gms | German Medical Science

GMS German Medical Science — an Interdisciplinary Journal

Association of the Scientific Medical Societies in Germany (AWMF)

ISSN 1612-3174

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

Guideline Intensive Care Medicine

  • DAS-Taskforce 2015
  • Ralf Baron - German Society of Neurology (DGN)
  • Andreas Binder - German Society of Neurology (DGN)
  • Rolf Biniek - German Society of Neurology (DGN)
  • Stephan Braune - German Society of Internal Medicine Intensive Care (DGIIN)
  • Hartmut Buerkle - German Society of Anaesthesiology and Intensive Care Medicine (DGAI)
  • Peter Dall - German Society of Gynecology & Obstetrics (DGGG)
  • Sueha Demirakca - German Society of Neonatology and Pediatric Intensive Care (GNPI)
  • Rahel Eckardt - German Society of Geriatrics (DGG)
  • Verena Eggers - German Society of Anaesthesiology and Intensive Care Medicine (DGAI)
  • Ingolf Eichler - German Society for Thoracic and Cardiovascular Surgery (DGTHG)
  • Ingo Fietze - German Sleep Society (DGSM)
  • Stephan Freys - German Society of Surgery (DGCH)
  • Andreas Fründ - German Association for Physiotherapy (ZVK)
  • Lars Garten - German Society of Neonatology and Pediatric Intensive Care (GNPI)
  • Bernhard Gohrbandt - German Society for Thoracic and Cardiovascular Surgery (DGTHG)
  • Irene Harth - German Society of Neonatology and Pediatric Intensive Care (GNPI)
  • Wolfgang Hartl - German Society of Surgery (DGCH)
  • Hans-Jürgen Heppner - German Society of Geriatrics (DGG)
  • Johannes Horter - German Society of Anaesthesiology and Intensive Care Medicine (DGAI)
  • Ralf Huth - German Society of Neonatology and Pediatric Intensive Care (GNPI)
  • Uwe Janssens - German Society of Internal Medicine Intensive Care (DGIIN)
  • Christine Jungk - German Society of Neurosurgery (DGNC)
  • Kristin Maria Kaeuper - German Society of Midwifery Science (DGHWi)
  • Paul Kessler - German Society of Anaesthesiology and Intensive Care Medicine (DGAI)
  • Stefan Kleinschmidt - German Society of Anaesthesiology and Intensive Care Medicine (DGAI)
  • Matthias Kochanek - German Society of Haematology and Oncology (DGHO)
  • Matthias Kumpf - German Society of Neonatology and Pediatric Intensive Care (GNPI)
  • Andreas Meiser - German Society of Anaesthesiology and Intensive Care Medicine (DGAI)
  • Anika Mueller - German Society of Anaesthesiology and Intensive Care Medicine (DGAI)
  • Maritta Orth - German Sleep Society (DGSM)
  • Christian Putensen - German Society of Anaesthesiology and Intensive Care Medicine (DGAI)
  • Bernd Roth - German Society of Neonatology and Pediatric Intensive Care (GNPI)
  • Michael Schaefer - German Pain Society (DGSS)
  • Rainhild Schaefers - German Society of Midwifery Science (DGHWi)
  • Peter Schellongowski - German Society of Haematology and Oncology (DGHO)
  • Monika Schindler - German Society of Neonatology and Pediatric Intensive Care (GNPI)
  • Reinhard Schmitt - German Society for Specialised Nursing and Allied Health Professions (DGF)
  • Jens Scholz - German Society of Anaesthesiology and Intensive Care Medicine (DGAI)
  • Stefan Schroeder - German Association for Psychiatry, Psychotherapy and Psychosomatics (DGPPN)
  • Gerhard Schwarzmann - German Society for Specialised Nursing and Allied Health Professions (DGF)
  • corresponding author Claudia Spies - German Society of Anaesthesiology and Intensive Care Medicine (DGAI)
  • Robert Stingele - German Society of Neurology (DGN)
  • Peter Tonner - German Society of Anaesthesiology and Intensive Care Medicine (DGAI)
  • Uwe Trieschmann - German Society of Anaesthesiology and Intensive Care Medicine (DGAI)
  • Michael Tryba - German Society of Anaesthesiology and Intensive Care Medicine (DGAI)
  • Frank Wappler - German Society of Anaesthesiology and Intensive Care Medicine (DGAI)
  • Christian Waydhas - German Interdisciplinary Association for Intensive Care and Emergency Medicine (DIVI)
  • Bjoern Weiss - German Society of Anaesthesiology and Intensive Care Medicine (DGAI)
  • Guido Weisshaar - German Society of Neonatology and Pediatric Intensive Care (GNPI)

GMS Ger Med Sci 2015;13:Doc19

doi: 10.3205/000223, urn:nbn:de:0183-0002238

This is the English version of the article.
The German version can be found at:

Received: September 25, 2015
Published: November 12, 2015
Published with erratum: November 16, 2015

© 2015 DAS-Taskforce 2015 et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at


In 2010, under the guidance of the DGAI (German Society of Anaesthesiology and Intensive Care Medicine) and DIVI (German Interdisciplinary Association for Intensive Care and Emergency Medicine), twelve German medical societies published the “Evidence- and Consensus-based Guidelines on the Management of Analgesia, Sedation and Delirium in Intensive Care”. Since then, several new studies and publications have considerably increased the body of evidence, including the new recommendations from the American College of Critical Care Medicine (ACCM) in conjunction with Society of Critical Care Medicine (SCCM) and American Society of Health-System Pharmacists (ASHP) from 2013. For this update, a major restructuring and extension of the guidelines were needed in order to cover new aspects of treatment, such as sleep and anxiety management. The literature was systematically searched and evaluated using the criteria of the Oxford Center of Evidence Based Medicine. The body of evidence used to formulate these recommendations was reviewed and approved by representatives of 17 national societies. Three grades of recommendation were used as follows: Grade “A” (strong recommendation), Grade “B” (recommendation) and Grade “0” (open recommendation). The result is a comprehensive, interdisciplinary, evidence and consensus-based set of level 3 guidelines. This publication was designed for all ICU professionals, and takes into account all critically ill patient populations. It represents a guide to symptom-oriented prevention, diagnosis, and treatment of delirium, anxiety, stress, and protocol-based analgesia, sedation, and sleep-management in intensive care medicine.

Keywords: guideline, evidence, analgesia, sedation, delirium, anxiety, stress, sleep, monitoring, treatment, intensive care, critical care, Germany


In 2010, twelve German medical societies published the Evidence- and Consensus-based Guidelines on the Management of Analgesia, Sedation and Delirium. Since this publication, the body of evidence in the field has increased considerably. Several new studies and publications, including the new recommendations from the American College of Critical Care Medicine (ACCM) in conjunction with Society of Critical Care Medicine (SCCM) and American Society of Health-System Pharmacists (ASHP) in 2013, make a substantial actualization of the German guidelines necessary. This update not only accounts for new evidence, but also contains a major restructuring and extension of the guidelines to cover new aspects of treatment, such as sleep and anxiety management.

This new version aims to provide practical guidance for the symptom-based prevention, diagnostics and therapy of delirium, anxiety, and agitation, as well as for the protocol-based analgesia, sedation, and sleep management during critical illness. Under the guidance of the German Society of Anaesthesiology and Intensive Care Medicine (DGAI) and German Interdisciplinary Association for Intensive Care and Emergency Medicine (DIVI), this is one of the most comprehensive guidelines worldwide, being developed and approved by 17 national societies.

These guidelines were developed for all professions working in the intensive care unit (ICU), and its recommendations encompass critically ill patients of all age groups and severity of illness, regardless of comorbidities.

Delirium and coma are the most common manifestations of acute brain dysfunction during critical illness. Pain, stress, and a disruption of the sleep-wake-cycle are typical symptoms observed during ICU treatment, all of which can lead to delirium and impair outcome. An early management of these symptoms improves recovery and long-term outcome, while reducing post-intensive-care-unit-syndrome (PICS) and mortality. The basic principle follows an “early goal directed therapy” (EGDT) with immediate and evidence-based targets for treatment, the assessment of the clinical situation with validated instruments, and the goal-directed pharmacological therapy. These measures are to be accompanied by non-pharmacological interventions aimed at prevention and treatment.

The critically ill patient should be awake and alert, without pain, anxiety, or delirium. Ultimately, this allows the patient to actively participate in their treatment and recovery.

The term “sedation” was left in the title intentionally: the indication and conduction of sedation require special attention in order not to harm the patient through oversedation, as this has been proven to negatively affect patient outcome. In the interest of the patients, the use of sedatives and analgesics must therefore be very carefully considered. The patient must be allowed to be as alert and oriented as possible, so that they may partake in the therapy and convalescence process, as evidence shows is feasible, practical, and safe.


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 evaluation 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 task-force 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 ( and the Guidelines International Network (G-I-N) ( In line with the AWMF-guideline 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 [2].

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 consensus-based 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 [3]. 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) [4], [5], [6], but also leads to cognitive long-term impairment, posttraumatic stress disorders (PTSD), and reduced quality of life [7]. 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 [8].

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 [9]. A pharmacological prevention is to be reserved only for patients at high risk for delirium, and is not generally recommended (Table 1 [Tab. 1], Table 2 [Tab. 2], Table 3 [Tab. 3]).

Monitoring of analgesia, sedation, delirium, anxiety, stress, and sleep

A basic concept of patient-oriented therapy in intensive-care 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 [10], [11].

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 8 hours) with a validated clinical scores and instruments (Figure 1 [Fig. 1]).

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 self-assessment 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 [12]. 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 [13]. 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 [14] (Table 4 [Tab. 4], Table 5 [Tab. 5], Table 6 [Tab. 6], Table 7 [Tab. 7], Table 8 [Tab. 8], Table 9 [Tab. 9]).

Treatment concepts

See Figure 2 [Fig. 2].

Non-pharmacological concepts

See Table 10 [Tab. 10].


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 [15], [16], [17], [18], 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 [19], and a patient-controlled analgesia is recommended as soon as the patient is sufficiently awake (RASS 0/-1 and no delirium) [20] (Table 11 [Tab. 11]).


The current evidence reveals that a measurable sedation should always be avoided, as long as there is no mandatory clinical indication for sedation [21], [22]. A deep sedation, also within the first 48 hours, is associated with increased mortality, prolonged mechanical ventilation, prolonged ICU-LOS, and hospitalization [23], [24], [25], [26]. 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 [27], [28], [29]. 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 [30]. 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 (Table 12 [Tab. 12]).

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 [31] (Table 13 [Tab. 13]).

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 non-pharmacological 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 (Table 14 [Tab. 14]).

Pharmacological therapy of delirium

Preventive measures for delirium are both safe and effective [32]. 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 [33]. In addition, the use of alpha-2 agonists is also suitable for a symptom-orientated therapy of delirium [34], [35]. A special situation is the alcohol withdrawal delirium in the ICU, for which long-acting benzodiazepines should be considered [36] (Table 15 [Tab. 15]).

Weaning from mechanical ventilation

The new German S2k-Guidelines on “Prolonged Weaning” AWMF (020/015) provides recommendations regarding weaning from mechanical ventilation [37]. The management of analgesia, sedation, and delirium influence the weaning process significantly [38]. In order to start weaning as early as possible, it is useful to combine sedation and weaning protocols (Table 16 [Tab. 16]).

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 [39]. Furthermore, the depth of blockade should be monitored [40], and the duration should be kept as short as possible (Table 17 [Tab. 17]).

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 [41]. An inadequate sedation (over- and under-sedation) should be avoided at all times, as this can lead to an acute deterioration of neurological and cardiovascular parameters (Table 18 [Tab. 18]).

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 (Table 19 [Tab. 19]).

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 [42]. This guideline should be used and evaluated in the light and in-line with the “guideline of limitations to intensive care treatment” [43] and the “basic principles for medical palliative care”, published by the German Medical Association [44] (Table 20 [Tab. 20]).

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 [45]. Especially for analgesia and sedation of burn-injured children, the use of standardized protocols and training programs should be used [46] (Table 21 [Tab. 21], Table 22 [Tab. 22]).

Multiple trauma patients

The German AWMF-guideline registered under 012/019 provides recommendations regarding patients with multiple trauma [47]. 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 [48] (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], [49] (Table 23 [Tab. 23]).

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 [50]. A frequent neurological examination is obligatory. The choice of sedatives should be in-line with recommendations made in the general part. An ideal analgesic/sedative for patients with elevated intracranial pressure should decrease ICP while sustaining an adequate cerebral perfusion pressure, as well as maintain cerebral hemodynamics, including cerebral autoregulation. Additionally, it should reduce the cerebral metabolic rate for oxygen (CMRO2), have anticonvulsive and neuroprotective properties, and should allow short wake-up times for the assessment of patients after a brief infusion interruption [51] (Table 24 [Tab. 24]).

