MCC.0b013e32834400b5 PMID: 21301333 54. González-López A, Albaiceta GM, Talbot K. Newly identified precipitating factors in mechanical ventilation- induced brain damage: implications for treating ICU delirium. Expert Rev Neurother. 2014;14(6):583-8. DOI: 10.1586/14737175.2014.915743 PMID: 24852225 55. Bilotta F, Lauretta MP, Borozdina A, Mizikov VM, Rosa G. Postoperative delirium: risk factors, diagnosis and perioperative care. Minerva Anestesiol. 2013;79(9):1066-76. PMID: 23511351 56. van Gool WA, van de Beek D, Eikelenboom P. Systemic infection and delirium: when cytokines and acetylcholine collide. Lancet. 2010;375(9716):773-5. DOI: 10.1016/S0140-6736(09)61158-2 PMID: 20189029 57. Hopkins RO, Suchyta MR, Snow GL, Jephson A, Weaver LK, Orme JF. Blood glucose dysregulation and cognitive outcome in ARDS survivors. Brain Inj. 2010;24(12):1478-84. DOI: 10.3109/02699052.2010.506861 PMID: 20858026 58. Bergeron N, Dubois MJ, Dumont M, Dial S, Skrobik Y. Intensive Care Delirium Screening Checklist: evaluation of a new screening tool. Intensive Care Med. 2001;27(5):859-64. DOI: 10.1007/s001340100909 PMID: 11430542 59. Ely EW, Margolin R, Francis J, May L, Truman B, Dittus R, et al. Evaluation of delirium in critically ill patients: validation of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Crit Care Med. 2001;29(7):1370-9. DOI: 10.1097/00003246-200107000-00012 PMID: 11445689 60. Gélinas C, Bérubé M, Chevrier A, Pun BT, Ely EW, Skrobik Y, et al. Delirium assessment tools in adult critically ill: A psychometric analysis and systematic review. Crit Care Nurse. 2018;38(1):38-49. DOI: 10.4037/ ccn2018633 PMID: 29437077 61. Egeland M, Zunszain PA, Pariante CM. Molecular mechanisms in the regulation of adult neurogenesis during stress. Nat Rev Neurosci. 2015;16(4):189-200. DOI: 10.1038/nrn3855 PMID: 25790864 62. Tipping CJ, Young PJ, Romero L, Saxena MK, Dulhunty J, Hodgson CL. A systematic review of measurements of physical function in critically ill adults. Crit Care Resusc. 2012;14(4):302-11. PMID: 23230880 63. Perpiñá-Galvañ J, Richart-Martínez M. Scales for evaluating self-perceived anxiety levels in patients admitted to intensive care units: a review. Am J Crit Care. 2009;18(6):571-80. DOI: 10.4037/ajcc2009682 PMID: 19880959 64. Treggiari MM, Romand JA, Yanez ND, Deem SA, Goldberg J, Hudson L, et al. Randomized trial of light versus deep sedation on mental health after critical illness. Crit Care Med. 2009;37(9):2527-34. DOI: 10.1097/ CCM.0b013e3181a5689f PMID: 19602975 65. Gabor JY, Cooper AB, Crombach SA, Lee B, Kadikar N, Bettger HE, et al. Contribution of the intensive care unit environment to sleep disruption in mechanically ventilated patients and healthy subjects. Am J Respir Crit Care Med. 2003;167(5):708-15. DOI: 10.1164/rccm.2201090 PMID: 12598213 66. Freedman NS, Gazendam J, Levan L, Pack AI, Schwab RJ. Abnormal sleep/wake cycles and the effect of environmental noise on sleep disruption in the intensive care unit. Am J Respir Crit Care Med. 2001;163(2):451-7. DOI: 10.1164/ajrccm.163.2.9912128 PMID: 11179121 67. Elliott R, Rai T, McKinley S. Factors affecting sleep in the critically ill: an observational study. J Crit Care. 2014;29(5):859-63. DOI: 10.1016/j.jcrc.2014.05.015 PMID: 24973105 68. Trompeo AC, Vidi Y, Locane MD, Braghiroli A, Mascia L, Bosma K, et al. Sleep disturbances in the critically ill patients: role of delirium and sedative agents. Minerva Anestesiol. 