Evidence and consensus based guideline for the management of delirium, analgesia, and sedation in intensive care medicine. Revision 2015 (DAS-Guideline 2015)  short version



# Methods
This guideline has the highest development credentials, S3, indicating that it is both evidence-and consensus based. The guideline task-force consisted of 49 voting members nominated by 17 participating national societies. These members formed work groups that identified main clinical issues and framed key-questions to be addressed. Should previous versions of the guideline not /no longer provide satisfactory resolutions to the selected topics, search strategies were developed to address the subject. The resulting recommendations were then collected in an early version and further discussed within the groups. The members interacted with each other via consensus-conferences, email, fax, or mail. Communication was managed by a coordinating group consisting of 4 members, as well as the chairing societies. A systematic literature search was performed by a special team under the supervision of an epidemiologist. Finally, the evalu-ation process was done by the individual working groups, which also set the level-of-evidence (LoE). All searches were performed between April and May of 2014. When necessary, new evidence was integrated manually. The LoE was determined, as in the previous version of the guideline, using the Oxford System [1]. The overview tables allow to identification the evidence for each individual manuscript. Literature was accessible for all taskforce members. The specific search strategies, searched terms, inclusion and exclusion criteria, as well as exact time frames, are all detailed in the methodological report. Sources were electronic databases (Medline  ), guideline networks, and (manually) abstracts and congress-publications. In order to identify "grey literature", all task-force members were asked to search for publications outside Medline and Embase and include relevant entries to the literature-data-base. Systematic guideline searches were conducted within the AWMF-registry (http://www.awmf. org/leitlinien.html) and the Guidelines International Network (G-I-N) (http://www.g-i-n.net). In line with the AWMFguideline developer manual, a consensus-based decision was used to assess whether recommendations from other guidelines could be adapted. Cultural adaptions were adopted in accordance with recommendations from the ADAPTE-Collaboration. Voting only took place following a full disclosure of potential conflicts of interest by the task-force members. The conflict of interest forms were stored centrally, and all task-force members declaring a conflict of interest were required to abstain from voting in the corresponding issues. This was consented in the task-force before the voting process. The voting-process itself was conducted during consensus-conferences, under the supervision of an independent observer from the AWMF. Alternatively, members could vote using an online DELPHI, as published and recommended in the AWMF-guideline developer manual. The used grades of recommendation (GoR) were A = strong recommendation (we recommend/one shall), B = recommendation (we suggest/one should), and O = open recommendation (one might consider) for or against any specific intervention. Significant deviations between LoE and GoR were generally possible if a member of the group requested upgrading or downgrading of a recommendation (e.g. due to ethical relevance or lack of research-possibilities). Expert opinions and consensusbased decisions were only allowed when the resolutions were highly relevant for clinical routine and there was lack of available evidence. The guideline was reviewed and approved by 17 scientific societies. Reviewers were all independent peers. All procedures are in adherence to the actualization protocol. The next regular update of the guideline is scheduled for 2018, although earlier modifications are permitted should significant new evidence arise.

## Management of delirium, analgesia, and sedation in adult intensive care
Risk and prevention of ICU related delirium Pain, stress, anxiety, and a disrupted sleep-wake cycle are common symptoms that occur in critically ill patients that increase the risk for ICU related delirium [bib_ref] Investigators; Canadian Critical Care Trials Group. Prevalence, risk factors, and outcomes of..., Mehta [/bib_ref]. Delirium is one of the most common manifestations of cerebral dysfunction in critically ill patients, which affects not only short-term recovery (in terms of prolonged ventilation and length of stay, as well as increased mortality) [bib_ref] Delirium as a predictor of mortality in mechanically ventilated patients in the..., Ely [/bib_ref] , [bib_ref] Incidence, risk factors and consequences of ICU delirium, Ouimet [/bib_ref] , [bib_ref] Impact of delirium on clinical outcome in critically ill patients: a meta-analysis, Zhang [/bib_ref] , but also leads to cognitive long-term impairment, posttraumatic stress disorders (PTSD), and reduced quality of life [bib_ref] BRAIN-ICU Study Investigators. Long-term cognitive impairment after critical illness, Pandharipande [/bib_ref]. These entities are part of the Post Intensive Care Unit Syndrome (PICS) that has been recently described in ICU survivors. Aside from managing the risk factors, several effective pharmacological and non-pharmacological prevention strategies can be used to prevent or treat ICU delirium.
In addition to baseline factors, the risk for delirium also comprises treatment associated factors, as well as psychological, social, and iatrogenic aspects [bib_ref] Risk factors for incident delirium among older people in acute hospital medical..., Ahmed [/bib_ref].
The presence or development of risk factors for delirium shall be closely evaluated in order to ensure the prompt introduction of preventive measures. The non-pharmacological measures were shown to be particularly effective in the prevention of delirium, and shall therefore be implemented for all critically ill patients. The excessive use of sedation shall be avoided, since a deep sedation were shown to deteriorate the clinical outcome. A pharmacological prevention is to be reserved only for patients at high risk for delirium, and is not generally recommended [fig_ref] Table 1: Risk factors for ICU-delirium [/fig_ref].
[All the tables are displayed following the (English) version of the article.]
Monitoring of analgesia, sedation, delirium, anxiety, stress, and sleep A basic concept of patient-oriented therapy in intensivecare is the definition of a patient-specific treatment goal, and the frequent assessment of the current status in order to promptly introduce or adjust interventions (Goal Directed Therapy). The definition and monitoring of treatment goals must be symptom-oriented, using validated scores and instruments. The use of such validated methods has a major impact on treatment: the systematic evaluation of pain, sedation, and delirium can significantly improve treatment of pain, reduce nosocomial infections, decrease duration of mechanical ventilation and hospitalization, as well as reduce mortality [bib_ref] Impact of systematic evaluation of pain and agitation in an intensive care..., Chanques [/bib_ref] , [bib_ref] Key performance indicators in intensive care medicine. A retrospective matched cohort study, Kastrup [/bib_ref]. Therefore, it should be a standard in all ICUs to define goals, measure, and document the current state of analgesia, sedation, and delirium once per shift (usually every The evaluation of anxiety with a validated scale is desirable, since anxiety is often not properly estimated, and thus not properly treated. There are short versions of standard psychological measurement instruments available (State-Trait Anxiety Inventory, state subscale [STAI-s], Brief Symptom Inventory Anxiety, subscale [BSI-A]) that allow a valid and reliable assessment of anxiety. From pain assessment, we know that one-dimensional selfassessment scales have proven to be especially practical to measure therapeutic needs and therapeutic response. From pain assessment studies, it is clear that the use one-dimensional self-assessment scales are particularly useful in evaluating the therapeutic needs and therapeutic response. Studies on anxiety show that similar scales (for example linear Visual Analogue Scale and the Faces Anxiety Scale) are also suitable to measure anxiety with good diagnostic validity . Further studies are needed to clarify whether the controllability of anxiolysis can also be monitored with these scales. Stress and disturbances of the sleep-wake cycle are further syndromes in ICU-patients that not only negatively affect recovery, but also constitute risk factors for serious complications. Nevertheless, there are currently no validated routine instrument for measuring stress and sleep, and the sole subjective assessment of vital signs by the ICU personnel is not suitable to monitor stress in critically ill patients [bib_ref] A systematic review of measurements of physical function in critically ill adults, Tipping [/bib_ref]. Regarding the sleep-wake cycle of ICU patients, not only is there a lack of suitable monitoring procedures that can be routinely used, but also no valid evaluation of sleep stages in critically ill subjects [bib_ref] Diurnal sedative changes during intensive care: impact on liberation from mechanical ventilation..., Seymour [/bib_ref] [fig_ref] Table 4: Monitoring -general aspects [/fig_ref].

## Treatment concepts
See .

## Non-pharmacological concepts
See [fig_ref] Table 1: Risk factors for ICU-delirium [/fig_ref].
Analgesia ICU-patients require an individualized pain management. Pain exerts considerable negative effects on recovery and is one of the most commonly reported stressors for ICU-patients. Therefore, a sufficient analgesia in all ICU patients -regardless of indication of sedation -should be ensured, and potentially painful procedures should be met with a preventive analgesic approach. In the ICU, the analgesia regimen is usually opioid based, [bib_ref] Short term analgesia based sedation in the Intensive Care Unit: morphine vs..., Carrer [/bib_ref] , [bib_ref] Remifentanil for tracheal tube tolerance: a case control study, Machata [/bib_ref] , [bib_ref] Intravenous paracetamol reduced the use of opioids, extubation time, and opioid-related adverse..., Memis [/bib_ref] , as the risk-benefit profile of non-opioid analgesics is still a matter of scientific discussion (low analgesic potential, but considerable side effects). A combination with regional analgesia can be used [bib_ref] Protective effects of epidural analgesia on pulmonary complications after abdominal and thoracic..., Popping [/bib_ref] , and a patient-controlled analgesia is recommended as soon as the patient is sufficiently awake (RASS 0/-1 and no delirium) [fig_ref] Table 1: Risk factors for ICU-delirium [/fig_ref].