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 [52], and fast-track strategies seem to reduce the incidence of postoperative delirium [53].

Delirium in cardiac surgical patients is associated with a higher mortality [54], so that a delirium screening with a validated tool – as generally recommended – is especially important [55], [56] (Table 25 [Tab. 25]).

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 [57], [58], [59], [60], [61] (Table 26 [Tab. 26]).

Special positioning of patients

Positioning therapy is used for prophylaxis and treatment of respiratory dysfunctions [62], 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, [63], [64], an excessive sedation should be avoided.

Analgesia, sedation, and delirium management in children


For the monitoring of analgesia, sedation, and delirium in children, there are validated monitoring scales are that take developmental stage into account [65]. Also in the pediatric intensive care, adequate monitoring and individual therapy goals are essential for successful patient-oriented care (Table 27 [Tab. 27], Table 28 [Tab. 28], Table 29 [Tab. 29]).

Generally, children aged ≥3 years are able to evaluate pain-levels. Even in children, a self-assessment of pain is superior to observational scales [66], and the Faces Pain Scale-revised has been well-established as a valid monitoring tool [67]. 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 [68], [69], [70].

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 [71], [72], [73], [74].

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, non-opioids, and regional analgesia, as well as for local anesthetics, co-analgesics and non-pharmacological procedures (Table 30 [Tab. 30], Table 31 [Tab. 31], Table 32 [Tab. 32], Table 33 [Tab. 33]). 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 [75].

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 (Table 34 [Tab. 34], Table 35 [Tab. 35]).

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 BESD-scale (German scale) are available.

Preventive measures such as reorientation, visual and hearing aids are especially indicated for elderly patients [76]. Regarding the treatment of delirium, a symptomatic treatment should consider the delirogenic effects of long-acting benzodiazepines [77], the cardiac side effects of neuroleptics, and the use of appropriately cautious dosages [78], [79], [80]. For the treatment of delirium, melatonin or melatonin-analogues should be considered at night to reduce the incidence and duration of delirium [81].

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 [82].

This includes the regular training of personnel in the implementation of the guidelines [83]. Special consideration for regional characteristics and internal Standard Operating Procedures improved the integration of guideline recommendations [83]. 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 (Table 36 [Tab. 36]).


Extended version of the guideline

The German extended version, patient version, and methodology report are available under


DAS Taskforce 2015: The task-force members (authors) are listed in alphabetical order.

Chairing medical societies: German Society of Anaesthesiology and Intensive Care Medicine (DGAI) and German Interdisciplinary Association for Intensive Care and Emergency Medicine (DIVI) with 15 participating medical societies$. All societies or their executive boards consented on the final version of the guidelines.

German Society of Anaesthesiology and Intensive Care Medicine (DGAI)
German Interdisciplinary Association for Intensive Care and Emergency Medicine (DIVI)
German Society of Surgery (DGCH)$
German Society for Specialised Nursing and Allied Health Professions (DGF)$
German Society of Geriatrics (DGG)$
German Society for Gynecology & Obstetrics (DGGG)$
German Society of Haematology and Oncology (DGHO)$
German Society of Midwifery Science (DGHWi)$
German Society of Internal Medicine Intensive Care (DGIIN)$
German Society of Neurosurgery (DGNC)$
German Society of Neurology (DGN)$
German Association for Psychiatry, Psychotherapy and Psychosomatics (DGPPN)$
German Sleep Society (DGSM)$
German Society for Thoracic and Cardiovascular Surgery (DGTHG)$
German Pain Society (DGSS)$
German Association for Physiotherapy (ZVK)$
German Society of Neonatology and Pediatric Intensive Care (GNPI)$

Conflicts of interest

The declarations of conflict of interest from all participants can be viewed upon request and are published on the AWMF homepage.


This guideline has been funded independently of interest groups by the DGAI.


We thank all participating societies for their work, their outstanding commitment and the sound review of the guideline before publication. Our special thanks to Rudolf Mörgeli for the thorough correction of the English version of the guideline.


