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 German guidelines for the management of analgesia, sedation and delirium in intensive care – short version

Review Article

  • author Jörg Martin - Department of Anesthesiology and Operative Intensive Care, Klinik am Eichert, Göppingen, Germany
  • author Anja Heymann - Department of Anesthesiology and Operative Intensive Care, Charité Campus Virchow, Berlin, Germany
  • author Katrin Bäsell - DRK Kliniken Berlin Köpenick, Berlin, Germany
  • author Ralf Baron - Department of Neurology, Christian-Albrechts University, Kiel, Germany
  • author Rolf Biniek - Department of Neurology, LVR-Klinik Bonn, Germany
  • author Hartmut Bürkle - Clinic for Anaesthesiology and Operative Intensive Care and Pain Clinic of Memmingen, Germany
  • author Peter Dall - Municipal Hospital of Lüneburg, Germany
  • author Christine Dictus - Department of Neurosurgery, University of Heidelberg, Germany
  • author Verena Eggers - Department of Anesthesiology and Intensive Care Medicine, Campus Virchow-Klinikum and Campus Charité Mitte, Berlin, Germany
  • author Ingolf Eichler - Department of Cardiac and Vascular Surgery, Klinikum Dortmund GgmbH, Germany
  • author Lothar Engelmann - Department of Internal Medicine and Intensive Care Medicine, University of Leipzig, Germany
  • author Lars Garten - Department of Neonatology, Charité University Medicine Berlin, Germany
  • author Wolfgang Hartl - Department of Surgery Grosshadern, University of Munich, Germany
  • author Ulrike Haase - Department of Anesthesiology and Intensive Care Medicine, Charité Campus Mitte, Berlin, Germany
  • author Ralf Huth - University Children's Hospital of Mainz, Germany
  • author Paul Kessler - Department of Anesthesiology and Intensive Care Medicine, Orthopedic University Hospital, Frankfurt, Germany
  • author Stefan Kleinschmidt - Department of Anesthesiology, Intensive Care Medicine and Pain Management, BG Trauma Clinic Ludwigshafen, Germany
  • author Wolfgang Koppert - Department of Anesthesiology and Intensive Care Medicine, Hannover Medical School, Germany
  • author Franz-Josef Kretz - Olgahospital, Department of Anesthesiology and Operative Intensive Care, Stuttgart, Germany
  • author Heinz Laubenthal - Bochum, Germany
  • author Guenter Marggraf - West German Heart Center Essen, Department of Thoracic and Cardiovascular Surgery, University Hospital Essen, Germany
  • author Andreas Meiser - Department of Anesthesiology, Intensive Care and Pain, Saarland University Hospital, Homburg, Germany
  • author Edmund Neugebauer - IFOM - Institute for Research in Operative Medicine, Institute for Surgical Research, Private University of Witten/ Herdecke GmbH, Köln, Germany
  • author Ulrike Neuhaus - Department of Anesthesiology and Operative Intensive Care, Charité Campus Virchow, Berlin, Germany
  • author Christian Putensen - Anesthesiology and Operative Intensive Care, University of Bonn, Germany
  • author Michael Quintel - Surgical Intensive Care, University of Göttingen, Germany
  • author Alexander Reske - Department of Anesthesiology and Intensive Care, Universitätsklinikum Carl Gustav Carus, Dresden, Germany
  • author Bernard Roth - Department of General Pediatrics, Cologne, Germany
  • author Jens Scholz - Department of Anesthesiology and Surgical Intensive Care, University Hospital of Schleswig-Holstein, Kiel, Germany
  • author Stefan Schröder - Department of Psychiatry and Psychotherapy, CMM Hospital Guestrow, Germany
  • author Dierk Schreiter - Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Dresden, Germany
  • author Jürgen Schüttler - Anaesthesiology Clinic University Hospital of Erlangen, Germany
  • author Gerhard Schwarzmann - Anaesthesiology, Surgical Intensive Care Unit, Frankfurt, Germany
  • author Robert Stingele - Department of Neurology, University Hospital of Schleswig-Holstein, Kiel, Germany
  • author Peter Tonner - Department of Anesthesiology and Intensive Care Medicine, Emergency Medicine Hospital Links der Weser GmbH, Bremen, Germany
  • author Philip Tränkle - Department of Internal Medicine, Division III, ICU 3IS, Tübingen, Germany
  • author Rolf Detlef Treede - Department of Neurophysiology, Center for Biomedicine and Medical Technology Mannheim (CBTM), Germany
  • author Tomislav Trupkovic - Department of Anesthesiology, Intensive Care Medicine and Pain Management, BG Trauma Clinic Ludwigshafen, Germany
  • author Michael Tryba - Anesthesiology and Operative Intensive Care, Klinikum Kassel, Germany
  • author Frank Wappler - Department of Anesthesiology and Operative Intensive Care, Hospital Cologne-Merheim, University of Witten/ Herdecke, Cologne, Germany
  • author Christian Waydhas - Department of Trauma Surgery, University Hospital Essen, Germany
  • corresponding author Claudia Spies - Department of Anesthesiology and Intensive Care Medicine, Campus Virchow-Klinikum and Campus Charité Mitte, Berlin, Germany