## Sedation
The current evidence reveals that a measurable sedation should always be avoided, as long as there is no mandatory clinical indication for sedation [bib_ref] Efficacy and safety of a paired sedation and ventilator weaning protocol for..., Girard [/bib_ref] , [bib_ref] Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation, Kress [/bib_ref]. A deep sedation, also within the first 48 hours, is associated with increased mortality, prolonged mechanical ventilation, prolonged ICU-LOS, and hospitalization, [bib_ref] SEDCOM (Safety and Efficacy of Dexmedetomidine Compared With Midazolam) Study Group. Delirium..., Shehabi [/bib_ref] , [bib_ref] Early deep sedation is associated with decreased in-hospital and two-year follow-up survival, Balzer [/bib_ref] , [bib_ref] Sedation Practice in Intensive Care Evaluation (SPICE) Study Investigators; ANZICS Clinical Trials..., Shehabi [/bib_ref]. Aside from specific indications (e.g. surgical indications, signs of increased intracranial pressure with impending herniation, or reduction of oxygen consumption in case of imminent hypoxia), the treatment goal should be an alert, cooperative patient who can tolerate the required interventions (RASS 0/-1). It is fundamental to achieve an adequate analgesia, which is accompanied by a specific treatment of possible symptoms, such as hallucinations, stress, and anxiety [bib_ref] Management of sedation in mechanically ventilated patients, Hogarth [/bib_ref] , [bib_ref] Sedation in the intensive care unit, Young [/bib_ref] , [bib_ref] A protocol of no sedation for critically ill patients receiving mechanical ventilation:..., Strom [/bib_ref]. A recent systematic review revealed a decreased importance of daily sedation interruptions (DSIs), which is no longer considered superior to protocol-driven management of sedation. The goal for light sedation should be set as early as possible, as the first 48 hours of sedation predict long-term outcome. Sedation should follow the principles of an "early goal directed therapy" with target-RASS 0/-1 [fig_ref] Table 1: Risk factors for ICU-delirium [/fig_ref].

## Moderate or deep sedation
If the indication for a deep sedation is provided, the target RASS and the time of the next re-evaluation must be defined. Sedation should be performed with a combination of hypnotic and analgesic agents, whereas the choice of hypnotic agent should be appropriate to level of sedation and controllability desired. Aside from propofol and benzodiazepines, volatile anesthetics are also feasible options. In the absence of contraindications, DSI protocol (e.g., Spontaneous Awakening Trial, SAT) and Spontaneous Breathing Trials (SBT) should be carried out daily in patients with RASS -2 [bib_ref] Canadian Critical Care Trials Group. Daily sedation interruption in mechanically ventilated critically..., Mehta [/bib_ref] [fig_ref] Table 1: Risk factors for ICU-delirium [/fig_ref].

## Symptom oriented sedative therapy
Aside from pain, the most common symptoms of critically ill patients are stress, anxiety, agitation, psychotic symptoms, and sleep disturbances, all of which require a targeted, symptom-oriented therapy. In addition to nonpharmacological strategies and a causal treatment, a pharmacological therapy may be necessary to control the symptoms. Alpha-2-agonists are available for stress-reduction and treatment of vegetative symptoms, and benzodiazepines can be used for anxiolysis [fig_ref] Table 1: Risk factors for ICU-delirium [/fig_ref].

## Pharmacological therapy of delirium
Preventive measures for delirium are both safe and effective [bib_ref] Pharmacological treatments of non-substance-withdrawal delirium: a systematic review of prospective trials, Friedman [/bib_ref]. If delirium does occur, it should be treated promptly and symptomatically. The treatment of psychotic symptoms (with or without delirium) may include low-dose neuroleptics [bib_ref] Atypical antipsychotics in the treatment of delirium, Wang [/bib_ref]. In addition, the use of alpha-2 : Symptom-based therapy and reduction of delirium, anxiety, stress, and protocol-based analgesia, sedation, and sleep-management in intensive care medicine Algorithm that focuses on a possible holistic management for adult critically ill patients. RASS: Richmond Agitation-Sedation Scale. Other scores (delirium, analgesia: observational/self-assessment), please, s.f. addendum at http://www.awmf.org/leitlinien/detail/ll/001-012.html.
agonists is also suitable for a symptom-orientated therapy of delirium, [bib_ref] MIND Trial Investigators. Feasibility, efficacy, and safety of antipsychotics for intensive care..., Girard [/bib_ref]. A special situation is the alcohol withdrawal delirium in the ICU, for which long-acting benzodiazepines should be considered [fig_ref] Table 1: Risk factors for ICU-delirium [/fig_ref].

## Weaning from mechanical ventilation
The new German S2k-Guidelines on "Prolonged Weaning" AWMF (020/015) provides recommendations regarding weaning from mechanical ventilation. The management of analgesia, sedation, and delirium influence the weaning process significantly [bib_ref] Weaning from mechanical ventilation and sedation, Luetz [/bib_ref]. In order to start weaning as early as possible, it is useful to combine sedation and weaning protocols [fig_ref] Table 1: Risk factors for ICU-delirium [/fig_ref].

## Treatment with neuromuscular blocking agents (nmba)
There is no indication for a general use of a neuromuscular blockade during intensive care treatment. During neuromuscular blockade, patients cannot be awake, actively participate in their recovery, nor benefit from physiotherapy. When there is a specific indication for NMBAs, adequate analgesia and sedation should be provided . Furthermore, the depth of blockade should be monitored [bib_ref] Pharmacodynamics of cisatracurium in the intensive care unit: an observational study, Dieye [/bib_ref] , and the duration should be kept as short as possible [fig_ref] Table 1: Risk factors for ICU-delirium [/fig_ref].

## Intra-and inter-hospital transports
Especially during intra-and inter-hospital transports, movements or changes in the position of the patient are potentially painful events. Therefore, a symptomatic therapy should be continued and possibly adjusted during a transport [bib_ref] Bispectral index monitoring in helicopter emergency medical services patients, Heegaard [/bib_ref]. An inadequate sedation (over-and undersedation) should be avoided at all times, as this can lead to an acute deterioration of neurological and cardiovascular parameters [fig_ref] Table 1: Risk factors for ICU-delirium [/fig_ref].
Analgesia, sedation, and delirium management in special patients

## Pregnant and breastfeeding women in the icu
The pharmacotherapy of pregnant and breastfeeding patients in the ICU is particularly challenging, as it must account for the effects of the drugs on the unborn or breast-fed child. Due to the lack of randomized-controlled trials, there is little evidence for pharmacotherapy of pregnant or breastfeeding women. Should there be an indication for opioids or sedatives during these periods, an adequate monitoring of the child is obligatory [fig_ref] Table 1: Risk factors for ICU-delirium [/fig_ref].

## End-of-life care
Impending death is a period that can be severely influenced by anxiety, stress, and pain. Dying patients require the same patient-centred care as other ICU patients. Frequent monitoring and sufficient pharmacotherapy should ensure the patient is free of discomfort, even if this leads to a acceleration of the dying process [bib_ref] Challenges in end-of-life care in the ICU, Carlet [/bib_ref]. This guideline should be used and evaluated in the light and in-line with the "guideline of limitations to intensive care treatment"and the "basic principles for medical palliative care", published by the German Medical Association [fig_ref] Table 2: Prevention and risk reduction [/fig_ref].

## Patients with severe burn injury
Severe burn injuries lead to strong pain, possible hyperalgesia, as well as a prolonged hospitalization. Aside from an adequate basic level of analgesia, additional analgesics (local and systemic) and/or procedural sedation may be necessary when performing various procedures (e.g. dressing changes). There are multimodal concepts for the use of analgesics, adjuvants, and non-pharmacological strategies regarding pain management in patients with severe burns [bib_ref] The management of pain in the burns unit, Richardson [/bib_ref]. Especially for analgesia and sedation of burn-injured children, the use of standardized protocols and training programs should be used [bib_ref] Analgesia and sedation for children undergoing burn wound care, Bayat [/bib_ref] [fig_ref] Table 1: Risk factors for ICU-delirium [/fig_ref].

## Multiple trauma patients
The German AWMF-guideline registered under 012/019 provides recommendations regarding patients with multiple trauma . There is no evidence for a clear superiority of a particular drug for analgesia in severely injured patients. Opioids (morphine, fentanyl, sufentanil, alfentanil, remifentanil), ketamine [bib_ref] Ketamine for continuous sedation of mechanically ventilated patients, Umunna [/bib_ref] (s-enantiomer, racemate), and adjuvant alpha-2-agonists (clonidine) are used routinely in the clinic. Due to an increased risk for adrenal insufficiency and numerous alternatives, etomidate should no longer be used for procedural sedation, and is no longer recommended in trauma patients. Nevertheless, there is no evidence that the administration of etomidate has long-term effects on outcome [47], [fig_ref] Table 2: Prevention and risk reduction [/fig_ref].

## Patients with intracranial hypertension
A main focus of the intensive care management of patients with severe traumatic brain injury is the reduction of secondary damage. Although there is little evidence that sedation directly lowers intra-cranial-pressure (ICP), the acute treatment of patients with elevated ICP starts with a deep sedation (RASS-5). There are no validated monitoring systems for this patient subgroup, so the general scores and monitoring instruments are used [bib_ref] Neurological examination of critically ill patients: a pragmatic approach, Sharshar [/bib_ref]. A frequent neurological examination is obligatory. The choice of sedatives should be in-line with recommendations made in the general part. An ideal analgesic/ [fig_ref] Table 2: Prevention and risk reduction [/fig_ref] properties, and should allow short wake-up times for the assessment of patients after a brief infusion interruption [bib_ref] Sedation in neurointensive care: advances in understanding and practice, Citerio [/bib_ref] [fig_ref] Table 2: Prevention and risk reduction [/fig_ref].

## Cardiac surgery
Fast-track concepts include a 2-hour sedation phase after uncomplicated cardiac surgery. In this setting, numerous analgesia and sedation protocols have proven to be advantageous [bib_ref] A greater analgesia, sedation, delirium order set quality score is associated with..., Dale [/bib_ref] , and fast-track strategies seem to reduce the incidence of postoperative delirium [bib_ref] Meta-analysis of factors which influence delirium following cardiac surgery, Lin [/bib_ref]. Delirium in cardiac surgical patients is associated with a higher mortality [bib_ref] Delirium in elderly patients and the risk of postdischarge mortality, institutionalization, and..., Witlox [/bib_ref] , so that a delirium screening with a validated tool -as generally recommended -is especially important [bib_ref] Postoperative delirium in a substudy of cardiothoracic surgical patients in the BAG-RECALL..., Whitlock [/bib_ref] , [bib_ref] Pregabalin has an opioidsparing effect in elderly patients after cardiac surgery: a..., Pesonen [/bib_ref] [fig_ref] Table 2: Prevention and risk reduction [/fig_ref].