OCEBM Levels of Evidence Working Group. The Oxford 2011 Levels of Evidence. Oxford Centre for Evidence-Based Medicine. Available from: External link
The ADAPTE Collaboration. The ADAPTE Process: Toolkit for Guideline Adaptation. Version 2.0. 2009. Available from: External link
Mehta S, Cook D, Devlin JW, Skrobik Y, Meade M, Fergusson D, Herridge M, Steinberg M, Granton J, Ferguson N, Tanios M, Dodek P, Fowler R, Burns K, Jacka M, Olafson K, Mallick R, Reynolds S, Keenan S, Burry L; SLEAP Investigators; Canadian Critical Care Trials Group. Prevalence, risk factors, and outcomes of delirium in mechanically ventilated adults. Crit Care Med. 2015 Mar;43(3):557-66. DOI: 10.1097/CCM.0000000000000727 External link
Ely EW, Shintani A, Truman B, Speroff T, Gordon SM, Harrell FE Jr, Inouye SK, Bernard GR, Dittus RS. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA. 2004 Apr;291(14):1753-62. DOI: 10.1001/jama.291.14.1753 External link
Ouimet S, Kavanagh BP, Gottfried SB, Skrobik Y. Incidence, risk factors and consequences of ICU delirium. Intensive Care Med. 2007 Jan;33(1):66-73. DOI: 10.1007/s00134-006-0399-8 External link
Zhang Z, Pan L, Ni H. Impact of delirium on clinical outcome in critically ill patients: a meta-analysis. Gen Hosp Psychiatry. 2013 Mar-Apr;35(2):105-11. DOI: 10.1016/j.genhosppsych.2012.11.003 External link
Pandharipande PP, Girard TD, Jackson JC, Morandi A, Thompson JL, Pun BT, Brummel NE, Hughes CG, Vasilevskis EE, Shintani AK, Moons KG, Geevarghese SK, Canonico A, Hopkins RO, Bernard GR, Dittus RS, Ely EW; BRAIN-ICU Study Investigators. Long-term cognitive impairment after critical illness. N Engl J Med. 2013 Oct;369(14):1306-16. DOI: 10.1056/NEJMoa1301372 External link
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 May;43(3):326-33. DOI: 10.1093/ageing/afu022 External link
Shehabi Y, Chan L, Kadiman S, Alias A, Ismail WN, Tan MA, Khoo TM, Ali SB, Saman MA, Shaltut A, Tan CC, Yong CY, Bailey M; Sedation Practice in Intensive Care Evaluation (SPICE) Study Group investigators. Sedation depth and long-term mortality in mechanically ventilated critically ill adults: a prospective longitudinal multicentre cohort study. Intensive Care Med. 2013 May;39(5):910-8. DOI: 10.1007/s00134-013-2830-2 External link
Chanques G, Jaber S, Barbotte E, Violet S, Sebbane M, Perrigault PF, Mann C, Lefrant JY, Eledjam JJ. Impact of systematic evaluation of pain and agitation in an intensive care unit. Crit Care Med. 2006 Jun;34(6):1691-9. DOI: 10.1097/01.CCM.0000218416.62457.56 External link
Kastrup M, von Dossow V, Seeling M, Ahlborn R, Tamarkin A, Conroy P, Boemke W, Wernecke KD, Spies C. Key performance indicators in intensive care medicine. A retrospective matched cohort study. J Int Med Res. 2009 Sep-Oct;37(5):1267-84. DOI: 10.1177/147323000903700502 External link
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 Nov;18(6):571-80. DOI: 10.4037/ajcc2009682 External link
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 Dec;14(4):302-11.
Seymour CW, Pandharipande PP, Koestner T, Hudson LD, Thompson JL, Shintani AK, Ely EW, Girard TD. Diurnal sedative changes during intensive care: impact on liberation from mechanical ventilation and delirium. Crit Care Med. 2012 Oct;40(10):2788-96. DOI: 10.1097/CCM.0b013e31825b8ade External link
But AK, Erdil F, Yucel A, Gedik E, Durmus M, Ersoy MO. The effects of single-dose tramadol on post-operative pain and morphine requirements after coronary artery bypass surgery. Acta Anaesthesiol Scand. 2007 May;51(5):601-6. DOI: 10.1111/j.1399-6576.2007.01275.x External link
Carrer S, Bocchi A, Candini M, Donegà L, Tartari S. Short term analgesia based sedation in the Intensive Care Unit: morphine vs remifentanil + morphine. Minerva Anestesiol. 2007 Jun;73(6):327-32.
Machata AM, Illievich UM, Gustorff B, Gonano C, Fässler K, Spiss CK. Remifentanil for tracheal tube tolerance: a case control study. Anaesthesia. 2007 Aug;62(8):796-801. DOI: 10.1111/j.1365-2044.2007.05100.x External link
Memis D, Inal MT, Kavalci G, Sezer A, Sut N. Intravenous paracetamol reduced the use of opioids, extubation time, and opioid-related adverse effects after major surgery in intensive care unit. J Crit Care. 2010 Sep;25(3):458-62. DOI: 10.1016/j.jcrc.2009.12.012 External link
Pöpping DM, Elia N, Marret E, Remy C, Tramèr MR. Protective effects of epidural analgesia on pulmonary complications after abdominal and thoracic surgery: a meta-analysis. Arch Surg. 2008 Oct;143(10):990-9; discussion 1000. DOI: 10.1001/archsurg.143.10.990 External link
Hudcova J, McNicol E, Quah C, Lau J, Carr DB. Patient controlled opioid analgesia versus conventional opioid analgesia for postoperative pain. Cochrane Database Syst Rev. 2006 Oct 18;(4):CD003348. DOI: 10.1002/14651858.cd003348.pub2 External link
Girard TD, Kress JP, Fuchs BD, Thomason JW, Schweickert WD, Pun BT, Taichman DB, Dunn JG, Pohlman AS, Kinniry PA, Jackson JC, Canonico AE, Light RW, Shintani AK, Thompson JL, Gordon SM, Hall JB, Dittus RS, Bernard GR, Ely EW. 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 Jan 12;371(9607):126-34. DOI: 10.1016/S0140-6736(08)60105-1 External link
Kress JP, Pohlman AS, O'Connor MF, Hall JB. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med. 2000 May;342(20):1471-7. DOI: 10.1056/NEJM200005183422002 External link
Shehabi Y, Bellomo R, Reade MC, Bailey M, Bass F, Howe B, McArthur C, Murray L, Seppelt IM, Webb S, Weisbrodt L; Sedation Practice in Intensive Care Evaluation Study Investigators; Australian and New Zealand Intensive Care Society Clinical Trials Group. Early goal-directed sedation versus standard sedation in mechanically ventilated critically ill patients: a pilot study*. Crit Care Med. 2013 Aug;41(8):1983-91. DOI: 10.1097/CCM.0b013e31828a437d External link
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 Dec;38(12):2311-8. DOI: 10.1097/CCM.0b013e3181f85759 External link
Balzer F, Weiß B, Kumpf O, Treskatsch S, Spies C, Wernecke KD, Krannich A, Kastrup M. Early deep sedation is associated with decreased in-hospital and two-year follow-up survival. Crit Care. 2015;19:197. DOI: 10.1186/s13054-015-0929-2 External link
Shehabi Y, Bellomo R, Reade MC, Bailey M, Bass F, Howe B, McArthur C, Seppelt IM, Webb S, Weisbrodt L. Sedation Practice in Intensive Care Evaluation (SPICE) Study Investigators; ANZICS Clinical Trials Group. Early intensive care sedation predicts long-term mortality in ventilated critically ill patients. Am J Respir Crit Care Med. 2012 Oct;186(8):724-31. DOI: 10.1164/rccm.201203-0522OC External link
Hogarth DK, Hall J. Management of sedation in mechanically ventilated patients. Curr Opin Crit Care. 2004 Feb;10(1):40-6. DOI: 10.1097/00075198-200402000-00007 External link
Young C, Knudsen N, Hilton A, Reves JG. Sedation in the intensive care unit. Crit Care Med. 2000 Mar;28(3):854-66. DOI: 10.1097/00003246-200003000-00041 External link
Strom T, Martinussen T, Toft P. A protocol of no sedation for critically ill patients receiving mechanical ventilation: a randomised trial. Lancet. 2010 Feb 6;375(9713):475-80. DOI: 10.1016/S0140-6736(09)62072-9 External link
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 Jul 9;7:CD009176. DOI: 10.1002/14651858.CD009176.pub2 External link
Mehta S, Burry L, Cook D, Fergusson D, Steinberg M, Granton J, Herridge M, Ferguson N, Devlin J, Tanios M, Dodek P, Fowler R, Burns K, Jacka M, Olafson K, Skrobik Y, Hébert P, Sabri E, Meade M; 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 Nov;308(19):1985-92. DOI: 10.1001/jama.2012.13872 External link
Friedman JI, Soleimani L, McGonigle DP, Egol C, Silverstein JH. Pharmacological treatments of non-substance-withdrawal delirium: a systematic review of prospective trials. Am J Psychiatry. 2014 Feb;171(2):151-9. DOI: 10.1176/appi.ajp.2013.13040458 External link
Wang HR, Woo YS, Bahk WM. Atypical antipsychotics in the treatment of delirium. Psychiatry Clin Neurosci. 2013 Jul;67(5):323-31. DOI: 10.1111/pcn.12066 External link
Riker RR, Shehabi Y, Bokesch PM, Ceraso D, Wisemandle W, Koura F, Whitten P, Margolis BD, Byrne DW, Ely EW, Rocha MG; SEDCOM (Safety and Efficacy of Dexmedetomidine Compared With Midazolam) Study Group. Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial. JAMA. 2009 Feb;301(5):489-99. DOI: 10.1001/jama.2009.56 External link
Girard TD, Pandharipande PP, Carson SS, Schmidt GA, Wright PE, Canonico AE, Pun BT, Thompson JL, Shintani AK, Meltzer HY, Bernard GR, Dittus RS, Ely EW. MIND Trial Investigators. Feasibility, efficacy, and safety of antipsychotics for intensive care unit delirium: the MIND randomized, placebo-controlled trial. Crit Care Med. 2010 Feb;38(2):428-37. DOI: 10.1097/CCM.0b013e3181c58715 External link
Lonergan E, Luxenberg J, Areosa Sastre A. Benzodiazepines for delirium. Cochrane Database Syst Rev. 2009 Oct 7;(4). DOI: 10.1002/14651858.cd006379.pub3 External link
Schönhofer B, Geiseler J, Dellweg D, Moerer O, Barchfeld T, Fuchs H, Karg O, Rosseau S, Sitter H, Weber-Carstens S, Westhoff M, Windisch W. [Prolonged weaning: S2k-guideline published by the German Respiratory Society]. Pneumologie. 2014 Jan;68(1):19-75. DOI: 10.1055/s-0033-1359038 External link
Luetz A, Goldmann A, Weber-Carstens S, Spies C. Weaning from mechanical ventilation and sedation. Curr Opin Anaesthesiol. 2012 Apr;25(2):164-9. DOI: 10.1097/ACO.0b013e32834f8ce7 External link
Piriyapatsom A, Bittner EA, Hines J, Schmidt UH. Sedation and paralysis. Respir Care. 2013 Jun;58(6):1024-37. DOI: 10.4187/respcare.02232 External link
Dieye E, Minville V, Asehnoune K, Conil C, Georges B, Cougot P, Fourcade O, Conil JM. Pharmacodynamics of cisatracurium in the intensive care unit: an observational study. Ann Intensive Care. 2014;4(1):3. DOI: 10.1186/2110-5820-4-3 External link
Heegaard W, Fringer RC, Frascone RJ, Pippert G, Miner J. Bispectral index monitoring in helicopter emergency medical services patients. Prehosp Emerg Care. 2009 Apr-Jun;13(2):193-7. DOI: 10.1080/10903120802706187 External link
Carlet J, Thijs LG, Antonelli M, Cassell J, Cox P, Hill N, Hinds C, Pimentel JM, Reinhart K, Thompson BT. Challenges in end-of-life care in the ICU. Statement of the 5th International Consensus Conference in Critical Care: Brussels, Belgium, April 2003. Intensive Care Med. 2004 May;30(5):770-84. DOI: 10.1007/s00134-004-2241-5 External link
Deutsche Gesellschaft für Anästhesiologie und Intensivmedizin. Leitlinie zu Grenzen der intensivmedizinischen Behandlungspflicht. Anästh Intensivmed. 1999;40:92-4.
Bundesärztekammer. Grundsätze zur ärztlichen Sterbebegleitung. Deutsches Ärzteblatt. 1998;95(39):A-2366-67. Available from: External link
Richardson P, Mustard L. The management of pain in the burns unit. Burns. 2009 Nov;35(7):921-36. DOI: 10.1016/j.burns.2009.03.003 External link
Bayat A, Ramaiah R, Bhananker SM. Analgesia and sedation for children undergoing burn wound care. Expert Rev Neurother. 2010 Nov;10(11):1747-59. DOI: 10.1586/ern.10.158 External link
Deutsche Gesellschaft für Unfallchirurgie. S3-Leitlinie Polytrauma/Schwerverletzten-Behandlung. AWMF; 2011. AWMF-Register Nr.012/019. Available from: External link
Umunna BP, Tekwani K, Barounis D, Kettaneh N, Kulstad E. Ketamine for continuous sedation of mechanically ventilated patients. J Emerg Trauma Shock. 2015 Jan-Mar;8(1):11-5. DOI: 10.4103/0974-2700.145414 External link
Bruder EA, Ball IM, Ridi S, Pickett W, Hohl C. Single induction dose of etomidate versus other induction agents for endotracheal intubation in critically ill patients. Cochrane Database Syst Rev. 2015 Jan 8;1:CD010225. DOI: 10.1002/14651858.CD010225.pub2 External link
Sharshar T, Citerio G, Andrews PJ, Chieregato A, Latronico N, Menon DK, Puybasset L, Sandroni C, Stevens RD. Neurological examination of critically ill patients: a pragmatic approach. Report of an ESICM expert panel. Intensive Care Med. 2014 Apr;40(4):484-95. DOI: 10.1007/s00134-014-3214-y External link