GMS Ger Med Sci 2010;8:Doc02

doi: 10.3205/000091, urn:nbn:de:0183-0000916

This is the original version of the article.
The translated version can be found at: http://www.egms.de/de/journals/gms/2010-8/000091.shtml

Received: December 4, 2009
Published: February 10, 2010

© 2010 Martin et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.


Abstract

Targeted monitoring of analgesia, sedation and delirium, as well as their appropriate management in critically ill patients is a standard of care in intensive care medicine. With the undisputed advantages of goal-oriented therapy established, there was a need to develop our own guidelines on analgesia and sedation in intensive care in Germany and these were published as 2nd Generation Guidelines in 2005. Through the dissemination of these guidelines in 2006, use of monitoring was shown to have improved from 8 to 51% and the use of protocol-based approaches increased to 46% (from 21%).

Between 2006–2009, the existing guidelines from the DGAI (Deutsche Gesellschaft für Anästhesiologie und Intensivmedizin) and DIVI (Deutsche Interdisziplinäre Vereinigung für Intensiv- und Notfallmedizin) were developed into 3rd Generation Guidelines for the securing and optimization of quality of analgesia, sedation and delirium management in the intensive care unit (ICU). In collaboration with another 10 professional societies, the literature has been reviewed using the criteria of the Oxford Center of Evidence Based Medicine. Using data from 671 reference works, text, diagrams and recommendations were drawn up. In the recommendations, Grade “A” (very strong recommendation), Grade “B” (strong recommendation) and Grade “0” (open recommendation) were agreed.

As a result of this process we now have an interdisciplinary and consensus-based set of 3rd Generation Guidelines that take into account all critically illness patient populations.

The use of protocols for analgesia, sedation and treatment of delirium are repeatedly demonstrated. These guidelines offer treatment recommendations for the ICU team. The implementation of scores and protocols into routine ICU practice is necessary for their success.

Keywords: guideline, evidence, analgesia, sedation, delirium, monitoring, treatment, intensive care


Introduction

Analgesia, sedation and delirium management are relevant to ICU course and outcome [1], [2], [3]. In these new guidelines, the current recommendations concerning these topics are integrated. They also address the specific features of many different groups of patients: children or the elderly, pregnant and lactating patients or patients with serious injuries. The fact that so many special requirements could be taken into account is thanks to intensive cooperation between medical and nursing experts from 12 different professional societies.


Methods

Creation process

The methodological approach was in accordance with the DELBI (German Instrument for the Methodological Assessment of Guidelines) criteria (http://www.versorgungsleitlinien.de/methodik/delbi/pdf/delbi05.pdf). The complete guidelines development process was supported and monitored by the Association of Scientific Medical Societies (AWMF) of Germany.

Initially, the objectives of the guidelines as well as management for the various key topics and patient groups were defined and formed by groups of experts from 12 disciplines. The following areas have been identified as priority areas:

1.
Need for guidelines
2.
Monitoring of analgesia, sedation and delirium in adults
3.
Treatment and weaning – analgesia, sedation and delirium in adults
4.
Regional anesthesia
5.
Neuromuscular blockade – monitoring, treatment
6.
Economy, quality assurance and implementation
7.
Special populations:
a. Burn patients
b. Multiply injured patients
c. Neurotrauma patients
d. Pregnant and lactating patients
e. Patients ≥ 65 years
f. Moribund/dying patients
8.
Monitoring and treatment of analgesia, sedation and delirium in neonates and troddlers [1].

Selection and evaluation of literature

A systematic literature search was conducted using pre-defined search terms for the priority areas and pre-selected databases.