## Patients on extracorporeal life support systems (ecls)
There is a grey area regarding the level of sedation for patients on ECLS, where safety-aspects and the ability to positively influence recovery must be balanced. Patients on ECLS have numerous delirium risk-factors. Hyperactive delirium or agitation can be life-threatening for these patients, so that a consequent monitoring and a symptomatic therapy of stress, anxiety, delirium, pain, and insomnia is essential to safely achieve a target RASS of 0 [bib_ref] Extracorporeal Co2 removal in hypercapnic patients at risk of noninvasive ventilation failure:..., Sorbo [/bib_ref] , [bib_ref] Extracorporeal membrane oxygenation in awake patients as bridge to lung transplantation, Fuehner [/bib_ref] , [bib_ref] Avoiding invasive mechanical ventilation by extracorporeal carbon dioxide removal in patients failing..., Kluge [/bib_ref] , [bib_ref] Extracorporeal CO2 removal as bridge to lung transplantation in life-threatening hypercapnia, Schellongowski [/bib_ref] , [fig_ref] Table 2: Prevention and risk reduction [/fig_ref].

## Special positioning of patients
Positioning therapy is used for prophylaxis and treatment of respiratory dysfunctions , and requires an individual sedation target. Changes of the position frequently represent a challenge for the symptomatic treatment of anxiety, stress, and pain. Therefore, a symptom-orientated therapy should be adapted for changing demands during positioning therapy. Though a deep sedation may be indicated for patient repositioning, , , an excessive sedation should be avoided.

## Analgesia, sedation, and delirium management in children monitoring
For the monitoring of analgesia, sedation, and delirium in children, there are validated monitoring scales are that take developmental stage into account . Also in the pediatric intensive care, adequate monitoring and individual therapy goals are essential for successful patientoriented care [fig_ref] Table 2: Prevention and risk reduction [/fig_ref].
Generally, children aged 3 years are able to evaluate pain-levels. Even in children, a self-assessment of pain is superior to observational scales , and the Faces Pain Scale-revised has been well-established as a valid monitoring tool . If children are unable to assess their pain, there are several age-appropriate observational pain assessment scales. However, both in very premature infants as well as in children and adolescents with neurocognitive impairment, those instruments have a limited value and tend to systematically underestimate pain [bib_ref] Judgments of pain in the neonatal intensive care setting: a survey of..., Breau [/bib_ref] , , . Combined pain and distress sedation scales have been validated for the monitoring of sedation in children. For premature and full-term neonates, the Neonatal Pain, Agitation and Sedation Scale (N-PASS) is available. For infants and toddlers, the COMFORTneo Scale and the Comfort-B Scale are available. Additionally, there are special scales for assessing opioid or sedative withdrawal following a continuous therapy. Children can also suffer from delirium, and their symptoms are often misinterpreted. The pediatric critical care community has a need for a systematic delirium screening with validated tools , , , .

## Treatment strategies in children
Critically ill children -like adults -require an individual pain therapy adapted to their current situation. This includes multimodal therapy strategies for opioids, nonopioids, and regional analgesia, as well as for local anesthetics, co-analgesics and non-pharmacological procedures [fig_ref] Table 3: Long-term consequences [/fig_ref]. When regarding analgesia in children, it is important to consider that pharmacokinetics and pharmacodynamics differ with age. Additional and supportive procedures for analgesia are also recommended for children. There are different non-pharmacological procedures available that can be used for co-analgesia, per example the administration of oral glucose, non-nutritive suction for neonates, or virtual reality for pediatric burn patients. Children require sedation, sometimes continuously, in order to undergo certain diagnostic and therapeutic procedures. For sedation in children, special personnel and structural prerequisites are required. Oversedation should be avoided as always, and careful titration is required to keep dosages as low as possible.
There is still a high demand for research regarding pediatric delirium. In principle, it is essential to detect delirious symptoms as early as possible and identify and neutralize potential causes. Current evidence revealed a combination of psychological, social (presence of family, toys, pictures of home, normal day-night rhythm, etc.), and pharmacological interventions to be effective .
Analgesia, sedation, and delirium management in elderly patients
The "clinical age" is determined by the biological age, frailty, comorbidities, long-term medication, and external influences. The ageing of the cardiovascular, respiratory, renal, and nervous-systems lead to changes in pharmacodynamics and kinetics. The inherent age cannot be based on a chronological age alone [fig_ref] Table 3: Long-term consequences [/fig_ref].
Elderly patients lack the resources to compensate for delirium-associated complications, thus a frequent and active screening for delirium is paramount. In principle, all monitoring instruments used for the adult patients may be used for elderly patients. To evaluate pain in patients with cognitive impairment or dementia, tools such as Faces Pain Scale, PAINAD-scale as well as the BESDscale (German scale) are available. Preventive measures such as reorientation, visual and hearing aids are especially indicated for elderly patients . Regarding the treatment of delirium, a symptomatic treatment should consider the delirogenic effects of longacting benzodiazepines , the cardiac side effects of neuroleptics, and the use of appropriately cautious dosages , , . For the treatment of delirium, melatonin or melatonin-analogues should be considered at night to reduce the incidence and duration of delirium .
Economy, quality assurance and implementation of the guideline
In terms of quality assurance, management of analgesia, sedation and delirium in the ICU should be conducted according to guidelines and subject to a continuous quality verification [bib_ref] American College of Critical Care Medicine. Clinical practice guidelines for the management..., Barr [/bib_ref]. This includes the regular training of personnel in the implementation of the guidelines [bib_ref] Large-scale implementation of sedation and delirium monitoring in the intensive care unit:..., Pun [/bib_ref]. Special consideration for regional characteristics and internal Standard Operating Procedures improved the integration of guideline recommendations [bib_ref] Large-scale implementation of sedation and delirium monitoring in the intensive care unit:..., Pun [/bib_ref]. As a follow-up to the surveys of 2002 and 2006, a current survey on the current implementation of the S3-guideline in clinical routine is being carried out and will be published. Before the next guideline update process, an additional survey will assess the level of implementation [fig_ref] Table 3: Long-term consequences [/fig_ref].

## Notes
Extended version of the guideline We recommend the use of validated scales for the therapy control of analgesia, sedation, anxiety, and delirium (10).
[10] 1b A The suitability and significance of diagnostic devices are still unclear. However, we recommend the use of such devices, in a supporting role, on patients who are deeply sedated (RASS -4/-5) or under neuromuscular blockade, so as to promptly identify under or oversedation [bib_ref] Monitoring sedation in critically ill patients: bispectral index, Ramsay and observer scales, Hernandez-Gancedo [/bib_ref] [bib_ref] Continuous nervous system monitoring, EEG, the bispectral index, and neuromuscular transmission, Arbour [/bib_ref] [bib_ref] Role of the bispectral index in sedation monitoring in the ICU, Leblanc [/bib_ref].
Upgrading: relevance [bib_ref] Monitoring sedation in critically ill patients: bispectral index, Ramsay and observer scales, Hernandez-Gancedo [/bib_ref] 2b [bib_ref] Continuous nervous system monitoring, EEG, the bispectral index, and neuromuscular transmission, Arbour [/bib_ref] 3b [bib_ref] Role of the bispectral index in sedation monitoring in the ICU, Leblanc [/bib_ref] 2a A 4. [bib_ref] Impact of systematic evaluation of pain and agitation in an intensive care..., Chanques [/bib_ref] We recommend the use of EEG monitoring in order to identify non-convulsive seizure activity in patients with reduces level of consciousness (e.g., hypoactive delirium, which does not respond to a pharmacological therapy) [bib_ref] Baseline EEG pattern on continuous ICU EEG monitoring and incidence of seizures, Swisher [/bib_ref].
Upgrading: clinical relevance / frequency [bib_ref] Baseline EEG pattern on continuous ICU EEG monitoring and incidence of seizures, Swisher [/bib_ref] 2b A According to the pain level and potential side effects, non-opioids and/or co-analgesics may be considered as alternative or adjunctive medication.

## Downgrading: individual indication
[129] 1a 0

## 5.b.4
A patient-controlled analgesia may be considered dependent on the patient's condition (RASS 0/-1, no delirium).

## Downgrading: feasibility
[20] 1a 0
[formula] 5.b.5 [/formula]
If the patient is awake and cooperative, patient-controlled analgesia (PCA) should be preferred over conventional application methods, as improved pain control and patient satisfaction are achieved.

## Downgrading: feasibility
[20] 1a B 5.b. [bib_ref] Impact of delirium on clinical outcome in critically ill patients: a meta-analysis, Zhang [/bib_ref] The possibility of a combination with regional analgesia (in particular epidural analgesia) should be considered [bib_ref] Protective effects of epidural analgesia on pulmonary complications after abdominal and thoracic..., Popping [/bib_ref]. The placement of regional catheters and initiation of therapy should take place as early as possible before surgery.