Citerio G, Cormio M. Sedation in neurointensive care: advances in understanding and practice. Curr Opin Crit Care. 2003 Apr;9(2):120-6. DOI: 10.1097/00075198-200304000-00007 External link
Dale CR, Bryson CL, Fan VS, Maynard C, Yanez ND 3rd, Treggiari MM. A greater analgesia, sedation, delirium order set quality score is associated with a decreased duration of mechanical ventilation in cardiovascular surgery patients. Crit Care Med. 2013 Nov;41(11):2610-7. DOI: 10.1097/CCM.0b013e31829a6ee7 External link
Lin Y, Chen J, Wang Z. Meta-analysis of factors which influence delirium following cardiac surgery. J Card Surg. 2012 Jul;27(4):481-92. DOI: 10.1111/j.1540-8191.2012.01472.x External link
Witlox J, Eurelings LS, de Jonghe JF, Kalisvaart KJ, Eikelenboom P, van Gool WA. Delirium in elderly patients and the risk of postdischarge mortality, institutionalization, and dementia: a meta-analysis. JAMA. 2010 Jul;304(4):443-51. DOI: 10.1001/jama.2010.1013 External link
Whitlock EL, Torres BA, Lin N, Helsten DL, Nadelson MR, Mashour GA, Avidan MS. Postoperative delirium in a substudy of cardiothoracic surgical patients in the BAG-RECALL clinical trial. Anesth Analg. 2014 Apr;118(4):809-17. DOI: 10.1213/ANE.0000000000000028 External link
Pesonen A, Suojaranta-Ylinen R, Hammaren E, Kontinen VK, Raivio P, Tarkkila P, Rosenberg PH. Pregabalin has an opioid-sparing effect in elderly patients after cardiac surgery: a randomized placebo-controlled trial. Br J Anaesth. 2011 Jun;106(6):873-81. DOI: 10.1093/bja/aer083 External link
Del Sorbo L, Pisani L, Filippini C, Fanelli V, Fasano L, Terragni P, Dell'Amore A, Urbino R, Mascia L, Evangelista A, Antro C, D'Amato R, Sucre MJ, Simonetti U, Persico P, Nava S, Ranieri VM. Extracorporeal Co2 removal in hypercapnic patients at risk of noninvasive ventilation failure: a matched cohort study with historical control. Crit Care Med. 2015 Jan;43(1):120-7. DOI: 10.1097/CCM.0000000000000607 External link
Fuehner T, Kuehn C, Hadem J, Wiesner O, Gottlieb J, Tudorache I, Olsson KM, Greer M, Sommer W, Welte T, Haverich A, Hoeper MM, Warnecke G. Extracorporeal membrane oxygenation in awake patients as bridge to lung transplantation. Am J Respir Crit Care Med. 2012 Apr;185(7):763-8. DOI: 10.1164/rccm.201109-1599OC External link
Kluge S, Braune SA, Engel M, Nierhaus A, Frings D, Ebelt H, Uhrig A, Metschke M, Wegscheider K, Suttorp N, Rousseau S. Avoiding invasive mechanical ventilation by extracorporeal carbon dioxide removal in patients failing noninvasive ventilation. Intensive Care Med. 2012 Oct;38(10):1632-9. DOI: 10.1007/s00134-012-2649-2 External link
Schellongowski P, Riss K, Staudinger T, Ullrich R, Krenn CG, Sitzwohl C, Bojic A, Wohlfarth P, Sperr WR, Rabitsch W, Aigner C, Taghavi S, Jaksch P, Klepetko W, Lang G. Extracorporeal CO2 removal as bridge to lung transplantation in life-threatening hypercapnia. Transpl Int. 2015 Mar;28(3):297-304. DOI: 10.1111/tri.12486 External link
Sommer W, Marsch G, Kaufeld T, Rontgen P, Beutel G, Tongers J, Warnecke G, Tudorache I, Schieffer B, Haverich A, Kuehn C. Cardiac awake extracorporeal life support-bridge to decision? Artif Organs. 2015 May;39(5):400-8. DOI: 10.1111/aor.12396 External link
Bein T. Lagerungstherapie zur Prophylaxe oder therapie von pulmonalen Funktionsstörungen. S2e-Leitlinie der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin (DGAI). Anästh Intensivmed. 2008;49(Suppl 1):S1-24.
McCunn M, Reynolds HN, Cottingham CA, Scalea TM, Habashi NM. Extracorporeal support in an adult with severe carbon monoxide poisoning and shock following smoke inhalation: a case report. Perfusion. 2000 Mar;15(2):169-73. DOI: 10.1177/026765910001500213 External link
Kredel M, Bischof L, Wurmb TE, Roewer N, Muellenbach RM. Combination of positioning therapy and venovenous extracorporeal membrane oxygenation in ARDS patients. Perfusion. 2014 Mar;29(2):171-7. DOI: 10.1177/0267659113502834 External link
Hummel P, van Dijk M. Pain assessment: current status and challenges. Semin Fetal Neonatal Med. 2006 Aug;11(4):237-45. DOI: 10.1016/j.siny.2006.02.004 External link
Colwell C, Clark L, Perkins R. Postoperative use of pediatric pain scales: children's self-report versus nurse assessment of pain intensity and affect. J Pediatr Nurs. 1996 Dec;11(6):375-82. DOI: 10.1016/S0882-5963(96)80082-0 External link
Hicks CL, von Baeyer CL, Spafford PA, van Korlaar I, Goodenough B. The Faces Pain Scale-Revised: toward a common metric in pediatric pain measurement. Pain. 2001 Aug;93(2):173-83. DOI: 10.1016/S0304-3959(01)00314-1 External link
Breau LM, McGrath PJ, Stevens B, Beyene J, Camfield C, Finley GA, Franck L, Gibbins S, Howlett A, McKeever P, O'Brien K, Ohlsson A. Judgments of pain in the neonatal intensive care setting: a survey of direct care staffs' perceptions of pain in infants at risk for neurological impairment. Clin J Pain. 2006 Feb;22(2):122-9.
Massaro M, Pastore S, Ventura A, Barbi E. Pain in cognitively impaired children: a focus for general pediatricians. Eur J Pediatr. 2013 Jan;172(1):9-14. DOI: 10.1007/s00431-012-1720-x External link
Stevens B, McGrath P, Gibbins S, Beyene J, Breau L, Camfield C, Finley A, Franck L, Howlett A, McKeever P, O'Brien K, Ohlsson A, Yamada J. Procedural pain in newborns at risk for neurologic impairment. Pain. 2003 Sep;105(1-2):27-35.
Smith HA, Brink E, Fuchs DC, Ely EW, Pandharipande PP. Pediatric delirium: monitoring and management in the pediatric intensive care unit. Pediatr Clin North Am. 2013 Jun;60(3):741-60. DOI: 10.1016/j.pcl.2013.02.010 External link
Janssen NJ, Tan EY, Staal M, Janssen EP, Leroy PL, Lousberg R, van Os J, Schieveld JN. On the utility of diagnostic instruments for pediatric delirium in critical illness: an evaluation of the Pediatric Anesthesia Emergence Delirium Scale, the Delirium Rating Scale 88, and the Delirium Rating Scale-Revised R-98. Intensive Care Med. 2011 Aug;37(8):1331-7. DOI: 10.1007/s00134-011-2244-y External link
Silver G, Traube C, Kearney J, Kelly D, Yoon MJ, Nash Moyal W, Gangopadhyay M, Shao H, Ward MJ. Detecting pediatric delirium: development of a rapid observational assessment tool. Intensive Care Med. 2012 Jun;38(6):1025-31. DOI: 10.1007/s00134-012-2518-z External link
Smith HA, Boyd J, Fuchs DC, Melvin K, Berry P, Shintani A, Eden SK, Terrell MK, Boswell T, Wolfram K, Sopfe J, Barr FE, Pandharipande PP, Ely EW. Diagnosing delirium in critically ill children: Validity and reliability of the Pediatric Confusion Assessment Method for the Intensive Care Unit. Crit Care Med. 2011 Jan;39(1):150-7. DOI: 10.1097/CCM.0b013e3181feb489 External link
Schieveld JN, Leroy PL, van Os J, Nicolai J, Vos GD, Leentjens AF. Pediatric delirium in critical illness: phenomenology, clinical correlates and treatment response in 40 cases in the pediatric intensive care unit. Intensive Care Med. 2007 Jun;33(6):1033-40. DOI: 10.1007/s00134-007-0637-8 External link
Inouye SK. A practical program for preventing delirium in hospitalized elderly patients. Cleve Clin J Med. 2004 Nov;71(11):890-6. DOI: 10.3949/ccjm.71.11.890 External link
Panitchote A, Tangvoraphonkchai K, Suebsoh N, Eamma W, Chanthonglarng B, Tiamkao S, Limpawattana P. Under-recognition of delirium in older adults by nurses in the intensive care unit setting. Aging Clin Exp Res. 2015 Oct;27(5):735-40. DOI: 10.1007/s40520-015-0323-6 External link
Spies CD, Otter HE, Hüske B, Sinha P, Neumann T, Rettig J, Lenzenhuber E, Kox WJ, Sellers EM. Alcohol withdrawal severity is decreased by symptom-orientated adjusted bolus therapy in the ICU. Intensive Care Med. 2003 Dec;29(12):2230-8. DOI: 10.1007/s00134-003-2033-3 External link
Spies CD, Rommelspacher H. Alcohol withdrawal in the surgical patient: prevention and treatment. Anesth Analg. 1999 Apr;88(4):946-54.
Lonergan E, Britton AM, Luxenberg J, Wyller T. Antipsychotics for delirium. Cochrane Database Syst Rev. 2007 Apr 18;(2):CD005594. DOI: 10.1002/14651858.cd005594.pub2 External link
Hatta K, Kishi Y, Wada K, Takeuchi T, Odawara T, Usui C, Nakamura H. DELIRIA-J Group. Preventive effects of ramelteon on delirium: a randomized placebo-controlled trial. JAMA Psychiatry. 2014 Apr;71(4):397-403. DOI: 10.1001/jamapsychiatry.2013.3320 External link
Barr J, Fraser GL, Puntillo K, Ely EW, Gélinas C, Dasta JF, Davidson JE, Devlin JW, Kress JP, Joffe AM, Coursin DB, Herr DL, Tung A, Robinson BR, Fontaine DK, Ramsay MA, Riker RR, Sessler CN, Pun B, Skrobik Y, Jaeschke R; American College of Critical Care Medicine. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med. 2013 Jan;41(1):263-306. DOI: 10.1097/CCM.0b013e3182783b72 External link
Pun BT, Gordon SM, Peterson JF, Shintani AK, Jackson JC, Foss J, Harding SD, Bernard GR, Dittus RS, Ely EW. Large-scale implementation of sedation and delirium monitoring in the intensive care unit: a report from two medical centers. Crit Care Med. 2005 Jun;33(6):1199-205. DOI: 10.1097/01.CCM.0000166867.78320.AC External link
Pisani MA, Murphy TE, Araujo KL, Slattum P, Van Ness PH, Inouye SK. Benzodiazepine and opioid use and the duration of intensive care unit delirium in an older population. Crit Care Med. 2009 Jan;37(1):177-83. DOI: 10.1097/CCM.0b013e318192fcf9 External link
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 Aug 13-27;167(15):1629-34. DOI: 10.1001/archinte.167.15.1629 External link
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 External link
Pandharipande P, Shintani A, Peterson J, Pun BT, Wilkinson GR, Dittus RS, Bernard GR, Ely EW. Lorazepam is an independent risk factor for transitioning to delirium in intensive care unit patients. Anesthesiology. 2006 Jan;104(1):21-6. DOI: 10.1097/00000542-200601000-00005 External link
Pandharipande P, Cotton BA, Shintani A, Thompson J, Pun BT, Morris JA Jr, Dittus R, Ely EW. Prevalence and risk factors for development of delirium in surgical and trauma intensive care unit patients. J Trauma. 2008 Jul;65(1):34-41. DOI: 10.1097/TA.0b013e31814b2c4d External link
Aizawa K, Kanai T, Saikawa Y, Takabayashi T, Kawano Y, Miyazawa N, Yamamoto T. A novel approach to the prevention of postoperative delirium in the elderly after gastrointestinal surgery. Surg Today. 2002;32(4):310-4. DOI: 10.1007/s005950200044 External link
Awissi DK, Bégin C, Moisan J, Lachaine J, Skrobik Y. I-SAVE study: impact of sedation, analgesia, and delirium protocols evaluated in the intensive care unit: an economic evaluation. Ann Pharmacother. 2012 Jan;46(1):21-8. DOI: 10.1345/aph.1Q284 External link
Inouye SK, Bogardus ST Jr, Charpentier PA, Leo-Summers L, Acampora D, Holford TR, Cooney LM Jr. A multicomponent intervention to prevent delirium in hospitalized older patients. N Engl J Med. 1999 Mar;340(9):669-76. DOI: 10.1056/NEJM199903043400901 External link
Needham DM, Korupolu R, Zanni JM, Pradhan P, Colantuoni E, Palmer JB, Brower RG, Fan E. Early physical medicine and rehabilitation for patients with acute respiratory failure: a quality improvement project. Arch Phys Med Rehabil. 2010 Apr;91(4):536-42. DOI: 10.1016/j.apmr.2010.01.002 External link
Ouimet S, Riker R, Bergeron N, Bergeon N, Cossette M, Kavanagh B, Skrobik Y. Subsyndromal delirium in the ICU: evidence for a disease spectrum. Intensive Care Med. 2007 Jun;33(6):1007-13. DOI: 10.1007/s00134-007-0618-y External link
Prakanrattana U, Prapaitrakool S. Efficacy of risperidone for prevention of postoperative delirium in cardiac surgery. Anaesth Intensive Care. 2007 Oct;35(5):714-9.
Schweickert WD, Pohlman MC, Pohlman AS, Nigos C, Pawlik AJ, Esbrook CL, Spears L, Miller M, Franczyk M, Deprizio D, Schmidt GA, Bowman A, Barr R, McCallister KE, Hall JB, Kress JP. Early physical and occupational therapy in mechanically ventilated, critically ill patients: a randomised controlled trial. Lancet. 2009 May 30;373(9678):1874-82. DOI: 10.1016/S0140-6736(09)60658-9 External link