For the Cochrane database and PubMed/MEDLINE, using the above-mentioned subjects, in the research period from 1995 to 2007, a total of 2418 papers were identified. After reviewing the literature and taking into account the exclusion criteria (language other than English/German, animal experiments, purely pharmacological model, only abstract, editorial or commentary) 671 publications were included.

The existing publications were classified in terms of their evidence level. We used the sign-50 criteria of the Oxford Center of Evidence Based Medicine (http://www.cebm.net/index.aspx?o=1025). Clinical studies were classified according to their scientific validity and value into different levels of evidence level (1–5), and an additional assessment of their clinical relevance (a–c) was also performed. Highest priority was given to meta-analyses of randomized, controlled clinical trials. The recommendations and the text were developed from a first draft.

The recommendations were reached via consensus procedures that were moderated by the AWMF. In reaching consensus particular emphasis was placed on the level of evidence, ethical aspects, patient preferences, clinical relevance, risk/benefit ratios and degree of applicability.

In the recommendations, grade “A” is a very strong recommendation that is represented using the phrase “should be”, Grade “B” is a strong recommendation (“should be”), and level “0” is an open recommendation (“can be”). The recommendation levels are derived from the requirements of the Council of Europe 2001 [4].


Monitoring

The systematic monitoring of pain, sedation and delirium, targeted protocols for the management of sedation, analgesia and delirium are associated with a lower incidence of nosocomial infections, a reduction in the duration of ventilation and length of ICU stay (LOS), lower mortality and lower resource consumption [5], [2], [6], [7], [8], [9]. The monitoring should be performed regularly (8-hourly) and be documented. A goal for sedation and analgesia should be set for each individual patient and delirium should be treated immediately. The level achieved should be monitored regularly, documented and the treatment should be adapted appropriately.

Monitoring of analgesia

Approximately 75% of ICU patients report severe pain during their treatment however over 80% of their care givers consider the analgesia provided by them to be adequate [10]. The best existing standard for assessment of pain is individual assessment by the patients themselves (Numeric Rating Scale NRS, Visual Analogue Scale VAS, Verbal Rating Scale VRS). For patients who are unable or unreliably able to communicate, subjective criteria such as movement, facial expression, physiological parameters such as blood pressure, heart rate, respiratory rate, lacrimation, sweating and changes in all these parameters after analgesic therapy as well as specific assessment tools (e.g. Behavioral Pain Scale BPS) should be considered. Adequate monitoring of analgesia is relevant to the outcome of critically ill patients [2].

Monitoring of sedation

Over-sedation is associated with prolonged ventilation times, higher incidence of pneumonia, hypotension, gastroparesis, delirium, longer stays, higher costs and a higher mortality [1]. After their stay in the ICU, these patients often have difficulty sleeping and more post-traumatic stress disorders [11]. A validated sedation scale like the Richmond Agitation and Sedation Scale (RASS) should routinely be used.

Monitoring of delirium

Thirty to eighty percent of ICU patients suffer delirium. Delirium is associated with 6 month mortality three times greater than background [12], higher costs [13], and a significant permanent cognitive deterioration [14]. A validated scale should be also be used for delirium monitoring. The Confusion Assessment Method for the ICU (CAM-ICU) and Intensive Care Delirium Screening Checklist (ICDSC) are the most widely used scales [15], [16].


Therapy

In the management of analgesia, sedation and delirium, patient-centered concepts with individual treatment goals are essential.

Analgesia

ICU patients should receive analgesia tailored to their individual requirements [17]. Patient-controlled administration is preferable if the patient is able for it [18], [19]. Non-opioid analgesics and adjuvant substances may be used when needed [20].

Regional analgesia

Prior to the use of regional analgesia, a careful and critical risk-benefit assessment should be performed for each individual patient. The risk-benefit analysis should be reassessed daily. Epidural catheter techniques can positively influence outcome [21], [22]. The decisive factor is atraumatic catheter placement and continuous monitoring of any neurological complications that require immediate intervention.

Sedation

A sedation-as-needed approach requires sufficient analgesia and optimized ventilation settings in advance [23], [24]. Sedation goals should be formulated in advance. Regular monitoring and appropriate adjustment of the medication is required to avoid both over- and under-sedation [1], [25], [26]. Because of the known negative consequences, deep sedation should be reserved for only a few specific indications (e.g. increased intracranial pressure). In cases of expected short duration of sedation, propofol and inhalative sedation or midazolam boli could all be used [27], [28]. In prolonged therapy, bolus lorazepam sedation is another option [29].