## Downgrading: feasibility, individual indication
[formula] [19] 1a B 5.b.7 [/formula]
Potentially painful interventions shall only be performed under adequate analgesia (local, regional, general anaesthesia, or sedation).
Upgrading: ethics 5 A

## Regional analgesia loe gor
6.1 Before employing regional anesthesia, an individual risk-benefit assessment should take place, and this assessment should be re-evaluated on a daily basis.
Upgrading: safety 5 B

## 6.2
In accordance with the indication and risk-benefit assessment, we recommend the preferred use of epidural catheters with local-anesthetics, as this has been shown to improve results on perioperative analgesia [bib_ref] Epidural anaesthesia and survival after intermediate-to-high risk non-cardiac surgery: a population-based cohort..., Wijeysundera [/bib_ref] , reduce pulmonary complications, improve intestinal motility and mobilization, as well as reduce ICU length of stay [bib_ref] The comparative effects of postoperative analgesic therapies on pulmonary outcome: cumulative meta-analyses..., Ballantyne [/bib_ref] when compared to intravenous opioid-treatment.
[130] 1a [bib_ref] Epidural anaesthesia and survival after intermediate-to-high risk non-cardiac surgery: a population-based cohort..., Wijeysundera [/bib_ref] 1b [bib_ref] The comparative effects of postoperative analgesic therapies on pulmonary outcome: cumulative meta-analyses..., Ballantyne [/bib_ref] 1a A 6. [bib_ref] Investigators; Canadian Critical Care Trials Group. Prevalence, risk factors, and outcomes of..., Mehta [/bib_ref] We suggest the use of an epidural catheter analgesia with either local anesthetics or in combination with an opioid, as these have been shown to be more effective than a sole epidural opioid administration in the treatment of pain [bib_ref] Epidural local anaesthetics versus opioid-based analgesic regimens on postoperative gastrointestinal paralysis, PONV..., Jorgensen [/bib_ref].
[133] 1a B 6.4 Neuraxial regional analgesia procedures should be atraumatic. If this is not possible, the procedure should be aborted and the patient should be closely monitored for possible complications.
Upgrading: relevance, safety We suggest the development of local standards for the use of regional analgesic techniques in the ICU, so as to improve patient safety and facilitate the decision making process [bib_ref] University of Virginia Long Term Mechanical Ventilation Team. Implementation of an institutional..., Burns [/bib_ref].

## Upgrading: relevance, safety
[138] 4 B In adult burn patients, the use of co-analgesics, such as gabapentin, may be considered adjunctively to opioids [bib_ref] Effects of gabapentin on morphine consumption and pain in severely burned patients, Cuignet [/bib_ref].
[184] 3b 0 B3. [bib_ref] Delirium as a predictor of mortality in mechanically ventilated patients in the..., Ely [/bib_ref] We suggest the use of ketamine to reduce secondary hyperalgesia [bib_ref] Ketamine, an NMDA receptor antagonist, suppresses spatial and temporal properties of burninduced..., Warncke [/bib_ref] [bib_ref] Effect of systemic N-methyl-D-aspartate receptor antagonist (ketamine) on primary and secondary hyperalgesia..., Ilkjaer [/bib_ref] , and the opioid demand (187) of burn patients.
[185] 1b [bib_ref] Effect of systemic N-methyl-D-aspartate receptor antagonist (ketamine) on primary and secondary hyperalgesia..., Ilkjaer [/bib_ref] 1b [bib_ref] Ketamine for long-term sedation and analgesia of a burn patient, Edrich [/bib_ref] 4 B B3. [bib_ref] Incidence, risk factors and consequences of ICU delirium, Ouimet [/bib_ref] We suggest the use of alpha-2 agonists for sedation, as they have been shown to be more effective on burn patients as other drugs (e.g. benzodiazepines) [bib_ref] A meta-analysis of analgesic and sedative effects of dexmedetomidine in burn patients, Asmussen [/bib_ref]. Downgrading: individual indication [bib_ref] A meta-analysis of analgesic and sedative effects of dexmedetomidine in burn patients, Asmussen [/bib_ref] 1a B B3. [bib_ref] Impact of delirium on clinical outcome in critically ill patients: a meta-analysis, Zhang [/bib_ref] The topical application of lidocaine may be considered during dressing changes, as it alleviates pain during the procedure [bib_ref] Effectiveness of a topical local anaesthetic spray as analgesia for dressing changes:..., Desai [/bib_ref].

## Downgrading: individual indication
[189] 1b 0 B3. [bib_ref] BRAIN-ICU Study Investigators. Long-term cognitive impairment after critical illness, Pandharipande [/bib_ref] We suggest using virtual reality (VR) as a non-pharmacological intervention, in additional to the pharmacological therapy of pain and anxiety [bib_ref] Grimmer-Somers K. The effectiveness of virtual reality on reducing pain and anxiety..., Morris [/bib_ref]. Downgrading: availability [bib_ref] Grimmer-Somers K. The effectiveness of virtual reality on reducing pain and anxiety..., Morris [/bib_ref] 1a B

## Burn-injured children loe gor
B3a.1 We recommend using standardized protocols and training programs for analgesia and sedation during dressing changes in burned children [bib_ref] Analgesia and sedation for children undergoing burn wound care, Bayat [/bib_ref].

## Upgrading: relevance
[formula] [46] 5 A B3a.2 [/formula]
For the of procedural pain, we suggest the use of ketamine over opioids [bib_ref] Superiority of oral ketamine as an analgesic and sedative for wound care..., Humphries [/bib_ref]. [bib_ref] Superiority of oral ketamine as an analgesic and sedative for wound care..., Humphries [/bib_ref] 2b B B3a.The combination of non-pharmacological procedures (massage in non-burned areas, hypnosis, and virtual reality) with opioids is more effective at alleviating pain than a single opioid analgesia. Therefore, we suggest using non-pharmacological procedures in combination with opioids in burn-injured children [bib_ref] Burn injuries benefit from massage therapy, Field [/bib_ref] , [bib_ref] Childrens' distress during burn treatment is reduced by massage therapy, Hernandez-Reif [/bib_ref] , [bib_ref] Psychological approaches during dressing changes of burned patients: a prospective randomised study..., Frenay [/bib_ref].
Downgrading: availability [bib_ref] Burn injuries benefit from massage therapy, Field [/bib_ref] 1b [bib_ref] Childrens' distress during burn treatment is reduced by massage therapy, Hernandez-Reif [/bib_ref] 1b [bib_ref] Psychological approaches during dressing changes of burned patients: a prospective randomised study..., Frenay [/bib_ref] 1b B B3a.3 For procedural sedation during dressing changes in burned children, the use of dexmedetomidine may be considered [bib_ref] A comparison of dexmedetomidine and midazolam for sedation in severe pediatric burn..., Fagin [/bib_ref].
Downgrading: off-label-use [bib_ref] A comparison of dexmedetomidine and midazolam for sedation in severe pediatric burn..., Fagin [/bib_ref] 1b 0 We suggest no longer the use of etomidate for procedural sedation on critically ill trauma patients [bib_ref] Increased risk of adrenal insufficiency following etomidate exposure in critically injured patients, Cotton [/bib_ref] [bib_ref] Adrenal suppression following a single dose of etomidate for rapid sequence induction:..., Hildreth [/bib_ref] [bib_ref] Single-dose etomidate for rapid sequence intubation may impact outcome after severe injury, Warner [/bib_ref].
Downgrading: inconsistent evidence1a [bib_ref] Increased risk of adrenal insufficiency following etomidate exposure in critically injured patients, Cotton [/bib_ref] 3b [bib_ref] Adrenal suppression following a single dose of etomidate for rapid sequence induction:..., Hildreth [/bib_ref] 1b [bib_ref] Single-dose etomidate for rapid sequence intubation may impact outcome after severe injury, Warner [/bib_ref] 2b1a B

## Patients with intracranial hypertension loe gor
B5.1 According to current evidence, there is no evidence for the use of a specific monitoring tool able to assess analgesia or sedation of ICU patients with with severe traumatic brain injury or intracranial hypertension. We recommend frequent neurological examinations in these patients [bib_ref] Neurological examination of critically ill patients: a pragmatic approach, Sharshar [/bib_ref].
[50] 1a A B5.2 In patients with severe traumatic brain injury or intracranial hypertension, we recommend an adequate analgesia and sedation with a well-defined sedation targets (in terms of target RASS) [bib_ref] Guidelines for the management of severe traumatic brain injury. XI. Anesthetics, analgesics,..., Bratton [/bib_ref]. [bib_ref] Guidelines for the management of severe traumatic brain injury. XI. Anesthetics, analgesics,..., Bratton [/bib_ref] 1a A B5. [bib_ref] Investigators; Canadian Critical Care Trials Group. Prevalence, risk factors, and outcomes of..., Mehta [/bib_ref] We suggest the use of ketamine racemate during mechanical ventilation (constant paCO2) and additive sedation with GABAA-receptor-agonists (suppression of excitation) in patients with severe traumatic brain injury and intracranial hypertension [bib_ref] Ketamine does not increase intracranial pressure compared with opioids: meta-analysis of randomized..., Wang [/bib_ref].
Downgrading: off-label-use1a [bib_ref] Ketamine does not increase intracranial pressure compared with opioids: meta-analysis of randomized..., Wang [/bib_ref] 1a B B5. [bib_ref] Delirium as a predictor of mortality in mechanically ventilated patients in the..., Ely [/bib_ref] We suggest the use of a ketamine-racemate / midazolam-based or an opioid / midazolambased sedation regimen in mechanically ventilated patients with severe traumatic brain injury and intracranial hypertension [bib_ref] Ketamine does not increase intracranial pressure compared with opioids: meta-analysis of randomized..., Wang [/bib_ref].

## Downgrading: off-label-use, individual indication
[201] 1a [bib_ref] Ketamine does not increase intracranial pressure compared with opioids: meta-analysis of randomized..., Wang [/bib_ref] 1a B B5.5 A S(+)-ketamine / methohexital-based or a fentanyl / methohexital-based sedation strategy may be considered in mechanically ventilated patients with severe traumatic brain injury and intracranial hypertension [bib_ref] Ketamine for analgosedative therapy in intensive care treatment of headinjured patients, Kolenda [/bib_ref] [bib_ref] Safety of sedation with ketamine in severe head injury patients: comparison with..., Bourgoin [/bib_ref].