Shehabi Y, Grant P, Wolfenden H, Hammond N, Bass F, Campbell M, Chen J. Prevalence of delirium with dexmedetomidine compared with morphine based therapy after cardiac surgery: a randomized controlled trial (DEXmedetomidine COmpared to Morphine-DEXCOM Study). Anesthesiology. 2009 Nov;111(5):1075-84. DOI: 10.1097/ALN.0b013e3181b6a783 External link
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 Aug;111(2):451-63. DOI: 10.1213/ANE.0b013e3181d7e1b8 External link
Wang W, Li HL, Wang DX, Zhu X, Li SL, Yao GQ, Chen KS, Gu XE, Zhu SN. Haloperidol prophylaxis decreases delirium incidence in elderly patients after noncardiac surgery: a randomized controlled trial*. Crit Care Med. 2012 Mar;40(3):731-9. DOI: 10.1097/CCM.0b013e3182376e4f External link
van den Boogaard M, Schoonhoven L, van Achterberg T, van der Hoeven JG, Pickkers P. Haloperidol prophylaxis in critically ill patients with a high risk for delirium. Crit Care. 2013;17(1):R9. DOI: 10.1186/cc11933 External link
Al-Qadheeb NS, Balk EM, Fraser GL, Skrobik Y, Riker RR, Kress JP, Whitehead S, Devlin JW. Randomized ICU trials do not demonstrate an association between interventions that reduce delirium duration and short-term mortality: a systematic review and meta-analysis. Crit Care Med. 2014 Jun;42(6):1442-54. DOI: 10.1097/CCM.0000000000000224 External link
Colombo R, Corona A, Praga F, Minari C, Giannotti C, Castelli A, Raimondi F. A reorientation strategy for reducing delirium in the critically ill. Results of an interventional study. Minerva Anestesiol. 2012 Sep;78(9):1026-33.
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 Jun;69(6):540-9. DOI: 10.1111/anae.12638 External link
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 Aug;79(8):944-63.
Wilcox ME, Brummel NE, Archer K, Ely EW, Jackson JC, Hopkins RO. Cognitive dysfunction in ICU patients: risk factors, predictors, and rehabilitation interventions. Crit Care Med. 2013 Sep;41(9 Suppl 1):S81-98. DOI: 10.1097/CCM.0b013e3182a16946 External link
Ely EW, Girard TD, Shintani AK, Jackson JC, Gordon SM, Thomason JW, Pun BT, Canonico AE, Light RW, Pandharipande P, Laskowitz DT. Apolipoprotein E4 polymorphism as a genetic predisposition to delirium in critically ill patients. Crit Care Med. 2007 Jan;35(1):112-7. DOI: 10.1097/01.CCM.0000251925.18961.CA External link
Girard TD, Jackson JC, Pandharipande PP, Pun BT, Thompson JL, Shintani AK, Gordon SM, Canonico AE, Dittus RS, Bernard GR, Ely EW. Delirium as a predictor of long-term cognitive impairment in survivors of critical illness. Crit Care Med. 2010 Jul;38(7):1513-20. DOI: 10.1097/CCM.0b013e3181e47be1 External link
Ely EW, Truman B, Shintani A, Thomason JW, Wheeler AP, Gordon S, Francis J, Speroff T, Gautam S, Margolin R, Sessler CN, Dittus RS, Bernard GR. Monitoring sedation status over time in ICU patients: reliability and validity of the Richmond Agitation-Sedation Scale (RASS). JAMA. 2003 Jun;289(22):2983-91. DOI: 10.1001/jama.289.22.2983 External link
Brodner G, Mertes N, Buerkle H, Marcus MA, Van Aken H. Acute pain management: analysis, implications and consequences after prospective experience with 6349 surgical patients. Eur J Anaesthesiol. 2000 Sep;17(9):566-75. DOI: 10.1097/00003643-200009000-00005 External link
Tsui SL, Irwin MG, Wong CM, Fung SK, Hui TW, Ng KF, Chan WS, O'Reagan AM. An audit of the safety of an acute pain service. Anaesthesia. 1997 Nov;52(11):1042-7. DOI: 10.1111/j.1365-2044.1997.232-az0371.x External link
Deutsche Interdisziplinäre Vereinigung für Schmerztherapie. S3-Leitlinie zur Behandlung akuter perioperativer und posttraumatischer Schmerzen. Stand: 21.05.2007 inkl. Änderungen vom 20. 04. 2009 [Internet]. AWMF; 2009. Available from: External link
Girard F, Moumdjian R, Boudreault D, Chouinard P, Bouthilier A, Sauvageau E, Ruel M, Girard DC. The effect of propofol sedation on the intracranial pressure of patients with an intracranial space-occupying lesion. Anesth Analg. 2004 Aug;99(2):573-7, table of contents. DOI: 10.1213/01.ANE.0000133138.86133.38 External link
Martin J, Bäsell K, Bürkle H, Hommel J, Huth G, Kessler P, Kretz FJ, Putensen C, Quintel M, Tonner P, Tryba M, Scholz J, Schüttler J, Wappler F, Spies C. Analgesie und Sedierung in der Intensivmedizin – Kurzversion: S2-Leitlinien der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin. Anästhesiol Intensivmed. 2005;Suppl. 1:1-20.
Sessler CN, Gosnell MS, Grap MJ, Brophy GM, O'Neal PV, Keane KA, Tesoro EP, Elswick RK. The Richmond Agitation-Sedation Scale: validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med. 2002 Nov;166(10):1338-44. DOI: 10.1164/rccm.2107138 External link
Hernández-Gancedo C, Pestaña D, Peña N, Royo C, Pérez-Chrzanowska H, Criado A. Monitoring sedation in critically ill patients: bispectral index, Ramsay and observer scales. Eur J Anaesthesiol. 2006 Aug;23(8):649-53. DOI: 10.1017/s0265021506000056 External link
Arbour R. Continuous nervous system monitoring, EEG, the bispectral index, and neuromuscular transmission. AACN Clin Issues. 2003 May;14(2):185-207. DOI: 10.1097/00044067-200305000-00009 External link
LeBlanc JM, Dasta JF, Kane-Gill SL. Role of the bispectral index in sedation monitoring in the ICU. Ann Pharmacother. 2006 Mar;40(3):490-500. DOI: 10.1345/aph.1E491 External link
Swisher CB, Shah D, Sinha SR, Husain AM. Baseline EEG pattern on continuous ICU EEG monitoring and incidence of seizures. J Clin Neurophysiol. 2015;32(2):147-51. DOI: 10.1097/WNP.0000000000000157 External link
Balas MC, Deutschman CS, Sullivan-Marx EM, Strumpf NE, Alston RP, Richmond TS. Delirium in older patients in surgical intensive care units. J Nurs Scholarsh. 2007;39(2):147-54. DOI: 10.1111/j.1547-5069.2007.00160.x External link
Peterson JF, Pun BT, Dittus RS, Thomason JW, Jackson JC, Shintani AK, Ely EW. Delirium and its motoric subtypes: a study of 614 critically ill patients. J Am Geriatr Soc. 2006 Mar;54(3):479-84. DOI: 10.1111/j.1532-5415.2005.00621.x External link
Luetz A, Heymann A, Radtke FM, Chenitir C, Neuhaus U, Nachtigall I, von Dossow V, Marz S, Eggers V, Heinz A, Wernecke KD, Spies CD. Different assessment tools for intensive care unit delirium: which score to use? Crit Care Med. 2010 Feb;38(2):409-18. DOI: 10.1097/CCM.0b013e3181cabb42 External link
Vasilevskis EE, Morandi A, Boehm L, Pandharipande PP, Girard TD, Jackson JC, Thompson JL, Shintani A, Gordon SM, Pun BT, Ely EW. Delirium and sedation recognition using validated instruments: reliability of bedside intensive care unit nursing assessments from 2007 to 2010. J Am Geriatr Soc. 2011 Nov;59 Suppl 2:S249-55. DOI: 10.1111/j.1532-5415.2011.03673.x External link
Chlan LL, Weinert CR, Heiderscheit A, Tracy MF, Skaar DJ, Guttormson JL, Savik K. Effects of patient-directed music intervention on anxiety and sedative exposure in critically ill patients receiving mechanical ventilatory support: a randomized clinical trial. JAMA. 2013 Jun;309(22):2335-44. DOI: 10.1001/jama.2013.5670 External link
Schenck CH, Mahowald MW. Injurious sleep behavior disorders (parasomnias) affecting patients on intensive care units. Intensive Care Med. 1991;17(4):219-24. DOI: 10.1007/BF01709881 External link
Friesner SA, Curry DM, Moddeman GR. Comparison of two pain-management strategies during chest tube removal: relaxation exercise with opioids and opioids alone. Heart Lung. 2006 Jul-Aug;35(4):269-76. DOI: 10.1016/j.hrtlng.2005.10.005 External link
Martorella G, Boitor M, Michaud C, Gélinas C. Feasibility and acceptability of hand massage therapy for pain management of postoperative cardiac surgery patients in the intensive care unit. Heart Lung. 2014 Sep-Oct;43(5):437-44. DOI: 10.1016/j.hrtlng.2014.06.047 External link
Van Rompaey B, Elseviers MM, Van Drom W, Fromont V, Jorens PG. The effect of earplugs during the night on the onset of delirium and sleep perception: a randomized controlled trial in intensive care patients. Crit Care. 2012;16(3):R73. DOI: 10.1186/cc11330 External link
Khalifezadeh A, Safazadeh S, Mehrabi T, Mansour BA. Reviewing the effect of nursing interventions on delirious patients admitted to intensive care unit of neurosurgery ward in Al-Zahra Hospital, Isfahan University of Medical Sciences. Iran J Nurs Midwifery Res. 2011;16(1):106-12.
Richman PS, Baram D, Varela M, Glass PS. Sedation during mechanical ventilation: a trial of benzodiazepine and opiate in combination. Crit Care Med. 2006 May;34(5):1395-401. DOI: 10.1097/01.CCM.0000215454.50964.F8 External link
Bell RF, Dahl JB, Moore RA, Kalso E. Perioperative ketamine for acute postoperative pain. Cochrane Database Syst Rev. 2006 Jan 25;(1):CD004603. Review. Update in: Cochrane Database Syst Rev. 2015;7:CD004603. DOI: 10.1002/14651858.cd004603.pub2 External link
Block BM, Liu SS, Rowlingson AJ, Cowan AR, Cowan JA Jr, Wu CL. Efficacy of postoperative epidural analgesia: a meta-analysis. JAMA. 2003 Nov;290(18):2455-63. DOI: 10.1001/jama.290.18.2455 External link
Wijeysundera DN, Beattie WS, Austin PC, Hux JE, Laupacis A. Epidural anaesthesia and survival after intermediate-to-high risk non-cardiac surgery: a population-based cohort study. Lancet. 2008 Aug 16;372(9638):562-9. DOI: 10.1016/S0140-6736(08)61121-6 External link
Ballantyne JC, Carr DB, deFerranti S, Suarez T, Lau J, Chalmers TC, Angelillo IF, Mosteller F. The comparative effects of postoperative analgesic therapies on pulmonary outcome: cumulative meta-analyses of randomized, controlled trials. Anesth Analg. 1998 Mar;86(3):598-612.
Jorgensen H, Wetterslev J, Møiniche S, Dahl JB. Epidural local anaesthetics versus opioid-based analgesic regimens on postoperative gastrointestinal paralysis, PONV and pain after abdominal surgery. Cochrane Database Syst Rev. 2000;(4):CD001893. DOI: 10.1002/14651858.CD001893 External link
Gogarten W, Buerkle H, Van Aken H. The quality of epidural anesthesia is crucial in the assessment of perioperative outcome. Anesth Analg. 2003 Jul;97(1):298.
Gogarten W, Van Aken H, Büttner J, Riess H, Wulf H, Bürkle H. Rückenmarksnahe Regionalanästhesien und Thromboembolieprophylaxe/antithrombotische Medikation. Anästh Intensivmed. 2007;48 Suppl. 4:109-24.
Vandermeulen EP, Van Aken H, Vermylen J. Anticoagulants and spinal-epidural anesthesia. Anesth Analg. 1994 Dec;79(6):1165-77. DOI: 10.1213/00000539-199412000-00024 External link
Brull R, McCartney CJ, Chan VW, El-Beheiry H. Neurological complications after regional anesthesia: contemporary estimates of risk. Anesth Analg. 2007 Apr;104(4):965-74. DOI: 10.1213/ External link
Burns SM, Earven S, Fisher C, Lewis R, Merrell P, Schubart JR, Truwit JD, Bleck TP; University of Virginia Long Term Mechanical Ventilation Team. Implementation of an institutional program to improve clinical and financial outcomes of mechanically ventilated patients: one-year outcomes and lessons learned. Crit Care Med. 2003 Dec;31(12):2752-63. DOI: 10.1097/01.CCM.0000094217.07170.75 External link
Arabi Y, Haddad S, Hawes R, Moore T, Pillay M, Naidu B, Issa A, Yeni B, Grant C, Alshimemeri A. Changing sedation practices in the intensive care unit--protocol implementation, multifaceted multidisciplinary approach and teamwork. Middle East J Anaesthesiol. 2007 Jun;19(2):429-47.
Arias-Rivera S, Sánchez-Sánchez Mdel M, Santos-Díaz R, Gallardo-Murillo J, Sánchez-Izquierdo R, Frutos-Vivar F, Ferguson ND, Esteban A. Effect of a nursing-implemented sedation protocol on weaning outcome. Crit Care Med. 2008 Jul;36(7):2054-60. DOI: 10.1097/CCM.0b013e31817bfd60 External link
Quenot JP, Ladoire S, Devoucoux F, Doise JM, Cailliod R, Cunin N, Aubé H, Blettery B, Charles PE. Effect of a nurse-implemented sedation protocol on the incidence of ventilator-associated pneumonia. Crit Care Med. 2007 Sep;35(9):2031-6. DOI: 10.1097/01.ccm.0000282733.83089.4d External link
Robinson BR, Mueller EW, Henson K, Branson RD, Barsoum S, Tsuei BJ. An analgesia-delirium-sedation protocol for critically ill trauma patients reduces ventilator days and hospital length of stay. J Trauma. 2008 Sep;65(3):517-26. DOI: 10.1097/TA.0b013e318181b8f6 External link