Weaning

In addition to a sedation protocol, a weaning protocol is strongly recommended, as this is also associated with improved survival [9]. During weaning, analgesics and sedatives with short context-sensitive half lives are preferable.

Delirium treatment

There is some evidence for the use of neuroleptics for both treatment and prophylaxis [30]. Additive alpha-2 agonists and benzodiazepines (which will mainly be used in cases of substance withdrawal) can be used [31], [32]. The prophylactic maintenance of day-night rhythm, re-orientation methods, cognitive stimulation and early mobilization are important elements [33], [34]. High priority should also be given to tapering of analgesics and sedatives in order to minimize risk of withdrawal [35].

Neuromuscular blockade

Both new ventilation modes and the advent of modern drugs for analgesia and sedation have allowed for adjustment of sedation to suit almost any clinical situation. ICU patients only rarely require profound sedation with additional muscle relaxation. Muscle relaxants should only be a method of last resort. Muscle relaxants are not an alternative to analgesia and sedation.


Economy, quality assurance and implementation

In level 1 university hospitals, about 20 percent of the total hospital budget will be spent on intensive care units, although only about 5 percent of the total number of hospital patients are treated in the ICU [36]. The drug costs in European intensive care units, according to the EURICUS III survey [37] are an average of 15.4 percent of the total hospital medication budget. Many of the sedatives, analgesics and neuromuscular blocking agents not only have high initial cost, but also cause indirect costs [38]. High indirect costs are caused in particular by unwanted medication effects such as increased ventilation times and higher incidence of pneumonia.

In order to achieve the reduction in costs that is external economic forces frequently dictate, a cost effectiveness analysis with special consideration of evidence-based therapies should be performed [39]. As a general objective, optimal therapy at reasonable prices should be demanded and unnecessary or even harmful therapies should be excluded.

The need for guidelines or standards in the interest of the safety of patients and medical staff is now undisputed consensus [40], [41].

Scientific evidence however will never be implemented completely into routine clinical practice in the ICU. Several studies have shown how big the gap between “best evidence” and “best practice” is. Approximately 30–40% of all patients are not treated according to current best scientific evidence and 20–25% will still be receiving potentially dangerous therapies [42].

The successful implementation of these guidelines requires resources such as personnel, skills such as effective time management and organization features such as high levels of motivation [43], [44]. For the lasting implementation of the guidelines into clinical practice, training in their execution as well as their content is needed (particularly during the early introductory phase) [45], [8], [46].


Special populations

Patients with severe burn injuries

For burn victims, adequate pain control and minimization of psychological stress is very important [47]. Efforts should be made minimize metabolic stress and so minimize oxygen consumption. The pain and stress associated with diagnostic and therapeutic interventions must be taken into account. The goals of activation and recovery of coordination must be balanced with the “stabilization” of the skin grafts.

A certain level of baseline analgesia will be needed in most cases. In procedures such as dressing changes, wound debridement in the therapy pool, etc. additional analgesia and/or sedation may be required.

Multiply injured trauma patients

Compared to other patient groups, critically-ill trauma patients are younger and consequently relatively unique with respect to metabolic activity, pharmacokinetics, pharmacodynamics, and relevant comorbidities. Adequate analgesia and sedation during acute care and follow-up intensive care is an indispensable part of the treatment. Particular emphasis is placed here on the use of the “conscious sedation” concept. Therapy should be individually tailored according to the individual pattern of injury, the surgical treatments required and the associated clinical/critical care course.

Patients with severe traumatic brain injury and/or intracranial hypertension

Traumatic brain injury is defined by a Glasgow-Coma-Scale <9 and despite all advance in diagnosis and therapy this remains the main cause of death among people aged younger than 45 years [48]. According to recent statistics in Germany, about 248,000 per year people suffer a brain trauma in Germany, of which 2750 will be fatal.Of these injuries, 91% are classified as mild, 4% as moderate and 5% as severe [49]. There is undisputed consensus that adequate analgesia and sedation are essential in the intensive therapy of these patients. Nevertheless there are insufficient data to confirm that conscious sedation per se reduces intracranial pressure and improves neurological outcome [50]. Adequate sedation is paramount in all therapeutic algorithms for the treatment of increased intracranial pressure [51] because psychomotor restlessness, pain and autonomic stress all adversely effect intracranial pressure (ICP), cerebral blood flow (CBF), cerebral perfusion pressure (CPP) and the cerebral metabolic rate for oxygen metabolism (CMRO2). In this respect, adequate analgesia makes an essential contribution to preventing or limiting secondary brain damage. Invasive monitoring of ICP and CPP is, in accordance with the guidelines of the Brain Trauma Foundation, indicated in patients with severe traumatic brain injury [52].