## Downgrading: individual indication
[203] 2b [bib_ref] Safety of sedation with ketamine in severe head injury patients: comparison with..., Bourgoin [/bib_ref] 2b 0 B5. [bib_ref] Impact of delirium on clinical outcome in critically ill patients: a meta-analysis, Zhang [/bib_ref] We suggest the monitoring the mean arterial pressure during continuous application of opioids (remifentanil, sufentanil, fentanyl, morphine) in patients with intracranial hypertension [bib_ref] Ketamine for analgosedative therapy in intensive care treatment of headinjured patients, Kolenda [/bib_ref] [bib_ref] Safety of sedation with ketamine in severe head injury patients: comparison with..., Bourgoin [/bib_ref] [bib_ref] Opioid sedation does not alter intracranial pressure in head injured patients, Lauer [/bib_ref]. [bib_ref] Ketamine for analgosedative therapy in intensive care treatment of headinjured patients, Kolenda [/bib_ref] [bib_ref] Safety of sedation with ketamine in severe head injury patients: comparison with..., Bourgoin [/bib_ref] [bib_ref] Opioid sedation does not alter intracranial pressure in head injured patients, Lauer [/bib_ref] 2b B B5. [bib_ref] BRAIN-ICU Study Investigators. Long-term cognitive impairment after critical illness, Pandharipande [/bib_ref] The favourable pharmacokinetics of remifentanil allows for a rapid neurological assessment. Therefore, we suggest the preferential use of remifentanil over other opioids for analgesia in NICU-patients, as long as the duration of sedation is expected to last less than 72 hours [bib_ref] Sedation in neurointensive care: advances in understanding and practice, Citerio [/bib_ref] [bib_ref] Critical care sedation for neuroscience patients, Mirski [/bib_ref].
[206] 2b [bib_ref] Critical care sedation for neuroscience patients, Mirski [/bib_ref] 2a [bib_ref] Sedation in neurointensive care: advances in understanding and practice, Citerio [/bib_ref] 2a2a2b B B5. [bib_ref] Risk factors for incident delirium among older people in acute hospital medical..., Ahmed [/bib_ref] We suggest avoiding bolus administration of opioids whenever possible. In the exceptional cases where it is necessary, MAP and ICP should be monitored [bib_ref] Sedation for critically ill adults with severe traumatic brain injury: a systematic..., Roberts [/bib_ref].
Downgrading: problem of steerability [bib_ref] Sedation for critically ill adults with severe traumatic brain injury: a systematic..., Roberts [/bib_ref] 1a B
B5.9 For traumatic brain injury patients, the propofol-based and midazolam-based sedation regimens are similarly safe. We suggest the preferential use of propofol if rapid neurological assessments are necessary [bib_ref] Sedation for critically ill adults with severe traumatic brain injury: a systematic..., Roberts [/bib_ref].

## Downgrading: individual medical situation/indication
[formula] [210] 1a B [/formula]
B5. [bib_ref] Impact of systematic evaluation of pain and agitation in an intensive care..., Chanques [/bib_ref] We do not recommend a high-dose barbiturate as prophylaxis for intracranial hypertension in patients with severe traumatic brain injury [bib_ref] Guidelines for the management of severe traumatic brain injury. XI. Anesthetics, analgesics,..., Bratton [/bib_ref] [bib_ref] The University of Toronto head injury treatment study: a prospective, randomized comparison..., Schwartz [/bib_ref] [bib_ref] Failure of prophylactic barbiturate coma in the treatment of severe head injury, Ward [/bib_ref] 

## Monitoring of sedation in children loe gor
[formula] C.1.b.1 [/formula]
The Neonatal Pain, Agitation and Sedation Scale (N-PASS) and the COMFORTneo scale may be considered for the depth of sedation assessment in premature and full-term infants [bib_ref] The Neonatal Pain, Agitation and Sedation Scale and the bedside nurse's assessment..., Hillman [/bib_ref] [bib_ref] Successful implementation of a neonatal pain and sedation protocol at 2 NICUs, Deindl [/bib_ref] [bib_ref] The Neonatal Pain, Agitation and Sedation Scale reliably detected oversedation but failed..., Giordano [/bib_ref] [bib_ref] Clinical reliability and validity of the N-PASS: neonatal pain, agitation and sedation..., Hummel [/bib_ref] [bib_ref] The COMFORT behavioural scale and the modified FLACC scale in paediatric intensive..., Johansson [/bib_ref] [bib_ref] COMFORT scale: a reliable and valid method to measure the amount of..., Wielenga [/bib_ref].
[228] 2b [bib_ref] Successful implementation of a neonatal pain and sedation protocol at 2 NICUs, Deindl [/bib_ref] 1b [bib_ref] The Neonatal Pain, Agitation and Sedation Scale reliably detected oversedation but failed..., Giordano [/bib_ref] 1b [bib_ref] Clinical reliability and validity of the N-PASS: neonatal pain, agitation and sedation..., Hummel [/bib_ref] 1b2b [bib_ref] The COMFORT behavioural scale and the modified FLACC scale in paediatric intensive..., Johansson [/bib_ref] 2b [bib_ref] COMFORT scale: a reliable and valid method to measure the amount of..., Wielenga [/bib_ref] 2b
[formula] 0 C.1.b.2 [/formula]
As an observational scale, we recommend using the Comfort-B Scale to assess the depth of sedation in neonates and children (238).
[238] 1b A
[formula] C.1.b.3 [/formula]
Following a continuous sedative therapy, we suggest considering the possibility of a sedative withdrawal (especially as seizure). The Finnegan-Score Monitoring tool is available to assess sedative-withdrawal in neonates, whereas the SOS and the WAT-1 scores are available for children and adolescents [bib_ref] Review of the assessment and management of neonatal abstinence syndrome, Bagley [/bib_ref] [bib_ref] Construction of the Sophia Observation withdrawal Symptomsscale (SOS) for critically ill children, Ista [/bib_ref] [bib_ref] The Withdrawal Assessment Tool-1 (WAT-1): an assessment instrument for monitoring opioid and..., Franck [/bib_ref].
[229] 1a [bib_ref] Construction of the Sophia Observation withdrawal Symptomsscale (SOS) for critically ill children, Ista [/bib_ref] 2b [bib_ref] The Withdrawal Assessment Tool-1 (WAT-1): an assessment instrument for monitoring opioid and..., Franck [/bib_ref] 1b B

## Non-pharmacological procedures in children loe gor

## C.2.b.1
We suggest regarding every corrigible environmental factor, and a attentive treatment should be ensured [bib_ref] Double-blind, placebo-controlled analgesic study of ibuprofen or rofecoxib in combination with paracetamol..., Pickering [/bib_ref].
Upgrading: relevance
[formula] [250] 4 B C.2.b.2 [/formula]
We suggest supporting a normal sleep pattern, particularly an adequate light and noise reduction, and the sleep-wake cycle of the patient should be considered.
Upgrading: relevance In older, critically ill children, we suggest the use of enteral sedatives as early as possible [bib_ref] A randomized controlled trial of sedation in the critically ill, Parkinson [/bib_ref].
[formula] [239] 5 B [/formula]

## Downgrading: individual indication
[260] 1b B C.2.c. [bib_ref] Impact of delirium on clinical outcome in critically ill patients: a meta-analysis, Zhang [/bib_ref] We recommend that the long-term sedation of neonates be undertaken only after critical risk-benefit analysis, and in very exceptional cases, such as life-threatening, otherwise uncontrollable agitation [bib_ref] Intravenous midazolam infusion for sedation of infants in the neonatal intensive care..., Ng [/bib_ref].
[formula] [261] 1a A C.2.c.7 [/formula]
In the rare cases when neonate sedation is required, we suggest the preferential use of morphine over midazolam. In order to avoid sedative withdrawal, one may consider gradually tapering-off these drugs following a continuous therapy. In patients with advanced dementia, the "PAINAD Scale" (pain assessment in advanced dementia) may be considered for pain assessment [bib_ref] Development and psychometric evaluation of the Pain Assessment in Advanced Dementia (PAINAD)..., Warden [/bib_ref].

## Downgrading: insufficient evidence at this point of the review

## 0

## Downgrading: individual indication

## Economy, quality assurance, and implementation of the guideline loe gor

## E.1
We recommend that the management of analgesia, sedation and delirium in the ICU be compliant to the guidelines, and subject to a continuous quality review [bib_ref] American College of Critical Care Medicine. Clinical practice guidelines for the management..., Barr [/bib_ref]. [bib_ref] American College of Critical Care Medicine. Clinical practice guidelines for the management..., Barr [/bib_ref] 1a A E.2 Provided that the ICU nursing staff shows specific and qualified knowledge, experience, and skill, they may control the management of analgesia and sedation (using a syringe pump) according to predetermined protocols and doctor's orders [bib_ref] Effect of a nurse-implemented sedation protocol on the incidence of ventilator-associated pneumonia, Quenot [/bib_ref] [bib_ref] Effect of a nursing-implemented sedation protocol on the duration of mechanical ventilation, Brook [/bib_ref] [bib_ref] Effect of a scoring system and protocol for sedation on duration of..., Brattebo [/bib_ref].
Downgrading: individual clinical setting [bib_ref] Effect of a nurse-implemented sedation protocol on the incidence of ventilator-associated pneumonia, Quenot [/bib_ref] 1b [bib_ref] Effect of a nursing-implemented sedation protocol on the duration of mechanical ventilation, Brook [/bib_ref] 1b [bib_ref] Effect of a scoring system and protocol for sedation on duration of..., Brattebo [/bib_ref] 3b 0 E.3 In order to increase therapeutic safety and to facilitate decision-making, we recommend the implementation of internal standards for analgesia, sedation and treatment of delirium (including the use of sedation protocols) [bib_ref] Efficacy and safety of a paired sedation and ventilator weaning protocol for..., Girard [/bib_ref] [bib_ref] Protocol-driven ventilator weaning: reviewing the evidence, Girard [/bib_ref].
[formula] [21] 1b [281] 2b A E.4 [/formula]
For the consistent implementation of guidelines and standards, we recommend the regular training of personnel in their application [bib_ref] Large-scale implementation of sedation and delirium monitoring in the intensive care unit:..., Pun [/bib_ref] [bib_ref] How to implement monitoring tools for sedation, pain and delirium in the..., Radtke [/bib_ref] [bib_ref] A systematic review of implementation strategies for assessment, prevention, and management of..., Trogrlic [/bib_ref].
[83] 2b [bib_ref] How to implement monitoring tools for sedation, pain and delirium in the..., Radtke [/bib_ref] 1b [bib_ref] A systematic review of implementation strategies for assessment, prevention, and management of..., Trogrlic [/bib_ref] 1a A [bib_ref] A systematic review of measurements of physical function in critically ill adults, Tipping [/bib_ref]. Zum Monitoring von Schlaf fehlt es an einer validen Beurteilung von Schlafstadien bei intensivmedizinischen Patienten, zum anderen an praktisch durchfuhrbaren Monitoringverfahren, die sich in die Routine eingliedern lassen [bib_ref] Diurnal sedative changes during intensive care: impact on liberation from mechanical ventilation..., Seymour [/bib_ref] (Tabelle 4-9).