Bucknall TK, Manias E, Presneill JJ. A randomized trial of protocol-directed sedation management for mechanical ventilation in an Australian intensive care unit. Crit Care Med. 2008 May;36(5):1444-50. DOI: 10.1097/CCM.0b013e318168f82d External link
DuBose JJ, Inaba K, Shiflett A, Trankiem C, Teixeira PG, Salim A, Rhee P, Demetriades D, Belzberg H. Measurable outcomes of quality improvement in the trauma intensive care unit: the impact of a daily quality rounding checklist. J Trauma. 2008 Jan;64(1):22-7; discussion 27-9. DOI: 10.1097/TA.0b013e318161b0c8 External link
Marshall J, Finn CA, Theodore AC. Impact of a clinical pharmacist-enforced intensive care unit sedation protocol on duration of mechanical ventilation and hospital stay. Crit Care Med. 2008 Feb;36(2):427-33. DOI: 10.1097/01.CCM.0000300275.63811.B3 External link
Ho KM, Ng JY. The use of propofol for medium and long-term sedation in critically ill adult patients: a meta-analysis. Intensive Care Med. 2008 Nov;34(11):1969-79. DOI: 10.1007/s00134-008-1186-5 External link
Fraser GL, Devlin JW, Worby CP, Alhazzani W, Barr J, Dasta JF, Kress JP, Davidson JE, Spencer FA. Benzodiazepine versus nonbenzodiazepine-based sedation for mechanically ventilated, critically ill adults: a systematic review and meta-analysis of randomized trials. Crit Care Med. 2013 Sep;41(9 Suppl 1):S30-8. DOI: 10.1097/CCM.0b013e3182a16898 External link
Kong KL. Inhalational anesthetics in the intensive care unit. Crit Care Clin. 1995 Oct;11(4):887-902.
Millane TA, Bennett ED, Grounds RM. Isoflurane and propofol for long-term sedation in the intensive care unit. A crossover study. Anaesthesia. 1992 Sep;47(9):768-74. DOI: 10.1111/j.1365-2044.1992.tb03254.x External link
Spencer EM, Willatts SM. Isoflurane for prolonged sedation in the intensive care unit; efficacy and safety. Intensive Care Med. 1992;18(7):415-21. DOI: 10.1007/BF01694344 External link
Bedi A, Murray JM, Dingley J, Stevenson MA, Fee JP. Use of xenon as a sedative for patients receiving critical care. Crit Care Med. 2003 Oct;31(10):2470-7. DOI: 10.1097/01.CCM.0000089934.66049.76 External link
Meiser A, Laubenthal H. Inhalational anaesthetics in the ICU: theory and practice of inhalational sedation in the ICU, economics, risk-benefit. Best Pract Res Clin Anaesthesiol. 2005 Sep;19(3):523-38. DOI: 10.1016/j.bpa.2005.02.006 External link
Sackey PV, Martling CR, Granath F, Radell PJ. Prolonged isoflurane sedation of intensive care unit patients with the Anesthetic Conserving Device. Crit Care Med. 2004 Nov;32(11):2241-6.
Hanafy MA. Clinical evaluation of inhalational sedation following coronary artery bypass grafting. Egypt J Anaesth. 2005;21:237-42.
Walder B, Elia N, Henzi I, Romand JR, Tramèr MR. A lack of evidence of superiority of propofol versus midazolam for sedation in mechanically ventilated critically ill patients: a qualitative and quantitative systematic review. Anesth Analg. 2001 Apr;92(4):975-83. DOI: 10.1097/00000539-200104000-00033 External link
Jakob SM, Ruokonen E, Grounds RM, Sarapohja T, Garratt C, Pocock SJ, Bratty JR, Takala J. Dexmedetomidine for Long-Term Sedation Investigators. Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials. JAMA. 2012 Mar;307(11):1151-60. DOI: 10.1001/jama.2012.304 External link
Triltsch AE, Welte M, von Homeyer P, Grosse J, Genähr A, Moshirzadeh M, Sidiropoulos A, Konertz W, Kox WJ, Spies CD. Bispectral index-guided sedation with dexmedetomidine in intensive care: a prospective, randomized, double blind, placebo-controlled phase II study. Crit Care Med. 2002 May;30(5):1007-14. DOI: 10.1097/00003246-200205000-00009 External link
Ruokonen E, Parviainen I, Jakob SM, Nunes S, Kaukonen M, Shepherd ST, Sarapohja T, Bratty JR, Takala J. "Dexmedetomidine for Continuous Sedation" Investigators. Dexmedetomidine versus propofol/midazolam for long-term sedation during mechanical ventilation. Intensive Care Med. 2009 Feb;35(2):282-90. DOI: 10.1007/s00134-008-1296-0 External link
Gabor JY, Cooper AB, Crombach SA, Lee B, Kadikar N, Bettger HE, Hanly PJ. Contribution of the intensive care unit environment to sleep disruption in mechanically ventilated patients and healthy subjects. Am J Respir Crit Care Med. 2003 Mar;167(5):708-15. DOI: 10.1164/rccm.2201090 External link
Girard TD, Pandharipande PP, Ely EW. Delirium in the intensive care unit. Crit Care. 2008;12 Suppl 3:S3. DOI: 10.1186/cc6149 External link
Spies CD, Dubisz N, Neumann T, Blum S, Müller C, Rommelspacher H, Brummer G, Specht M, Sanft C, Hannemann L, Striebel HW, Schaffartzik W. Therapy of alcohol withdrawal syndrome in intensive care unit patients following trauma: results of a prospective, randomized trial. Crit Care Med. 1996 Mar;24(3):414-22. DOI: 10.1097/00003246-199603000-00009 External link
Ely EW, Baker AM, Dunagan DP, Burke HL, Smith AC, Kelly PT, Johnson MM, Browder RW, Bowton DL, Haponik EF. Effect on the duration of mechanical ventilation of identifying patients capable of breathing spontaneously. N Engl J Med. 1996 Dec;335(25):1864-9. DOI: 10.1056/NEJM199612193352502 External link
Warren J, Fromm RE Jr, Orr RA, Rotello LC, Horst HM. American College of Critical Care Medicine. Guidelines for the inter- and intrahospital transport of critically ill patients. Crit Care Med. 2004 Jan;32(1):256-62. DOI: 10.1097/01.CCM.0000104917.39204.0A External link
Dunn MJ, Gwinnutt CL, Gray AJ. Critical care in the emergency department: patient transfer. Emerg Med J. 2007 Jan;24(1):40-4. DOI: 10.1136/emj.2006.042044 External link
Oyelese Y, Ananth CV. Postpartum hemorrhage: epidemiology, risk factors, and causes. Clin Obstet Gynecol. 2010 Mar;53(1):147-56. DOI: 10.1097/GRF.0b013e3181cc406d External link
Loftus JR, Hill H, Cohen SE. Placental transfer and neonatal effects of epidural sufentanil and fentanyl administered with bupivacaine during labor. Anesthesiology. 1995 Aug;83(2):300-8. DOI: 10.1097/00000542-199508000-00010 External link
Steer PL, Biddle CJ, Marley WS, Lantz RK, Sulik PL. Concentration of fentanyl in colostrum after an analgesic dose. Can J Anaesth. 1992 Mar;39(3):231-5. DOI: 10.1007/BF03008782 External link
Lejeune C, Aubisson S, Simmat-Durand L, Cneude F, Piquet M, Gourarier L; Groupe d'Etudes Grossesse et addictions. Syndromes de sevrage des nouveau-nes de meres toxicomanes substituees par la methadone ou la buprenorphine haut dosage [Withdrawal syndromes of newborns of pregnant drug abusers maintained under methadone or high-dose buprenorphine: 246 cases]. Ann Med Interne (Paris). 2001 Nov;152 Suppl 7:21-7.
Barry WS, Meinzinger MM, Howse CR. Ibuprofen overdose and exposure in utero: results from a postmarketing voluntary reporting system. Am J Med. 1984 Jul 13;77(1A):35-9. DOI: 10.1016/S0002-9343(84)80016-9 External link
Nielsen GL, Sørensen HT, Larsen H, Pedersen L. Risk of adverse birth outcome and miscarriage in pregnant users of non-steroidal anti-inflammatory drugs: population based observational study and case-control study. BMJ. 2001 Feb;322(7281):266-70. DOI: 10.1136/bmj.322.7281.266 External link
Briggs GG. Medication use during the perinatal period. J Am Pharm Assoc (Wash). 1998 Nov-Dec;38(6):717-26; quiz 726-7.
Niederhoff H, Zahradnik HP. Analgesics during pregnancy. Am J Med. 1983 Nov 14;75(5A):117-20. DOI: 10.1016/0002-9343(83)90242-5 External link
Thulstrup AM, Sørensen HT, Nielsen GL, Andersen L, Barrett D, Vilstrup H, Olsen J. Fetal growth and adverse birth outcomes in women receiving prescriptions for acetaminophen during pregnancy. EuroMap Study Group. Am J Perinatol. 1999;16(7):321-6. DOI: 10.1055/s-2007-993879 External link
Notarianni LJ, Oldham HG, Bennett PN. Passage of paracetamol into breast milk and its subsequent metabolism by the neonate. Br J Clin Pharmacol. 1987 Jul;24(1):63-7. DOI: 10.1111/j.1365-2125.1987.tb03137.x External link
Seymour MP, Jefferies TM, Floyd AJ, Notarianni LJ. Routine determination of organochlorine pesticides and polychlorinated biphenyls in human milk using capillary gas chromatography-mass spectrometry. Analyst. 1987 Apr;112(4):427-31. DOI: 10.1039/an9871200427 External link
Bar-Oz B, Bulkowstein M, Benyamini L, Greenberg R, Soriano I, Zimmerman D, Bortnik O, Berkovitch M. Use of antibiotic and analgesic drugs during lactation. Drug Saf. 2003;26(13):925-35. DOI: 10.2165/00002018-200326130-00002 External link
Halpern SH, Levine T, Wilson DB, MacDonell J, Katsiris SE, Leighton BL. Effect of labor analgesia on breastfeeding success. Birth. 1999 Jun;26(2):83-8. DOI: 10.1046/j.1523-536x.1999.00083.x External link
Gaiser R. Neonatal effects of labor analgesia. Int Anesthesiol Clin. 2002;40(4):49-65. DOI: 10.1097/00004311-200210000-00006 External link
Albani A, Addamo P, Renghi A, Voltolin G, Peano L, Ivani G. Influenza sulla frequenza di allattamento al seno delle tecniche di anestesia regionale nel parto cesareo e nel parto per via vaginale [The effect on breastfeeding rate of regional anesthesia technique for cesarean and vaginal childbirth]. Minerva Anestesiol. 1999 Sep;65(9):625-30.
Madadi P, Ross CJ, Hayden MR, Carleton BC, Gaedigk A, Leeder JS, Koren G. Pharmacogenetics of neonatal opioid toxicity following maternal use of codeine during breastfeeding: a case-control study. Clin Pharmacol Ther. 2009 Jan;85(1):31-5. DOI: 10.1038/clpt.2008.157 External link
Pham TN, Otto A, Young SR, Kramer CB, Heimbach DM, Gibran NS, Klein MB. Early withdrawal of life support in severe burn injury. J Burn Care Res. 2012 Jan-Feb;33(1):130-5. DOI: 10.1097/BCR.0b013e31823e598d External link
Moyer DD. Review article: terminal delirium in geriatric patients with cancer at end of life. Am J Hosp Palliat Care. 2011 Feb;28(1):44-51. DOI: 10.1177/1049909110376755 External link
Wasiak J, Mahar P, McGuinness SK, Spinks A, Danilla S, Cleland H. Intravenous lidocaine for the treatment of background or procedural burn pain. Cochrane Database Syst Rev. 2012 Jun 13;6:CD005622. DOI: 10.1002/14651858.CD005622.pub3 External link
Cuignet O, Pirson J, Soudon O, Zizi M. Effects of gabapentin on morphine consumption and pain in severely burned patients. Burns. 2007 Feb;33(1):81-6. DOI: 10.1016/j.burns.2006.04.020 External link
Warncke T, Stubhaug A, Jørum E. Ketamine, an NMDA receptor antagonist, suppresses spatial and temporal properties of burn-induced secondary hyperalgesia in man: a double-blind, cross-over comparison with morphine and placebo. Pain. 1997 Aug;72(1-2):99-106. DOI: 10.1016/S0304-3959(97)00006-7 External link
Ilkjaer S, Petersen KL, Brennum J, Wernberg M, Dahl JB. Effect of systemic N-methyl-D-aspartate receptor antagonist (ketamine) on primary and secondary hyperalgesia in humans. Br J Anaesth. 1996 Jun;76(6):829-34. DOI: 10.1093/bja/76.6.829 External link
Edrich T, Friedrich AD, Eltzschig HK, Felbinger TW. Ketamine for long-term sedation and analgesia of a burn patient. Anesth Analg. 2004 Sep;99(3):893-5, table of contents. DOI: 10.1213/01.ANE.0000133002.42742.92 External link
Asmussen S, Maybauer DM, Fraser JF, Jennings K, George S, Maybauer MO. A meta-analysis of analgesic and sedative effects of dexmedetomidine in burn patients. Burns. 2013 Jun;39(4):625-31. DOI: 10.1016/j.burns.2013.01.008 External link
Desai C, Wood FM, Schug SA, Parsons RW, Fridlender C, Sunderland VB. Effectiveness of a topical local anaesthetic spray as analgesia for dressing changes: a double-blinded randomised pilot trial comparing an emulsion with an aqueous lidocaine formulation. Burns. 2014 Feb;40(1):106-12. DOI: 10.1016/j.burns.2013.05.013 External link
Morris LD, Louw QA, Grimmer-Somers K. The effectiveness of virtual reality on reducing pain and anxiety in burn injury patients: a systematic review. Clin J Pain. 2009 Nov-Dec;25(9):815-26. DOI: 10.1097/AJP.0b013e3181aaa909 External link