The ideal sedative/analgesic in neurosurgical intensive care should

  • reduce the ICP while maintaining an adequate CPP
  • maintain cerebral hemodynamics, including autoregulation
  • minimize cerebral metabolic rate for oxygen metabolism (CMRO2)
  • have both anticonvulsant and neuroprotective properties
  • allow to rapid neurological assessment of patients after discontinuation [53].

Since sedation can interfere with neurological assessment, compromises must sometimes be made. A combination therapy should be chosen that includes short-acting agents, to enable a rapid neurological assessment. Therefore combinations of short acting sedatives and analgesics recommended. Sedation protocols performing a daily interruption of sedation [1] are not sufficiently evaluated in patients with underlying cerebral disease yet.

In addition to adequate analgesia, which is essential in severe cerebral trauma, additional analgesia and sedation must be provided for nursing interventions and any surgical interventions. In the acute phase of intensive treatment deep-sedation (RASS score of –5) should generally be targeted, especially if intracranial hypertension (ICP >15–20 mmHg) is present [52], [54].

Pregnant and lactating patients

During pregnancy and lactation, all necessary measures must be undertaken with regard to the child. Both non-opioids and opioids may be given under certain conditions. Regarding sedation in pregnant women, there is relatively little evidence available.

Elderly patients

Clinical age is determined by biological age, comorbidity, medication and external influences. Age-related changes in the cardiovascular, pulmonary, renal and nervous system lead to different pharmacodynamics and pharmacokinetics. There are changes in volume of distribution, therapeutic indices and duration of action for many medications and dosages should be adjusted accordingly. While the monitoring of sedation with standard scores is still acceptable, self-assessment of pain can be complicated by cognitive impairment. Regarding the development of delirium, elderly patients are particularly vulnerable as they often have predisposing risk factors such as neurodegenerative diseases, cerebral hypoperfusion, chronic hypoxia, infection, drug overdose, deafness, etc. Preventive measures such as visual and hearing aids, reorientation and cognitive stimulation are frequently indicated in the elderly [33].

The analgesic and sedative therapy should be titrated from lower doses and with smaller titrations. Medications with a short and context-insensitive halftime or regional techniques are preferred in older patients.

Moribund and dying patients

If the limits of intensive care treatment methods have been reached, the duties of medical staff change towards helping the dying.

These guidelines must be viewed in the context of published German federal guidelines for the health care professional’s duty of care in intensive care and in the context of the regulations of the German Medical Association for end-of-life care (http://www.dgai.de/06pdf/13_557-Leitlinie.pdf) [55].

Analgesia and sedation and monitoring of delirium in newborns and in children

The same standards for monitoring in adults are generally applicable to children of all ages.

Monitoring analgesia in neonates and toddlers

Pain detection in neonatology and pediatrics is contingent on the developmental age of the patient. The developmental age dependent differences in children’s concepts of pain are reflected in their pain experience and expression of pain [56], [57], [58], [59]. In the literature, several pain assessment tools for different age groups, diagnostic groups and pain types are available. These include tools for ventilated and non-ventilated patients, acute postoperative patients or patients with procedure-associated pain and patients with chronic pain.

Monitoring sedation in neonates and toddlers

If sedation is required, individual patient-oriented therapy with 8-hourly review of the sedation goal using a validated monitoring tool is recommended for each age group.

Monitoring of delirium in neonates and toddlers

Pediatric patients are particularly vulnerable to toxic, metabolic or traumatic cerebral nervous system (CNS) insults and more prone to develop delirium due to fever, regardless of the cause [60]. It is likely that only the most serious cases are diagnosed and properly treated. Just as in adults, delirium may present in children in a hypo- or hyper-active from, or in a mixed form. In children too, the hypo-active form is often confused with depression, while hyper-active forms are often misinterpreted as uncontrolled pain.

Other causes of delirium are similar to adult patients and should be actively sought (a useful mnemonic for the causes of delirium is: I WATCH DEATH) [61]. Children of preschool age may be just as vulnerable to delirium as geriatric patients because of cerebral growth and remodeling processes [60].