## Therapeutische konzepte
Siehe Abbildung 2.

## Nicht-pharmakologische konzepte
Siehe Tabelle 10.

## Analgesie
Intensivmedizinisch-behandelte Patienten bedurfen einer individuell angepassten Schmerztherapie. Schmerzen haben deutlich negative Auswirkungen auf den Genesungsprozess und sind die haufigsten subjektiv empfundenen Stressoren bei Intensivpatienten. Daher muss eine suffiziente Analgesie bei allen Intensivpatienten -unab-hangig von der Indikation einer Sedierung-durchgefuhrt werden. Dabei erfolgen potentiell schmerzhafte Manahmen unter praventiver analgetischer Abschirmung. Die Analgesie wird auf der Intensivstation vorwiegend Opioidbasiert durchgefuhrt, [bib_ref] Short term analgesia based sedation in the Intensive Care Unit: morphine vs..., Carrer [/bib_ref] , [bib_ref] Remifentanil for tracheal tube tolerance: a case control study, Machata [/bib_ref] , [bib_ref] Intravenous paracetamol reduced the use of opioids, extubation time, and opioid-related adverse..., Memis [/bib_ref]. Die Rolle von Nicht-Opioid-Analgetika wird neu diskutiert, weil beispielsweise NSAID ein vergleichsweise geringes analgetisches Potential bei einem gleichzeitig fur Intensivpatienten ungunstigen Nebenwirkungsprofil aufweisen. Eine patientenkontrollierten Analgesie wird empfohlen, sobald der Zustand des Patienten dies ermoglicht (RASS 0/-1 und kein Delir). Auch eine Kombination mit Regionalverfahren ist moglich [bib_ref] Protective effects of epidural analgesia on pulmonary complications after abdominal and thoracic..., Popping [/bib_ref] (Tabelle 11).

## Sedierung
Die aktuelle Evidenz belegt, dass eine messbare Sedierung immer vermieden werden soll, solange keine zwingende Indikation fur eine solche vorliegt [bib_ref] Efficacy and safety of a paired sedation and ventilator weaning protocol for..., Girard [/bib_ref] , [bib_ref] Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation, Kress [/bib_ref]. Eine tiefe Sedierung auch innerhalb der ersten 48 h geht mit einer erhohten Mortalitat, einer prolongierten Beatmungsdauer und einer verlangerten Intensiv-und Krankenhausverweildauer einher, [bib_ref] SEDCOM (Safety and Efficacy of Dexmedetomidine Compared With Midazolam) Study Group. Delirium..., Shehabi [/bib_ref] , [bib_ref] Early deep sedation is associated with decreased in-hospital and two-year follow-up survival, Balzer [/bib_ref] , [bib_ref] Sedation Practice in Intensive Care Evaluation (SPICE) Study Investigators; ANZICS Clinical Trials..., Shehabi [/bib_ref]. Auerhalb spezieller Indikationen (z.B. chirurgische Indikationen, Hirndrucksymptomatik mit drohender Einklemmung oder zur Reduktion des Sauerstoffverbrauchs bei drohender Hypoxie), soll das Ziel ein wacher, kooperativer Patient, der die intensivmedizinisch erforderlichen Manahmen gut toleriert (RASS 0/-1) sein. Grundlage ist die suffiziente Analgesie, die von einer moglichst spezifischen Therapie von Symptomen, wie Halluzinationen, Stress und Angst begleitet wird [bib_ref] Management of sedation in mechanically ventilated patients, Hogarth [/bib_ref] , [bib_ref] Sedation in the intensive care unit, Young [/bib_ref] , [bib_ref] A protocol of no sedation for critically ill patients receiving mechanical ventilation:..., Strom [/bib_ref]. Patienten bedurfen keiner Aufwachversuche, wenn keine Sedierung durchgefuhrt wird. Der Stellenwert von taglichen Sedierungsunterbrechungen (daily sedation interruption (DSI)) zeigt sich in einem aktuellen systematischen Review nicht mehr der protokollbasierten Sedierung uberlegen. Der Ziel-RASS 0/-1 soll so fruh wie moglich etabliert werden, da die ersten 48h der Intensivbehandlung entscheidend fur das Behandlungsergebnis sehen. Daher sollte ein Sedierungsprotokoll dem Prinzip der "early goal directed therapy" folgen (Tabelle 12).

## Moderate oder tiefe sedierung

## Pharmakologische therapie des delirs
Praventive Manahmen zur Vermeidung eines Delirs sind effektiv und sicher durchfuhrbar [bib_ref] Pharmacological treatments of non-substance-withdrawal delirium: a systematic review of prospective trials, Friedman [/bib_ref]. Falls ein Delir dennoch auftritt, muss es zeitnah symptomorientiert behandelt werden. Die Behandlung von produktiv-psychotischen Symptomen (im Rahmen eines Delirs oder auch ohne Delir) kann mit niedrig-dosierten Neuroleptika erfolgen [bib_ref] Atypical antipsychotics in the treatment of delirium, Wang [/bib_ref]. Ebenfalls ist der Einsatz von Alpha-2-Agonisten zur Delirtherapie geeignet, [bib_ref] MIND Trial Investigators. Feasibility, efficacy, and safety of antipsychotics for intensive care..., Girard [/bib_ref]. Eine Besonderheit stellt das Alkoholentzugsdelir auf Intensivstationen dar, bei dem langwirksame Benzodiazepine indiziert sind(Tabelle 15).

## Entwohnung von der beatmung
Das Prozedere der Beatmungsentwohnung wird in der neuen S2k-Leitlinie "Prolongiertes Weaning" uber die AWMF-Leitlinie (020/015) dargestellt. Das Management von Analgesie, Sedierung und Delirmanagement beeinflusst den Weaning-Prozess mageblich [bib_ref] Weaning from mechanical ventilation and sedation, Luetz [/bib_ref]. Um das Weaning zu einem fruhestmoglichen Zeitpunkt beginnen zu konnen, empfiehlt sich ein Weaningsprotokoll mit einem Sedierungsprotokoll zu kombinieren (Tabelle 16).

## Neuromuskulare blockade (nmb)

## Kardiochirurgische patienten
Fast-track-Konzepte nach unkomplizierten kardiochirurgischen Verlaufen beinhalten eine postoperative Kurzzeitsedierung in den ersten zwei Stunden nach der Operation. In diesem Setting haben sich zahlreiche Analgesieund Sedierungsprotokolle als vorteilhaft erwiesen [bib_ref] A greater analgesia, sedation, delirium order set quality score is associated with..., Dale [/bib_ref]. Fast-track-Konzepte scheinen somit die Inzidenz fur ein postoperatives Delir zu reduzieren [bib_ref] Meta-analysis of factors which influence delirium following cardiac surgery, Lin [/bib_ref]. Gerade bei kardiochirurgischen Patienten wurde eine durch ein Delir erhohte Mortalitat nachgewiesen [bib_ref] Delirium in elderly patients and the risk of postdischarge mortality, institutionalization, and..., Witlox [/bib_ref]. Daher ist ein Delirscreening mit validem Instrumentwie im allgemeinen Teil empfohlen -besonders wichtig [bib_ref] Postoperative delirium in a substudy of cardiothoracic surgical patients in the BAG-RECALL..., Whitlock [/bib_ref] , [bib_ref] Pregabalin has an opioidsparing effect in elderly patients after cardiac surgery: a..., Pesonen [/bib_ref] (Tabelle 25).

## Patienten mit extrakorporalen herz-und lungenersatzverfahren
Patienten mit extrakorporalen Herz-und Lungenersatzverfahren befinden sich bezuglich des Grades an zu erzielender Wachheit in einem Spannungsfeld zwischen Sicherheitsaspekten und der Moglichkeit wach aktiv den eigenen Heilverlauf zu beeinflussen.
Patienten an extrakorporalen Herz-und Lungenersatzverfahren weisen etliche Risikofaktoren fur das Auftreten eines Delirs auf. Agitation und ein hyperaktives Delir stellen ein vital bedrohliches Sicherheitsrisiko dar. Daher ist ein engmaschiges Monitoring und eine symptomorientierte Therapie von Stress, Angst, Delir, Schmerzen und Schlaflosigkeit essentiell, um einen Ziel-RASS = 0 bei Patienten an extrakorporalen Herz-und Lungenersatzverfahren sicher durchzufuhren [bib_ref] Extracorporeal Co2 removal in hypercapnic patients at risk of noninvasive ventilation failure:..., Sorbo [/bib_ref] , [bib_ref] Extracorporeal membrane oxygenation in awake patients as bridge to lung transplantation, Fuehner [/bib_ref] , [bib_ref] Avoiding invasive mechanical ventilation by extracorporeal carbon dioxide removal in patients failing..., Kluge [/bib_ref] , [bib_ref] Extracorporeal CO2 removal as bridge to lung transplantation in life-threatening hypercapnia, Schellongowski [/bib_ref] ,(Tabelle 26).