Humphries Y, Melson M, Gore D. Superiority of oral ketamine as an analgesic and sedative for wound care procedures in the pediatric patient with burns. J Burn Care Rehabil. 1997 Jan-Feb;18(1 Pt 1):34-6. DOI: 10.1097/00004630-199701000-00006 External link
Field T, Peck M, Krugman S, Tuchel T, Schanberg S, Kuhn C, Burman I. Burn injuries benefit from massage therapy. J Burn Care Rehabil. 1998 May-Jun;19(3):241-4. DOI: 10.1097/00004630-199805000-00010 External link
Hernandez-Reif M, Field T, Largie S, Hart S, Redzepi M, Nierenberg B, Peck TM. Childrens' distress during burn treatment is reduced by massage therapy. J Burn Care Rehabil. 2001 Mar-Apr;22(2):191-5.
Frenay MC, Faymonville ME, Devlieger S, Albert A, Vanderkelen A. Psychological approaches during dressing changes of burned patients: a prospective randomised study comparing hypnosis against stress reducing strategy. Burns. 2001 Dec;27(8):793-9. DOI: 10.1016/S0305-4179(01)00035-3 External link
Fagin A, Palmieri T, Greenhalgh D, Sen S. A comparison of dexmedetomidine and midazolam for sedation in severe pediatric burn injury. J Burn Care Res. 2012 Nov-Dec;33(6):759-63. DOI: 10.1097/BCR.0b013e318254d48e External link
Cotton BA, Guillamondegui OD, Fleming SB, Carpenter RO, Patel SH, Morris JA Jr, Arbogast PG. Increased risk of adrenal insufficiency following etomidate exposure in critically injured patients. Arch Surg. 2008 Jan;143(1):62-7; discussion 67. DOI: 10.1001/archsurg.143.1.62 External link
Hildreth AN, Mejia VA, Maxwell RA, Smith PW, Dart BW, Barker DE. Adrenal suppression following a single dose of etomidate for rapid sequence induction: a prospective randomized study. J Trauma. 2008 Sep;65(3):573-9. DOI: 10.1097/TA.0b013e31818255e8 External link
Warner KJ, Cuschieri J, Jurkovich GJ, Bulger EM. Single-dose etomidate for rapid sequence intubation may impact outcome after severe injury. J Trauma. 2009 Jul;67(1):45-50. DOI: 10.1097/TA.0b013e3181a92a70 External link
Matthes G, Bernhard M, Kanz KG, Waydhas C, Fischbacher M, Fischer M, Böttiger BW. Notfallnarkose, Atemwegsmanagement und Beatmung beim Polytrauma. Hintergrund und Kernaussagen der interdisziplinären S3-Leitlinie Polytrauma [Emergency anesthesia, airway management and ventilation in major trauma. Background and key messages of the interdisciplinary S3 guidelines for major trauma patients]. Unfallchirurg. 2012 Mar;115(3):251-64; quiz 265-6. DOI: 10.1007/s00113-011-2138-z External link
Bratton SL, Chestnut RM, Ghajar J, McConnell Hammond FF, Harris OA, Hartl R, Manley GT, Nemecek A, Newell DW, Rosenthal G, Schouten J, Shutter L, Timmons SD, Ullman JS, Videtta W, Wilberger JE, Wright DW. Guidelines for the management of severe traumatic brain injury. XI. Anesthetics, analgesics, and sedatives. J Neurotrauma. 2007;24 Suppl 1:S71-6. DOI: 10.1089/neu.2007.9985 External link
Cohen L, Athaide V, Wickham ME, Doyle-Waters MM, Rose NG, Hohl CM. The effect of ketamine on intracranial and cerebral perfusion pressure and health outcomes: a systematic review. Ann Emerg Med. 2015 Jan;65(1):43-51.e2. DOI: 10.1016/j.annemergmed.2014.06.018 External link
Wang X, Ding X, Tong Y, Zong J, Zhao X, Ren H, Li Q. Ketamine does not increase intracranial pressure compared with opioids: meta-analysis of randomized controlled trials. J Anesth. 2014 Dec;28(6):821-7. DOI: 10.1007/s00540-014-1845-3 External link
Kolenda H, Gremmelt A, Rading S, Braun U, Markakis E. Ketamine for analgosedative therapy in intensive care treatment of head-injured patients. Acta Neurochir (Wien). 1996;138(10):1193-9. Erratum in: Acta Neurochir (Wien) 1997;139(12):1193. DOI: 10.1007/BF01809750 External link
Bourgoin A, Albanèse J, Wereszczynski N, Charbit M, Vialet R, Martin C. Safety of sedation with ketamine in severe head injury patients: comparison with sufentanil. Crit Care Med. 2003 Mar;31(3):711-7. DOI: 10.1097/01.CCM.0000044505.24727.16 External link
Lauer KK, Connolly LA, Schmeling WT. Opioid sedation does not alter intracranial pressure in head injured patients. Can J Anaesth. 1997 Sep;44(9):929-33. DOI: 10.1007/BF03011963 External link
Karabinis A, Mandragos K, Stergiopoulos S, Komnos A, Soukup J, Speelberg B, Kirkham AJ. Safety and efficacy of analgesia-based sedation with remifentanil versus standard hypnotic-based regimens in intensive care unit patients with brain injuries: a randomised, controlled trial [ISRCTN50308308]. Crit Care. 2004 Aug;8(4):R268-80. DOI: 10.1186/cc2896 External link
Mirski MA, Hemstreet MK. Critical care sedation for neuroscience patients. J Neurol Sci. 2007 Oct;261(1-2):16-34. DOI: 10.1016/j.jns.2007.04.028 External link
Cohen J, Royston D. Remifentanil. Curr Opin Crit Care. 2001 Aug;7(4):227-31. DOI: 10.1097/00075198-200108000-00003 External link
Bauer C, Kreuer S, Ketter R, Grundmann U, Wilhelm W.Remifentanil-Propofol- versus Fentanyl-Midazolam-Kombination bei intrakraniellen Eingriffen: Einfluss von Anästhesietechnik und Intensivanalgosedierung auf Beatmungszeiten und Dauer des Intensivaufenthalts [Remifentanil-propofol versus fentanyl-midazolam combinations for intracranial surgery: influence of anaesthesia technique and intensive sedation on ventilation times and duration of stay in the ICU]. Anaesthesist. 2007 Feb;56(2):128-32. DOI: 10.1007/s00101-006-1130-4 External link
Roberts DJ, Hall RI, Kramer AH, Robertson HL, Gallagher CN, Zygun DA. Sedation for critically ill adults with severe traumatic brain injury: a systematic review of randomized controlled trials. Crit Care Med. 2011 Dec;39(12):2743-51. DOI: 10.1097/CCM.0b013e318228236f External link
Schwartz ML, Tator CH, Rowed DW, Reid SR, Meguro K, Andrews DF. The University of Toronto head injury treatment study: a prospective, randomized comparison of pentobarbital and mannitol. Can J Neurol Sci. 1984 Nov;11(4):434-40.
Ward JD, Becker DP, Miller JD, Choi SC, Marmarou A, Wood C, Newlon PG, Keenan R. Failure of prophylactic barbiturate coma in the treatment of severe head injury. J Neurosurg. 1985 Mar;62(3):383-8. DOI: 10.3171/jns.1985.62.3.0383 External link
Bratton SL, Chestnut RM, Ghajar J, McConnell Hammond FF, Harris OA, Hartl R, Manley GT, Nemecek A, Newell DW, Rosenthal G, Schouten J, Shutter L, Timmons SD, Ullman JS, Videtta W, Wilberger JE, Wright DW. Guidelines for the management of severe traumatic brain injury. XV. Steroids. J Neurotrauma. 2007;24 Suppl 1:S91-5. DOI: 10.1089/neu.2007.9981 External link
Roberts I. Barbiturates for acute traumatic brain injury. Cochrane Database Syst Rev. 2000;(2):CD000033. DOI: 10.1002/14651858.CD000033 External link
Eisenberg HM, Frankowski RF, Contant CF, Marshall LF, Walker MD. High-dose barbiturate control of elevated intracranial pressure in patients with severe head injury. J Neurosurg. 1988 Jul;69(1):15-23. DOI: 10.3171/jns.1988.69.1.0015 External link
Perez-Barcena J, Llompart-Pou JA, Homar J, Abadal JM, Raurich JM, Frontera G, Brell M. Pentobarbital versus thiopental in the treatment of refractory intracranial hypertension in patients with traumatic brain injury: a randomized controlled trial. Crit Care. 2008;12(4):R112. DOI: 10.1186/cc6999 External link
Casey E, Lane A, Kuriakose D, McGeary S, Hayes N, Phelan D, Buggy D. Bolus remifentanil for chest drain removal in ICU: a randomized double-blind comparison of three modes of analgesia in post-cardiac surgical patients. Intensive Care Med. 2010 Aug;36(8):1380-5. DOI: 10.1007/s00134-010-1836-2 External link
Muellejans B, Matthey T, Scholpp J, Schill M. Sedation in the intensive care unit with remifentanil/propofol versus midazolam/fentanyl: a randomised, open-label, pharmacoeconomic trial. Crit Care. 2006;10(3):R91. DOI: 10.1186/cc4939 External link
Bainbridge D, Martin JE, Cheng DC. Patient-controlled versus nurse-controlled analgesia after cardiac surgery--a meta-analysis. Can J Anaesth. 2006 May;53(5):492-9. DOI: 10.1007/BF03022623 External link
Tramm R, Hodgson C, Ilic D, Sheldrake J, Pellegrino V. Identification and prevalence of PTSD risk factors in ECMO patients: A single centre study. Aust Crit Care. 2015 Feb;28(1):31-6. DOI: 10.1016/j.aucc.2014.04.005 External link
Rahimi RA, Skrzat J, Reddy DR, Zanni JM, Fan E, Stephens RS, Needham DM. Physical rehabilitation of patients in the intensive care unit requiring extracorporeal membrane oxygenation: a small case series. Phys Ther. 2013 Feb;93(2):248-55. DOI: 10.2522/ptj.20120336 External link
Peters JW, Koot HM, Grunau RE, de Boer J, van Druenen MJ, Tibboel D, Duivenvoorden HJ. Neonatal Facial Coding System for assessing postoperative pain in infants: item reduction is valid and feasible. Clin J Pain. 2003 Nov-Dec;19(6):353-63. DOI: 10.1097/00002508-200311000-00003 External link
Buttner W, Finke W, Hilleke M, Reckert S, Vsianska L, Brambrink A. Entwicklung eines Fremdbeobachtungsbogens zur Beurteilung des postoperativen Schmerzes bei Saeuglingen [Development of an observational scale for assessment of postoperative pain in infants]. Anasthesiol Intensivmed Notfallmed Schmerzther. 1998 Jun;33(6):353-61. DOI: 10.1055/s-2007-994263 External link
Buttner W, Finke W. Analysis of behavioural and physiological parameters for the assessment of postoperative analgesic demand in newborns, infants and young children: a comprehensive report on seven consecutive studies. Paediatr Anaesth. 2000;10(3):303-18. DOI: 10.1046/j.1460-9592.2000.00530.x External link
van Dijk M, Roofthooft DW, Anand KJ, Guldemond F, de Graaf J, Simons S, de Jager Y, van Goudoever JB, Tibboel D. Taking up the challenge of measuring prolonged pain in (premature) neonates: the COMFORTneo scale seems promising. Clin J Pain. 2009 Sep;25(7):607-16. DOI: 10.1097/AJP.0b013e3181a5b52a External link
Breau LM, McGrath PJ, Camfield CS, Finley GA. Psychometric properties of the non-communicating children's pain checklist-revised. Pain. 2002 Sep;99(1-2):349-57. DOI: 10.1016/S0304-3959(02)00179-3 External link
Hunt A, Goldman A, Seers K, Crichton N, Mastroyannopoulou K, Moffat V, Oulton K, Brady M. Clinical validation of the paediatric pain profile. Dev Med Child Neurol. 2004 Jan;46(1):9-18. DOI: 10.1111/j.1469-8749.2004.tb00428.x External link
Hillman BA, Tabrizi MN, Gauda EB, Carson KA, Aucott SW. The Neonatal Pain, Agitation and Sedation Scale and the bedside nurse's assessment of neonates. J Perinatol. 2015 Feb;35(2):128-31. DOI: 10.1038/jp.2014.154 External link
Bagley SM, Wachman EM, Holland E, Brogly SB. Review of the assessment and management of neonatal abstinence syndrome. Addict Sci Clin Pract. 2014;9(1):19. DOI: 10.1186/1940-0640-9-19 External link
Ista E, van Dijk M, de Hoog M, Tibboel D, Duivenvoorden HJ. Construction of the Sophia Observation withdrawal Symptoms-scale (SOS) for critically ill children. Intensive Care Med. 2009 Jun;35(6):1075-81. DOI: 10.1007/s00134-009-1487-3 External link
Franck LS, Harris SK, Soetenga DJ, Amling JK, Curley MA. The Withdrawal Assessment Tool-1 (WAT-1): an assessment instrument for monitoring opioid and benzodiazepine withdrawal symptoms in pediatric patients. Pediatr Crit Care Med. 2008 Nov;9(6):573-80. DOI: 10.1097/PCC.0b013e31818c8328 External link
Deindl P, Unterasinger L, Kappler G, Werther T, Czaba C, Giordano V, Frantal S, Berger A, Pollak A, Olischar M. Successful implementation of a neonatal pain and sedation protocol at 2 NICUs. Pediatrics. 2013 Jul;132(1):e211-8. DOI: 10.1542/peds.2012-2346 External link
Giordano V, Deindl P, Kuttner S, Waldhör T, Berger A, Olischar M. The Neonatal Pain, Agitation and Sedation Scale reliably detected oversedation but failed to differentiate between other sedation levels. Acta Paediatr. 2014 Dec;103(12):e515-21. DOI: 10.1111/apa.12770 External link
Hummel P, Puchalski M, Creech SD, Weiss MG. Clinical reliability and validity of the N-PASS: neonatal pain, agitation and sedation scale with prolonged pain. J Perinatol. 2008 Jan;28(1):55-60. DOI: 10.1038/ External link