Analgesic, sedative and delirium therapy in neonates and toddlers

Analgesic treatment in neonates and toddlers

Critically ill children, like adults require tailored pain therapy. Most of the basic principles of analgesic therapy in adult medicine are applicable, but there are some differences that require a unique approach.

The pharmacokinetics and pharmacodynamics of analgesics change with age: in neonates, immaturity of some hepatic enzymes result in reduced clearance, while in children from 2 to 6 years, the drug may be metabolized faster due to a higher relative liver weight [62].

Pediatric analgesic therapy is also based on the World Health Organization (WHO) ladder for pain therapy (http://www.who.int/en/).

Adequate monitoring is essential during analgesic therapy in children due to the potential for serious adverse events. This is particularly true during the use of opioids.

Sedative treatment in neonates and toddlers

Many diagnostic and therapeutic procedures, or those requiring a co-operative, or very quiet patient, can only be performed under sedation. In some cases, continuous sedation of critically ill children in the pediatric or neonatal intensive care is necessary despite adequate analgesia. Sedation in children requires special personnel and structural conditions [63].

Delirium therapy in neonates and toddlers

There are hardly any data for the incidence of delirium in critically ill children. In a study by Schieveld, a cumulative incidence of 5% at a mean age of 7.6 years was described [64].

Due to the limits of the currently available data, only the principle of combined psycho-social measures (presence of family, favorite toys, pictures of home, normal day-night rhythm, etc.) and pharmacological intervention for the treatment of delirium in children can be recommended [64], [65], [66].


Next steps

Implementation of the guidelines

To assess any the changes in practice regarding pain, over- and under-sedation and delirium prevention in the intensive care, an investigation will be conducted one year after the release of these 3rd Generation Guidelines. The investigation will be analogous to that performed after the publication of the 2nd Generation Guidelines [67]. Through this investigation it should be evaluated whether the recommendations of the guidelines have been adopted into practice, and in this way incorporated into the real world therapy and whether a change in patient management is appreciable and what influence on this various approaches to implementation had.

Further evaluation needed

Many of the scores used in the literature do not exist in validated German translations. If there was no validated German version available, it was created by the guideline authors. It is desirable that as many of these instruments as possible are validated in German ICUs over the coming years.


Tables and schemes

The detailed recommendations are listed in Attachment 1 [Attach. 1].


Notes

Long version of the guideline

The long version of the guideline in German language is available from http://leitlinien.net/001-012.htm.

Validity and Update

These guidelines are based on the best scientific advice currently available for each of the above topics. The Guidelines were approved by the Executive Committees of all participating scientific societies between October and December 2009. They are valid up to December 2014. The DGAI and DIVI will together with the participating societies, nominate a project team and management for the updating of the guidelines.

In the case of new relevant scientific evidence that would require a revision of the recommendations, a direct communication will follow.

Authorship

The authors are members of the working group on analgesia, sedation and delirium management in intensive care of the DGAI (Deutsche Gesellschaft für Anästhesiologie und Intensivmedizin), DGCH (Deutsche Gesellschaft für Chirurgie), DGF (Deutsche Gesellschaft für Fachkrankenpflege), DGGG (Deutsche Gesellschaft für Gynäkologie), DIVI (Deutsche Interdisziplinäre Vereinigung für Intensiv- und Notfallmedizin), DGIIN (Deutsche Gesellschaft für Internistische Intensivmedizin), GNPI (Gesellschaft für Neonatologie und pädiatrische Intensivmedizin), DGNC (Deutsche Gesellschaft für Neurochirurgie), DGN (Deutsche Gesellschaft für Neurologie), DGPPN (Deutsche Gesellschaft für Psychiatrie, Psychotherapie und Nervenheilkunde), DGSS (Deutsche Gesellschaft zum Studium des Schmerzes), and DGTHG (Deutsche Gesellschaft für Thorax-, Gefäß- und Herzchirurgie).

The two authors first mentioned, J. Martin and A. Heymann, contributed equally to this work.

AWMF support by PD I. Kopp, Institute for Theoretical Medicine, Marburg.

Conflict of interest

The declarations of conflict of interest of all participants can be viewed on request, from the respective professional societies.

Funding

This guideline was funded by the DGAI independent of any interest groups.

Acknowledgements

We are most grateful to Dr. Martin Mac-Guill, Dublin, formerly working at the Charité University Hospital Berlin, who helped us with the translation.


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