## Patienten mit spezieller lagerungstherapie
Lagerungstherapien dienen der Prophylaxe und Behandlung von pulmonalen Funktionsstorungen und bedurfen eines individuellen Sedierungsziels. Positionsanderungen stellen haufig eine Herausforderung fur die symptomorientierte Therapie von Angst, Stress und Schmerzen dar. Ihre symptomorientierte Therapie muss daher wahrend einer Lagerungstherapie angepasst werden. Zur Umlagerung im Rahmen der Lagerungstherapie kann eine tiefe Sedierung indiziert sein , . Auch dabei muss eine Ubersedierung vermieden werden. [bib_ref] Burn injuries benefit from massage therapy, Field [/bib_ref] , [bib_ref] Childrens' distress during burn treatment is reduced by massage therapy, Hernandez-Reif [/bib_ref] , [bib_ref] Psychological approaches during dressing changes of burned patients: a prospective randomised study..., Frenay [/bib_ref].
Downgrading: Verfugbarkeit [bib_ref] Burn injuries benefit from massage therapy, Field [/bib_ref] 1b [bib_ref] Childrens' distress during burn treatment is reduced by massage therapy, Hernandez-Reif [/bib_ref] 1b [bib_ref] Psychological approaches during dressing changes of burned patients: a prospective randomised study..., Frenay [/bib_ref] 1b B B3a.3 Zur prozeduralen Sedierung zum Verbandswechsel brandverletzter Kinder kann Dexmedetomidin verwendet werden [bib_ref] A comparison of dexmedetomidine and midazolam for sedation in severe pediatric burn..., Fagin [/bib_ref].
Downgrading: off-label-use [bib_ref] A comparison of dexmedetomidine and midazolam for sedation in severe pediatric burn..., Fagin [/bib_ref] 1b 0 [bib_ref] Increased risk of adrenal insufficiency following etomidate exposure in critically injured patients, Cotton [/bib_ref] [bib_ref] Adrenal suppression following a single dose of etomidate for rapid sequence induction:..., Hildreth [/bib_ref] [bib_ref] Single-dose etomidate for rapid sequence intubation may impact outcome after severe injury, Warner [/bib_ref] ,.
Upgrading: Inkonsistente Evidenz1a [bib_ref] Increased risk of adrenal insufficiency following etomidate exposure in critically injured patients, Cotton [/bib_ref] 3b [bib_ref] Adrenal suppression following a single dose of etomidate for rapid sequence induction:..., Hildreth [/bib_ref] 1b [bib_ref] Single-dose etomidate for rapid sequence intubation may impact outcome after severe injury, Warner [/bib_ref] 2b
[fig] Figure 1: Algorithm for monitoring of sedation, delirium, and pain in adult patients RASS: Richmond Agitation, Sedation Scale; CAM-ICU: Confusion Assessment Method for the Intensive Care Unit; ICDSC: Intensive Care Delirium Screening Checklist; BPS: Behavioral Pain Scale; BPS-NI: Behavioral Pain Scale, not intubated; CPOT: Critical Care Pain Observation Tool; FPS-R: Faces Pain Scale, revised 8 hours) with a validated clinical scores and instruments (Figure 1). [/fig]
[table] Table 1: Risk factors for ICU-delirium [/table]
[table] Table 2: Prevention and risk reduction [/table]
[table] Table 3: Long-term consequences [/table]
[table] Table 4: Monitoring -general aspects [/table]
[table] Table 5: Monitoring of analgesia [/table]
[table] Table 6: Monitoring of sedation [/table]
[table] Table 7: Monitoring of delirium [/table]
[table] Table 8: Monitoring of anxiety [/table]
[table] Table 9: Monitoring of sleep [/table]
[table] Tabelle 22: Das brandverletze Kind B4.1 Ketamin kann in Kombination mit Midazolam und/oder Propofol fur Kurzeingriffe benutzt werden. Etomidate sollte nicht mehr fur eine prozedurale Sedierung bei polytraumatisierten Patienten verwendet werden [/table]
[table] 1a B: Tabelle 23: Polytraumatisierte Patienten Tabellen S. 12/18 Patienten mit erhohtem intrakraniellen Druck LoE GoR B5.1 Anhand der aktuellen Datenlage kann keine Empfehlung fur die Anwendung eines bestimmten Instruments zum Monitoring von Analgesie oder Sedierung bei intensivmedizinisch-behandelten Patienten mit schwerem SHT und intrakranieller Hypertension gegeben werden. Eine neurologische Untersuchung soll bei diesen Patienten engmaschig durchgefuhrt werden(50). Eine adaquate Analgesie und Sedierung nach Ziel-RASS soll in der Therapie von Patienten mit schwerem Schadel-Hirn-Trauma und/oder intrakranieller Hypertension durchgefuhrt werden(200). Razemat sollte bei kontrollierter Beatmung (paCO2 konstant) und additiver Sedierung mit GABA-Rezeptor-Agonisten (Unterdruckung der exzitatorischen Komponente) auch bei Schadel-Hirn-traumatisierten Patienten mit intrakranieller Hypertension erwogen werden(201,202). Ein Ketamin-Razemat/Midazolam-basiertes oder ein Opioid/Midazolam-basiertes Sedierungs-Regime sollten bei mechanisch beatmeten Schadel-Hirn-traumatisierten Patienten mit intrakranieller Hypertension eingesetzt werden(201,202). Ketamin/Methohexital-basiertes oder ein Fentanyl/Methohexital-basiertes Sedierungs-Regime konnen bei mechanisch beatmeten Schadel-Hirn-traumatisierten Patienten mit intrakranieller Hypertension eingesetzt werden (203), (204). Eine kontinuierliche intravenose Applikation von Opioiden (Remifentanil, Sufentanil, Fentanyl, Morphin) sollte bei Patienten mit intrakranieller Hypertension stets unter Kontrolle des MAP erfolgen (203-205). Auf Grund der gunstigen Pharmakokinetik und der damit verbundenen raschen neurologischen Beurteilbarkeit sollte Remifentanil im Vergleich mit anderen Opioiden vorrangig zur Analgosedierung von Neurointensivpatienten verwendet werden, sofern die Analgosedierung als kurzfristig erforderlich eingeschatzt wird (maximal 72 Stunden) (51), (206-209). Bolusgaben von Opioiden sollten moglichst vermieden werden und nur in Ausnahmen unter MAP-und ICP-Kontrolle gegeben werden (210). Ein Propofol-basiertes oder ein Midazolam-basiertes Sedierungs-Regime zur Sedierung Schadel-Hirn-traumatisierter Patienten sind gleichermaen sicher. Wenn rasche neurologische Beurteilbarkeit gewunscht ist, sollte Propofol bevorzugt werden (210). B5.10 Eine hochdosierte Barbiturat-Therapie zur Prophylaxe einer intrakraniellen Hypertension soll bei Patienten mit schwerem Schadel-Hirn-Trauma nicht erfolgen (200), (211), (212). Eine hochdosierte Barbiturat-Therapie unter EEG-Monitoring sollte bei Patienten mit schwerem Schadel-Hirn-Trauma nur bei anderweitig (medikamentos und chirurgisch) nicht beherrschbarer intrakranieller Hypertension eingesetzt werden, sofern hamodynamische Stabilitat gewahrleistet ist (213-216). Tabelle 24: Patienten mit erhohtem intrakraniellen Druck Tabellen S. 13/18 B6.1 Fur die Analgesie additiv zur Sedierung sollten kurz-wirksame Opioid-Analgetika wie beispielsweise Remifentanil (217, 218) verwendet werden. Bei wachen, adaquaten Patienten sollte eine "Patient-Controlled-Analgesia" einer "Nurse-Controlled-Analgesia" vorgezogen werden (219). Patienten mit extrakorporalen Herz-und Lungenersatzverfahren LoE GoR B7.1 Besonders unter der Anwendung extrakorporaler Herz-und Lungenersatzverfahren soll ein zielgesteuerter Wachheitsgrad durch regelmaiges klinisches Monitoring und kontinuierliche Dosisanpassung an den Sedierungsbedarf erreicht werden. Der Ziel-RASS an extrakorporalen Herz-und Lungenersatzverfahren sollte folgende Faktoren berucksichtigen: Patienten an extrakorporalen Herz-und Lungenersatzverfahren haben etliche Risikofaktoren fur das Auftreten einer PTSD (220), ein hoherer Grad an Wachheit ist mit der Moglichkeit zur aktiven Teilnahme an physiotherapeutischen Ubungen verbunden (221) und ein Ziel-RASS = 0 ist sicher durchfuhrbar (57-61). Tabelle 26: Patienten mit extrakorporalen Herz-und Lungenersatzverfahren Tabellen S. 14/18 Monitoring von Analgesie bei Kindern LoE GoR C.1.a.1 Altersgemae, validierte Scoringsysteme sollen bei Kindern zur Therapiesteuerung und Uberwachung von Analgesie, Sedierung und Delir eingesetzt werden (65). C.1.a.2 In der padiatrischen Intensivmedizin sollen patientenorientierte Therapiekonzepte zur Analgesie, Sedierung, Angst und Delir mit individueller patientenspezifischer Festlegung von Therapiezielen angewendet werden. Kinder sollen nach Moglichkeit ihre Schmerzen selbst einschatzen (66). Bei Kindern sollen Verhaltensmerkmale wie Gesichtsausdruck, Weinen, Motorik, Korperhaltung, Aktivitat, Ruhelosigkeit, Apathie und die auere Erscheinung von der Schmerzerfassung als stichhaltige Indikatoren fur das Vorhandensein von Schmerz berucksichtigt werden (222, 223). Fur Kinder etwa ab dem 4. Lebensjahr soll zur Selbsteinschatzung am besten die Faces Pain Scale -Revised (67) verwendet werden. Ab dem Schulalter ist auch der alternative Einsatz numerischer Rating-Skalen oder visueller Analog-Skalen moglich. Die kindliche Unbehagen-und Schmerz-Skala (KUSS) oder die Comfort-B Scale sollen als validierte und praktikable