2011;77(6):604-12. PMID: 21617624 69. Richards KC, O’Sullivan PS, Phillips RL. Measurement of sleep in critically ill patients. J Nurs Meas. 2000;8(2):131-44. DOI: 10.1891/1061-3749.8.2.131 PMID: 11227580 70. Rivosecchi RM, Kane-Gill SL, Svec S, Campbell S, Smithburger PL. The implementation of a nonpharmacologic protocol to prevent intensive care delirium. J Crit Care. 2016;31(1):206-11. DOI: 10.1016/j.jcrc.2015.09.031 PMID: 26596509 306 ANAESTHESIOLOGY, INTENSIVE CARE Zdrav Vestn | May – June 2021 | Volume 90 | https://doi.org/10.6016/ZdravVestn.3055 71. Colombo R, Corona A, Praga F, Minari C, Giannotti C, Castelli A, et al. A reorientation strategy for reducing delirium in the critically ill. Results of an interventional study. Minerva Anestesiol. 2012;78(9):1026-33. PMID: 22772860 72. Patel J, Baldwin J, Bunting P, Laha S. The effect of a multicomponent multidisciplinary bundle of interventions on sleep and delirium in medical and surgical intensive care patients. Anaesthesia. 2014;69(6):540-9. DOI: 10.1111/anae.12638 PMID: 24813132 73. Nannapaneni S, Lee SJ, Kashiouris M, Elmer JL, Thakur LK. 2015;34(2):94-100. DOI: 10.1080/21548331.2015.1015389 PMID: 25687293 74. Alway A, Halm MA, Shilhanek M, St Pierre J. Do earplugs and eye masks affect sleep and delirium outcomes in the critically ill? Am J Crit Care. 2013;22(4):357-60. DOI: 10.4037/ajcc2013545 PMID: 23817826 75. Taguchi T, Yano M, Kido Y. Influence of bright light therapy on postoperative patients: a pilot study. Intensive Crit Care Nurs. 2007;23(5):289-97. DOI: 10.1016/j.iccn.2007.04.004 PMID: 17692522 76. Hoyer EH, Friedman M, Lavezza A, Wagner-Kosmakos K, Lewis-Cherry R, Skolnik JL, et al. Promoting mobility and reducing length of stay in hospitalized general medicine patients: A quality-improvement project. J Hosp Med. 2016;11(5):341-7. DOI: 10.1002/jhm.2546 PMID: 26849277 77. Thompson DR, Hamilton DK, Cadenhead CD, Swoboda SM, Schwindel SM, Anderson DC, et al. Guidelines for intensive care unit design. Crit Care Med. 2012;40(5):1586-600. DOI: 10.1097/CCM.0b013e3182413bb2 PMID: 22511137 78. Nydahl P, Sricharoenchai T, Chandra S, Kundt FS, Huang M, Fischill M, et al. Safety of patient mobilization and rehabilitation in the intensive care unit. Systematic review with meta-analysis. Ann Am Thorac Soc. 2017;14(5):766-77. DOI: 10.1513/AnnalsATS.201611-843SR PMID: 28231030 79. Inouye SK, Westendorp RG, Saczynski JS. Delirium in elderly people. Lancet. 2014;383(9920):911-22. DOI: 10.1016/S0140-6736(13)60688-1 PMID: 23992774 80. Bregar B, Možgan B. Posebni varovalni ukrepi – primerjava s tujino. In: Bregar B, Novak JP. Posebni varovalni ukrepi v teoriji in praksi. Ljubljana: Zbornica zdravstvene in babiške nege Slovenije; 2012. pp. 13-21.