Ista E, van Dijk M, Tibboel D, de Hoog M. Assessment of sedation levels in pediatric intensive care patients can be improved by using the COMFORT "behavior" scale. Pediatr Crit Care Med. 2005 Jan;6(1):58-63. DOI: 10.1097/01.PCC.0000149318.40279.1A External link
Johansson M, Kokinsky E. The COMFORT behavioural scale and the modified FLACC scale in paediatric intensive care. Nurs Crit Care. 2009 May-Jun;14(3):122-30. DOI: 10.1111/j.1478-5153.2009.00323.x External link
Wielenga JM, De Vos R, de Leeuw R, De Haan RJ. COMFORT scale: a reliable and valid method to measure the amount of stress of ventilated preterm infants. Neonatal Netw. 2004 Mar-Apr;23(2):39-44. DOI: 10.1891/0730-0832.23.2.39 External link
van Dijk M, de Boer JB, Koot HM, Tibboel D, Passchier J, Duivenvoorden HJ. The reliability and validity of the COMFORT scale as a postoperative pain instrument in 0 to 3-year-old infants. Pain. 2000 Feb;84(2-3):367-77. DOI: 10.1016/S0304-3959(99)00239-0 External link
Playfor SD. Analgesia and sedation in critically ill children. Arch Dis Child Educ Pract Ed. 2008 Jun;93(3):87-92. DOI: 10.1136/adc.2007.119628 External link
Lynn A, Nespeca MK, Bratton SL, Strauss SG, Shen DD. Clearance of morphine in postoperative infants during intravenous infusion: the influence of age and surgery. Anesth Analg. 1998 May;86(5):958-63.
Farrington EA, McGuinness GA, Johnson GF, Erenberg A, Leff RD. Continuous intravenous morphine infusion in postoperative newborn infants. Am J Perinatol. 1993 Jan;10(1):84-7. DOI: 10.1055/s-2007-994711 External link
Tarkkila P, Saarnivaara L. Ketoprofen, diclofenac or ketorolac for pain after tonsillectomy in adults? Br J Anaesth. 1999 Jan;82(1):56-60. DOI: 10.1093/bja/82.1.56 External link
Oztekin S, Hepaguslar H, Kar AA, Ozzeybek D, Artikaslan O, Elar Z. Preemptive diclofenac reduces morphine use after remifentanil-based anaesthesia for tonsillectomy. Paediatr Anaesth. 2002 Oct;12(8):694-9. DOI: 10.1046/j.1460-9592.2002.00950.x External link
Pickering AE, Bridge HS, Nolan J, Stoddart PA. Double-blind, placebo-controlled analgesic study of ibuprofen or rofecoxib in combination with paracetamol for tonsillectomy in children. Br J Anaesth. 2002 Jan;88(1):72-7. DOI: 10.1093/bja/88.1.72 External link
Viitanen H, Tuominen N, Vaaraniemi H, Nikanne E, Annila P. Analgesic efficacy of rectal acetaminophen and ibuprofen alone or in combination for paediatric day-case adenoidectomy. Br J Anaesth. 2003 Sep;91(3):363-7. DOI: 10.1093/bja/aeg196 External link
Moore RP, Wester T, Sunder R, Schrock C, Park TS. Peri-operative pain management in children with cerebral palsy: comparative efficacy of epidural vs systemic analgesia protocols. Paediatr Anaesth. 2013 Aug;23(8):720-5. DOI: 10.1111/pan.12187 External link
Monitto CL, Greenberg RS, Kost-Byerly S, Wetzel R, Billett C, Lebet RM, Yaster M. The safety and efficacy of parent-/nurse-controlled analgesia in patients less than six years of age. Anesth Analg. 2000 Sep;91(3):573-9. DOI: 10.1213/00000539-200009000-00014 External link
Stevens B, Yamada J, Ohlsson A. Sucrose for analgesia in newborn infants undergoing painful procedures. Cochrane Database Syst Rev. 2004;(3):CD001069. DOI: 10.1002/14651858.cd001069.pub2 External link
Cignacco E, Hamers JP, Stoffel L, van Lingen RA, Gessler P, McDougall J, Nelle M. The efficacy of non-pharmacological interventions in the management of procedural pain in preterm and term neonates. A systematic literature review. Eur J Pain. 2007 Feb;11(2):139-52. DOI: 10.1016/j.ejpain.2006.02.010 External link
Taylor A, Walker C, Butt W. Can children recall their experiences of admission to an intensive care unit? Crit Care Resusc. 2000 Dec;2(4):253-9.
Hartman ME, McCrory DC, Schulman SR. Efficacy of sedation regimens to facilitate mechanical ventilation in the pediatric intensive care unit: a systematic review. Pediatr Crit Care Med. 2009 Mar;10(2):246-55. DOI: 10.1097/PCC.0b013e31819a3bb9 External link
Lamas A, Lopez-Herce J. Monitoring sedation in the critically ill child. Anaesthesia. 2010 May;65(5):516-24. DOI: 10.1111/j.1365-2044.2010.06263.x External link
de Wildt SN, de Hoog M, Vinks AA, Joosten KF, van Dijk M, van den Anker JN. Pharmacodynamics of midazolam in pediatric intensive care patients. Ther Drug Monit. 2005 Feb;27(1):98-102. DOI: 10.1097/00007691-200502000-00018 External link
Gupta P, Whiteside W, Sabati A, Tesoro TM, Gossett JM, Tobias JD, Roth SJ. Safety and efficacy of prolonged dexmedetomidine use in critically ill children with heart disease*. Pediatr Crit Care Med. 2012 Nov;13(6):660-6. DOI: 10.1097/PCC.0b013e318253c7f1 External link
Hünseler C, Balling G, Röhlig C, Blickheuser R, Trieschmann U, Lieser U, Dohna-Schwake C, Gebauer C, Möller O, Hering F, Hoehn T, Schubert S, Hentschel R, Huth RG, Müller A, Müller C, Wassmer G, Hahn M, Harnischmacher U, Behr J, Roth B. Clonidine Study Group. Continuous infusion of clonidine in ventilated newborns and infants: a randomized controlled trial. Pediatr Crit Care Med. 2014 Jul;15(6):511-22. DOI: 10.1097/PCC.0000000000000151 External link
Tobias JD, Berkenbosch JW. Sedation during mechanical ventilation in infants and children: dexmedetomidine versus midazolam. South Med J. 2004 May;97(5):451-5. DOI: 10.1097/00007611-200405000-00007 External link
Whalen LD, Di Gennaro JL, Irby GA, Yanay O, Zimmerman JJ. Long-term dexmedetomidine use and safety profile among critically ill children and neonates. Pediatr Crit Care Med. 2014 Oct;15(8):706-14. DOI: 10.1097/PCC.0000000000000200 External link
Gupta K, Gupta VK, Jayashree M, Muralindharan J, Singhi S. Randomized controlled trial of interrupted versus continuous sedative infusions in ventilated children. Pediatr Crit Care Med. 2012 Mar;13(2):131-5. DOI: 10.1097/PCC.0b013e31820aba48 External link
Verlaat CW, Heesen GP, Vet NJ, de Hoog M, van der Hoeven JG, Kox M, Pickkers P. Randomized controlled trial of daily interruption of sedatives in critically ill children. Paediatr Anaesth. 2014 Feb;24(2):151-6. DOI: 10.1111/pan.12245 External link
Parkinson L, Hughes J, Gill A, Billingham I, Ratcliffe J, Choonara I. A randomized controlled trial of sedation in the critically ill. Paediatr Anaesth. 1997;7(5):405-10. DOI: 10.1046/j.1460-9592.1997.d01-109.x External link
Ng E, Taddio A, Ohlsson A. Intravenous midazolam infusion for sedation of infants in the neonatal intensive care unit. Cochrane Database Syst Rev. 2003;(1):CD002052. DOI: 10.1002/14651858.cd002052 External link
Bellù R, de Waal KA, Zanini R. Opioids for neonates receiving mechanical ventilation. Cochrane Database Syst Rev. 2008 Jan 23;(1):CD004212. DOI: 10.1002/14651858.cd004212.pub3 External link
Brusseau R, McCann ME. Anaesthesia for urgent and emergency surgery. Early Hum Dev. 2010 Nov;86(11):703-14. DOI: 10.1016/j.earlhumdev.2010.08.008 External link
Davidson AJ. Anesthesia and neurotoxicity to the developing brain: the clinical relevance. Paediatr Anaesth. 2011 Jul;21(7):716-21. DOI: 10.1111/j.1460-9592.2010.03506.x External link
Istaphanous GK, Ward CG, Loepke AW. The impact of the perioperative period on neurocognitive development, with a focus on pharmacological concerns. Best Pract Res Clin Anaesthesiol. 2010 Sep;24(3):433-49. DOI: 10.1016/j.bpa.2010.02.013 External link
Loepke AW. Developmental neurotoxicity of sedatives and anesthetics: a concern for neonatal and pediatric critical care medicine? Pediatr Crit Care Med. 2010 Mar;11(2):217-26. DOI: 10.1097/PCC.0b013e3181b80383 External link
Patel P, Sun L. Update on neonatal anesthetic neurotoxicity: insight into molecular mechanisms and relevance to humans. Anesthesiology. 2009 Apr;110(4):703-8. DOI: 10.1097/ALN.0b013e31819c42a4 External link
Sun L. Early childhood general anaesthesia exposure and neurocognitive development. Br J Anaesth. 2010 Dec;105 Suppl 1:i61-8. DOI: 10.1093/bja/aeq302 External link
Ward CG, Loepke AW. Anesthetics and sedatives: toxic or protective for the developing brain? Pharmacol Res. 2012 Mar;65(3):271-4. DOI: 10.1016/j.phrs.2011.10.001 External link
Brown RL, Henke A, Greenhalgh DG, Warden GD. The use of haloperidol in the agitated, critically ill pediatric patient with burns. J Burn Care Rehabil. 1996 Jan-Feb;17(1):34-8. DOI: 10.1097/00004630-199601000-00009 External link
Harrison AM, Lugo RA, Lee WE, Appachi E, Bourdakos D, Davis SJ, McHugh MJ, Weise KL. The use of haloperidol in agitated critically ill children. Clin Pediatr (Phila). 2002 Jan-Feb;41(1):51-4. DOI: 10.1177/000992280204100111 External link
Balas MC, Happ MB, Yang W, Chelluri L, Richmond T. Outcomes Associated With Delirium in Older Patients in Surgical ICUs. Chest. 2009 Jan;135(1):18-25. DOI: 10.1378/chest.08-1456 External link
Warden V, Hurley AC, Volicer L. Development and psychometric evaluation of the Pain Assessment in Advanced Dementia (PAINAD) scale. J Am Med Dir Assoc. 2003 Jan-Feb;4(1):9-15. DOI: 10.1097/01.JAM.0000043422.31640.F7 External link
Basler HD, Huger D, Kunz R, Luckmann J, Lukas A, Nikolaus T, Schuler MS. Beurteilung von Schmerz bei Demenz (BESD). Untersuchung zur Validitaet eines Verfahrens zur Beobachtung des Schmerzverhaltens [Assessment of pain in advanced dementia. Construct validity of the German PAINAD]. Schmerz. 2006 Nov;20(6):519-26. DOI: 10.1007/s00482-006-0490-7 External link
Herr KA, Mobily PR, Kohout FJ, Wagenaar D. Evaluation of the Faces Pain Scale for use with the elderly. Clin J Pain. 1998 Mar;14(1):29-38. DOI: 10.1097/00002508-199803000-00005 External link
Gamberini M, Bolliger D, Lurati Buse GA, Burkhart CS, Grapow M, Gagneux A, Filipovic M, Seeberger MD, Pargger H, Siegemund M, Carrel T, Seiler WO, Berres M, Strebel SP, Monsch AU, Steiner LA. Rivastigmine for the prevention of postoperative delirium in elderly patients undergoing elective cardiac surgery--a randomized controlled trial. Crit Care Med. 2009 May;37(5):1762-8. DOI: 10.1097/CCM.0b013e31819da780 External link
Barr J, Zomorodi K, Bertaccini EJ, Shafer SL, Geller E. A double-blind, randomized comparison of i.v. lorazepam versus midazolam for sedation of ICU patients via a pharmacologic model. Anesthesiology. 2001 Aug;95(2):286-98. DOI: 10.1097/00000542-200108000-00007 External link
Chew ML, Mulsant BH, Pollock BG. Serum anticholinergic activity and cognition in patients with moderate-to-severe dementia. Am J Geriatr Psychiatry. 2005 Jun;13(6):535-8. DOI: 10.1176/appi.ajgp.13.6.535 External link
Brook AD, Ahrens TS, Schaiff R, Prentice D, Sherman G, Shannon W, Kollef MH. Effect of a nursing-implemented sedation protocol on the duration of mechanical ventilation. Crit Care Med. 1999 Dec;27(12):2609-15. DOI: 10.1097/00003246-199912000-00001 External link
Brattebo G, Hofoss D, Flaatten H, Muri AK, Gjerde S, Plsek PE. Effect of a scoring system and protocol for sedation on duration of patients' need for ventilator support in a surgical intensive care unit. BMJ. 2002 Jun;324(7350):1386-9. DOI: 10.1136/bmj.324.7350.1386 External link
Girard TD, Ely EW. Protocol-driven ventilator weaning: reviewing the evidence. Clin Chest Med. 2008 Jun;29(2):241-52, v. DOI: 10.1016/j.ccm.2008.02.004 External link
Radtke FM, Heymann A, Franck M, Maechler F, Drews T, Luetz A, Nachtigall I, Wernecke KD, Spies CD. How to implement monitoring tools for sedation, pain and delirium in the intensive care unit: an experimental cohort study. Intensive Care Med. 2012 Dec;38(12):1974-81. DOI: 10.1007/s00134-012-2658-1 External link
Trogrlic Z, van der Jagt M, Bakker J, Balas MC, Ely EW, van der Voort PH, Ista E. A systematic review of implementation strategies for assessment, prevention, and management of ICU delirium and their effect on clinical outcomes. Crit Care. 2015;19:157. DOI: 10.1186/s13054-015-0886-9 External link
Riker RR, Fraser GL. Monitoring sedation, agitation, analgesia, neuromuscular blockade, and delirium in adult ICU patients. Semin Respir Crit Care Med. 2001;22(2):189-98. DOI: 10.1055/s-2001-13832 External link


In the initial publication the author Irene Harth was erroneously omitted in the html version.