Fremdbeurteilungsskala zur Einschatzung des akuten postoperativen Schmerzes bei nicht-beatmeten Sauglingen bis zu Kindern von etwa 4 Jahren verwendet werden (224, 225). C.1.a.7 Die Comfort-B Scale soll zur Fremdbeurteilung des akuten postoperativen Schmerzes bei beatmeten Sauglingen bis zu Kindern von etwa 4 Jahren verwendet werden (225). [225] 1b A C.1.a.8 Fur die Beurteilung von Schmerzen bei Kindern und Jugendlichen, die sich auf Grund schwerer kognitiver Beintrachtigung nicht mitteilen konnen, sollen speziell validierte Messinstrumente (z.B. Paediatric Pain Profile oder Non-Communicating Children's Pain Checklist Revised) verwendet werden (226, 227). Eine Evidenz-basierte Empfehlung fur eine bestimmte neonatale "Schmerz"-Skala kann derzeit nicht ausgesprochen werden. Bei prolongierten Schmerzzustanden konnen z.B. die COMFORTneo scale oder die Neonatal Pain, Agitation and Sedation Scale (N-PASS) angewandt werden (225, 228). C.1.a.10 Die Moglichkeit eines Opioid-Entzugssyndroms sollte nach kontinuierlicher Therapie bedacht werden (229). Als Messinstrumente zur Beurteilung eines Opioid-Entzuges konnen im Neugeborenenalter der Finnegan-Score bzw. bei alteren Kindern und Jugendlichen die SOS (230) oder das WAT-1 (231) eingesetzt werden. Tabelle 27: Monitoring von Analgesie bei Kindern Tabellen S. 15/18 Monitoring von Sedierung bei Kindern LoE GoR C.1.b.1 Die Neonatal Pain, Agitation and Sedation Scale (N-PASS) oder die COMFORTneo scale konnen fur die Beurteilung von Sedierungstiefe bei Fruh-und Reifgeborenen verwendet werden (228, 232-237). Die Comfort-B Scale soll zur Fremdbeurteilung der Sedierungstiefe von Sauglingen und Kindern verwendet werden (238). Die Moglichkeit eines Sedativa-Entzugssyndroms (insbesondere Krampfanfalle) sollte nach kontinuierlicher Therapie bedacht werden. Als Messinstrumente zur Beurteilung eines Sedativa-Entzuges konnen im Neugeborenenalter der Finnegan-Score bzw. bei alteren Kindern und Jugendlichen die SOS oder das WAT-1 eingesetzt werden (229-231). Monitoring des Delirs bei Kindern LoE GoR C.1.c.1 Es soll ein regelmaiges gezieltes Screening auf delirante Symptome mit einem validierten, padiatrischen Delir-Score (z.B. pCAM-ICU, CAP-D oder PAED-Scale) durchgefuhrt werden (72-74). Tabelle 29: Monitoring des Delirs bei Kindern Analgesie bei Kindern LoE GoR C.2.a.1 Kritisch kranke Kinder auf Intensivstationen sollen eine an die individuelle Situation angepasste Schmerztherapie erhalten, unabhangig von der Notwendigkeit einer Sedierung (239). Die kontinuierliche intravenose Infusion eines Opiods sollte auf der neonatologischen und padiatrischen Intensivstation bei starken Schmerzen angewendet werden (240), (241). Zur Vermeidung eines Opioid-Entzugssyndroms sollten Opioide nach kontinuierlicher Therapie nach Moglichkeit ausgeschlichen werden. Upgrading: hohe klinische Relevanz und praktische Erfahrung 5 B C.2.a.4 Bei starken Schmerzen soll bei alteren Kindern eine Schmerzbekampfung mittels eines Opioides in Kombination mit einem Nichtopioid erfolgen (242-245). Lokale und regionale periphere und ruckenmarksnahe Analgesieverfahren sollten bei der analgetischen Therapie berucksichtigt werden (246). Patienten-kontrollierte Analgesie (PCA) kann nutzlich sein bei Kindern ab ca 5 Jahren, bei Kindern < 6 Jahren kann eine Eltern-und/oder Pflege-kontrollierte Analgesie eingesetzt werden (247). Zusatzliche Manahmen zur Schmerzreduktion sollen bei akuten, prozeduralen Schmerzen des Neugeborenen erwogen werden, wie die Gabe von oralen Zuckerstoffen (z.B. Glukose oder Saccharose), sowie der Einsatz nicht-pharmakologischer Manahmen (nicht-nutritives Saugen, Stillen, Fascilitated tucking, Kanguruhpflege, etc.) (248, 249). Tabellen S. 16/18 Nicht-pharmakologische Manahmen bei Kindern LoE GoR C.2.b.1 Bei Kindern sollte auf jeden korrigierbaren Umgebungsfaktor geachtet werden und eine fursorgliche Behandlung gewahrleistet sein (250). Ein normales Schlafmuster sollte gefordert werden, insbesondere sollte auf eine adaquate Beleuchtung, Reduktion von Larm und einen moglichst angepassten Tag-Nacht-Rhythmus der Patienten geachtet werden (239). Tabelle 31: Nicht-pharmakologische Manahmen bei Kindern Bei Notwendigkeit einer Dauersedierung sollte eine sorgfaltige Titration auf die niedrigst mogliche Dosis erfolgen. Ein Sedierungskonzept, das in randomisierten kontrollierten Studien gepruft wurde, liegt im Kindesalter nicht vor (251, 252). Midazolam kann zur Sedierung alterer, kritisch kranker Kinder verwendet werden, die einer intravenoser Sedierung bedurfen. Diese kann kontinuierlich verabreicht werden (253). C.2.c.3 Zur Sedierung von padiatrischen ICU-Patienten kann die kontinuierliche intravenose Applikation von Alpha2-Agonisten (Clonidin oder Dexmedetomidin) zur vegetativen Dampfung adjuvant oder alternativ zur Sedierung mit Midazolam verwendet werden (254-257). Tagliche Sedierungspausen konnen bei Sauglingen und Kleinkindern erwogen werden, um eine Ubersedierung zu vermeiden (258, 259). Bei alteren, kritisch kranken Kindern sollten nach Moglichkeit fruhzeitig enterale Sedativa eingesetzt werden (260). Eine dauerhafte Sedierung von Neonaten soll nur in absoluten Ausnahmefallen, z.B. bei lebensbedrohlichen, nicht anderweitig beeinflussbaren Unruhezustanden, und unter besonderer Berucksichtigung des Nutzen-Risiko-Verhaltnisses erfolgen (261). Wenn im Einzelfall bei Neonaten eine Sedierung notwendig ist, sollte bevorzugt Morphin gegenuber Midazolam eingesetzt werden (262). Downgrading: nicht ausreichende Evidenz in diesem Punkt des Reviews Bei Neonaten und Fruhgeborenen sollte der Einsatz von Chloralhydrat und Phenobarbital nur im begrundeten Einzelfall und nach sorgfaltiger Risiko-/Nutzenabwagung erfolgen, insbesondere im Hinblick auf die zerebrale Entwicklung (263-269) und einer Verlangerung der Beatmungsdauer. Zur Vermeidung eines Sedativa-Entzugssyndroms konnen diese Medikamente nach kontinuierlicher Therapie nach Moglichkeit ausgeschlichen werden. Tabelle 32: Sedierung bei Kindern Tabellen S. 17/18 Delirtherapie bei Kindern LoE GoR C.2.d.1 Die Therapie des Delirs bei Kindern sollte symptomorientiert, pharmakologisch, nichtpharmakologisch, mit psychosozialen Interventionen erfolgen und eine Differentialdiagnostik zur kausalen Ursachen beinhalten (75, 270, 271). Tabelle 33: Delirtherapie bei Kindern Es soll ein regelmaiges, aktives Screening fur Delir insbesondere bei alteren Patienten, erfolgen, da Alter ein starker Pradiktor fur ein hypoaktives Delir bei intensivmedizinisch-behandelten Patienten ist (272), (119), (120). Bei Patienten mit fortgeschrittener Demenz kann die "BESD" (Beurteilung von Schmerzen bei Demenz) zur Schmerzeinschatzung eingesetzt werden (273), (274). Die Faces Pain Scale (FPS) und die Numeric Rating Skala (NRS) sind reliabel und valide und sollen bei alteren Patienten zur Erfassung der Schmerz-Intensitat eingesetzt werden (275). Tabelle 34: Monitoring bei alteren Patienten Therapeutische Konzepte bei alteren Patienten LoE GoR D2.1 Prophylaktisch sollte bei geriatrischen Patienten mit weiteren Risikofaktoren fur ein Delir niedrig dosiertes Haloperidol oder Rivastigmin eingesetzt werden (98, 276) Prophylaktisch sollte bei geriatrischen Patienten zur Pravention eines Delirs nachts Melatonin eingesetzt werden (81). Benzodiazepine sollen bei alteren Patienten nur nach strenger Indikationsprufung zur Sedierung verwendet und auch nur titriert nach Ziel-RASS verwendet werden (277). Anticholinerge Medikamente sollen auf Grund ihres hohen Delir-Risikos bei alteren Patienten gemieden werden (278). Tabelle 35: Therapeutische Konzepte bei alteren Patienten Tabellen S. 18/18 Okonomie, Qualitatssicherung und Implementierung der Leitlinie LoE GoR E.1 Analgesie, Sedierung und Delirmanagement auf der Intensivstation sollen Leitlinien konform erfolgen und einer Qualitatssicherung unterliegen (82). Unter der Voraussetzung, dass das Intensivpflegepersonal (Fachpflegestandard) spezielle und qualifizierte Kenntnisse, Erfahrungen und Fertigkeiten vorweist, kann die Steuerung der Analgesie und Sedierung (mittels einer Spritzenpumpe) nach vorgegebenen Protokollen und arztlicher Anordnung durch das Pflegepersonal erfolgen (141, 279, 280). Mit dem Ziel die Therapiesicherheit zu erhohen und Entscheidungsfindungen zu erleichtern, soll die Implementierung klinikinterner Standards zur Analgesie, Sedierung und Delirtherapie (einschlielich der Anwendung von Sedierungsprotokollen) erfolgen (21, 281). Zur konsequenten Umsetzung von Leitlinien bzw. Standards soll eine Schulung des Personals in deren Anwendung erfolgen (83, 282, 283). Tabelle 36: Okonomie, Qualitatssicherung und Implementierung der Leitlinie [/table]